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Introduction: Although chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) predominantly affects large myelinated fibers, many patients have pain. The aim of this paper is to systematically review the current literature regarding CIDP with a particular focus on epidemiological and clinical characteristics of painful CIDP. Methods: A systematic literature search was conducted on PubMed database. Results: Our search strategy identified 146 articles. Thirty-eight papers, reporting on 991 patients, met the inclusion criteria and were used for this review. The pooled estimate of the prevalence of pain at any point within the course of CIDP was 46% (95% CI 36–57%). Immune treatment of CIDP might be adequate as monotherapy for the management of pain. Treatment specific to pain currently shows effectiveness as adjuvant treatment when CIDP is treated and pain persists. Conclusions: Pain in CIDP is an underexplored field. Future research should focus on the natural history, phenomenology, and management of pain in CIDP. [ABSTRACT FROM AUTHOR]

The article offers information on the schedule of the 34th Meeting of the European Society of Neuroradiology (ESNR), the 18th Advanced Course and the 2nd Interventional Course in Athens, Greece from September 17 to 20, 2009. Some of the studies presented include one on myelin maturation and white matter development in an embryologic perspective. Other research focus on radiologic-pathologic correlation in white matter diseases and classifications of spinal cord arteriovenous malformations.

Multiple Sclerosis (MS) is a well-known, chronic demyelinating disease of the Central Nervous System (CNS) and one of the most common causes of disability in young adults. In this context, one of the major challenges in patients' rehabilitation is to maintain the gained motor abilities in terms of functional independence. This could be partially obtained by applying new emerging and cutting-edge virtual/augmented reality and serious game technologies for a playful, noninvasive treatment that was demonstrated to be quite efficient and effective in enhancing the clinical status of patients and their (re)integration into society. Recently, Cloud computing and Internet of Things (IoT) emerged as technologies that can potentially revolutionize patients' care. To achieve such a goal, a system that on one hand gathers patients' clinical parameters through a network of medical IoT devices equipped with sensors and that, on the other hand, sends the collected data to a hospital Cloud for processing and analytics is required. In this paper, we assess the effectiveness of a Nintendo Wii Fit® Plus Balance Board (WFBB) used as an IoT medical device adopted in a rehabilitation training program aimed at improving the physical abilities of MS patients (pwMS). In particular, the main scientific contribution of this paper is twofold: (i) to present a preliminary new pilot study investigating whether exercises based on the Nintendo Wii Fit® balance board included in a rehabilitation training program could improve physical abilities and Quality of Life (QoL) of patients compared to that of a conventional four-week rehabilitation training program; (ii) to discuss how such a rehabilitation training program could be adopted in the perspective of near future networks of medical IoT-based rehabilitation devices, interconnected with a hospital Cloud system for big data processing to improve patients' therapies and support the scientific research about motor rehabilitation. Results demonstrate the advantages of our approach from both health and technological points of view. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is a severe demyelinating disease mediated by cells of the innate and adaptive immune system, especially pathogenic T lymphocytes that produce the pro-inflammatory cytokine granulocyte-macrophage colony stimulating factor (GM-CSF). Although the factors and molecules that drive the genesis of these cells are not completely known, some were discovered and shown to promote the development of such cells, such as dietary factors. In this regard, iron, the most abundant chemical element on Earth, has been implicated in the development of pathogenic T lymphocytes and in MS development via its effects on neurons and glia. Therefore, the aim of this paper is to revise the state-of-art regarding the role of iron metabolism in cells of key importance to MS pathophysiology, such as pathogenic CD4+ T cells and CNS resident cells. Harnessing the knowledge of iron metabolism may aid in the discovery of new molecular targets and in the development of new drugs that tackle MS and other diseases that share similar pathophysiology. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease (CTD), the main features of which are multiple serum autoantibodies and extensive involvement of multiple systems. The onset age of patients varies from childhood to middle age, with nearly 1/5 in childhood. Sjogren's syndrome (SS) is also an autoimmune disease characterized by high-degree lymphocytic infiltration of exocrine glands, usually occurring in middle-aged and older women, and rarely in childhood. Neuromyelitis optica spectrum disorder (NMOSD) is an immune-mediated inflammatory demyelinating disease of the central nervous system (CNS) mainly involving the optic nerve and spinal cord. The coexistence of NMOSD and SLE and/or SS is well recognized by both neurologists and rheumatologists, but cases in children have been rarely reported. In this paper, we reported a case of a girl with onset at age 5 clinically featured by recurrent parotid gland enlargement, pancytopenia, hypocomplementemia, multiple positive serum antibodies, and cirrhosis. She was initially diagnosed with SS/SLE overlap syndrome at age 5. Four years later, the patient suffered a sudden vision loss and was examined to have positive AQP4 antibodies in serum and cerebrospinal fluid (CSF), and long segmental spinal swelling, in line with the diagnostic criteria for NMOSD. Up to now, the current patient is of the youngest onset age to develop SS/SLE coexisting with NMOSD, also with cirrhosis. It is important for clinicians to be aware of the possibility of CTDs coexisting with NMOSD in children, especially in those with positive anti-multiple autoantibodies, and to decrease the rate of missed diagnosis. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Chronic graft-versus-host disease (cGVHD) represents a serious complication of allogeneic haematopoietic stem cell transplant that occurs in 20%-80% of patients. A leading hypothesis posits that chronic CNS-GHVD onset stems from sequential CNS infiltration of donor CD8 SP + sp T cells, donor CD4 SP + sp T cells and donor bone marrow-derived macrophages (BMDMs). 4 Polchlopek Blasiak K, Simonetta F, Vargas MI, Chalandon Y. Central nervous system graft-versus-host disease (CNS-GvHD) after allogeneic haematopoietic stem cell transplantation. [Extracted from the article]

Schizophrenia, as a common mental disease, seriously threatens the physical and mental health of human beings. It is characterized by many mental and behavioral disorders, such as uncoordinated thinking and emotional mode which separated from the actual living environment. Patients with schizophrenia are prone to relapse and deterioration due to their long course of disease, resulting in the loss of labor force. It has been proved that the occurrence and development of schizophrenia is closely related to the abnormal development of oligodendrocytes, which have the function of myelin formation and the dysfunction of myelin sheath itself. For a comprehensive understanding of myelin abnormal effects on the pathogenesis of schizophrenia, this paper is to review the literature, then summarize and discuss the animal experimental literature related to the abnormal myelin sheath in schizophrenia from the perspectives of behavioristics, neuroimaging, protein expression and stereology, in order to further clarify the influence of the abnormal myelin sheath on the pathogenesis of schizophrenia and provide ideas for the diagnosis of schizophrenia and the research and development of new drugs. [ABSTRACT FROM AUTHOR]

Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disease characterized by recurrent episodes of fever and serositis caused by mutations in the MEFV gene, while Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the CNS with genetic and environmental etiology. The two diseases rarely occur in association with relevant implications for clinical management and drug choice. In this paper, we present the case of a 53-year-old male with an autosomal dominant FMF since childhood who presented acute paresthesia at the right part of the body. He performed a brain and spinal cord MRI, which showed multiple brain lesions and a gd-enhancing lesion in the cervical spinal cord, and then received a diagnosis of MS. He then started Interferonβ-1a which was effective but not tolerated and caused hepatotoxicity, and then shifted to Rituximab with 3-month clinical and neuroradiological efficacy. [ABSTRACT FROM AUTHOR]

The author discusses whether a useful yearly review of cognition in relapsing multiple sclerosis (MS) is or is not beyond most neurologists. He says that the significance of evaluating cognition at all stages of MS has been given weight by a series of papers from the Italian group led by Maria Pia Amato et al. He adds that these papers showed (among other findings) that patients with obviously benign MS after 18 years of illness could be subdivided into two groups.

The most prominent pathological features of multiple sclerosis (MS) are demyelination and neurodegeneration. The exact pathogenesis of MS is unknown, but it is generally regarded as a T cell-mediated autoimmune disease. Increasing evidence, however, suggests that other components of the immune system, particularly B cells and antibodies, contribute to the cumulative CNS damage and worsening disability that characterize the disease course in many patients. We have previously described strongly elevated T cell reactivity to an extracellular domain of the most abundant CNS myelin protein, myelin proteolipid protein (PLP) in people with MS. The current paper addresses the question of whether this region of PLP is also a target of autoantibodies in MS. Here we show that serum levels of isotype-switched anti-PLP181−230 specific antibodies are significantly elevated in patients with MS compared to healthy individuals and patients with other neurological diseases. These anti-PLP181−230 antibodies can also live-label PLP-transfected cells, confirming that they can recognize native PLP expressed at the cell surface. Importantly, the antibodies are only elevated in patients who carry HLA molecules that allow strong T cell responses to PLP. In that subgroup of patients, there is a positive correlation between the levels of anti-PLP181−230 antibodies and the severity of MS. These results demonstrate that anti-PLP antibodies have potentially important roles to play in the pathogenesis of MS. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Recognizing the need for more evidence-based multiple sclerosis (MS) rehabilitation, in the mid-2000s several initiatives were undertaken to explore why there had been a paucity of such research and to determine strategies to reverse this pattern. Expert-Opinion-Paper In 2004 the National Multiple Sclerosis Society (NMSS) convened an expert opinion panel, reviewed evidence-based MS rehabilitation research, and published the paper on the web. It was concluded that much of the MS rehabilitation carried out was based on experience, with little research backing it up. Increasing the Quality and Quantity of MS Rehabilitation Research Largely as a result of the conclusions of the Expert-Opinion-Paper, the NMSS convened a conference of a large number of MS and rehabilitation experts in New York in May, 2005. This conference made many recommendations of ways to increase the quantity and quality of MS research. State of the Science Conference In September, 2006, a follow-up conference was held in Washington, D.C… This conference, primarily sponsored by the University of Washington Multiple Sclerosis Rehabilitation Research and Training Center (MS RRTC), focused on some of the under-studied "hidden" disabilities present in persons with MS. This paper discusses the details and recommendations of these latter two conferences. [ABSTRACT FROM AUTHOR]

• Behavioural tests using the CPZ model focus mainly on motor, anxiety and cognition but not other common clinical symptoms in MS like pain or fatigue. • Most histological correlations associated with behavioural deficits were found to be inappropriate. • CPZ-feeding alone may be a useful tool to model some behavioural aspects of demyelinating diseases but it should not be regarded as a model of MS per se. The feeding of cuprizone (CPZ) to animals has been extensively used to model the processes of demyelination and remyelination, with many papers adopting a narrative linked to demyelinating conditions like multiple sclerosis (MS), the aetiology of which is unknown. However, no current animal model faithfully replicates the myriad of symptoms seen in the clinical condition of MS. CPZ ingestion causes mitochondrial and endoplasmic reticulum stress and subsequent apoptosis of oligodendrocytes leads to central nervous system demyelination and glial cell activation. Although there are a wide variety of behavioural tests available for characterizing the functional deficits in animal models of disease, including that of CPZ-induced deficits, they have focused on a narrow subset of outcomes such as motor performance, cognition, and anxiety. The literature has not been systematically reviewed in relation to these or other symptoms associated with clinical MS. This paper reviews these tests and makes recommendations as to which are the most important in order to better understand the role of this model in examining aspects of demyelinating diseases like MS. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a complex human neurodegenerative dysimmune disease of the central nervous system (CNS) which is characterized by chronic inflammation, demyelination, loss of blood‐brain barrier (BBB) integrity, neuronal loss, reactive astrogliosis, and oligodendrocyte depletion. It can result in physical disability and severe neurological and cognitive deficits. Research indicates that MS prevalence has significantly increased in many regions around the world since 1990. The specific elements that trigger MS remain unknown. In this paper, the critical role played by mitochondria dysfunction and oxidative stress in MS pathogenesis, progression, and clinical symptoms are elucidated. Their interactions with the key factors in the disease, as well as treatment strategies, are discussed. [ABSTRACT FROM AUTHOR]

Some theorists have provided insight into the phenomenon of disability, and others have provided conceptual notions of childhood. Still others have provided theoretical expectations of what life is like for a child when mother or father has a disability or chronic illness. When children whose parents have multiple sclerosis described their own experiences, much of what theorists had postulated was a poor fit with children' s responses. This paper will explore differences between children' s descriptions of life with a parent who has MS, and the theoretical expectations of what their lives should be like according to previous literature. The paper concludes with the suggestions that historical sociology, with its recognition of both agency and structure interacting over time, may be an effective way to understand anyone' s place on the disability/empowerment continuum, and may serve to illuminate the pathway of children with disabled parents in particular. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system (CNS) and is characterized by a high degree of heterogeneity in progression and treatment response. Mitochondrial dysfunction is increasingly recognized as an important feature of MS pathology and may be relevant for clinical disease progression. This paper systematically reviews published evidence concerning the role of mitochondrial abnormalities with MS. Literature searched using the Web of Science, PMC/Medline via PubMed and Scopus databases up to May 2017 with no time and language limitation. After quality assessment, 9 articles were included in the study. All data extraction was conducted by two reviewers independently. Based on the results of the studies, it seems that mitochondrial DNA abnormality and mitochondrial dysfunction may be due to primary inflammation in MS or may be occurred itself before any inflammation, but definitely contributes to axonal degeneration and disease progression. Mitochondrial abnormality contributes to axonal degeneration in MS and disease progression. [ABSTRACT FROM AUTHOR]

Supervised exercise training has substantial benefits for persons with multiple sclerosis (MS), yet 80% of those with MS do not meet recommended levels of moderate-to-vigorous physical activity (MVPA). This same problem persisted for decades in the general population of adults and prompted a paradigm shift away from “exercise training for fitness” toward “physical activity for health.” The paradigm shift reflects a public health approach of promoting lifestyle physical activity through behavioral interventions that teach people the skills, techniques, and strategies based on established theories for modifying and self-regulating health behaviors. This paper describes: (a) the definitions of and difference between structured exercise training and lifestyle physical activity; (b) the importance and potential impact of the paradigm shift; (c) consequences of lifestyle physical activity in MS; and (d) behavioral interventions for changing lifestyle physical activity in MS. The paper introduces the “new kid on the MS block” with the hope that lifestyle physical activity might become an accepted partner alongside exercise training for inclusion in comprehensive MS care. [ABSTRACT FROM AUTHOR]

The objective of this observational study in nine European countries was to establish the current cost of MS at different levels of disease severity. The study used a prevalence-based bottom-up to estimate costs from a societal perspective. Patients were recruited via patient organizations and neurology centres and asked by mail to complete a detailed questionnaire concerning their resource consumption, work capacity, quality of life and current disease status. Resources included all health-care and social services, personal expenditures, informal care and temporary or definitive work absence. Quality of life was collected as utility and disease information collected related to functional capacity, relapses and fatigue. The data were analyzed separately for each country, using local unit costs but a fully standardized methodology. A total of 13 186 patients at all levels of disease severity participated in the survey, with an average response rate of around 40% (range 20–75%). This paper describes the methodology used for the study, while results are presented in the individual country reports. [ABSTRACT FROM AUTHOR]

Background: To improve the consistency of standardized Expanded Disability Status Scale (EDSS) assessments, an electronic data capture tool and analysis tool was developed, Neurostatus e-Scoring (NESC). This tool allows real-time feedback by comparing entries with established scoring rules. Objective: To test whether using NESC reduces inconsistencies as compared to the paper-and-pencil version of the Expanded Disability Status Scale (pEDSS). Methods: In all, 100 multiple sclerosis (MS) patients were assessed in random order on the same day by pairs of neurologists, one using pEDSS and one NESC. We compared inter-rater reliability and frequency of inconsistencies in Neurostatus subscores, functional system (FS) scores, ambulation and EDSS steps. Results: Inconsistencies of any type were more likely to occur when using pEDSS (mean odds ratio (95% confidence interval (CI)) = 2.93 (1.62; 5.29)). This was also the case for FS score inconsistencies (2.54 (1.40; 4.61)) and more likely for patients in the lower EDSS range (≤3.5 vs >3.5) (5.32 (1.19; 23.77)). Overall, inter-rater agreement for the assessed Neurostatus subscores was high (median and inter-quartile range = 0.84 (0.73, 0.81)). Conclusion: Our data provide class II evidence that the use of NESC increases consistency of standardized EDSS assessments, and may thus have the potential to decrease noise and increase power of MS clinical trials. [ABSTRACT FROM AUTHOR]

One significant characteristic of Multiple Sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system, is the evolution of highly variable patterns of white matter lesions. Based on geostatistical metrics, the MS-Lesion Pattern Discrimination Plot reduces complex three- and four-dimensional configurations of MS-White Matter Lesions to a well-arranged and standardized two-dimensional plot that facilitates follow-up, cross-sectional and medication impact analysis. Here, we present a script that generates the MS-Lesion Pattern Discrimination Plot, using the widespread statistical computing environment R. Input data to the script are Nifti-1 or Analyze-7.5 files with individual MS-White Matter Lesion masks in Montreal Normal Brain geometry. The MS-Lesion Pattern Discrimination Plot, variogram plots and associated fitting statistics are output to the R console and exported to standard graphics and text files. Besides reviewing relevant geostatistical basics and commenting on implementation details for smooth customization and extension, the paper guides through generating MS-Lesion Pattern Discrimination Plots using publicly available synthetic MS-Lesion patterns. The paper is accompanied by the R script LDPgenerator.r, a small sample data set and associated graphics for comparison. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a chronic, progressive, and disabling disease of the central nervous system with dramatic variations in the combination and severity of symptoms it can produce. The lack of reliable disease-specific health-related quality of life (HRQL) measures for use in clinical trials prompted the development of the Neurology Quality of Life (Neuro-QOL) instrument, which includes 13 scales that assess physical, emotional, cognitive, and social domains, for use in a variety of neurological illnesses. Objective: The objective of this research paper is to conduct an initial assessment of the reliability and validation of the Neuro-QOL short forms (SFs) in MS. Methods: We assessed reliability, concurrent validity, known groups validity, and responsiveness between cross-sectional and longitudinal data in 161 recruited MS patients. Results: Internal consistency was high for all measures (α = 0.81--0.95) and ICCs were within the acceptable range (0.76-0.91); concurrent and known groups validity were highest with the Global HRQL question. Longitudinal assessment was limited by the lack of disease progression in the group. Conclusions: The Neuro-QOL SFs demonstrate good internal consistency, test-re-test reliability, and concurrent and known groups validity in this MS population, supporting the validity of Neuro-QOL in adults with MS. [ABSTRACT FROM AUTHOR]

Background: The impact of new asymptomatic spinal cord lesions (a-SL) in multiple sclerosis (MS) course is poorly characterized. Objective: The objective of this research paper is to assess the prognostic value of a-SL in predicting MS course. Methods: Relapsing--remitting MS patients who received serial MRI (brain and spinal) at baseline (t1) and within 12 to 36 months (t2) during clinical stability, and had a follow-up (t2--t3) ≥24 months were included. Relapses and disability progression were evaluated between t2 and t3. Results: Of 413 consecutive screened MS patients, 103 patients (65 females, median age 43 years) were included. After a median t1-t2 interval of 17 (IQR 13--26) months, 25.2% and 43.7% patients had ≥1 new a-SL (a-SL+) and asymptomatic brain lesions (a-BL+), respectively. Relapse risk between t2 and t3 (median interval: 42 (IQR 32--57.5) months) was significantly increased in a-SL+ and/or a-BL+ vs a-BL-- and a-SL-- (HR = 2.31, 95% CI = 1.13--4.72, p = 0.02). No differences in the risk of disability progression were found in a-SL+ and/or a-BL+ vs a-SL- and a-BL--. Conclusion: a-SL occur in one-quarter of clinically stable RRMS, and combined with a-BL contribute significantly in predicting future disease course. [ABSTRACT FROM AUTHOR]

Background: In search of the missing heritability in multiple sclerosis (MS), additional approaches adding to the genetic discoveries of large genome-wide association studies are warranted. Objective: The objective of this research paper is to search for rare genetic MS risk variants in the genetically homogenous population of the isolated Faroe Islands. Methods: Twenty-nine Faroese MS cases and 28 controls were genotyped with the HumanOmniExpressExome- chip. The individuals make up 1596 pair-combinations in which we searched for identicalby- descent shared segments using the PLINK-program. Results: A segment spanning 63 SNPs with excess case-case-pair sharing was identified (0.00173 < p > 0.00212). A haplotype consisting of 42 of the 63 identified SNPs which spanned the entire the Sortilinrelated vacuolar protein sorting 10 domain containing receptor 3 (SORCS3) gene had a carrier frequency of 0.34 in cases but was not present in any controls (p = 0.0008). Conclusion: This study revealed an oversharing in case-case-pairs of a segment spanning 63 SNPs and the entire SORCS3. While not previously associated with MS, SORCS3 appears to be important in neuronal plasticity through its binding of neurotrophin factors and involvement in glutamate homeostasis. Although additional work is needed to scrutinise the genetic effect of the SORCS3-covering haplotype, this study suggests that SORCS3 may also be important in MS pathogenesis. [ABSTRACT FROM AUTHOR]

Background: MRI studies have shown gray-matter abnormalities in fatigued multiple sclerosis (MS) patients. However, given that physical disability is highly correlated to MS fatigue, it is often difficult to disentangle its effect in these MRI findings. Objective: The objective of this research paper is to investigate gray-matter damage in mildly disabled MS patients, addressing which variables were better related to fatigue while controlling for physical disability and depression. Methods: Forty-nine relapsing--remitting MS (RRMS) patients and 30 controls underwent MRI (3T). Fatigue was assessed using the Fatigue Severity Scale (FSS). Multivariate logistic regression was performed to assess the contribution of clinical and MRI metrics to fatigue. Statistical analyses were performed controlling for disability and depression. Results: Fatigue was present in 22 (44.9%) patients. FSS score was highly correlated with EDSS (p = 0.00001). Patients with fatigue had lower brain cortical and subcortical gray-matter volumes. However, after controlling for EDSS, only the caudate and the accumbens volumes remained statistically significant. Conclusions: Fatigued MS patients have a global cortical and subcortical gray-matter atrophy that seems largely related to higher physical disability. However, striatal structures involved in effort-reward functions exhibited smaller volumes in fatigued patients, independently of physical disability and depressive symptoms, supporting the theory of cortico-striatal network impairment in MS fatigue. [ABSTRACT FROM AUTHOR]

Motivated by an imaging study, the paper develops a non-parametric testing procedure for testing the null hypothesis that two samples of curves observed at discrete grids and with noise have the same underlying distribution. The objective is to compare formally white matter tract profiles between healthy individuals and multiple-sclerosis patients, as assessed by conventional diffusion tensor imaging measures. We propose to decompose the curves by using functional principal component analysis of a mixture process, which we refer to as marginal functional principal component analysis. This approach reduces the dimension of the testing problem in a way that enables the use of traditional non-parametric univariate testing procedures. The procedure is computationally efficient and accommodates different sampling designs. Numerical studies are presented to validate the size and power properties of the test in many realistic scenarios. In these cases, the test proposed has been found to be more powerful than its primary competitor. Application to the diffusion tensor imaging data reveals that all the tracts studied are associated with multiple sclerosis and the choice of the diffusion tensor image measurement is important when assessing axonal disruption. [ABSTRACT FROM AUTHOR]

Background: The role of genetic factors in influencing the clinical expression of multiple sclerosis (MS) is unclear. Objective: The objective of this paper is to identify genes, pathways and networks implicated in age at onset (AAO) and severity, measured using the Multiple Sclerosis Severity Score (MSSS), of primary-progressive MS (PPMS). Methods: We conducted a genome-wide association study (GWAS) of 470 PPMS patients of Italian origin:. Allelic association of 296,589 SNPs with AAO and MSSS was calculated. Pathway and network analyses were also conducted using different tools. Results: No single association signal exceeded genome-wide significance in AAO and MSSS analyses. Nominally associated genes to AAO and MSSS were enriched in both traits for 10 pathways, including: “oxidative phosphorylation” (FDRAAO=9*10−4; FDRMSSS=3.0*10−2), “citrate (TCA) cycle” (FDRAAO=1.6*10−2; FDRMSSS=3.2*10−3), and “B cell receptor signaling” (FDRAAO=3.1*10−2; FDRMSSS=2.2*10−3). In addition, an enrichment of “chemokine signaling pathway” (FDR=9*10−4) for AAO and of “leukocyte transendothelial migration” (FDR=2.4*10−3) for MSSS trait was observed, among others. Network analysis revealed that p53 and CREB1 were central hubs for AAO and MSSS traits, respectively. Conclusions: Despite the fact that no major effect signals emerged in the present GWAS, our data suggest that genetic variants acting in the context of oxidative stress and immune dysfunction could modulate the onset and severity of PPMS. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is an autoimmune, inflammatory, demyelinating and degenerative disease of the central nervous system (CNS). To date, there is no definitive imaging biomarker for diagnosing MS. The current diagnostic criteria are mainly based on clinical relapses supported by the presence of white matter lesions (WMLs) on MRI. However, misdiagnosis of MS is still a significant clinical problem. The paramagnetic, iron rims (IRs) around white matter lesions have been proposed to be an imaging biomarker in MS. This study aimed to carry out a systematic mapping review to explore the detection of iron rim lesions (IRLs), on clinical MR scans, and describe the characteristics of IRLs presence in MS versus other MS-mimic disorders. Methods: Publications from 2001 on IRs lesions were reviewed in three databases: PubMed, Web of Science and Embase. From the initial result set 718 publications, a final total of 38 papers were selected. Results: The study revealed an increasing interest in iron/paramagnetic rims lesions studies. IRs were more frequently found in periventricular regions and appear to be absent in MS-mimics. Conclusions IR is proposed as a promising imaging biomarker for MS. [ABSTRACT FROM AUTHOR]

Background: Despite sensitivity of MRI to diagnose multiple sclerosis (MS), prognostic biomarkers are still needed for optimized treatment. Objective: The objective of this paper is to identify cerebrospinal fluid (CSF) diagnostic biomarkers of MS using quantitative proteomics and to analyze their expression at different disease stages. Methods: We conducted differential analysis of the CSF proteome from control and relapsing–remitting MS (RRMS) patients followed by verification by ELISA of candidate biomarkers in CSF and serum in control, clinically isolated syndrome (CIS), RRMS and progressive MS (PMS) patients. Results: Twenty-two of the 527 quantified proteins exhibited different abundances in control and RRMS CSF. These include chitinase 3-like protein 1 (CHI3L1) and 2 (CHI3L2), which showed a strong expression in brain of MS patients, especially in astrocytes and microglial cells from white matter plaques. CSF and serum CHI3L1 levels increased with the disease stage and CIS patients with high CSF (>189 ng/ml) and serum (>33 ng/ml) CHI3L1 converted more rapidly to RRMS (log rank test, p < 0.05 and p < 0.001, respectively). In contrast, CSF CHI3L2 levels were lower in PMS than in RRMS patients. Accordingly, CSF CHI3L1/CHI3L2 ratio accurately discriminated PMS from RRMS. Conclusions: CSF CHI3L1 and CHI3L2 and serum CHI3L1 might help to define MS disease stage and have a prognostic value in CIS. [ABSTRACT FROM AUTHOR]

Background and objective: Presentations of MS in fictional literature have not been previously researched. This paper surveys and analyses these portrayals of the disease for the first time. Material and methods: Relevant works in English and German were identified by means of keyword searches in online public access catalogues and search engines as well as old-fashioned research. The neurological and literary evaluation of these 7000 pages of text combines qualitative and quantitative methods. Results: Between 1954 and 2012 at least 55 literary works appeared with an MS motif (35 novels, 18 poems, one novella and one drama). The authors were predominantly female and a third of them suffered from the disease. Patients in the novels largely reflect real epidemiology as regards symptoms and disease progression, while diagnostic and therapeutic options play a secondary role. From a literary point of view, ‘entwicklungsromane’, ‘relationship novels’ and ‘young adult books’ can be discerned. MS is often portrayed in metaphoric language as the enemy: a demon, an animalistic being, prison or an abyss. Conclusion: The MS motif evidences a medicalization of the literature as well as a literary portrayal of anthropological experiences. Well-written novels can contribute to the de-stigmatization of MS and impart basic medical knowledge. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) and antiphospholipid syndrome (APS) share common clinical, laboratory and radiological features. We reviewed all the English papers on MS and APS published in the literature from 1965 to 2014 using PubMed and Google Scholar. We found that APS can mimic antiphospholipid antibodies (aPL)-positive MS in many ways in its clinical presentation. Nevertheless, APS diagnosis, clinical manifestations and management differ from those of MS. aPL were found in MS patients with titers ranging from 2% to 88%. The distribution and volume of lesions on magnetic resonance imaging (MRI) may help to differentiate MS from primary APS. In addition, atypical MS presentation can guide physicians toward an alternative diagnosis, especially when features of thrombosis and/or history of connective tissue disease are present. In that case, an anticoagulation trial could be worthwhile. [ABSTRACT FROM AUTHOR]

Autologous hematopoietic stem cell transplantation (AHSCT) has been proposed as a rescue treatment in multiple sclerosis (MS) patients not responding to first- or second-line therapies. To date, most of the treated cases had a secondary progressive disease course. However, patients with high inflammatory activity, but no secondary progression of the disease, could be candidates to take greater advantage of AHSCT. In this paper, we report two cases with very active, relapsing-remitting (RR) MS, who underwent AHSCT, and obtained a dramatic resolution to disease activity. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an inflammatory and autoimmune neurological disorder which leads to demyelination. Although the etiology of MS is yet to be known, it appears that regulating the immune system and suppressing inflammatory pathways may possibly have a favorable effect on the healing of this disease. Evidence suggests that probiotics consumption via gut microbiome alteration devises beneficial effects in improving immune and inflammatory responses in MS. All articles were systematically searched (in the main databases) for this paper. Two investigators independently scrutinized full texts of the potentially eligible articles. The quality of the study was evaluated using standardized tools. The methodological quality of seven studies included in this review ranged from fair to good. The findings illustrated that there were statistically significant improvements in the static and dynamic balance in patients and animals with MS. In the paper in hand, the effects of probiotics administration on immune and inflammatory markers in MS disease are evaluated. In addition, the limitations and knowledge gaps were reported while proposing a possible mechanism of probiotics therapy in modulating immune and inflammatory responses. This systematic review indicated that the probiotics could improve immune and inflammatory parameters, the cytokines and cells in MS disease. Probiotics may have efficient effects in management and treatment of MS. More studies are required to clarify the effect of supplementation with probiotics and their mechanisms in MS disease. [ABSTRACT FROM AUTHOR]

Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been considered to be closely relevant to an inflammatory demyelinating disease of the central nervous system (CNS). Glial fibrillary acidic protein (GFAP) immunoglobulin G (IgG) has been identified as a biomarker for a novel autoimmune astrocytopathy. However, coexistence of MOG-IgG and GFAP-IgG is extremely unusual and only one patient has been described with simultaneous presence of MOG-IgG in serum and GFAP-IgG in cerebrospinal fluid (CSF). Herein, we reported the first case of overlapping syndrome of MOG-IgG-associated disease (MOG-AD) and autoimmune GFAP astrocytopathy in whom MOG-IgG and GFAP-IgG were detected both in serum and CSF. A 20-year-old male patient was referred to our department with the presentation of decreased vision, diplopia and weakness of right limb with unknown reasons. Magnetic resonance imaging (MRI) revealed multiple intracranial lesions presenting hypointensity on T1-weighted images, hyperintensity on T2-weighted and FLAIR images and patchy contrast enhancement. MOG-IgG and GFAP-IgG were detected both in serum and CSF, and the titers of both antibodies fluctuated with the severity of disease. Treatment strategy employing intravenous methylprednisolone pulse therapy followed by oral prednisone with slow tapering resulted in an improvement of his symptoms and a sustained remission. Coexistence of MOG-IgG and GFAP-IgG with distinct underlying pathogeneses necessitates the recommendations to screen all recognized pathogenic antibodies against CNS antigens when an autoimmune disease is suspected, since it shows great significance for definite diagnosis of disease and treatment strategy options. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis is a neuro-inflammatory disease that affects adults and children and causes somatic and cognitive symptoms. Diagnosis after the first clinical symptoms is challenging, involves laboratory and magnetic resonance imaging work-up and is often inconclusive unless subsequent clinical attacks occur. Neurofilament light chains are structural proteins within neurons. Levels of this marker in cerebrospinal fluid, plasma and serum are consistently higher in patients with an initial clinical demyelinating attack that later go on to develop multiple sclerosis. Evidence concerning serum levels of this biomarker in children with multiple sclerosis is scarce. Our aim is to review and analyze the evidence available for patients with multiple sclerosis, under the age of 18. Methods: We conducted a systematic search of PubMed/Medline, Embase, Cochrane Database, and ProQuest. Human studies that provided data on serum levels of Neurofilament light chains in pediatric patients with MS, measured at the time of the first demyelinating attack and before treatment were included in meta-analysis. Results: Three studies satisfied the inclusion criteria. 157 pediatric patients with multiple sclerosis and 270 hospital-based controls that did not present with this condition were included in the analysis. A fixed effects meta-analysis showed that the standardized mean difference between patients and controls is 1.82, with a 95% confidence interval of [1.56–2.08]. Conclusion: Pediatric patients with multiple sclerosis show higher levels of serum neurofilament light chains at their first clinical demyelinating attack compared to pediatric hospital-based controls. [ABSTRACT FROM AUTHOR]

Purpose – The purpose of this paper is to increase awareness and compliance of The National Institute for Health and Care Excellence (NICE) Guidance regarding cognitive impairment in multiple sclerosis (MS). Design/methodology/approach – Assessments were offered routinely to consecutive inpatients with MS and to 20 per cent of outpatients. Once consent was gained, a cognitive assessment and subjective measure of cognition was completed with the patient, as well as a disability scale completed by the Medical Consultant. Individually targeted cognitive rehabilitation advice was provided using a bespoke advice leaflet. Afterwards, those who completed the assessment were asked to provide feedback on their experience. Findings – The percentage that were classed as below average cognitively and the pattern of impairment was comparable to previous findings. Memory was rated the most affected by the largest number of MS individuals and a strong relationship was found between objective and subjective measures of attention. The average functional disability level was rated at 6.99. Evaluations for the service provided were positive; over half of the sample was unaware of NICE Guidance on this issue but 100 per cent would recommend this service and provided optimistic quotes. Practical implications – This evaluation has enabled greater numbers to receive the recommended services and provided a useful baseline assessment of cognitive impairment and of patient attitudes towards this service. Resulting from this process, a new service framework has been proposed and presented at a local level. The advice leaflet developed for this process has been well received by patients and colleagues resulting in its submission to become an official NHS leaflet. Originality/value – Developed clinical governance of NHS services to patients with MS in offering improved assessment and management of cognitive problems. This is in contrast to the national trend showing little improvement of MS care and the lack of NICE implementation by the MS Trust and Royal College of Physicians audit. Furthermore, the bespoke advice leaflet developed for patients and carers of MS demonstrates originality of information provided. [ABSTRACT FROM AUTHOR]

Background: Growing evidence suggests that vitamin D deficiency may be one of the most important environmentalfactors for the development of multiple sclerosis (MS).Objectives: The objectives of this paper are to evaluate serum 25-hydroxyvitamin D (25(OH)D) levels in patients withclinically isolated syndromes (CIS) and to examine whether they are related to MS risk.Methods: This is a retrospective study of 100 CIS patients hospitalized from 2000 to 2009 at San Raffaele Hospital,Milan, Italy. We evaluated baseline 25(OH)D level as well as clinical, brain magnetic resonance imaging (MRI) andcerebrospinal fluid (CSF) data.Results: A total of 52% of CIS patients had vitamin D deficiency (25(OH)D < 50 nmol/l). During follow-up (median: 7.17years), 55 patients developed clinically definite MS (CDMS). Patients with very low (< 10th percentile) and low (< 25thpercentile) 25(OH)D levels were particularly at risk of CDMS (HRs (95% CIs): 2.12 (0.91–4.96) and 1.61 (0.85–3.03),respectively), while no further reduction in the HRs of disease was observed at high levels of 25(OH)D. This associationwas even stronger after adjustment for additional risk factors for CDMS development (HRs (95% CIs) for 25(OH)Dlevels < 10th and 25th percentiles: 3.34 (1.32–8.45) and 2.04 (0.96–4.36), respectively).Conclusion: Low serum vitamin D is associated with increased MS risk in patients with CIS [ABSTRACT FROM AUTHOR]

Objective: The objective of this paper is to identify clinical or magnetic resonance imaging (MRI) predictors of longtermclinical progression in a large cohort of multiple sclerosis (MS) patients.Methods: A total of 241 relapsing–remitting (RR) MS patients were included in a nine-year follow-up (FU) study. Thereference MRIs were acquired at baseline (BL) as part of a multicenter, cross-sectional, clinical-MRI study. VolumetricMRI metrics were measured by a fully automated, operator-independent, multi-parametric segmentation method. Clinicalprogression was evaluated as defined by: conversion from RR to secondary progressive (SP) disease course; progressionof Expanded Disability Status Scale (EDSS); achievement and time to reach EDSS 4.Results: We concluded that conversion from RR to SP (OR 0.79; CI 0.7–0.9), progression of EDSS (OR 0.85; CI 0.77–0.93), achievement of EDSS 4 (OR 0.8; CI 0.7–0.9), and time to reach EDSS 4 (HR 0.88; CI 0.82–0.94) were all predictedby BL gray matter (GM) volume and, except for progression of EDSS, by BL EDSS (respectively: (OR 2.88; CI 1.9–4.36),(OR 2.7; CI 1.7–4.2), (HR 3.86; CI 1.94–7.70)).Conclusions: BL GM volume and EDSS are the best long-term predictors of disease progression in RRMS patients witha relatively long and mild disease. [ABSTRACT FROM AUTHOR]

Background: Degeneration of central nervous system normal appearing white matter (NAWM) underlies disability andprogression in multiple sclerosis (MS). Axon loss typifies NAWM degeneration.Objective: The objective of this paper is to assess correlation between cortical lesion load and magnetisation transferratio (MTR) of the NAWM in MS. This was in order to test the hypothesis that cortical lesions cause NAWM degeneration.Methods: Nineteen patients with MS underwent 7 Tesla magnetisation-prepared-rapid-acquisition-gradient-echo(MPRAGE), and magnetisation transfer ratio (MTR) brain magnetic resonance imaging (MRI). Cortical lesions wereidentified using MPRAGE and MTR images of cortical ribbons. White matter lesions (WMLs) were segmented usingMPRAGE images. WML maps were subtracted from white matter volumes to produce NAWM masks. Pearsoncorrelation was calculated for NAWM MTR vs cortical lesion load, and WML volumes.Results: Cortical lesion volumes and counts all had significant correlation with NAWM mean MTR. The strongestcorrelation was with cortical lesion volumes obtained using MTR images (r = –0.6874, p = 0.0006). WML volume had nosignificant correlation with NAWM mean MTR (r = –0.08706, p = 0.3615).Conclusion: Our findings are consistent with the hypothesis that cortical lesions cause NAWM degeneration. This implicatescortical lesions in the pathogenesis of NAWM axon loss, which underpins long-term disability and progression in MS. [ABSTRACT FROM AUTHOR]

Background:The accrual of brain focal pathology is considered a good substrate of disability in relapsing–remittingmultiple sclerosis (RRMS). However, knowledge on long-term lesion evolution and its relationship with disabilityprogression is poor.Objective:The objective of this paper is to evaluate in RRMS the long-term clinical relevance of brain lesion evolution.Methods:In 58 RRMS patients we acquired, using the same scanner and protocol, brain magnetic resonance imaging(MRI) at baseline and 10±0.5 years later. MRI data were correlated with disability changes as measured by the ExpandedDisability Status Scale (EDSS).Results:The annualized 10-year lesion volume (LV) growth was +0.25±0.5 cm3 (+6.7±8.7%) for T2-weighted (T2-W)lesions and +0.20±0.31 cm3 (+11.5±12.3%) for T1-weighted (T1-W) lesions. The univariate analysis showed moderatecorrelations between baseline MRI measures and EDSS at 10 years (p < 0.001). Also, 10-year EDSS worsening correlatedwith LV growth and the number of new/enlarging lesions measured over the same period (p < 0.005). In the stepwisemultiple regression analysis, EDSS worsening over 10 years was best correlated with the combination of baseline T1-Wlesion count and increasing T1-W LV (R = 0.61, p < 0.001).Conclusion:In RRMS patients, long-term brain lesion accrual is associated with worsening in clinical disability. This isparticularly true for hypointense, destructive lesions. [ABSTRACT FROM AUTHOR]

Click here to view the accompanying paper in this issue. [ABSTRACT FROM AUTHOR]

Background:A female/male (F/M) ratio increase over time in multiple sclerosis (MS) patients was demonstrated in many countries around the world. So far, a direct comparison of sex ratio time-trends among MS populations from different geographical areas was not carried out. Objective: In this paper we assessed and compared sex ratio trends, over a 60-year span, in MS populations belonging to different latitudinal areas. Methods: Data of a cohort of 15,996 (F = 11,290; M = 4,706) definite MS with birth years ranging from 1930 to 1989 were extracted from the international MSBase registry and the New Zealand MS database. Gender ratios were calculated by six decades based on year of birth and were adjusted for the F/M born-alive ratio derived from the respective national registries of births. Results: Adjusted sex ratios showed a significant increase from the first to the last decade in the whole MS sample (from 2.35 to 2.73; p = 0.03) and in the subgroups belonging to the areas between 83° N and 45° N (from 1.93 to 4.55; p<0.0001) and between 45° N to 35° N (from 1.46 to 2.30; p<0.05) latitude, while a sex ratio stability over time was found in the subgroup from areas between 12° S and 55° S latitude. The sex ratio increase mainly affected relapsing-remitting (RR) MS. Conclusions: Our results confirm a general sex ratio increase over time in RRMS and also demonstrate a latitudinal gradient of this increase. These findings add useful information for planning case-control studies aimed to explore sex-related factors responsible for MS development. [ABSTRACT FROM AUTHOR]

Background: We noticed that a hypothesis based on the effect of geomagnetic disturbances (GMD) has the ability to explain special features of multiple sclerosis (MS). Areas around geomagnetic 60 degree latitude (GM60L) experience the greatest amount of GMD. The easiest way to evaluate our hypothesis was to test the association of MS prevalence (MSP) with angular distance to geomagnetic 60 degree latitude (AMAG60) and compare it with the known association of MS with geographical latitude (GL). We did the same with angular distance to geographic 60 degree latitude (AGRAPH60) as a control. Methods: English written papers with MSP keywords, done in Europe (EUR), North America (NA) or Australasia (AUS) were retrieved from the PubMed. Geomagnetic coordinates were determined for each location and AMAG60 was calculated as absolute value of numerical difference between its geomagnetic latitude from GM60L. By an ecological study with using meta-regression analyses, the relationship of MSP with GL, AMAG60 and AGRAPH60 were evaluated separately. MSP data were weighted by square root of number of prevalent cases. Models were compared by their adjusted R square (AR2) and standard error of estimate (SEE). Results: 111 MSP data were entered in the study. In each continent, AMAG60 had the best correlation with MSP, the largest AR2 (0.47, 0.42 and 0.84 for EUR, NA and AUS, respectively) and the least SEE. Merging both hemispheres data, AMAG60 explained 56% of MSP variations with the least SEE (R = 0.75, AR2 = 0.56, SEE = 57), while GL explained 17% (R = 0.41, AR2 = 0.17, SEE = 78.5) and AGRAPH60 explained 12% of that variations with the highest SEE (R = 0.35, AR2 = 0.12, SEE = 80.5). Conclusions: Our results confirmed that AMAG60 is the best describer of MSP variations and has the strongest association with MSP distribution. They clarified that the well-known latitudinal gradient of MSP may be actually a gradient related to GM60L. Moreover, the location of GM60L can elucidate why MSP has parabolic and linear gradient in the north and south hemisphere, respectively. This preliminary evaluation supported that GMD can be the mysterious environmental risk factor for MS. We believe that this hypothesis deserves to be considered for further validation studies. [ABSTRACT FROM AUTHOR]

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Copyright of Timisoara Physical Education & Rehabilitation Journal is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: To explore variables associated with self-reported communicative participation in a sample (n = 498) of community-dwelling adults with multiple sclerosis (MS). Method: A battery of questionnaires was administered online or on paper per participant preference. Data were analyzed using multiple linear backward stepwise regression. The dependent variable was an item response theory score of communicative participation measured by a subset of items from the Communicative Participation Item Bank asking respondents to rate how much their health condition interfered with participation in real-life speech communication situations. Thirteen independent variables were included in the model as self-reported symptoms: problems thinking, slurred speech, vision loss, pain, mobility, depression, fatigue, perceived social support, age, education level, employment status, gender, and MS duration. Results: Fatigue, slurred speech, depression, problems thinking, employment status, and social support were significantly associated with communicative participation, accounting for 48.7% of the variance. Conclusions: Communicative participation is significantly associated with multiple variables, only some of which reflect communication disorders. If the goal of intervention is to improve communicative participation, intervention may need to extend beyond traditional speech-language pathology boundaries to include other health symptoms as well as personal, social, and physical environments. [ABSTRACT FROM AUTHOR]

Background Multiple sclerosis (MS) is considered rare in China and reports on MS in the English literature are few. Methods A systematic literature search for articles with MS was made, particularly for papers published in the Chinese medical journals from mainland China. Results In China, the first case of MS was described in the medical records from Xiehe hospital in 1926, and the first autopsy case of MS was reported from Huashan hospital in 1957. Although reports on MS based on the information from hospital case-series have been increased gradually in the recent decades, there is no national surveillance on MS frequency in the population and population-based surveys on MS were few in China. Generally for Chinese patients with MS the mean age at onset of MS is around 30 years, with a few cases younger than 20 years; the most frequent site of the lesions in the central nervous system, based on the clinical symptoms or signs, is the spinal cord (usually more than 60%); there are few patients with a family history of MS; almost all patients are treated with corticosteroids. Reported prevalence rates of MS from population surveys in China are rather low (1-2 per 100,000) and higher in females than in males, which are comparable with the results from other populations in Asia. Conclusion The clinical and epidemiological aspects of MS in China are, in general, similar to that from other populations in Asia. Epidemiological studies and national surveillance on MS are required in China. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) has revolutionized the diagnosis and management of patients with multiple sclerosis (MS). Conventional MRI metrics are employed as primary endpoints in proof-of-concept clinical trials evaluating new drugs for MS and as secondary endpoints in definitive phase III trials. Metrics derived from non-conventional MRI techniques are now emerging and hold significant promise since they appear to be more correlated with the most disabling features of MS. However, none of these has been approved for use as a surrogate endpoint for accumulation of physical disability, which is the most important clinical endpoint of this disease. Taking into account the large numbers of patients needed, the extensive exposure to placebo, and the relatively long duration required for phase III clinical trials to show a meaningful effect on progression of disability, the need for a valid, reliable, and objective paraclinical marker of disease evolution cannot be overemphasized. This paper reviews the most up-to-date data regarding MRI techniques, their relationship with central nervous system pathology, as well as with clinical endpoints, and proposes future insights into the use of MRI metrics as surrogate endpoints in clinical trials of MS. [ABSTRACT FROM AUTHOR]

Using meta-analytic procedures, this study examined the overall effect of exercise training interventions on quality of life (QOL) among individuals with multiple sclerosis (MS). We searched MEDLINE, PSYCHINFO and CURRENT CONTENTS PLUS for the period of 1960 to November 2006 using the key words exercise, physical activity and physical fitness in conjunction with QOL and MS. We further conducted a manual search of bibliographies of the retrieved papers as well as literature reviews and contacted study authors about additional studies. Twenty-five journal articles were located and reviewed, and only 13 provided enough data to compute effect sizes expressed as Cohen's d. One hundred and nine effect sizes were retrieved from the 13 studies with 484 MS participants and yielded a weighted mean effect size of g = 0.23 (95% CI = 0.15, 0.31). There were larger effects associated with MS-specific measures of QOL and fatigue as an index of QOL. The nature of the exercise stimulus further influenced the magnitude of the mean effect size. The cumulative evidence supports that exercise training is associated with a small improvement in QOL among individuals with MS. [ABSTRACT FROM AUTHOR]