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

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.