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Despite intensive research, the aetiology of multiple sclerosis (MS) remains unknown. Cerebrospinal fluid proteomics has the potential to reveal mechanisms of MS pathogenesis, but analyses must account for disease heterogeneity. We previously reported explorative multivariate analysis by hierarchical clustering of proteomics data of MS patients and controls, which resulted in two groups of individuals. Grouping reflected increased levels of intrathecal inflammatory response proteins and decreased levels of proteins involved in neural development in one group relative to the other group. MS patients and controls were present in both groups. Here we reanalysed these data and we also reanalysed data from an independent cohort of patients diagnosed with clinically isolated syndrome (CIS), who have symptoms of MS without evidence of dissemination in space and/or time. Some, but not all, CIS patients had intrathecal inflammation. The analyses reported here identified a common protein signature of MS/CIS that was not linked to elevated intrathecal inflammation. The signature included low levels of complement proteins, semaphorin-7A, reelin, neural cell adhesion molecules, inter-alpha-trypsin inhibitor heavy chain H2, transforming growth factor beta 1, follistatin-related protein 1, malate dehydrogenase 1 cytoplasmic, plasma retinol-binding protein, biotinidase, and transferrin, all known to play roles in neural development. Low levels of these proteins suggest that MS/CIS patients suffer from abnormally low oxidative capacity that results in disrupted neural development from an early stage of the disease. [ABSTRACT FROM AUTHOR]

Aim: The International Paediatric Multiple Sclerosis Study Group (IPMSSG) has proposed criteria for acute disseminated encephalomyelitis (ADEM) not evaluated in clinical practice. Our objective was to assess epidemiological implications of the IPMSSG criteria for ADEM in a cohort study using prospectively collected data.Method: We identified all diagnosed cases of ADEM in Denmark between 2008 and 2015 from the Danish National Patient Register by International Classification of Diseases 10 codes assigned to acute demyelinating episodes, and we reviewed all medical records to validate ADEM.Results: We found 52 children up to the age of 18 years with a verified clinical diagnosis of ADEM (incidence rate 0.54/100 000 person-years; all had abnormal brain magnetic resonance imaging). Only 18 (35%) fulfilled the IPMSSG criteria regarding encephalopathy and polyfocal neurological deficits. Among all 52 children with ADEM, 33 per cent had clinical sequelae after a median follow-up of 4 years 6 months (range: 10mo-8y 3mo). Surprisingly, none progressed to multiphasic ADEM or multiple sclerosis, but median age at end of follow-up was only 10 years 9 months (range: 2y-24y 3mo).Interpretation: Among 52 children with ADEM, none converted to multiphasic ADEM or multiple sclerosis (median follow-up: 4y 6mo; range: 10mo-8y 3mo). Applying the IPMSSG criteria to all children with a diagnosis of ADEM leaves 65 per cent of the cases without a diagnosis and lowers the incidence rate of paediatric ADEM.What This Paper Adds: The incidence of paediatric acute disseminated encephalomyelitis (ADEM) was 0.54 per 100 000 person-years in children younger than 18 years. Only 35 per cent of children with ADEM fulfilled the International Paediatric Study Group consensus criteria. ADEM in clinical practice was primarily based on magnetic resonance imaging findings. Paediatric neurologists diagnosed ADEM in the absence of encephalopathy. None of the children with ADEM progressed to multiple sclerosis/multiphasic ADEM during follow-up. [ABSTRACT FROM AUTHOR]

Background: The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability. Objectives: (1) To assess the current literature and available data on functional performance outcome measures (PerfOs) and (2) to determine suitability of using PerfOs to quantify MS disability in MS clinical trials. Methods: (1) Identify disability dimensions common in MS; (2) conduct a comprehensive literature review of measures for those dimensions; (3) develop an MS Clinical Data Interchange Standards Consortium (CDISC) data standard; (4) create a database of standardized, pooled clinical trial data; (5) analyze the pooled data to assess psychometric properties of candidate measures; and (6) work with regulatory agencies to use the measures as primary or secondary outcomes in MS clinical trials. Conclusion: Considerable data exist supporting measures of the functional domains ambulation, manual dexterity, vision, and cognition. A CDISC standard for MS (http://www.cdisc.org/therapeutic#MS) was published, allowing pooling of clinical trial data. MSOAC member organizations contributed clinical data from 16 trials, including 14,370 subjects. Data from placebo-arm subjects are available to qualified researchers. This integrated, standardized dataset is being analyzed to support qualification of disability endpoints by regulatory agencies. [ABSTRACT FROM AUTHOR]

Although immune attack against central nervous system (CNS)myelin is a central feature of multiple sclerosis (MS), its root cause is unresolved. In this report, we provide direct evidence that subtle biochemical modifications to brain myelin elicit pathological immune responses with radiological and histological properties similar to MS lesions. A subtle myelinopathy induced by abbreviated cuprizone treatment, coupled with subsequent immune stimulation, resulted in lesions of inflammatory demyelination. The degree of myelin injury dictated the resulting immune response; biochemical damage that was too limited or too extensive failed to trigger overt pathology. An inhibitor of peptidyl arginine deiminases (PADs), enzymes that alter myelin structure and correlate with MS lesion severity, mitigated pathology even when administered only during the myelin-altering phase. Moreover, cultured splenocytes were reactive against donor myelin isolates, a response that was substantially muted when splenocytes were exposed to myelin from donors treated with PAD inhibitors. By showing that a primary biochemical myelinopathy can trigger secondary pathological inflammation, "cuprizone autoimmune encephalitis" potentially reconciles conflicting theories about MS pathogenesis and provides a strong rationale for investigating myelin as a primary target for early, preventative therapy. [ABSTRACT FROM AUTHOR]

The article focuses on the mitigation of in multi-regional trials implementation in multiple sclerosis (MS). Topics discussed include the brief introduction of MS, its treatment, its causes such as infection and environment, the development of its drug, the clinical trials in MS, and the mitigation strategies like protocol design, participation burden for patients, and factors related to therapy.

Introduction: To estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated. Objectives and Methods: This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption and work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, from the societal perspective, in EUR 2015. Results: A total of 382 patients (mean age: 54 years) participated in the Netherlands; 81% were below retirement age and of these, 31% were employed. Employment was inversely related to disease severity, and MS affected productivity at work for 82% of patients. Overall, 96% and 73% of patients experienced fatigue and cognitive difficulties, respectively, as a problem. Mean utility and annual costs were 0.744 and €23,100 at Expanded Disability Status Scale (EDSS) 0–3, 0.595 and €32,300 at EDSS 4–6.5, and 0.297 and €50,500 at EDSS 7–9. The mean cost of a relapse was estimated at €3000. Conclusion: This study provides current data on MS in the Netherlands that are important for the development of health policies and to estimate the value of current and future treatments. [ABSTRACT FROM AUTHOR]

Introduction: In order to estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated. Objectives and methods: This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption and work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, from the societal perspective, in EUR 2015. Results: A total of 1010 patients (mean age = 45 years) participated in Italy. In total, 94% were below retirement age, and of these, 56% were employed. Employment was related to disability, and MS affected productivity at work in 77% of the patients. Overall, 96% and 65% of the patients experienced fatigue and cognitive difficulties as a problem, respectively. Mean utility and total annual costs were 0.735 and €22,900 at Expanded Disability Status Scale (EDSS) of 0–3, 0.534 and €40,100 at EDSS of 4–6.5, and 0.135 and €53,300 at EDSS of 7–9. The mean cost of a relapse was estimated to be €2600. Conclusion: This study illustrates the burden of MS on Italian patients and provides current data on MS that are important for the development of health policies. [ABSTRACT FROM AUTHOR]

Introduction: In order to estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated. Objectives and methods: This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption and work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of disability, from the societal perspective, in EUR (2015). Results: A total of 779 patients (mean age = 57 years) participated; 72% were below retirement age and of these, 36% were employed. Employment was related to disease severity, and MS affected productivity at work for 84% of patients. Overall, 96% and 72% of the patients experienced fatigue and cognition as a problem. Mean utility and annual costs were 0.735 and 11,400GBP at Expanded Disability Status Scale (EDSS) = 0–3, 0.534 and 22,700GBP at EDSS = 4–6.5, and 0.135 and 36,500GBP at EDSS = 7–9. The mean cost of a relapse was estimated at 790GBP. Conclusion: This study illustrates the burden of MS on UK patients and provides current data on MS that are important for development of health policies. [ABSTRACT FROM AUTHOR]

Background: In order to estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated. Objective and methods: This study is part of a cross-sectional retrospective study in 16 European countries collecting current data on resource consumption, work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, from the societal perspective, in 2015 Polish Zloty (PLN). Results: A total of 411 MS patients (mean age = 40 years) participated in Poland; 94% were below retirement age, and of these, 59% were employed. Employment was related to disability, and MS affected productivity for 85% of those working. Overall, 97% and 71% of patients experienced fatigue and cognition as important problems, respectively. Mean utility and total annual costs were 0.686 and 48,700 PLN at Expanded Disability Status Scale (EDSS) 0–3, 0.521 and 59,200 PLN at EDSS 4–6.5 and 0.208 and 81,600 PLN at EDSS 7–9, respectively. The average cost of a relapse was 3,900 PLN. Conclusion: This study illustrates the burden of MS on Polish patients and provides current data that are important for developing health policies. [ABSTRACT FROM AUTHOR]

Background: In order to assess the value of management strategies in multiple sclerosis (MS), outcome data have to be combined with cost data. This, in turn, requires that cost data be regularly updated. Objective and methods: This study is part of a cross-sectional retrospective study in 16 countries collecting current data on resource consumption, work capacity and health-related quality of life (HQoL). Descriptive analyses are presented by level of severity; costs are estimated in the societal perspective, in RUB 2015. Results: A total of 208 patients (mean age: 38.5 years) participated in the Russian study; 97% were below retirement age, and of these, 49% were employed. MS was reported to affect productivity at work in 63% of patients. Overall, 87% and 41% of patients felt that fatigue and cognition were a problem. The mean utility and costs were 0.769 and 578,000 RUB at Expanded Disability Status Scale (EDSS) 0–3, 0.509 and 826,000 RUB at EDSS 4–6.5, and 0.071 and 1,013,000 RUB at EDSS 7–9. The average cost of a relapse was 33,000 RUB. Conclusion: This study illustrates the burden of MS on Russian patients and provides current data that are important for developing health policies. [ABSTRACT FROM AUTHOR]

Background: In order to assess the value of management strategies in multiple sclerosis (MS), outcome data have to be combined with cost data. This, in turn, requires that cost data be regularly updated. Objective and methods: This study is part of a cross-sectional retrospective study in 16 countries collecting current data on resource consumption, work capacity and health-related quality of life (HRQoL). Descriptive analyses are presented by level of severity; costs are estimated in the societal perspective, in EUR 2015. Results: A total of 535 patients (mean age 48.5 years) participated; 92% were below retirement age and of these, 43% were employed. Employment was related to disease severity, and MS was felt to affect productivity at work by 72% of patients, most often through fatigue. Overall, 98% and 74% of patients felt that fatigue and cognition were a problem. Mean utility and costs were 0.756 and €16,500 at the Expanded Disability Status Scale (EDSS) 0–3, 0.572 and €28,700 at EDSS 4–6.5 and 0.206 and €34,400 at EDSS 7–9. The average cost of a relapse was estimated at €2930. Conclusion: This study illustrates the burden of MS on Portuguese patients and provides current data that are important for the development of health policies. [ABSTRACT FROM AUTHOR]

Introduction: To estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated. Objectives and methods: This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption and work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, from the societal perspective, in CHF 2015. Results: A total of 721 patients (mean age 48 years) participated in Switzerland; 90% were below retirement age, and of these, 65% were employed. Employment was related to disease severity, and MS affected productivity at work for 69% of patients. Overall, 93% and 64% of patients experienced fatigue and cognition as a problem, respectively. The mean utility and annual costs were 0.799 and 29,600CHF at Expanded Disability Status Scale (EDSS) 0–3, 0.614 and 66,800CHF at EDSS 4–6.5 and 0.348 and 110,800CHF at EDSS 7–9, respectively. The mean cost of a relapse was estimated at 7600CHF. Conclusion: This study provides current data on MS in Switzerland that are important for development of health policies and to estimate the value of current and future treatments. [ABSTRACT FROM AUTHOR]

Background: To assess the value of management strategies in multiple sclerosis (MS), outcome data have to be combined with cost data. This requires that cost data be regularly updated. Objective and methods: This study is part of a cross-sectional retrospective study in 16 countries collecting current data on resource consumption, work capacity and health-related quality of life (HRQoL). Descriptive analyses are presented by level of severity; costs are estimated in the societal perspective, in 2015 SEK. Results: A total of 1864 patients (mean age 56 years) participated in Sweden; 74% were below retirement age, and of these, 55% were employed. MS was reported to affect productivity at work in 78% of patients. Overall, 94% and 72% of patients felt that fatigue and cognition were a problem, respectively. The mean utility and costs were 0.757 and 244,000SEK at Expanded Disability Status Scale (EDSS) 0–3, 0.563 and 384,000SEK at EDSS 4–6.5 and 0.202 and 888,000SEK at EDSS 7–9, respectively. The average cost of a relapse was 36,900SEK. Conclusion: This study illustrates the burden of MS on Swedish patients and provides current data that are important for the development of health policies. [ABSTRACT FROM AUTHOR]

Introduction: In order to estimate the value of interventions in multiple sclerosis (MS) where lifetime costs and outcomes cannot be observed, outcome data have to be combined with costs. This requires that cost data be regularly updated. Objectives and methods: This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption, work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, from the societal perspective, in EUR 2015. Results: A total of 462 patients (mean age 43 years) participated in Spain; 96% were below retirement age and of these, 45% were employed. Employment was related to disability, and MS affected productivity at work for 72% of those working. Overall, 92% and 64% of patients experienced fatigue and cognitive difficulties as a problem, respectively. Mean utility and total annual costs were estimated at 0.772 and €20,600 at Expanded Disability Status Scale (EDSS) 0–3, 0.486 and €48,500 at EDSS 4–6.5 and 0.182 and €68,700 at EDSS 7–9, respectively. The mean cost of a relapse was €2050. Conclusion: This study illustrates the burden of MS on Spanish patients and provides current data that are important for development of health policies. [ABSTRACT FROM AUTHOR]

Introduction: In order to estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated. Objectives and methods: This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption and work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, from the societal perspective, in EUR 2015. Results: A total of 1856 patients (mean age: 54 years) participated in Belgium; 66% were below retirement age, and of these, 44% were employed. Employment was related to disease severity, and MS affected productivity at work in 85% of the patients. Overall, 95% and 72% of the patients experienced fatigue and cognitive difficulties, respectively, as a problem. Mean utility and annual costs were 0.703 and €26,400 at Expanded Disability Status Scale (EDSS) 0–3, 0.478 and €45,300 at EDSS 4–6.5, and 0.193 and €62,000 at EDSS 7–9. The mean cost of a relapse was estimated to be €3000. Conclusion: This study provides current data on MS in Belgium that are important for development of health policies and for estimating the value of current and future treatments. [ABSTRACT FROM AUTHOR]

Introduction: To estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated. Objectives and methods: This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption and work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, from the societal perspective, in EUR 2015. Results: A total of 5475 patients (mean age 52 years) participated in Germany. In all, 84% were below retirement age, and of these, 51% were employed. Employment was related to disease severity, and MS affected productivity at work for 80% of patients. Overall, 96% and 78% of patients experienced fatigue and cognitive difficulties as a problem, respectively. The mean utility and total annual costs were 0.786 and 28,200€ at Expanded Disability Status Scale (EDSS) 0–3, 0.586 and €44,000 at EDSS 4–6.5 and 0.273 and €62,700 at EDSS 7–9, respectively. The mean cost of a relapse was estimated at €2500. Conclusion: This study provides current health economic data on MS in Germany that are important for the development of health policies and for estimating the value of the current and future treatments. [ABSTRACT FROM AUTHOR]

Background: To estimate the value of treatments in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with cost data. This, in turn, requires that cost data be regularly updated. Objectives and Methods: This study is part of a cross-sectional retrospective study in 16 countries collecting current data on resource consumption, work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, from the societal perspective, in 2015 Danish Kronor (DKK). Results: A total of 830 patients (mean age of 54 years) participated; 78% were below retirement age and of these, 43% were employed. Employment was related to disease severity, and MS was felt to affect productivity at work by 73% of patients, most often through fatigue. Overall, 95% and 65% of patients felt that fatigue and cognition, respectively, were a problem. Mean utility and costs were 0.770 and 196,900DKK at Expanded Disability Status Scale (EDSS) 0–3, 0.619 and 287,300DKK at EDSS 4–6.5, and 0.302 and 533,250DKK at EDSS 7–9. The average cost of a relapse was estimated at 19,000DKK. Conclusion: This study illustrates the burden of MS on Danish patients and provides current data that are important for the development of health policies. [ABSTRACT FROM AUTHOR]

Introduction: To estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated. Objectives and methods: This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption and work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, in the societal perspective, in EUR 2015. Results: A total of 491 patients (mean age 47 years) participated; 82% were below retirement age, and of these 56% were employed. Employment was related to disease severity, and MS affected productivity at work for 90% of patients. Overall, 95% and 67% of patients experienced fatigue and cognition as a problem, respectively. The mean utility and annual costs were 0.735 and €22,600 at Expanded Disability Status Scale (EDSS) 0–3, 0.500 and €38,100 at EDSS 4–6.5, and 0.337 and €48,100 at EDSS 7–9, respectively. The average cost of a relapse was estimated at €2300. Conclusion: This study provides current data on MS in France that are important for developments of health policies and to estimate the value of current and future treatments. [ABSTRACT FROM AUTHOR]

Introduction: In order to estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated. Objectives and methods: This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption and work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, in the societal perspective, in CZK 2015. Results: A total of 747 patients (mean age 47 years) participated; 86% were below retirement age and of these, 49% were employed. Employment was related to disease severity, and MS affected productivity at work for 82% of those working. Overall, 92% and 66% of patients experienced fatigue and cognitive difficulties as a problem. Mean utility and annual costs were 0.832 and 257,000CZK at Expanded Disability Status Scale (EDSS) 0–3, 0.530 and 425,500CZK at EDSS 4–6.5 and 0.141 and 489,000CZK at EDSS 7–9. The average cost of a relapse was estimated at 12,600CZK. Conclusion: This study provides current data on MS in the Czech Republic that are important for the development of health policies. [ABSTRACT FROM AUTHOR]

Introduction: To estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated. Objectives and methods: This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption, work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of disability, from the societal perspective, in HUF 2015. Results: A total of 521 patients (mean age 47 years) participated; 85% were below retirement age, and of these, 47% were employed. Employment was related to disability and MS affected productivity at work for 82% of those working. Overall, 94% and 66% of patients experienced fatigue and cognitive difficulties as a problem, respectively. The mean utility and annual costs were 0.691 and 3,432,000HUF at Expanded Disability Status Scale (EDSS) 0–3, 0.491 and 5,262,000HUF at EDSS 4–6.5 and 0.076 and 6,235,000HUF at EDSS 7–9, respectively. The average cost of a relapse was estimated at 240,500HUF. Conclusion: This study illustrates the burden of MS on Hungarian patients and provides current data that are important for the development of health policies. [ABSTRACT FROM AUTHOR]

Introduction: This article describes the methods used to perform this large European-wide burden-of-illness study on multiple sclerosis (MS) using individual patient data. Methods: The study collected all MS-related resource consumption, workforce participation, prevalent disease symptoms and health-related quality of life (HRQoL). Patients were recruited by national patient associations and, after informed consent, completed a specific questionnaire either on-line or on paper. Analyses were performed by country as well as for the study overall. Costs were estimated from the societal perspective, using publicly available unit costs and reported in national currencies and in EUR 2015 adjusted for purchasing power parity. The results are reported by disease severity groups according to self-assessed Expanded Disability Status Scale (EDSS) (mild, moderate, severe) and by EDSS point to highlight the development of costs as disability progresses. Results: A total of 16,808 patients in 16 countries participated in the study: Austria, Belgium, Denmark, Czech Republic, France, Germany, Hungary, Italy, the Netherlands, Poland, Portugal, Russia, Spain, Sweden, Switzerland and the United Kingdom. Conclusion: This study, endorsed by the European Platform of MS Societies, provides up-to-date information on costs and expands the previously available information on HRQoL and symptoms. [ABSTRACT FROM AUTHOR]

Introduction: In order to estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated. Objectives and Methods: This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption and work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, from the societal perspective, in EUR 2015. Results: A total of 516 patients (mean age, 53 years) participated in Austria; 72% were below retirement age, and of these, 46% were employed. Employment was related to disability, and MS affected productivity at work for 77% of those working. Overall, 94% and 67% of patients experienced fatigue and cognition as a problem. Mean utility and total annual costs were 0.778 and 25,100€ at Expanded Disability Status Scale (EDSS) 0–3, 0.579 and 44,100€ at EDSS 4–6.5, and 0.244 and 73,800€ at EDSS 7–9. The mean cost of a relapse was estimated at 2563€. Conclusion: This study illustrates the burden of MS on Austrian patients and provides current data on MS that are important for development of health policies. [ABSTRACT FROM AUTHOR]

Background: Autoantibodies, in particular those against aquaporin-4 and myelin-oligodendrocyte glycoprotein (MOG), aid as biomarkers in the differential diagnosis of demyelination. Here, we report on discovery of autoantibodies against flotillin in patients with multiple sclerosis (MS).Methods: The target antigen was identified by histo-immunoprecipitation using the patients' sera and cryosections of rat or pig cerebellum combined with mass spectrometrical analysis. Correct identification was ascertained by indirect immunofluorescence and neutralization tests using the target antigens recombinantly expressed in HEK293 cells.Results: Serum and CSF of the index patient produced a fine-granular IgG indirect immunofluorescence staining of the hippocampal and cerebellar molecular layers. Flotillin-1 and flotillin-2 were identified as target autoantigens. They also reacted with recombinant human flotillin-1/2 co-expressed in HEK293 cells, but not with the individual flotillins in fixed- and live-cell assays. Moreover, neutralization using flotillin-1/2, but not the single flotillins, abolished the tissue reactivity of patient serum. Screening of 521 patients, for whom anti-aquaporin-4 testing was requested and negative, revealed 8 additional patients with anti-flotillin-1/2 autoantibodies. All eight were negative for anti-MOG. Six patients ex post fulfilled the revised McDonald criteria for MS. Vice versa, screening of 538 MS sera revealed anti-flotillin-1/2 autoantibodies in eight patients. The autoantibodies were not found in a cohort of 67 patients with other neural autoantibody-associated syndromes and in 444 healthy blood donors.Conclusions: Autoantibodies against the flotillin-1/2 heterocomplex, a peripheral membrane protein that is involved in axon outgrowth and regeneration of the optic nerve, are present in 1-2% of patients with bona fide MS. [ABSTRACT FROM AUTHOR]

The article discusses several studies related to multiple sclerosis as discussed at the Annual RIMS Conference held in 2017. Topics discussed include balance right in multiple sclerosis; comparison between patients with multiple sclerosis and Parkinson disease; and randomized controlled trial of a home-based palliative approach for people with severe multiple sclerosis.

Background: Intermittent theta burst stimulation (iTBS) of the primary motor cortex improves transiently lower limbs spasticity in multiple sclerosis (MS). However, the cerebral mechanisms underlying this effect have never been investigated. Objective: To assess whether modulation of spasticity induced by iTBS is underlined by functional reorganization of the primary motor cortices. Methods: A total of 17 patients with MS suffering from lower limbs spasticity were randomized to receive real iTBS or sham iTBS during the first half of a 5-week indoor rehabilitation programme. Spasticity was assessed using the Modified Ashworth Scale and the Visual Analogue Scale at baseline, after the stimulation session and at the end of the rehabilitation programme. Resting-state functional magnetic resonance imaging (fMRI) was performed at the three time points, and brain functional networks topology was analysed using graph-theoretical approach. Results: At the end of stimulation, improvement of spasticity was greater in real iTBS group than in sham iTBS group (p = 0.026). iTBS had a significant effect on the balance of the connectivity degree between the stimulated and the homologous primary motor cortex (p = 0.005). Changes in inter-hemispheric balance were correlated with improvement of spasticity (rho = 0.56, p = 0.015). Conclusion: This longitudinal resting-state fMRI study evidences that functional reorganization of the primary motor cortices may underlie the effect of iTBS on spasticity in MS. [ABSTRACT FROM AUTHOR]

Background: Information processing speed (IPS) is a prevalent cognitive impairment in multiple sclerosis (MS). Objectives: This review aims to summarize the methods applied to assess IPS in MS and its theoretical conceptualization. A PubMed search was performed to select articles published between 1 January 2004 and 31 December 2013, resulting in 157 articles included. Results: The majority (54%) of studies assessed IPS with heterogeneous samples (several disease courses). Studies often report controlling for presence of other neurological disorders (60.5%), age (58.6%), education (51.6%), alcohol history (47.8%), or use of steroids (39.5%). Potential confounding variables, such as recent relapses (50.3%), history of developmental disorders (19.1%), and visual problems (29.9%), were often neglected. Assessments used to study IPS were heterogeneous (ranging from simple to complex tasks) among the studies under review, with 62 different tasks used. Only 9.6% of articles defined the construct of IPS and 22.3% discussed IPS in relation to a theoretical model. Future directions: The challenges for the upcoming decade include clarification of the definition of IPS as well as its theoretical conceptualization and a consensus on assessment. Based on the results obtained, we propose a new theoretical model, the tri-factor model of IPS. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is a highly heterogeneous disease; the quantitative assessment of disease progression is problematic for many reasons, including the lack of objective methods to measure disability and the long follow-up times needed to detect relevant and stable changes. For these reasons, the importance of prognostic markers, markers of response to treatments and of surrogate endpoints, is crucial in multiple sclerosis research. Aim of this report is to clarify some basic definitions and methodological issues about baseline factors to be considered prognostic markers or markers of response to treatment; to define the dynamic role that variables must have to be considered surrogate markers in relation to specific treatments. [ABSTRACT FROM AUTHOR]

Background and purpose Growth hormone (GH)/insulin-like growth factor 1 ( IGF-1) axis abnormalities in multiple sclerosis ( MS) suggest their role in its pathogenesis. Interferon β ( IFN-β) efficacy could be mediated also by an increase of IGF-1 levels. A 2-year longitudinal study was performed to estimate the prevalence of GH and/or IGF-1 deficiency in clinically isolated syndrome ( CIS) patients and their correlation with conversion to MS in IFN treated patients. Methods Clinical and demographic features of CIS patients were collected before the start of IFN-β-1b. IGF-1 levels and GH response after arginine and GH releasing hormone + arginine stimulation tests were assessed. Clinical and magnetic resonance imaging evaluations were performed at baseline, 1 year and 2 years. Results Thirty CIS patients (24 female) were enrolled. At baseline, four patients (13%) showed a hypothalamic GH deficiency ( GHD), whilst no one had a pituitary GHD. Baseline demographic, clinical and radiological data were not related to GHD, whilst IGF-1 levels were inversely related to age ( P < 0.001) and GH levels ( P = 0.03). GH and IGF-1 serum mean levels were not significantly modified after 1 and 2 years of treatment in the whole group, although 3/4 GHD patients experienced a normalization of GH levels, whilst one dropped out. After 2 years of treatment 13/28 (46%) patients converted to MS. The presence of GHD and GH and IGF-1 levels were not predictive of relapses, new T2 lesions or conversion occurrence. Conclusions Growth hormone/ IGF-1 axis function was found to be frequently altered in CIS patients, but this was not related to MS conversion. Patients experienced an improvement of GHD during IFN therapy. Longer follow-up is necessary to assess its impact on disease progression. [ABSTRACT FROM AUTHOR]

Memory impairment is an early and disabling manifestation of multiple sclerosis whose anatomical and biological substrates are still poorly understood. We thus investigated whether memory impairment encountered at the early stage of the disease could be explained by a differential vulnerability of particular hippocampal subfields. By using experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, we identified that early memory impairment was associated with selective alteration of the dentate gyrus as pinpointed in vivo with diffusion-tensor-imaging (DTI). Neuromorphometric analyses and electrophysiological recordings confirmed dendritic degeneration, alteration in glutamatergic synaptic transmission and impaired long-term synaptic potentiation selectively in the dentate gyrus, but not in CA1, together with a more severe pattern of microglial activation in this subfield. Systemic injections of the microglial inhibitor minocycline prevented DTI, morphological, electrophysiological and behavioral impairments in EAE-mice. Furthermore, daily infusions of minocycline specifically within the dentate gyrus were sufficient to prevent memory impairment in EAE-mice while infusions of minocycline within CA1 were inefficient. We conclude that early memory impairment in EAE is due to a selective disruption of the dentate gyrus associated with microglia activation. These results open new pathophysiological, imaging, and therapeutic perspectives for memory impairment in multiple sclerosis. [ABSTRACT FROM AUTHOR]

Objective: Proton density (PD) mapping requires correction for the receive profile (RP), which is frequently performed via bias-field correction. An alternative RP-mapping method utilizes a comparison of uncorrected PD-maps and a value ρ(T1) directly derived from T1-maps via the Fatouros equation. This may be problematic in multiple sclerosis (MS), if respective parameters are only valid for healthy brain tissue. We aimed to investigate whether the alternative method yields correct PD values in MS patients. Materials/methods: PD mapping was performed on 27 patients with relapsing-remitting MS and 27 healthy controls, utilizing both methods, yielding reference PD values (PD, bias-field method) and PD (alternative method). Results: PD-values closely matched PD, both for patients and controls. In contrast, ρ(T1) differed by up to 3 % from PD and the voxel-wise correlation between PD and ρ(T1) was reduced in a patient subgroup with a higher degree of disability. Still, discrepancies between ρ(T1) and PD were almost identical across different tissue types, thus translating into a scaling factor, which cancelled out during normalization to 100 % in CSF, yielding a good agreement between PD and PD. Conclusion: RP correction utilizing the auxiliary parameter ρ(T1) derived via the Fatouros equation provides accurate PD results in MS patients, in spite of discrepancies between ρ(T1) and actual PD values. [ABSTRACT FROM AUTHOR]

Background and purpose Birth cohort effects have greatly shaped long-term trends in multiple sclerosis ( MS). This study examined whether birth cohort effects have also determined trends in the sex ratio. Methods Age−period−cohort analyses were applied to Swiss mortality data, 1901−2010, using logit models. Sex was introduced as an additional main effect (overall effect) and in interaction terms with A, P and C. Results Birth cohort effects strongly impacted the trends of MS risk in Switzerland, with a peak in cohorts born in the 1910s and 1920s. Similarly, birth cohort effects accounted for the change in the sex ratios during the 20th century. The balanced sex ratio at the beginning of the 20th century has been superseded by a ratio with a preponderance of women. Despite similarities in timing, the patterns of overall and sex-specific birth cohort estimates were not congruent. Conclusion The change in the sex ratio in MS is driven by birth cohort related factors. Overall and sex-specific trends indicate that the appearance of MS has changed dramatically in the 20th century. The driving force behind these trends is related to yet unknown environmental factors. [ABSTRACT FROM AUTHOR]

To investigate the occurrence of vascular comorbidities before and after the clinical onset of multiple sclerosis. In this combined case-control and cohort study, all Danish born citizens with onset of multiple sclerosis 1980-2005 were identified from the Danish Multiple Sclerosis Registry and randomly matched with controls regarding year of birth, gender, and municipality on January 1st in the year of multiple sclerosis (MS) onset (index date). Individual-level information on comorbidities was obtained from several independent nationwide registries and linked to the study population by unique personal identification numbers. To assess the presence of vascular comorbidities before and after MS onset, cases and controls were followed from January 1977 to the index date, and from the index date through December 2012. We used logistic regression to calculate odds ratios (ORs) and Cox regression to calculate hazard ratios (HRs). Before the index date, MS cases had a decreased probability for cerebrovascular comorbidity [OR 0.69 (95 % CI 0.48-0.99, p = 0.043)], and a numerically but not statistically significant decreased probability for cardiovascular comorbidity [OR 0.87 (95 % CI 0.71-1.07, p = 0.188)]. After the index date, MS cases had an increased risk for cerebrovascular comorbidity [HR 1.84 (95 % CI 1.69-2.00, p < 0.0005)], and for cardiovascular comorbidity [HR 1.08 (95 % CI 1.02-1.15, p = 0.013)]. The lower occurrence of cerebrovascular comorbidities in cases prior to MS onset could be due to protective immune mechanisms, while the higher occurrence of vascular comorbidities in cases after MS onset could be because of converging causal pathways of the coexisting diseases. These findings deserve to be studied closer in a broader spectrum of comorbidities in MS. [ABSTRACT FROM AUTHOR]

Background Anxiety and depression are common in multiple sclerosis ( MS). We evaluated the prevalence and factors associated with anxiety, depression and fatigue at the 5-year review of a longitudinal cohort study following a first clinical diagnosis of CNS demyelination ( FCD). Methods Cases with a FCD were recruited soon after diagnosis and followed annually thereafter. A variety of environmental, behavioural and clinical covariates were measured at five-year review. Anxiety and depression were measured using the Hospital Anxiety & Depression Scale ( HADS), and fatigue by the Fatigue Severity Scale ( FSS). Results Of the 236 cases, 40.2% had clinical anxiety (median HADS-A: 6.0), 16.0% had clinical depression (median HADS-D: 3.0), and 41.3% had clinical fatigue (median FSS: 4.56). The co-occurrence of all three symptoms was 3.76 times greater than expectation. Younger age, higher disability, concussion or other disease diagnosis were independently associated with a higher anxiety score; male sex, higher disability, being unemployed, less physical activity, and antidepressant and/or anxiolytic-sedative medication use were independently associated with a higher depression score. Higher disability, immunomodulatory medication use, other disease diagnosis and anxiolytic-sedative medication use were independently associated with having fatigue, while female sex, higher BMI, having had a concussion, being unemployed and higher disability were associated with a higher fatigue score. Conclusion These results support previous findings of the commonality of anxiety, depression and fatigue in established MS and extend this to post- FCD and early MS cases. The clustering of the three symptoms indicates that they may share common antecedents. [ABSTRACT FROM AUTHOR]

Objectives The purpose of our study is to investigate whether socioeconomic indicators such as education, financial concerns, employment, and living status are associated with disease progression in relapsing-onset and progressive-onset Multiple Sclerosis ( MS). Materials and methods We performed a cross-sectional survey among individuals with MS, registered by the Flemish MS society and included socioeconomic indicators. A Cox proportional hazard regression was performed with the time from MS onset and from birth to reach an ambulatory disability milestone corresponding to Expanded Disability Status Scale ( EDSS) 6 (requiring a cane) as outcome measure, adjusted for gender, age at MS onset, and immunomodulatory treatment. Results Among the participants with relapsing-onset MS, subjects reporting education for more than 12 years had a reduced risk of reaching EDSS 6 compared to subjects reporting education for less than 12 years [ HR from onset 0.68 (95% CI 0.49-0.95); HR from birth 0.71 (95% CI 0.51-0.99)]. In progressive-onset MS, longer education was associated with an increased hazard to reach EDSS 6 [ HR from onset 1.25 (95% CI 0.91-1.70); HR from birth 1.39 (95% CI 1.02-1.90)]. Conclusions Our study shows an association of self-reported levels of education with disability progression in MS, with the highest level being protective in relapsing-onset MS. [ABSTRACT FROM AUTHOR]

Objective The aims of the present study were to examine psychometric properties of the Spielberger State-Trait Anxiety Inventory ( STAI-Y-1 and STAI-Y-2, respectively) in a Multiple Sclerosis ( MS) population and to identify a cut-off score to detect those MS patients with high level of state and/or trait anxiety who could be more vulnerable to development of depression and/or cognitive defects. Material and methods The STAI-Y-1 and STAI-Y-2 was completed by a group of patients ( n = 175) affected by MS and a group of healthy subjects ( n = 150) matched for age, educational level, and gender. In MS patients internal consistency, divergent and discriminant validities were evaluated. Construct validity was examined by exploratory factor analysis for each scale. Results There was no missing data, no floor or ceiling effects for both scales. The two scales showed high internal consistency, good divergent, and Known-groups validities. To identify high levels of state and trait anxiety in a patient with MS, we proposed three gender specific screening cut-off values (1, 1.5, 2 SD) for the STAI-Y-1 and the STAI-Y-2. Conclusions The findings showed that the STAI-Y-1 and the STAI-Y-2 are a valid tool for clinical use in MS patients and can be useful to measure the severity of anxiety and to identify those patients with high anxiety to introduce them in specific non-pharmacological intervention. [ABSTRACT FROM AUTHOR]

Background: No molecular marker can monitor disease progression and treatment efficacy in multiple sclerosis (MS). Circulating microparticles represent a potential snapshot of disease activity at the blood brain barrier. Objectives and methods: To profile plasma microparticles by flow cytometry in MS and determine how fingolimod could impact endothelial microparticles production. Results: In non-treated MS patients compared to healthy and fingolimod-treated patients, endothelial microparticles were higher, while B-cell-microparticle numbers were lower. Fingolimod dramatically reduced tumour necrosis factor (TNF)-induced endothelial microparticle release in vitro. Conclusion: Fingolimod restored dysregulated endothelial and B-cell-microparticle numbers, which could serve as a biomarker in MS. [ABSTRACT FROM AUTHOR]

Objective: To compare the frequency and pattern of cognitive impairment (CI) between patients with neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). Methods: A total of 82 NMOSD patients, 58 MS patients, and 45 healthy controls (HCs) underwent a neuropsychological assessment. Results: CI was observed in 29% of NMOSD and 50% of MS patients (p < 0.001); CI was considered present if a patient scored lower than the fifth percentile compared with HCs in at least three domains. A lower frequency of CI was consistently found when CI was indicated by at least two failed tests (p < 0.001). MS patients performed worse than did NMOSD patients on verbal learning and verbal and visual memory tests. Levels of education and depression and the interval from disease onset to treatment were associated with a negative influence on cognition in patients with NMOSD. Conclusion: CI in patients with NMOSD may be not as common as in patients with MS. MS patients exhibited severe impairment, particularly on learning and memory tests, compared with NMOSD patients. Differential prevalence and patterns of CI between NMOSD and MS patients suggest that the two diseases have different mechanisms of brain injury. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether fatigue is a consequence or a predictive trait of disease worsening. Objective: To investigate the predictive value of fatigue toward conversion to confirmed moderate–severe disability in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: We retrospectively selected from the Comprehensive Longitudinal Investigations in MS at the Brigham and Women’s Hospital (CLIMB) study cohort RRMS patients who converted to confirmed (⩾2 years) Expanded Disability Status Scale (EDSS) score ⩾3 within a follow-up period ⩾3 years. We contrasted the Modified Fatigue Impact Scale (MFIS) score of 33 converters, obtained at least 1 year before conversion to EDSS ⩾3, with that of 33 non-converter RRMS patients matched for baseline characteristics. Results: Total MFIS score was higher in converter versus non-converter MS patients (median 37 vs 13; p < 0.0001). EDSS and Center for Epidemiological Studies Depression scale (CES-D) scores were also higher in the converters (median EDSS 1.5 vs 0, p < 0.0001; median CES-D 30 vs 24, p < 0.0001) and were both associated with MFIS score (EDSS: rho = 0.42, p = 0.0005; CES-D: rho = 0.72, p < 0.0001). After adjusting for EDSS and CES-D in multivariate analysis, MFIS remained a significant predictor of subsequent conversion to confirmed EDSS ⩾3. Conclusion: Fatigue is a promising indicator of risk for conversion to confirmed moderate–severe disability in RRMS patients. [ABSTRACT FROM AUTHOR]

Background: Epidemiological findings suggest a relationship between multiple sclerosis (MS) and cardiovascular disease (CVD) risk factors, although the nature of this relationship is not well understood. Objective: We used genome-wide association study (GWAS) data to identify shared genetic factors (pleiotropy) between MS and CVD risk factors. Methods: Using summary statistics from a large, recent GWAS (total n > 250,000 individuals), we investigated overlap in single nucleotide polymorphisms (SNPs) associated with MS and a number of CVD risk factors including triglycerides (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, body mass index, waist-to-hip ratio, type 2 diabetes, systolic blood pressure, and C-reactive protein level. Results and conclusion: Using conditional enrichment plots, we found 30-fold enrichment of MS SNPs for different levels of association with LDL and TG SNPs, with a corresponding reduction in conditional false discovery rate (FDR). We identified 133 pleiotropic loci outside the extended major histocompatibility complex with conditional FDR < 0.01, of which 65 are novel. These pleiotropic loci were located on 21 different chromosomes. Our findings point to overlapping pathobiology between clinically diagnosed MS and cardiovascular risk factors and identify novel common variants associated with increased MS risk. [ABSTRACT FROM AUTHOR]

Background: Using diffusion tensor imaging (DTI), it was previously found that demyelinated gray matter (GM) lesions have increased fractional anisotropy (FA) when compared to normal-appearing gray matter (NAGM) in multiple sclerosis (MS). The biological substrate underlying this FA change is so far unclear; both neurodegenerative changes and microglial activation have been proposed as causal contributors. Objective: To test the proposed hypothesis that microglia activation is responsible for increased FA in cortical GM lesions. Methods: We investigated post-mortem cortical DTI changes in hemispheric, coronally cut sections and investigated the underlying histopathology using immunohistochemistry. Results: Overall, there were few activated microglia/macrophages, and no difference between GM lesions and NAGM was observed. However, cell density was increased in GM lesions compared to NAGM (309.67 ± standard deviation (SD) 124.44 vs 249.95 ± SD 56.75, p = 0.002). Conclusion: FA increase was not due to lesional and non-lesional differences in microglia activation and/or proliferation. We found an increase in general cellular density without a notable difference in cellular size, that is, tissue compaction, as a possible alternative explanation. [ABSTRACT FROM AUTHOR]

Background: Cognitive and motor abilities in multiple sclerosis (MS) are typically quantified using reliable, consensus standard tests validated in the MS population. While these performance measures are associated with vocational disability in parametric analyses, translation of raw scores into anchors reflecting clinically relevant, functional impairment requires further research. Objective: To examine performance-based motor and cognitive outcomes among definitive anchors that designate varying degrees of functional impairment, thereby establishing benchmarks for score interpretation. Methods: We evaluated MS patients and healthy controls, all undergoing a brief test battery. Outcomes were derived from the MS Functional Composite (MSFC) and the Brief International Cognitive Assessment for MS (BICAMS). Functional impairment anchors were (1) disability benefits, (2) employed with negative work events, and (3) employed without problems. Results: All measures yielded statistically significant differences across all levels of work status, after accounting for the effects of age and education. Benchmark values distinguished the functional impairment groups. When evaluated in combination, the Timed 25-Foot Walk and the Symbol Digit Modalities Test were the most robust predictors of functional decline. Conclusion: We have established benchmark scores for popular motor and cognitive tests that are associated with specific degrees of impairment in work status. [ABSTRACT FROM AUTHOR]

Background: Although many individuals with multiple sclerosis (MS) experience depression, there are no studies on the frequency and effect of peripartum depression among parents with MS. Objective: To examine the frequency of peripartum depression in individuals with MS and its potential association with children’s psychiatric disorders. Methods: We conducted a cohort study in British Columbia, Canada, using linked health databases, of parents with MS and their children, and age-matched unaffected parent–child dyads. The diagnosis of peripartum depression, MS and psychiatric disorders in children was based on information from hospital admission, physician visit and drug prescription claims. Results: Peripartum depression was significantly more common among MS parents (n = 360) versus unaffected (n = 1207) parents (25.8% vs 18.5%, p value 0.02), especially among MS affected fathers versus unaffected fathers (25.7% vs 10.2%, p value < 0.001). The incidence of psychiatric disorders in children was 3.3 and 2.7 per 100 child-years among children with and without an MS parent, respectively. The rate of psychiatric disorders was significantly higher in children with an MS parent (vs without, hazard ratio (HR): 1.34; 95% confidence interval (CI): 1.03–1.74) and among children with parents who had peripartum depression (HR: 1.87; 95% CI: 1.36–2.55). Conclusion: Parental MS is associated with a higher risk of peripartum depression and increases the risk of psychiatric disorders in children. [ABSTRACT FROM AUTHOR]

Background: Glycosylation alterations have been associated with the development of several human diseases and their animal models, including multiple sclerosis. Objectives: We aimed to determine whether immunoglobulin G galactosylation might be changed in multiple sclerosis. Methods: Immunoglobulin G was isolated from serum and cerebrospinal fluid of patients with multiple sclerosis or viral meningitis and control patients without history of inflammatory or autoimmune disease. A lectin-based assay was used to investigate potential galactosylation modifications of immunoglobulin G. Results and conclusion: Galactosylation of immunoglobulin G isolated from cerebrospinal fluid of control patients was found to be age- and gender-dependent. In addition, immunoglobulin G galactosylation was significantly altered in cerebrospinal fluid but not in serum of multiple sclerosis patients. Furthermore, this modification was correlated with an active progression of multiple sclerosis. Finally, the loss of galactosyl moieties was not simply associated with inflammation as no such change was detected in viral meningitis patients characterized by brain inflammation. [ABSTRACT FROM AUTHOR]

Background: The transparent ocular structure enables quantitative analysis of microvasculature of retina, a neuronal tissue affected by multiple sclerosis (MS). Objective: The aim of this study was to determine whether the retinal blood flow velocity and flow volume at the macula are impaired in patients with relapsing remitting multiple sclerosis (RRMS). Methods: A total of 17 RRMS patients and 17 age- and gender-matched healthy subjects were assessed. A retinal function imager was used to measure the blood flow velocity of retinal arterioles and venules and to calculate the total perifoveal blood flow volume. Results: The blood flow velocities of the retinal arterioles (3.34 ± 0.89 mm/s) and venules (2.61 ± 0.6 mm/s) were significantly lower in MS patients than normal subjects (arteriole: 4.10 ± 0.87 mm/s; venule: 3.22 ± 0.65 mm/s, both p = 0.01). In addition, the total perifoveal blood flow volume in arterioles (3.74 ± 1.64 nL/s) and venules (3.81 ± 1.60 nL/s) were significantly lower in MS patients than in normal subjects (arteriole: 4.87 ± 1.41 nL/s, p = 0.02; venule: 4.71 ± 1.64 nL/s, p = 0.04). Conclusion: The impaired retinal microcirculation in RRMS patients indicates microvascular dysfunction in MS. [ABSTRACT FROM AUTHOR]