THE AVONEX CHANNEL: 15 STUDIES IN FRIDAY'S NEWS

PLUS: 1485 new Studies we posted from 11/1 to Thursday 2/6 Start at the Bottom!

A study was done to assess the cost-effectiveness of the Disease Modifying Treatments (DMT), Glatiramer Acetate (GA) and Interferon beta-1a (IFN) in monotherapy alone and in combination for the prevention of relapses among Spanish patients aged between 18 and 60 years old with established Relapsing-Remitting Multiple Scerosis (RRMS).
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Article reviews the current understanding of the interactions between multiple sclerosis (MS) and pregnancy, and implications for reproductive counseling. This is a key topic in MS because the typical patient is a young woman of childbearing age.Pregnancy has a profound effect on MS disease activity. Identification of the responsible mechanisms for this effect should lead to new disease insights and therapeutic strategies.
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Pain-related mood influences pain perception differently in fibromyalgia and multiple sclerosis.
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Gait disorders need to be identified and managed early in the course of MS, using a multimodal approach that needs to be adjusted over time based on the results of periodic assessments.
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Fatigue needs to be recognized as an important condition that is not only a symptom but may also be quantified and can be modified by various measures depending on the underlying cause.
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The observed association between reproductive history and MS risk is restricted to a limited time period preceding the index year, with similar findings in both sexes, which contradicts biologic impact of pregnancy on MS risk and argues in favor of reverse causality, i.e. that fecundity is affected by yet-undiagnosed MS.
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The frequency of WM signal abnormalities and radiologically isolated syndrome is higher in the healthy relatives of patients with multiple sclerosis patients compared with non-familial healthy control subjects.
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Presence of fatigue and depressive symptoms influenced the self-assessment of quality of life. Complex care of MS patient should consider diagnosis and treatment of fatigue and depression which could improve their quality of life.
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The instrumented treadmill may be an effective tool in assessing ambulation capabilities of people with MS.
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This review focuses on the neuroimaging of gray matter pathology in MS, the effect of the accumulation of gray matter pathology on clinical and cognitive disability, and the effect of disease-modifying agents on various measures of gray matter damage.
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In RRMS patients, long-term brain lesion accrual is associated with worsening in clinical disability. This is particularly true for hypointense, destructive lesions.
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A comprehensive understanding of pediatric optic neuritis and its management remains elusive. A randomized clinical trial would potentially increase our knowledge and benefit the afflicted patients.
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MS patients with no clinical disability have discrete changes in gait that can be evidenced by perceived impact on walking and kinematic evaluation, mainly of ankle movement. Moreover, there is a decrease in perceived balance confidence and an increase in perceived fatigue, which are correlated despite having different origins.

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Chronic cerebrospinal venous insufficiency is rarely observed in children or young adults with pediatric-onset MS. Venous anatomy and flow rates indicate that venous outflow is intact in pediatric patients with MS. Our findings argue against chronic cerebrospinal venous insufficiency as a component of MS etiology.
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Cellular degeneration in MS lesions leads to waves of iron liberation, which may propagate neurodegeneration together with inflammatory oxidative burst

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1485 STUDIES FROM 11/1 to Thursday 2/6 are below:

Current guidelines have recognized the benefits of early treatment of MS with DMTs. However, there are a number of barriers to implementing early MS treatment. Early diagnosis and treatment of MS can be hindered because patients may delay consulting a physician about their neurological symptoms or may be reluctant to start DMT. Read study at National Institute of Health

Due to the current lack of appropriate clinical guidance and insufficient head-to-head data on disease-modifying drugs, strategies for health plans and clinical management have been designed using the best available evidence. Undoubtedly, management of this class will continue to evolve with the launch of newer agents.
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A period of diagnostic uncertainty regarding the transition from RRMS to SPMS existed in many of our patients. Potential reasons included the subtle nature of early progressive disease and caution in applying a progressive label, in light of the lack of evidence-based treatments as well as third-party payer concerns. Delay in definitive identification of an SPMS phenotype has a variety of implications related to patient care and research.
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This study supports the concept that modifications of the tear proteome can reflect biological abnormalities associated with multiple sclerosis and perhaps other inflammatory conditions affecting the CNS. In addition, alpha-1-antichymotrypsin elevation in tear fluid emerges as a promising biomarker for the diagnosis of multiple sclerosis.

The present study examined the functioning of explicit and implicit memory in MS. Results showed that implicit memory was not significantly impaired in the MS subjects, and that they were impaired on recall but not recognition. A correlation was found between implicit memory performance and disability status in MS patients.

This is the first study to demonstrate an increase IR prevalence and the association between IR and adiposity with disability assessed by EDSS in patients with MS. IR seems to be associated with chronic inflammatory process and oxidative stress in patients with MS. More studies are warranted to elucidate the mechanisms by which IR and adiposity could contribute to the progression and disability in patients with MS.

It is suggested that because the veracity of ambiguous illnesses is often questioned, this might represent a potent stressor in women with such illnesses, and even coping methods typically thought to be useful in other conditions, are not associated with diminished distress among those with CFS/fibromyalgia.

Diffusion restriction of the optic nerve in patients with acute visual deficit.

We found no genetic overlap between BD and MS. Considered together, our findings demonstrate genetic pleiotropy between SCZ and MS and suggest that the MHC signals may differentiate SCZ from BD susceptibility.

Overall, most of the MS sample remained stable in their HRQOL over time. However, approximately four out of every ten patients experienced a clinically important decline in their HRQOL. While the association was statistically significant, the sociodemographic and disease-related factors linked with decline did not strongly predict decline over a 5-year period.

Implication for Rehabilitation Vocational rehabilitation can be effective in maintaining people with MS in their employment and help to remove some of the physical and emotional barriers that can develop. Employers and employees with MS must work together to effectively manage the MS in the workplace; a health professional can facilitate, support and encourage this dynamic process.

Participants were required to recall the information immediately, 30 minutes, and 1 week following initial learning. Significantly more words were recalled from the generated condition relative to the provided condition. Self-generation may be influenced by variables such as task meaningfulness during learning and memory. In addition, type of task (functional versus laboratory) has a significant effect on memory. Implications for cognitive rehabilitation in MS are discussed.

There is still remarkably little research on this common and, to patients, very significant issue of bowel management. The available evidence is almost uniformly of low methodological quality. The clinical significance of some of the research findings presented here is difficult to interpret, not least because each intervention has only been addressed in individual trials, against control rather than compared against each other, and the interventions are very different from each other.

The proposed neurogenic bladder symptom score is a novel patient-reported outcome measure. Further work is underway to perform a data-based item reduction and to assess the validity and reliability of this instrument.

Memory impairment is prevalent in multiple sclerosis (MS). Retrieval practice is a powerful memory technique whereby retrieving information (quizzing oneself) leads to better memory than restudying.

Control of spasticity in a multiple sclerosis model using central nervous system-excluded CB1 cannabinoid receptor agonists

Vowel Acoustics in Parkinson's Disease and Multiple Sclerosis: Comparison of Clear, Loud, and Slow Speaking Conditions

Predictors of effectiveness of multidisciplinary rehabilitation treatment on motor dysfunction in multiple sclerosis.

A Randomized, Double-Blind, Placebo-Controlled Trial of Duloxetine for the Treatment of Pain in Patients with Multiple Sclerosis.

Fatty fish intake is associated with decreased occurrence of multiple sclerosis

Modifications of the tear proteome can reflect biological abnormalities associated with multiple sclerosis and perhaps other inflammatory conditions affecting the CNS. In addition, alpha-1-antichymotrypsin elevation in tear fluid emerges as a promising biomarker for the diagnosis of multiple sclerosis.

A correlation was found between implicit memory performance and disability status in MS patients. Findings also suggest the possibility of long-term priming of implicit memory in the control subjects. The implications of these results are discussed.

IR seems to be associated with chronic inflammatory process and oxidative stress in patients with MS. More studies are warranted to elucidate the mechanisms by which IR and adiposity could contribute to the progression and disability in patients with MS.

Although more research is needed, screening programs for depression in MS may facilitate access to services for all MS patients while reducing health disparities in Black American patients and removing barriers to early intervention and ongoing care.

The data in the study did not suggest reversed causality between childbirth and MS.

There are currently nine approved disease modifying therapies for relapsing forms of multiple sclerosis, with six distinct mechanisms of action. All have side effects, and none are cures. When a patient cannot tolerate therapy, or there is unacceptable breakthrough disease activity, the most common approach is to change drug. No universal guidelines exist for switching therapy.

Putative mechanisms involved in MS worsening after ART include: temporary interruption of disease modified therapies, stressful events associated with infertility, and immunological changes induced by hormones such as increase in pro-inflammatory cytokines and anti-MOG antibodies, as well as an increase in immune cell migration across the blood-brain-barrier. Overall, neurologists should be aware of this risk and discuss the pros and cons of the procedures with MS patients.

Work capacity and HRQoL among individuals diagnosed with MS are highly influenced by fatigue which can be considered as a key symptom. Work capacity was influenced by heat-sensitivity, cognitive difficulties and emotional distress and significant predictive factors besides fatigue, were physical disability (EDSS), age, sex, and level of education. Remaining at work also gives a better HRQoL.

Cognitive impairment in MS: impact of white matter integrity, gray matter volume, and lesions.

Our study emphasizes the high prevalence of PVC in MS patients. Regarding the nature of neuro-ophthalmologic deficit, our results suggest that persistent optic neuropathy, as part of the progressive evolution of the disease, is not rare. We also demonstrate that isolated ocular motor dysfunctions induce visual disability in daily life.

Magnetic susceptibility of MS lesions increased rapidly as it changed from enhanced to nonenhanced, it attained a high susceptibility value relative to NAWM during its initial few years (approximately 4 years), and it gradually dissipated back to susceptibility similar to that of NAWM as it aged, which may provide new insight into pathophysiologic features of MS lesions.

In a cohort with different stages of MS, higher EA attenuated the negative effects of white matter lesion burden and third ventricle width (suggestive of thalamic atrophy) on cognitive performance. Actively enhancing cognitive reserve might thus be a means to reduce or prevent cognitive problems in MS in parallel to disease modifying drugs.

These data suggest that retrograde (trans-synaptic) axonal degeneration stops at the inner nuclear layer, a neuronal network capable of plasticity. In contrast, there seems to be no neuroplasticity of the primary visual cortex, rendering the structure vulnerable to anterograde (trans-synaptic) degeneration.

Simultaneous characterizations of changes in tonic and phasic reflexes and nonreflex changes in joint elastic stiffness and viscosity in neurological disorders may help us gain insight into mechanisms underlying spasticity and develop impairment-specific treatment.

Very rapid functional changes in the excitability of cortical circuits involved in motor control can be induced by steroids, before any process of remyelination or axonal regeneration has time to occur. The net effect of steroids on the balance between intracortical GABAergic inhibition and glutamatergic facilitation was in favour of weaker inhibition or stronger facilitation, which could lead to improving the motor performance in MS patients.

The inflammatory mechanisms associated with lesion formation in MS are to a large extent reflected in experimental models of inflammatory demyelination, such as autoimmune encephalomyelitis. This is not the case for the amplification mechanisms of oxidative injury, which mainly operate in the progressive stage of the disease. GLIA 2014.

We found no genetic overlap between BD and MS. Considered together, our findings demonstrate genetic pleiotropy between SCZ and MS and suggest that the MHC signals may differentiate SCZ from BD susceptibility

PPUN is an infrequent, ocular manifestation noted during an acute attack of MS, and was observed in 5% of the present cases. Brainstem lesions in these cases primarily involved the pontine tegmentum and the caudal medulla. These findings support the theory that upbeat nystagmus is attributable to damage to the upward vestibulo-ocular reflex pathway related to the vestibular nucleus, VTT, and interconnecting pathways.

This study was designed to evaluate the effects of a 12-week detraining period on muscle strength (isometric and endurance) and muscle power of multiple sclerosis (MS) patients that had previously carried out a 12-week resistance training program (RTP). A 12-week RTP improved MVIC and muscle power in MS patients. Additionally, 12 weeks of detraining blunted strength training adaptations in MS patients, although muscle power training adaptations were still evident after the detraining period.

Of the common rehabilitation diagnoses we studied, musculoskeletal conditions such and back pain and arthritis likely have the most impact on the health care system due to their high prevalence and impact on disability.

Efforts that center on bridging the larger fields of aging and disability in order to build new knowledge and engage in knowledge translation and translational research are critical for building capacity to support persons aging with disability in LTSS. Generating the investment in bridging aging and disability research across stakeholder group, including researchers and funders, is vital for these efforts.

Health professionals treating informal caregivers, as well as those treating people with MS, need to be aware of respite, support, and intervention programs available to MS caregivers and refer them to these programs, which could reduce the negative impact of caregiving on employment.

This new instrument, which was developed with input from clinicians as well as MS patients, meets the current content validity and psychometric testing thresholds established by the US Food and Drug Administration, with high sensitivity and specificity.

In this study, program feasibility was demonstrated in several ways. There were no declines in cognitive function over the 5-month period. Despite unchanged cognitive function, participants may value the improved mood enough to continue both the structured and unstructured physical activity. The role of unstructured physical activity in concert with periodic structured exercise programs merits further investigation.

Many prescribers of disease-modifying therapies (DMTs) for multiple sclerosis (MS) believe that interferon beta (IFNβ) is more likely than glatiramer acetate (GA) to increase depression during the course of MS treatment.

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The majority of Italian neurologists participating in our study have a good perception of their ability to manage this difficult communicating process and believe in the great effect this moment may have on a life-long disease experience. Improving communication skills may help the therapeutic alliance, enhancing patients' acceptance of the disease, as well as motivation and adherence to treatment.

It is possible that, with further such supportive data, international guidelines on MS treatment in young women who intend to get pregnant may need to be revised.

A significant interaction between Alerting and Executive Control was also found in the MS patients (p = .007). Early relapsing-remitting multiple sclerosis particularly affects the Alerting domain of attention, whereas the Orienting and Executive Control domains are not affected.

The GM is atrophic in MS. Although lower WM volume is associated with greater disability, as might be expected, WM volume was on average in the normal range. This paradoxical result might be explained by the presence of coexisting pathological processes, such as tissue damage and repair, that cause both atrophy and hypertrophy and that underlie the observed disability.

ApEn results revealed that the natural fluctuations present during gait in the stride length and step width time series are more regular and repeatable in patients with MS. These changes implied that patients with MS may exhibit reduced capacity to adapt and respond to perturbations during gait.

the value of intrathecal triamcinolone acetonid (TCA) in MS is still a controversial issue. Bearing in mind that only limited data are available and due to its invasive application form repeated TCA administration can be recommended as one therapy option in MS with a progressive clinical course and predominantly spinal symptoms.

This article will review recent developments in MS treatments focusing on oral agents (cladribine, fingolimod, BG00012, teriflunomide and laquinimod) and novel monoclonal antibodies (alemtumzumab, daclizumab, ocrelizumab, ofatumumab).

The findings suggest that aquatic exercise training can effectively improve fatigue and HRQOL of patients with MS and should be considered in the management of this relatively common public health problem.

This paper introduces a novel methodology for the segmentation of brain MS lesions in MRI volumes using a new clustering algorithm named SCPFCM. SCPFCM uses membership, typicality and spatial information to cluster each voxel. The proposed method relies on an initial segmentation of MS lesions in T1-w and T2-w images by applying SCPFCM algorithm, and the T1 image is then used as a mask and is compared with T2 image. The proposed method was applied to 10 clinical MRI datasets. The results obtained on different types of lesions have been evaluated by comparison with manual segmentations.

We herein give an overview of the knowledge available to date. Affective and emotional disturbances together with other comorbidities interfering with cognition are also reviewed. Finally, possible suggestions and future directions for the assessment of cognitive capabilities in children with MS are envisioned.

Posturometric measures in participants with MS were significantly worse than in HC (all P values <.0001); however, only the center of pressure (COP) path with open eyes condition had substantial test-retest reliability. Static posturography was more sensitive (88% vs 37%) and accurate (75% vs 63%), but slightly less specific (67% vs 81%), than the BBS in predicting accidental falls. A logistic regression analysis revealed that the worse the COP path, the greater the risk for accidental falls (odds ratio = 1.08; P < .0001), even after adjusting for sex, age, disease duration, body mass index, MS subtype, Expanded Disability Status Scale, and BBS score.

There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators. Results of the ongoing trial are eagerly anticipated in order to provide clarity.

Percutaneous surgery for patients with MS-TN is less likely to provide pain relief than similar operations performed for patients with idiopathic TN. New trigeminal deficits did not correlate with better facial pain outcomes, supporting the concept that many patients with MS-TN have centrally mediated pain.

FAMOS recordings can discriminate fatigued MS patients from healthy controls. The data indicate that fatigued MS patients have vagus nerve dysfunction during cognitive tests and disturbed sympathovagal balance during stressful physical tests. [Box: see text].

Due to complexity of the animal models, pathological mechanisms are also examined in central nervous system cell culture systems including co-cultures, aggregate cultures and brain slice cultures. Here we critically review in vitro and in vivo models used to investigate MS. Since knowledge gained from these models forms the basis for the development of new therapeutic approaches for MS, we address the applicability of the models. Finally, we provide guidance for using and reporting animal studies with the aim of improving translational studies to the clinic.

In this small, uncontrolled pilot study, there was a significant improvement in fatigue in those who completed the study. Given the small sample size and completer rate, further evaluation of this multimodal therapy is warranted.

These data suggest that retrograde (trans-synaptic) axonal degeneration stops at the inner nuclear layer, a neuronal network capable of plasticity. In contrast, there seems to be no neuroplasticity of the primary visual cortex, rendering the structure vulnerable to anterograde (trans-synaptic) degeneration.

The number of patients becoming pregnant during fingolimod therapy remains small and does not permit firm conclusions to be drawn about fetal safety of fingolimod in humans. Given the known risks of teratogenicity in animals and the present data, women of childbearing potential should use effective contraception during fingolimod therapy and for 2 months after discontinuation.

The relapse rate in children with multiple sclerosis is higher than in adult-onset disease. Following acute treatment, recovery after the first attacks is usually excellent, but patients with childhood-onset multiple sclerosis reach permanent disability or enter the secondary progressive disease course 10 years younger than patients with adult-onset multiple sclerosis.

Currently, various pharmacological agents such as antiepielptics, non-steroidal anti-inflammatory agents, and even corticosteroids are used to suppress various painful conditions associated with MS. Non-pharmacological procedures such as massage therapy have also been used in the treatment of MS patients. The authors present a review of recent findings in pathophysiology and management of pain in MS patients.

We report the case of a woman with multiple sclerosis who developed a severe neurological condition following natalizumab (NZB) withdrawal and soon after fingolimod (FTY) initiation. FTY was started 3.5 months after a two-year NZB treatment. Fifteen days later, she suffered partial repetitive seizures followed by a tonicoclonic seizure. This was associated with attention difficulties and an increased asthenia. Brain MRI follow-up disclosed large demyelinating active lesions in favour of disease reactivation. This case suggests that FTY introduction may occur less than three months after NZB withdrawal.

Such cross-sectional data suggest that aerobic, balance, and resistance training might be avenues for improving CPS in this population. The authors report no conflicts of interest and thank Swathi Balantrapu, Jason Silberman, Stefanie Fitterer, and Rachel Japp for assistance in data acquisition.

Pain should be regularly assessed and appropriately treated to improve functioning and quality of life for patients with MS.

In this review, we will illustrate these fundamental issues by considering the previously proposed relationship between month of birth and multiple sclerosis.

Since methionine metabolism can be manipulated by supplementation of vitamins and amino acids, our data provide a rationale for novel ideas of preventive and therapeutic strategies in RRMS.

Current alcohol use was prevalent in this sample, and excessive use was associated with men, younger age, and more education. Reported drug use was minimal and associated with greater disability, more self-reported depression, but fewer anxiety symptoms.

The thicknesses, particularly of the innermost retinal layers (RNFL, GCC), were significantly related to the heterogeneous disease course in MS. The relative preservation of these layers in primary progressive and benign MS suggests rather limited susceptibility of the retina to neurodegeneration, which may be relevant for future neurodegenerative treatment trials employing OCT as a secondary outcome measure in primary progressive MS.

The results obtained in the current study demonstrate that absolute myelin water content can reliably be determined in a multicentre environment using standard MR sequences. The optimised protocol allows for a measurement of four quantitative parameters with full brain coverage in only 10 min. This might expedite a more widespread future use of quantitative MRI methods for clinical research and diagnosis.

The results demonstrate that paired analysis can strongly improve longitudinal correlation (from -0.148 to -0.303 in this sample) and may produce segmentations that are more sensitive to clinically relevant changes.

peptide-based immunotherapy could provide improved clinical status or life-long remission to MS patients. Substantiation of this premise requires a follow-up examination by other investigators and institutions with larger and more extensive clinical trials.

The changing landscape of voltage-gated calcium channels in neurovascular disorders and in neurodegenerative diseases.

Although cognitive performance as measured on the PASAT-3s does not correlate with a patient's perceived quality of life in a multivariate model, it remains an important predictor for the patient's usual activities.

By applying source-space analyses, this study provides a detailed topographical view of abnormal brain activity in MS patients, especially localized to occipital areas. Interestingly, poor cognitive performance was related to high resting-state alpha1 power indicating that changes in oscillatory activity might be of value as an objective measure of disease burden in MS patients.

OASIS obtains the estimated probability for each voxel to be part of a lesion by weighting each imaging modality with coefficient weights. These coefficients are explicit, obtained using standard model fitting techniques, and can be reused in other imaging studies. This fully automated method allows sensitive and specific detection of lesion presence and may be rapidly applied to large collections of images.

THESE FINDINGS SUGGEST THAT: i.) frequently applied and quantitatively evaluated DTI could be used as a sensitive imaging technique for detection of pathological processes associated with MS not detectable with conventional imaging strategies, ii.) temporary pathological processes in the "normal-appearing" thalamus may explain waxing and waning symptoms like episodes of central pain, and iii.) cross-sectional case examinations on (MS) patients with central pain should be performed to investigate how often thalamic alterations occur together with central pain.

The segmented results were also in close agreement with the corrected results as assessed by Bland-Altman and regression analyses. Finally, our lesion segmentation was validated using the MS lesion segmentation grand challenge dataset (MICCAI 2008).

The MS cohort was characterized by relatively low clinical disability and short disease duration. An automatic pipeline was developed for identifying images with poor quality and artifacts. The global and regional cortical thicknesses were determined using FreeSurfer software. Our results indicate significant cortical thinning in multiple regions in the MS patient cohort relative to the controls.

The speed of processing is impaired in MS patients. Consequently, more evaluation and planning treatment programs based of speed processing for memory in these patients are necessary for them because of the role of memory in daily activities of life.

Grey matter (GM) damage is one of the key factors associated with long-term accumulation of disability and cognitive impairment in MS.

The intervention significantly increased informed choice and relevant risk knowledge without negative side effects.

In our study, we found that both methods (VEP and GDx) can be used for the detection of optic nerve damage, but VEP was found to be superior in evaluating whole brain demyelinization and axonal degeneration. Both VEP and MRI, but not GDx, have an important role in monitoring disease progression in MS patients, independent of the ON history.

The decrease of NAA and increase of mI within white and gray matters in MS patients do not show a significant relationship with cognitive performance or fatigue.

Magnetic susceptibility of MS lesions increased rapidly as it changed from enhanced to nonenhanced, it attained a high susceptibility value relative to NAWM during its initial few years (approximately 4 years), and it gradually dissipated back to susceptibility similar to that of NAWM as it aged, which may provide new insight into pathophysiologic features of MS lesions.

In a cohort with different stages of MS, higher EA attenuated the negative effects of white matter lesion burden and third ventricle width (suggestive of thalamic atrophy) on cognitive performance. Actively enhancing cognitive reserve might thus be a means to reduce or prevent cognitive problems in MS in parallel to disease modifying drugs.

Grey matter damage - global and regional - has the potential to become a marker of disease activity, complementary to the currently used magnetic resonance markers (global brain atrophy and T2 hyperintense lesions). Furthermore, it may improve the prediction of the future disease course and response to therapy in individual patients and may also become a reliable additional surrogate marker of treatment effect.

results confirm the important role of the immune system and specifically B cells in MS and suggest that MS risk variants exert a gene regulatory role. Previous studies assessing MS risk variants in T cells may be missing important effects in B cells. Similar analyses in other immunological cell types relevant to MS and functional studies are necessary to fully elucidate how genes contribute to MS pathogenesis.

Fatigue management program outcomes for people with MS are moderated by age, gender, and impairment.

Our findings indicate a primary retinal pathology involving the inner nuclear layer in primary progressive MS. Results in eyes without history of optic neuritis suggest possible subclinical episodes of optic neuritis or retrograde trans-synaptic degeneration of retinal ganglion cells and their axons.

Diffusion histogram analysis provided stable surrogates of disability in MS and proved sensitive for monitoring disease progression during a median of 12 months. Advanced neuroaxonal pathology at baseline was indicative of an increased risk for sustained progression during a median of 12 months, independent of intercurrent relapses.

6MWT (6 minute walk test) performance in persons with MS was explained by balance confidence (ABC) and stair-climbing ability (FST). The ABC and FST may be practical clinical measures for explaining walking ability and determining risk for disablement in persons with MS.

Lesions in strategic brain WM tracts contribute to cognitive impairment in MS through a multisystem disconnection syndrome.

The purpose of this article is to review the literature on MS in childhood and adolescence, including the clinical presentation of the disease in this group, neuropathology and pathogenesis, magnetic resonance imaging findings, as well as neuropsychological and psychosocial considerations.

The complex array of interacting parenting difficulties was mirrored by a similarly multifaceted assortment of resources required to address the parenting difficulties. Findings delineate key interrelated parenting needs that can be targeted by services and policy development.

Patient empowerment and participatory medicine, as part of predictive, preventive, personalized and participatory medicine, are especially crucial in paving the way towards optimized healthcare in complex and chronic neurological diseases, such as multiple sclerosis.

New techniques such as PET imaging, magnetic resonance spectroscopy, magnetic resonance relaxometry, iron-sensitive imaging and perfusion MRI will also be overviewed, with their potential roles in monitoring disease course and activity.

Decrease of activity of antioxidant system in patients with secondary progression multiple sclerosis (SPMS) was more pronounced and remained unchanged after the treatment. This is consistent with the more severe clinical course of thise disease.

Chronically ill people are frequent users of complementary and alternative medicine (CAM). Some patients experience great benefits from their use of CAM, like patient "XX" in this case report. XX was diagnosed with secondary progressive multiple sclerosis in 2004 and has reported a "best case" after the use of Dr Birgitta Brunes' unconventional treatment.

There are several studies suggesting multiple sclerosis as one of the causes of symptomatic Restless Leg Syndrome (RLS).

Health professionals treating informal caregivers, as well as those treating people with MS, need to be aware of respite, support, and intervention programs available to MS caregivers and refer them to these programs, which could reduce the negative impact of caregiving on employment.

New instrument study to develop and validate a reliable, sensitive, and specific screening tool for patients with bladder problems related to MS

Aerobic exercise in people with multiple sclerosis Helps

significant improvements in fatigue were maintained over time, and cognitive performance improved or remained stable up to 48 weeks after initiation of natalizumab in MS patients with some degree of fatigue.

patients, migraines with aura strongly correlated with MS exacerbations, suggesting that they might be useful as a marker for flare-up onset.

findings show that relationship matters (RM) results in improved couple functioning and additional psychological health benefits for individuals with MS and their romantic support partners.

MS caregivers had significantly more burden than noncaregivers, and for some measures, even AD caregivers. The results reveal the hidden toll on those providing care for MS patients and highlight the need for health-care providers to recognize their burden so that appropriate measures can be implemented.

Training professionals to discuss emotional issues with clients and increasing collaboration with agencies that provide emotional support will facilitate a more holistic approach to care for MSers.

results showed no significant relationship between depression levels and interferon treatment. Significant associations were observed between depression and both age and disability status, with younger, more disabled patients tending to be more depressed.

Future studies could examine cost-effectiveness over extended periods of time (eg, 15-20 years) and more closely examine the cost-effectiveness of natalizumab (Tysabri) relative to the four primary DMDs.

Cognition and physical disability in predicting health-related quality of life in multiple sclerosis.

Physical assessments indicated that people with MS may be able to improve their fitness levels by using Wii Fit. Future studies should incorporate behavior change strategies to promote long-term use of Wii Fit, and explore whether individuals with more severe symptoms of MS can safely use Wii Fit.

Walking was ranked number 1 for both the first and second most common types of physical activity self-selected by people with MS, and it was ranked number 4 as the third most common type of self-selected physical activity. Collectively, 79% of the sample reported walking as a frequent form of self-selected physical activity in the previous year. Other notable types of physical activities self-selected by people with MS were gardening (44%), weight training (34%), bicycling (30%), and calisthenics (20%). This information may assist clinicians and practitioners in the development of physical activity programs and recommendations for people with MS.

The use of disease-modifying and symptomatic therapies in pregnancy is problematic and such treatments are normally discontinued.

Preventing brain volume loss may therefore have important clinical implications affecting treatment decisions, with several clinical trials now demonstrating an effect of disease-modifying treatments (DMTs) on reducing brain volume loss in MS.

Findings clearly indicate that slow postural responses to external perturbations in patients with MS contribute to disturbances in balance control, both during standing and walking.

The Memory, Attention, and Problem Solving Skills for Persons with Multiple Sclerosis (MAPSS-MS) intervention was feasible and well-accepted by participants. Given the large relative increase in use of compensatory strategies by the intervention group, it holds promise for enhancing cognitive function in persons with multiple sclerosis.

Acupuncture could only partly and temporarily reduce the pain in MSers

MS patients have higher depression and anxiety levels than control subjects. Anxiety and depressive symptoms also seem to progress according to the severity of the disease.
Here, we review different strategies for the characterization of the epigenome and how these strategies could be used to implement new studies to explore how alterations of chromatin architecture establish a dysregulated transcriptional state in the context of MS.

In the present article we illustrate the current hypotheses related to an environmental impact on the onset of PBC and MS as two representative conditions investigated with complementary approaches.

Our study suggests that executive dysfunction did not compromise the reliability and the validity of the self-reported quality of life (QoL) questionnaires.

Color vision is strongly associated with retinal thinning in multiple sclerosis.

Youth with MS are at risk of difficulties in behavioral and emotional health. Relations with parents emerged as a key factor influencing the emotional well-being of youth with MS, suggesting an important role for family-centered care in this population.

In patients with RRMS who have a poor response, switch to another disease modifying drug DMD may reduce the clinical activity of the disease.

Exposure to cigarette smoke is emerging as a viable environmental risk factor for MS that contributes to both increased disease susceptibility and more rapid disease advancement.

We developed a robot-assisted rehabilitation protocol, specifically designed to treat cerebellar and motor symptoms in subjects with Multiple Sclerosis

It is reported herein that the regulation of markers involved in demyelination and neuroprotection processes occurring during EAE, a well-established MS animal model, is gender- and time-dependent. These findings might contribute to gender- and phase disease-based therapy strategies.

Massage therapy could be more effective than exercise therapy. Moreover, the combination of massage and exercise therapy may be a little more effective than exercise therapy alone.

Disease status and sex interact to produce differences in the strength of functional connectivity from the posterior cingulate to the caudate and the left dorsal lateral prefrontal cortex.

Work disability is common in multiple sclerosis (MS) and cognitive disorder discriminates disabled from employed patients. These data provide preliminary support for the validity of online vocational monitoring in MS.

This review will discuss the evidence supporting the detrimental and beneficial aspects of macrophages/microglia in models of MS, provide a discussion of the mechanisms underlying the dichotomous roles, and describe a few therapies in clinical use in MS that impinge on the activity of macrophages/microglia.

Clear speech maximized peripheral and nonperipheral vowel space areas for speakers with PD and MS while also reducing rate and increasing vocal intensity. These results suggest that a speech style focused on increasing articulatory amplitude yields the most robust changes in vowel segmental articulation.

The broader the MS drug market becomes, the harder it will be for the clinician to help the patient decide which therapeutic strategy to opt for.

mortality is an unambiguously valid long-term outcome in randomized controlled trials. It usefully combines the net impact of treatment efficacy on longevity and adverse events, which may reduce it.

Investigation is required for better understanding of the potential of protective effects of antioxidants in cellular immunology of MS neurodegeneration.

memory deficits in MS are a result of deficits in initial learning; moreover, initial learning mediates the relationship between brain atrophy and subsequent retrieval, thereby supporting the core learning-deficit hypothesis of memory impairment in MS.

Implications for Rehabilitation All types of coping are associated positively with mental component of Quality of life. Coping focused on stopping negative emotions and thoughts seems to be very adaptive for patients with MS. This type of coping can help patients with chronic conditions when problem-focused coping can not effectively solve the problem.

There was no interaction between age and sex suggestive of an effect of reproductive aging on clinical or radiologic progression. Prospective analyses across the menopausal transition are needed.

Results confirm an association between spasticity severity and QoL in patients with MS. The correlation between 0-10 NRS scores and QoL was stronger than that between modified Ashworth scale scores and QoL.

Depression in MS is linked to atrophy of cortical regions located in the bilateral frontal lobes. A distributed pattern of GM atrophy contributes to the concomitant presence of depression and fatigue in these patients.

Long-term physical disability was independently linked with atrophy of the spinal cord and brain T2 lesion load, and less consistently, with brain grey matter atrophy. Combinations of spinal cord and brain MRI measures may be required to capture clinically-relevant information in people with MS of long disease duration.

Mental prediction of motor actions is not well preserved in MS where motor and cognitive functional changes are present. Differences in performing imagined task with dominant and non-dominant arm could be related to increased cognitive effort required for performing non-dominant movements.

A combined medical-community job-retention program is feasible in MS. However, patients do not generally wish to take advantage of job-retention services until an employment crisis develops.

The article presents recommendations for policymakers, service providers, and consumers to improve the bleak career development prospects for Americans with multiple sclerosis

current findings should raise the level of awareness of psoriasis among patients with MS, and of the need to consider a potential exacerbation of psoriasis by interferon-β therapy.

Absolute values of within-day variability on walking tests at fastest speed were independent of disability level and greater with short compared to long walking tests.

This review aims to investigate the epidemiology and pathophysiology of SD in male patients, provide an insight into multidisciplinary diagnostic and therapeutic approaches, and focus on the need of proper counseling.

While understanding mechanisms underlying DMT toxicities is incomplete, it is important to further develop this knowledge to minimize risk to patients and to ensure future therapies have the most advantageous benefit-risk profiles.

Access to care in rural areas and areas at a greater distance from a major medical center represent notable barriers to rehabilitation and other multiple sclerosis-related care.

The use of risk mitigation strategies can help clinicians tailor MS treatment recommendations for individual patients.

Conventional and emerging imaging techniques greatly inform our understanding of MS. These techniques are integral in diagnosis, in evaluating new treatments for MS, and for following patients in the clinical setting.

This article is meant to help clinicians recognize and treat this fascinating set of underrecognized phenomena in MS and perhaps save patients trips to the emergency department, extraneous testing, and ineffective intervention.

Although it is not yet possible to predict which treatment is best suited to a given patient, it is nevertheless important to have a perspective of the possible agents and their efficacy and safety, and a plan regarding how to use them in order to maximize benefit and minimize harm in controlling relapsing MS.

observations stress the importance of developing imaging techniques able to capture early inflammatory cortical demyelination in order to better understand the disease pathogenesis and to determine the impact of potential disease-modifying therapies on the cortex.

Tysabri (Natalizumab) recipients generally experienced improved health-related quality of life at 1-2 years. Natalizumab was generally well tolerated in pivotal trials. The only adverse events that were more frequent with natalizumab monotherapy than with placebo were fatigue and allergic reactions.

Axonal damage in ganglion cells of the visual pathway can be detected based on structural measures provided by OCT in MS patients and by the N95 component and N95/P50 index of PERG, thus providing good correlation between function and structure.

Sodium accumulation is present in progressive MS patients, more restricted to the motor system in PPMS and more widespread in SPMS. Local brain sodium accumulation appears as a promising marker to monitor patients with progressive MS.

a patient-reported questionnaire on satisfaction with communication of the multiple sclerosis diagnosis.

The current status and future challenges in the field of multiple sclerosis (MS) therapy

Impairments in visuospatial abilities are commonly reported in children and adolescents with multiple sclerosis (MS)

positive effect of exercise on the physical impact of MS and fatigue. The group nature of the classes may have contributed to the positive effects seen on the psychological impact of MS.

The prevalence of distinct types of orthostatic autonomic dysfunction in different phases of RRMS seems to be in direct correlation with the EDSS

The prevalence of falls is high in this population of persons with MS, and the impact of MS and of fatigue is greater in fallers.

Patients with MS have an increased risk of fractures. Caregivers should aim to optimize bone health in MS patients.

MSers frequently reported fatigue and mobility impairments as barriers to engagement in nutritional behaviors and often described family members as the "gatekeepers" for food selection and preparation

Slowed processing speed is the primary cognitive deficit in multiple sclerosis. Evaluation of anxiety and patient education about objective measures versus subjective perceptions of slowed processing speed may be helpful to MS patients who report significant cognitive slowing.

There is a global latitude gradient in MS prevalence, and incidence of MS is increasing (particularly in females).

Sleep disturbances in MS patients may occur independently from demographic and disease-related variables, but they are often influenced by the symptoms of MS and therapies used. Sleep disturbances may contribute to fatigue in the course of MS.

The diagnosis of early-onset MS is based on findings from a complete history and physical examination along with brain and spine imaging.

Depression is the commonest psychiatric manifestation but still remains largely underdiagnosed and undertreated.

Sexual Dysfunction, a frequent problem for MS patients, is associated with gender. Women reported more SD than men. Secondary SD symptoms were the most common complaints for both men and women. Nonetheless women had more secondary SD symptoms than men. The emotional dimension of SD is related with disability.

Patients carrying the HFE C282Y variant seem to have a worse prognosis. The HLA-DRB1*15 and PTPN22 1858T variants were associated with a better outcome in this population.

MS patients receiving immunomodulatory therapies other than interferon beta should be considered for a vaccine response analysis and perhaps be offered a second dose of the Flu vaccine, in cases of insufficient protection.

Depression and sleep disturbance in patients with MS is significantly correlated with associated fatigue

Findings highlight hope as an important protective coping resource for coping with MS

A positive patient-therapist alliance may relate to positive neuropsychological rehabilitation outcome in MS.

The prevalence of MS among Iranian immigrants to Canada is greater than the overall prevalence of MS in Iran by a factor of at least four

Detection of brain lesions disseminated in space and time by magnetic resonance imaging remains a cornerstone for the diagnosis of clinically definite multiple sclerosis.

Our data suggest that treatment with natalizumab results in broader changes in the T-cell immune repertoire beyond lymphocyte migration.

Gray matter dysfunction is involved early in MS, and also may be integral for the initial clinical presentation.

A new model could be used for design of future longitudinal studies and clinical trials, as well as for the evaluation of new therapies for MS

atDCS can be considered during neural rehabilitation to facilitate motor recovery in MS

The change in motion sensor output of ~800 steps/day appears to represent a lower-bound estimate of clinically meaningful change in free-living walking behavior in interventions of MS.

Deep immersion in creative activities may offer the experience of respite from worry about MS.

Existing trials of modafinil for fatigue and EDS associated with PD, MS, TBI and PPS provided inconsistent results. The majority of the studies had small sample sizes. Modafinil is not yet sufficient to be recommended for these medical conditions until solid data are available.

Those using bilateral assistance for gait have the highest prevalence of fallers, and those with walking limitations and not yet using an aid had the greatest prevalence of multiple falls.

Physical therapy has a positive impact on fatigue, and the MFIS seems to be a good outcome measure in ambulatory patients. The AI and MFIS seem to be not indicated for use in non-ambulatory patients.

only a small proportion of persons with MS are achieving adequate amounts of daily MVPA
We provide data using an objective physical activity measure and a large sample to indicate that only a small proportion of persons with MS are achieving adequate amounts of daily MVPA.

Perfectionism and physical disability predict depression in multiple sclerosis.
Our results suggest a means of reconciling inconsistent findings regarding physical disability and depression in MS and offer a potential target for psychotherapy.

Memory in multiple sclerosis is linked to glutamate concentration in grey matter regions.
The relationship between memory and glutamate concentration, which is unique to MS patients, suggests the reliance of memory on glutamatergic systems in MS.

Genetic burden in multiple sclerosis families.
Comparing with previous reference point for MS genetics (17 SNPs), we underlined the corrective consequences of the integration of the new findings from GWAS and meta-analysis.

A gene pathway analysis highlights the role of cellular adhesion molecules in multiple sclerosis susceptibility.
Filtering by a percentage of CAM genes up to 50% and rejecting enriched signals mainly driven by transcription factors, we highlighted five networks associated with MS susceptibility. One of them, constituted of ITGAL, ICAM1 and ICAM3 genes, could be of interest to develop novel therapeutic
targets.
Variability in the CIITA gene interacts with HLA in multiple sclerosis.
These findings further underscore the biological importance of HLA for MS risk.

Diagnosis and differential diagnosis of multiple sclerosis.
The diagnostic criteria for MS have been revised several times over the years, most recently giving rise to the McDonald 2010 criteria. The diagnosis of MS begins with a patient who presents with symptoms typical for the disease, termed the "clinically isolated syndrome," which most commonly affects the optic nerves, brainstem, or spinal cord. If the patient's symptoms and imaging are typical for MS, the clinician can then apply the appropriate diagnostic criteria. If atypical clinical or imaging findings are present, alternative etiologies must be pursued as appropriate

Levofloxacin-induced delirium in a patient suffering from schizoaffective disorder and multiple sclerosis.
Although levofloxacin-induced delirium is a rare adverse event, physicians should be aware of the occurrence of this serious, but potentially reversible CNS complication of levofloxacin, even in psychotic patients.

Spinal cord lesions and disability in Hispanics with multiple sclerosis.
These results suggest that LESCLs are a more important marker of disability in MS than OSMS and may be an early indicator of more aggressive disease in this population.

T-cell homeostasis in pediatric multiple sclerosis: old cells in young patients.
The homeostatic changes detected in the T-cell compartment in pMS are similar to those in adult-onset disease. With ratios between naive and memory T-cell subsets matching those of 20- to 30-years-older controls, signs of early thymic involution are already found in pMS, suggesting that an intrinsic compromise in thymic-dependent T-cell neogenesis might contribute to MS pathogenesis.

MAPT gene rs1052553 variant is not associated with the risk for multiple sclerosis.
These results suggest that MAPT rs1052553 polymorphism is not related with the risk for relapsing bout onset MS.

Strategies for protecting oligodendrocytes and enhancing remyelination in multiple sclerosis.
Combining immunomodulatory therapy with strategies to protect oligodendrocytes from further degeneration and enhance remyelination presents a very real means to improve clinical outcome for chronic progressive patients in the near future. Here we lay out a combination therapy approach to treating MS and survey the current literature on promising drug candidates potentially capable of mediating oligodendrocyte protection and enhancing remyelination.

Plasma osteopontin levels are associated with disease activity in the patients with multiple sclerosis and neuromyelitis optica.
These are the first results to suggest that plasma OPN in NMO patients may be a useful marker, playing an important role in inflammation, disease activity, and disease progression, as well as MS.

Comorbidities at multiple sclerosis diagnosis.
The mean age at request for ALD status for MS in patients with no comorbidity was 33.6 ± 7.2 years, whereas it was 36.9 ± 6.5 years in those with comorbidities. Comorbidities at MS notification are rare. Psychiatric disorders and diabetes were more frequent in MS patients than in the general population.

Personalization of multiple sclerosis treatments: using the chelation therapy approach.
The two personalized protocols presented here tend to confirm the hypothesis of TMP as an environmental or iatrogenic trigger for MS, especially when inadequate detoxification lies at the root. Cleansing by chelation therapy, properly understood, can be efficacious, especially bearing in mind the altered cellular water ratio.

Serum vitamin d levels in Indian patients with multiple sclerosis.
An age-matched control group of 202 patients who did not have a diagnosis of MS were included. In our study group 76.9 % had vitamin D level less than 20 ng/ml compared to 65.5 % of control group (p value of 0.019). Our study revealed a trend towards low vitamin D values in Indian MS patients.

Revised Diagnostic Criteria of Multiple Sclerosis.
The most recent 2010 McDonald criteria simplify requirements for DIS and DIT and may allow for an earlier diagnosis of MS from a single baseline brain MRI if there are both silent gadolinium-enhancing and nonenhancing lesions. Despite these important advances in the diagnosis of MS, some questions still remain regarding the application and the implications of the new criteria in the daily clinical practice and in clinical trials. Most importantly, thorough clinical evaluation and judgment along with careful differential diagnosis still remain the basics in the diagnosis of MS.

Gender differences in multiple sclerosis: induction of estrogen signaling in male and progesterone signaling in female lesions.
these findings suggest that there are gender differences in the CNS of MS patients that may affect lesion pathogenesis, that is, in males, estrogen synthesis and signaling are induced; whereas in females, progestogen synthesis and signaling are induced. These differences may represent contributing factors to gender differences in the prevalence and course of MS.

Retrospective US database analysis of persistence with glatiramer acetate vs. available disease-modifying therapies for multiple sclerosis: 2001-2010.
Persistence rates for GA were 80% for the 12-, 24- and 36-month time periods in contrast with the full DMT-treated cohorts whose persistence rates never exceeded 70.0%. Although there were more gaps in therapy of 15 days or more with all DMT over time, the proportion of GA users re-initiating therapy increased with follow-up contributing to the steady persistence. Therapy persistence is essential to achieve the desired outcomes in MS.

Implementation of the 'Sapere Migliora' information aid for newly diagnosed people with multiple sclerosis in routine clinical practice: a late-phase controlled trial.
This study shows that the entire IA is not superior to the booklet/website alone, and that both are comparable in efficacy to the intervention arm of the SIMS-Trial.

We know how to prescribe Tysabri (natalizumab) for multiple sclerosis, but do we know how to withdraw it?
The present study shows the very different manners in which expert neurologists from 14 MS units in Brazil stopped natalizumab in their patients. The authors concluded that pharmacovigilance on natalizumab must persist after the drug is withdrawn in order to have enough data for adequate recommendations.

[Treatment of relapses of multiple sclerosis (a review)].
Algorithms of using these medications for MS relapse treatment, data on plasmapheresis and perspectives of other therapeutic methods are reviewed.

Urinary dysfunction in women with multiple sclerosis: analysis of 61 patients from rio de janeiro, Brazil.
An urodynamic evaluation and simple urinalysis should be included in the routine testing during disease follow-up due to the high incidence of neurogenic bladder and other urologic complications.

Sun exposure and multiple sclerosis risk in Norway and Italy: The EnvIMS study.
Converging evidence from different measures underlines the beneficial effect of sun exposure on MS risk.

Patient subgroup analyses of the treatment effect of subcutaneous Betaseron (interferon β-1a) on development of multiple sclerosis in the randomized controlled REFLEX study.
The effect of sc IFN β-1a was not substantially influenced by baseline patient demographic and disease characteristics, or baseline presence/absence of McDonald 2010 MS.

Low DPP4 expression and activity in multiple sclerosis.
Our data indicate a putative role for DPP4 in MS pathophysiology and suggest that a deeper understanding of surface versus shed DPP4 biology is warranted.

Investigation of immune and CNS-mediated effects of Gilenya (fingolimod) in the focal delayed-type hypersensitivity multiple sclerosis model.
Fingolimod had different beneficial effects during different stages of DTH, reducing BBB breakdown and lesion development/brain tissue damage whilst reducing lymphocyte recruitment when BBB breakdown was apparent, but reducing demyelination independent of lymphocyte infiltration behind an intact BBB. These results suggest a direct CNS effect of fingolimod in this model.

MR venography in children and adolescents with multiple sclerosis does not show increased prevalence of extracranial veins anomalies.
We found no evidence to suggest that MS children and adolescents have more extracranial veins anomalies than healthy patients. Considering the risk of such treatment, endovascular interventions should be discourage.

Autophagy-related gene16L2, a potential serum biomarker of multiple sclerosis evaluated by bead-based proteomic technology.
our results suggest that Atg16L2 may play an important role in T cells autophagy and serve as a potential biomarker to predict clinical relapse of MS.

Mobilization of progenitors in the subventricular zone to undergo oligodendrogenesis in the Theiler's virus model of multiple sclerosis: implications for remyelination at lesions sites.
These data suggest that the inflammation induced by the Theiler's virus not only provokes strong preclinical demyelination but also, it is correlated with oligodendrocyte generation in the adult SVZ, cells that along with resident progenitor cells contribute to the prompt remyelination observed in the corpus callosum.

Study of fatigue frequency and its association with sociodemographic and clinical variables in patients with multiple sclerosis.
Fatigue was a frequent sign in studied MS patients, and was associated with type of disease, interferon, gender, and duration of disease. There was no association between fatigue and age, education, and marital state. It is important to pay more attention to fatigue in MS patients, and use quantitative tools for its assessment.

Trunk muscle activity during walking in persons with multiple sclerosis: The influence of body weight support.
Based on the results, it is recommended to decrease the percentage BWS as fast as possible beneath 30% BWS.

Caregiver burden, quality of life and walking ability in different disability levels of multiple sclerosis.
The impairments on disability level, walking and QOL of MS patients were related to OQL declines and increased burden of their caregivers. Therefore, it may be important to provide acceptable education and support strategies with individual intervention while defining the needs and goals of the MS patients and their caregivers to improve the rehabilitation success.

Intrathecal immune reset in multiple sclerosis: Exploring a new concept.
We review the literature in support of the rationale for treating MS with intrathecal drugs dedicated to clearing the local immune response. Since many targets are involved, achieving this goal may require a combination of monoclonal antibodies targeting each cell sub-type. Hope might be rekindled with a one-shot intrathecal multi-drug treatment in progressive MS.

Protective and Detrimental Roles for Regulatory T Cells in a Viral Model for Multiple Sclerosis.
The exacerbation of acute disease was associated with increased virus titers and decreased immune cell recruitment in the CNS. Therapeutic iTreg treatment reduced inflammatory demyelination during chronic disease. Immunologically, iTreg treatment increased interleukin-10 production from B cells, CD4⁺ T cells, and dendritic cells, which may contribute to the decreased CNS inflammation.

The challenges of measuring disability accumulation in relapsing-remitting multiple sclerosis: evidence from interferon beta treatments.
Measuring effects on disability accumulation in relapsing-remitting MS is also difficult in clinical trial situations because of the protracted evolution of the disease and the ethical and practical implications of long-term placebo-controlled trials, which may have implications for clinicians considering treatment options. Despite these issues, interferon-beta therapies have decades of follow-up data, with which it is possible to evaluate prognostic factors for the accumulation of disability in relapsing-remitting MS.

[Teriflunomide is a new peroral disease-modifying drug for multiple sclerosis (a review)].
The review presents the data concerning the mechanism of action, pharmacokinetics as well as results of clinical studies. Teriflunomide has received the regulatory approval in the USA, Argentina, Australia, South Korea, Chile and EU. The submission of a regulatory dossier is performed in Russia.

[Smoking as a risk factor of development and progression of multiple sclerosis (a review and experimental data)].
The primary progressive MS course was more often observed in the group of smoking patients. The more favorable prognosis in terms of sensitivity and visual symptoms of disease onset were found in nonsmokers.Forms with a late onset prevailed in smokers.

Confounding in association studies: month of birth and multiple sclerosis.
In this review, we will illustrate these fundamental issues by considering the previously proposed relationship between month of birth and multiple sclerosis. This much discussed but false positive association serves as a reminder of just how heterogeneous even easily measured environmental risk factors can be, and how easily case control studies can be confounded by seemingly minor differences in ascertainment.

Genetic variants of homocysteine metabolism and Multiple Sclerosis: A case-control study.
Since methionine metabolism can be manipulated by supplementation of vitamins and amino acids, our data provide a rationale for novel ideas of preventive and therapeutic strategies in RRMS.

Alcohol and substance use in multiple sclerosis.
Current alcohol use was prevalent in this sample, and excessive use was associated with men, younger age, and more education. Reported drug use was minimal and associated with greater disability, more self-reported depression, but fewer anxiety symptoms.

Disease course heterogeneity and OCT in multiple sclerosis.
The thicknesses, particularly of the innermost retinal layers (RNFL, GCC), were significantly related to the heterogeneous disease course in MS. The relative preservation of these layers in primary progressive and benign MS suggests rather limited susceptibility of the retina to neurodegeneration, which may be relevant for future neurodegenerative treatment trials employing OCT as a secondary outcome measure in primary progressive MS.

Delay in the diagnosis of multiple sclerosis in Croatia.
A specifically designed demyelinating disease diagnostic clinic offers a better service than other existing models in the diagnosis and management of MS patients.

Challenges in multiple sclerosis; how to define occurence of progression.
In patient with present cortical lesions even in earliest stages of MS depending on severity of grey matter involvement more efficacious therapy like second or even third line therapy should start.

Pseudobulbar affect (PBA): prevalence and management.
A recent therapeutic breakthrough occurred with the approval by the Food and Drug Administration of a dextromethorphan/quinidine combination as being safe and effective for treatment of PBA. Side effect profiles and contraindications differ for the various treatment options, and the clinician must be familiar with these when choosing the best therapy for an individual, particularly elderly patients and those with multiple comorbidities and concomitant medications.

The relation between Vitamin D status with fatigue and depressive symptoms of multiple sclerosis.
More interventional studies for determining the role of Vitamin D supplements in this regard is recommended.

Optic neuritis is associated with inner nuclear layer thickening and microcystic macular edema independently of multiple sclerosis.
This study shows that both MME and INL thickening occur in various neuro-inflammatory disorders associated with ON. We also demonstrate that detection and analysis of MME by OCT is not limited to B-scans, but also possible using SLO images.

Presence and significant determinants of cognitive impairment in a large sample of patients with multiple sclerosis.
Our results corroborate the evidence about the presence and the nature of cognitive impairment in a large sample of patients with MS. Furthermore, our findings identify significant clinical and demographic determinants of cognitive impairment in a large sample of MS patients for the first time. Implications for further research and clinical practice were discussed.

Body composition in multiple sclerosis.
Body mass index values, the effect of spasticity, the increased number of drugs used and the relationship between skeletal muscle and bone which interacts with impaired motor function leading to body composition alterations in multiple sclerosis are reviewed.

Pathological correlates of magnetic resonance imaging texture heterogeneity in multiple sclerosis.
Texture analysis performed on routine clinical magnetic resonance images may be a potential measure of tissue integrity. Tissues with more severe myelin and axonal pathology are associated with greater texture heterogeneity.

Modeling of cognitive impairment by disease duration in multiple sclerosis: a cross-sectional study.
The rates of cognitive impairment in this large sample of MS patients were lower than previously reported and severe cognitive impairment was evident only in a relatively small group of patients. Cognitive impairment differed significantly from expected normal distribution only at five years from onset, suggesting the existence of a therapeutic window during which patients may benefit from interventions to maintain cognitive health.

Cognitive and clinical dysfunction, altered MEG resting-state networks and thalamic atrophy in multiple sclerosis.
These findings illustrate the relationship between thalamic atrophy, altered functional connectivity and clinical and cognitive dysfunction in MS, which could serve as a bridge to understand how neurodegeneration is associated with altered functional connectivity and subsequently clinical and cognitive decline.

Cerebral venous thrombosis after high dose steroid in multiple sclerosis: a case report.
We report a case of 32-year-old woman with no previous history of recent LP, who developed

Plasma levels of neuron specific enolase quantify the extent of neuronal injury in murine models of ischemic stroke and multiple sclerosis.
Plasma NSE is a valid and simple experimental biomarker that allows quantifying the degree of neuronal injury in a non-invasive approach.

Vitamin d3 concentration correlates with the severity of multiple sclerosis.
Our findings not only further disclose the lower level of vitamin D in MS patients in comparison with healthy controls, but also support the association between vitamin D and disease severity in MS.

Oropharyngeal dysphagia in patients with multiple sclerosis: do the disease classification scales reflect dysphagia severity?
Dysphagia is common in MS patients, especially in those with greater impairment of neurological functions.

1H magnetic resonance spectroscopy in multiple sclerosis and related disorders.
In this review article we present the main brain and spinal cord (1)H-MRS features in MS, their diagnostic value in differentiating pseudotumoral demyelinating lesions from primary brain tumors, and their relationship with clinical variables. Last, some data related to the use of (1)H-MRS in therapeutic trials is presented.

Multitasking in multiple sclerosis: can it inform vocational functioning?
Multitasking ability may play an important role in performance at work for individuals with MS. Given that multitasking was associated with vocational functioning, future efforts should assess the usefulness of incorporating multitasking ability into rehabilitation planning.

Hunting for autoantibodies in multiple sclerosis.
The identification of these targets, to better understand the pathogenesis and develop specific immune therapies, has been the focus of MS research during the last decades.

Coexistence of multiple sclerosis and ankylosing spondylitis: report of two cases.
The remaining effective therapeutic options for MS are either contradictory for AS (interferon-β), have no definite data regarding their safety/efficacy in AS (glatiramer acetate, azathioprine, natalizumab, fingolimod), or their efficacy in MS-AS is associated with increased treatment risks (rituximab). Any of these proposed treatments may require active patient's informed consent.

The nature of verbal memory impairment in multiple sclerosis: a list-learning and meta-analytic study.
Deficient acquisition may result from demyelination in relevant white matter tracts that reduces encoding efficiency as a result of impaired speed of information processing.

Altered likelihood of brain activation in attention and working memory networks in patients with multiple sclerosis: An ALE meta-analysis.
With this meta-analytic approach previous results of investigations examining cognitive function using fMRI are summarized and compared. Therefore a more general view on cognitive dysfunction in this heterogeneous disease is enabled.

Improved Characterization of Visual Evoked Potentials in Multiple Sclerosis by Topographic Analysis.
Sensitivity was increased in tVEP versus cVEP: 72 % versus 60 % for diagnosis, and 88 % versus 77 % for hON. The advantage of tVEP was most pronounced in pathological VEPs, in which cVEPs were often ambiguous. TVEP is a reliable, valid, and sensitive method of objectively quantifying pathological VEP in particular. In combination with other EP modalities, tVEP may improve the monitoring of disease course in MS.

The relationship of cognitive impairment with neurological and psychiatric variables in multiple sclerosis patients.
Conclusion: Psychomotor speed and memory were primarily impaired in MS patients and CI was closely associated with clinical aspects of MS rather than depression and anxiety.

Different mechanisms of inflammation induced in virus and autoimmune-mediated models of multiple sclerosis in C57BL6 mice.
The presence of dual mechanisms of demyelination may be responsible for the failure of immunosuppression to promote long-term remission in many MS patients.

Change in quality of life and predictors of change among patients with multiple sclerosis: a prospective cohort study.
Our study suggests that baseline demographic and clinical characteristics could be applied as prognostic markers of the HRQOL for patients diagnosed with MS.

Anti Mycobacterium avium subsp. paratuberculosis heat shock protein 70 antibodies in the sera of Sardinian patients with multiple sclerosis.
Our study confirms that mycobacterial HSP70 might be involved in MS, and provides another piece of evidence sustaining the role played by MAP in MS in the context of Sardinian population

Circulating dendritic cells of multiple sclerosis patients are proinflammatory and their frequency is correlated with MS-associated genetic risk factors.
DCs in MS are in a pro-inflammatory state, have a migratory phenotype and are affected by genetic risk factors, thereby contributing to pathogenic responses.

MitoQ, a mitochondria-targeted antioxidant, delays disease progression and alleviates pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis.
These protective effects are likely via multiple mechanisms, including the attenuation of the robust immune response. These results suggest that MitoQ may be a new candidate for the treatment of MS.

Frequency, characteristics and consequences of falls in multiple sclerosis: findings from a cohort study.
People with MS experience high numbers of falls, with associated injuries. Falls occur during a wide range of activities, reflecting their potential impact on daily life. Evaluating the characteristics of individuals who experience frequent near falls but few actual falls may be valuable for research and clinical practice.

Recent progress in omics-driven analysis of MS to unravel pathological mechanisms.
In this review, we will discuss the recent findings of the genomic, transcriptomic and proteomic fields for MS and aim to make a unifying model.

Active cognitive reserve influences the regional atrophy to cognition link in multiple sclerosis.
Results suggest that recreational activities protect against brain atrophy's detrimental influence on cognition.

Immunomodulatory and therapeutic effects of Hot-nature diet and co-supplemented hemp seed, evening primrose oils intervention in multiple sclerosis patients.
The co-supplemented hemp seed and evening primrose oils with Hot-nature diet have beneficial effects in improving of clinical score in RRMS patients which were confirmed by immunological findings.

Identifying Symptom Co-Occurrence in Persons With Multiple Sclerosis.
These preliminary findings indicate co-occurrence of several disabling symptoms from the overall self-report MS-Related Symptom Scale and 3-month recall. This information will guide health care professionals in developing targeted interventions and improve outcomes.

Body-worn sensors capture variability, but not decline, of gait and balance measures in multiple sclerosis over 18 months.
the moderately disabled MS cohort demonstrated greater variation in between-visit performance than did the less disabled MS cohort or controls (Bonferroni-corrected p<0.05). Variability may be a key indicator of worsening gait and balance disability in MS.

Cost effectiveness of oromucosal cannabis-based medicine (Sativex®) for spasticity in multiple sclerosis.
Using a willingness-to-pay threshold of £30 000 per QALY, Sativex® appears unlikely to be considered cost effective by UK funders of healthcare for spasticity in MS. This is unfortunate, since it appears that Sativex® use is likely to benefit some patients in the management of this common consequence of MS.

Randomized controlled trial of a teleconference fatigue management plus physical activity intervention in adults with multiple sclerosis: rationale and research protocol.
The proposed study is novel, in that it represents a multi-disciplinary effort to merge two promising lines of research on MS: fatigue management and physical activity promotion. Collectively, the proposed study will be the largest randomized controlled trial to examine the effects of a lifestyle physical activity intervention in people with MS.

The clinical overlap of multiple sclerosis and headache.
The recent development of novel treatment options for MS requires practitioners to be aware of polypharmacy and potential drug interactions.

Occupational attainment as a marker of cognitive reserve in multiple sclerosis.
Information regarding an individual's occupation is easily acquired and may serve as a useful proxy for cognitive reserve in clinical settings.

Remyelination therapy for multiple sclerosis.
The next frontier in MS therapeutics will supplement immunomodulation with agents that directly foster myelin repair, with aims to delay disease progression and recover lost neurological functions.

Treatment with 4-aminopyridine improves upper limb tremor of a patient with multiple sclerosis: a video case report.
The finding calls for further prospective studies to determine the usefulness of 4-aminopyridine or its sustained-release form dalfampridine in treating patients with tremor and MS.

Low degree of cortical pathology is associated with benign course of multiple sclerosis.
Our data confirmed that a significantly milder cortical pathology characterizes the most favorable clinical course of MS. Measures of focal and diffuse grey matter should be combined to increase the accuracy in the identification of a benign MS course.

Cerebrospinal fluid biomarkers of β-amyloid metabolism in multiple sclerosis.
We confirmed and extended our previous observations of altered CSF sAPP and Aβ peptide levels in MS patients. We found that natalizumab therapy may be able to counteract the altered APP metabolism in MS. The CSF Aβ isoform distribution was found to be distinct in SPMS patients, as compared to the controls.

Use and acceptance of electronic communication by patients with multiple sclerosis: a multicenter questionnaire study.
The majority of MS patients seen at specialist centers already use modern communication technology regularly. New forms of electronic communication appear to have high levels of acceptance for exchanging information about MS between patients and health care providers. Such methods should be integrated into eHealth services such as electronic health records and patient relationship management systems.

Cortical lesion load associates with progression of disability in multiple sclerosis.
the combination of grey and white matter parameters gives a more comprehensive view of multiple sclerosis pathology and allows a better understanding of the progressive phase of the disease, which, however, seems more related to cortical damage than to subcortical white matter changes.

Brain atrophy at onset and physical disability in multiple sclerosis.
Brain atrophy rates during the first year of disease were predictive of disease progression in our population.

Influence of cognitive function on speech and articulation rate in multiple sclerosis.
Self-generated speech, in this study, was not found to relate more strongly to cognitive tests than simple reading. Implications for further research are discussed.

Extra-hippocampal subcortical limbic involvement predicts episodic recall performance in multiple sclerosis.
These findings indicate that structural and ultrastructural alterations in subcortical limbic components beyond the hippocampus predict performance of episodic recall in MS patients with mild memory dysfunction.

Daclizumab therapy for multiple sclerosis.
In conclusion, daclizumab therapy, which is currently in phase III testing for inflammatory MS, has a unique MOA that does not limit migration of immune cells into the intrathecal compartment, but rather provides multifactorial immunomodulatory effects with resultant inhibition of MS-related inflammation.

Effectiveness of energy conservation treatment in reducing fatigue in multiple sclerosis: a systematic review and meta-analysis.
The systematic review results provide evidence that in the short-term, ECM treatment can be more effective than no treatment (waiting controls) in reducing the impact of fatigue and in improving 3 QoL scales-role physical, social function, and mental health-in fatigued patients with MS. More RCTs that also study long-term results are needed.

HERV-W polymorphism in chromosome X is associated with multiple sclerosis risk and with differential expression of MSRV.
Our present work supports the hypothesis of a direct involvement of HERV-W/MSRV in MS pathogenesis, identifying a genetic marker on chromosome X that could be one of the causes underlying the gender differences in MS.

Isolated bilateral horizontal gaze palsy as first manifestation of multiple sclerosis.
This is a unique video report of isolated bilateral horizontal gaze palsy as the initial manifestation of demyelinating CNS disease, which lead to definite diagnosis of relapsing remitting multiple sclerosis.

Reducing survey burden: feasibility and validity of PROMIS measures in multiple sclerosis.
Our results provide evidence of the construct validity of PROMIS for use with MS patients. Several aspects of the PROMIS CATs made them an important resource, including: (a) less time was required to complete them; (b) missing data was reduced; and (c) the automatic scoring referenced the general population. Our findings support the use of PROMIS in MS research and may have broader implications for clinical care, as well.

Central nervous system lymphoma initially diagnosed as tumefactive multiple sclerosis after brain biopsy.
This led to a revised diagnosis of primary central nervous system lymphoma (PCNSL). Because PCNSL mimics MS both clinically and radiologically, PCNSL is difficult to diagnose. Performing repeated brain biopsies may therefore be required when PCNSL is strongly suspected.

Estimating time to disease progression comparing transition models and survival methods--an analysis of multiple sclerosis data.
This article compares the transition model approach to survival analysis methods, and discusses the differences in the interpretations of the estimated parameters. It applies both models to data obtained from two phase 3 clinical trials and finds that both yield positive effects for the new treatment compared to placebo, and provide similar estimates for the probability of disability progression over time. The transition model enables calculation of covariate-specific transition matrices that describe the short-term effect of treatment and other covariates on the disability process.

Quantification of gait kinematics and walking ability of people with multiple sclerosis who are new users of functional electrical stimulation.
The acute application of functional electrical stimulation resulted in an orthotic effect through a change in ankle and knee kinematics and increased walking speed over a short distance in people with multiple sclerosis who experience foot drop.

Perceived and actual arm performance in multiple sclerosis: relationship with clinical tests according to hand dominance.
Real-life arm performance is decreased in wheelchair-bound MS patients and can be best predicted by measures on 'body functions & structures' level and fine motor control. Hand dominance influenced the magnitude of relationships.

Vagus somatosensory-evoked potentials are prolonged in patients with multiple sclerosis with brainstem involvement.
A subgroup of patients with signs of brainstem affection showed a trend for longer P1 latencies (F(1,11)=5916, P=0.033) as compared with the group without. We take this result as further hint for VSEP to be generated at brainstem level which needs confirmation in larger-scale studies and other brainstem-affecting diseases. The method could be suitable for the demonstration of the involvement of differential brainstem nuclei in various neurodegenerative diseases.

Resequencing and fine-mapping of the chromosome 12q13-14 locus associated with multiple sclerosis refines the number of implicated genes.
We concluded that our pools enriched with Nimblegen's solution phase hybridization capture had better sensitivity to detect true variants than the pools enriched with long-range PCR, whilst specificity was better in the long-range PCR-enriched pools compared with solution phase hybridization capture enriched pools; this result has important implications for the design of future fine-mapping studies.

Evaluation of the effects of reflexology on quality of life and symptomatic relief in multiple sclerosis patients with moderate to severe disability; a pilot study.
The results do not support the use of reflexology for symptom relief in a more disabled multiple sclerosis population and are strongly suggestive of a placebo response. This study demonstrates, however, that reflexology can be delivered and is well tolerated by people who are moderately to severely affected by multiple sclerosis.

Early treatment with high-dose interferon beta-1a reverses cognitive and cortical plasticity deﬁcits in multiple sclerosis.
These results suggest that cognitive and synaptic plasticity deﬁcits may be rescued during high-doseIFN beta-1a treatment in newly-diagnosed RRMS patients with Gd+ lesions.

A case of prolonged delayed postdural puncture headache in a patient with multiple sclerosis exacerbated by air travel.
This case report highlights a case of a young female patient who suffered from a severe incapacitating PDPH headache during high-altitude flight with a commercial jet.

Multiple sclerosis and the blood-central nervous system barrier.
The MS drug natalizumab, a humanized monoclonal antibody against α4-β1-integrin, blocks this interaction and thus reduces the movement of immune cells into the CNS. This paper further elaborates on the role of the BCNSB in the pathophysiology and pharmacotherapy of MS

Cognitive behavioural therapy for the treatment of depression in people with multiple sclerosis: a systematic review and meta-analysis.
CBT can be an effective treatment for depression in MS. Further research should explore optimal durations and modalities of treatment for patients with different characteristics.

Postpartum relapses increase the risk of disability progression in multiple sclerosis: the role of disease modifying drugs.
Our findings show an increased risk of postpartum relapses and disability accrual in women with higher disease activity before and during pregnancy. Since it may reduce the risk of postpartum relapses, early DMD resumption should be encouraged, particularly in patients with more active disease.

Sleep-disordered breathing in multiple sclerosis.
These data suggest a predisposition for obstructive sleep apnea and accompanying central apneas among patients with MS, particularly among those with brainstem involvement.

The efficacy and safety of daclizumab and its potential role in the treatment of multiple sclerosis.
Ongoing phase III clinical trials in RRMS are expected to provide definite information on the efficacy and safety of daclizumab and to determine its place in the fast-growing armamentarium of MS therapies.

Social Cognitive Predictors of Physical Activity in Relapsing-Remitting Multiple Sclerosis.
This prospective study suggests that self-efficacy, functional limitations, and goal setting might represent modifiable targets of behavioral interventions for increasing physical activity among persons with RRMS.

Cranberry versus placebo in the prevention of urinary infections in multiple sclerosis: a multicenter, randomized, placebo-controlled, double-blind trial.
Taking cranberry extract versus placebo twice a day did not prevent UTI occurrence in MS patients with urinary disorders. Trial Registration NCT00280592.

Bi-exponential diffusion signal decay in normal appearing white matter of multiple sclerosis.
These data demonstrated that the myelin content of the white matter affects diffusion in relapsing-remitting subtype of multiple sclerosis that is possibly a consequence of the shift between different water fractions.

Late-onset clozapine-induced agranulocytosis in a patient with comorbid multiple sclerosis.
This case highlights the need for frequent blood count monitoring on clozapine even after the initial 6 months of starting treatment especially in patients with a past history of drop in white blood cell counts as well as with a comorbid autoimmune disorder.

Anorectal dysfunction in multiple sclerosis: a systematic review.
Anorectal dysfunction is a common manifestation in MS that significantly affects quality of life. Therapies are at best moderately effective and often cumbersome, highlighting the need for simple and more helpful interventions.

MRI correlates of disability in African-Americans with multiple sclerosis.
By studying a quite large sample of well demographically and clinically matched CA and AA patients with a homogeneous MRI protocol we showed that higher lesion accumulation, rather than pronounced brain volume decrease might explain the early progress to ambulatory assistance of AAs with MS.

Efficacy of statins in combination with interferon therapy in multiple sclerosis: a meta-analysis.
A meta-analysis revealed that the addition of statins to interferon therapy did not significantly influence the relapse risk, disease progression, or EDSS scores in patients with RRMS.

Oligoclonal bands in the cerebrospinal fluid and increased brain atrophy in early stages of relapsing-remitting multiple sclerosis.
IgG-OB in the CSF was related to neurodegeneration magnetic resonance (MR) markers in early RRMS.

Investigation of the relationship between vitamin D and bone mineral density in newly diagnosed multiple sclerosis.
This is compatible with shared etiologic or pathogenic factors in MS and osteopenia/osteoporosis, and calls for an active approach to optimize bone health in early stages of MS.

Internal jugular veins out flow in patients with multiple sclerosis:a catheter venography study.
There is a high prevalence of abnormal delayed flow through IJVs in patients with MS. Venous angioplasty was effective in only a minority of patients with SDF.

A simple score for estimating the long-term risk of fracture in patients with multiple sclerosis.
This is the first clinical risk score for fracture risk estimation involving MS as a risk factor.

A PROMIS fatigue short form for use by individuals who have multiple sclerosis.
The PROMIS-Fatigue(MS) was derived to have content validity in MS samples. The validity of the measure was further supported by the ability of PROMIS-Fatigue(MS) items to discriminate among groups expected to differ in levels of fatigue. We recommend its use in measuring the fatigue of individuals with MS.

Subjective and perceptual analysis of voice quality and relationship with neurological disfunction in multiple sclerosis patients.
Significant number of MS patients experienced voice problems. We did not establish any significant correlation between the intensity of the voice disorders and EDSS, except between EDSS and asthenia item of the GRBAS scale. The patients with low EDSS may have serious voice problems and vice versa.

Treatment of multiple sclerosis and neuromyelitis optica in children and adolescents.
There are limited studies informing the use of these medications in children with NMO. This review provides a comprehensive analysis of the published literature on therapeutic interventions in children and adolescents with MS and NMO.

Working memory performance of early MS patients correlates inversely with modularity increases in resting state functional connectivity networks.
given the early stage of the MS patients included in this study, network modularity could be considered a promising biomarker for detection of earliest-stage brain network reorganization, and possibly of disease progression.

Severe deterioration of newly diagnosed Takayasu arteritis in a patient re-treated with interferon beta-1α for concomitant longstanding multiple sclerosis.
An evaluation using Doppler ultrasound of the supra-aortic vessels revealed severe stenosis of the left axillary artery. The IFN beta-1α was withdrawn, with prompt clinical and laboratory improvement of the vasculitis.

The importance of physician-patient relationship for improvement of adherence to long-term therapy: data of survey in a cohort of multiple sclerosis patients with mild and moderate disability.
Our conclusion reveals that, to improve the adherence to long-term therapy and the perceived utility of treatment, a particular attention should be devoted to physician-patient relationship.

B cells undergo unique compartmentalized redistribution in multiple sclerosis.
Notably, BC-redistribution closely resembles alterations detectable in systemic autoimmunity associated with active RA and impacts BC-function Together with unique effects of DMDs on BC-homeostasis these findings underline the important role of BC in MS.

[Recent progress in multiple sclerosis research: astrocytopathy in demyelinating diseases].
Since a similar loss of AQP4 without perivascular deposition of immunoglobulin and complement is also observed in autopsied CNS tissues from NMO and MS cases, I consider that autoantibody-independent astrocytopathy may widely occur in human CNS demyelinating diseases, including Baló's disease, MS and NMO.

Multiple Sclerosis Severity Scale and whole-brain N-acetylaspartate concentration for patients' assessment.
Since the WBNAA loss rate is similar in both phenotypes, the only difference between them is their clinical classification, characterized by MSSS and EDSS. This may indicate that 'benign' MS probably reflects fortuitous sparing of clinically eloquent brain regions and better utilization of brain plasticity.

Exploring Physical Activity in Women with Multiple Sclerosis: Associations with Fear of Falling and Underlying Impairments.
Future physical activity of women with multiple sclerosis was best predicted by FoF independent of physical and mental functioning. Increased FoF was associated with greater lower extremity strength asymmetry and decreased limits of stability rather than with the experience of falls.

SIRT1 is decreased during relapses in patients with multiple sclerosis.
we investigated the role of SIRT1 in the expression of FasL and found a significant increase in FasL expression and apoptosis after inhibition of SIRT1 expression. Our data suggest that SIRT1 may represent a biomarker of relapses and a potential new target for therapeutic intervention in MS.

Iron chelation and multiple sclerosis.
More recently developed chelators, deferasirox and deferiprone, are more desirable for possible use in MS given their oral administration, and importantly, deferiprone can cross the blood-brain barrier. However, experiences from other conditions indicate that the potential for adverse events during chelation therapy necessitates close patient monitoring and a carefully considered administration regimen.

Anatomical distribution of central nervous system plaques in multiple sclerosis: an Iranian experience.
The specificities of conventional and DW MRI were 86.6 and 96.6%, respectively, so DW MRI may detect lesions that are not obvious by routine methods.

The etiology of multiple sclerosis: genetic evidence for the involvement of the human endogenous retrovirus HERV-Fc1.
We have investigated the role of human endogenous retroviruses in multiple sclerosis by analyzing the DNA of patients and controls in 4 cohorts for associations between multiple sclerosis and polymorphisms near viral restriction genes or near endogenous retroviral loci with one or more intact or almost-intact genes.

The endocannabinoid anandamide downregulates IL-23 and IL-12 subunits in a viral model of multiple sclerosis: evidence for a cross-talk between IL-12p70/IL-23 axis and IL-10 in microglial cells.
This suggests that by altering the cytokine network, AEA could indirectly modify the type of immune responses within the CNS. Accordingly, pharmacological modulation of endocannabinoids might be a useful tool for treating neuroinflammatory diseases.

Alcohol as a Modifiable Lifestyle Factor Affecting Multiple Sclerosis Risk.
Our findings may have relevance for clinical practice because they give no support for advising patients with MS to completely refrain from alcohol.

Higher Circulating Levels of Chemokine CCL20 in Patients with Multiple Sclerosis: Evaluation of the Influences of Chemokine Gene Polymorphism, Gender, Treatment and Disease Pattern.
These results showed higher levels of CCL20 in patients that represent that the chemokine may play an important role in the pathogenesis of MS. The rs6749704 polymorphism was an associated SPMS pattern. The levels of CCL20 were not influenced by gender, disease pattern and treatment.

Cortical thickness at the time of the initial attack in two patients with paediatric relapsing-remitting multiple sclerosis.
Cortical atrophy is already present at the time of onset of MS. Studies with larger patient populations that have a more homogenous clinical presentation could identify the time of onset of cortical atrophy and use this parameter as a prognostic and/or treatment marker of MS.

Clinical experience with THC:CBD oromucosal spray in patients with multiple sclerosis-related spasticity.
No new safety signals were noted with THC:CBD spray during the evaluation period. In this routine clinical practice setting at an MS clinic in Germany, THC:CBD spray was effective and well tolerated as add-on therapy or as monotherapy in a relevant proportion of patients with resistant MS spasticity.

Multicontrast MR imaging at 7T in multiple sclerosis: highest lesion detection in cortical gray matter with 3D-FLAIR.
When using recommended clinical sequences at 7T, the best way to detect cortical GM lesions is with 3D-FLAIR and not by GM-specific 3D-DIR or by conventional 2D-T2WI and 3D-T1WI sequences.

Efferent manifestations of multiple sclerosis.
This review will briefly touch on the anatomy as well as the signs and symptoms associated with MS-related dysfunction involving these systems.

Cerebrospinal fluid IL-21 levels in Neuromyelitis Optica and multiple sclerosis.
The concentration of CSF IL-21 was noticeably elevated and might have a positive correlation with humoral immune activity in NMO.

Pharyngeal electrical stimulation for dysphagia associated with multiple sclerosis: a pilot study.
No specific treatment for oro-pharyngeal dysphagia related to MS has been described to date. Our preliminary findings suggest a potential benefit of intraluminal electrical pharyngeal stimulation for the treatment of dysphagia caused by MS.

Vitamin D in multiple sclerosis: implications for assessment and treatment.
the authors advise that the serum concentration of 25-hydroxyvitamin D is monitored in order to prevent bone deficit, and that a serum level of 75-125 nmol/l is targeted. This level is sufficient for maintenance of bone health, is not known to be associated with adverse events, and is in the range that has been associated with low risk of developing MS and low disease activity.

Behavioral interventions in multiple sclerosis: a biopsychosocial perspective.
recent evidence suggests that group education or face-to-face behavioral interventions may decrease inflammatory disease activity (such as relapse rate or lesion formation measured by MRI). Therefore, behavioral interventions not only ameliorate symptoms but may have the potential to modify the disease process itself.

Commercially available accelerometry as an ecologically valid measure of ambulation in individuals with multiple sclerosis.
Collectively, the authors believe the time is ripe for the application of commercially available accelerometers as an outcome measure of community ambulation in MS. Such an application has the potential to maximize the understanding of ambulatory impairments in real-world conditions for clinical research and practice involving individuals with MS.

Neurodegeneration in multiple sclerosis: novel treatment strategies.
Here, the authors' review recently elucidated molecular insights into inflammatory neuronal/axonal pathology in MS and discuss the resulting options regarding neuroprotective and regenerative treatment strategies.

Increased HLA-E expression in white matter lesions in multiple sclerosis.
These results suggest the potential for an effect in central nervous system pathogenesis from HLA-E modulation in stressed tissue. Co-localization with infiltrating CD8+ cells implicates a possible role for HLA-E-restricted regulatory CD8+ cells, as has been proposed in other autoimmune diseases.

ADvanced IMage Algebra (ADIMA): a novel method for depicting multiple sclerosis lesion heterogeneity, as demonstrated by quantitative MRI.
ADIMA enabled the simple classification of WML into two groups having different quantitative magnetic resonance properties, which can be reproducibly distinguished.

Long-term treatment risks in multiple sclerosis: risk knowledge and risk perception in a large cohort of mitoxantrone-treated patients.
Risk awareness of mitoxantrone-treated patients is insufficient, but can be increased by EBPI without increasing worries. Continued patient information during and after treatment should be implemented in management algorithms.

Transcriptional profiling of microdissected areas of active multiple sclerosis lesions reveals activation of heat shock protein genes.
To identify changes in HSP genes in relation to different areas of the plaque, we used genome-wide microarray analysis. We detected a significant change in the transcriptional profile of the demyelinated region compared with NAWM. In particular, overall expression of different HSP genes was upregulated in different areas of chronic-active lesion. These changes were linked to an upregulation of heat shock factor 4 (HSF4). This is the first global analysis of transcriptional changes in HSPs in the central nervous system during MS. The results support a relationship between HSP activation and lesion activity.

Bridging the gap from genetic association to functional understanding: the next generation of mouse models of multiple sclerosis.
A new generation of humanized mice aims to tighten the gap between mouse and human, such that MS-associated genetic variants can be modeled more physiologically and systematically.

Pre-specified subgroup analyses of a placebo-controlled phase III trial (TEMSO) of oral Aubagio (teriflunomide) in relapsing multiple sclerosis.
The positive effects of teriflunomide were demonstrated consistently across subgroups in TEMSO.

[Basic mechanisms of action of Gilenya (fingolimod) in relation to multiple sclerosis].
In multiple sclerosis patients, the available evidence indicates that fingolimod efficacy is directly associated with impairment of circulation of several T cell subsets and possibly B cells. Animal studies raise the possibility that an additional effect on glial cells might also contribute to the clinical efficacy.

Acute exacerbation of multiple sclerosis presenting with facial metamorphopsia and palinopsia.
These symptoms appear to be related to active demyelination that either involved the optic radiations in the visual pathway or the visual association area in the temporo-occipital region of the left hemisphere.

Immune modulating peptides for the treatment and suppression of multiple sclerosis.
the objectives of this review are to (a) summarize the immunological basis for the development of MS, (b) discuss specific and non-specific peptides tested in EAE and in humans, and (c) briefly address some problems and potential solutions with these novel therapies.

Differences and similarities in the evolution of morphologic brain abnormalities between paediatric and adult-onset multiple sclerosis.
Our observation of a morphologically more aggressive disease evolution paralleled by less disability in pMS than in aMS (defined using EDSS) suggests a higher compensatory capacity in pMS. This fact may obscure the need for treatment of pMS patients with disease modifying treatments (DMTs) based solely on clinical observation.

Switch-associated protein 70 antibodies in multiple sclerosis: relationship between increased serum levels and clinical relapse.
Detection of SWAP70 antibodies during the attack period might suggest that SWAP70 is involved in MS relapse pathogenesis. Whether serum SWAP70 antibody detection may be utilized as an MS relapse predictor should be tested in prospective studies.

Elevated type I interferon-like activity in a subset of multiple sclerosis patients: molecular basis and clinical relevance.
Therapeutic IFN-beta induces the transcription of several genes involved in IFN-related pathways. In a subgroup of MS patients, the expression of these genes is already increased before therapy initiation, possibly driven by an overexpression of ISGF3. Patients with high and low endogenous IFN-like activity showed similar clinical long-term courses of disease. Different results were obtained for different IFN-beta drug preparations, and this merits further investigation.

Body mass index and waist circumference in persons aging with muscular dystrophy, multiple sclerosis, post-polio syndrome, and spinal cord injury.
The presence of group differences in BMI and absence of group differences in WC suggests that BMI may not accurately represent health risk in SCI, MD, and possibly MS, because of biasing elements of the conditions, such as changes in body composition and mobility limitations.

Accumulation of cortical hyperphosphorylated neurofilaments as a marker of neurodegeneration in multiple sclerosis.
MS is associated with the widespread accumulation of hyperphosphorylated neurofilament protein in neuronal somata, with the most marked accumulation in regions of cortical demyelination. This aberrant localisation of hyperphosphorylated neurofilament protein may contribute to neuronal dysfunction and degeneration in MS patients.

Assessment of disease activity in multiple sclerosis phenotypes with combined gadolinium- and superparamagnetic iron oxide-enhanced MR imaging.
The combination of gadolinium and USPIO in patients with MS can help identify additional active lesions compared with the current standard, the gadolinium-only approach, even in progressive forms of MS. Lesions that enhance with both agents may exhibit a more aggressive evolution than those that enhance with only one contrast agent.

No impact of adult attachment and temperament on clinical variability in patients with clinically isolated syndrome and early multiple sclerosis.
Although harm avoidance may be related to subclinical disease activity in early RRMS adult attachment and temperament do not seem to contribute to differences between CIS and RRMS or clinical variability in early multiple sclerosis.

Cognitive impairment in neuro-Behcet's disease and multiple sclerosis: a comparative study.
In California Verbal Learning Test, both short- and long-term delayed recall and cued recognition were worse in neuro-Behcet's cases. They had impaired semantic clustering and increased false positives. Stroop Test was also more impaired in neuro-Behcet's cases. They needed significantly more trials to complete the first category of the Wisconsin Card Sorting Test and had a poorer total Frontal Behavioral Inventory Score. Our results suggest that neuro-Behcet's patients have a more severe "frontal"-executive dysfunction than MS patients.

Interpretation and visualization of non-linear data fusion in kernel space: study on metabolomic characterization of progression of multiple sclerosis.
We find that fusion in kernel space allows for efficient and reliable discrimination of classes (MScl and early stage). This data fusion approach achieves better class prediction accuracy than analysis of individual datasets and the commonly used mid-level fusion. The prediction accuracy on an independent test set (8 samples) reaches 100%. Additionally, the classification model obtained on fused kernels is simpler in terms of complexity, i.e. just one latent variable was sufficient. Finally, visualization of variables importance in kernel space was achieved.

Multiple Kernel Learning Captures a Systems-Level Functional Connectivity Biomarker Signature in Amyotrophic Lateral Sclerosis.
This type of analysis has potential to non-invasively define a biomarker signature at the systems-level. As the understanding of neurodegenerative disorders moves towards studying pre-symptomatic changes, there is potential for this type of approach to generate biomarkers for the testing of neuroprotective strategies.

Association between a Genetic Variant of Type-1 Cannabinoid Receptor and Inflammatory Neurodegeneration in Multiple Sclerosis.
Our results demonstrate the biological relevance of the (AAT)_n CNR1 repeats in the inflammatory neurodegenerative damage of MS.

Immunochip analysis identifies multiple susceptibility Loci for systemic sclerosis.
Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.

Motor and sensory responses after percutaneous tibial nerve stimulation in multiple sclerosis patients with lower urinary tract symptoms treated in daily practice.
A sensory response, either alone or in combination with a motor response, is more frequent and seems to be better associated with a successful outcome of PTNS than motor response alone.

Corticosteroid-resistant multiple colonic ulcers in a patient with systemic lupus erythematosus/systemic sclerosis overlap syndrome effectively treated with intravenous cyclophosphamide pulse therapy.
We report a rare case of a 17-year-old female with overlap syndrome (systemic lupus erythematosus and systemic sclerosis) who developed severe abdominal pain and bloody diarrhea accompanied by central nervous system lupus.

Long term follow up of peripheral lymphocyte subsets in a cohort of multiple sclerosis patients treated with natalizumab.
In conclusion, effective natalizumab treatment of RRMS patients was associated with the persistence of its biological effects through a stable increase of peripheral lymphocytes, mainly B cells, and an unchanged proportion of T cell subsets in long follow up.

Biomarkers of treatment response in multiple sclerosis.
Here we review current and emerging biomarkers, as well as study concepts for identification of new biomarkers in MS.

Novel therapeutics in multiple sclerosis management: clinical applications.
This multimedia webcast educational activity will cover the current state of MS science, current therapies in MS, emerging treatments in clinical trials for MS as well as differences between physicians in diagnosis and management of MS and their evolving practices.

Diffusion tensor-MRI evidence for extra-axonal neuronal degeneration in caudate and thalamic nuclei of patients with multiple sclerosis.
Increased FA in the caudate and the thalamus may constitute a sensitive marker of MS pathologic processes, such as loss of dendrites and/or swelling of neuronal cell bodies.

Behavioural symptoms and impairments in multiple sclerosis: a systematic review and meta-analysis.
In conclusion the objective behavioural impairments and especially subjective symptoms are present in patients with MS. These manifestations should be taken into account in the diagnostics and treatment of the disease.

Characteristics of multiple sclerosis in aboriginals living in British Columbia, Canada.
We identified a small, but important cohort of aboriginals with MS; being the largest identified to date. There was evidence of more rapid MS progression in aboriginals compared with non-aboriginals.

A prospective, randomized, controlled trial of autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: a position paper.
Objectives of the trial, patient selection, transplant technology and outcome assessment were extensively discussed. The outcome of this process is summarized in the present paper, with the goal of establishing the background and advancing the development of a prospective, randomized, controlled multicentre trial to assess the clinical efficacy of HSCT for the treatment of highly active MS.

Effect of gender on late-onset multiple sclerosis.
Women with LOMS have a different trajectory in terms of disease progression than women with AOMS. The effect of menopause combined with race/ethnicity on the MS disease course requires further investigation.

Evidence for the different physiological significance of the 6- and 2-minute walk tests in multiple sclerosis.
The pattern of change in V·O2 indicates that there are different metabolic systems providing energy for ambulation during the 6MW in MS subjects and steady state aerobic metabolism is reached during the last 3 minutes of the 6MW. By extension, the first 3 minutes would represent a test of mixed aerobic and anaerobic work, whereas the second 3 minutes would represent a test of aerobic work during walking.

Multiple sclerosis: pathogenesis and treatment.
FDA approved agents include four preparations of interferon β (Avonex, Rebif, Betaseron and Extavia), glatiramer acetate (Copaxone), mitoxantrone (Novantrone), natalizumab (Tysabri) and fingolimod (Gilenya). There are several drug undergoing phase II and III trials. The heterogeneity of the MS disease process, individual patient response, and medication toxicities continue to challenge the treating physician.

Step-rate thresholds for physical activity intensity in persons with multiple sclerosis.
The relationship between METs and step-rate is altered in persons with MS, lowering their step-rate thresholds for activity intensity, especially for persons with MS who have higher levels of walking impairment.

Il-17 And Glutamte Excitotoxicity In The Pathogenesis Of Multiple Sclerosis.
The results suggest that Th17 cells might enhance and use glutamate excitotoxicity as an effector mechanism in the MS pathogenesis. Furthermore, Th17 immune response, as well as neutrophils, could be more important for MS onset rather than further disease development and progression, what could explain why some MS clinical trials, targeting Th17 cells in the later stage of the disease, failed to provide any clinical benefit.

Surgery and risk for multiple sclerosis: a systematic review and meta-analysis of case-control studies.
We found a small but statistically significant and clinically important increased risk for developing multiple sclerosis, in those with tonsillectomy and appendectomy at ≤ 20 years of age. There was no convincing evidence to support the association of other surgeries and the risk for multiple sclerosis. Well-designed prospective etiological studies, pertaining to the risk for developing multiple sclerosis, ought to be conducted and should include the examination of various surgeries as risk factors.

The ominous sequence in patients with tuberous sclerosis complex.
The sequence of progressively proliferative renal angiomyolipoma, facial angiofibroma, West syndrome and TSC2 gene mutations might be prognostic ominous factors.

Direct and indirect cost burden associated with multiple sclerosis relapses: excess costs of persons with MS and their spouse caregivers.
Relapse severity was significantly and increasingly associated with greater direct and indirect costs in MS patients. More frequent relapses also translated into a significant cost burden in spouse caregivers.

Neural networks to identify multiple sclerosis with optical coherence tomography.
Compared with the OCT-provided parameters, the ANN had the largest area under the ROC curve. Conclusions: Measurements of RNFL thickness obtained with Spectralis OCT have a good ability to differentiate between healthy and individuals with multiple sclerosis. Based on the area under the ROC curve, the ANN performed better than any single OCT parameter.

Combining self-help and professional help to minimize barriers to physical activity in persons with multiple sclerosis: a trial of the "Blue Prescription" approach in New Zealand.
Evidence indicated that the Blue Prescription approach can provide a collaborative and flexible way for physical therapists to work with individuals with MS, to increase participation in community-based physical activity. To further develop the approach, there is a need to address issues related to the use of standardized measures and develop strategies to train physical therapists in collaborative approaches for promotion of physical activity.The integration of self-help and professional help provided by the Blue Prescription approach appeared to result in successful promotion of physical activity in persons with MS. Additional testing is required to examine its efficacy in other health care systems, in conditions beyond MS, and in terms of its economic impact.

Alteration of prolyl oligopeptidase and activated α-2-macroglobulin in multiple sclerosis subtypes and in the clinically isolated syndrome.
Our results open new lines of research on the role of PREP and α2M* in MS, aiming to relate them to the diagnosis and prognosis of this devastating disease.

Tract-specific white matter correlates of fatigue and cognitive impairment in benign multiple sclerosis.
These findings suggest that fatigue and cognitive impairment are quite frequent in BMS patients and are, at least in part, related to micro-structural damage and T2LV of WM tracts connecting the brain cortical and sub-cortical regions of the two hemispheres.

Validity of the dynamic gait index in people with multiple sclerosis.
The DGI is a valid measure of dynamic balance during walking for ambulatory people with multiple sclerosis. With the cutoff point of ≤19, sensitivity was high in identifying people at risk of falls.

Lack of adiponectin leads to increased lymphocyte activation and increased disease severity in a mouse model of multiple sclerosis.
Treatment with globular adiponectin in vivo ameliorated EAE, and was associated with an increase in Treg cells. These data indicate that adiponectin is an important regulator of T-cell functions during EAE, suggesting a new avenue of investigation for MS treatment.

Modelling the cost effectiveness of disease-modifying treatments for multiple sclerosis: issues to consider.
the cost effectiveness of DMTs outside North America and Europe is currently unknown, with the lack of country-specific data as the major limiting factor. We suggest that limited data should not preclude analyses, as models may be built and updated in the future as data become available. Disclosure of modelling methods and assumptions could improve the transferability and applicability of models designed to reflect different healthcare systems.

Compromised motor imagery ability in individuals with multiple sclerosis and mild physical disability: an ERP study.
The results of the present study demonstrate MI impairment in patients with MS at both the behavioral and neural level. Neuronal activity dysfunction (decreased and delayed activity) in patients with MS provides new insights into MI impairment. Furthermore, our findings suggest the contribution of working memory dysfunction to compromised MI ability in patients with MS.

Characteristic cerebrospinal fluid cytokine/chemokine profiles in neuromyelitis optica, relapsing remitting or primary progressive multiple sclerosis.
Our findings suggest distinct cytokine/chemokine alterations in CSF exist among NMO, RRMS and PPMS. In NMO, over-expression of a cluster of Th17- and Th1-related proinflammatory cytokines/chemokines is characteristic, while in PPMS, increased CCL4 and CXCL10 levels may reflect on-going low grade T cell and macrophage/microglia inflammation in the central nervous system. In RRMS, only a mild elevation of proinflammatory cytokines/chemokines was detectable at relapse.

Baseline gene expression signatures in monocytes from multiple sclerosis patients treated with interferon-beta.
Purified monocytes from IFNb non-responders were characterized by an over-expression of type I IFN responsive genes, which confirms the type I IFN signature in monocytes suggested from previous studies. Other relevant signaling pathways that were up-regulated in IFNb non-responders were related with the mitochondrial function and processes such as protein synthesis and antigen presentation, and together with the type I IFN signaling pathway, may also be playing roles in the response to IFNb.

Proxy measurements in multiple sclerosis: agreement on different patient-reported outcome scales.
Partners of patients with MS can be a useful source of information for several PRO scales, especially when the focus is on physical functioning. For psychological functioning this seems to be less reliable.

Gain-of-function of P2X7 receptor gene variants in multiple sclerosis.
These findings may contribute to define the genetic background predisposing for multiple sclerosis and its pathophysiology.

[Reduced emotional reactivity to negative stimuli in multiple sclerosis, preliminary results].
These data suggest disorders in emotional processes in R-MS, mainly a poor reactivity to negative stimuli which may have an impact on everyday life. A larger population should be studied to confirm these modifications of emotion.

Immune mechanisms underlying the beneficial effects of autologous hematopoietic stem cell transplantation in multiple sclerosis.
We discuss here the possibility that both AHSCT and T-cell depleting therapies may re-program alternatively the immune system, and why transplantation of CD34+ hematopoietic stem cells may offer AHSCT a possible advantage regarding long-term remission.

Myelin regeneration in multiple sclerosis: targeting endogenous stem cells.
We highlight recent studies on factors that influence endogenous remyelination and potential promising pharmacological targets that may be considered for enhancing central nervous system remyelination.

Cell therapy for multiple sclerosis.
An initial clinical trial has established the probable safety of their intravenous and intrathecal delivery. Short-term follow-up observed immunomodulatory effects and clinical benefit justifying further clinical trials.

Self-assessment of cognition in Multiple Sclerosis: the role of personality and anxiety.
: Overall, patient self-reports of cognition did not correspond well to neuropsychological performance. Anxiety and conscientiousness contributed significantly to patients' perceptions of their cognitive failings and thus should be taken into account when addressing these complaints.

Morphological and haemodynamic abnormalities in the jugular veins of patients with multiple sclerosis.
In our group of patients, patients suffering from MS had significantly more IJV morphological changes and haemodynamic abnormalities when compared with healthy individuals not suffering from MS. These findings can be well demonstrated by non-invasive and cost-effective Doppler ultrasound.

Factors influencing healthy aging with multiple sclerosis: a qualitative study.
This two-tiered conceptual model of health aging, based on the perspectives of older persons with MS, provides a potential framework for the development of MS self-management program curricula aimed at optimizing quality of life. Further empirical testing may validate its utility in predicting healthy aging with MS.

A single-arm, open-label study of alemtuzumab in treatment-refractory patients with multiple sclerosis.
Alemtuzumab effectively reduced relapse rates and improved clinical scores in patients with active relapsing-remitting multiple sclerosis not controlled by interferon therapy.

Retinal periphlebitis in patients with multiple sclerosis.
The presence of RP is a reliable indicator of MS activity and might be considered as a parameter for monitoring the disease activity and effects of the treatment.

Functional adaptive changes within the hippocampal memory system of patients with multiple sclerosis.
These findings are important for future cognitive therapeutic studies, since cognitive intervention might be most effective before cognitive impairment is present and when adaptive changes of the brain are most prominent.

Patterns of dietary and herbal supplement use by multiple sclerosis patients.
The proportion of controls and MS patients after MS onset who reported using an individual HS was generally similar. The most commonly used HS in patients after MS was evening primrose oil (40.4%) followed by cranberry fruit extract (35.2%). There was no evidence for associations with progressive disease course or with choice of disease-modifying treatment. Dietary supplements are used more frequently by MS patients than controls. Use tends to increase after MS onset compared to before, especially for DS. The use of HS by MS patients is only modestly greater than by controls.

Genome-wide homozygosity and multiple sclerosis in Orkney and Shetland Islanders.
Three participants were removed on the basis of pedigree-genomic anomalies (n=263). Three measures of genome-wide homozygosity were generated for each individual, and association with MS was assessed using logistic regression models. No effect of genome-wide homozygosity was detected, indicating that inbreeding and consanguinity are not risk factors for MS in this population.

Targeting VIP and PACAP receptor signalling: new therapeutic strategies in multiple sclerosis.
Here, we will discuss the immunomodulatory and neuroprotective actions of VIP and PACAP and their signalling pathways, and then extensively review the structure-activity relationship data and biophysical interaction studies of these peptides with their cognate receptors.

Neuroendocrine Immunoregulation in Multiple Sclerosis

In conclusion, dysfunction of the neuroendocrine-immune system in patients with autoimmune diseases, including MS, seems to be important in the pathogenesis of these diseases. Increasing the knowledge of the neuroendocrine-immune system in MS can help to elucidate the underlying mechanisms of the inflammatory responses in MS and mutatis mutandis in other autoimmune diseases. Furthermore, intensive research on the modulatory function of the neuroendocrine-immune system may provide new therapeutic approaches for the treatment of MS in the near future.

Multiple sclerosis impairs regional functional connectivity in the cerebellum

Using regional homogeneity of resting-state fluctuations in the BOLD-signal as index of local functional connectivity, we show that local functional connectivity is impaired in the left cerebellum in MS. Regional homogeneity was found to be reduced in lobules V and VI of the left cerebellar hemisphere in patients with MS relative to controls. Further, patients with higher EDSS scores displayed less local connectivity in Crus I and dentate nucleus of left cerebellum. Similar trends were present in homologous regions of the right cerebellum. Post-hoc analyses showed that patients with higher lesion load of the left cerebellar peduncle showed more reduced local cerebellar connectivity.

Altered likelihood of brain activation in attention and working memory networks in patients with multiple sclerosis: An ALE meta-analysis

Two meta-analyses of previously published fMRI studies investigating attention and working memory were conducted for MS patients and healthy controls, respectively. Resulting maps were contrasted to compare brain activation in patients and healthy controls. Significantly increased brain activation in the inferior parietal lobule and the dorsolateral prefrontal cortex was detected for healthy controls. In contrast, higher neuronal activation in MS patients was obtained in the left ventrolateral prefrontal cortex and the right premotor area. With this meta-analytic approach previous results of investigations examining cognitive function using fMRI are summarized and compared. Therefore a more general view on cognitive dysfunction in this heterogeneous disease is enabled.

Abnormal blood–brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI

Our results emphasize the importance of BBB pathology in MS, which we find to be most prominent in the periventricular NAWM, an area prone to development of MS lesions. Both the facts that recent relapse appears to cause widespread BBB disruption and that immunomodulatory treatment seems to attenuate this effect indicate that BBB permeability is intricately linked to the presence of MS relapse activity. This may reveal further insights into the pathophysiology of MS.

Increasing Bone Sclerosis During Bortezomib Therapy in Multiple Myeloma Patients: Results of a Reduced-Dose Whole-Body MDCT Study.
Bone remineralization may occur during bortezomib-based therapy for MM in a substantial proportion of patients. The extent, location, and patterns of sclerosis differ among patients and are unpredictable. Sclerosis was documented even in patients showing suboptimal hematologic response.

Multiple Sclerosis Outcome Assessments Consortium: Genesis and initial project plan.
The European Medicines Agency (EMA) and FDA will provide parallel consultation and review. The consensus approach with engagement by all of the stakeholders, prominently including patients with MS, should also increase acceptance of the measure by clinicians and patients.

Multiple Autoimmune-Associated Variants Confer Decreased IL-2R Signaling in CD4(+)CD25(hi) T Cells of Type 1 Diabetic and Multiple Sclerosis Patients.
In addition to risk variants in IL2RA, we found that the T1D-associated risk variant of PTPN2rs1893217 independently contributed to diminished IL-2R signaling. However, even when holding genotype constant at IL2RA and PTPN2, we still observed a significant signaling defect in T1D and MS patients. Together, these data suggest that multiple mechanisms converge in disease leading to decreased response to IL-2, a phenotype that may eventually lead to loss of tolerance and autoimmunity.

Teriflunomide for the treatment of multiple sclerosis.
In this article, we review recent phase II and phase III clinical trial data, and discuss the potential of teriflunomide for the treatment of relapsing forms of MS.

Pathophysiological background and clinical characteristics of sleep disorders in multiple sclerosis.
Immunological background in disease development in both multiple sclerosis and sleep disorders have been proposed as possible common pathophysiological mechanism and recent findings of disrupted melatonin pathways in MS patients suggest multi-level causative mechanism of the development of sleep disorders in MS.

Autonomic dysfunction in multiple sclerosis.
Reports about frequency of AD in MS patients vary notably between groups. Nevertheless its impact on quality of life is substantial but, unfortunately, often overlooked. The aim of this article is to present a concise review of various symptoms and signs of autonomic system dysfunction in MS.

Interferon-beta and disability progression in relapsing-remitting multiple sclerosis.
This observational study further supports the notion that IFN-beta could have potential beneficial effect on disease progression in RRMS.

Adherence to disease-modifying therapies and attitudes regarding disease in patients with multiple sclerosis.
The analysis of results included 299 patients. Among the patients 18.5% missed at least one medication dose in the past 28 days. Patients taking Avonex were significantly more adherent then patients on other DMTs (p=0.005). Our study showed a higher then expected adherence among Slovenian patients with MS (81.5%). Our research did not confirm the influence of side effects or patients' attitudes regarding illness and therapy on adherence. However we found unexpectedly high percentage (71.8%) of patients belief that psychological factors are involved in MS aetiology.

Retinal nerve fiber thickness and MRI white matter abnormalities in healthy relatives of multiple sclerosis patients.
There is an association between decreased RNFL thickness on OCT and increased WM injury in healthy relatives of MS patients. Further studies should explore the pathophysiology of these findings.

Recent insights into the pathology of multiple sclerosis and neuromyelitis optica.
These recent findings contribute to a better understanding of different mechanisms leading to inflammatory demyelination.

SIRT1 Activating compounds reduce oxidative stress mediated neuronal loss in viral induced CNS demyelinating disease
Results demonstrate that SIRT1 activating compounds prevent neuronal loss in viral-induced demyelinating disease similar to their effects in autoimmune-mediated disease.

Neuroendocrine Immunoregulation in Multiple Sclerosis.
Here we provide an overview of the complex system of crosstalk between the neuroendocrine and immune system as well as reported dysfunctions involved in the pathogenesis of autoimmunity, including MS. Finally, possible strategies to intervene with the neuroendocrine-immune system for MS patient management will be discussed. Ultimately, a better understanding of the interactions between the neuroendocrine system and the immune system can open up new therapeutic approaches for the treatment of MS as well as other autoimmune diseases.

Endocannabinoid pathways and their role in multiple sclerosis-related muscular dysfunction.
These findings with Sativex are very promising and offer encouragement for MS patients, the majority of whom will develop spasticity-related disabling and recalcitrant symptoms. Furthermore, research into the endocannabinoid system may offer potential in other neurodegenerative, inflammatory and pain disorders.

Pathophysiology, assessment and management of multiple sclerosis spasticity: an update.
The endocannabinoid system modulator, Sativex(®) (nabiximols, USAN name), provides an alternative therapeutic approach in the management of MS spasticity.

Multiple sclerosis in pregnancy.
Preconceptual counseling to discuss the safety of medications in pregnancy, the antepartum period along with what the patient can expect during birth, and the postpartum period will be discussed.

Early axonal damage and progressive myelin pathology define the kinetics of CNS histopathology in a mouse model of multiple sclerosis.
The data underline the need for neuroprotection in MS and suggest the MOG model as a highly valuable tool for the assessment of different therapeutic strategies.

Mitochondrial dysfunction and neurodegeneration in multiple sclerosis.
his focused review highlights recent evidence supporting this hypothesis, with particular emphasis on our in vitro and in vivo work with the mitochondria-targeted redox enzyme p66ShcA.

Cognitive reserve in multiple sclerosis.
We review evidence that benefits of intellectual enrichment on cognitive status may stem from more efficient patterns of brain function. We discuss clinical implications and highlight important unanswered questions for future research on reserve against cognitive impairment in MS.

Exploring the implications of small-area variation in the incidence of multiple sclerosis.
This may require an examination of macro-level differences in environmental exposures between high- and low-incidence regions of the world.

Common genetic variants in the plasminogen activation pathway are not associated with multiple sclerosis.
gene expression levels were analysed according to genotype: no associations were observed. In conclusion despite the consistent evidence for the role of MMP9 and the plasminogen activation cascade in MS, we found no associations between genotype nor gene expression. This suggested there are other potentially modifiable factors influencing gene expression in MS.

The emerging role of p38 mitogen-activated protein kinase in multiple sclerosis and its models.
we review the evidence from mouse and human studies supporting the role of p38 MAPK in regulating key immunopathogenic mechanisms underlying autoimmune inflammatory disease of the central nervous system and the potential of targeting this pathway as a disease-modifying therapy in MS.

Defining and scoring response to IFN-β in multiple sclerosis.
In this Review, we focus on the many definitions of clinical response to IFN-β and explore the markers that can be used to predict this response. We also highlight advantages and limitations of the existing scoring systems in light of future expansion of these models to biological markers and to other classes of emerging therapies for MS.

Update on therapeutic options for multiple sclerosis.
The disorder has long been associated with clinical relapses and a disabling course. However, there has been a rapid expansion in the available treatment options for MS, and new insights into existing therapies, as decades of research has begun to produce tangible treatment results leading to newly approved an emerging therapies.

MicroRNA regulate immune pathways in T-cells in multiple sclerosis (MS).
These findings indicate that microRNA may be important regulatory molecules in T-cells in MS.

Responsiveness of the Multiple Sclerosis International Quality of Life questionnaire to disability change: a longitudinal study.
Whereas specific dimensions of MusiQoL identified EDSS changes, the MusiQoL index did not detect disability changes in worsened MS patients in a 24-month observational study. Future responsiveness validation studies should include longer follow-up and more representative samples.

Entrapment syndrome of multiple nerves in graft-versus-host disease.
Electron microscopy demonstrated alterations of the myelin sheaths and marked depletion of normal-sized myelinated nerve fibers. Conclusions: In addition to polyneuropathy, chronic GVHD can be associated with peripheral nerve entrapment syndromes and should be added to the differential diagnosis of compressive neuropathies. Muscle Nerve 49: 138-142, 2014.

Multiple sclerosis: risk factors and their interactions.
these factors appear to act synergistically and the risk of MS in individuals exposed to more than one factor combines multiplicatively. Current evidence suggests that a large part of MS could be prevented and understanding how and when during life risk factors act will ultimately aid the development of prevention strategies.

Potential control of multiple sclerosis by cannabis and the endocannabinoid system.
This review appraises the current knowledge of cannabinoid biology particularly as it pertains to MS and outlines potential future therapeutic strategies for the treatment of disease progression in MS.

Mechanisms in the development of multiple sclerosis lesions: reconciling autoimmune and neurodegenerative factors.
This scenario is fully consistent with known causative factors and the pathology of MS, and with the effects of various therapies. It also helps explain why MS develops only in humans.

Disease modifying drugs in multiple sclerosis: mechanisms of action and new drugs in the horizon.
Overall, the anti-inflammatory strategy has been mostly successful but drugs that have protection and repair mechanisms are still missing.

Health care-resource utilization before and after natalizumab initiation in multiple sclerosis patients in the US.
The initiation of natalizumab was associated with significant decreases in MS-related inpatient stays, and corticosteroid use with corresponding decreases in length of stay and costs among natalizumab users with and without DMTs in the prior year.

Cerebral lesions of multiple sclerosis: is gadolinium always irreplaceable in assessing lesion activity?
The assessment of MS lesion activity should include a careful evaluation of T2-weighted images in addition to contrast enhancement assessment. The presence of an accompanying peripheral thin rim of hypointensity on T2-weighted images related best with contrast enhancement and subsequent lesion activity and may represent an additional pattern for disease activity assessment when gadolinium examination is contraindicated or influenced by prior therapy.

Reduced sick leave in multiple sclerosis after one year of natalizumab treatment. A prospective ad hoc analysis of the TYNERGY trial.
This ad-hoc analysis of prospectively collected data supported our previous retrospective study and thus indicates a positive relationship between natalizumab treatment and improvement in work ability.

Walking and cognition, but not symptoms, correlate with dual task cost of walking in multiple sclerosis.
Walking performance might be a target of interventions for reducing the DTC of walking in MS.

Eosinophilic Fasciitis Occurring under Treatment with Natalizumab for Multiple Sclerosis.
Peripheral blood eosinophilia has been described under treatment with natalizumab, but we herein report the first case to our knowledge of eosinophilic fasciitis as a possible complication of this medication.

Interleukin-1β and Interleukin-1 Receptor Antagonist Appear in Grey Matter Additionally to White Matter Lesions during Experimental Multiple Sclerosis.
The appearance of IL-1β expressing cells in GM within the CNS during cr-EAE may explain the occurrence of several clinical deficits present in EAE and MS which cannot be attributed solely to the presence of IL-1β in WM. Endogenously produced IL-1ra seems not capable to counteract IL-1β-induced effects. We put forward that IL-1β may behold promise as a target to address GM, in addition to WM, related pathology in MS.

Structural correlates of subjective and objective memory performance in multiple sclerosis.
Our data suggest that verbal and nonverbal memory as well as perceived retrospective and prospective memory deficits are related to alterations of discrete anatomical structures in the low-disability phase of MS.

In multiple sclerosis oligoclonal bands connect to peripheral B cell responses.
Our data provide a high-resolution molecular analysis of OCB and strongly support the concept that OCB are not merely the terminal result of a targeted immune response in MS but represent a component of active B cell immunity that is dynamically supported on both sides of the blood-brain barrier.

Effect of daclizumab high-yield process in patients with highly active relapsing-remitting multiple sclerosis.
DAC HYP efficacy was similar across the spectrum of MS disease activity as assessed prior to treatment initiation.

Guidelines on the clinical use for the detection of neutralizing antibodies (NAbs) to IFN beta in multiple sclerosis therapy: report from the Italian Multiple Sclerosis Study group.
In this paper, we report the panel's recommendations for the use of IFNβ Nabs detection in the early identification of IFNβ non-responsiveness and the management of patients on IFNβ treatment in Italy, according to a model of therapeutically appropriate care.

Evaluating the effects of amantadin, modafinil and acetyl-l-carnitine on fatigue in multiple sclerosis - result of a pilot randomized, blind study.
One month treatment with amantadine improved fatigue in patients with relapsing-remitting MS as evaluated by MFIS. No or only a trend of improvement was seen in patients treated with modafinil or ALCAR, respectively.

Idiopathic acute transverse myelitis: outcome and conversion to multiple sclerosis in a large series

At least 13% of patients who fulfill the TMCWG criteria for definite and possible IATM will convert to MS. Functional recovery in IATM is poorer in patients with urinary sphincter dysfunction at admission or LETM on MRI.

Depression and sleep disturbances in patients with multiple sclerosis and correlation with associated fatigue

Depression and sleep disturbance in patients with MS is significantly correlated with associated fatigue.

Multiple Sclerosis in the Mount Etna Region: Possible Role of Volcanogenic Trace Elements

We found a higher prevalence and incidence of Multiple Sclerosis among populations living in the eastern flank of Mount Etna. According to our data a possible role of TE cannot be ruled out as possible co-factor in the MS pathogenesis. However larger epidemiological study are needed to confirm this hypothesis.

ExtaviJect® 30G device for subcutaneous self-injection of interferon beta-1b for multiple sclerosis: a prospective European study

ExtaviJect 30G was convenient to use and was associated with high levels of compliance.

Interleukin-10 expression during the acute phase is a putative prerequisite for delayed viral elimination in a murine model for multiple sclerosis.
Results substantiate the hypothesis that an imbalanced cytokine milieu during the early infection phase contributes to ineffective antiviral immunity in animals with a susceptible genetic background.

Ethical challenges in paediatric clinical trials in multiple sclerosis.
Future treatment trials in children and adolescents with MS will require a multicentre design, definition and selection of key outcome measures, and identification of the most promising therapies. Risks versus benefits of each specific treatment should be weighed and comprehensively discussed.

Quantification of retinal neural loss in patients with neuromyelitis optica and multiple sclerosis with or without optic neuritis using Fourier-domain optical coherence tomography.
Although FD-OCT RNFL and macular thickness measurements can reveal subclinical or optic neuritis-related abnormalities in NMO-spectrum and MS patients, abnormalities are predominant in the macula of MS patients and in RFNL measurements in NMO patients. The correlation between OCT and VF abnormalities was stronger in NMO than in MS, suggesting the two conditions differ regarding structural and functional damage.

[HTLV-1-associated myelopathy/tropical spastic paraparesis: a differential diagnosis in multiple sclerosis].
The therapy is limited to symptomatic treatment. Transmission of HTLV-1 can occur vertically by breast feeding, through sexual contact or via infected blood products. Based on a clinical case report, we present here a current review on the pathophysiology, epidemiology, clinical manifestations, diagnosis and treatment of HAM/TSP.

Vitamin D levels in Hispanics with multiple sclerosis.
We found that the relationship between vitamin D and MS differs by Hispanic ethnicity. Hypovitaminosis D was significantly more common among Hispanics than among whites with MS, and the majority of Hispanics were vitamin D insufficient. Interestingly, there was no association between vitamin D levels and season or increasing disability in the Hispanics. Our findings imply that factors influencing vitamin D levels and possibly vitamin D requirements may vary by ethnicity in patients with MS. These results should be confirmed in larger, prospective multi-ethnic cohort studies.

Bruxism and temporal bone hypermobility in patients with multiple sclerosis.
The increase in magnitude of bi-temporal bone intracranial expansion was approximately six times greater in subjects with MS compared to controls. Therefore, jaw clenching/bruxism is associated with more marked displacement of the temporal bones and expansion of the cranial cavity in patients with MS than in control subjects.

Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial.
Smoked cannabis was superior to placebo in symptom and pain reduction in participants with treatment-resistant spasticity. Future studies should examine whether different doses can result in similar beneficial effects with less cognitive impact.

Importance of human leukocyte antigen (HLA) class I and II alleles on the risk of multiple sclerosis.
In conclusion, these results confirms a complex role of HLA class I and II genes that goes beyond DRB1*15 and A*02, in particular by including all three classical HLA class I genes as well as functional interactions between DRB1*15 and several alleles of DRB1 and class I genes.

Shape analysis of the corpus callosum and cerebellum in female MS patients with different clinical phenotypes.
this study revealed CC and cerebellar shape change in RRMS and SPMS, and showed that deformations both in CC and cerebellum advances with the disease progression.

Disease-modifying drugs for multiple sclerosis and JC virus expression.
The small number of patients on other therapies precluded meaningful comment about their effects. No obvious effect of the platform DMDs on JCV prevalence was observed even for the interferon-βs.

Exploration of the relationships between regional grey matter atrophy and cognition in multiple sclerosis.
These findings clarify the pathophysiology of cognitive impairment in MS, and propose measures which could be considered for longitudinal monitoring of patients.

Abnormal blood-brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI.
Our results emphasize the importance of BBB pathology in MS, which we find to be most prominent in the periventricular NAWM, an area prone to development of MS lesions. Both the facts that recent relapse appears to cause widespread BBB disruption and that immunomodulatory treatment seems to attenuate this effect indicate that BBB permeability is intricately linked to the presence of MS relapse activity. This may reveal further insights into the pathophysiology of MS.

Multiple sclerosis impairs regional functional connectivity in the cerebellum.
In patients, two clusters in the left posterior cerebellum expressed a reduction in regional homogeneity with increasing global disability as reflected by the Expanded Disability Status Scale (EDSS) score or higher ataxia scores. The two clusters were mainly located in Crus I and extended into Crus II and the dentate nucleus but with little spatial overlap. These findings suggest a link between impaired regional integration in the cerebellum and general disability and ataxia.

Upper limb motor rehabilitation impacts white matter microstructure in multiple sclerosis.
these findings indicate the importance of administering, when possible, a rehabilitation treatment consisting of voluntary movements. We also demonstrated that the beneficial effects of a rehabilitation treatment are task-dependent and selective in their target; this becomes crucial towards the implementation of tailored rehabilitative approaches.

Mitochondrial dysfunction contributes to neurodegeneration in multiple sclerosis.
This review provides a comprehensive overview on the current knowledge regarding mitochondrial dysfunction in MS. Importantly, more insight into the cause and consequences of impaired mitochondrial function provide a basis for mitochondrial-targeted medicine to combat progressive MS.

[Multiple sclerosis and familial Mediterranean fever: a case report].
Neurological complications of FMF are rare. It is important to rule out a neuro-Behçet disease in a FMF patient with neurological disorders. Previous studies and case reports on the association between FMF and MS have failed to draw a clear conclusion as to whether this is a true association or a simple coincidence. In our patient's clinical situation, we found no argument for changing the treatment of MS and FMF.

[Approaches to segment multiple-sclerosis lesions on conventional brain MRI].
Different sets of criteria are currently used for the diagnosis of multiple sclerosis (MS). Some are based on clinical features, while others are related to imaging findings. Among the image processing systems, specific criteria include spatial dissemination of lesions in one image or their temporal dissemination in images acquired at different time points. In addition, the evolution of the lesion load can be used to evaluate treatment efficiency in MS clinical research. Consequently, obtaining a precise segmentation of the MS lesion appears to be crucial. In the literature, a number of semi-automated or completely automated approaches have been proposed enabling a reduction of the inter- and intra-expert variability for manual delineations. A comprehensive state-of-the-art classification of the most representative systems is presented here.

[High prevalence of restless legs syndrome in multiple sclerosis].
Prevalence of RLS seems to be doubled in MS patients compared to the general population. This finding warrants further study. Identification of this syndrome in MS patients might lead to specific treatments

Concomitant radiochemotherapy in a patient with multiple sclerosis and glioblastoma.
This report demonstrates that concomitant radiochemotherapy according to the STUPP protocol, was safe in our patient with respect to the radiological as well as the clinical course of multiple sclerosis.

[Choice of early and escalation treatment options for multiple sclerosis].
Here we summarize available data from studies on early treatment with immunomodulatory drugs for a first demyelinating event, also referred to as clinically isolated syndrome. Furthermore, options for the escalation of immunomodulatory therapy will be discussed, e.g. with the recently licensed monoclonal antibody natalizumab.

Cognitive impairment in multiple sclerosis.
It is only through further studies that it will be possible to identify patients with, or at risk of, cognitive impairment and to provide appropriate therapy to limit the effects of this potentially devastating symptom.

Differential diagnosis of suspected multiple sclerosis: a consensus approach.
Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision.

Interferon-beta bioactivity measurement in multiple sclerosis: feasibility for routine clinical practice.
Our data suggest that for IFN beta bioactivity screening a single post-injection measurement seems reasonable. However, MxA induction measurement based on both pre- and post-IFN beta injection samples at second measurement is somewhat more precise in determining ultimate IFN beta bioactivity status.

Development of autoimmune hepatitis type 1 after pulsed methylprednisolone therapy for multiple sclerosis: a case report.
A 43-year-old woman with multiple sclerosis (MS) was treated with pulsed methylprednisolone and interferon beta at a hospital. Four weeks after initiating treatment, liver dysfunction occurred and she was referred and admitted to our hospital. Clinical and laboratory findings were consistent with and fulfilled the criteria for drug-induced hepatitis, but not for autoimmune hepatitis (AIH). She was successfully treated with corticosteroids. As ataxia developed after 1 year, she was treated with pulsed methylprednisolone for 3 d, then readmitted to our hospital when liver dysfunction occurred. Clinical and laboratory findings led to the diagnosis of AIH. To the best of our knowledge, this is the second case of AIH developed after pulsed methylprednisolone for MS.

[The social and familial dimension: experiences of caregivers and people with multiple sclerosis. The GEDMA study].
The social stigma, the lack of work and coming to terms with MS were the greatest issues for the patient, while support from the family network, the relationship that should be established with the patient, the impact of MS on children and the role played by remunerated work were the main dimensions of the disease for the caregiver.

[Acute disseminated encephalomyelitis: study of factors involved in a possible development towards multiple sclerosis].
Some clinical and paraclinical patterns are considered to confer risk of developing MS when present in ADEM patients. Our study has aimed to: a) describe a series of 29 patients (22 children and 9 adults) admitted in our hospital and diagnosed of ADEM between 1990 and 2005; b) study those patients considered to have risk patterns of developing MS, and c) compare the child and adult populations of our series. After a median 55 month follow-up, 6 children (27%) and no adults developed MS. In our series, risk patterns for developing MS predicted conversion to MS more accurately in children than in adults. Eight patients (6 children and 2 adults) had sequelae, cognitive in 6 of them. Our work supports that also observed in recent publications: that both conversion to MS or presence of sequelae after an episode of ADEM are more frequent than traditionally considered.

[A possible effect of the immunomodulating therapy with beta-interferons and glatimer acetate on the development of thyroid disease in patients with multiple sclerosis].
The dynamics of thyroid gland structure during the treatment with DMD was followed during one year. Beta-interferons provoked the development of hypothyreosis. The study of thyroid gland in MS patients, in particular, those treated with DMD is needed.

[Phagocyte activity and the interferon system in patients with different types of multiple sclerosis].
The most marked changes in the phagocyte section of immunity and in the interferon system were seen in patients with primary progressive and secondary progressive MS. The data obtained may be used in diagnosis and choice of treatment in MS patients.

[Antibodies to native and denatured DNA in multiple sclerosis].
The higher levels of antibodies were found in patients with remitting MS compared to primarily- and secondary progressive MS. The results obtained support the hypothesis that anti-DNA antibodies to DNA are the key component of the pathogenesis and their level depends on the immunoreactivity of the patient and MS course.

Perinatal outcomes in women with multiple sclerosis exposed to disease-modifying drugs.
The incidence of DMD exposure was relatively low and no cases were intentional. Further studies are needed to ascertain the safety of DMD exposure during pregnancy in MS.

The effects of heat stress on cognition in persons with multiple sclerosis.
A significant increase in core body temperature during heat stress is associated with a mild and reversible worsening of the PASAT 3" performance, while visual vigilance performance seems to remain almost unaffected.

Assessment of lesion pathology in a new animal model of MS by multiparametric MRI and DTI.
In conclusion, the combined information from different DTI parameters allows for a more precise identification of solely demyelinated lesions versus demyelinated and acutely inflamed lesions. These findings are of relevance for offering individualized, stage-adapted therapies for MS patients.

B cell-derived IL-15 enhances CD8 T cell cytotoxicity and is increased in multiple sclerosis patients.
Exposure of CD8 T cells to this cytokine enhanced their ability to kill glial cells as well as to migrate across an in vitro inflamed human blood-brain barrier. The elevated levels of IL-15 in patients relative to controls, the greater susceptibility of CD8 T cells from patients to IL-15, in addition to the enhanced cytotoxic responses by IL-15-exposed CD8 T cells, stresses the potential of therapeutic strategies to reduce peripheral sources of IL-15 in MS.

IL2RA gene polymorphism rs2104286 A>G seen in multiple sclerosis is associated with intermediate uveitis: possible parallel pathways?
These findings suggest an association of the rs2104286 polymorphism with intermediate uveitis, but not with HLA-B27-associated acute anterior uveitis. Because this polymorphism was associated with multiple sclerosis in previous studies, the authors suggest possible parallel pathways between multiple sclerosis and intermediate uveitis but not HLA-B27-associated uveitis.

Endocrine and phototransduction effects in the prevention of multiple sclerosis.
It presents published studies as evidence and suggests a number of straightforward tests of these theories which could allow clinicians to advise their MS patients to take appropriate actions to help slow down or prevent disease progression.

Mannose binding lectin mediated complement pathway in multiple sclerosis.
These findings suggest a potential activation of MBL complement pathway in MS that may possibly alter the risk or progression of MS disease.

Correlates of stages of change for physical activity in adults with multiple sclerosis.
The overall accuracy of predicting stages of change was 58.75%. Behavioral (r(2) = .35) and cognitive processes (r(2) = .17) accounted for the most variance, followed by mobility (r(2) = .11) and self-efficacy (r(2) = .05). Results provide support for evaluating whether TTM-based interventions can promote PA in adults with MS.

Data mining for response shift patterns in multiple sclerosis patients using recursive partitioning tree analysis.
PCS and MCS change scores are obfuscated by response shifts. The contingent true scores for PCS change scores are not comparable across patient groups.

Impaired neurosteroid synthesis in multiple sclerosis.
The findings also indicate that allopregnanolone and perhaps other neurosteroid-like compounds might represent potential biomarkers or therapies for multiple sclerosis.

VCAM-1-targeted magnetic resonance imaging reveals subclinical disease in a mouse model of multiple sclerosis.
These findings describe a highly sensitive molecular imaging tool that may enable detection of currently invisible pathology in MS, thus accelerating diagnosis, guiding treatment, and enabling quantitative disease assessment.

Statin therapy and multiple sclerosis disability in a population-based cohort.
In this cohort, disability progression did not differ between those receiving statin therapy and controls. These findings support the hypothesis that statins, in doses currently prescribed for hyperlipidemia, do not affect the long-term course of MS.

JCV epidemiology in MS (JEMS)-Epidemiology of anti-JCV antibody prevalence in multiple sclerosis patients-Portuguese data.
The results of Portuguese MS patients participating in the JEMS study present some differences when compared with the global population and literature results. An overall prevalence higher than expected raises awareness for data confirmation with greater sample size studies.

Morphostructural MRI abnormalities related to neuropsychiatric disorders associated to multiple sclerosis.
It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS.

Methodology of an International Study of People with Multiple Sclerosis Recruited through Web 2.0 Platforms: Demographics, Lifestyle, and Disease Characteristics.
This paper describes the study methodology in detail and provides an overview of baseline participant demographics, clinical characteristics, summary outcome variables, and health and lifestyle behaviours. The sample described is unique due to the nature of recruitment through online media and due to the engagement of the group, which appears to be well informed and proactive in lifestyle modification. Conclusion. This sample provides a sound platform to undertake novel exploratory analyses of the association between a variety of lifestyle factors and MS outcomes.

Prognostic risk estimates of patients with multiple sclerosis and their physicians: comparison to an online analytical risk counseling tool.
While the OLAP tool was rated understandable and acceptable, it was only of modest interest and did not change patients' prognostic estimates. The results suggest, however, that patients had some idea regarding their prognosis and which factors were most important in this regard. Future work with OLAP should assess long-term prognostic estimates and clarify its usefulness for patients and physicians facing treatment decisions.

Patients with neuromyelitis optica have a more severe disease than patients with relapsingremitting multiple sclerosis, including higher risk of dying of a demyelinating disease.
The odds ratio for reaching EDSS 6.0 and being deceased due to NMO in comparison to RRMS were, respectively, 3.14 and 12.15. Conclusion: Patients with NMO have a more severe disease than patients with RRMS, including higher risk of dying of a demyelinating disease.

Disease-specific molecular events in cortical multiple sclerosis lesions.
we confirmed by immunohistochemistry that oxidative damage in cortical multiple sclerosis lesions is associated with oligodendrocyte and neuronal injury, the latter also affecting axons and dendrites. Our study provides new insights into the complex mechanisms of neurodegeneration and regeneration in the cortex of patients with multiple sclerosis.

Extracellular matrix metalloproteinase inducer shows active perivascular cuffs in multiple sclerosis.
In summary, we describe the prominence of extracellular matrix metalloproteinase inducer in central nervous system inflammatory perivascular cuffs, emphasize its dual role in matrix metalloproteinase induction and leucocyte adhesion, and highlight the elevation of extracellular matrix metalloproteinase inducer as an orchestrator of the infiltration of leucocytes into the central nervous system parenchyma.

Three times weekly glatiramer acetate in relapsing-remitting multiple sclerosis.
GA 40mg sc tiw is a safe and effective regimen for the treatment of RRMS, providing the convenience of fewer sc injections per week.

Changing associations between cognitive impairment and imaging in multiple sclerosis as the disease progresses.
In a previous study of the same cohort, gray-matter atrophy measured shortly after CIS failed to predict development of cognitive impairment years later. Our findings suggest that gray-matter pathology, reflected by atrophy measurements, becomes increasingly important in determining cognition as MS progresses.

Evaluation of cytokines in multiple sclerosis patients treated with mesenchymal stem cells.
Intrathecal injection of MSCs does not affect cytokine variation in peripheral blood. Because the condition of most of our patients either improved or stabilized after stem cell therapy (SCT), we speculate that the immunomodulatory or neuroregenerative effects of MSC are exerted locally in the central nervous system.

Costs and quality of life in multiple sclerosis patients with spasticity.
The results of this study show that MS spasticity is associated with a substantial burden on society in terms of costs and HRQoL.

Driving performance in persons with mild to moderate symptoms of multiple sclerosis.
Subjects with mild to moderate MS are able to prioritize the driving task above the DA task. The relationship between depression and driving performance in MS merits further investigation.

Pharmacokinetic evaluation of teriflunomide for the treatment of multiple sclerosis.
While teriflunomide is no more effective than a number of other agents that are used in the treatment of MS, it has a favorable side-effect profile and the convenience of once a day oral administration. As such, it is likely to be a popular agent in the treatment of MS over the next 5 years.

Early white matter changes in childhood multiple sclerosis: a diffusion tensor imaging study.
The microstructure of white matter is altered early in the disease course in childhood multiple sclerosis.

Association of Expanded Disability Status Scale and Cytokines after Intervention with Co-supplemented Hemp Seed, Evening Primrose Oils and Hot-natured Diet in Multiple Sclerosis Patients.
Our study shows that co-supplemented hemp seed and evening primrose oils with hot-natured diet can have beneficial effects in improving clinical symptoms in relapsing remitting MS patients and significant correlation was found between EDSS and immunological findings.

Demyelinating disease in SLE: Is it multiple sclerosis or lupus?
This review discusses clinical, pathophysiological, radiological and therapeutic concepts of demyelinating disease of the CNS in SLE, focussing on its differentiation from MS and its relation with other CNS demyelinating processes, such as transverse myelitis, optic neuritis and neuromyelitis optica.

New insights into an autoimmune mechanism, pharmacological treatment and relationship between multiple sclerosis and inflammatory bowel disease.
In this article, we provide a detailed review of the linkage and potential interchangeable medication between IBD and MS in addition to Natalizumab, Trichuris suis egg therapy and vitamin D. Different treatment strategies may have potential in treating both diseases in the future.

Control of spasticity in a multiple sclerosis model using central nervous system-excluded CB1 cannabinoid receptor agonists.
A cannabinoid drug pump is polymorphic and functionally lacking in many laboratory (C57BL/6, 129, CD-1) mice used for transgenesis, pharmacology, and toxicology studies. This phenotype was mapped and controlled by 1-3 genetic loci. ABCC1 within a cluster showing linkage is a cannabinoid CNS-drug pump. Global and conditional CB₁ receptor-knockout mice were used as controls.

Prevalence of extracranial venous narrowing on catheter venography in people with multiple sclerosis, their siblings, and unrelated healthy controls: a blinded, case-control study.
This study shows that chronic cerebrospinal venous insufficiency occurs rarely in both patients with multiple sclerosis and in healthy people. Extracranial venous narrowing of greater than 50% is a frequent finding in patients with multiple sclerosis, unaffected siblings, and unrelated controls. The ultrasound criteria are neither sensitive nor specific for narrowing on catheter venography. The significance of venous narrowing to multiple sclerosis symptomatology remains unknown.

Disease Modifying Therapies Modulate Cardiovascular Risk Factors in Multiple Sclerosis Patients.
There is an association between higher CV risk factors and the use of DMTs. Furthermore, the use of CV and related drugs is associated with MS disease severity. This article is protected by copyright. All rights reserved.

Biopsy findings of symptomatic cerebral X-linked adrenoleukodystrophy and histological differentiation from multiple sclerosis.
Ultrastructural examination to determine the typical laminar inclusions in X-ALD is not always possible. Here, we report on two patients who underwent brain biopsy before the diagnosis of CALD was made. We describe the pathological findings of the biopsied brain lesions and point out histological characteristics which help to differentiate CALD and MS in routine diagnostics.

Can we switch microglia's phenotype to foster neuroprotection? Focus on multiple sclerosis.
While activated microglia have been observed in many neurological diseases of diverse etiology, "activation" indeed does not reveal the functional state of the cells which are often engaged in highly different roles. Indeed, microglia can play both detrimental and beneficial roles depending on inputs and feedback signals arising from the neural environment; such paradoxical roles are associated with phenotypes that range from so-called "classically activated", with highly pro-inflammatory features, to "alternatively activated" associated with a repair-oriented profile.

Predictors of successful acceptance of home telemanagement in veterans with Multiple Sclerosis.
The feasibility of the MS HAT system was assessed by (1) analyzing attitudinal surveys of veterans with MS who used the MS HAT system at home for over a month; (2) identifying factors affecting acceptance of the MS HAT system; (3) reviewing adherence of MS HAT users to self-testing regimen; (4) analyzing veteran feedback on MS HAT functionality using semi-structured qualitative interviews.

Time and time-frequency analysis of near-infrared signals for the assessment of ozone autohemotherapy long-term effects in multiple sclerosis.
The MS subjects showed a marked increase of the CYT-c activity and concentration about 40 minutes after the end of the autohemotherapy, possibly revealing a reduction of the chronic oxidative stress level typical of MS sufferers. From a technical point of view, this preliminary study showed that NIRS could be useful to show the effects of ozone autohemotherapy at cerebral level, in a long term monitoring. The clinical result of this study is the quantitative measurement of the CYT-c level changes in MS induced by ozone autohemotherapy.

Decoding movement intent of patient with multiple sclerosis for the powered lower extremity exoskeleton.
The designed intent recognition algorithm can accurately classify the subject's intended movements with 98.73% accuracy in static states and correctly predict the activity transitions about 100 to 130 ms before the actual transitions were made. These promising results indicate the potential of designed intent recognition interface for volitional control of powered lower extremity exoskeletons.

Monitoring technology for wheelchair users with advanced multiple sclerosis.
The sensors collect information related to the main issues of MS patients: fatigue, heat sensitivity and low mobility. Preliminary results show the signals as the wheelchair is moving, stopped and tilting. The system is able to capture sufficient relevant information to provide suggestions and alarms in a future stage. The system will be tested at The Boston Home, a specialized residence for adults with advanced MS.

Comprehensive Analysis of Human Endogenous Retrovirus Group HERV-W Locus Transcription in Multiple Sclerosis Brain Lesions by High-Throughput Amplicon Sequencing.
However, we obtained evidence for interindividual differences in HERV-W transcript levels. Reporter gene assays indicated promoter activity of many HERV-W long terminal repeats (LTRs), including structurally incomplete LTRs. Our comprehensive analysis of HERV-W transcription in the human brain thus provides important information on the biology of HERV-W in MS lesions and normal human brain, implications for study design, and mechanisms by which HERV-W may (or may not) be involved in MS.

A regenerative approach to the treatment of multiple sclerosis.
Evidence from a cuprizone-induced model of demyelination, in vitro and in vivo T-cell assays and EAE adoptive transfer experiments indicated that the observed efficacy of this drug results directly from an enhancement of remyelination rather than immune suppression. Pharmacological studies indicate that benztropine functions by a mechanism that involves direct antagonism of M1 and/or M3 muscarinic receptors. These studies should facilitate the development of effective new therapies for the treatment of multiple sclerosis that complement established immunosuppressive approaches.

Predictors and dynamics of postpartum relapses in women with multiple sclerosis.
Results confirm a favourable effect on relapses as pregnancy proceeds, and an early postpartum peak. Pre-conception DMT exposure and low ARR were independently protective against postpartum relapse. This novel finding could provide clinicians with a strategy to minimise postpartum relapse risk in women with MS planning pregnancy.

Immunological and clinical consequences of splenectomy in a multiple sclerosis patient treated with natalizumab.
Splenectomy may increase the risk for the development of natalizumab-associated PML via effects on the B cell compartment. It may be regarded as a risk factor in MS patients independent from the duration of disease.

Predicting autoimmunity after alemtuzumab treatment of multiple sclerosis.
Currently available IL-21 ELISA kits should not be used to counsel individuals with multiple sclerosis considering treatment with alemtuzumab.

Inhibitor IκBα promoter functional polymorphisms in patients with multiple sclerosis.
This study reveals that polymorphisms in the IκBα promoter (-881 A/G, -826 C/T) are strongly associated with the susceptibility of Iranian MS patients

Systematic Review of Occupational Therapy-Related Interventions for People With Multiple Sclerosis: Part 2. Impairment.
art 1 (Yu & Mathiowetz, 2014) reviewed evidence for the effectiveness of activity- and participation-based interventions for people with MS. In contrast to the top-down approach, enabling occupational performance can be achieved through remediating impaired personal abilities. Therefore, Part 2 focuses on occupational therapy interventions targeting impairment. Studies included in this review focused on improving client factors and performance skills in people with MS, including cognition, emotional regulation, and motor and praxis skills.

Systematic Review of Occupational Therapy-Related Interventions for People With Multiple Sclerosis: Part 1. Activity and Participation.
This article focuses on occupational therapy interventions aimed at activity and participation, including programs (e.g., inpatient and outpatient rehabilitation) in which an occupational therapy practitioner was one member of the team. Part 2 (Yu & Mathiowetz, 2014) focuses on interventions within the scope of occupational therapy to remediate impairment (e.g., exercise, cognition, emotional regulation).

Fingolimod to treat severe multiple sclerosis after natalizumab-associated progressive multifocal leukoencephalopathy: a valid option?
The outcome was positive on clinical and MRI disease activity, without worsening of the progressive multifocal leukoencephalopathy. These observations suggest that using fingolimod for severe multiple sclerosis after natalizumab-associated progressive multifocal leukoencephalopathy may be an option, under close clinical and radiological monitoring.

A molecular view of multiple sclerosis and experimental autoimmune encephalitis: What can we learn from the epitope data?
This work provides a reference point for the scientific community of the universe of available data for MS-related adaptive immunity in the context of EAE and human disease.

Neurodegeneration progresses despite complete elimination of clinical relapses in a mouse model of multiple sclerosis.
These findings are consistent with both a partial uncoupling of inflammation and neurodegeneration and that the regenerative response of remyelination is negatively correlated with inflammation. These findings strongly support the need for early combinatorial treatment of immunomodulatory therapies and neuroprotective treatments to prevent long-term neurodegeneration in multiple sclerosis.

Off-pump coronary surgery in a patient with multiple sclerosis.
The issues pertaining to the performance of coronary surgery revascularization on patients with multiple sclerosis are discussed.

Smokers with multiple sclerosis are more likely to report comorbid autoimmune diseases.
Smoking is associated with an increased risk of CAD in MS.

Intrathecal baclofen in multiple sclerosis: too little, too late?
Delivery of ITB therapy requires expertly trained staff and proper facilities for pump management. This article summarizes the findings and recommendations of an expert panel on the use of ITB therapy in the MS population and the role of the physician and comprehensive care team in patient selection, screening, and management.

Aggregation of multiple sclerosis genetic risk variants in multiple and single case families.
The primary interest in the MSGB concept resides in its capacity to integrate cumulative genetic contributions to MS risk. This analysis underlines the high variability of family load with known common variants. This novel approach can be extended to other genetically complex diseases. Despite the emphasis on assembling large case-control datasets, multigenerational, multiaffected families remain an invaluable resource for advancing the understanding of the genetic architecture of complex traits.

Fatigue in multiple sclerosis is closely related to sleep disorders: a polysomnographic cross-sectional study.
Our results demonstrate a clear and significant relationship between fatigue and sleep disorders.

The impact of parasite infections on the course of multiple sclerosis.
These new observations on parasite infections associated to MS indicate that parasite regulation of host immunity can alter the course of MS.

Neuroimaging in multiple sclerosis: neurotherapeutic implications.
Advancements that hold promise for the future include new techniques that are sensitive to diffuse changes, the increased use of higher field scanners, measures that capture disease related changes in gray matter, and the use of combined structural and functional imaging approaches to assess the complex and evolving disease process that occurs during the course of MS.

Reduced thymic output and peripheral naïve CD4 T-cell alterations in primary progressive multiple sclerosis (PPMS).
We conclude PPMS patients have peripheral immune alterations related to reduced thymic output.

[Processes of free radical lipid peroxidation with a particular regard to the role of paraoxonase-1 in the pathogenesis of multiple sclerosis].
Oxidative stress is an imbalance between free radicals production and antioxidant defences. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can attact and demage a variety of critical biological molecules, including lipids, essential cellular proteins and DNA and may be exert in pathogenesis of many disorders. Products of lipid peroxidation can be easily reliably detected in biological fluids and tissues, yielding sensitive and specific signals of lipid peroxidation occurred in vivo

Prevalence of cytomegalovirus infection and its role in total immunoglobulin pattern in Iranian patients with different subtypes of multiple sclerosis.
The results extend the observation of an increased frequency of CMV-DNA in patients, in contrast with controls (p<0.001). Furthermore, systemic CMV infections were found in 25.5% of patients and only 3.2% of controls (p<0.001). There was significant difference in the titers of anti-CMV IgG and total IgE in patient and controls (P<0.001). These results support the hypothesis that CMV may contribute to MS thought to establish systemic infection process and induce immune response.

Pregnancy in multiple sclerosis: clinical and self-report scales.
A concomitant improvement in the SF36 domains vitality (p < 0.001) and general health (p = 0.001) was found in patients. At the final visit, at least 9 months after delivery, no worsening of EDSS, GNDS, MSIS-29 or SF36 was observed compared with the (for MS, beneficial) third trimester. Duration of disease, relapses in the year preceding pregnancy or relapses during pregnancy were not associated with postpartum relapse. QoL is improved during pregnancy. Although relapse rate was increased directly after delivery, in the mid long term after delivery no adverse effects of pregnancy on MS were found.

Promoting return of function in multiple sclerosis: An integrated approach.
Most of the currently available disease modifying agents proved to be very effective in managing the relapse rate, however progressive neuronal damage continues to occur and leads to progressive accumulation of irreversible disability. For this reason, any therapeutic strategy aimed at restoration of function must take into account not only immunomodulation, but also axonal protection and new myelin formation. We further highlight the importance of an holistic approach, which considers the variability of therapeutic responsiveness as the result of the interplay between genetic differences and the epigenome, which is in turn affected by gender, age and differences in life style including diet, exercise, smoking and social interaction.

Thalamo-striato-cortical determinants to fatigue in multiple sclerosis.
The findings of the present study indicate that the thalamo-striato-cortical network is involved in the pathophysiology of fatigue in MS, and provide support for the theory of central fatigue. However, due to the limited number of participants and the somewhat heterogeneous sample of MS participants, these results have to be regarded as tentative, though they might serve as a basis for future studies.

Therapeutic laquinimod treatment decreases inflammation, initiates axon remyelination, and improves motor deficit in a mouse model of multiple sclerosis.
Our results support a potential neuroprotective, in addition to immunomodulatory, effect of LQ treatment in inhibiting ongoing MS/EAE disease progression.

Insights into the Mechanisms of the Therapeutic Efficacy of Alemtuzumab in Multiple Sclerosis.
several lines of evidence suggest that the long-term clinical effects of alemtuzumab are attributable to qualitative changes in repopulating lymphocyte subsets potentially leading to a rebalancing of the immune system. Here, we review the contribution of data from animal models, ex vivo human studies, and clinical trials to the understanding of the mechanisms underlying the therapeutic effect of alemtuzumab in patients with RRMS.

Autoantibodies to Non-myelin Antigens as Contributors to the Pathogenesis of Multiple Sclerosis.
The purpose of this review is to analyze recent studies that examine the role that autoantibodies to non-myelin antigens might play in the pathogenesis of MS.

Outcome Measures for Individuals With Multiple Sclerosis: Recommendations From the American Physical Therapy Association Neurology Section Task Force.
The MSTF reviewed 63 OMs. A modified Delphi process was used to build consensus on recommendations for PWMS across the disability spectrum and in various health care settings. Nearly half of the OMs received ratings of 3 or 4 (Recommended or Highly Recommended, respectively) for use in in-patient rehabilitation and outpatient settings, and three of four MS- related disability groupings. The MSTF concluded that the recommendations have broad applicability for clinicians working with PWMS across the disability spectrum, in any health care setting. The recommendations can assist with making sound decisions when selecting OMs for PWMS.

Daclizumab for relapsing remitting multiple sclerosis.
There was no increased number of patients in any adverse events (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.89 to 1.07) or serious adverse events in daclizumab groups compared with placebo (RR 1.15, 95% CI 0.29 to 4.54). Infections were the most frequent adverse events in treated participants and were resolved with standard therapies. One trial was still ongoing.

Discovery of novel disease-specific and membrane-associated markers in a mouse model of multiple sclerosis.
These data provide a unique mechanistic insight into the dynamics of peripheral immune cell infiltration into CNS-privileged sites at a molecular level and has identified several candidate markers which represent promising targets for future multiple sclerosis therapies. The mass spectrometry proteomics data associated with this manuscript have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000255.

Sleep disorders in multiple sclerosis and their relationship to fatigue.
Nocturia may impact MS-related fatigue and should be considered. The treatment of underlying SD led to an improvement of MS-related fatigue. From a scientific point of view, SD should be examined in all studies investigating MS-related fatigue and be considered as a relevant confounder.

[The impact of the vitamin D in neurological diseases and neurorehabilitation: from demencia to multiple sclerosis. Part I: the role of the vitamin D in the prevetion and treatment of multiple sclerosis].
here is no consensus for the role of vitamin D in multiple sclerosis yet, but until the achieving this, the diagnosis and the treatment of the vitamin D deficiency is crucial for scelrosis multiplex patients and in cases of elevated risk. Data shows, that in patient with multiple sclerosis the normal vitamin D level is suboptimal, however the exact role of vitamin D and doses must be clarified by interventional studies.

Functional magnetic resonance imaging of working memory among multiple sclerosis patients.
Normal performance of a challenging VWM task among high-functioning MS patients is associated with a shift toward greater activity in regions related to sensorimotor functions and anterior attentional/executive components of the VWM system. Posterior memory storage systems appeared unaffected, while portions of the visual processing and subvocal rehearsal systems were less active. Although a shift in neural activity was noted relative to HC participants, deviation from regions normally involved in VWM function was not observed in this patient sample.

The management of multiple sclerosis: current and future therapies.
A multidisciplinary team approach is essential in the overall management of the patient with MS, particularly when assessing their needs as a basis for both inpatient rehabilitation programs and in the provision of a comprehensive community-based service.

Factor structure of Guy's Neurological Disability Scale in a sample of Dutch patients with multiple sclerosis.
Guy's Neurological Disability Scale (GNDS) is designed to assess disability (i.e. activity limitations) in patients with multiple sclerosis. It contains 12 functional domains, each indicating a level of disability. Four domain scores and a total score can be calculated.
Results showed a clear factor structure of the GNDS. It justifies the use of the total score of the GNDS. In addition, three sub-scale scores could be used.

Escalation to natalizumab or switching among immunomodulators in relapsing multiple sclerosis.
To evaluate whether an escalation approach was more effective in suppressing clinical and magnetic resonance imaging (MRI) activity than switching among immunomodulators in relapsing-remitting multiple sclerosis (RRMS) patients. We suggest that an escalation to natalizumab is more effective than switching among immunomodulators in RRMS patients who failed a first-line treatment.

The molecular basis of nutritional intervention in multiple sclerosis: a narrative review.
The control of gut dysbiosis and the combination of hypo-caloric, low-fat diets with specific vitamins, oligoelements and dietary integrators, including fish oil and polyphenols, may slow-down the progression of the disease and ameliorate the wellness of MS patients.

Bowel biofeedback treatment in patients with multiple sclerosis and bowel symptoms.
This study aimed to identify effect of biofeedback on bowel symptoms, mood, and anorectal physiology in patients with multiple sclerosis. Biofeedback improves bowel symptoms, depression, and 5-second endurance squeeze pressure in patients with multiple sclerosis.

Redox regulation of cellular stress response in multiple sclerosis.
Our data strongly support a pivotal role for redox homeostasis disruption in the pathogenesis of MS and, consistently with the notion that new therapies that prevent neurodegeneration through nonimmunomodulatory mechanisms can have a tremendous potential to work synergistically with current MS therapies, unravel important targets for new cytoprotective strategies.

Diffuse coronary ectasia complicated by myocardial infarction in a patient with multiple sclerosis-transradial dethrombosis and one-year coronary computed tomography angiography follow-up.
The higher thrombotic burden in MS with CAE was analyzed and possible common pathophysiologic pathways were discovered in the imbalance between proteolytic activities of metalloproteinases and endogenous tissue inhibitor, with subsequent increased proteolysis leading to a risk for coronary plaque rupture. The one-year clinical and angiographic follow-up with coronary computed tomography (CT) angiography, together with long-term antiplatelet therapy, was also evaluated.

Sun exposure, vitamin D intake and progression to disability among veterans with progressive multiple sclerosis.
These results suggest that exposure to vitamin D before MS onset might slow disease-related neurodegeneration and thus delay progression to disability among patients with the progressive subtype.

Pulse pressure is associated with walking impairment in multiple sclerosis.
There was no association between any PP measure and 6 MW distance in controls (p>0.05 for all). In conclusion, PP is a predictor of gait performance in persons with MS. These findings suggest that vascular senescence and altered ventricular-vascular coupling may contribute, in part, to the deterioration of physical function in persons with MS.

Diffusion tensor imaging and cognitive speed in children with multiple sclerosis.
To compare white matter (WM) integrity in children with MS and healthy children using diffusion tensor imaging (DTI), and correlate DTI findings with disease activity, lesion burden, and cognitive processing speed. MS participants displayed lower FA values in the genu (p<0.005), splenium (p<0.001) and in NAWM of bilateral parietal, temporal, and occipital lobes (p<0.001) versus controls. FA and MD in the thalamus did not differ between groups. Higher lesion volumes correlated with reduced FA in CC and hemispheric NAWM. DTI metrics did not correlate with EDSS. FA values in CC regions correlated with Visual Matching (p<0.001) and SDMT (p<0.005) in MS participants only.

Functional outcomes after management of end-stage neurological bladder dysfunction with ileal conduit in a multiple sclerosis population: a monocentric experience.
To assess the outcome of cutaneous noncontinent urinary diversion (CNCUD) for neurogenic bladder management in multiple sclerosis (MS) patients. Cystectomy and CNCUD are indicated in MS-impaired patients who are refractory to medical treatment and they can result in disappearance of neurological bladder symptoms. CNCUD appears to be the procedure of choice to improve the quality of life of selected patients, despite the fact that it is associated with high perioperative morbidity.

Extra-cranial venous flow in patients with multiple sclerosis.
We found no evidence to suggest that MS patients have excess of CCSVI. In addition we failed to observe a typical venous flow pattern in MS patients. Until carefully designed controlled studies to investigate CCVSI have been completed, invasive and potentially dangerous endovascular procedures as therapy for MS should be discouraged.

Potential association of vitamin D receptor polymorphism Taq1 with multiple sclerosis.
We have identified weak evidence of an association between a common variation within the VDR gene and MS, in the largest study reported to date of this candidate gene. There appears to be a relationship between polymorphisms in the VDR and the risk of MS, which is potentially modified by HLA-DRB1*1501.

Increased risk of multiple sclerosis among women with migraine in the Nurses' Health Study II.
Using a large, cohort of women-nurses, history of migraine was associated with an increased risk of MS. However, the difference in absolute risk of MS in migraineurs and non-migraineurs was small.

TRAIL/TRAIL receptor system and susceptibility to multiple sclerosis.
The combination of the alleles G/T/A in these SNPs appears to be associated with a reduced risk of developing MS (p = 2.12×10(-5), OR = 0.59). These results suggest that genes of the TRAIL/TRAIL receptor system exerts a genetic influence on MS.

Sleep disturbances in multiple sclerosis.
Sleep disturbances are more common in MS patients than in the general population and limit these patients' quality of life. Therefore, we believe that these disturbances should be a focal point in any multidisciplinary treatment for MS.

EBNA-1 IgG titers in Sardinian multiple sclerosis patients and controls.
results confirm previous findings and strengthen the association between EBV and MS in Sardinia.

Temporal and spatial evolution of grey matter atrophy in primary progressive multiple sclerosis.
findings provide new insights into the characteristics of GM atrophy across the brain in MS, and have potential consequences for the selection of brain atrophy as an outcome measure in neuroprotective clinical trials.

Prevalence of epilepsy in a cohort of patients with multiple sclerosis.
Patients with epilepsy and MS are younger and have an earlier onset of symptoms. Since most seizures were partial, the presence of cortical lesions and progressive brain atrophy could probably be the pathophysiological mechanism underlying this association.

Resveratrol exacerbates both autoimmune and viral models of multiple sclerosis.
findings indicate that caution should be exercised in potential therapeutic applications of resveratrol in human inflammatory demyelinating diseases, including multiple sclerosis.

Antigenic epitopes of MAP2694 homologous to T-cell receptor gamma-chain are highly recognized in multiple sclerosis Sardinian patients.
Two out of 58 synthetic 9-mers were strongly recognized by MS patients' antibodies compared to controls. A competitive inhibition assay demonstrated that these two epitopes are immunodominant antibody targets within MAP2694 protein, as sera pre-adsorbed with these peptides were able to significantly block the antibody reaction to the MAP2694 protein, even if at a lesser extent than MAP2694 protein itself.

Emerging injectable therapies for multiple sclerosis.
Ofatumumab is a monoclonal antibody that has shown efficacy in a small phase 2 trial. Animal models suggest that anti-LINGO1 antibody has remyelinating potential, and phase 2 trials of the antibody are underway. Further clarification of purported mechanisms of action and continued surveillance will be essential to establish the safety and clinical efficacy of these drugs in patients with relapsing-remitting MS.

Idiopathic acute transverse myelitis: outcome and conversion to multiple sclerosis in a large series.
At least 13% of patients who fulfill the TMCWG criteria for definite and possible IATM will convert to MS. Functional recovery in IATM is poorer in patients with urinary sphincter dysfunction at admission or LETM on MRI.

Preference-based Health status in a German outpatient cohort with multiple sclerosis.
MS considerably impairs patients' health status. Guidelines aiming to improve self-reported health status should include treatment options for depression and fatigue. Physicians should be aware of depression and fatigue as co-morbidities. Future studies should consider the minimal clinical difference when health status is a primary outcome.

A systematic review of pharmacological pain management in multiple sclerosis.
Our objective was to systematically review pain management strategies for the reduction of non-spastic and non-trigeminal neuralgic pain in MS patients. More trials with rigorous design and reporting are needed to determine effective treatments for specific pain types presenting in people living with MS.

Gene expression analysis of relapsing-remitting, primary progressive and secondary progressive multiple sclerosis.
We hypothesized that different MS subtypes would show differences in gene expression that could be traced to specific subsets of peripheral blood mononuclear cells (PBMCs). Differences in gene expression, which could be traced to B cells, CD8+ T cells and monocytes, were found between MS patients and HCs but only minor differences were observed between MS subgroups.

A novel nanoparticle containing MOG peptide with BTLA induces T cell tolerance and prevents multiple sclerosis.
These findings suggested that DCs transduced with nanoparticle could induce specific CD4+ T-cells tolerance, which provided a promising therapeutic means to negatively manipulate immune response for autoimmune diseases without inhibition of the immune response to irrelevant Ag.

[Consensus document on spasticity in patients with multiple sclerosis].
The recommendations included in this consensus can be a useful tool for improving the quality of life of multiple sclerosis patients, as they enable improved diagnosis and treatment of spasticity.

Diagnostic ability of a new method for measuring haemoglobin levels in the optic nerve head in multiple sclerosis patients.
Measurements of optic disc Hb levels obtained with Laguna ONhE software had good ability detecting optic atrophy and axonal loss in MS patients. This method had good reliability and is easy to implement in routine clinical practice.

Modulation of oxidative stress, apoptosis, and calcium entry in leukocytes of patients with multiple sclerosis by Hypericum perforatum.
We observed that HP-induced protective effects on oxidative stress and [Ca²⁺]_i concentrations by modulating transient receptor potential and voltage gated calcium channel in the patients with MS. Thus, it may provide useful treatment of neutrophil activity in the patients.

Use of health services in people with multiple sclerosis with and without depressive symptoms: a two-year prospective study.
The issues underlying the differences in the use of healthcare need to be explored further, as well as the plausible implications for the organization of healthcare services for people with MS and depressive symptoms. Furthermore, the life situations of caregivers of people with MS and depressive symptoms should be considered, and appropriate interventions supplied in order to diminish caregiver burden.

[New and emerging treatments for multiple sclerosis].
A better knowledge of fundamental pathophysiology is associated with the development of new molecules targeting the immunological cascade of the disease as well as the mechanisms promoting remyelination and repair.

Serum levels of brain-derived neurotrophic factor (BNDF) in multiple sclerosis patients with Trichuris suis ova therapy.
The serum Brain-derived neurotrophic factor (BDNF) levels of these four patients were assessed before, during and after therapy with TSO and showed significant decrease of BDNF during TSO therapy (p < 0.05).

Disconnection mechanism and regional cortical atrophy contribute to impaired processing of facial expressions and theory of mind in multiple sclerosis: a structural MRI study.
Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed), processing of emotions (right entorhinal cortex) and socially relevant information (left temporal pole). Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients.

Quick screening of cognitive function in Indian multiple sclerosis patients using Montreal cognitive assessment test-short version.
Cognitive impairments in multiple sclerosis (MS) are now well recognized worldwide, but unfortunately this domain has been less explored in India due to many undermining factors. The aim of this study was to evaluate cognitive impairments in Indian MS patients with visual or upper limb motor problems with the help of short version of Montreal cognitive assessment test (MoCA).
The 12 points, short version of MoCA, is a useful brief screening tool for quick and early detection of mild cognitive impairments in subjects with MS. It can be administered to patients having visual and motor problems. It is of potential use by primary care physicians, nurses, and other allied health professionals who need a quick screening test. No formal training for administration is required. Financial and time constraints should not limit the use of the proposed instrument.

Interleukin 2 receptor α chain gene polymorphisms and risks of multiple sclerosis and neuromyelitis optica in southern Japanese.
Interleukin 2 receptor α subunit (IL2RA) is a genetic risk for multiple sclerosis (MS) in Caucasians. However, the association between MS and IL2RA in Japanese idiopathic demyelinating diseases of the central nervous system has not been examined. Although the possibility that IL2RA is a risk factor for MS development was not confirmed in this Japanese population, IL2RA gene polymorphisms were able to modify the disease activity in female MS patients, but had no influence on either susceptibility or disease phenotype in NMO/NMOSD patients.

Association Between IL-6-174G/C Polymorphism and Risk of Multiple Sclerosis: A Meta-Analysis.
This meta-analysis provides evidence that the IL-6-174G/C polymorphism may be a risk factor for the development of MS in Asians. Further association studies with a larger sample size are required to confirm the result in different populations.

Dilated Virchow-Robin spaces and multiple sclerosis: 3 T magnetic resonance study.
Our results confirm previous reports regarding the increase in VRSd in nonactive phases of MS and support the immunological role of the VRS within the central nervous system. The lack of correlation between VRSd and the degree of GCA and their prevailing localisation in atypical sites in MS patients make VRSd a potential marker of inflammatory-demyelinating disease.

Catechol-O-Methyltransferase Val158Met Polymorphism (rs4680) Is Associated With Pain in Multiple Sclerosis.
This study suggests that the Val158Met polymorphism is associated with the presence of pain in MS, but it is not a risk factor for MS itself because the presence of the Met/Met genotype was more prevalent in those patients with pain. This study provides further evidence of potential genetic factors that predispose patients with MS to develop pain.

Teriflunomide for the treatment of relapsing multiple sclerosis: a review of clinical data.
To review the pharmacology and clinical data for teriflunomide in relapsing multiple sclerosis (MS).
Teriflunomide is an effective and safe oral treatment option for relapsing MS. It can be used as monotherapy or added to an interferon or glatiramer acetate. It reduces the rate of relapse and may slow disease progression. The advantages of this drug are the convenience of oral administration and good tolerability. The disadvantage is the lack of long-term safety data and data about the benefit of combination therapy.

ExtaviJect® 30G device for subcutaneous self-injection of interferon beta-1b for multiple sclerosis: a prospective European study.
The ExtaviJect® 30G autoinjector was developed to facilitate parenteral self-administration of interferon beta-1b (Extavia®), a first-line disease-modifying therapy in patients with multiple sclerosis. Our aim was to assess patient compliance with treatment when using the autoinjector, patients' and nurses' experiences of using the device, its tolerability, and patient satisfaction.
ExtaviJect 30G was convenient to use and was associated with high levels of compliance.

Evaluation of the Persian version of modified fatigue impact scale in Iranian patients with multiple sclerosis.
Fatigue, a major cause of disability in individuals with multiple sclerosis (MS), is associated with reduced quality of life. The aim of this study was to evaluate the reliability and reproducibility of the Persian version of Modified Fatigue Impact Scale (MFIS) in Iranian patients with MS.
According to our findings, the Persian version of the MFIS has a good reliability and reproducibility for assessment of fatigue in patients with MS.

MicroRNAs and multiple sclerosis: from physiopathology toward therapy.
The miRNAs in central nervous system lesions and peripheral blood are potential biomarkers for diagnostic and prognostic use. Also, miRNA mimics, small-molecule inhibitors of specific miRNAs, and antisense oligonucleotides could be therapeutic weapons that facilitate us to combat the disease.

Increased breast cancer risk for patients with multiple sclerosis: a nationwide population-based cohort study.
Studies have suggested that multiple sclerosis (MS) might be linked to an overall reduced cancer rate, but a positive relationship is also found for several types of cancer. This study determines whether MS is associated with cancer risk in Taiwan. The nationwide population-based cohort study revealed that Taiwanese patients with MS have a higher risk of developing overall cancer types and breast cancer in particular.

Multiple sclerosis and risk of Parkinson's disease: a Danish nationwide cohort study.
Case reports have observed a co-occurrence of multiple sclerosis (MS) and Parkinson's disease (PD) and it has been hypothesized that MS lesions could affect dopaminergic pathways causing parkinsonism. Our aim was to examine the association between MS and PD in a historically prospective cohort study using Danish nationwide register data. Our data do not suggest an increased risk of PD amongst patients with MS.

Incidence and prevalence of multiple sclerosis in the UK 1990-2010: a descriptive study in the General Practice Research Database.
To estimate the incidence and prevalence of multiple sclerosis (MS) by age and describe secular trends and geographic variations within the UK over the 20-year period between 1990 and 2010 and hence to provide updated information on the impact of MS throughout the UK.
We estimate that 126 669 people were living with MS in the UK in 2010 (203.4 per 100 000 population) and that 6003 new cases were diagnosed that year (9.64 per 100 000/year). There is an increasing population living longer with MS, which has important implications for resource allocation for MS in the UK.

Surface-based analysis reveals regions of reduced cortical magnetization transfer ratio in patients with multiple sclerosis: A proposed method for imaging subpial demyelination.
These findings suggest that our method is a plausible in vivo imaging technique for quantifying subpial cortical demyelinating lesions in patients with multiple sclerosis and, furthermore, can be applied at the typical clinical field strength of 1.5 T. Hum Brain Mapp, 2013.

C9ORF72 repeat expansion not detected in patients with multiple sclerosis.
In this study, we sought to evaluate the presence of the C9ORF72 repeat expansion in a cohort consisting of 314 patients with MS and 222 control subjects. No pathogenic expansion was found in MS and control populations, suggesting that C9ORF72 does not play a major role in MS pathogenesis

Determination of Brain Volumes Using Quantitative MR Imaging in Patients with Multiple Sclerosis.
There were statistically significant differences between both RR (P<0.05) and SP (P<0.05) compared with control subjects but no differences between RR and SP volumes. MRI-estimated cerebrum volumes may be help to evaluate patients' clinical status and provide a simple index to assess the efficiency of therapy.

Investigation of heterogeneity in the association between interferon beta and disability progression in multiple sclerosis: an observational study.
It was recently reported that there was no significant overall association between interferon beta exposure and disability progression in relapsing-remitting multiple sclerosis (RRMS) patients in an observational study from Canada. In the current study, the potential for heterogeneity in the association between exposure to interferon beta and disability progression across patients' baseline characteristics was investigated. RRMS patients with more frequent relapses at baseline may be more likely to benefit from interferon beta treatment with respect to long-term disability progression.

Multiple sclerosis in the mount etna region: possible role of volcanogenic trace elements.
To evaluate the possible association between Multiple Sclerosis and exposure to volcanogenic trace elements. We found a higher prevalence and incidence of Multiple Sclerosis among populations living in the eastern flank of Mount Etna. According to our data a possible role of TE cannot be ruled out as possible co-factor in the MS pathogenesis. However larger epidemiological study are needed to confirm this hypothesis.

Comparison of 3D Cube FLAIR with 2D FLAIR for Multiple Sclerosis Imaging at 3 Tesla.
The difference was mostly accounted for by supratentorial lesions (N = 372 vs. N = 216) while the infratentorial lesion counts were low in both sequences. SNRs and CNRs were significantly higher in CUBE FLAIR with the exception of the CNR of lesion to gray matter, which was not significantly different. Conclusion: Cube FLAIR showed a higher sensitivity for MS lesions compared to a 2 D FLAIR sequence. 3 D FLAIR might replace 2 D FLAIR sequences in MS imaging in the future.

Antibodies to Interferon beta in Patients with Multiple Sclerosis Receiving CinnoVex, Rebif, and Betaferon.
The proportion of BAb+ was 38.1% for Betaferon, 21.9% for Rebif, and 26.8% for CinnoVex. Five BAb-positive MS patients were lost to follow-up; thus 31 BAb-positive MS patients were studied for NAbs. NAbs were present in 25 (80.6%) of BAb-positive MS patients receiving IFN-β. In conclusion, the three IFN-β preparations have different degrees of immunogenicity.

Methylation differences at the HLA-DRB1 locus in CD4+ T-Cells are associated with multiple sclerosis.
To identify methylation changes associated with MS, we performed a genome-wide DNA methylation analysis of CD4+ T cells from 30 patients with relapsing-remitting MS and 28 healthy controls using Illumina 450K methylation arrays. Our findings provide the first evidence for association of DNA methylation at HLA-DRB1 in relation to MS risk. Further studies are now warranted to validate and understand how these findings are involved in MS pathology.

MicroRNA-155 modulates Th1 and Th17 cell differentiation and is associated with multiple sclerosis and experimental autoimmune encephalomyelitis.
These findings demonstrate that miR-155 confers susceptibility to EAE by affecting inflammatory T cell responses and can be a new target for therapy of multiple sclerosis.

Up-regulation of inducible heat shock protein-70 expression in multiple sclerosis patients.
Our data hint at altered immune responses in MS and may indicate either a state of chronic stress or increased vulnerability to physiological immune responses in MS patients.

Early recognition and diagnosis of multiple sclerosis.
Prevalence rates for MS vary depending on geography, and susceptibility for MS appears to be influenced by both environmental and genetic risk factors.

The nervous system's potential role in multiple sclerosis associated bone loss.
This review summarizes common risk factors, physiologic and genetic, that may contribute to the etiology and progression of osteoporosis in MS patients as well as providing insight into nervous system control of bone metabolism and homeostasis.

Microsatellite polymorphism in haem oxygenase 1 gene promoter in multiple sclerosis.
The observed absence of effect of the HMOX1 promoter (GT)n polymorphism could be attributed to its known dualistic role in the pathogenesis of autoimmune disorders. As a secondary outcome, we have seen that disease-modifying drugs have the potential to delay disability progression in patients with multiple sclerosis.

Detecting cortical lesions in multiple sclerosis at 7 T using white matter signal attenuation.
Despite the B1 inhomogeneities common at ultra-high field strengths, WHAT with an adiabatic inversion pulse showed good cortical lesion detection and would be a valuable component of clinical MS imaging protocols.

Magnetic resonance spectroscopic findings of chronic lesions in two subtypes of multiple sclerosis: primary progressive versus relapsing remitting.
We compared brain metabolite concentrations and ratios in patients with PPMS and RRMS by magnetic resonance spectroscopic imaging (MRSI). MRS is a potential way to differentiate PPMS and RRMS.

Depression and sleep disturbances in patients with multiple sclerosis and correlation with associated fatigue.
To observe prevalence of depression and sleep disturbances in multiple sclerosis (MS) patients and their correlation with associated fatigue. Depression and sleep disturbance in patients with MS is significantly correlated with associated fatigue.

Multiple Sclerosis: Lessons from Molecular Neuropathology.
The molecular characterization of the demyelinating factor may provide an important clue for the understanding of MS pathogenesis in the future.

Intensity Based Methods for Brain MRI Longitudinal Registration. A Study on Multiple Sclerosis Patients.
We then focus on assessing which is the best registration method for longitudinal MRI images of MS patients. In order to analyze the results obtained for all studied criteria, we use both descriptive statistics and statistical inference: one way ANOVA, pairwise t-tests and permutation tests.

Subcortical Deep Gray Matter Pathology in Patients with Multiple Sclerosis Is Associated with White Matter Lesion Burden and Atrophy but Not with Cortical Atrophy: A Diffusion Tensor MRI Study.
These findings suggest that subcortical deep gray matter abnormalities are associated with white matter lesion burden and atrophy, whereas cortical atrophy is not associated with microstructural alterations of subcortical deep gray matter structures in patients with MS.

Transcranial brain photoplethysmography to study the venules of cerebral cortex in patients with multiple sclerosis.
To evaluate the utility of a transcranial brain photoplethysmography parameter as a potential marker for patients with multiple sclerosis. Our study reveals that a minor increase in cerebral blood volume on the frontal cortex of both sides in sitting position is associated with a diagnosis of multiple sclerosis and might be a new marker.

Cutaneous and pulmonary sarcoidosis following treatment of multiple sclerosis with interferon-beta-1b: a case report.
Sarcoidosis is considered one of the most common multiple sclerosis imitators with involvement of the central nervous system. However, although rare, sarcoidosis can develop following treatment with interferon-beta-1b and should be considered in patients with multiple sclerosis treated with beta-interferons who develop pulmonary or extra-pulmonary manifestations of sarcoidosis. Interferon-beta-1b discontinuation is the first and most important step in the treatment of such cases followed by treatment with corticosteroids.

Inflammation in neurodegenerative diseases - an update.
A better understanding of how immune responses are involved in neuronal damage and regeneration, as reviewed here, will be essential to develop effective therapies to improve quality of life, and mitigating the personal, economic and social impact of these diseases. This article is protected by copyright. All rights reserved.

Self-tolerance in multiple sclerosis.
Regulatory T cells suppress the general local immune response via bystander effects rather than through individual antigen-specific responses. Interestingly, the beneficial effects of currently approved immunomodulators (interferons β and glatiramer acetate) are associated with a restored regulatory T cell homeostasis. However, the feedback regulation between Th1 and Th17 effector cells and regulatory T cells is not so simple and tolerogenic mechanisms also involve other regulatory cells such as B cells, dendritic cells and CD56(bright) natural killer cells.

Sex-related factors in multiple sclerosis susceptibility and progression.
The unravelling of the mechanisms underlying these clinical observations in the laboratory and application of the results to the clinical setting is a unique and potentially fruitful strategy to develop novel therapeutic approaches for MS.

Increased determinism in brain electrical activity occurs in association with multiple sclerosis.
Increased determinism (decreased complexity) of brain electrical activity has been associated with some brain diseases. Our objective was to determine whether a similar association occurred for multiple sclerosis (MS). The mean±SD of %R for the MS subjects was 6·6±1·3%, compared with 5·1±1·3% in the normal group (P = 0·017), indicating that brain activity in the subjects with MS was less complex, as hypothesized. The groups were not distinguishable using %D or spectral analysis.

Multiple sclerosis and sexual dysfunction.
Maintaining a healthy sexual life with MS is an important priority. The treatment of SD requires multidisciplinary teamwork and cooperation among specialists, individual patients, partners and the society.

Treatment update in multiple sclerosis.
This paper details currently available treatments and some that are expected to reach the market shortly.

Can we overcome the 'clinico-radiological paradox' in multiple sclerosis?
conventional MRI is highly predictive of clinical disability in MS when pattern-based algorithms are used for prediction. Thus, the so-called clinico-radiological paradox is not apparent when using suitable analysis techniques.

The symptom inventory disability-specific short forms for multiple sclerosis: reliability and factor structure.
To further the development of the 99-item Symptom Inventory (SI) for multiple sclerosis (MS) using modern test theory methods to create 3 disability-specific short forms for MS patient subgroups identified using Performance Scale (PS) items. This study provides empirical support for a 10-scale symptom measure for use in MS clinical research, with short forms in 5 scales tailored to have good specificity for people with mild, moderate, and severe disability and single forms for the remaining 5 scales. The PS items can serve as a screener for these disability-specific short forms, which provide choice and flexibility that are similar to a computerized adaptive test but without the reliance on real-time computer infrastructure.

Pharmacological treatment for memory disorder in multiple sclerosis.
We found no convincing evidence to support the efficacy of pharmacological symptomatic treatment for MS-associated memory disorder because most of available RCTs had a limited quality. Whether pharmacological treatment is effective for memory disorder in patients with MS remains inconclusive. However, there is moderate-quality evidence that donepezil 10 mg daily was not effective in improving memory in MS patients with mild memory impairment, but had a good tolerability. Adverse events such as nausea, diarrhoea and abnormal dreams were not frequent but were associated with treatment. Ginkgo biloba, memantine and rivastigmine were safe and well tolerated and no serious adverse effects were reported. Future large-scale RCTs with higher methodological quality are needed.

A Review of Safety-Related Pregnancy Data Surrounding the Oral Disease-Modifying Drugs for Multiple Sclerosis.
Using existing information from published clinical trials and drug monographs, as well as recent conference proceedings, this review summarizes the mechanism of action (in relation to embryogenesis and pregnancy) and existing animal or human pregnancy-related data for approved (fingolimod, teriflunomide and dimethyl fumarate) and investigational (laquinimod and firategrast) oral DMDs for MS.

Multiple Sclerosis Disease Progression and Paradichlorobenzene: A Tale of Mothballs and Toilet Cleaner.

Partial recovery after severe immune reconstitution inflammatory syndrome in a multiple sclerosis patient with progressive multifocal leukoencephalopathy.
There is still difficulty in differentiating PML progression from IRIS onset and there is not a clear description in the literature about different clinical forms of IRIS, prognostic factors and guidelines to properly treat this complication in order to reduce the residual disability of the patient surviving this treatment complication.

Risk acceptance in multiple sclerosis patients on natalizumab treatment.
We aimed to investigate the ability of natalizumab (NTZ)-treated patients to assume treatment-associated risks and the factors involved in such risk acceptance. Risk acceptance is a multifactorial phenomenon, which might be partly explained by an adaptive process, in light of the higher risk acceptance amongst NTZ-treated patients and, especially, amongst those who are JCV seropositive but still have low PML risk, but which seems also intimately related to personality traits.

Ten Years of Proteomics in Multiple Sclerosis.
In this review, we summarize these data, presenting their value to the current knowledge of the disease mechanisms, as well as their importance as identification of biomarkers or treatment targets.

Using existing data to identify candidate items for a health state classification system in multiple sclerosis.
This study produced a health state classifier system based on items impacted upon by MS, and demonstrated the potential to discriminate the health impact of the disease.

Magnetization transfer and adiabatic T1ρ MRI reveal abnormalities in normal-appearing white matter of subjects with multiple sclerosis.
With the goal of exploring the sensitivity of novel MRI parameters to detect such abnormalities, we implemented an inversion-prepared magnetization transfer (MT) protocol and adiabatic T1ρ and T2ρ rotating frame relaxation methods. The results suggest degenerative processes occurring in the NAWM of MS, likely not accompanied by significant abnormalities in iron content.

Toll-like receptor 3 differently modulates inflammation in progressive or benign multiple sclerosis.

Coexistence of systemic lupus erythematosus and multiple sclerosis: Prevalence, clinical characteristics, and natural history.
The coexistence of systemic lupus erythematosus (SLE) and multiple sclerosis (MS) in the same individual has rarely been described. Our objective was to report on the prevalence, clinical characteristics, and prognosis of cases fulfilling the criteria for both SLE and MS. Occurrence of both diseases in the same individual is rare, corroborating data that suggest distinct molecular signatures. SLE and MS coexistence was not associated with a severe phenotype for either entity.

Body fluid biomarkers in multiple sclerosis.
Despite the need for biomarkers and extensive research to identify them, validation and clinical application of biomarkers is still an unmet need in multiple sclerosis, and large gaps remain between exploratory biomarkers proposed in many studies, validated biomarkers, and biomarkers that are integrated into routine clinical practice.

Clinical presentation of pediatric multiple sclerosis before puberty.
To facilitate early diagnosis it is important to recognize that pre-pubertal MS presents with a specific pattern of symptoms that is maintained over the first two disease years.

Plasma homocysteine levels in patients with multiple sclerosis in the Greek population.
In recent years, there has been increasing interest in the role of plasma homocysteine (Hcy) as a possible risk factor for several diseases of the central nervous system. The aim of this study was to determine the plasma levels of Hcy in a group of multiple sclerosis (MS) patients from a Greek population and the possible correlation with age, disability status, activity or duration of disease, sex, and treatment. The preliminary data suggest that Hcy levels were not elevated in our sample of Greek MS patients, which does not support previous findings of a significant correlation between elevated serum Hcy levels and MS. Further studies to establish a possible association between MS and Hcy levels in the context of different ethnic groups with different habits are needed.

Circulating levels of soluble apoptosis-related molecules in patients with multiple sclerosis.
These findings support a role of TRAIL in the pathogenesis of MS, especially during the acute phases of the disease.

Predictors of changes in suicidality in multiple sclerosis over time.
Interventions aimed at evaluating and monitoring depression over time should be considered in order to reduce the risk of suicidality. Implications for Rehabilitation Due to the inconsistency and unpredictability of MS, depression should be assessed routinely. Given the high prevalence of depression and suicidality in MS, mental health services should be available and encouraged by healthcare providers treating individuals with MS.

Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells.
umarates improve multiple sclerosis (MS) and psoriasis, two diseases in which both IL-12 and IL-23 promote pathogenic T helper (Th) cell differentiation. However, both diseases show opposing responses to most established therapies. First, we show in humans that fumarate treatment induces IL-4-producing Th2 cells in vivo and generates type II dendritic cells (DCs) that produce IL-10 instead of IL-12 and IL-23. In mice, fumarates also generate type II DCs that induce IL-4-producing Th2 cells in vitro and in vivo and protect mice from experimental autoimmune encephalomyelitis.

Adversarial growth in patients with multiple sclerosis and their partners: relationships with illness perceptions, disability and distress.
The findings support the idea of a 'communal search for meaning' where patients and their partners experience the trauma of having a chronic illness and subsequently find positive aspects together.

Down syndrome presenting with multiple sclerosis, thyroid dysfunction, and diabetes mellitus. Multiple autoimmune disorders in a genetic disorder.
An association of DS and other autoimmune disease has been previously reported, and we report one case of DS in coexistence with MS, diabetes mellitus, and thyroid diseases. We suggest that MS, such as other autoimmune diseases, is prevalent in DS patients.

B cells in multiple sclerosis: connecting the dots.

Cesarean delivery may increase the risk of multiple sclerosis.
This study was designed to evaluate whether mode of delivery (vaginal versus cesarean section), as a perinatal factor, affects susceptibility to MS. Our results suggest that those born by vaginal delivery are at a lower risk of subsequent MS. These preliminary findings will need to be addressed in a much larger and preferably prospective study.

Evaluation of a new model of short-term palliative care for people severely affected with multiple sclerosis: a randomised fast-track trial to test timing of referral and how long the effect is maintained.
Receiving PC earlier has a similar effect on reducing symptoms but greater effects on reducing care giver burden, compared to later referral. In this phase II trial, the authors lacked the power to detect small differences. The effect of PC is maintained for 6 weeks after withdrawal but then appears to wane.

A cross-sectional, multicentre study of the therapeutic management of multiple sclerosis relapses in Italy.
Our study confirms the therapeutic attitude of multiple sclerosis specialists in treating relapses with high-dose intravenous corticosteroids in a day hospital setting, with a tapering in a proportion of cases. The main reasons for prescription are relapse severity and symptom evolution.

Differentiating patterns of oligoclonal banding in the cerebrospinal fluid improves diagnostic utility for multiple sclerosis.
The diagnostic significance of oligoclonal bands in CSF for MS/CIS can be improved by restricting interpretation to the delta banding pattern alone.

The possible underlying pathophysiological mechanisms for development of multiple sclerosis in familial Mediterranean fever.
Due to mitochondrial energy deficit, remyelination may not be achieved, and therefore, axonal damage increases. Thus, at the end of these pathophysiological processes, MS findings may occur in the FMF patients especially with irregular use of colchicine.

Fatigue and heat sensitivity in patients with multiple sclerosis.
Fatigue is one of the most common and troubling symptoms of multiple sclerosis (MS), and heat is often reported as a trigger. Although it is assumed that this heat sensitivity is specific for MS, the evidence for disease specificity is limited. We studied the relationship between fatigue, heat sensitivity, and environmental temperature, and its specificity for MS. Our findings support the assumption that heat sensitivity regarding fatigue has an MS-specific component. Although patients with MS experience a relationship between environmental temperature and fatigue, objective assessment by climatological data could not confirm this.

Physical activity, self-efficacy, and health-related quality of life in persons with multiple sclerosis: analysis of associations between individual-level changes over one year.
Physical activity and self-efficacy both might be important targets of subsequent behavioral and self-management interventions for improving the HRQOL of persons with MS, although self-efficacy is seemingly more important than physical activity.

Supervised resistance training results in changes in postural control in patients with multiple sclerosis.
The findings suggested that postural control of MS patients could be affected by a supervised resistance training intervention.

Advances in imaging to support the development of novel therapies for multiple sclerosis.
Higher-field MR scanners and new positron emission tomography (PET) radioligands are providing new insights into cellular and pathophysiological abnormalities, and should be valuable in future therapeutic trials. Retinal axonal loss measured using optical coherence tomography (OCT) can assess acute neuroprotection in optic neuritis.

Patient satisfaction in rehabilitation of patients with multiple sclerosis.
The motor and non-motor symptoms of multiple sclerosis often result in a substantially reduced health-related quality of life. We surveyed patient satisfaction and own evaluation of the benefit of a period spent at a specialised rehabilitation centre. Patients who have had stays at the Hakadal MS rehabilitation centre are satisfied and feel that the stay will be of great importance to their level of functioning and mastery.

Impairment of heme synthesis in myelin as potential trigger of multiple sclerosis.
According to the present hypothesis, MS can be primarily triggered by environmental factors acting on a genetic susceptibility, while the immune response may be a consequence of a primary oxidative damage due to reactive oxygen species produced consequently to an imbalance of cytochromes and respiratory chains in the sheath.

Caregiving in multiple sclerosis.
Rehabilitation medicine professionals should be aware of the high risk of caregiver burden. Assessment of caregiver needs and appropriate intervention will help minimize the burden on caregivers.

Exercise in multiple sclerosis.
General guidelines are available for exercise prescription for the MS population. There are several recommendations that may help improve the quality of future MS exercise trials.

[The first experience of the use the Russian Betaseron biosimilar (infibeta) in the daily practice of the Moscow Center of Multiple Sclerosis.]
Good tolerability comparable to that of the original drug was observed during the first year of treatment. There was no refusal from therapy with infibeta, which indicated sufficiently strong adherence to this type of treatment.

[Clinical characteristics of multiple sclerosis in the Tomsk region.]
The more favorable course of disease (the lesser severity of disability and slower rate of MS progression) was found in women.

[Clinical and electrophysiological and molecular genetic characteristics of the course of relapsing-remitting multiple sclerosis.]

Current evaluation of alemtuzumab in multiple sclerosis.
Alemtuzumab offers induction strategy for very active relapsing MS patients who have failed conventional therapy, and possibly selected treatment-naive patients. Alemtuzumab use is likely to be restricted to specialized MS centers, with long-term monitoring to determine the true risk for adverse effects.

Natalizumab for multiple sclerosis: appraising risk versus benefit, a seemingly demanding tango.
Serious adverse effect such as PML warrant extreme caution and heightened clinical vigilance while prescribing the drug. If used with prudence, the drug can be instrumental in treatment of patients with inadequate response to the first-line medications.

Dimethyl Fumarate (Tecfidera): A New Oral Agent for Multiple Sclerosis.
To describe the clinical evidence supporting the safety, efficacy, and clinical utility of oral dimethyl fumarate for the treatment of multiple sclerosis (MS). In March 2013, dimethyl fumarate was approved as a third oral option for patients with relapsing forms of MS. Although no head-to-head trials have been conducted, a comparison of data from phase III trials suggests that the efficacy of dimethyl fumarate is comparable to that of existing oral agents and may offer a preferable safety profile.

Optic coherence tomography findings in relapsing-remitting multiple sclerosis patients of the northwest of Iran.
Optical coherence tomography (OCT) is a simple, high-resolution technique to quantify the thickness of retinal nerve fiber layer (RNFL) and macula volume, which provide an indirect measurement of axonal damage in multiple sclerosis (MS). This study aimed to evaluate OCT finding in relapsing-remitting MS patients of the northwest of Iran and compare them with a normal control group.
Findings of the present study in the northwest of Iran buttress the idea that RNFL thickness can be greatly affected by MS. Our results also indicate that this effect is associated with ON and MS duration and severity.

PET imaging of demyelination and remyelination in the cuprizone mouse model for multiple sclerosis: A comparison between [11C]CIC and [11C]MeDAS.
Taken together, the results of this comparative study between [¹¹C]CIC and [¹¹C]MeDAS clearly show that [¹¹C]MeDAS is the preferred PET tracer to monitor myelin changes in the brain and spinal cord in vivo.

Clinical relevance and functional consequences of the TNFRSF1A multiple sclerosis locus.
We set out to characterize the clinical impact and functional consequences of rs1800693(G), the multiple sclerosis (MS) susceptibility allele found in the TNFRSF1A locus. The MS rs1800693(G) susceptibility allele affects the magnitude of monocyte responses to TNF-α stimulation, and the TNF pathway may be one network in which the effect of multiple MS genes becomes integrated.

Interventions for children coping with parental multiple sclerosis: a systematic review.
Evidence demonstrates children of parents with MS who increase their coping skills, social support, and knowledge of the disease process exhibit decreased emotional distress and increased overall life satisfaction.

Effects of BG-12 (dimethyl fumarate) on health-related quality of life in patients with relapsing-remitting multiple sclerosis: findings from the CONFIRM study.
Coupled with clinical and neuroradiological benefits, these HRQoL results further support BG-12 as an effective oral treatment for relapsing MS.

Isolation of Clostridium perfringens Type B in an Individual at First Clinical Presentation of Multiple Sclerosis Provides Clues for Environmental Triggers of the Disease.
We examined sera and CSF obtained from two tissue banks and found that immunoreactivity to ETX is 10 times more prevalent in people with MS than in healthy controls, indicating prior exposure to ETX in the MS population. C. perfringens epsilon toxin fits mechanistically with nascent MS lesion formation since these lesions are characterized by BBB permeability and oligodendrocyte cell death in the absence of an adaptive immune infiltrate.

Major depression and multiple sclerosis - a case report.
Existing therapies that target immune modulation are largely ineffective in halting the progression of the disease and are fraught with severe side effects. Therefore, managing the comorbidities of MS is of utmost importance for long-term patient care and quality of life.

Genetic characterization of gliomas arising in patients with multiple sclerosis.
We conclude that gliomas in MS patients have genetic features paralleling counterparts in non-MS patients. There is no strong genetic evidence for GBMs to be secondary GBMs.

Wnt signaling in the pathogenesis of multiple sclerosis-associated chronic pain.
Our data collectively suggest that Wnt signaling pathways are up-regulated in the SCDH of the EAE mice and that aberrant activation of Wnt signaling contributes to the development of EAE-related chronic pain.

Cognitive reserve and patient-reported outcomes in multiple sclerosis.
The present work investigates the relationship between cognitive reserve and demographic characteristics, health behaviors, and patient-reported outcomes (PROs). This expanded measurement of cognitive reserve captures both the passive and active aspects of the construct, and there is a consistent and substantial relationship with PROs. Individuals with high passive and/or active reserve are healthier and experience higher levels of well-being.

Limiting multiple sclerosis related axonopathy by blocking Nogo receptor and CRMP-2 phosphorylation.
We conclude that phosphorylation of CRMP-2 may be downstream of NgR1 activation and play a role in axonal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis. Blockade of Nogo-A/NgR1 interaction may serve as a viable therapeutic target in multiple sclerosis.

MP2RAGE multiple sclerosis magnetic resonance imaging at 3 T.
he results show that the 3D T1-weighted high-resolution MP2RAGE contrast provides a sensitive means for MS lesion assessment. The additional quantitative T1 relaxation time maps obtained with the MP2RAGE provide further potential diagnostic and prognostic information that could help (a) to better discriminate lesion subtypes and (b) to stage and predict the activity and the evolution of MS. Results also indicate that the T2-weighted double-inversion recovery and FLAIR-SPACE contrasts are attractive complements to the MP2RAGE for lesion detection.

Patient perceptions of multiple sclerosis and its treatment.
Patient understanding of treatment for disease enhances treatment adherence. Greater patient involvement in disease management requires better communication between physicians and their patients.

Meanings, motivations, and strategies for engaging in physical activity among women with multiple sclerosis.
The aim of the current study was to better understand the adoption and maintenance of physical activity from the perspective of women with multiple sclerosis (MS). A consideration of these beliefs, motivations, and strategies may be useful for designing behavioral interventions to increase physical activity that are sensitive to the needs and preferences of women with MS.

Chronic cerebrospinal venous insufficiency and venous stenoses in multiple sclerosis.
The traditional view that multiple sclerosis (MS) is an autoimmune disease has recently been challenged by the claim that MS is caused by chronic cerebrospinal venous insufficiency (CCSVI). Although several studies have questioned this vascular theory, the CCSVI controversy is still ongoing. Our aim was to assess the prevalence of CCSVI in Danish MS patients using sonography and compare these findings with MRI measures of venous flow and morphology. Our results do not corroborate the presence of vascular pathology in RRMS and we found no evidence supporting the CCSVI hypothesis.

Discovery of fingolimod, the sphingosine 1-phosphate receptor modulator and its application for the therapy of multiple sclerosis.

Cognitive rehabilitation correlates with the functional connectivity of the anterior cingulate cortex in patients with multiple sclerosis.
A significant "treatment × time" interaction was found for the increased FC of the right IPL and for the decreased FC of the right ITG. In the TG only, significant correlations (p < 0.001) were found between improvement of PASAT performance and RS FC of the ACC with the right MFG (r = 0.88) and right IPL (r = 0.76). In MS, cognitive rehabilitation correlates with changes in RS FC of brain regions subserving the trained functions. fMRI might be useful to monitor rehabilitative strategies in MS.

A patient with Leiden V mutation, multiple sclerosis, psoriasis, and sicca syndrome: could celecoxib and fingolimod adversely affect the heart?
The paper describes the case of a patient affected by a combination of genetic and autoimmune diseases (multiple sclerosis, psoriatic arthritis, Leiden V mutation, and sicca syndrome) and hypertension. The psoriatic arthritis was treated with celecoxib and multiple sclerosis with fingolimod. The patient developed high fever and endocarditis, resulting in severe mitral regurgitation, atrial fibrillation, and congestive heart failure. Evidence is suggestive of adverse effects of potent immunosuppressive and anti-inflammatory therapies with biologic agents and the cardiovascular system. Fingolimod increases susceptibility to infections and induced endocarditis resulting in severe mitral regurgitation, atrial fibrillation, and congestive heart failure. Managed care systems limit the contact among basic care physicians and specialists. However, the process by which the optimal decision may be reached for a patient with a complex pathology is shared decision making, where the risk of severe complications and medical expenses may be reduced.

Quality of life and depression in multiple sclerosis patients: longitudinal results of the BetaPlus study.
compared to baseline the proportion of depressive patients decreased. Coping strategies as well as supportive elements such as autoinjectors and nurses had a significant impact on QoL and depression. However, the study had the general limitations of a non-controlled design.

Natalizumab is effective in multiple sclerosis patients switching from other disease modifying therapies in clinical practice.
Natalizumab showed to decrease ARR, stabilize EDSS, increase the percentage of CELs free patients and decrease the number of CELs in a group of 50 poor responders to classical DMT, after the first 12 months of therapy.

Balance impairment in people with multiple sclerosis: preliminary evidence for the Balance Evaluation Systems Test.

Acute demyelinating lesions with restricted diffusion in multiple sclerosis.
It is widely accepted that typical acute demyelinating lesions in relapsing-remitting multiple sclerosis(RRMS) exhibit vasogenic edema with increased diffusion, as demonstrated by an increased apparent diffusion coefficient on MRI. In contrast, acute ischemic lesions demonstrate cytotoxic edema with restricted diffusion. Recent reports have documented selected cases of acute demyelinating lesions exhibiting restricted diffusion (ADLRD) in MS. We aimed to assess the morphologies, distributions, signal characteristics and changes over time of nine ADLRD. An additional goal was to obtain clinical correlations and relate our findings to all previously published case reports describing ADLRD. Our results and review of prior published cases suggest that ADLRD represent a new variant of MS lesion. The restricted diffusion that is a characteristic of ADLRD on MRI is a new challenge in the differential diagnosis of stroke in young adults. The pathogenesis of ADLRD remains to be understood.

Disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with daclizumab high-yield process in the SELECT study.
The objective of this paper is to assess the proportion of DAC HYP- versus placebo-treated patients who were free from disease activity.
At one year, DAC HYP resulted in a meaningful increase in the proportion of relapsing-remitting MS patients who were disease-activity free versus placebo.

Desirability and expectations of the UK MS Register: Views of people with MS.
This study elicited the views of people with Multiple Sclerosis (PwMS) on the desirability and expectations regarding a UK Register for MS. The security and accessibility of the website, the validity of the data, and mismatches between the expected and actual uses, are all issues of importance in the development of e-health tools, if PwMS are to be successfully engaged over time.

Elevated levels of PPAR-gamma in the cerebrospinal fluid of patients with multiple sclerosis.
Controlling for potential confounders, the CSF levels of PPARγ further displayed a moderate but significant association with clinical severity. Corroborating with prior experimental findings, these results may contribute to our understanding about the role of PPARγ in MS, and may implicate this protein as a potential CSF biomarker of the disease.

Microglia in normal appearing white matter of multiple sclerosis are alerted but immunosuppressed.
The activation status of microglia in NAWM of MS patients likely reflects a response to ongoing neuroinflammation, which coincides with upregulation of immunoregulatory molecules to prevent full activation and damage to the vulnerable milieu.

Healthcare provider beliefs about exercise and fatigue in people with multiple sclerosis.
Healthcare providers are encouraged to consider strategies of active listening and careful observation when providing individualized exercise programs for people with MS-related fatigue. In addition, recognition and understanding of the complex nature of fatigue by the interdisciplinary team might facilitate more positive exercise experiences for this population.

Neuropsychological rehabilitation has beneficial effects on perceived cognitive deficits in multiple sclerosis during nine-month follow-up.
The aim of the present study was to evaluate whether short-term neuropsychological rehabilitation has long-term beneficial effects in a nine-month follow-up. The beneficial effects of strategy-oriented neuropsychological rehabilitation on perceived cognitive deficits in MS may be maintained for at least one year after the beginning of the intervention.

Matrix metalloproteinases and their pathological upregulation in multiple sclerosis: an overview.
Recently many studies, both in animals and humans, have been conducted to better elucidate the underlying causes, mechanisms and pathophysiology of MS. In this review, we discuss the potential role of pathological upregulation of MMPs in MS and future challenges which if properly addressed might help in development of potential cure for this disease.

The impact of sexual dysfunction on health-related quality of life in people with multiple sclerosis.
The objective of this paper is to examine the impact of sexual dysfunction on HrQoL in a large national sample using The Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19). In patients with MS, sexual dysfunction has a much larger detrimental impact on the mental health aspects of HrQoL than severity of physical disability.

Autoantigens and autoantibodies in multiple sclerosis.
The overactive pro-inflammatory Th1 cells and clonal expansion of B cells initiate an inflammatory cascade with several cellular and molecular immune components participating in MS pathogenic mechanisms. In this scenario, autoantibodies and autoantigens have a significant role in immunopathogenesis, diagnosis and therapeutic targets of MS. In this review, we try to introduce the autoantigens and autoantibodies and explain their roles in pathogenesis of MS.

Gene expression changes underlying cortical pathology: clues to understanding neurological disability in multiple sclerosis.
In this review, we summarize existing data from gene expression changes in cortical tissues from MS brains and how they may provide clues to the pathogenesis.

Chromosomal radiosensitivity in patients with multiple sclerosis.
Induced micronuclei yield was significantly lower in the irradiated samples from treated relapsing-remitting multiple sclerosis patients than in healthy controls and relapsing-remitting not treated patients. Intrinsic sensitivity of lymphocytes subpopulations to the apoptotic effect of immunomodulatory treatment could be responsible for this result.

The improvement of cognitive functions is associated with a decrease of plasma Osteopontin levels in Natalizumab treated relapsing multiple sclerosis.
To investigate the effect of two-years Natalizumab treatment on plasma Osteopontin levels, cognitive performances and fatigue in relapsing multiple sclerosis (RRMS) patients. Natalizumab treatment reduces plasma Osteopontin levels and improves cognition and fatigue in RRMS patients. The results suggest that the improvement of cognitive functions is associated to a decrease of plasma Osteopontin levels.

Multiple sclerosis-associated retrovirus and related human endogenous retrovirus-W in patients with multiple sclerosis: a literature review.
Evidence suggests that both retroviruses may be endogenous to humans and that failure to suppress viral activity may not be restricted to patients with multiple sclerosis and therefore an unlikely cause of the disease.

Endogenous retroviruses and multiple sclerosis-new pieces to the puzzle.
Thus, these new findings regarding the etiology and pathogenesis of MS, suggest alternative ways to challenge autoimmune diseases.

Home-based exercise program and fall-risk reduction in older adults with multiple sclerosis: phase 1 randomized controlled trial.
Home-based exercise was found to be feasible, safe, and effective for reducing physiological fall risk in older adults with multiple sclerosis. Our findings support the implementation of a larger trial to reduce fall risk in persons with multiple sclerosis.

Fatigue in multiple sclerosis: relationship with disease duration, physical disability, disease pattern, age and sex.
The analysis of covariance revealed that there is no difference in the covariance-adjusted means for fatigue among two disease groups (relapsing remitting and secondary progressive) except for EDSS. MS patients with longer disease duration, higher EDSS and progressive type of disease suffer from fatigue more than cases with lower EDSS, duration of disease and relapsing type of the disease.
Do generic utility measures capture what is important to the quality of life of people with multiple sclerosis?
Although the generic utility measures included certain items that were important to people with MS, there were several that were missing. An important consequence of this mismatch was that values of QOL derived from the PGI were importantly and significantly lower than those estimated using any of the generic utility measures. This could have a substantial impact in evaluating the effect of interventions for people with MS.

Prevalence and predictors of depression in Iranian patients with multiple sclerosis: a population-based study.
A significant association was found between fatigue and antidepressant use (P = 0.001, OR = 6.81, 95 % CI = 2.26-20.48). Our findings demonstrate that depression is significantly associated with fatigue and older age, regardless of other factors. Moreover, despite the high prevalence of depression in MS, most patients do not receive adequate treatment.

Vitamin D and multiple sclerosis: where do we go from here?
Vitamin D as a treatment for MS is an emerging concept and both current and anticipated data will be covered. Lastly, we discuss future challenges, ideas on how to move from association to causation, and the prospect of primary prevention of this disabling disease.

Atypical idiopathic inflammatory demyelinating lesions: prognostic implications and relation to multiple sclerosis.
Our findings confirm the previously reported subtypes of AIIDLs. Most types confer a relatively low risk of further clinical attacks, except for ring-like lesions and the combination with MS-typical lesions.

Relationship between NF-κB1 -94 ins/del ATTG polymorphism and susceptibility of multiple sclerosis in Iranian MS patients.
To conclude, our study showed no association between -94 ins/del ATTG polymorphism and risk of multiple sclerosis in Iranian patients.

Do generic utility measures capture what is important to the quality of life of people with multiple sclerosis?
Although the generic utility measures included certain items that were important to people with MS, there were several that were missing. An important consequence of this mismatch was that values of QOL derived from the PGI were importantly and significantly lower than those estimated using any of the generic utility measures. This could have a substantial impact in evaluating the effect of interventions for people with MS.

Advances in the management of multiple sclerosis spasticity: experiences from recent studies and everyday clinical practice.
Follow-up studies in Sativex responders support continued benefit without the need to increase doses for at least 1 year. Sativex appears to be a promising solution for a meaningful proportion of patients with MS-related spasticity who have inadequate response to current antispasticity medications.

[The CD100 semaphorin expression on peripheral blood T-lymphocytes in patients with relapsing-remitting multiple sclerosis.]
These data suggest the use of semaphorin as a possible therapeutic target in pathological inflammation in MS.

[Epidemiological characteristics of multiple sclerosis in the Kabardino-Balkaria Republic.]
The higher prevalence of MS in Nalchik may be explained by adverse environmental factors increasing the risk of MS. A case-control study revealed the higher risk for people under 15 years old living very close to chemical and biological plants.

Validation of patient determined disease steps (PDDS) scale scores in persons with multiple sclerosis.
The Patient Determined Disease Steps (PDDS) is a promising patient-reported outcome (PRO) of disability in multiple sclerosis (MS). To date, there is limited evidence regarding the validity of PDDS scores, despite its sound conceptual development and broad inclusion in MS research.This study examined the validity of the PDDS based on (1) the association with Expanded Disability Status Scale (EDSS) scores and (2) the pattern of associations between PDDS and EDSS scores with Functional System (FS) scores as well as ambulatory and other outcomes. This study provides novel evidence supporting the PDDS as valid PRO of disability in MS.

Effect of 4-aminopyridine on vision in multiple sclerosis patients with optic neuropathy.
The objective of this randomized, double-blind, placebo-controlled, crossover study was to examine if patients with optic neuropathy would derive a therapeutic benefit from 4-aminopyridine (4-AP) treatment. Furthermore, the study was intended to determine if patients with certain P100 latencies or retinal nerve fiber layer (RNFL) measures would be more likely to respond to therapy.
4-Aminopyridine is useful for improving vision in patients with demyelinating optic neuropathy. Future clinical trials may be able to enrich a patient population for potential responders using OCT and VEP measures. Selecting patients for future trials should use RNFL measures as part of inclusion/exclusion criteria.

Longitudinal 7-year follow-up of chronic pain in persons with multiple sclerosis in the community.
This study provides longitudinal insight into the complex multidimensional chronic pain-related disability in pwMS over a longer period. Improved clinician understanding of the course of chronic pain, early intervention, and patient self-management may decrease pain-related disability and contribute to their overall well-being.

Increased concentrations of glutamate and glutamine in normal-appearing white matter of patients with multiple sclerosis and normal MR imaging brain scans.
The results suggest that Glx may be an important marker for pathology in non-lesional white matter in MS. Moreover, Glx is related to the severity of MS independent of number of lesions in the patient. In contrast, increased glial density indicated by increased mIns and decreased neuronal density indicated by the decreased tNA, were only observed in NAWM of typical CDMS patients with white matter lesions.

Cortisol awakening response is linked to disease course and progression in multiple sclerosis.
Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has frequently been reported in multiple sclerosis (MS). So far, HPA axis function in MS has predominantly been studied under pharmacological stimulation which is associated with a series of methodological caveats. Knowledge of circadian cortisol patterns and cortisol awakening response (CAR) is still limited.
Circadian cortisol release, in particular CAR, shows a course specific pattern with most pronounced release in RRMS. There is also some evidence for greater CAR in RRMS patients with EDSS progression. As a consequence, CAR might be of predictive value in terms of neurological disability in RRMS patients. The possible role of neuroendocrine-immune interactions in MS pathogenesis is further discussed.

Functional connectivity changes within specific networks parallel the clinical evolution of multiple sclerosis.
In multiple sclerosis (MS), the location of focal lesions does not always correlate with clinical symptoms, suggesting disconnection as a major pathophysiological mechanism. Resting-state (RS) functional magnetic resonance imaging (fMRI) is believed to reflect brain functional connectivity (FC) within specific neuronal networks. FC changes seem to parallel patients' clinical state and capability of compensating for the severity of clinical/cognitive disabilities.

Novel therapeutic options for multiple sclerosis.
Half a dozen immunomodulators with proven efficacy in RRMS are now undergoing evaluation in Phase III trials in the CPMS indication. Neuroprotective drugs that prevent demyelination and/or improve remyelination would be interesting for CPMS, but these drugs are currently in the early development phase and their efficacy has not been demonstrated yet.

Therapeutic Efficacy of Suppressing the JAK/STAT Pathway in Multiple Models of Experimental Autoimmune Encephalomyelitis.
In vivo AZD1480 treatment impairs both the priming and expansion of T cells and attenuates Ag presentation functions of myeloid cells. Inhibition of the JAK/STAT pathway has clinical efficacy in multiple preclinical models of MS, suggesting the feasibility of the JAK/STAT pathway as a target for neuroinflammatory diseases.

Randomized controlled trial of physical activity, cognition, and walking in multiple sclerosis.
The current study supports physical activity as a promising tool for managing cognitive impairment and impaired walking performance in persons with MS, and suggests that physical activity might have specific effects on cognition and non-specific effects on walking performance in this population.

Self-Efficacy as a Predictor of Self-Reported Physical, Cognitive, and Social Functioning in Multiple Sclerosis.
Self-efficacy plays a significant role in individual adjustment to MS across multiple areas of functional outcome beyond that which is accounted for by disease-related variables and symptoms of depression. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Iron depletion induced by bloodletting and followed by rhEPO administration as a therapeutic strategy in progressive multiple sclerosis: A pilot, open-label study with neurophysiological measurements.
To evaluate the concept that iron depletion (ID) induced by bloodletting and followed by recombinant human erythropoietin (rhEPO) administration could be a therapeutic strategy in progressive multiple sclerosis (PMS) and that it could be assessed by neurophysiological measurements. The combined ID-rhEPO therapy could authorize a prolonged administration of rhEPO in PMS patients, able to modify cortical excitability of the glutamatergic and gabaergic circuits. These preliminary data are encouraging to design a larger, controlled therapeutical trial to assess the value of such a strategy to improve functional symptoms in PMS patients, and maybe to prevent axonal degeneration. Neurophysiological measurements based on cortical excitability studies could provide sensitive parameters to evaluate treatment-induced changes in this context.

Evoked potentials in multiple sclerosis.
This article is a brief overview of additional ways in which central nervous system (CNS) physiology-as measured by EPs-can still contribute value in the management of MS in the era of MRIs.

Co-occurring Depression and Pain in Multiple Sclerosis.
the article discusses how existing treatments of pain and depression could be adapted to address shared mechanisms and overcome barriers to treatment utilization.

Cognition, cognitive dysfunction, and cognitive rehabilitation in multiple sclerosis.
The functional impact of cognitive problems expected with MS is emphasized, accompanied by examples of cognitive retraining approaches used to manage them and improve day-to-day performance.

Gait impairment and optimizing mobility in multiple sclerosis.
Compensation through appropriate prescription of assistive devices, bracing, and wheelchairs will help improve safety. Rehabilitation can make a significant impact on achieving and maintaining quality of life and independence.

Clinical case reviews in multiple sclerosis spasticity: experiences from around Europe.
Assessment of the European clinical experience is intended to provide a better understanding of the prescribing regulations for MS spasticity treatments, facilitate identification of suitable candidate patients for Sativex and increase awareness of alternative management approaches for MS-related spasticity.

[Relationship between biochemical parameters of cerebrospinal fluid and the course of multiple sclerosis.]
The relative risk of exacerbation of the disease in the next three years was associated with the level of tumor necrosis factor alpha and matrix metalloproteinase-2.

Guideline for the diagnosis and management of multiple sclerosis: A Southern African perspective.
This guideline, written on behalf of the Multiple Sclerosis Society of South Africa, aims to assist in the diagnosis and treatment of MS in Southern Africa.

[Controlled research on multiple sclerosis treated with electroacupuncture and acupoint injection].
To observe the clinical efficacy of multiple sclerosis (MS) treated with electroacupuncture and acupoint injection. EA and AI co-act on reducing disability and improving the life quality in the treatment of MS and have achieved coordinately the significant effects.

Management of Relapsing-Remitting Multiple Sclerosis [Internet].
The emergence of novel oral and injectable agents necessitates consideration of their place in therapy, including the potential for combination therapy. Thus, the comparative clinical and cost-effectiveness of currently available and emerging disease-modifying agents for RRMS, both alone and in combination, need to be determined.

Cystoid macular oedema after fingolimod treatment in multiple sclerosis.
Attention to visual changes and periodic funduscopic examinations are an important part of monitoring while using fingolimod. In our patient early recognition and discontinuation of fingolimod did not result in resolution of the CME.

Optimizing therapeutics in the management of patients with multiple sclerosis: a review of drug efficacy, dosing, and mechanisms of action.

Clinical, MRI, and CSF Markers of Disability Progression in Multiple Sclerosis.
Current relevant literature addressing the topic of clinical, MRI, and CSF markers as predictors of MS disability progression is reviewed here.

Cerebrospinal fluid pleocytosis in multiple sclerosis patients with lesions showing reduced diffusion.
The ADC reduction and CSF pleocytosis were observed only early after symptom onset, which suggests that both are typically early and transient phenomena.

A biopsychosocial model of resilience for multiple sclerosis.
The findings lend support to psychological interventions which focus on promoting the personal resources and assets needed to cope effectively with multiple sclerosis.

Objective duplex ultrasound evaluation of the extracranial circulation in multiple sclerosis patients undergoing venoplasty of internal jugular vein stenoses: A pilot study.
Chronic cerebrospinal venous insufficiency (CCSVI) is a condition associated with multiple sclerosis(MS) and manifested by stenoses in the extracranial venous circulation. There is a need for an objective non-invasive assessment of CCSVI that is able to accurately identify the location of stenoses and quantify physiological changes in blood flows following treatment.
The ECDU examination described provides a reliable objective assessment of IJV and VV stenoses and, with the use of BVFs, can quantify the degree of obstruction. These results support the use of ECDU as a non-invasive post-operative assessment of the success of venoplasty. The ability of ECDU to measure GACBF provides an additional parameter to monitor vascular pathophysiology in MS patients. The current findings support the view that the early symptomatic benefits observed after venoplasty for stenoses in the extracranial venous circulation may be the result of increased cerebral perfusion.

Increase in the prevalence of multiple sclerosis over a 17-year period in Osona, Catalonia, Spain.
The prevalence of multiple sclerosis cases in Osona has increased over the past 17 years to being one of the highest reported in Spain.

Cluster-tic syndrome as the initial manifestation of multiple sclerosis.
he association between cluster-tic syndrome and MS is an exception, and the mechanism of the pain is still unknown; therefore, this case might suggest a pathophysiological relationship between the trigeminal main sensory nucleus and cluster-tic syndrome.

Cost-effectiveness analysis of interferon beta-1b for the treatment of patients with a first clinical event suggestive of multiple sclerosis.
To assess, from a Swedish societal perspective, the cost effectiveness of interferon β-1b (IFNB-1b) after an initial clinical event suggestive of multiple sclerosis (MS) (ie, early treatment) compared with treatment after onset of clinically definite MS (CDMS) (ie, delayed treatment).
Early treatment with IFNB-1b for a first clinical event suggestive of MS was found to improve patient outcomes while controlling costs.

Characterizing contrast-enhancing and re-enhancing lesions in multiple sclerosis.
In multiple sclerosis (MS), contrast-enhancing lesions (CELs) in T1-weighted postcontrast MRI are considered markers of blood-brain barrier breakdown. It remains unknown if re-enhancement can be considered a radiologic indicator of different pathology in CELs. We investigated 1) the incidence of re-enhancing lesions (re-CELs) from chronic lesions; 2) differences in size, magnetization transfer ratio (MTR), and likelihood to appear as acute black holes (aBHs) between new lesions (n-CELs) and re-CELs; and 3) associations between re-CELs and features indicating more advanced disease.
Nearly 20% of CELs represent the reoccurrence of enhancement in chronic plaques. Re-CELs represent larger areas of inflammation, not necessarily associated with larger areas of edema.

Association of multiple sclerosis with restless legs syndrome and other sleep disorders in women.
To assess the association of multiple sclerosis (MS) with concurrent restless legs syndrome (RLS) and daytime sleepiness. We also prospectively examined whether women with MS had an increased risk of developing RLS during 4 years of follow-up. Women with MS had a significantly higher prevalence of RLS and daytime sleepiness and an increased risk of developing RLS in the future.

Microcystic macular oedema in multiple sclerosis is associated with disease severity.
Microcystic macular oedema may also contribute to visual dysfunction beyond that explained by nerve fibre layer loss. Microcystic changes need to be assessed, and potentially adjusted for, in clinical trials that evaluate macular volume as a marker of retinal ganglion cell survival. These findings also have implications for clinical monitoring in patients with multiple sclerosis on sphingosine 1-phosphate receptor modulating agents.

Biplanar MRI for the assessment of the spinal cord in multiple sclerosis.
To investigate the entire spinal cord (SC) of multiple sclerosis (MS) patients with biplanar MRI and to relate these MRI findings to clinical functional scores. Biplanar MRI facilitates a comprehensive identification, localization, and grading of pathological SC findings in MS patients. This improves the confidence and utility of SC imaging.

Periventricular demyelination and axonal pathology is associated with subependymal virus spread in a murine model for multiple sclerosis.
Theiler's murine encephalomyelitis virus (TMEV) infection of mice is a widely used animal model for demyelinating disorders, such as multiple sclerosis (MS). The aim of the present study was to identify topographical differences of TMEV spread and demyelination in the brain of experimentally infected susceptible SJL/J mice and resistant C57BL/6 mice. Summarized, the demonstration of ependymal infection and subjacent spread into the brain parenchyma as well as regional virus clearance despite ongoing demyelination and axonal damage in other CNS compartments allows new insights into TME pathogenesis. This novel aspect of TMEV CNS interaction will enhance the understanding of region-specific susceptibilities to injury and regenerative capacities of the brain in this MS model.

Decreased frontal lobe gray matter perfusion in cognitively impaired patients with secondary-progressive multiple sclerosis detected by the bookend technique.
There is increasing evidence implicating microvascular impairment in MS pathogenesis. Perfusion imaging offers a unique opportunity to investigate the functional impact of GM pathology. We sought to quantify differences in MR imaging-based bookend-derived cerebral perfusion between cognitively impaired and nonimpaired patients with SPMS. Bookend-derived GM qCBV was significantly reduced in cognitively impaired patients with SPMS in functionally relevant brain regions.

Immunoadsorption therapy in patients with multiple sclerosis with steroid-refractory optical neuritis.
In multiple sclerosis relapses refractory to intravenous corticosteroid therapy, plasma exchange is recommended. Immunoadsorption (IA) is regarded as an alternative therapy, but its efficacy and putative mechanism of action still needs to be established. IA was effective in the treatment of corticosteroid-refractory optic neuritis. IA influenced the humoral immune response. Strikingly, however, we found strong evidence that demyelination products and immunological mediators were also cleared from plasma by IA.

Faith as a Resource in Patients with Multiple Sclerosis Is Associated with a Positive Interpretation of Illness and Experience of Gratitude/Awe.
The aim of this cross-sectional anonymous survey with standardized questionnaires was to investigate which resources to cope were used by patients with multiple sclerosis (MS). We focussed on patients' conviction that their faith might be a strong hold in difficult times and on their engagement in different forms of spirituality. The ability to reflect on what is essential in life, to appreciate and value life, and also the conviction that illness may have meaning and could be regarded as a chance for development was low in R-S- individuals which either may have no specific interest or are less willing to reflect these issues.

Improved differentiation between MS and vascular brain lesions using FLAIR* at 7 Tesla.
To investigate whether a new magnetic resonance image (MRI) technique called T2*-weighted fluid attenuation inversion recovery (FLAIR*) can differentiate between multiple sclerosis (MS) and vascular brain lesions, at 7 Tesla (T). 7-T FLAIR* improves differentiation between MS and vascular lesions based on lesion location, perivascular orientation and presence of hypointense (rims around) lesions.

Relative changes in ankle and hip control during bilateral joint movements in persons with multiple sclerosis.
The purpose of this study was to quantify hip and ankle impairments contributing to movement dysfunction in multiple sclerosis (MS). Rehabilitation strategies targeting ankle recovery or compensation using the hip might improve movement function in MS.

Evolution of Quality of Life in Renal Transplant Recipients and Patients With Multiple Sclerosis: A Follow-up Study.
We aimed to compare the evolution of quality of life in 2 medical conditions under immunotherapy (cadaveric renal transplantation [G1] and multiple sclerosis [G2]), and to assess the clinical significance of the results compared with a representative age-adjusted sample of the general Spanish population (G3). Renal transplant recipients need specialized health care 1 year after transplantation because they still display relevant impairment in daily functioning compared with the general population.

Future directions of multiple sclerosis rehabilitation research.
he conference was presented by the University of Washington's Multiple Sclerosis Rehabilitation Research and Training Center and focused on the current state of research into secondary conditions, outcomes measurement, employment, and the utility of psychotherapeutic interventions. This article discusses the details and recommendations of this conference.

Visual issues in multiple sclerosis.
Multiple sclerosis has several ophthalmic manifestations, including optic neuritis, internuclear ophthalmoplegia, and nystagmus. The presentation, treatment, and prognosis of visual complaints secondary to multiple sclerosis are discussed. Additionally, the use of optical coherence tomography and complications related to the use of fingolimod are considered.

Bladder management in multiple sclerosis.

Multiple Sclerosis and Fatigue: Understanding the Patient's Needs.
(1) To assess, from the perspective of individuals living with MS, the relevance of a subset of items from the PROMIS fatigue item bank. (2) To identify additional aspects of fatigue that individuals with MS believe are important for clinicians when asking about their fatigue experience.

Movement disorders in multiple sclerosis.
This article reviews terminology used to describe movement disorders, discusses individual movement disorders and their occurrence in patients with multiple sclerosis, and reviews treatment options.

Activities of daily living: evaluation and treatment in persons with multiple sclerosis.
Occupational therapy assessment and treatment of impairments related to movement, sensory-related symptoms, fatigue, and cognitive impairments can have a significant impact on the quality of life of persons with multiple sclerosis.

Spasticity management in multiple sclerosis.
Choice of treatment hinges on a combination of the extent of symptoms, patient preference, and availability of services.

BCG vaccine for clinically isolated syndrome and MS: Infections and protective immunity.
Can infections ever be beneficial for MS? The long-held yet unproven "hygiene hypothesis" proposes that certain infections early in life might reduce the risk of developing autoimmune diseases by inducing protective immunity.² In addition, parasitic intestinal infections in people with MS may reduce disease activity.³ It follows that better sanitation and common use of disinfectants and antibiotics may account in part for the increased prevalence of MS and other autoimmune diseases in North America and much of Europe, compared with Africa, South America, and parts of Asia. If true, might we harness this natural phenomenon to develop new treatments for MS?

Can we optimize our teams? Multidisciplinary care for multiple sclerosis.
Using a multidisciplinary approach, the Auvergne MS network has explored other avenues of domiciliary-based care to seek improvements in the patient-centered management of MS. These include: access to high-dose methylprednisolone in the home, ensuring appropriate supervision and support; participation in national clinical research programs coordinated from hospital centers of excellence; provision of multidisciplinary clinic services where healthcare professionals across different disciplines can attend to the patient on the same day in the same center of care; development of individual and group-based cognitive therapy programs; educational programs focusing on the management of fatigue and cognitive impairment associated with MS; and educational programs focusing on optimal use of immunomodulating agents in MS patients.

Measuring symptoms and wellness in the multiple sclerosis patient: issues in measurement.
This review examines some important basic principles of measurement and considers issues as they apply to examples of measures used for patients with multisymptomatic illnesses such as multiple sclerosis, with a particular focus on application of the spasticity 0-10 Numerical Rating Scale and its correlation with the Patient Global Impression of Change scale.

Environmental factors in multiple sclerosis.
If confirmed, these findings suggest that a high proportion of MS cases could be effectively prevented by vitamin D supplementation. Furthermore, there is growing evidence that vitamin D insufficiency is a risk factor for conversion from clinically isolated syndrome to MS and for MS progression. Both prevention and treatment trials with vitamin D are needed to confirm these findings and to determine optimal levels of vitamin D.

Endogenous and Recombinant Type I Interferons and Disease Activity in Multiple Sclerosis

Oligoclonal Band Status in Scandinavian Multiple Sclerosis Patients Is Associated with Specific Genetic Risk Alleles

A technical approach to dissecting and assessing cadaveric veins pertinent to chronic cerebrospinal venous insufficiency in multiple sclerosis

To establish a detailed technical procedure for studying the anatomical correlates of chronic cerebrospinal venous insufficiency in cadavers of multiple sclerosis and control subjects, and to present our findings of the normal anatomic venous structures, with reference to previous descriptions from the literature. Post-mortem studies can provide valuable information about the architecture of intraluminal structures. In addition to providing a more thorough understanding of the extracranial venous system, we hope that our discussion and technical approach to dissection will help with future gross anatomical inspection of CCSVI.

Mitochondrial changes within axons in multiple sclerosis

Genetic Association of Multiple Sclerosis with the Marker rs391745 near the Endogenous Retroviral Locus HERV-Fc1: Analysis of Disease Subtypes

In this study of 1181 MS patients and 1886 controls we found that Bout Onset MS was associated with the C-allele of the marker rs391745 near the HERV-Fc1 locus (p

0.003), while primary progressive disease was not. The ability to see genetic differences between subtypes of MS near this gene speaks for the involvement of the virus HERV-Fc1 locus in modifying the disease course of MS.

Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)

Cognitive impairment in MS impacts negatively on many patients at all disease stages and in all subtypes. Full clinical cognitive assessment is expensive, requiring expert staff and special equipment. Test versions and normative data are not available for all languages and cultures. A brief cognitive assessment for MS has been recommended. A validation protocol has been prepared for language groups and validation studies have commenced.

Efficacy of Vitamin D Supplementation in Multiple Sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial

Demyelination Causes Synaptic Alterations in Hippocampi from Multiple Sclerosis Patients

Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system. While the clinical impact of gray matter pathology in MS brains is unknown, 30–40% of MS patients demonstrate memory impairment. The molecular basis of this memory dysfunction has not yet been investigated in MS patients.

Mitochondrial DNA deletions and neurodegeneration in multiple sclerosis

Cerebral atrophy is a correlate of clinical progression in multiple sclerosis (MS). Mitochondria are now established to play a part in the pathogenesis of MS. Uniquely, mitochondria harbor their own mitochondrial DNA (mtDNA), essential for maintaining a healthy central nervous system. We explored mitochondrial respiratory chain activity and mtDNA deletions in single neurons from secondary progressive MS (SPMS) cases.

Role of HDAC3 on p53 Expression and Apoptosis in T Cells of Patients with Multiple Sclerosis

Histone deacetylase 3 (HDAC3) belongs to a family of proteins which plays an important role in protein acetylation, chromatin remodeling and transcription of genes, including those that are involved in cell proliferation and cell death. While increased expression of HDAC3 is seen in neoplastic cells, the role of HDAC3 in T cells and their role in autoimmune disease is not known. MS patients, when compared to controls, show an increased expression of HDAC3 and relative resistance to TSA induced apoptosis in T cells. Increased expression of HDAC3 in PBMC of MS patients may render putative autoreactive lymphocytes resistance to apoptosis and thereby contribute to autoimmunity.

Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation

Short and Long Term Variation in Ultraviolet Radiation and Multiple Sclerosis

We found that season and solar cycles have some role in MS susceptibility and life duration. However, this is an exploratory analysis and further work is needed to discern the association.

Getting the Balance Right: A randomised controlled trial of physiotherapy and Exercise Interventions for ambulatory people with multiple sclerosis

Cellular sources of dysregulated cytokines in relapsing-remitting multiple sclerosis

Numerous cytokines are implicated in the immunopathogenesis of multiple sclerosis (MS), but studies are often limited to whole blood (WB) or peripheral blood mononuclear cells (PBMCs), thereby omitting important information about the cellular origin of the cytokines. Knowledge about the relation between blood and cerebrospinal fluid (CSF) cell expression of cytokines and the cellular source of CSF cytokines is even more scarce. In CSF-cell studies, B-cells appear to be enriched in RRMS and associated with expression of pro-inflammatory cytokines; contrarily, monocytes are relatively scarce in CSF from RRMS patients and are associated with IL10 expression. Thus, our findings suggest a pathogenetic role of B-cells and an immunoregulatory role of monocytes in RRMS.

Increased promoter methylation of the immune regulatory gene SHP-1 in leukocytes of multiple sclerosis subjects

As SHP-1 is deficient in MS leukocytes and SHP-1-regulated proinflammatory genes are correspondingly upregulated, we propose that increased SHP-1 promoter methylation may relate in part to decreased SHP-1 expression and increased leukocyte-mediated inflammation in MS.

Genome-wide Association Study in a High-Risk Isolate for Multiple Sclerosis Reveals Associated Variants in STAT3 Gene

The protective haplotype for MS in STAT3 is a risk allele for Crohn disease, implying that STAT3represents a shared risk locus for at least two autoimmune diseases. This study also demonstrates the potential of special isolated populations in search for variants contributing to complex traits.

Pharmacokinetic profile of dalfampridine extended release: clinical relevance in patients with multiple sclerosis.

Cognitive impairment occurs in children and adolescents with multiple sclerosis: results from a United States network.
In the largest sample studied to date, we measured cognitive functioning in children and adolescents with pediatric multiple sclerosis (n = 187) as well as those with clinically isolated syndrome (n = 44). A diagnosis of multiple sclerosis (odds ratio = 3.60, confidence interval = 1.07, 12.36, P = .04) and overall neurologic disability (odds ratio = 1.47, confidence interval = 1.10, 2.10, P = .03) were the only independent predictors of cognitive impairment. Cognitive impairment may occur early in these patients, and prompt recognition is critical for their care.

Progressive degeneration of the retinal nerve fiber layer in patients with multiple sclerosis.
To quantify changes in the retinal nerve fiber layer (RNFL) of patients with multiple sclerosis (MS) over 3 years and to evaluate whether treatment protects against RNFL degeneration. Progressive axonal loss can be detected in the optic nerve fiber layer of MS patients. Analysis of the RNFL by OCT can be useful for evaluating MS progression and efficacy of treatment as a neuroprotective factor against axonal degeneration.

Environmental factors and their regulation of immunity in multiple sclerosis.
Epidemiological and clinical studies have shown that environmental factors such as infections, smoking and vitamin D are associated with the risk of developing multiple sclerosis (MS). Some of these factors also play a role in the MS disease course. We are currently beginning to understand how environmental factors may impact immune function in MS on a cellular and molecular level. Here we review epidemiological, clinical and basic immunological studies on the environmental factors, viral and parasitic infections, smoking, and vitamin D and relate epidemiological findings with their likely pathophysiology in MS.

Gait variability and disability in multiple sclerosis.
Gait variability is clinically relevant in some populations, but there is limited documentation of gait variability in persons with multiple sclerosis (MS). EDSS was positively correlated with step length variability and individuals with MS who used assistive devices to walk had significantly greater step length variability than those who walked independently (p's<.05). EDSS was correlated with step time and length variability even when age was taken into account. Additionally, Fisher's z test of partial correlations revealed that average gait parameters were more closely related to disability status than gait variability in individuals with MS. This suggests that focusing on average gait parameters may be more important than variability in therapeutic interventions in MS.

Epigenetics and miRNAs in the diagnosis and treatment of multiple sclerosis.

Measurement and clinical effect of grey matter pathology in multiple sclerosis.
During the past 10 years, the intense involvement of the grey matter of the CNS in the pathology of multiple sclerosis has become evident. By focusing on the latest insights into the in-vivo measurement of grey matter lesions and atrophy, we can assess their clinical effects.

Genetic and infectious profiles of Japanese multiple sclerosis patients.
Nationwide surveys conducted in Japan over the past thirty years have revealed a four-fold increase in the estimated number of multiple sclerosis (MS) patients, a decrease in the age at onset, and successive increases in patients with conventional MS, which shows an involvement of multiple sites in the central nervous system, including the cerebrum and cerebellum. We aimed to clarify whether genetic and infectious backgrounds correlate to distinct disease phenotypes of MS in Japanese patients. Our study suggests that MS patients harboring DRB1*0405, a genetic risk factor for MS in the Japanese population, have a younger age at onset and a relatively benign disease course, while DRB1*0405-negative MS patients have features similar to Western-type MS in terms of association with Epstein-Barr virus infection and DRB1*1501. The recent increase of MS in young Japanese people may be caused, in part, by an increase in DRB1*0405-positive MS patients.

Multiple sclerosis and glutamate excitotoxicity.

A wireless body measurement system to study fatigue in multiple sclerosis.

Benign course of tumour-like multiple sclerosis. Report of five cases and literature review.
Multiple sclerosis (MS) with initial neuroradiological features suggestive of brain tumour (tumour-like MS) may represent a challenging diagnosis. Our report of clinical, radiological and pathological features of five tumour-like MS cases confirms that it is mandatory to consider a demyelinating process in the differential diagnosis of tumour-like brain lesions. Many tumour-like MS cases may have a favourable long term prognosis.

New-onset multiple sclerosis associated with adalimumab treatment in rheumatoid arthritis: a case report and literature review.
A review of the literature revealed another 15 cases of MS associated with anti-TNF-α treatment, emphasizing the importance of detecting neurological symptoms and discontinuing the anti-TNF-α therapy.

A gender-related action of IFNbeta-therapy was found in multiple sclerosis.
Understanding how sexual dimorphism affects the physiological and pathological responses of the immune system is of considerable clinical importance and could lead to new approaches in therapy. Sexual dimorphism has already been noted as an important factor in autoimmune diseases: the aim of this study was to establish whether sexual dimorphism in autoimmune diseases is the result of differing pathways being involved in the regulation of T-helper (Th) cell network homeostasis.
The identification of gender-specific drugs is of considerable importance in translational medicine and will undoubtedly lead to more appropriate therapeutic strategies and more successful treatment.

Suicide risk in multiple sclerosis: a systematic review of current literature.
Studies have shown that suicidal ideation is often revealed among patients suffering from Multiple Sclerosis (MS). Mental health assessment of physically ill patients should form part of routine clinical evaluation, particularly in chronic illness. Clinicians should be aware of the fact that suicidality may occur with higher frequency in MS patients, the available data suggest that the risk of self-harm is higher than expected in MS patients.

The development of myelin repair agents for treatment of multiple sclerosis: progress and challenges.
Multiple Sclerosis (MS) is an inflammatory demyelinating disorder which affects the central nervous system. Multiple sclerosis treatment has traditionally focused on preventing inflammatory damage to the myelin sheath. Finally, we aim to highlight the challenges in the identification and development of such therapeutics.

OTC Meds May Prevent Marijuana-Induced Memory Problems
"Our results suggest that the unwanted side effects of cannabis could be eliminated or reduced, while retaining its beneficial effects, by administering a COX-2 inhibitor along with THC for the treatment of intractable medical conditions," Dr. Chen summarized.

Autoimmune T-Cell Reactivity to Myelin Proteolipids and Glycolipids in Multiple Sclerosis.
this review considers the question of what would be required to prove a definite role for autoreactivity against proteolipids and glycolipids in the pathogenesis of MS.

Increased B cell and cytotoxic NK cell proportions and increased T cell responsiveness in blood of natalizumab-treated multiple sclerosis patients.
Changes in the blood lymphocyte composition probably both mediate and reflect the effects of natalizumab treatment in multiple sclerosis, with implications for treatment benefits and risks.
Our data confirms that natalizumab treatment increases the number of lymphocytes in blood, likely mirroring the expression of VLA-4 being highest on NK and B cells. This finding supports reduction of lymphocyte extravasation as a main mode of action, although the differential effects on subpopulation composition suggests that cell-signalling may also be affected. The systemic increase in T cell responsiveness reflects the increase in numbers, and while augmenting anti-infectious responses systemically, localized responses may become correspondingly decreased.

Emotional Change-Associated T Cell Mobilization at the Early Stage of a Mouse Model of Multiple Sclerosis.
The validation of these findings in the clinic might help to better understand the cause of the emotional and psychological burden of patients suffering MS or other autoimmune diseases. Most importantly our study suggests novel therapeutic venues for the treatment of the emotional changes associated with autoimmunity.

Erythrocyte membrane Fatty acids in multiple sclerosis patients and hot-nature dietary intervention with co-supplemented hemp-seed and evening-primrose oils.
We concluded that Hot-nature dietary intervention with co-supplemented hemp seed and evening primrose oils caused an increase PUFAs in MS patients and improvement in the erythrocyte membrane fatty acids composition. This could be an indication of restored plasma stores, and a reflection of disease severity reduction.

Mass lesions in the brain: tumor or multiple sclerosis? Clinical and imaging characteristics and course from a single reference center.
Although MRI, CSF and pathologic examination help in differential diagnosis of the mass lesions, close follow-up is still crucial for the definite diagnosis. A higher MS conversion rate was found in patients with a younger TDL onset age.

Application of the 2012 revised diagnostic definitions for paediatric multiple sclerosis and immune-mediated central nervous system demyelination disorders.
Recently, the International Paediatric Multiple Sclerosis Study Group (IPMSSG) definitions for the diagnosis of immune-mediated acquired demyelinating syndromes (ADS) of the central nervous system, including paediatric multiple sclerosis (MS), have been revised. MS diagnosis can be made reliable and early using the 2012 IPMSSG consensus definitions. This is beneficial for adequate counselling of children and their families and for early treatment possibilities.

Analysis of CYP27B1 in multiple sclerosis.
he analysis of genetic variability in CYP27B1 and its effect on risk of multiple sclerosis (MS) has yielded conflicting results. Here we describe a study to genetically characterize CYP27B1 and elucidate its role on MS risk in the Canadian population. Sequencing CYP27B1 failed to identify mutations known to cause loss of enzymatic activity, however genotyping of p.R389H in cases and controls identified the mutation in one multi-incident family (allele frequency=0.03%) in which the p.R389H mutation segregates with disease in five family members diagnosed with MS, thus providing additional support for CYP27B1 p.R389H in the pathogenicity of MS.

Daclizumab, an IL-2 modulating antibody for treatment of multiple sclerosis.
In recently completed randomized trials in RRMS, treatment with daclizumab monotherapy compared with placebo resulted in clinically meaningful and statistically significant reductions in relapses, active lesions on brain MRI and slowing of disability progression. A large Phase III trial in RRMS is ongoing.

Abnormal nerve conduction study findings indicating the existence of peripheral neuropathy in multiple sclerosis and neuromyelitis optica.

Synaptic Plasticity and PDGF Signaling Defects Underlie Clinical Progression in Multiple Sclerosis.

Association between multiple sclerosis and epilepsy: large population-based record-linkage studies.
Multiple sclerosis (MS) and epilepsy are both fairly common and it follows that they may sometimes occur together in the same people by chance. We sought to determine whether hospitalisation for MS and hospitalisation for epilepsy occur together more often than expected by chance alone. MS and epilepsy occur together more commonly than by chance. One possible explanation is that an MS lesion acts as a focus of an epileptic seizure; but other possibilities are discussed. Clinicians should be aware of the risk of epilepsy in people with MS. The findings may also suggest clues for researchers in developing hypotheses about underlying mechanisms for the two conditions.

Advances in the management of multiple sclerosis spasticity: multiple sclerosis spasticity guidelines.

Present and future of fMRI in multiple sclerosis.
As shown in brain studies, these investigations have detected increased recruitment in MS patients compared with healthy controls. At present, fMRI is a useful research tool, and reliable analysis and display methods have been developed. Future perspectives include development of fMRI paradigms for patients with MS-related disability and application of this technique in longitudinal studies to define the temporal evolution of functional cortical changes in different MS phenotypes as well as the effects of various therapeutic approaches on central nervous system plasticity.

Decoding multiple sclerosis: an update on genomics and future directions.
Ongoing efforts to fully characterize the repertoire of genes that predispose to MS and modulate its presentation is discussed. Functional characterization of even a moderate genetic effect on MS pathogenesis by a known gene or group of genes can assist in elucidating fundamental mechanisms of disease expression and yield important therapeutic opportunities.

[Brain metabolism in multiple sclerosis: effects of neurotrophic therapy.]

[Differential diagnosis of multiple sclerosis with pediatric onset: the experience of the Moscow Division for treatment of children and adolescents with multiple sclerosis.]

[Pregnancy and delivery in women with multiple sclerosis: a retrospective analysis.]
Patients who did not receive DMD had more relapses to the 3rd and 6th months after delivery. In conclusion, the use of DMD before the pregnancy is an important factor for prevention of relapses during pregnancy and after delivery.

Guideline for the diagnosis and management of multiple sclerosis in children.
The International Paediatric MS Study Group (IPMSSG) was formulated to clarify the diagnostic and therapeutic dilemmas in this population. This guideline was adapted from the International Paediatric Multiple Sclerosis Study Group guideline and endorsed by PANDA, South Africa.

Depression as a predictor of occupational transition in a multiple sclerosis cohort.
Adjustments for ambulation status, physical and mental quality of life composite scores and fatigue impact attenuated or eliminated the association. While depression commonly occurs around the time of occupational transitions in MS, it does not appear to be an independent or direct cause of such transitions.

Extremely low-frequency pulsed magnetic fields and multiple sclerosis: effects on neurotransmission alone or also on immunomodulation? Building a working hypothesis.

Effects of Multiple Sclerosis on Female Sexuality: A Controlled Study.
Sexual functions are negatively affected in MS women. Sexual functions in MS women seem to be associated with enhanced disability, pain, duration of the disease, and degree of concomitant depression. Therefore, women with MS should also be evaluated in terms of sexual function during routine follow-ups. Gumus H, Akpinar Z, and Yilmaz H. Effects of multiple sclerosis on female sexuality: A controlled study. J Sex Med

MicroRNA Expression Aberration in Chinese Patients with Relapsing Remitting Multiple Sclerosis.

Comparison of IFN-β inducible gene expression in primary-progressive and relapsing-remitting multiple sclerosis.

Consequences of perinatal bisphenol A exposure in a mouse model of multiple sclerosis.
These results demonstrate the effect of BPA on the trajectory of TVID, and illustrate how multiple factors collectively influence autoimmune disease.

Clinically meaningful performance benchmarks in MS: Timed 25-Foot Walk and the real world.
Identify and validate clinically meaningful Timed 25-Foot Walk (T25FW) performance benchmarks in individuals living with multiple sclerosis (MS). Using a cross-sectional design, we identified 2 clinically meaningful T25FW benchmarks of ≥6 seconds (6-7.99) and ≥8 seconds. Longitudinal and larger studies are needed to confirm the clinical utility and relevance of these proposed T25FW benchmarks and to parse out whether there are additional benchmarks in the lower (<6 seconds) and higher (>10 seconds) ranges of performance.

Effects of exercise on fitness and cognition in progressive MS: a randomized, controlled pilot trial.
To investigate the potential of standardized exercise as a therapeutic intervention for progressive MS, in a randomized-controlled pilot trial. This study indicated that aerobic training is feasible and could be beneficial for patients with progressive MS. Larger exercise studies are needed to confirm the effect on cognition.

Central auditory processing and word discrimination in patients with multiple sclerosis.
Results of the present study showed that patients with MS had defect in aspects of central auditory processing consisting of temporal resolution, auditory pattern and the memory for auditory task and difficulty in discrimination of speech in noisy environment that are related to the involvement of central nervous system.

Early pathological alterations of lower lumbar cords detected by ultrahigh-field MRI in a mouse multiple sclerosis model.
These results suggest that inflammation-mediated alterations in the lower lumbar cord change the homeostasis of the spinal cord and demonstrate that ultrahigh-field MRI enables the detection of previously invisible pathological alterations in EAE.

Automated extraction of clinical traits of multiple sclerosis in electronic medical records.
The clinical course of multiple sclerosis (MS) is highly variable, and research data collection is costly and time consuming. We evaluated natural language processing techniques applied to electronic medical records (EMR) to identify MS patients and the key clinical traits of their disease course. This collection of clinical data represents one of the largest databases of detailed, clinical traits available for research on MS. This work demonstrates that detailed clinical information is recorded in the EMR and can be extracted for research purposes with high reliability.

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Inflammatory Cortical Demyelination in Early Multiple Sclerosis

Cortical disease has emerged as a critical aspect of the pathogenesis of multiple sclerosis, being associated with disease progression and cognitive impairment. Most studies of cortical lesions have focused on autopsy findings in patients with long-standing, chronic, progressive multiple sclerosis, and the noninflammatory nature of these lesions has been emphasized. Magnetic resonance imaging studies indicate that cortical damage occurs early in the disease.

Ocular pathology in multiple sclerosis: retinal atrophy and inflammation irrespective of disease duration

Microcystic macular oedema in multiple sclerosis is associated with disease severity

Macular oedema typically results from blood–retinal barrier disruption. It has recently been reported that patients with multiple sclerosis treated with FTY-720 (fingolimod) may exhibit macular oedema. Multiple sclerosis is not otherwise thought to be associated with macular oedema except in the context of comorbid clinical uveitis. Despite a lack of myelin, the retina is a site of inflammation and microglial activation in multiple sclerosis and demonstrates significant neuronal and axonal loss.

FOXP3, CBLB and ITCH gene expression and cytotoxic T lymphocyte antigen 4 expression on CD4⁺CD25^high T cells in multiple sclerosis

MRI in multiple sclerosis: current status and future prospects

Many promising MRI approaches for research or clinical management of multiple sclerosis (MS) have recently emerged, or are under development or refinement. Advanced MRI methods need to be assessed to determine whether they allow earlier diagnosis or better identification of phenotypes. Improved post-processing should allow more efficient and complete extraction of information from images.

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

Magnetic resonance imaging as a surrogate outcome for multiple sclerosis relapses

Magnetic resonance imaging (MRI) of lesions in the brain may be the best current candidate for a surrogate biological marker of clinical outcomes in relapsing remitting multiple sclerosis (MS), based on its role as an objective indicator of disease pathology. No biological surrogate marker has yet been validated for MS clinical outcomes. Confidence intervals for correlations between CELs and MS relapses exclude the possibility that CELs can be a good surrogate for relapses over the time scales we investigated. Further exploration of surrogacy between MRI measures and MS clinical outcomes may require improved datasets, the development of MRI techniques that couple better to clinical disease, and the ability to test a wide range of imaging- and clinically-based hypotheses for surrogacy.

Presenting evidence-based health information for people with multiple sclerosis: the IN-DEEP project protocol

Increasingly, evidence-based health information, in particular evidence from systematic reviews, is being made available to lay audiences, in addition to health professionals. Research efforts have focused on different formats for the lay presentation of health information. However, there is a paucity of data on how patients integrate evidence-based health information with other factors such as their preferences for information and experiences with information-seeking. The aim of this project is to explore how people with multiple sclerosis (MS) integrate health information with their needs, experiences, preferences and values and how these factors can be incorporated into an online resource of evidence-based health information provision for people with MS and their families.

The potential of mesenchymal stromal cells as a novel cellular therapy for multiple sclerosis

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the CNS for which only partially effective therapies exist. Intense research defining the underlying immune pathophysiology is advancing both the understanding of MS as well as revealing potential targets for disease intervention. Mesenchymal stromal cell (MSC) therapy has the potential to modulate aberrant immune responses causing demyelination and axonal injury associated with MS, as well as to repair and restore damaged CNS tissue and cells.

Epstein–Barr virus infection is not a characteristic feature of multiple sclerosis brain

A comprehensive assessment of cerebellar damage in multiple sclerosis using diffusion tractography and volumetric analysis

White matter (WM) and grey matter (GM) brain damage in multiple sclerosis (MS) is widespread, but the extent of cerebellar involvement and impact on disability needs to be clarified. These findings indicate reduced fibre coherence in the main cerebellar connections, and link damage in the whole cerebellar WM, and, in particular, in the superior cerebellar peduncle, to motor deficit in PPMS.

Setting a research agenda for progressive multiple sclerosis: The International Collaborative on Progressive MS

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis.

The Impact of Osteopontin Gene Variations on Multiple Sclerosis Development and Progression

Clinically Isolated Syndromes Suggestive of Multiple Sclerosis: An Optical Coherence Tomography Study

Optical coherence tomography (OCT) is a simple, high-resolution technique to quantify the thickness of retinal nerve fiber layer (RNFL), which provides an indirect measurement of axonal damage in multiple sclerosis (MS). This study aimed to evaluate RNFL thickness in patients at presentation with clinically isolated syndromes (CIS) suggestive of MS.

Patterns of Retinal Damage Facilitate Differential Diagnosis between Susac Syndrome and MS

Susac syndrome, a rare but probably underdiagnosed combination of encephalopathy, hearing loss, and visual deficits due to branch retinal artery occlusion of unknown aetiology has to be considered as differential diagnosis in various conditions. Particularly, differentiation from multiple sclerosis is often challenging since both clinical presentation and diagnostic findings may overlap. Optical coherence tomography is a powerful and easy to perform diagnostic tool to analyse the morphological integrity of retinal structures and is increasingly established to depict characteristic patterns of retinal pathology in multiple sclerosis. Against this background we hypothesised that differential patterns of retinal pathology facilitate a reliable differentiation between Susac syndrome and multiple sclerosis.

Advanced MRI in Multiple Sclerosis: Current Status and Future Challenges

A Transdermal Myeloid Peptide Patch to Treat MS
Although antigen-specific autoimmunity is thought to play a critical role in the pathogenesis of multiple sclerosis, all currently available therapies reduce global immune function without targeting the specific antigens involved. The goal of this 1-year, double-blind, placebo-controlled cohort study was to examine the efficacy and safety of transdermally applied myelin peptides as antigen-specific therapy in multiple sclerosis.

Sjögren Syndrome: An A-to-Z Update
A steady growth in the number of abstracts and sessions devoted to Sjögren syndrome is apparent over the past decade of ACR meetings. It is encouraging that many pharmaceutical companies are now expressing interest in Sjögren syndrome as a therapeutic target. The dearth of effective therapies for systemic manifestations of Sjögren syndrome contrasts with the large number of therapies for rheumatoid arthritis and studies for psoriatic arthritis. Multiple sclerosis and fibromyalgia have also benefited from recently approved therapies.

Synaptic plasticity in multiple sclerosis and in experimental autoimmune encephalomyelitis.
Approximately half of all patients with multiple sclerosis (MS) experience cognitive dysfunction, including learning and memory impairment. Recent studies suggest that hippocampal pathology is involved, although the mechanisms underlying these deficits remain poorly understood. Evidence obtained from a mouse model of MS, the experimental autoimmune encephalomyelitis (EAE), suggests that in the hippocampus of EAE mice long-term potentiation (LTP) is favoured over long-term depression in response to repetitive synaptic activation, through a mechanism dependent on enhanced IL-1β released from infiltrating lymphocytes or activated microglia.

The risk of Bipolar Disorders in Multiple Sclerosis.
The aim was to determine the risk of Mood Disorders (MD), particularly Bipolar Disorders (BD), in Multiple Sclerosis (MS) using standardized psychiatric diagnostic tools. This study was the first to show an association between BD and MS using standardized diagnostic tools and a case-control design. The results suggest a risk of under-diagnosis of BD (particularly type II) in MS and caution in prescribing ADs to people with depressive episodes in MS without prior excluding BD. The association between auto-immune degenerative diseases (like MS) and BD may be an interesting field for the study of the pathogenic hypothesis.

A Meta-analysis of the relation between chemokine receptor 5 delta32 polymorphism and multiple sclerosis susceptibility.
he aim of this study was to determine whether the functional chemokine receptor 5 delta32 (CCR5-Δ32) polymorphism is associated with multiple sclerosis (MS) susceptibility.

Long-term effects of dalfampridine in patients with multiple sclerosis.
Dalfampridine is the extended-release formulation of 4-aminopyridine and is approved for the symptomatic treatment of impaired mobility in patients with multiple sclerosis. Our aim was to examine the short- and long-term effects of treatment with dalfampridine on motoric and cognitive assessment parameters of multiple sclerosis (MS) patients over 9-12months. Dalfampridine shows positive short- and long-term effects on motoric and cognitive assessment parameters in an open-label observational study in a cohort of patients with MS.

Oxidative modification of blood serum proteins in multiple sclerosis after interferon or mitoxantrone treatment.
his study was aimed at (i) comparison of the usefulness of serum protein oxidation parameters for assessment of oxidative stress (OS) in multiple sclerosis (MS), and (ii) comparison of OS in MS patients subject to various therapies. Elevated glycophore level was noted in relapsing-remitting (RRMS) patients without treatment and patients treated with interferons β1a and β1b (10.33±3.27, 8.02±2.22 and 8.56±2.45 vs control 5.27±0.73 fluorescence units (FU)/mg protein).

Cross-sectional area variations of internal jugular veins during supine head rotation in multiple sclerosis patients with chronic cerebrospinal venous insufficiency: a prospective diagnostic controlled study with duplex ultrasound investigation.
Normally, chronic cerebrospinal venous insufficiency (CCSVI) has been studied using echo-colour Doppler (ECD). Subjects are examined in the supine and sitting positions, in accordance with a static protocol without rotation of the head. A dynamic approach, to assess venous sizes with different degrees of head rotation, has only been performed to improve jugular venous catheterisation. These echographic studies have suggested that head rotation to the contralateral side increases the cross-sectional area (CSA) of the internal jugular veins (IJVs) in supine subjects. Our goal was to evaluate the behaviour of CSA of the IJVs during supine head rotation in multiple sclerosis (MS) patients with CCSVI, compared to healthy controls (HCs). A dynamic ECD approach allowed us to detect IJVs with a significant increase in their CSAs during head rotation, but only in MS subjects. This feature, most likely the expression of congenital wall miopragia, could be secondary to dysregulation of collagen synthesis, but further histochemical studies will be needed to confirm this hypothesis.

Assessment of upper limb motor function in patients with multiple sclerosis using the Virtual Peg Insertion Test: A pilot study.
Quantifying and tracking upper limb impairment is of key importance to the understanding of disease progress, establishing patient-tailored therapy protocols and for optimal care provision. This paper presents the results of a pilot study on the assessment of upper limb motor function in patients with multiple sclerosis (MS) with the Virtual Peg Insertion Test (VPIT). The test consists in a goal-directed reaching task using a commercial haptic display combined with an instrumented handle and virtual environment, and allows for the extraction of objective kinematic and dynamic parameters.

A telerehabilitation program improves postural control in multiple sclerosis patients: a spanish preliminary study.
ostural control disorders are among the most frequent motor disorder symptoms associated with multiple sclerosis. This study aims to demonstrate the potential improvements in postural control among patients with multiple sclerosis who complete a telerehabilitation program that represents a feasible alternative to physical therapy for situations in which conventional treatment is not available.

Novel Immunomodulatory Approaches for the Management of Multiple Sclerosis.
We provide a focused review of novel immunomodulatory approaches for the treatment of multiple sclerosis, the most common acquired inflammatory demyelinating disease of humans. The requirement for such a review was stimulated by the emerging application of novel oral medications and the need for the practicing physician to place these within the treatment paradigm.

A nine-year population-based cohort study on the risk of multiple sclerosis in patients with optic neuritis.
Patients with optic neuritis (ON) are at an increased risk of developing multiple sclerosis (MS), an illness that may result in physical dysfunction and short life expectancy. Information on the conversion rate to MS of patients with ON is essential in determining the impact of ON on the incidence of MS. Previous Taiwanese studies on the risk of MS in patients with ON were all hospital based, thereby limiting the generalizability of the findings.

Mood and coping in clinically isolated syndrome and multiple sclerosis.
Few studies have examined behavioural changes in the early phase of multiple sclerosis (MS). The aim of the study is to investigate mood alterations and to explore coping strategies regarding patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS). This study highlights transient mood alterations and an improving of adaptive coping over a period of time in patients with CIS and RRMS. Similar emotional reactions and coping in clinical subgroups suggest that these factors are independent from the type of information provided during the communication of the diagnosis.

Improvement of driving skills in persons with Relapsing-Remitting Multiple Sclerosis: a pilot study.
To determine the potential to improve driving-related skills using a simulator-based program in persons with Relapsing Remitting Multiple Sclerosis (RRMS). This pilot study demonstrates the potential of using a simulator to improve driving-related visual, cognitive, and on-road skills in individuals with RRMS, particularly those with EDSS > 3. Future randomized controlled trials with adequate power are needed to expand this field of study.

Group specific vein-atlasing: An application for analyzing the venous system under normal and multiple sclerosis conditions.
To create a group-specific vein-atlas based on healthy control subjects to visualize the average venous system under normal conditions and to compare the venous volume portion in multiple sclerosis (MS) lesions with that atlas. The developed vein-atlas shows the average venous system of a specific population and allows, therefore, the evaluation of the venous system of individual subjects.

The association of alcohol consumption and smoking with quality of life, disability and disease activity in an international sample of people with multiple sclerosis.
Modifiable lifestyle factors represent important targets for preventive intervention in multiple sclerosis (MS). We aimed to explore the association of cigarette smoking and alcohol consumption with major MS morbidity outcomes. This cross-sectional study supports previous research showing a link between morbidity indicators in MS and alcohol use and smoking. While people with MS should be advised of the potential risks of smoking, any risks and benefits of alcohol consumption require validation using a prospective cohort of people with MS.

Burden of disease in multiple sclerosis patients with spasticity in Germany: mobility improvement study (Move I).
To describe the current management patterns of multiple sclerosis (MS) patients with spasticity in Germany and the impact of MS spasticity on quality of life (QoL) and associated costs.
MS patients with spasticity suffer a significant burden because of resulting disabilities and reduced QoL, especially in cases of severe spasticity. Moreover, spasticity causes high costs that increase with increasing severity.

Pediatric Multiple Sclerosis: Current Concepts and Consensus Definitions.

Risk evaluation and monitoring in multiple sclerosis therapeutics.
Risk for multiple sclerosis (MS) disease-modifying therapies (DMT) must be assessed on an ongoing basis. Early concerns regarding the first-approved DMTs for MS have been mitigated, but recently licensed therapies have been linked to possibly greater risks. It is difficult to produce a general risk-assessment algorithm for all MS therapies. Specific algorithms are required for each DMT in every treated-patient population. New and evolving risks must be evaluated and communicated rapidly to allow patients and physicians to be well informed and able to share treatment decisions.

Five-year results from a phase 2 study of oral fingolimod in relapsing multiple sclerosis.
We present here results at 60 months (M), from the extension component of a phase 2, randomized, placebo-controlled, double-blind, six-month study evaluating oral fingolimod (1.25 mg or 5 mg daily) in relapsing multiple sclerosis. Placebo patients from the core study were re-randomized to fingolimod 1.25 mg or 5 mg in the extension. All patients received 1.25 mg fingolimod after the M24 visit. A total of 140/281 (49.8%) patients completed M60. Fingolimod treatment was associated with a low annualized relapse rate (0.2 relapses/ year), low MRI activity, and a modest rate of disability progression in those treated for five years. No new safety issues were reported.

Immunology for understanding the pathogenesis of multiple sclerosis.

The coexistence of well- and ill-being in persons with multiple sclerosis, their caregivers and health professionals.
Studies on emotional distress and health-related quality of life (HRQOL) broadened the traditional bio-medical focus in MS research, but little attention was paid to general well-being indicators.
Well-being coexists with ill-being. It can counterbalance the negative effects of disease or caregiving, and its measurement could complement and support medical intervention.

[Autonomic nervous system alteration in multiple sclerosis patients with urinary symptoms. Clinical, urodynamic and cardiovascular study].
To assess symptoms related to autonomic nervous system alteration in a population of patients suffering from multiple sclerosis (MS) and presenting with urinary symptoms. In this series, the prevalence of dysautonomia was high in patients suffering from MS and presenting with urinary disorders.

Fine-Mapping the Genetic Association of the Major Histocompatibility Complex in Multiple Sclerosis: HLA and Non-HLA Effects.
The major histocompatibility complex (MHC) region is strongly associated with multiple sclerosis (MS) susceptibility. HLA-DRB1*15:01 has the strongest effect, and several other alleles have been reported at different levels of validation. Using SNP data from genome-wide studies, we imputed and tested classical alleles and amino acid polymorphisms in 8 classical human leukocyte antigen (HLA) genes in 5,091 cases and 9,595 controls.

The reliability and validity study of the Kinesthetic and Visual Imagery Questionnaire in individuals with Multiple Sclerosis.
Motor imagery (MI) has been recently considered as an adjunct to physical rehabilitation in patients with multiple sclerosis (MS). It is necessary to assess MI abilities and benefits in patients with MS by using a reliable tool. The Kinesthetic and Visual Imagery Questionnaire (KVIQ) was recently developed to assess MI ability in patients with stroke and other disabilities. Considering the different underlying pathologies, the present study aimed to examine the validity and reliability of the KVIQ in MS patients. The results of the present study revealed that the KVIQ is a valid and reliable tool for assessing MI in MS patients.

Pregnancy and Fetal Outcomes After Glatiramer Acetate Exposure in Patients With Multiple Sclerosis
Only few studies have assessed safety of in utero exposure to glatiramer acetate (GA). Following a previous study assessing the safety of interferon beta (IFNB) pregnancy exposure in multiple sclerosis (MS), we aimed to assess pregnancy and fetal outcomes after in utero exposure to GA, using the same dataset, with a specific focus on the risk of spontaneous abortion. Data in our cohort show that mother's GA exposure is not associated with a higher frequency of spontaneous abortion, neither other negative pregnancy and fetal outcomes. Our findings point to the safety of in utero GA exposure and can support neurologists in the therapeutic counselling of MS women planning a pregnancy.

Smoking and Two Human Leukocyte Antigen Genes Interact to Increase the Risk for Multiple Sclerosis
Both genetic and environmental factors display low or modest associations with multiple sclerosis. Hypothetically, gene–environment interactions may exert much stronger effects. In this study, we investigated potential interactions between genetic risk factors and smoking in relation to risk of developing multiple sclerosis. A population-based case–control study involving incident cases of multiple sclerosis (843 cases, 1209 controls) was performed in Sweden. Cases and controls were classified according to their smoking status and human leukocyte antigen DRB1 as well as human leukocyte antigen A genotypes.

Treating Multiple Sclerosis With Monoclonal Antibodies

Current Disease-Modifying Therapies in Multiple Sclerosis

Chemotherapeutics in the Treatment of Multiple Sclerosis

The month of birth effect in multiple sclerosis: systematic review, meta-analysis and effect of latitude.
Month of birth has previously been described as a risk factor for multiple sclerosis (MS). This has been hypothesised to be related to maternal vitamin D levels during pregnancy, although conclusive evidence to support this is lacking. To date, no large studies of latitudinal variation in the month of birth effect have been performed to advance this hypothesis. Month of birth has a significant effect on subsequent MS risk. This is likely to be due to ultraviolet light exposure and maternal vitamin D levels, as demonstrated by the relationship between risk and latitude.

Carnitine for fatigue in multiple sclerosis.
Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients. There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators. Results of the ongoing trial are eagerly anticipated in order to provide clarity.

Cognitive Impairment Occurs in Children and Adolescents With Multiple Sclerosis: Results From a United States Network

Treating multiple sclerosis with monoclonal antibodies: a 2013 update.

Objectively quantified physical activity in persons with multiple sclerosis.
To investigate levels of moderate-to-vigorous physical activity (MVPA) in a large sample of persons with multiple sclerosis (MS) and controls using accelerometry as a measure of physical activity, and to compare the rates of meeting public health guidelines for MVPA (ie, 30min/d) between persons with MS and controls. We provide data using an objective physical activity measure and a large sample to indicate that only a small proportion of persons with MS are achieving adequate amounts of daily MVPA.

Management of lower urinary tract dysfunction in multiple sclerosis: A systematic review and Turkish consensus report.
Since lower urinary tract dysfunction (LUTD) related to multiple sclerosis (MS) has a different behavior pattern than other types of neurogenic voiding dysfunction, we aimed to prepare a national consensus report for the management of LUTD due to multiple sclerosis in light of available literature. Patients with MS and LUTD could be best managed through the use of this consensus report.

Relevance of Spinal Cord Abnormalities to Clinical Disability in Multiple Sclerosis: MR Imaging Findings in a Large Cohort of Patients.
To determine whether spinal cord atrophy differs among disease subtypes in multiple sclerosis (MS) and whether it offers diagnostic and clinical correlative information beyond that provided by other magnetic resonance (MR) imaging markers.Spinal cord abnormalities have a strong effect on clinical disability in MS. MR imaging-derived UCCA was found to be the most significant spinal cord parameter for explaining EDSS score.

New Data on How MS Patients Fare Long-Term

Tumefactive Multiple Sclerosis in Taiwan

To review patients with tumefactive MS and compare them with those in other studies investigating tumefactive demyelinating lesions and our Taiwanese typical MS patients. Tumefactive MS is not common in Taiwan. Although the tumefactive demyelinating lesions seem to be terrible initially, their prognosis is relatively more favorable than expected.

Quantification of multiple-sclerosis-related brain atrophy in two heterogeneous MRI datasets using mixed-effects modeling

Role Preferences of People with Multiple Sclerosis: Image-Revised, Computerized Self-Administered Version of the Control Preference Scale

A novel oral nutraceutical formula of omega-3 and omega-6 fatty acids with vitamins (PLP10) in relapsing remitting multiple sclerosis: a randomised, double-blind, placebo-controlled proof-of-concept clinical trial

Blood-Brain Barrier Permeability of Normal Appearing White Matter in Relapsing-Remitting Multiple Sclerosis

Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons

The genetics of multiple sclerosis: review of current and emerging candidates

Immunology and Oxidative Stress in Multiple Sclerosis: Clinical and Basic Approach.

TNFRSF1A in multiple sclerosis: A tale of soluble receptors and signaling cascades.

Current recommendations for multiple sclerosis treatment in pregnancy and puerperium.

Prevalence and incidence of Multiple Sclerosis in Campobasso (Molise region chieftown, southern Italy).
Multiple Sclerosis in southern Italy was not epidemiologically studied until 2006 in Salerno (Campania region), with data based on the registry of district MS centers established since 1996 by Italian Ministry of Health. This paper reports data about Molise region by the same metodology as Campanian study. Prevalence is coherent with previous Campanian data, and with last epidemiologic papers on middle Italy, confirming also the validity of MS district centers registries. A possible underestimation of data, for some patients could still migrate to northern centers, could contribute to the differences in incidence. Nevertheless, prevalence data confirm southern Italy as high risk area for MS, and stands against a latitude gradient in this country.

Adverse events after endovascular treatment of chronic cerebro-spinal venous insufficiency (CCSVI) in patients with multiple sclerosis.

RebiSmart™ (version 1.5) device for multiple sclerosis treatment delivery and adherence.

First-line disease-modifying drugs for the treatment of multiple sclerosis (MS) are mostly administered by injection. Although these treatments can control the symptoms and progression of the disease to some extent, patients often fail to adhere to their therapy in the long term, so may not obtain the maximum clinical benefits. As injection-related problems are common barriers to adherence, autoinjectors have been developed to improve the ease and convenience of self-injection.
The device is the first electronic autoinjector for use in MS and offers several innovative features, including adjustable injection settings and an electronic dosing log, which may improve adherence. The dosing log can be reviewed with the patient, allowing the physician to open a dialogue to discuss possible issues with treatment adherence. The use of multidose cartridges also provides a softer impact on the environment and easier disposal. The hidden needle helps avoid needle phobia and reduces the risk of needle stick injury.

Assess, compare and enhance the status of Persons with Multiple Sclerosis (MS) in Europe: a European Register for MS.

Prevalence of multiple sclerosis in Dubai, United Arab Emirates.

High nationwide prevalence of multiple sclerosis in Sweden.

Drug Class Review: Disease-modifying Drugs for Multiple Sclerosis: Final Update 1 Report [Internet].
We compared the effectiveness and safety of disease-modifying drugs for the treatment of multiple sclerosis: Glatiramer acetate (Copaxone^®), interferon beta-1a (Avonex^®, Rebif^®), interferon beta-1b (Betaseron^®, Extavia^®), mitoxantrone (Novantrone^®), and natalizumab (Tysabri^®). There was fair evidence that interferon beta-1a IM (Avonex^®) is less effective than interferon beta-1a SC (Rebif^®) and interferon beta-1b (Betaseron^®) for preventing relapse in patients with relapsing remitting multiple sclerosis. On other outcomes and in other populations, direct evidence is either lacking or shows few differences in effectiveness or safety among the disease-modifying drugs used to treat multiple sclerosis.

The town of Cabar, Croatia, familiar pseudocluster for multiple sclerosis--descriptive epidemiological study.

Association of UV radiation with multiple sclerosis prevalence and sex ratio in France.
French farmers and their families constitute an informative population to study multiple sclerosis (MS) prevalence and related epidemiology. We carried out an ecological study to evaluate the association of MS prevalence and ultraviolet (UV) radiation, a candidate climatologic risk factor.
The findings suggest that regional UVB radiation is predictive of corresponding MS prevalence rates and supports the hypothesis that sunlight exposure influences MS risk. The evidence also supports a potential role for gender-specific effects of UVB exposure.

The polymorphisms of the TNF-α gene in multiple sclerosis?--a meta-analysis.
The association between multiple sclerosis (MS) and tumor necrosis factor-alpha gene (TNF-α) polymorphisms has been analyzed in several studies, but conflicting results have been reported. The main purpose of this study was to integrate previous findings and explore whether the three single nucleotide polymorphisms (SNPs; -238G/A, -308G/A, and -376G/A) of TNF-α are associated with susceptibility to MS. A total of 2,639 patients and 3,303 controls from 21 studies, which were identified by searching the ISI Web of Knowledge database and the PubMed database up to December 2009, were collected for this meta-analysis.

All-cause health care utilization and costs associated with newly diagnosed multiple sclerosis in the United States.

A seasonal periodicity in relapses of multiple sclerosis? A single-center, population-based, preliminary study conducted in Bologna, Italy.

Treatment of Multiple Sclerosis With Chinese Scalp Acupuncture.
Chinese scalp acupuncture is a contemporary acupuncture technique with just 40 years of history. It integrates traditional Chinese needling methods with Western medical knowledge of the cerebral cortex and has been proven to be a very effective technique for treating multiple sclerosis (MS) and other central nervous system disorders. A 65-year-old male patient who had had MS for 20 years was treated with Chinese scalp acupuncture. The motor area, sensory area, foot motor and sensory area, balance area, hearing and dizziness area, and tremor area were stimulated once a week for 10 weeks, then once a month for six sessions. After the 16 treatments, the patient showed remarkable improvements. He was able to stand and walk without any problems. The numbness and tingling in his limbs did not bother him anymore. He had more energy and had not experienced incontinence of urine or dizziness after the first treatment. He was able to return to work full time. At this writing, the patient has been in remission for 26 months. This case demonstrates that Chinese scalp acupuncture can be a very effective treatment for patients with MS. Chinese scalp acupuncture holds the potential to expand treatment options for MS in both conventional and complementary or integrative therapies. It can not only relieve symptoms, increase the patient's quality of life, and slow and reverse the progression of physical disability but also reduce the number of relapses and help patients with multiple sclerosis to remain in remission.

Transcranial direct current stimulation (tDCS) for fatigue in multiple sclerosis.

Visual search as a tool for a quick and reliable assessment of cognitive functions in patients with multiple sclerosis.
Despite the high frequency of cognitive impairment in multiple sclerosis, its assessment has not gained entrance into clinical routine yet, due to lack of time-saving and suitable tests for patients with multiple sclerosis. Visual search is a promising instrument for the assessment of cognitive functions and potentially cognitive changes in patients with multiple sclerosis thanks to its good discriminatory power and insusceptibility to practice effects.

Current and Future Therapies for Multiple Sclerosis.

Decreased circulating miRNA levels in patients with primary progressive multiple sclerosis.

Characteristics influencing therapy switch behavior after suboptimal response to first-line treatment in patients with multiple sclerosis.
The objective of this paper is to identify patient characteristics and clinical events predictive of therapy switching in patients with suboptimal response to DMT. Younger patients with disease activity, especially MRI changes, are more likely to have their therapy switched sooner than patients who are older at the time of MS diagnosis and DMT initiation.

Genetic burden of common variants in progressive and bout-onset multiple sclerosis.
The contribution of genetic variants underlying the susceptibility to different clinical courses of multiple sclerosis (MS) is still unclear. Our results suggest that the liability of disease is better captured by common genetic variants in BOMS than PrMS cases. The absence of inflammatory activity and male gender further raise the difference between clinical courses.

Age-Related Vascular Differences Among Patients Suffering from Multiple Sclerosis.

Role of Pathogens in Multiple Sclerosis.

Transplantation of umbilical cord and bone marrow-derived mesenchymal stem cells in a patient with relapsing-remitting multiple sclerosis.

Combination of robot-assisted and conventional body-weight-supported treadmill training improves gait in persons with multiple sclerosis: a pilot study.
The majority of persons with multiple sclerosis (MS) experience problems with gait, which they characterize as highly disabling impairments that adversely impact their quality of life. Thus, it is crucial to develop effective therapies to improve mobility for these individuals. The purpose of this study was to determine whether combination gait training, using robot-assisted treadmill training followed by conventional body-weight-supported treadmill training within the same session, improved gait and balance in individuals with MS. Combination of robot with body-weight-supported treadmill training gait training is feasible and improved 6MWT and FRT distances in persons with MS.Video Abstract available (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A62) for more insights from the authors.

Targeting the Immune System in Multiple Sclerosis

Endogenous Retroviruses and Multiple Sclerosis

Evidence for a two-stage disability progression in multiple sclerosis.

Sodium accumulation is associated with disability and a progressive course in multiple sclerosis.

Multiple sclerosis presenting initially with a worsening of migraine symptoms

Multiple sclerosis (MS) is a chronic autoimmune disease that targets myelinated axons in the central nervous system. Headache has been reported as a subtle symptom of the onset of MS, with a variable frequency of 1.6–28.5%; however, it remains unclear whether headache is a true symptom of MS onset. Here, we report the case of a female patient who had a history of migraine without aura and experienced worsening of migraine-headache symptoms as the initial manifestation of MS. Three similar cases were reported previously; however, unlike this case, those cases had no history of migraine without aura.

Presence and Significant Determinants of Cognitive Impairment in a Large Sample of Patients with Multiple Sclerosis

To investigate the presence and the nature of cognitive impairment in a large sample of patients with Multiple Sclerosis (MS), and to identify clinical and demographic determinants of cognitive impairment in MS. Our results corroborate the evidence about the presence and the nature of cognitive impairment in a large sample of patients with MS. Furthermore, our findings identify significant clinical and demographic determinants of cognitive impairment in a large sample of MS patients for the first time. Implications for further research and clinical practice were discussed.

Gait Variability and Multiple Sclerosis

Multiple Sclerosis and the Blood-Central Nervous System Barrier

Factors for Lower Walking Speed in Persons with Multiple Sclerosis

Sex and gender issues in multiple sclerosis

Multiple sclerosis (MS) is universally found to be more prevalent in women than men. This has led to extensive studies of differences in the immune system or nervous system between women and men, which might be caused by the effects of gonadal hormones, genetic differences, and different environmental exposures and modern lifestyle in men and women. We review the effects of sex and gender from a genetic, immunological and clinical point of view. We discuss the effects of sex on the clinical expression of MS and responses to therapy, as well as issues concerning pregnancy.

Muscle oxygen consumption by NIRS and mobility in multiple sclerosis patients

The study of muscle metabolism by near-infrared spectroscopy (NIRS) has been poorly implemented in multiple sclerosis (MS). Aims of the study were to compare resting muscle oxygen consumption (rmVO₂) at gastrocnemius in MS patients and in age-matched healthy controls (HC) measured using NIRS, and to evaluate its possible relationship with patients’ mobility.

Impact of Mobility Impairment on Indirect Costs and Health-Related Quality of Life in Multiple Sclerosis

Magnetic Resonance Disease Severity Scale (MRDSS) for patients with multiple sclerosis: a longitudinal study

Multiple Sclerosis, Relapses, and the Mechanism of Action of Adrenocorticotropic Hormone

Predicting Falls in People with Multiple Sclerosis: Fall History Is as Accurate as More Complex Measures

Background. Many people with MS fall, but the best method for identifying those at increased fall risk is not known. Objective. To compare how accurately fall history, questionnaires, and physical tests predict future falls and injurious falls in people with MS. Methods. 52 people with MS were asked if they had fallen in the past 2 months and the past year. Subjects were also assessed with the Activities-specific Balance Confidence, Falls Efficacy Scale-International, and Multiple Sclerosis Walking Scale-12 questionnaires, the Expanded Disability Status Scale, Timed 25-Foot Walk, and computerized dynamic posturography and recorded their falls daily for the following 6 months with calendars. The ability of baseline assessments to predict future falls was compared using receiver operator curves and logistic regression. Results. All tests individually provided similar fall prediction (area under the curve (AUC) 0.60–0.75). A fall in the past year was the best predictor of falls (AUC 0.75, sensitivity 0.89, specificity 0.56) or injurious falls (AUC 0.69, sensitivity 0.96, specificity 0.41) in the following 6 months. Conclusion. Simply asking people with MS if they have fallen in the past year predicts future falls and injurious falls as well as more complex, expensive, or time-consuming approaches.

Birth hospitalization in mothers with multiple sclerosis and their newborns

Work capacity and health-related quality of life among individuals with multiple sclerosis reduced by fatigue: a cross-sectional study

Impaired toll-like receptor 8 signaling in multiple sclerosis

Preservation of motor skill learning in patients with multiple sclerosis

Several studies have demonstrated benefits of rehabilitation in multiple sclerosis (MS). However, the neuroscientific foundations for rehabilitation in MS are poorly established. Mechanisms for short- and long-term plasticity may compensate for impaired functional connectivity in MS to mediate behavioural improvements. Future studies are needed to define the neurobiological substrates of this plasticity and the extent to which mechanisms of plasticity in patients may be distinct from those used for motor learning in controls.

Sexual Dysfunction in Male Patients with Multiple Sclerosis: A Need for Counseling!
Sexuality and sexual health are significant factors in determining the quality of life (QoL). Multiple sclerosis (MS) is one of the most serious causes of neurological disability in young adults, therefore it can considerably reduce sexuality. Physical and cognitive symptoms of MS as well as mental and psycho-social issues can directly affect sexual life and body representation, causing reduced libido and self-esteem. Male patients with MS frequently develop sexual dysfunction (SD) as a result of their neurological impairment: in fact physical, psychological and neuropsychological changes indirectly interfere in the sexual response. Thus, MS physicians' greater concern on SD has led to the enhancement of diagnostic and therapeutic diagnoses on neurogenic SD. Given the increasing number of people coping with MS, a more effective focus on MS-related problems, including SD, is absolutely essential to provide the patients and their partner with the necessary information to achieve a better sexual health and consequently improve their QoL. This review aims to investigate the epidemiology and pathophysiology of SD in male patients, provide an insight into multidisciplinary diagnostic and therapeutic approaches, and focus on the need of proper counseling.

The relationship between fear of falling to spatiotemporal gait parameters measured by an instrumented treadmill in people with multiple sclerosis.
People with multiple sclerosis (MS) identify mobility limitations as one of the greatest challenges of this disease. Continued loss of mobility and falls are among their greatest concerns for the future. Our objective was to determine if fear of falling is associated with spatial and temporal gait parameters in persons with MS, when measured by an instrumented treadmill.

Targeting the Immune System in Multiple Sclerosis

Epstein-Barr virus neutralizing antibody levels and risk of multiple sclerosis

Chronic Multiple Sclerosis Lesions: Characterization with High-Field-Strength MR Imaging

Down-regulation of Myelin Gene Expression in Human Oligodendrocytes by Nitric Oxide: Implications for Demyelination in Multiple Sclerosis.

Profile of Circulatory Metabolites in a Relapsing-remitting Animal Model of Multiple Sclerosis using Global Metabolomics.

The stress-buffering effects of hope on changes in adjustment to caregiving in multiple sclerosis.

Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains.
sing the Illumina 450K array and a stringent statistical analysis with age and gender correction, we report genome-wide differences in DNA methylation between pathology-free regions derived from human multiple sclerosis-affected and control brains. Differences were subtle, but widespread and reproducible in an independent validation cohort.

[Paroxysmal dystonia and multiple sclerosis.]
Movement disorders are uncommon in multiple sclerosis, except for tremor. Patients rarely have paroxysmal dystonia (or tonic spasm), which can be the presenting manifestation of the disease.
Dystonia is an under-recognized aspect of paroxysmal events during multiple sclerosis. It might involve ephaptic transmission among abnormal demyelinated neurons; this ectopic excitation can arise at variable levels of the corticospinal tract, but the analysis of reported cases and those described in this study shows that impairment of the posterior limb of the internal capsule seems to be a prevalent topography. Inflammation is likely to play a role because steroids often improve these phenomena. In this article, we review the clinical aspects, pathophysiology and outcome of paroxysmal dystonia in multiple sclerosis.

Bone marrow mesenchymal stromal cells isolated from multiple sclerosis patients have distinct gene expression profile and decreased suppressive function compared with healthy counterparts.
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system, due to immune reaction against myelin proteins. Multipotent mesenchymal stromal cells (MSCs) present immunosuppressive effects and have been used for the treatment of autoimmune diseases. In our study, gene expression profile and in vitro immunomodulatory function tests were used to compare bone marrow?derived MSCs obtained from MS patients, at pre? and post?autologous hematopoietic stem cell transplantation (AHSCT), with those from healthy donors.

[Cognitive deficits and dementia in patients with multiple sclerosis: status quo and open questions].
Multiple sclerosis (MS) is the most common chronic immune-mediated disease which goes along with serious somatic and psychic symptoms. Whereas recent research rather focussed on the neurological symptoms of MS, there is nowadays an increasing interest among researchers in psychological symptoms of the disease.

Frequency analysis approach to study balance control in individuals with multiple sclerosis.
The ability to control balance is often compromised in people with multiple sclerosis (MS) and is considered to be a strong contributing factor toward their increased risk of falls. The observed redistribution of the COP power spectrum when vision is absent indicates that people with MS rely more on the vestibular/somatosensory and proprioceptive systems. The outcome of the study suggests that the COP frequency analysis could be used in identifying the possible sources of balance impairment in people with MS.

Deficits in memory and visuospatial learning correlate with regional hippocampal atrophy in MS.
The hippocampus has a critical role in episodic memory and visuospatial learning and consolidation. We assessed the patterns of whole and regional hippocampal atrophy in a large group of multiple sclerosis (MS) patients, and their correlations with neuropsychological impairment.

CCL2 induction by 1,25(OH)2D3 in dendritic cells from healthy donors and multiple sclerosis patients.

Stress as Provoking Factor for the First and Repeated Multiple Sclerosis Seizures

Multiple sclerosis is an inflammatory, autoimmune, disease of the white mass of the brain, which sometimes may involve the gray matter (subcortical and ones in the anterior horns of the spinal cord) with the chronic nature and generally with progressive course. As a possible cause of this disease state are listed genetic predisposition, early viral infections and environmental factors, with special effects of stress as a provoking factor in first episode of the disease and relapses because stress leads to modulation of the immune system and immune response to various causes. An intensive stressor is certainly one of the triggers for the development of Multiple Sclerosis, as the first episode and worsening of previously established disease.

Study provides first class 1 evidence for cognitive rehabilitation in MS
Although disabling cognitive problems that affect functional performance and employment are common in persons with MS, there are very few evidence-based protocols for cognitive rehabilitation in MS.

New understanding, warning signs, and potential treatments for multiple sclerosis
Scientists are gaining a new level of understanding of multiple sclerosis (MS) that may lead to new treatments and approaches to controlling the chronic disease, according to new research released at Neuroscience 2013, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news about brain science and health.

Neuroimaging study sheds light on mechanisms of cognitive fatigue in multiple sclerosis
A new study by Kessler Foundation scientists sheds light on the mechanisms underlying cognitive fatigue in individuals with multiple sclerosis. Cognitive fatigue is fatigue resulting from mental work rather than from physical labor. Genova H et al: Examination of cognitive fatigue in multiple sclerosis using functional magnetic resonance imaging and diffusion tensor imaging" was published in PlosOne. This is the first study to use neuroimaging to investigate aspects of cognitive fatigue. The study was funded by grants from the National MS Society and Kessler Foundation.

Aerobic Exercise Benefits Memory in Persons With MS

A research study headed by Victoria Leavitt, Ph.D. and James Sumowski, Ph.D., of Kessler Foundation, provides the first evidence for beneficial effects of aerobic exercise on brain and memory in individuals with multiple sclerosis (MS). The article, "Aerobic exercise increases hippocampal volume and improves memory in multiple sclerosis: Preliminary findings," was released as an epub ahead of print on October 4 by Neurocase: The Neural Basis of Cognition.

Variation Within DNA Repair Pathway Genes and Risk of Multiple Sclerosis

Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system with a prominent genetic component. The primary genetic risk factor is the human leukocyte antigen (HLA)-DRB1*1501 allele; however, much of the remaining genetic contribution to MS has not been elucidated. The authors investigated the relation between variation in DNA repair pathway genes and risk of MS. Single-locus association testing, epistatic tests of interactions, logistic regression modeling, and nonparametric Random Forests analyses were performed by using genotypes from 1,343 MS cases and 1,379 healthy controls of European ancestry. A total of 485 single nucleotide polymorphisms within 72 genes related to DNA repair pathways were investigated, including base excision repair, nucleotide excision repair, and double-strand breaks repair.

Mortality following a brain tumour diagnosis in patients with multiple sclerosis

As brain tumours and their treatment may theoretically have a poorer prognosis in inflammatory central nervous system diseases such as multiple sclerosis (MS), all-cause mortality following a brain tumour diagnosis was compared between patients with and without MS. The potential role of age at tumour diagnosis was also examined. Younger age at tumour diagnosis may contribute to mortality reduction in those with high-grade and uncertain-grade brain tumours. Survival following a brain tumour is not worse in patients with MS; even after age at brain tumour diagnosis and grade of malignancy are taken into account.

Evaluation of the Effect of Progressive Relaxation Exercises on Fatigue and Sleep Quality in Patients with Multiple Sclerosis

Fatigue and sleep problems are very commonly observed in patients with multiple sclerosis (MS). The Progressive Muscle Relaxation Technique (PMRT), used as one of the alternative methods in recent years, is reported to have benefits such as facilitating sleep and reducing sensitivity against fatigue. This research was conducted to investigate the effect of PMRT on fatigue and sleep quality in patients with MS. This study supports the effect of PMRT on fatigue and sleep quality in patients with MS, and it is recommended that further studies be conducted on this subject in the future.

Responsiveness of walking-based outcome measures after multiple sclerosis relapses following steroid pulses

The aim of this study was to examine the impact of intravenous methylprednisolone therapy (IVMP) on the recovery of walking ability in patients experiencing multiple sclerosis (MS) relapses, to compare the responsiveness of walking-based measures, and to estimate the impact of different walking-based measures responsiveness on clinical trials. All applied walking-based measures showed significant improvement of walking ability 1 month after the IVMP. Responsiveness of various walking-based measures notably differ, thus affecting sample size calculations.

Cognitive impairment and “invisible symptoms” are not associated with CCSVI in MS

We investigated the association between chronic cerebrospinal venous insufficiency (CCSVI) and cognitive impairment (CI) in multiple sclerosis (MS). Moreover, we evaluated the association between CCSVI and other frequent self-reported MS symptoms. Our findings suggest a lack of association between CCSVI and CI in MS patients. Fatigue, depressive, bladder/sexual symptoms and self-reported quality of life are not associated with CCSVI.

Combination therapy with mitoxantrone and plasma exchange in aggressive relapsing remitting multiple sclerosis: A preliminary clinical study

The efficacy of mitoxantrone induction therapy in rapidly worsening multiple sclerosis (MS) is well established. Plasma exchange is also applied as an adjuvant in exacerbations of relapsing MS. The aim of this study was to compare the efficacy of combination therapy with mitoxantrone and plasma exchange versus mitoxantrone alone in patients with aggressive MS. Administration of mitoxantrone as an induction therapy in patients of aggressive relapsing remitting MS results in significant improvement of their clinical state and MRI activity. However, combination of plasma exchange with mitoxantrone gives no more benefits than mitoxantrone alone and sometimes worsens the situation possibly by reduction of mitoxantrone efficacy as a result of plasma exchange.

The Clinical Relevance of Force Platform Measures in Multiple Sclerosis: A Review

Disease-specific molecular events in cortical multiple sclerosis lesions

Tobacco smoking and disability progression in multiple sclerosis: United Kingdom cohort study

Adding to the Burden: Gastrointestinal Symptoms and Syndromes in Multiple Sclerosis

A passive exoskeleton can push your life up: application on multiple sclerosis patients.
n the present study, we report the benefits of a passive and fully articulated exoskeleton on multiple sclerosis patients by means of behavioral and electrophysiological measures, paying particular attention to the prefrontal cortex activity.

Pupillary response to sparse multifocal stimuli in multiple sclerosis patients.
The objective of this paper is to investigate the pattern of abnormalities and establish the diagnostic power of multifocal objective pupil perimetry (mfPOP) in multiple sclerosis (MS).
mfPOP is well tolerated and potentially has a role in the diagnosis and assessment of patients with MS.

Long-term effects of whole body cryostimulation on uric acid concentration in plasma of secondary progressive multiple sclerosis patients.
Uric acid (UA) has been suggested to be a marker of multiple sclerosis (MS) activity. Whole body cryostimulation (WBCT) is a new form of additional treatment and becoming popular in medicine. Objectives. The aims of this study were to determine the long-term effects of WBCT on the level of plasma UA in selected group of MS patients only with secondary progressive (SPMS) clinical form and verify results with functional state of patients assessed by expanded disability status scale (EDSS).

An RCT to treat learning impairment in multiple sclerosis: The MEMREHAB trial.
To examine the efficacy of the modified Story Memory Technique (mSMT), a 10-session behavioral intervention teaching context and imagery to facilitate learning, to improve learning and memory abilities in persons with multiple sclerosis (MS). The mSMT is effective for improving learning and memory in MS.

Body Mass Index in Multiple Sclerosis: Associations with CSF Neurotransmitter Metabolite Levels.
Body weight and height of patients with relapsing-remitting multiple sclerosis (RRMS) or clinically isolated syndrome suggesting MS (CIS) in the age range 18 to 60 years (154 males and 315 females) were compared with those of subjects (146 males and 212 females) free of any major neurological disease. In drug-free patients, CSF levels of the metabolites of noradrenaline (MHPG), serotonin (5-HIAA), and dopamine (HVA), neurotransmitters involved in eating behavior, were estimated in searching for associations with body mass index (BMI).

Treatment of pediatric multiple sclerosis.
Multiple sclerosis (MS) in children and adolescents has received increased attention during the past decade. Although not tested in randomized placebo-controlled trials, first-line disease-modifying therapies are widely used in patients with MS who are younger than 18 years.

Accuracy of Postcontrast 3D Turbo Spin Echo MR Sequence for the Detection of Enhanced Inflammatory Lesions in Patients with Multiple Sclerosis.

MicroRNA Profiling May Provide Biomarkers for Monitoring MS

Shorter Washout Reduces MS Relapse Switching Off Natalizumab

Sodium May Make MS Worse
OPENHAGEN, Denmark — A study for the first time links higher sodium intake with increased clinical and radiologic disease activity in people with multiple sclerosis (MS).
A high-sodium diet has recently been shown to worsen disease in the animal model of MS, experimental autoimmune encephalomyelitis. "Our study adds some evidence that this effect might be also present in humans as individuals that consume high amounts of sodium have a higher number of lesions on MRI and also more clinical bouts," Mauricio Farez, MD, from the Institute for Neurological Research, Buenos Aires, Argentina, told Medscape Medical News.

Cholesterol Transport Protein Implicated in MS

Don't Freeze Medicare Rates, Docs Tell Congress

Doctors Complain They Will Be Paid Less by Exchange Plans

Cognitive Therapy, Meds Equal in Curbing Depression Relapse

EU patent call sets stage for Tecfidera launch in Europe

Omega-3 Fatty Acids of No Benefit in Multiple Sclerosis
The finding, from the 4-year Omega-3 Fatty Acid Treatment in Multiple Sclerosis (OFAMS) trial, goes against those of preliminary studies that suggested omega-3 supplementation would have a protective effect in MS, lead author Øivind Torkildsen, MD, PhD, from Haukeland University Hospital, Bergen, Norway, told Medscape Medical News.

Masitinib Treatment in Patients With Progressive Multiple Sclerosis

Plasmacytoid Dendritic Cells and Immunotherapy in Multiple Sclerosis

Influence of multiple sclerosis, age and degree of disability, in the position of the contrast sensitivity curve peak.

A polymorphism in the resistin gene promoter and the risk of multiple sclerosis.

The Evaluation of the Retinal Nerve Fiber Layer in Multiple Sclerosis with Special-Domain Optical Coherence Tomography.

Y-39983, a Selective Rho-Kinase Inhibitor, Attenuates Experimental Autoimmune Encephalomyelitis via Inhibition of Demyelination.

Nuclear factor kappa B (NF-κB) in multiple sclerosis pathology.

Discovery of peptoid ligands for anti-aquaporin 4 antibodies.

A pragmatic parallel arm multi-centre randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based fatigue management programme (FACETS) for people with multiple sclerosis

Immune competence after alemtuzumab treatment of multiple sclerosis

Retinal periphlebitis is associated with multiple sclerosis severity

Cytomegalovirus seropositivity is negatively associated with multiple sclerosis

Endogenous Retroviruses and Multiple Sclerosis

Interdependence and Contributions of Sun Exposure and Vitamin D to MRI Measures in Multiple Sclerosis

Exercise and Disease Progression in Multiple Sclerosis
It has been suggested that exercise (or physical activity) might have the potential to have an impact on multiple sclerosis (MS) pathology and thereby slow down the disease process in MS patients. The objective of this literature review was to identify the literature linking physical exercise (or activity) and MS disease progression.

Revisiting Statins in Multiple Sclerosis

A Role in Monitoring Multiple Sclerosis?

Possible Immune Target Identified in Multiple Sclerosis
t is assumed that in MS, the immune system recognizes proteins of the myelin sheath as antigenic, setting in motion an inflammatory reaction resulting in demyelination of the axons, breakdown of the blood-brain barrier, and the formation of lesions. However, the exact target of the immune response involved in MS has continually eluded researchers.

Smoking: Effects on Multiple Sclerosis Susceptibility and Disease Progression
Multiple sclerosis (MS) is associated with both genetic and environmental factors that influence disease susceptibility. Exposure to cigarette smoke is emerging as a viable environmental risk factor for MS that contributes to both increased disease susceptibility and more rapid disease advancement. The relative risk for MS development is approximately 1.5 for smokers compared with nonsmokers. Furthermore, there may be important interactions between smoking, an individual's genetic background, and other environmental risk exposures. This review summarizes the current evidence supporting the association of smoking with MS risk and disease course, with additional comments on causation.

Behavioral Interventions in Multiple Sclerosis
Managing uncertainty is a major challenge associated with the diagnosis of multiple sclerosis (MS). In addition to physical symptoms, neuropsychiatric symptoms are highly prevalent in this disease. Depression in particular is more common in MS than in other chronic diseases. While substantial achievements have been made in the therapy of MS and an increasing number of immunomodulatory treatments are now available, the long-term benefits of these are still a matter of debate. Importantly, while the approved therapies show good efficacy on inflammatory lesions and relapse rate, and may slow certain aspects of disease progression, improvements in function have rarely been reported.

Neurogenesis In The Chronic Lesions Of Multiple Sclerosis
Subcortical white matter in the adult human brain contains a population of interneurons that helps regulate cerebral blood flow. We investigated the fate of these neurons following subcortical white matter demyelination. Immunohistochemistry was used to examine neurons in normal-appearing subcortical white matter and seven acute and 59 chronic demyelinated lesions in brains from nine patients with multiple sclerosis and four controls.

Women With Multiple Sclerosis Have High Rate of Migraine

Lung Volume Recruitment in Multiple Sclerosis

Prevalence of fatigue in patients with multiple sclerosis and its effect on the quality of life

Multiple Sclerosis Cases Hit 2.3 Million Worldwide

Multiple Sclerosis: Autoimmune or Neurodegenerative?

Therapeutic Decision Making in a New Drug Era in Multiple Sclerosis

Cortical Lesions in Multiple Sclerosis

Studies Show Promise for Angioplasty in Multiple Sclerosis

Plasmacytoid Dendritic Cells and Immunotherapy in Multiple Sclerosis
Plasmacytoid dendritic cells (pDCs) are specialized APCs implicated in the pathogenesis of many human diseases.

Jacobian integration method increases the statistical power to measure gray matter atrophy in multiple sclerosis.

Brain atrophy: an in-vivo measure of disease activity in multiple sclerosis.

Exercise therapy and multiple sclerosis: a systematic review.
Multiple sclerosis (MS) is an incurable disease, and despite current pharmacologic treatment being effective in reducing relapse rates and lesion burden, there is little evidence that these treatments work as effectively in preventing disability progression. In such cases, non-pharmacologic techniques such as exercise therapy with rehabilitation purposes may play an important role.

Using magnetic resonance imaging in animal models to guide drug development in multiple sclerosis.
Major advances are taking place in the development of therapeutics for multiple sclerosis (MS), with a move past traditional immunomodulatory/immunosuppressive therapies toward medications aimed at promoting remyelination or neuroprotection. With an increase in diversity of MS therapies comes the need to assess the effectiveness of such therapies.

Cortical plasticity predicts recovery from relapse in multiple sclerosis.
Relapsing-remitting multiple sclerosis (RRMS) is characterized by the occurrence of clinical relapses, followed by remitting phases of a neurological deficit. Clinical remission after a relapse can be complete, with a return to baseline function that was present before, but is sometimes only partial or absent. Remyelination and repair of the neuronal damage do contribute to recovery, but they are usually incomplete. Synaptic plasticity may contribute to symptom recovery after a relapse in MS; and PAS, measured during a relapse, may be used as a predictor of recovery.

Disclosure of diagnosis of multiple sclerosis in the workplace positively affects employment status and job tenure.
For many employees with multiple sclerosis (MS), disclosure of their diagnosis at work is seen as a high-risk strategy that might lead to diminished perceptions of their capabilities by supervisors and colleagues, if not outright discrimination. The consequence of this mistrust surrounding the disclosure process is that employees with MS may leave it until too late to effectively manage symptoms at work. This study provides the first empirical support for the positive role of disclosure in maintaining employment status, measured both as job retention and tenure in current employment.

Extending technology-aided leisure and communication programs to persons with spinal cord injury and post-coma multiple disabilities.

Clinical and demographic factors affecting disease severity in patients with multiple sclerosis.
The clinical course of multiple sclerosis (MS) evolves over many years. Its prognosis is highly variable among affected individuals, i.e. while some suffer from early severe disabilities, others remain ambulatory and functional for many years. We used Multiple Sclerosis Severity Score (MSSS) and the new classification for MS severity Herbert et al. introduced in 2006 according to MSSS, to investigate some clinical and demographic factors as potential indicators of disease severity in in MS. Early prediction of disease severity by demographic and clinical features is currently impossible. We need to determine stronger predictors, possibly a combination of demographic, clinical, biomarkers, and imaging findings.

Magnetic Resonance Monitoring of Lesion Evolution in Multiple Sclerosis
Disease activity in multiple sclerosis (MS) is strongly linked to the formation of new lesions, which involves a complex sequence of inflammatory, degenerative, and reparative processes. Conventional magnetic resonance imaging (MRI) techniques, such as T2-weighted and gadolinium-enhanced T1-weighted sequences, are highly sensitive in demonstrating the spatial and temporal dissemination of demyelinating plaques in the brain and spinal cord. Hence, these techniques can provide quantitative assessment of disease activity in patients with MS, and they are commonly used in monitoring treatment efficacy in clinical trials and in individual cases. However, the correlation between conventional MRI measures of disease activity and the clinical manifestations of the disease, particularly irreversible disability, is weak.

Employment and multiple sclerosis in new zealand.

A preliminary path analysis: Effect of psychopathological symptoms, mental and physical dysfunctions related to quality of life and body mass index on fatigue severity of Iranian patients with multiple sclerosis.
Multiple sclerosis (MS) is a neurological disease with fatigue as most prevalent symptom. Psychopathological symptoms, physical and mental dysfunctions and body mass abnormalities potentially could deteriorate fatigue. Thus, in this study, we aimed at evaluating the effect of these factors on fatigue severity of MS patients. Present study made the role of psychopathological symptoms and physical and mental dysfunctions prominent in exacerbation of fatigue severity. Moreover, we can refer to more sensible effect of physical dysfunction related to life on fatigue.

Growth Hormone and Disease Severity in Early Stage of Multiple Sclerosis.

The Fluctuating Natural Course of CCSVI in MS Patients and Controls, a Prospective Follow-Up.
OBJECTIVES: A new treatable venous disorder, chronic cerebrospinal venous insufficiency (CCSVI), has been proposed in patients with multiple sclerosis. The natural course of CCSVI has not been examined yet. This is crucial given the fact that surgical procedures are increasingly offered to MS patients to treat venous stenosis.
CONCLUSIONS: ECD examination shows a fluctuating natural course of the extracranial venous haemodynamics, which makes determination of CCSVI by ECD examination unreliable.

Evolutive Study of Relapsing-Remitting Multiple Sclerosis with Cervical Proton Magnetic Resonance Spectroscopy. A Case Report.

Spasticity in patients with multiple sclerosis - clinical characteristics, treatment and quality of life.
Aims: To gain real-life data on demographic and clinical characteristics, treatment patterns, treatment satisfaction and quality-of-life of multiple sclerosis-related spasticity (MSS) in Germany.
Conclusions: Spasticity and its symptoms impair personal well-being and quality-of-life. Treatment of spasticity with drugs and physiotherapy is common, but satisfaction with the currently available anti-spastic pharmacotherapy is low.

The molecular study of IFNβ pleiotropic roles in MS treatment.
MS) is one of the most important autoimmune diseases recognized by demyelination and axonal lesion. It is the most common cause of disability in the young population. Various immunomodulatory and immunosuppressive therapies, including different formulations of interferon beta (IFNβ), glatiramer acetate (GA), mitoxantrone, and natalizumab are available for this disease. However, interferon has been the best prescribed.

Dietary pattern and risk of multiple sclerosis.
It has been suggested that nutrition might play a role in the etiology of multiple sclerosis (MS). However, dietary patterns associated with MS risk are unknown. This study was conducted to compare the dietary patterns of patients with MS and healthy controls to find the relationship between dietary patterns and MS. Our findings showed that the risk of RRMS can be affected by major dietary patterns.

Optical coherence tomography versus visual evoked potential in multiple sclerosis patients.
Optical coherence tomography (OCT) is a non-invasive instrument, which can be used to estimate the thickness of the retinal nerve fibre layer (RNFL) and provides an indirect measurement of axonal destruction in multiple sclerosis (MS). The main aim of this study was to find out any correlations between P100 latency in visual evoked potential (VEP) and RNFL thickness.
OCT does have good correlations with P100 latency, indicating retinal non-myelinated axonal involvement in early stages in addition to the myelinated axonal involvement. However, it cannot be used as the sole test in evaluating visual pathway in optic neuritis and complementary tests as VEPs are recommended.

Reversible therapy-related dysplastic hematopoiesis following Beta Interferon Therapy in Multiple Sclerosis Patients: Report of 2 Cases.
Interferon beta-la and -1b have been increasingly used for the treatment of multiple sclerosis (MS). The most frequent systemic adverse effects are flu-like symptoms. Laboratory abnormalities include asymptomatic leukopenia and elevated hepatic transaminases. Myelodysplastic Syndrome (MDS) refers to a spectrum of hematological disorders which can occur in different situations. Several hematological abnormalities have been reported following interferon therapy. Both of our cases were reversible; although treatment with IFNβ-1a and-1b is safe and well tolerated in the majority of population, we should be careful about this premalignant hematological disorder.

Effect of honey bee venom on lewis rats with experimental allergic encephalomyelitis, a model for multiple sclerosis.
(MS) is a progressive and autoimmune neurodegenerative disease of the central nervous system (CNS). This disease is recognized through symptoms like inflammation, demyelination and the destruction of neurological actions. Experimental allergic encephalomyelitis (EAE) is a widely accepted animal model for MS. EAE is created in animals by injecting the tissue of myelin basic protein (MBP), CNS, or myelin oligodendrocyte glycoprotein (MOG) along with the adjuvant. EAE and MS are similar diseases. Honey Bee venom (Apis mellifera) contains a variety of low and high molecular weight peptides and proteins, including melittin, apamin, adolapin, mast cell degranulating peptide and phospholipase A2.

Neuroprotection in a novel mouse model of multiple sclerosis.

Mortality following a brain tumour diagnosis in patients with multiple sclerosis.
As brain tumours and their treatment may theoretically have a poorer prognosis in inflammatory central nervous system diseases such as multiple sclerosis (MS), all-cause mortality following a brain tumour diagnosis was compared between patients with and without MS. The potential role of age at tumour diagnosis was also examined. Younger age at tumour diagnosis may contribute to mortality reduction in those with high-grade and uncertain-grade brain tumours. Survival following a brain tumour is not worse in patients with MS; even after age at brain tumour diagnosis and grade of malignancy are taken into account.

Let's rehabilitate cognitive rehabilitation in multiple sclerosis.
Up to 60% of patients with multiple sclerosis (MS) experience cognitive dysfunction, with prominent involvement of complex attention, information processing speed, executive functions, episodic memory, and visuospatial abilities. Since MS-related cognitive deficits can substantially affect a wide range of daily life activities (e.g., work, driving, social integration, and adherence to medication regimens), it is imperative that we identify and develop strategies to alleviate them.

Efficacy and safety of BG-12 (dimethyl fumarate) and other disease modifying therapies for the treatment of relapsing-remitting multiple sclerosis: a systematic review and mixed treatment comparison.
Currently, direct comparative evidence or head-to-head data between BG-12 (dimethyl fumarate) and other disease-modifying treatments (DMTs) is limited. This study is a systematic review and data synthesis of published randomized clinical trials comparing the efficacy and safety of existing DMTs to BG-12 for Relapsing-Remitting Multiple Sclerosis (RRMS). Based on indirect comparison, BG-12 offers an effective oral treatment option for patients with RRMS with an overall promising efficacy and safety profile compared to currently approved DMTs. Key limitations of the systematic review were the large heterogeneity in patients enrolled, and the variability in the definition of outcomes in included trials.

Prevalence of joint contractures and muscle weakness in people with multiple sclerosis.
Abstract Objectives: To investigate the prevalence of joint contracture (limited passive range of joint motion) and muscle weakness in a population with multiple sclerosis (MS). A secondary aim was to establish normative data of functional tests of mobility and balance of people with MS who are still ambulant. These data show that in addition to muscle weakness joint contractures are highly prevalent among people with MS, especially in the ankle joint. This implicates that prevention of contracture is crucial in providing rehabilitation to people with MS. Implications for Rehabilitation Joint contractures are highly prevalent of people with MS, especially in the lower limb, even at an early stage. While many interventions such as stretching and serial casting have been implemented to reduce contractures, there is not yet strong evidence for their effectiveness. Further research is required.

Relating relapse and T2 lesion changes to disability progression in multiple sclerosis: a systematic literature review and regression analysis.
In the treatment of multiple sclerosis (MS), the most important therapeutic aim of disease-modifying treatments (DMTs) is to prevent or postpone long-term disability. Given the typically slow progression observed in the majority of relapsing-remitting MS (RRMS) patients, the primary endpoint for most randomized clinical trials (RCTs) is a reduction in relapse rate. It is widely assumed that reducing relapse rate will slow disability progression. Similarly, MRI studies suggest that reducing T2 lesions will be associated with slowing long-term disability in MS. The objective of this study was to evaluate the relationship between treatment effects on relapse rates and active T2 lesions to differences in disease progression (as measured by the Expanded Disability Status Scale [EDSS]) in trials evaluating patients with clinically isolated syndrome (CIS), RRMS, and secondary progressive MS (SPMS). Treatment differences in relapse reduction and T2 lesions are positively related to differences in disease progression over the first two years of treatment.

Treatment options for patients with multiple sclerosis who have a suboptimal response to interferon-β therapy.
Although the first-line disease-modifying therapies (DMTs) interferon beta and glatiramer acetate have a favourable benefit-to-risk profile, they are only partially effective for treating relapsing-remitting multiple sclerosis (RRMS). The optimization of treatment in patients who do not show a maximum response to first-line therapy is critical for achieving the best long-term outcomes. Treatment strategies for patients with a suboptimal response include switching to another first-line DMT or a second-line DMT. Natalizumab and fingolimod are approved for RRMS with high disease activity in the European Union and Canada. A descriptive comparison of fingolimod and natalizumab is provided in the context of the decision-making process of how and when to switch patients who have a suboptimal response to first-line therapy.

Patient-related factors may affect the outcome of neuropsychological rehabilitation in multiple sclerosis.
The aim of this study was to identify factors associated with neuropsychological rehabilitation outcome in patients with multiple sclerosis (MS). Patient-related factors may affect neuropsychological rehabilitation outcome in MS.

Low contrast visual acuity testing is associated with cognitive performance in multiple sclerosis: a cross-sectional pilot study.

Effect of treadmill training on fatigue in multiple sclerosis: a pilot study.
People with multiple sclerosis (PwMS) tend to be less physically active than the general population. Limited physical activity increases fatigue, possibly affecting other functions such as balance. Treadmill training is a promising method to ameliorate these symptoms. The aim of this study was to assess the effect of treadmill training on fatigue and balance.

Multiple Sclerosis International Federation: Stimulating international cooperation in researc.

A novel pH-sensitive interferon-β (INF-β) oral delivery system for application in multiple sclerosis.

Lower Serum Levels of Th2-Related Chemokine CCL22 in Women Patients with Multiple Sclerosis: A Comparison Between Patients and Healthy Women.

The glutathione S-transferase T1 deletion is associated with susceptibility to multiple sclerosis.

The influence of disease duration, clinical course, and immunosuppressive therapy on the synthesis of intrathecal oligoclonal IgG bands in multiple sclerosis.

Metabolomic approach to human brain spectroscopy identifies associations between clinical features and the frontal lobe metabolome in multiple sclerosis.

Muscle-specific kinase antibody positive myaesthenia gravis and multiple sclerosis co-presentation: A case report and literature review.

Electroconvulsive therapy in patient with psychotic depression and multiple sclerosis.

Fatigue and sleep-disordered breathing in multiple sclerosis: a clinically relevant association?
Objective. To evaluate the importance of routine respirography in MS patients with severe fatigue and to explore the effects of treatment with continuous positive airway pressure (CPAP).
Conclusion. Respirography in MS patients with severe fatigue should be considered in daily medical practice, because SDB frequency is high and CPAP therapy reduces fatigue severity.

Factors affecting bone mineral density in multiple sclerosis patients.
BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease which can cause many disabilities for the patient. Recent data suggests that MS patients have higher risk for osteoporosis. This study was performed to investigate if the osteoporosis prevalence is higher in MS patients and to determine the possible factors affecting bone mineral density (BMD).
CONCLUSION: As a result of this study, bone loss inevitably occurs in MS patients. The major factor of BMD loss is immobility. Osteoporosis should be managed as part of MS patients' treatment protocols.

Comparison of serum levels of copper and zinc among multiple sclerosis patients and control group.

Can multiple sclerosis as a cognitive disorder influence patients' dreams?
Dream should be considered as a kind of cognitive ability that is formed parallel to other cognitive capabilities like language. On the other hand, multiple sclerosis (MS) is a complex disease that can involve different aspects of our cognition. Therefore, MS may influence patients' dreams. In fact, we do not know what the importance of dream is in MS, but further studies may introduce dream and dreaming as a sign of improvement or progression in MS disease.

The relation between peptide hormones and sex hormone in patients with multiple sclerosis.
BACKGROUND: Hormones can play a significant role in the pathogenesis of multiple sclerosis (MS). The aim of this study was to compare levels of ghrelin, leptin, and testosterone hormones of MS patients with healthy subjects, and assess the relationship between levels of peptide hormone and sex hormones in MS patients.
CONCLUSION: According to the results, there was no significant difference between peptide and sex hormones of MS patients and healthy persons. Furthermore, there was no significant relationship between peptide and sex hormones of MS patients and healthy persons.

Is serum vitamin D levels associated with disability in patients with newly diagnosed multiple sclerosis?
BACKGROUND: Although the precise etiology of multiple sclerosis (MS) is unknown, it seems that both genetic and environmental factors are important. Recent studies suggest that low serum vitamin D levels are important environmental factor in MS. The aim of this study was to compare the serum levels of vitamin D between MS patients and healthy subjects, and to determine its association with disability in MS patients.
CONCLUSION: Our findings did not suggest a protective association for serum vitamin D levels against disability in MS patients.

Prevalence of fatigue in patients with multiple sclerosis and its effect on the quality of life.
OBJECTIVE: This prospective study was carried out to observe the prevalence of fatigue in patients with multiple sclerosis (MS) and its effect on quality-of-life (QoL).
CONCLUSION: Prevalence of fatigue was found to be high in the MS patients in the study. All four domains of QoL were significantly more impaired in the group with fatigue than in those without fatigue.

Baló's concentric sclerosis in a girl with interesting presentation.

Neurological manifestations in patients with antiphospholipid syndrome.

Physical trauma and risk of multiple sclerosis: A systematic review and meta-analysis of observational studies.

Relating relapse and T2 lesion changes to disability progression in multiple sclerosis: a systematic literature review and regression analysis.

Anesthetic technique in a patient with multiple sclerosis scheduled for laparoscopic nephrectomy for a renal tumor: a case report.

Prevalence of chronic cerebrospinal venous insufficiency in multiple sclerosis: a blinded sonographic evaluation.

Cladribine interferes with IL-1β synaptic effects in experimental multiple sclerosis.

Elevated and dysregulated bone morphogenic proteins in immune cells of patients with relapsing-remitting multiple sclerosis.

Promoting Remyelination in Multiple Sclerosis-Recent Advances.

Anesthetic technique in a patient with multiple sclerosis scheduled for laparoscopic nephrectomy for a renal tumor: a case report.

Modeling disease severity in multiple sclerosis using electronic health records.

Prevalence of chronic cerebrospinal venous insufficiency in multiple sclerosis: a blinded sonographic evaluation.
Chronic cerebrospinal venous insufficiency is a haemodynamic condition strongly associated with multiple sclerosis and is not found in normal controls. The addition of M-mode ultrasound to the diagnostic protocol allows improved observation of venous valve abnormalities.

Clinical Outcomes Following Surgical Management of Coexistent Cervical Stenosis and Multiple Sclerosis: A Cohort Controlled Analysis.
Myelopathic patients with coexisting MS and CS improve after surgery, although at a lower rate and to a lesser degree than those without MS. Therefore, surgery should be considered for these patients. MS patients should be informed that 1) myelopathy symptoms are less likely to be alleviated completely or may only be alleviated temporarily due to progression of MS, and 2) that surgery can help alleviate neck pain and radicular symptoms.

[Impact of physical activity level on alexithymia and coping strategies in an over-40 multiple sclerosis population: A pilot study.]
This study provides insight for future research about the impact of physical activity on multiple sclerosis.

What do multiple sclerosis patients and their caregivers perceive as unmet needs?
A better understanding of MS patient needs, starting from the point of view of patients and caregivers, could have a great impact on quality of life and on management of the disease.

Treatment options for patients with multiple sclerosis who have a suboptimal response to interferon-β therapy.

A descriptive comparison of fingolimod and natalizumab is provided in the context of the decision-making process of how and when to switch patients who have a suboptimal response to first-line therapy.

Prolonged-release fampridine improves walking in a proportion of patients with multiple sclerosis.
Fampridine is indicated to improve walking in adult multiple sclerosis (MS) patients. Indications vary between countries and the prescribing neurologist should be aware of the labeling and indication in his own country.

Prevalence of joint contractures and muscle weakness in people with multiple sclerosis.
Abstract Objectives: To investigate the prevalence of joint contracture (limited passive range of joint motion) and muscle weakness in a population with multiple sclerosis (MS). A secondary aim was to establish normative data of functional tests of mobility and balance of people with MS who are still ambulant. Design: Cross-sectional study.

Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics.

Examination of Cognitive Fatigue in Multiple Sclerosis using Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging.

Preserved Antigen-Specific Immune Response in Patients with Multiple Sclerosis Responding to IFNβ-Therapy.

Care ethics for guiding the process of multiple sclerosis diagnosis.

Assessment of cardiac safety during fingolimod treatment initiation in a real-world relapsing multiple sclerosis population: a phase 3b, open-label study.

Is There Extra Cost of Institutional Care for MS Patients?
hroughout life, patients with multiple sclerosis (MS) require increasing levels of support, rehabilitative services, and eventual skilled nursing facility (SNF) care. There are concerns that access to SNF care for MS patients is limited because of perceived higher costs of their care. This study compares costs of caring for an MS patient versus those of a typical SNF patient. We merged SNF cost report data with the 2001-2006 Nursing Home Minimum Data Set (MDS) to calculate percentage of MS residents-days and facility case-mix indices (CMIs).

Cost minimisation analysis of fingolimod vs natalizumab as a second line of treatment for relapsing-remitting multiple sclerosis.
Fingolimod is more efficient than natalizumab as a second-line treatment option for relapsing-remitting multiple sclerosis and it generates savings for the Spanish national health system.

[Need for creating Polish registry of multiple sclerosis patients].

Predictors of effectiveness of multidisciplinary rehabilitation treatment on motor dysfunction in multiple sclerosis.
These data confirm that an intensive inpatient rehabilitation program is able to produce a short-term relevant improvement on clinical and functional outcome measures and suggest some clinical features which can be considered as potential predictors of the outcome of rehabilitative intervention.

The Promoter SNP, but not the Alternative Splicing SNP, is Linked to Multiple Sclerosis Among Jordanian Patients.

Rare Inflammatory Diseases of the White Matter and Mimics of Multiple Sclerosis and Related Disorders.

Effects of a 4-month Ananda Yoga Program on Physical and Mental Health Outcomes for Persons With Multiple Sclerosis.

Adding to the burden: gastrointestinal symptoms and syndromes in multiple sclerosis.

Retinal Nerve Fiber Layer Thickness, Brain Atrophy, and Disability in Multiple Sclerosis Patients.
This study shows that RNFL thickness correlates with BCR and with MS subtypes. Additionally, our study indicates that OCT is better suited for MS assessment than GDx. We conclude that the damage of retinal axons appears related to brain damage in patients with MS.

Functional brain network analysis using minimum spanning trees in Multiple Sclerosis: An MEG source-space study.

Impact of delayed diagnosis and treatment in clinically isolated syndrome and multiple sclerosis.

Multiple sclerosis research: diagnostics, disease-modifying treatments, and emerging therapies.
Multiple sclerosis (MS) is a complex disease that affects the central nervous system. It is believed to be an immune mediated disease, and although the etiology remains unknown, it is believed to occur from a combination of genetic risk factors and environmental risk factors. There is no single diagnostic test for MS, and diagnostic criteria have been developed to aid the provider in making an accurate and timely diagnosis.

Regional brain atrophy and functional connectivity changes related to fatigue in multiple sclerosis.
Fatigue is one of the most frequent symptoms in multiple sclerosis (MS), and recent studies have described a relationship between the sensorimotor cortex and its afferent and efferent pathways as a substrate of fatigue. The objectives of this study were to assess the neural correlates of fatigue in MS through gray matter (GM) and white matter (WM) atrophy, and resting state functional connectivity (rs-FC) of the sensorimotor network (SMN).  Efficacy and safety of laquinimod in multiple sclerosis: current status.

Voxel-Wise Displacement as Independent Features in Classification of Multiple Sclerosis.

Activation of MSRV-Type Endogenous Retroviruses during Infectious Mononucleosis and Epstein-Barr Virus Latency: The Missing Link with Multiple Sclerosis?

A Mathematical Framework for the Registration and Analysis of Multi-Fascicle Models for Population Studies of the Brain Microstructure.

Percutaneous sclerotherapy with ethanolamine oleate for venous malformations of the head and neck.
Percutaneous sclerotherapy with ethanolamine oleate appears to be safe and effective for the treatment of venous malformations and should be considered when treating these complex lesions. The efficacy of this agent appears to match or exceed that of other sclerosants used for such treatment, and further investigation in prospective controlled research is warranted.

No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis.

Multiple sclerosis-induced neuropathic pain: pharmacological management and pathophysiological insights from rodent EAE models.
In patients with multiple sclerosis (MS), pain is a frequent and disabling symptom. The prevalence is in the range 29-86 % depending upon the assessment protocols utilised and the definition of pain applied. Neuropathic pain that develops secondary to demyelination, neuroinflammation and axonal damage in the central nervous system is the most distressing and difficult type of pain to treat.

Risk of multiple sclerosis after optic neuritis in patients with normal baseline brain MRI.
When assessing and managing a patient with optic neuritis (ON), the risk of future development of multiple sclerosis (MS) is an important issue, as this can be the first presentation of the disease. Although the presence of lesions on baseline brain MRI is the strongest predictor of MS conversion, some patients with normal imaging also develop MS.

Characteristics of multiple sclerosis in the Middle East with special reference to the applicability of international guidelines to the region.
Abstract We have reviewed the clinical literature with reference to the local applicability of guidelines for the diagnosis and management of multiple sclerosis (MS) in the Middle East.

Quantitative MRI analysis in children with multiple sclerosis: a multicenter feasibility pilot study.
Assessment of MRI lesion LV characteristics is feasible in a multicenter cohort of children with MS.

Assessments of nursing home guidelines for quality of care provided to residents with multiple sclerosis.

IL-12, but not IL-23, induces the expression of IL-7 in microglia and macrophages: Implications for multiple sclerosis.

TNFRSF1A in multiple sclerosis: A tale of soluble receptors and signaling cascades
   Pentti J. Tienari and Reinhard Hohlfeld
   Neurology. published 30 October 2013,
   10.1212/01.wnl.0000436624.56026.eb
   http://www.neurology.org/cgi/content/abstract/01.wnl.0000436624.56026.ebv1?ct=ct

Clinical relevance and functional consequences of the TNFRSF1A multiple sclerosis locus
   Linda Ottoboni, Irene Y. Frohlich, Michelle Lee, Brian C. Healy,
   Brendan T. Keenan, Zongqi Xia, Tanuja Chitnis, Charles R. Guttmann,
   Samia J. Khoury, Howard L. Weiner, David A. Hafler, and Philip L. De
   Jager
   Neurology. published 30 October 2013,
   10.1212/01.wnl.0000436612.66328.8a
   http://www.neurology.org/cgi/content/abstract/01.wnl.0000436612.66328.8av1?ct=ct

Early pathological alterations of lower lumbar cords detected by ultrahigh-field MRI in a mouse multiple sclerosis model   Yuki Mori, Masaaki Murakami, Yasunobu Arima, Dasong Zhu, Yasuo
   Terayama, Yutaka Komai, Yuji Nakatsuji, Daisuke Kamimura, and
   Yoshichika Yoshioka
   Int. Immunol. published 29 October 2013, 10.1093/intimm/dxt044
   http://intimm.oxfordjournals.org/cgi/content/abstract/dxt044v2?ct=ct

Alemtuzumab-Related Thyroid Dysfunction in a Phase 2 Trial of Patients with
Relapsing-Remitting Multiple Sclerosis   Gilbert H. Daniels, Anton Vladic, Vesna Brinar, Igor Zavalishin,
   William Valente, Pedro Oyuela, Jeffrey Palmer, and David H. Margolin
   J. Clin. Endocrinol. Metab. published 29 October 2013,
   10.1210/jc.2013-2201
   http://jcem.endojournals.org/cgi/content/abstract/jc.2013-2201v1?ct=ct

Assessments of nursing home guidelines for quality of care provided to residents with multiple sclerosis.

Multiple Sclerosis International Federation: Stimulating international cooperation in research.The MS International Federation (MSIF), established in 1967, links the activities of over 85 national multiple sclerosis (MS) societies worldwide. Over those 45 years, and particularly in the last 20, it has seen dramatic changes in our understanding, treatment, and multidisciplinary management of people with MS.

Multiple sclerosis research: diagnostics, disease-modifying treatments, and emerging therapies.

Effects of walking direction and cognitive challenges on gait in persons with multiple sclerosis.

Long-term impact of interferon beta-1b in patients with CIS: 8-year follow-up of BENEFIT.

No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis.

Dalfampridine improves walking speed, walking endurance, and
Neuroimaging biomarkers of neurodegenerative diseases and dementia.

community participation in veterans with multiple sclerosis: a longitudinal cohort study.

Efficacy and safety of BG-12 (dimethyl fumarate) and other disease modifying therapies for the treatment of relapsing-remitting multiple sclerosis: a systematic review and mixed treatment comparison.

Low contrast visual acuity testing is associated with cognitive performance in multiple sclerosis: a cross-sectional pilot study.
Our data show that: a) cognitive impairment and performance in visual function tests such as low contrast sensitivity testing are associated; b) the main cognitive domains correlating with visual test performance are information processing speed and, to a lesser degree, memory; This preliminary data needs to be substantiated in further studies investigating patients with a higher cognitive burden, healthy controls and in longitudinal settings.

Retinal Nerve Fiber Layer Thickness, Brain Atrophy, and Disability in Multiple Sclerosis Patients.

Review of laquinimod and its therapeutic potential in multiple sclerosis.

Teriflunomide: A Review of Its Use in Relapsing Multiple Sclerosis.

Effect of treadmill training on fatigue in multiple sclerosis: a pilot study.

The Regulation of Reactive Changes Around Multiple Sclerosis Lesions by Phosphorylated Signal Transducer and Activator of Transcription.

Evidence for a two-stage disability progression in multiple sclerosis

It is well documented that disability accumulation in multiple sclerosis is correlated with axonal injury and that the extent of axonal injury is correlated with the degree of inflammation. However, the interdependence between focal inflammation, diffuse inflammation and neurodegeneration, and their relative contribution to clinical deficits, remains ambiguous.

Impact of natalizumab on patient-reported outcomes in multiple sclerosis: a longitudinal study

PRO measures were improved with natalizumab in a real-world setting. The improvements were observed as early as after 3 months and sustained over a 12-month period. The improvements in PROs show that, in clinical practice, the clinical benefits of natalizumab are translated into patient-reported benefits.

Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease

The association between MS disease and the MSRV-type HERV-W element now appears quite strong, as evidenced ex-vivo from serum and PBMC with post-mortem confirmation in brain lesions. Chronic progressive MS, RRMS and clinically isolated syndrome show different ELISA (Enzyme-Linked Immunosorbent Assay) and/or PCR profiles suggestive of an increase with disease evolution, and amplicon sequencing confirms the association with particular HERV-W elements.

Differential diagnosis of suspected multiple sclerosis: a consensus approach

Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision.

The clinical potential of blood-proteomics in multiple sclerosis

We demonstrated for the first time, albeit only with preliminary data, the aprioristic possibility of distinguishing naive and IFN-treated MS groups from controls, and naive from IFN-treated MS patients using a blood sample-based methodology (i.e. proteomics) alone. The functional profile of the identified molecules provides new pathophysiological insight into MS. Future development of these techniques could open up novel applications in terms of molecular diagnosis and therapy monitoring in MS patients.

Stress and the risk of multiple sclerosis

These results do not support a major role of stress in the development of the disease, but repeated and more focused measures of stress are needed to firmly exclude stress as a potential risk factor for MS.

Randomized controlled trial of a teleconference fatigue management plus physical activity intervention in adults with multiple sclerosis: rationale and research protocol

Poor Sleep in Patients with Multiple Sclerosis

Poor sleep is common in patients with MS. Early identification and treatment of modifiable risk factors may improve sleep and quality of life in MS.

Estrogen Treatment in Multiple Sclerosis

Epidural analgesia and cesarean delivery in multiple sclerosis post-partum relapses: the Italian cohort study

Our findings, show no correlation between EA, CD and postpartum relapses and disability. Therefore these procedures can safely be applied in MS patients. On the other hand, post-partum relapses are significantly associated with increased disability, which calls for the need of preventive therapies after delivery.

Increased mitochondrial content in remyelinated axons: implications for multiple sclerosis

A combined post-mortem magnetic resonance imaging and quantitative histological study of multiple sclerosis pathology

Vitamin D in African Americans with multiple sclerosis

Retinal Axonal Loss Begins Early in the Course of Multiple Sclerosis and Is Similar between Progressive Phenotypes

No sex-specific difference in disease trajectory in multiple sclerosis patients before and after age 50