Search

The CSF gamma-globulin patterns found by electrofocusing in multiple sclerosis can be classified into five (a-e) mean patterns, where the individual bands lie very close together. However, in some patients with verified or probable multiple sclerosis conspicuous bands are found. The electrofocusing patterns from 28 such cases were compared with those reported by Kjellin and Vesterberg and with 20 cases of verified multiple sclerosis collected by chance. Differences were found with regard to the frequency of the different mean patterns, the occurrence of a double fraction in region '5', a single fraction in region '7' and a highly alkaline fraction. The electrofocusing findings have been compared with the clinical data of the 28 patients. There seems to be some correlation between the patterns of conspicuous bands and the duration and course of the disorder as well as probable sites of the CNS lesions. No indication was found, that either a high CSF gamma-globulin value and/or in a high degree of barrier damage was a prerequisite for the occurrence of conspicuous bands in the CSF gamma-globulin region. The aberrant electrofocusing patterns might be genetically determined or caused by some unusual agents (possible viral) or autoimmune reactions, modified by other than gentically divergent factors.

Background: Authors have been advocating the research ideology that a computer-aided diagnosis (CAD) system trained using lots of patient data and physiological signals and images based on adroit integration of advanced signal processing and artificial intelligence (AI)/machine learning techniques in an automated fashion can assist neurologists, neurosurgeons, radiologists, and other medical providers to make better clinical decisions. Summary: This paper presents a state-of-the-art review of research on automated diagnosis of 5 neurological disorders in the past 2 decades using AI techniques: epilepsy, Parkinson's disease, Alzheimer's disease, multiple sclerosis, and ischemic brain stroke using physiological signals and images. Recent research articles on different feature extraction methods, dimensionality reduction techniques, feature selection, and classification techniques are reviewed. Key Message: CAD systems using AI and advanced signal processing techniques can assist clinicians in analyzing and interpreting physiological signals and images more effectively. [ABSTRACT FROM AUTHOR]

Since 2009, the (CCSVI) model of multiple sclerosis has drawn much attention, and the associated surgical 'venoplasty' interventions have often been advertised as a novel idea. In fact, it is a new incarnation of various vessel-based therapies attempted for multiple sclerosis in the past, dating back to the 1930s, when Tracy Jackson Putnam (1894-1975) attempted pharmacological anticoagulation. This was followed in the 1940s by Richard M. Brickner's (1896-1959) studies of vasodilatory drugs, which further inspired trials of sympathectomy and ganglionectomy. In the 1950s, Ilya Mark Scheinker (1902-1954) studied vasopressor therapy, while Roy Laver Swank (1909-2008) investigated the effects of a low saturated fat diet in his patients. This paper discusses the longer history of these therapeutic endeavours and the aetiological theories that inspired them., (Copyright © 2013 S. Karger AG, Basel.)

Recent studies outline apoptosis of oligodendrocytes (OLDs) as an early event prior to the formation of the demyelinated plaque and post-translational modifications (PTMs) of myelin basic protein as characteristic processes of normal-appearing white matter in multiple sclerosis (MS). We reviewed reports using the following keywords: apoptosis, PTMs, autoimmunity and multiple sclerosis in all possible combinations. Introductory basic scientific information is included for the non-experts. Given the standard and ongoing studies, we raise the hypothesis that, at least in some cases, defective apoptosis of OLDs, early in the course of the disease, and post-translationally modified molecules lead to the activation of immune responses and eventually to autoimmunity. Autoimmune reactions and epitope spreading that take place in the course of the disease might obscure the initial events and leave most investigators blind to etiopathogenesis. Our paper outlines the need for studies at the very early stages of the disease, as well as sequential ones, in order to give us a valuable hint about the clarification of the cause(s) of the different clinical subtypes of MS., (Copyright (c) 2010 S. Karger AG, Basel.)

Background: Relapse is a relatively sudden worsening of neurological status in multiple sclerosis patients. The aim of this paper is to describe the frequency and timing of the subsequent clinical remission, and factors linked to a possible lack of recovery., Methods: Two hundred and twenty-three relapses in 62 multiple sclerosis patients were examined retrospectively. Kurtzke's Expanded Disability Status Scale (EDSS) scores were calculated every 3 months from 1 year before to 1 year after. Remission was defined as improvement vs. the EDSS as scored during the relapse. Recovery was defined as return to the EDSS as scored before the relapse., Results: The frequency of improvement was 78% at 3 months, 86% at 6, and lower in males (65 vs. 81%). The frequency of recovery was 55% at 3 months, 71% at 6. Kaplan-Meier curves showed stabilization after 6 months, with improvement in 90% of patients, 100% without further relapses. Relapses without recovery were only 30%; 15% excluding short-term relapses., Conclusions: Incomplete remissions do not appear to be linked to the evolution of the relapse, but to further relapses in the following months; in other words, to the short-term relapse rate., ((c) 2007 S. Karger AG, Basel)

Besides immunomodulation and immunosuppression, the specific treatment of symptoms is an essential component of the overall management of multiple sclerosis (MS). Symptomatic treatment is aimed at the elimination or reduction of symptoms impairing the functional abilities and quality of life of the affected patients. Moreover, with symptomatic treatment the development of a secondary physical impairment due to an existing one may be avoided. Many therapeutic techniques as well as different drugs are used for the treatment of MS symptoms, but only a few of them have been investigated, especially in MS patients, and are approved by the national health authorities. Despite an overwhelming number of publications, only a few evidence-based studies exist and consensus reports are very rare, too. Therefore, it seemed necessary to develop a consensus statement on symptomatic treatment of MS comprising existing evidence-based literature as well as therapeutic experience of neurologists who have dealt with these problems over a long time. This consensus paper contains proposals for the treatment of the most common MS symptoms: disorders of motor function and coordination, of cranial nerve function, of autonomic, cognitive, and psychological functions as well as MS-related pain syndromes and epileptic seizures., (Copyright 2006 S. Karger AG, Basel.)

Modern understanding of multiple sclerosis is firmly founded on the labours of many neuroscientists of the last two centuries. The cost of the disease to its victims is nowhere better displayed than in their personal accounts of their illnesses. Two figures stand out: the high-born aristocrat, Augustus D'Este and his diaries of the early 19th century and the courageous if histrionic Bruce Frederick Cummings in the early 20th century. This paper cannot do justice to their major contributions, but seeks to summarise them to give the flavour of their symptoms, disabilities and the way they were regarded by doctors and the people at large. The early medical studies of Carswell, Cruveilhier, Charcot and many others are briefly reviewed as relevant settings to these personal histories., ((c) 2005 S. Karger AG, Basel)

Matrix metalloproteinases (MMPs) are zinc-dependent enzymes involved in remodeling extracellular matrix and cell-matrix interactions. A pathogenic role of MMPs in neurological disorders is likely. This paper focuses on serological clinical aspects only. In multiple sclerosis, higher serum MMP-3 is seen during relapses. Lower serum MMP-8 and -9 levels correlate with fewer contrast-enhanced T2-weighted MRI lesions, and serum MMP-9 can be used in monitoring treatment. In myasthenia gravis, serum MMP-2, -3, and -9 levels are elevated in both generalized and ocular diseases. A proportion of the patients have markedly increased serum MMP-3. In acute stroke, higher serum MMP-9 correlates with larger infarct volume, stroke severity, and worse functional outcome, and serum MMP-3 is significantly lower than in several other neurological disorders and healthy controls. In amyotrophic lateral sclerosis, serum MMP-2 correlates with disease progression, and both serum MMP-1 and -2 are elevated. In Alzheimer's disease, serum MMP-3, -9, and -10 are elevated. In migraine, serum MMP-2 is elevated, and also MMP-9 in those patients with migraine without aura. MMP-9 is implicated in the pathogenesis of experimental epilepsy. A pathogenic role of MMPs in these conditions could be related to their ability to degrade extracellular matrix. MMPs may also facilitate autoimmunity. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 pandemic represents one of the most challenging issues that have recently influenced everyday life in countries all over the world. Understanding the risk of this disease is of high importance in patients with multiple sclerosis (MS) as they represent a vulnerable population through their treatment with disease-modifying therapies (DMTs). Infective episodes may trigger relapses and lead to deterioration of the health condition. Summary: Vaccination is an important preventive measure against infectious diseases. In MS patients, concerns have been raised about the effectiveness of vaccines in patients on various immunomodulatory drugs and about their possible adverse effects including impairment of neurological functions. The objectives of this article were to summarize the current knowledge on immune responses to the COVID-19 vaccines and their safety in MS patients and to provide practical guidance based on the data available to date. Key Messages: Although MS is not associated with a higher risk of COVID-19, this infection can trigger relapses or pseudo-relapses. Vaccines against SARS-CoV-2 are recommended for all MS patients who are not in the active phase of the disease, despite the fact that there is still a lack of long-term reliable data on the effectiveness and safety of vaccines against COVID-19. Some DMTs can reduce vaccine humoral responses, but might still provide some protection and adequate T-cell response. To optimize the effectiveness of vaccination, the ideal timing of vaccine application and DMTs dosing regimen is crucial. [ABSTRACT FROM AUTHOR]

The paper reports the results of recordings and maps of event-related potentials (ERPs) in patients with Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and in subjects affected by dementia in multiple sclerosis (MS). ERPs were recorded from 19 scalp electrode derivations using both visual and acoustic paradigms. In 43% of AD patients, ERPs were normal; in 20%, although present, ERP components were delayed, while in the other 37% none of the N2 and P3 peaks could be recorded, because of abnormal topography of potentials on the scalp. In patients with PSP, the normal ERP sequence was not identified. In patients with MS delayed ERPs (50%), abnormal topography of ERPs (30%) and absence of ERPs (20%) were observed. The follow-up of AD patients showed a progressive alteration of ERPs. ERP topography alterations were observed in AD, PSP and MS patients with poorest cognitive performances.

Introduction: Multiple sclerosis (MS) is a common neurological disorder in societies. The most common symptoms in patients with MS are gait disorders and spasticity. Pharmacological therapies have mild therapeutic influence with more side effects for management of these symptoms. There is evidence that neuro-rehabilitation techniques have more appropriate effects rather than pharmacological therapies. In this regard, some studies indicated the beneficial effects of brain stimulation techniques on gait improvement and decreasing spasticity in patients with MS, while the others have not shown any efficacy. Accordingly, conducting a meta-analysis study in this issue is very important. Methods: A systematic search was performed in PubMed, Scopus, and ISI Web of Science from database inception on December 6, 2020, to find interventional studies assessing the effects of neuromodulators (transcranial direct-current stimulation [tDCS] or transcranial magnetic stimulation [TMS]) on spasticity, balance, and gait in patients with MS. The included studies were qualitatively assessed by the Physiotherapy Evidence Database (PEDro) scale. Finally, the homogeneity studies were analyzed by Stata software. Study-specific results were pooled by using a random-effects model. Results: A total of seven studies were included in the analysis. In the pooled analysis of studies, a significant effect of the TMS technique on spasticity was observed in patients with MS: −0.80 (95% CI: −1.31, −0.29). In addition, no significant effect of the single-session tDCS technique on gait speed was observed in patients with MS: 0.11 (95% CI: −0.11, 0.32). Conclusions: One of the main causes of discrepancy in the findings of included studies is the number of sessions for using neuromodulator techniques. A single session of anodal tDCS is not enough to improve gait in patients with MS. In addition, meta-analysis shows that multi-session TMS is effective intervention for decreasing spasticity in patients with MS. [ABSTRACT FROM AUTHOR]

The discovery of the oligoclonal IgG bands (OCB) in the cerebrospinal fluid (CSF) was a major step forward in the understanding of multiple sclerosis (MS) and other inflammatory diseases of the central nervous system. Separation of IgG molecules produced by different B cell clones was not possible until agar electrophoresis was invented in 1950. The key observation that led to the discovery of OCB can be dated back to 1959, when Karcher, van Sande and Lowenthal reported that agar electrophoresis subdivided CSF γ-globulins from a patient with subacute sclerosing panencephalitis into several individual fractions, which were distinguishable with densitometry. OCB were detected in CSF from patients with trypanosomiasis, neurosyphilis and MS by the same research group in 1960. The discovery of OCB was preceded by the detection of intrathecal IgG synthesis with Tiselilus’ moving boundary electrophoresis by Kabat in 1942. This method did not allow separation of IgG molecules produced by different B cell clones, and it is therefore a misconception that Kabat discovered the OCB. The discovery of OCB led to the still prevailing concept that MS is mediated by clonally expanded lymphocytes, and provided the basis for modern diagnostic procedures in MS. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Preliminary observational studies with multiple sclerosis (MS) patients have reported strong correlations between an increase in hypointense lesion load (black holes) on T1-weighted spin echo images, and an increase in disability. Objective: We assessed the relationship of hypointense lesions to the clinical course of disease among 50 relapsing-remitting MS patients in the controlled setting of a randomized clinical trial. Methods: Fifty patients with relapsing-remitting disease were enrolled in a randomized double-blind two-arm (cladribine vs. placebo) clinical trial of 1-year duration. All patients had monthly clinical evaluations and MRIs over the course of the trial. Multivariate techniques were used to identify predictors of clinical severity from information on exacerbations, MRIs, baseline clinical parameters, and demographics. Results: At baseline, clinical severity is weakly related to counts of black holes, with rank correlations between counts and clinical scores (EDSS and SNRS) of absolute magnitude 0.3. Rates of appearance of new black holes over the course of the trial are higher for patients with more severe disease at baseline (EDSS ≥ 4) than for the less severe patients. Changes in clinical severity over the course of the trial are best predicted by baseline neurologic scores and numbers of exacerbations, with black holes adding no further improvement in prediction. Conclusions: Numbers of exacerbations seem more critical to short-term clinical outcomes in relapsing-remitting MS, as reflected by patients’ clinical scores, rather than black holes. Various imaging methods and MRI indices capture complementary information relating to MS disease processes. The determination of which processes are affected by different drugs should lead to more effective treatment of MS patients.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: Optic neuritis (ON) is an inflammation of the optic nerve that can be associated with a multitude of different systemic conditions and primary CNS disorders. In children, only around 25% of unilateral ON cases are considered idiopathic. Despite being considered a clinical diagnosis per se, neuroimaging plays a crucial role in the diagnostic pathway for these patients. Methods: Demographic, clinical, and imaging data of all patients presenting with unilateral ON at a tertiary paediatric centre over 40 months (January 1, 2016, to April 30, 2019) were retrospectively analyzed. Results: A total of 10 patients filled the inclusion criteria. The average age of presentation was 14.1 years. Patients in this series had ON associated with multiple sclerosis (n = 2), anti-MOG demyelinating disorders (n = 2), and neuromyelitis optica with anti-AQP4 antibodies (n = 1). ON was determined to be secondary to Toxocara canis infection in 1 case and a side effect of anti-TNFα therapy (adalimumab) in another. MR imaging showed T2 hyperintensity and/or gadolinium enhancement of one of the optic nerves in all but 3 patients, and coincidentally these were the cases with monophasic idiopathic ON (average follow-up period of 2 years). Additional brain MR findings directly contributed to the final diagnosis in half of the cases. Conclusions: These cases are demonstrative of the wide range of possible causes of unilateral ON in the paediatric population. The absence of typical ON features in MR imaging was strongly suggestive of idiopathic ON in this cohort (p < 0.01). [ABSTRACT FROM AUTHOR]

>bold<>italic/italic<>/bold< Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that leads to inflammation, demyelination and neurodegeneration. Viral aetiology has been suspected to be an MS trigger for a long time, and herpesviruses (HSs) are among the potential pathogens involved. >bold<>italic/italic<>/bold< The present investigation aims to detect the presence of antibodies against the herpes simplex virus (HSV), varicella-zoster virus, Epstein-Barr virus (EBV), human cytomegalovirus (CMV) and human herpesvirus 6 (HHV6) in the serum of MS patients and control individuals in north-eastern Poland. >bold<>italic/italic<>/bold< Plasma was collected from 141 MS patients and 44 blood donors who served as the control group. These individuals were assessed for the presence of antibodies using an enzyme-linked immunosorbent assay. >bold<>italic/italic<>/bold< The statistical analysis showed a higher probability of EBV (>italic/italic< = 0.037, OR 4.359) and HHV6 (>italic/italic< = 0.020, OR 3.343) antibody presence in patients with MS compared to that in the control group. In the MS patient group, the prevalence of CMV IgG antibodies was significantly higher in females (>italic/italic< = 0.025). Patients who tested positive for anti-EBV IgG were diagnosed 7.9 years earlier than patients who tested negative for anti-EBV IgG (>italic/italic< = 0.048). >bold<>italic/italic<>/bold< The study showed that MS patients in north-eastern Poland were more likely to be seropositive for EBV and HHV6 than healthy individuals. Further work should be undertaken in other regions of Poland and other European countries with particular attention paid to testing seropositivity in all HSs, particularly in the MS patient population, to evaluate the impact of HSs on MS patients in different environments. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the effectiveness of cognitive rehabilitation in a group of multiple sclerosis (MS) patients. Methods: Thirty-four patients were included in this study and randomly allocated either to treatment with multidisciplinary rehabilitation plus cognitive training or to treatment with multidisciplinary rehabilitation alone. Results: After 3 months of cognitive treatment, the patients assigned to the rehabilitation plus cognitive training group displayed an improvement in the cognitive test of executive function and a marked improvement in quality of life (QoL). The patients treated with multidisciplinary rehabilitation without cognitive training improved in the physical composite score alone. Both groups of patients displayed an improvement in depression, though the improvement was confirmed at the 6-month follow-up examination (p = 0.036) only in patients treated with multidisciplinary rehabilitation plus cognitive training. Conclusions: Our results indicate that the multidisciplinary rehabilitation treatment is the best approach to treat MS. The specific effect of each treatment needs to be assessed to be able to determine its role within a multidisciplinary approach. Cognitive rehabilitation is an important aspect of this multidisciplinary approach insofar as it may improve the QoL of MS people. [ABSTRACT FROM AUTHOR]

Background/Aims: Appropriate and timely screening instruments that sensitively capture the cognitive functioning of multiple sclerosis (MS) patients are the need of the hour. We evaluated newly derived regression-based norms for the Symbol Digit Modalities Test (SDMT) in a Dutch-speaking sample, as an indicator of the cognitive state of MS patients. Methods: Regression-based norms for the SDMT were created from a healthy control sample (n = 96) and used to convert MS patients' (n = 157) raw scores to demographically adjusted Z-scores, correcting for the effects of age, age 2, gender, and education. Conventional and regression-based norms were compared on their impairment-classification rates and related to other neuropsychological measures. Results: The regression analyses revealed that age was the only significantly influencing demographic in our healthy sample. Regression-based norms for the SDMT more readily detected impairment in MS patients than conventional normalization methods (32 patients instead of 15). Patients changing from an SDMT-preserved to -impaired status (n = 17) were also impaired on other cognitive domains (p < 0.05), except for visuospatial memory (p = 0.34). Conclusions: Regression-based norms for the SDMT more readily detect abnormal performance in MS patients than conventional norms, identifying those patients at highest risk for cognitive impairment, which was supported by a worse performance on other neuropsychological measures. [ABSTRACT FROM AUTHOR]

Background: Tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex® ) is an add-on therapy for moderate- to-severe multiple sclerosis (MS)-related drug-resistant spasticity (MSS). Aim: The MOVE-2 EU study collected data from everyday clinical practice concerning the effectiveness and tolerability of THC:CBD. Methods: This was an observational, prospective, multicentre, non-interventional study. Patients with resistant MSS prescribed add-on THC:CBD oromucosal spray according to approved labelling, were followed for 3 months. After 1 month, only responders ( ⩽ 20% improvement in spasticity) continued treatment. The main endpoints were the evolution of MSS and associated symptoms, quality of life (QoL) and tolerability. Results: Four hundred and thirty three patients (55% female) were recruited (98% in Italy). The mean duration of MSS was 7.4 years and baclofen was used by 78.1% of participants. Three hundred and forty nine participants continued with THC:CBD oromucosal spray after 1 month, and 281 after 3 months. THC:CBD mean dosage was 6 sprays/day. MSS scores and spasticityrelated symptoms (spasms, fatigue, pain, sleep quality and bladder dysfunction) were significantly improved by THC:CBD at 3 months, as were activities of daily living, and QoL (EQ-5D VAS). Adverse events, none of which were severe or serious, were reported by 10.4% of patients. Conclusions: In everyday clinical practice, THC:CBD oromucosal spray provided symptomatic relief of MSS and related troublesome symptoms. [ABSTRACT FROM AUTHOR]

Background/Aims: The immunomodulatory effect of glatiramer acetate may help in reducing multiple sclerosis (MS)-related fatigue; however, evidence to prove this notion especially after switching from another immunomodulatory therapy is limited. We assessed the 6-month effect of glatiramer acetate on MS-related fatigue in patients switching from interferon-β (IFN-β) in clinical practice. Methods: This was an observational study including 54 patients with relapsing-remitting MS that showed moderate/severe fatigue primarily caused by MS before switching from IFN-β to glatiramer acetate and received glatiramer acetate for ≥ 6 months in daily practice. Study data were retrospectively collected through chart review at treatment switch and over the following 6 months on glatiramer acetate. Results: Over the 6-month administration of glatiramer acetate, scores on the Modified Fatigue Impact Scale decreased: overall (p < 0.001), physical scale (p < 0.001), cognitive scale (p < 0.001), and psychosocial scale (p < 0.001). The Work Productivity and Activity Impairment Questionnaire showed improvements in work (p = 0.009) and other daily activity impairment (p < 0.001). Health-related quality of life as per the Multiple Sclerosis Impact Scale also improved: physical score (p < 0.001) and psychological score (p < 0.001). Conclusion: Patients with moderate/severe fatigue switching from IFN-β to glatiramer acetate may benefit from fatigue improvements that contribute to reduce their work/activity impairment and improve their quality of life. [ABSTRACT FROM AUTHOR]

Background: Lower thermal and discomfort thresholds may predispose multiple sclerosis (MS) patients to chronic pain, but a possible effect of fibromyalgia (FM) comorbidity has never been investigated. Aims were to investigate the thermal and discomfort thresholds in the evaluation of pain intensity between MS patients with FM (PFM+) and MS patients with pain not associated to FM (PFM−). Methods: One hundred thirty three MS patients were investigated for chronic pain. FM was assessed according to the 1990 ACR diagnostic criteria. An algometer was used to measure the thresholds in the patients and 60 matched healthy subjects. Results: Chronic pain was present in 88 (66.2%) patients; 12 (13.6%) had neuropathic pain, 22 (17.3%) were PFM+ and 65 (48.9%) PFM−. PFM+ were predominantly female (p = 0.03) and had a greater EDSS (p = 0.01) than NoP; no other significant differences emerged than PFM−. The thresholds were lower in MS patients than controls (p < 0.01), mainly in the PFM+. FM severity influenced the thermal threshold (p < 0.001), while the female gender influenced the discomfort threshold (p < 0.001). Conclusion: Thermal and discomfort thresholds were lower in patients than controls and were the lowest in PFM+. Their more severely impaired thermal threshold supports a neurophysiological basis of such association. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: The relationship between multiple sclerosis (MS) and anemia has not been clarified sufficiently. In this retrospective, cross-sectional, case-control study we evaluated in MS patients: (1) prevalence of anemia relative to sex- and age-matched controls; (2) relationships between patients' demographic, clinical and drug-related characteristics and anemia; (3) effect of anemia on the risk of developing MS. Methods: 187 consecutive MS patients (51 males, mean age (±SD) 44.5 ± 10.7 years) and 200 controls (56 males, mean age 45.5 ± 12 years) were included in the study. Anemia was defined as hemoglobin <12 g/dl for females and <13 g/dl for males. Results: There was a significant difference in the prevalence of anemia between MS patients and controls (35 (18.7%) and 19 (9.5%), respectively, p = 0.009). We did not find any association between patients' characteristics and anemia. The occurrence of anemia increased more than twice the risk of developing MS (odds ratio: 2.19, 95% confidence interval 1.19-4.0). Conclusion: Our study showed a consistent association between anemia and MS. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: In 1996, the clinical course of multiple sclerosis (MS) was characterized as relapsing-remitting, primary progressive, secondary progressive or progressive relapsing. Since then, an increased understanding of MS and its pathology prompted a re-examination of these clinical phenotypes. Main recommendations of the 2013 revisions are provided herein. Summary: Clinically isolated syndrome has been added, and progressive relapsing MS has been eliminated, from the clinical course descriptions. All forms of MS should be further subcategorized as either active or non-active. Active MS is defined as the occurrence of clinical relapse or the presence of new T2 or gadolinium-enhancing lesions over a specified period of time, preferably at least one year. An additional subcategory for patients with progressive MS differentiates between those who have shown signs of disability progression over a given time period and those who have remained stable. The term 'worsening' is recommended to describe patients whose disease is advancing for any reason, whereas 'disease progression' should be reserved for those with progressive disease who are truly progressing (as opposed to worsening from a relapse). The term 'benign' should be used with caution as the course of MS can worsen at any time, even after many years of apparent stability. Key Messages: Newer characterizations of MS phenotypes include a consideration of disease activity (based on the clinical relapse rate and imaging findings) and disease progression. Accurate clinical course descriptions are useful for communication, prognostication, clinical trial design and to guide everyday clinical decision-making. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The European Multiple Sclerosis Platform (EMSP) is an umbrella organization for national multiple sclerosis (MS) patients' associations in 34 European countries. Its focus is to improve the quality of life (QoL) of individuals with MS and inform society about the challenges of living with this chronic and debilitating disease. Summary: The EMSP, which is comprised of 39 MS societies across Europe, represents the interests of more than 600,000 individuals with MS and another 1.5 million persons affected by the disease, including family and caregivers. The organization works to achieve high quality, equitable treatment and support for persons with MS throughout Europe, as reflected in its main activities and projects. These include: the European Code of Good Practice in MS; a European MS register (EUReMS); a MS Barometer to assess QoL; the MS Nurse PROfessional curriculum to provide standards for MS nurse training; a photographic exhibition entitled Under Pressure; the Believe and Achieve project which focuses on employment for young people with MS; and collaboration in World MS Day, an international MS awareness day. Key Messages: The activities and projects of the EMSP are geared towards making a difference in the lives of individuals with MS in Europe and their wider support networks, including physicians, neurologists, nurses and carers. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The pseudotumoral form of multiple sclerosis (MS) is a rare condition with few descriptions in the literature. It supposes a diagnostic challenge especially when appearing at the onset of disease. Methods: We retrospectively describe a case series of pseudotumoral MS patients that attended our hospital from 2004, analyzing demographic, clinical and radiological variables. We classified the lesions according to the recently proposed morphologic classification (infiltrative, megacystic, Baló or ring-like) and according to the contrast enhancement pattern (nodular, complete ring, incomplete ring and diffuse). Results: Fourteen patients (11 female, 3 male), with a mean age of 35 years, were identified. All of them suffered from a relapsing-remitting form of MS. Eleven patients (78.57%) had symptomatic pseudotumoral lesions (PL), being the form of clinical presentation in the majority of those patients that were symptomatic (81.81%). Several patients presented atypical clinical manifestations such as cognitive impairment (21.42%) and epileptic seizures (14.28%). Full recovery was found in 53.84% of all symptomatic episodes. After a mean follow-up of 43 months, recurrent PL episodes were seldom observed (21.42%), the annualized relapse rate was 0.95 and the mean final Expanded Disability Status Scale score was 1.5. The majority of PLs were supratentorial, coexisted with typical demyelinating plaques and showed the ring-like morphology and the ring pattern of contrast enhancement. Three patients had more than one PL on the same scan, all of the lesions with similar morphology. Conclusions: Our findings contribute to a better characterization of pseudotumoral forms of MS. However, larger studies are required to define this atypical entity more exactly. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: Neuromyelitis optica spectrum disorders (NMOSDs) and multiple sclerosis (MS) are distinct clinical entities but are poorly distinguished by serum markers, including serum anti-aquaporin-4 (AQP4-Ab). We examined if testing for serum anti-nuclear antibodies (ANAs) and AQP4-Ab improved diagnostic sensitivity for NMOSDs. Methods: Chinese patients with NMOSDs (n = 74) or MS (n = 49) were screened for serum ANAs (all patients) and AQP4-Ab (58/74 NMOSDs and 45/49 MS patients). The NMOSDs group included patients with neuromyelitis optica (NMO; n = 53), recurrent longitudinally extensive transverse myelitis (rLETM; n = 20), and recurrent optic neuritis (n = 1). Results: The seroprevalence rate for ANAs was significantly higher in the NMOSDs group than the MS group (45.9 vs. 2%; p < 0.01). Similarly, AQP4-Ab seroprevalence was higher in NMOSDs than MS (56.9 vs. 4.4%; p < 0.01). Sensitivities and specificities for diagnosing NMOSDs were 51.7 and 97.8% using ANAs, 56.9 and 95.6% using AQP4-Ab, and 74.1 and 93.3% using both assays. Conclusion: Patients with NMO or rLETM had higher ANA seroprevalence than MS patients. Combined detection of both ANAs and AQP4-Ab improves the sensitivity of NMOSDs diagnosis without compromising specificity. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: There is a wide variation in the prevalence of multiple sclerosis (MS) in different geographical regions and the epidemiology of MS in Iran has been a major topic of concern during the last decade. Several population-based studies have shown a sharp increase in the prevalence and incidence of MS in this region. In this study, for the first time, the aim was to provide a comprehensive review regarding the incidence and prevalence of MS across Iran. Methods: A comprehensive literature search was performed using PubMed, Embase, and Web of Science. We also did a manual search of reference lists from primary articles and relevant reviews. Databases of ongoing research and unpublished literature were also searched. Results: A total of 22 relevant studies were reviewed and 11 studies met the inclusion criteria. Incidence data were found in 5 studies and ranged from 0.68 to 9.1/100,000 per year in the Iranian population. Prevalence was reported in all studies and ranged from 5.3 to 74.28/100,000 with the higher prevalence among females (female/male ratio ranged from 1.8 to 3.6). The most prevalent subtype of MS was the relapsing-remitting form (65.8-87.8%). The sensory disturbance was the most initial presentation. Conclusion: The incidence and prevalence of MS in Iran has been increasing rapidly, especially in females. Future research should focus on determining the epidemiological features of MS in the neglected provinces with different ethnicities. Such an effort along with further research towards improvement of data on previously studied areas can enable a field to be opened up to identify the patterns of MS in varied genetic backgrounds and environments of Iran. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To assess the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) in patients with clinically isolated syndrome (CIS). Methods: 130 European CIS patients and 60 relatives completed the MSNQ. Results: The mean (SD) MSNQ score for CIS patients was 15.5 (10.8) and for their informants 11.3 (9.6). Neither the CIS patient nor relative MSNQ report scores correlated with any of the cognitive test scores in the Brief Repeatable Battery of Neuropsychological Tests, but they were significantly related to psychosocial scales including depression. Conclusions: In CIS, patient and relative MSNQ scores are influenced by psychosocial variables rather than actual objective cognitive status. Formal cognitive test assessment is recommended for CIS patients. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: We conducted a longitudinal prospective study to evaluate the long-term effect of pregnancy on the progression of multiple sclerosis (MS). Method: Parous female MS patients were extracted from the database of Isfahan Multiple Sclerosis Society (IMSS). Through comparing the annual relapsing rate during a mean of 4 years before pregnancy versus a mean of 6 years after delivery, MS progression influenced by the pregnancy was analyzed. Result: 102 female patients were included in our study. The mean annual relapsing rate 4 years prior to pregnancy was significantly higher than at the subsequent 6 years after delivery (1.06 vs. 0.45, p < 0.001). In addition, the annual relapsing rate in years prior to pregnancy was significantly higher than each trimester of gestation (p < 0.001). Furthermore, there was a 2.2-fold increased risk of having a relapse in individuals who had experienced more relapses prior to pregnancy, and a 0.8-fold decreased in the risk of having more relapses with older age at the onset of MS. Conclusion: Although the course of MS was deteriorated 3 months after delivery, it was not statistically significant comparing annual relapsing rates during the years prior to pregnancy. Moreover, the rate of disease progression slowed down in the 6-year period monitored after delivery. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Large cavitary lesions are not typical for multiple sclerosis (MS). Cavitary white matter changes may be seen in megalencephalic leukoencephalopathy with subcortical cysts, Alexander disease, mitochondrial leukoencephalopathies, vanishing white matter disease, leukoencephalopathy with calcifications and cysts, cytomegalovirus infection, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Objective: To analyze clinical and radiological characteristics in MS patients with large cavitary lesions. Methods: We studied MS patients with large cavitary brain lesions. Patient characteristics, disease onset/duration/subtype, expanded disability status scale (EDSS), Mini Mental State (MMS), corpus callosum lesions, history of segmental myelitis, CSF oligoclonal bands (OCB), visual evoked potentials (VEP), vanishing white matter disease genetic analysis, and characteristics of the cavitary lesions were analyzed. Results: Nine patients were analyzed, 1 man and 8 women. Mean age of disease onset was 38.5 years. Mean disease duration was 9 years. Three patients had initial relapsing-remitting MS and 6 patients had primary-progressive MS. Mean EDSS was 4.5. Mean MMS was 20/30. Segmental myelitis was present in 6 cases. OCB were found in 6 patients. VEP was performed in 6 patients, and pathological in all but one. Vanishing white matter disease genetic analysis was performed and negative in 5 patients. Inferior corpus callosum lesions were seen in all patients with available sagittal FLAIR sequences. Cavitary lesions were strictly supratentorial, and located inside the diffuse leukoencephalopathy, with often a posterior predominance. Conclusion: MS patients with large cavitary lesions seem to represent an MS subgroup, predominantly women, with relatively late disease onset, predominantly primary-progressive type, relatively high EDSS scores, and severe cognitive dysfunction. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Many studies have demonstrated the relationship between multiple sclerosis (MS) and cognition disorder. The objective of this study was to investigate the coping style of patients with mild frontal cognitive disorder. Methods: 135 patients with MS were divided into two groups as a function of their cognitive states ('mild frontal cognitive impairments' or 'without frontal cognitive impairments'). All were seen for a semi-structured interview in order to collect socio-demographic and clinical information, after which there was an assessment of their cognitive and mental states and fatigue (FAB, MADRS). Then, all patients completed three self-report questionnaires concerning their coping strategies (WCC, CHIP) as well as their fatigue state. Results: No significant differences were observed between the two groups as to coping strategies and mood. However, patients with mild cognitive impairments tended to use more emotion-focused coping strategies, especially self-blame (F(133) = 2.2; p = 0.14) and diversion (F(133) = 1.35; p = 0.24) than patients without cognitive impairments. Patients with mild cognitive impairments were more fatigued than other patients. Discussion: Our study showed that patients with mild cognitive impairments did not differ significantly of other MS patients with regard to coping strategies. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Previous studies suggest beneficial effects of exercise in multiple sclerosis (MS). However, knowledge on the effects of physical activity on the immune system is limited. Objective: To assess potential relationships between cardiorespiratory fitness, cognitive function, and immune parameters in physically active and inactive MS patients. Methods: We identified 83 patients with relapsing-remitting disease, an unrestricted walking range, and stable interferon-β treatment from our data base. Based on the subjective report of physical activity, the lower/inactive (n = 21) and upper/active quartiles (n = 21) of patients were selected. We assessed the frequency of T cells, B cells, NK cells, monocytes and regulatory T cell populations by flow cytometry, measured brain-derived neurotrophic factor and vitamin D serum levels by ELISA, and conducted spiroergometry and transcranial sonography. Results: Physical activity and cardiorespiratory fitness were not associated with brain-derived neurotrophic factor, frequency of T regulatory cells or any other immune cell subpopulation. However, we found a positive correlation of vitamin D serum levels with cardiorespiratory fitness. Conclusion: Overall, we found no negative effect of physical activity on the immune system. The association between vitamin D and cardiorespiratory fitness most likely reflects longer hours of sunlight exposure in active patients, suggesting a desirable 'side- effect' of physical activity. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Patients with multiple sclerosis (MS) report sleep disturbances (SD) and excessive daytime sleepiness (EDS) more frequently than the general population. Our objectives were to evaluate SD and EDS in MS patients and to test the reliability of subjective sleep questionnaires. Methods: Demographic and clinical characteristics of unselected consecutive patients with MS were collected. Different questionnaires were used to assess quality of sleep, daytime sleepiness, fatigue, anxiety, depression and quality of life (QoL). Nocturnal polysomnography and Multiple Sleep Latency Test (MSLT) were performed in 25 selected MS patients with fatigue and with or without EDS. Results: 205 MS patients were enrolled. More than half of the MS patients were classified as 'poor sleepers'. In multivariate analysis, SD were correlated with disability, fatigue, depression, QoL, and pain, but not with EDS. Subjective sleepiness evaluated with the Epworth Sleepiness Scale and SD with the Pittsburgh Sleep Quality Index were not correlated with the results of the objective assessments of vigilance (MSLT) and sleep. Conclusions: SD and EDS are frequent among MS patients. Objective assessment of vigilance and sleep can be challenging but MS patients who are poor sleepers should receive immediate assessment and treatment in order to improve QoL. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim: To determine whether corpus callosum atrophy predicts future clinical deterioration in multiple sclerosis. Methods: In 39 multiple sclerosis patients the area of corpus callosum in the sagittal plane, T2 and T1 lesion volumes, brain parenchymal fraction and brain atrophy were determined at baseline and 1 year after treatment initiation. Non-parametric and multiple regression models were built to identify the most reliable predictors of disability and of its changes over 9 years. Results: Corpus callosum atrophy during the first year of treatment was the best predictor of disability (r = -0.56) and of its increase at 9 years (r = 0.65). Corpus callosum atrophy of at least 2% predicted increase in disability with 93% sensitivity and 73% specificity (odds ratio = 35). Conclusion: Corpus callosum atrophy is a simple and accurate predictor of future disability accumulation and is feasible for routine clinical practice. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Hypothermia is a rare condition in patients with multiple sclerosis (MS). Only 17 patients have been reported so far. Case Report: We report 2 patients with a long history of MS who presented with severe acute hypothermia associated with thrombocytopenia and hepatic cytolysis. Both patients presented with an aggravation of their neurological status, psychomotor slowing and confusion. There was no clinical or biological sign of infection. Magnetic resonance imaging (1.5 T) revealed bilateral preoptic T2-weighted lesions for 1 patient. The neurological status of one patient was worse after the episode of hypothermia than before, which suggests that hypothermia could be a factor of poor prognosis concerning disease progression. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Immunomodulating therapies may prevent relapses in multiple sclerosis and stabilize neurological status. However, little is known about the influence particularly of newer drugs on cognitive functions. We conducted an open-label prospective study to demonstrate whether natalizumab is apt to improve cognitive functions and mood in 29 patients tested psychometrically while under treatment for 6 months. We found improvements in some measures of attention, memory, mood, and well-being, but no deterioration, although patients suffered from their diseases for more than 10 years and had an EDSS score of 3.5. It is concluded that natalizumab is able to stabilize or improve cognition and mood even in longer-lasting multiple sclerosis. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: To measure the Timed Up and Go (TUG), imagined TUG (iTUG), and the difference of time between these two tests (delta time) in 20 patients with relapsing-remitting multiple sclerosis (RRMS) and 20 healthy age-matched controls and to examine whether an association with cognitive functions, motor impairment, and behavioral changes can be determined. Methods: The mean ± SD of TUG, iTUG and delta time were used as outcomes. Spatiotemporal gait parameters were recorded by a 12-camera optoelectronic system during straight walking at usual self-selected speed. Cognitive functions were assessed by a standardized neuropsychological examination. Results: Patients performed the TUG slower than the controls (10.00 ± 1.70 s vs. 8.71 ± 1.04 s, p = 0.01, respectively). The TUG was correlated with gait parameters, cognitive functions, and behavior, whereas delta time was correlated only with cognitive functions. Conclusion: TUG represents an interesting test to reveal subtle deficits in RRMS patients with low disability and is related to motor, cognitive, and behavioral functioning. Combining with the TUG, delta time could easily give additional information on specific cognitive functions in the assessment of patients with RRMS. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: To estimate costs of multiple sclerosis (MS) in a German cohort according to severity of the disease and clinical symptoms. Methods: 144 patients were recruited from an MS outpatient clinic. Costs were calculated according to current German health-economic guidelines from the perspective of the social health insurance system. Patients were either interviewed or completed a questionnaire. Cost assessment covered a 3-month period. Health outcomes were: Expanded Disability Status Scale, MS Functional Composite, Functional Assessment of MS, fatigue, depression (Beck Depression Inventory II) and patients' socioeconomic status. Multivariate linear regression identified independent cost predictors. Results: Total quarterly costs per patient were EUR 10,329 (95% CI 9,357-11,390). Direct costs were EUR 5,344 for the social health insurance system and EUR 140 for the patient. Drugs represented the major share of direct costs (and 35% of total costs); indirect costs accounted for 47% of total costs. Univariate and multivariate analyses identified age, disability, fatigue and depression as independent predictors for total, indirect or drug costs. Conclusion: MS represents a high economic burden, with direct costs exceeding indirect costs. To reduce costs, research should focus on prevention that slows down progression of MS. Rehabilitation and symptomatic treatment may have merits in decreasing indirect costs. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Heat-shock proteins (HSPs) are antigen-presenting protein-aggregation-preventing chaperones, induced by cellular stress in eukaryotic cells. In this review, we focus on recent HSP advances in neurological disorders. In myasthenia gravis, patients responding to immunosuppressive therapy have reduced serum HSP-71 antibodies. Generalized and ocular myasthenia gravis patients have elevated serum HSP-70 antibodies, indicating common pathogenic mechanisms. In Guillain-Barré syndrome, HSP-70 antibodies are elevated in serum and cerebrospinal fluid, and serum levels are higher than in myasthenia gravis and multiple sclerosis. In multiple sclerosis, serum HSP-27 antibodies are elevated during relapses providing disease activation marker, while α,β-crystallin expression in brain lesions indicates remission phase initiation. In acute stroke, serum HSP-27 antibodies are elevated irrespective of stroke type and duration. In epilepsy, HSP-27 is induced in patients' astrocytes and cerebral blood vessel walls, and α,β-crystallin is expressed in epileptic foci. In neurodegenerative disorders such as Alzheimer dementia and Parkinson's disease, HSPs are upregulated in brain tissue, and α,β-crystallin modulates superoxide dismutase-1 (SOD-1) tissue accumulation in familial amyotrophic lateral sclerosis. HSPs play an important role in antigen-presentation and tolerance development. Antibody-mediated interference with their function alters immune responses causing neuropathology. The role of HSPs in clinical neurology should be the subject of future investigation. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We evaluated 30 patients with clinically definite multiple sclerosis (MS) and 8 patients with neuromyelitis optica (NMO) to investigate correlations between Th1/Th2 balance, disease activity, effects of interferon (IFN)-β treatment, and expressions of chemokine receptors CXCR3 and CCR4 on CD4+ and CD8+ T cells in peripheral blood. MS and NMO patients in the relapsing phase showed a significantly increased CD4+CXCR3+/CD4+CCR4+ ratio and CD8+CXCR3+/CD8+CCR4+ ratio compared with respective patients in the remission phase. After IFN-β treatment, the CD4+CXCR3+/CD4+CCR4+ ratio and CD8+CXCR3+/CD8+CCR4+ ratio were significantly decreased compared with the relapsing phase and slightly lower than in the remission phase. The CD8+CXCR3+/CD8+CCR4+ ratio showed a more marked change associated with disease activity than CD4+ T cells in MS and NMO patients. Moreover, in patients in the relapsing phase of NMO, the CD4+CXCR3+/CD4+CCR4+ ratio and CD8+CXCR3+/CD8+CCR4+ ratio were significantly higher than in MS patients in the relapsing phase. We confirmed marked changes in the CD8+CXCR3+/CD8+CCR4+ ratio according to disease activity and treatment of MS and NMO. Furthermore, this ratio was more strongly linked to immune and inflammatory activity in NMO patients than in MS patients, and may represent an important factor in differentiating the pathogenesis of MS and NMO. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: Multiple sclerosis (MS) is a demyelinating neurodegenerative inflammatory autoimmune disease. Restless legs syndrome (RLS) is characterized as a strong urge to move the legs to stop abnormal sensations there. In this study, we aimed to investigate whether or not the increased RLS frequency seen in MS could be associated with depression and fatigue. Methods: The study involved 98 patients with definite MS and 129 healthy volunteers. The Beck Depression Inventory and Fatigue Severity Scale were used to assess all participants. The patients and the healthy volunteers were examined for RLS according to the criteria of the International Restless Legs Syndrome Study Group. Results: When the factors related to RLS in MS were evaluated, there were significant relationships found among age, type of MS, pyramidal symptoms, intestinal and bladder symptoms, number of lesions in MR, depression, and fatigue. Risk factors for RLS were also seen more frequently in the MS group than in the healthy volunteers. Conclusion: RLS was seen 2.55 times more frequently in patients with MS than in the control group. This was due to the existence of numerous factors rather than a single factor - including depression and fatigue. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Results for the e4/e2 alleles of the ApoE gene as markers of susceptibility, clinical and radiological progression, and cognitive deterioration in patients with multiple sclerosis (MS) are contradictory. Aim: The usefulness of these markers in predicting the response to interferon-β-1b (IFNβ-1b) was evaluated. Material and Methods: 95 patients with relapsing-remitting MS treated with IFNβ-1b (mean follow-up 7.44 years) were studied. We correlated the e4 and e2 alleles with the time to the first relapse or to a 1-point worsening on the Expanded Disability Status Scale, time to moderate disability, progression index, and treatment discontinuation due to inefficacy. Results: We found no association between the e4 allele and any of the variables. The e2 allele was associated with increased time to moderate disability. Conclusion: The e4 allele of ApoE has no prognostic value for the response to IFNβ-1b. The e2 allele delayed the progression of disability in our MS patient cohort. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The number of contrast-enhancing brain lesions is used as an endpoint in multiple sclerosis (MS) clinical trials. However, the incidence of asymptomatic contrast-enhancing brain lesions (AEBLs) in Japanese patients with MS has not been determined. Objective: To describe the number of AEBLs per scan in Japanese patients with relapsing-remitting MS (RRMS). Methods: We reviewed the medical records of 23 Japanese patients with RRMS who showed (1) a stable or improving condition for at least 30 days before a magnetic resonance imaging (MRI) examination and (2) at least one relapse in the preceding year or two relapses in the preceding 2 years. Results: The percentage of patients with AEBLs was 39.1% (9/23 patients) and the number of AEBLs per scan was 0.37. Conclusions: The results suggest that the disease activity shown by brain MRI was lower in Japanese patients with MS compared with that in Caucasian patients. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The patterns of Th1/Th2 cytokines in relapsing-remitting multiple sclerosis were analyzed to evaluate their relevance as biomarkers of therapy response to glatiramer acetate (GA). Serum interferon-γ (IFN-γ), osteopontin and interleukin (IL)-2, IL-4, and IL-10 were measured in 19 relapsing-remitting multiple sclerosis patients treated with GA in a prospective study over 3 years. The quotient (IL-2 + IFN-γ)/(IL-4 + IL-10) was elevated in patients with relapses as compared to relapse-free patients after 12 (p = 0.04), 24 (p = 0.02) and 36 months (p = 0.04). Our study indicates that specific patterns of Th1/Th2 cytokines predict the response to GA therapy. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The post-marketing international Global Adherence Project investigated adherence to disease-modifying therapy for relapsing-remitting multiple sclerosis. We report adherence data from the first 2 years in the Spanish subset of patients (n = 254 at baseline). The overall adherence rate was 85.4%. Patients taking intramuscular (IM) interferon-β (IFNβ)-1a were significantly more adherent (96.4%) compared with patients taking subcutaneous (SC) IFNβ-1a 22 μg (79.1%; p = 0.0064), SC IFNβ-1a 44 μg (79.6%; p = 0.0064) and glatiramer acetate (82.7%; p = 0.0184). At year 1 (n = 142), the overall adherence rate was 86.6%. Patients on IM IFNβ-1a were significantly more adherent than patients on SC IFNβ-1a 22 μg (93.9 vs. 66.7%; p = 0.0251). At year 2 (n = 131), the overall adherence rate was 82% (87.5% for IM IFNβ-1a, 80.0% for SC IFNβ-1a 22 μg, 77.8% for SC IFNβ-1a 44 μg, 85.2% for IFNβ-1b, and 80.0% for glatiramer acetate). In conclusion, adherence remained high among all disease-modifying therapies over the first 2 years of the study and was significantly higher for IM IFNβ-1a, at visit 1, compared with SC IFNβ-1a. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Objective: It was the aim of this study to determine the prevalence of anti-aquaporin 4 antibody (anti-AQP4 Ab) and long spinal cord lesions in neuromyelitis optica (NMO) and multiple sclerosis (MS) patients in Taiwan. Asia has a relatively high rate of NMO compared with MS patients. Anti-AQP4 Ab is an important marker for NMO worldwide, but serological data and clinical profiles of NMO patients in Taiwan have not been reported. Methods: This retrospective study compared the clinical symptoms, demographics, spinal cord lesion length and AQP4 Ab status of 34 patients with NMO with 34 patients diagnosed with conventional MS. Results: Our NMO patients were predominantly middle-aged women (median age 45 years), exhibited many relapses (1.0/year) and displayed a higher Expanded Disability Status Scale score (4.75) than conventional MS patients. NMO patients exhibited long spinal cord lesions as detected by MRI. Forty-one percent of the NMO patients had detectable anti-AQP4 Ab. The Expanded Disability Status Scale score was significantly higher in AQP4 Ab- NMO patients. Conclusion: The prevalence of AQP4 Ab in a Taiwanese NMO group was 41%. Long spinal cord lesions and detection of AQP4 Ab helped to differentiate NMO patients from MS patients. Long spinal cord lesions with the anti-AQP4 Ab test may allow for an earlier diagnosis of NMO and improve therapeutic decisions. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Severe side effects such as cardiotoxicity and leukemia limit long-term use of mitoxantrone (MTX) despite its recommendation in patients with malignant forms of relapsing remitting (RR) and secondary progressive (SP) multiple sclerosis (MS). Methods: We analyzed data on tolerability, measured as compliance with the treatment, and patients' acceptance of an alternative MTX treatment schedule in 12 patients with aggressive RRMS or SPMS treated for at least 3 years with low/delayed dose MTX. Results: Twelve patients received 9-17 cycles of MTX treatment, with individual median doses of 7.6-12.16 mg/m2/course during 36 to 114 (median 49.5) months resulting in cumulative doses of 101.9-143.0 mg/m2 per patient. The overall follow-up period was 37-122 (median 69.5) months. Treatment was well tolerated and appreciated by patients according to the Treatment Satisfaction-Visual Analogue Scale. No significant safety findings were seen concerning cardiological, hematological and oncological follow-up. The patients showed a stabilization of disease progression and a reduced annual relapse rate. Conclusions: Delayed, and/or dose-reduced, long-term MTX regimens over several years might represent a feasible alternative treatment for MS patients without any other therapeutic options. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Iran was formerly considered to be located in a low prevalence zone for multiple sclerosis (MS). During the last decade the number of patients has increased. This study was conducted to estimate the prevalence of MS in the capital city of the country. Methods: We re-evaluated the files of all patients who had registered at the Iranian Multiple Sclerosis Society during a 10-year period. Results: 8,146 patients (72.3% female, 27.7% male) with a female-to-male ratio of 2.60 had registered. Mean age of disease onset was 27.24 (SD: 8.32). A relapsing-remitting pattern was recognized in 84.9% of the patients. The number of new registrations tripled from 2002 to 2008 and the female-to-male ratio increased from 2 to 3.12. The prevalence of MS in Tehran is estimated to be at least 51.9 per 100,000. Visual impairment was the main presenting symptom. Conclusions: It seems that the prevalence of MS has increased to a medium-to-high risk level in Iran. The mean age of onset was similar to other studies but the calculated prevalence of early onset MS was increased. The cumulative data indicates that the female-to-male ratio is increasing annually. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Estimates of the prevalence of cognitive impairment among patients with multiple sclerosis (MS) range between 40 and 70%. The current cerebral functional system (CFS) of the Expanded Disability Status Scale (EDSS) is subjective. Aim: To define a new cerebral functional system (NCFS) based on neuropsychological evaluation (NE). Methods: We prospectively included 215 MS patients. NE evaluated cognitive functions. Fatigue was assessed with the Fatigue Impact Scale. The NCFS was devised with grades from 0 to 5, excluding depression but including fatigue. Grade 1 of the NCFS was integrated in the EDSS as other functional scores. The NCFS and new EDSS including the NCFS were compared with the current CFS and EDSS. Results: 215 patients (69% women, 67% with relapsing-remitting MS, median EDSS 3.0) were assessed. 98% of these patients presented fatigue and/or cognitive impairment with the NCFS compared to 62% with the CFS. The NCFS was higher than the CFS, and the EDSS had changed in 31% of the 113 patients with an EDSS <3.5. Change in functional score was not correlated to current age or age at onset of MS. Conclusions: We propose a new CFS grading based on NE, including fatigue, and integrating grade 1 at EDSS. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Natalizumab inhibits adherence of leukocytes to the cerebral endothelium. Since leukocytes play a role in regulating vascular tone, natalizumab may also affect cerebral vasoregulation. The aim of this observational study was to investigate whether neurovascular coupling and cerebral autoregulation are altered following routine clinical infusion of natalizumab in patients with relapsing-remitting multiple sclerosis. Methods: In 18 patients receiving regular infusion of 300 mg natalizumab, neurovascular coupling to visual stimulation and dynamic cerebral autoregulation (phase and gain of 0.1-Hz oscillations) were measured by transcranial Doppler ultrasound (before, and 2 h and 2 days after the infusion). A repeated examination 28 days after infusion served as a control situation. Results: Neurovascular coupling was altered 2 h and 2 days after infusion with an overshooting initial hemodynamic response. After 28 days, neurovascular coupling was similar to values before the infusion. Dynamic cerebral autoregulation, cerebral blood flow velocity and pulsatility index in the middle and posterior cerebral artery were unaltered. Conclusion: Natalizumab infusion is associated with a temporarily increased initial hyperemia to functional activation. Such a hyperreactivity suggests an increased bioavailability of nitric oxide during functional activation. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: The onset of multiple sclerosis (MS) in Greece has not been systematically studied. We sought to provide data on the onset of MS in Greece with detailed information regarding initial symptoms, and to confirm the prognostic significance of demographic and clinical factors at onset. Methods: We studied 1,034 consecutive patients with MS and independently assessed 265 patients ‘seen at onset’. We used the MS severity score and survival analysis (time to reach an Expanded Disability Status Scale score of 4.0) to evaluate the prognostic significance of factors at onset. Results: Female-to-male ratio was 1.9:1 and mean age at onset was 30.7 ± 9.9 years. MS was primary progressive in 9.6%. Initial symptoms were optic neuritis in 20.1%, brainstem dysfunction in 14.7%, dysfunction of long tracts in 49.3%, cerebral dysfunction in 1% and a combination of symptoms in 14.9%. In ‘seen at onset’ patients, detailed data on initial symptoms are presented. Female gender, earlier age at onset, ‘bout onset’ and onset with optic neuritis were associated with less severe disease and longer time to disability. Conclusion: The onset of MS in Greece is similar to Western populations. Initial symptoms are within the expected spectrum. Prognostic significance of factors at onset is as previously identified. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]