Multiple Sclerosis International The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Comparison of Antioxidant Status and Vitamin D Levels between Multiple Sclerosis Patients and Healthy Matched Subjects Mon, 14 Apr 2014 12:54:20 +0000 Objective. The aim of the present study was to compare the serum levels of total antioxidant status (TAS) and 25(OH) D3 and dietary intake of multiple sclerosis (MS) patients with those of normal subjects. Method. Thirty-seven MS patients (31 women) and the same number of healthy matched controls were compared for their serum levels and dietary intake of 25(OH) D3 and TAS. Sun exposure and the intake of antioxidants and vitamin D rich foods were estimated through face-to-face interview and food frequency questionnaire. Results. Dietary intake of antioxidants and vitamin D rich foods, vitamin C, vitamin A, and folate was not significantly different between the two groups. There were also no significant differences in the mean levels of 25(OH) D3 and TAS between the study groups. Both groups had low serum levels of 25(OH) D3 and total antioxidants. Conclusion. No significant differences were detected in serum levels and dietary intake of vitamin D and antioxidants between MS patients and healthy controls. All subjects had low antioxidant status and vitamin D levels. Ehsan Hejazi, Reza Amani, Naser SharafodinZadeh, and Bahman Cheraghian Copyright © 2014 Ehsan Hejazi et al. All rights reserved. Oral Dalfampridine Improves Standing Balance Detected at Static Posturography in Multiple Sclerosis Thu, 27 Mar 2014 09:37:09 +0000 We report a 14-week post-marketing experience on 20 patients with multiple sclerosis (MS) who started prolonged-release (PR) oral dalfampridine 10 mg twice daily according to European Medicine Agency criteria. They underwent serial static posturography assessments and the dizziness handicap inventory (DHI) to investigate whether PR dalfampridine could impact standing balance and self-reported perception of balance. The incidence of accidental falls per person per month was also recorded throughout the study. Eight (40%) patients, who had a relevant improvement in walking speed, were defined as treatment responders. They showed a significant improvement of standing balance (with respect to pretreatment assessment) when contrasted with 12 (60%) nonresponders ( = 3.959, ). No significant changes in DHI score, as well as in its functional, physical, and emotional subscales, were found in both responders and nonresponders at the end of study (all P values are ≥0.2). Treatment response did not affect the incidence of accidental falls. Future studies based on larger sample sizes, and with longer followup, are required to confirm the beneficial effect of PR dalfampridine on standing balance. Luca Prosperini, Costanza Giannì, Deborah Fortuna, Maria Rita Marchetti, and Carlo Pozzilli Copyright © 2014 Luca Prosperini et al. All rights reserved. Correlations between MRI and Information Processing Speed in MS: A Meta-Analysis Tue, 25 Mar 2014 13:03:41 +0000 Objectives. To examine relationships between conventional MRI measures and the paced auditory serial addition test (PASAT) and symbol digit modalities test (SDMT). Methods. A systematic literature review was conducted. Included studies had ≥30 multiple sclerosis (MS) patients, administered the SDMT or PASAT, and measured T2LV or brain atrophy. Meta-analysis of MRI/information processing speed (IPS) correlations, analysis of MRI/IPS significance tests to account for reporting bias, and binomial testing to detect trends when comparing correlation strengths of SDMT versus PASAT and T2LV versus atrophy were conducted. Results. The 39 studies identified frequently reported only significant correlations, suggesting reporting bias. Direct meta-analysis was only feasible for correlations between SDMT and T2LV (, ) and atrophy in patients with mixed-MS subtypes (, ). Familywise Holm-Bonferroni testing found that selective reporting was not the source of at least half of significant results reported. Binomial tests () favored SDMT over PASAT in strength of MRI correlations. Conclusions. A moderate-to-strong correlation exists between impaired IPS and MRI in mixed MS populations. Correlations with MRI were stronger for SDMT than for PASAT. Neither heterogeneity among populations nor reporting bias appeared to be responsible for these findings. S. M. Rao, A. L. Martin, R. Huelin, E. Wissinger, Z. Khankhel, E. Kim, and K. Fahrbach Copyright © 2014 S. M. Rao et al. All rights reserved. Oxygen Cost of Walking in Persons with Multiple Sclerosis: Disability Matters, but Why? Thu, 06 Mar 2014 07:19:02 +0000 Background. The oxygen cost (O2 cost) of walking is elevated in persons with MS, particularly as a function of increasing disability status. Objective. The current study examined symptomatic (i.e., fatigue, pain, anxiety, and depression) and gait (i.e., velocity, cadence, and step length) variables that might explain why disability status is associated with O2 cost of walking in persons with MS. Materials and Methods. 82 participants completed the Patient-Determined Disease Steps, Fatigue Severity Scale, McGill Pain Questionnaire, and Hospital Anxiety and Depression Scale and undertook 2 trials of walking on a GAITRite electronic walkway. Participants then completed a six-minute walk test with concurrent assessment of expired gases for quantifying oxygen consumption and O2 cost of walking. Results. Disability () as well as fatigue (), gait velocity (), cadence (), and step length () were associated with the O2 cost of walking. Cadence (), but not step length () or fatigue (), explained the association between disability and the O2 cost of walking. Conclusions. These results highlight cadence as a target of rehabilitation for increasing metabolic efficiency during walking among those with MS, particularly as a function of worsening disability. Brian M. Sandroff, Rachel E. Klaren, Lara A. Pilutti, and Robert W. Motl Copyright © 2014 Brian M. Sandroff et al. All rights reserved. What Do Healthcare Providers Advise Women with Multiple Sclerosis Regarding Pregnancy? Wed, 05 Mar 2014 15:54:18 +0000 Pregnancy in multiple sclerosis (MS) is considered safe for both the woman and the child. Nevertheless, pregnancy issues in MS are complex both from a patient’s and a provider’s perspective. In an anonymous survey, 28 healthcare providers in the United States reported on the management of multiple sclerosis (MS) during pregnancy. Participants were asked about their recommendations to patients about the use of disease modifying therapies during pregnancy and breastfeeding and general recommendations about MS and pregnancy. Healthcare providers were also asked about sources from which they receive information about the management of patients with MS. Results suggested that healthcare providers do not discourage pregnancy for women with MS, recommend that women not use disease modifying therapies while pregnant, and have a positive view of breastfeeding for women with MS. Results also indicated the need for guidelines on patient management for pregnant women with MS. Annette Wundes, Roxanna N. Pebdani, and Dagmar Amtmann Copyright © 2014 Annette Wundes et al. All rights reserved. Fatigue Is Associated with Poor Sleep in People with Multiple Sclerosis and Cognitive Impairment Wed, 05 Mar 2014 13:31:44 +0000 Background. Fatigue is the most common symptom in people with multiple sclerosis (MS). Poor sleep also occurs in this population. Objective. The objective of this study was to determine the relationship between fatigue and sleep quality in people with MS and cognitive impairment. Method. This cross-sectional study assessed relationships among fatigue, assessed with the Modified Fatigue Impact Scale (MFIS) and the Fatigue Severity Scale (FSS), sleep quality assessed with the Pittsburg Sleep Quality Index (PSQI), and demographics in 121 people with MS and cognitive impairment. Results. Fatigue was significantly correlated with poor sleep quality (MFIS: , ; FSS: , ). FSS scores were also significantly correlated with the PSQI subscore for daytime dysfunction and MFIS scores were significantly correlated with disability, age, and the PSQI subscores for sleep quality, sleep duration, and daytime dysfunction. Conclusions. This study demonstrates a relationship between fatigue and sleep quality in individuals with MS and cognitive impairment. Michelle H. Cameron, Vanessa Peterson, Eilis A. Boudreau, Ashley Downs, Jesus Lovera, Edward Kim, Garnett P. McMillan, Aaron P. Turner, Jodie K. Haselkorn, and Dennis Bourdette Copyright © 2014 Michelle H. Cameron et al. All rights reserved. Costs of Formal and Informal Home Care and Quality of Life for Patients with Multiple Sclerosis in Sweden Tue, 04 Mar 2014 14:59:29 +0000 Disease progression in multiple sclerosis leads to dramatic changes in a person's ability to perform daily activities and increases reliance on external help. This study aims to describe and to estimate costs of formal/informal home care and quality of life related to multiple sclerosis. A mailed survey to a random sample of MS sufferers collected data on the number of hours of home care received, type of help, productivity losses, quality of life, and disease characteristics. Costs for home care were estimated in 2012 € and factors that may influence the likelihood of getting home care were also evaluated. Formal care was given to 27% of the respondents at an average of 238.7 hrs/month at a mean monthly cost of €2873/person with MS. Informal care was received by 49% of the respondents at an average of 47.3 hrs/month at a mean monthly cost of €389/person with MS. Utilities across disease severity are as follows: mild MS = 0.709 (sd = 0.233), moderate MS = 0.562 (sd = 0.232), and severe MS = 0.284 (sd = 0.283). Total home care costs increased with increasing disease severity. Informal caregiving contributes significantly to MS home care in Sweden. Marianne Svensson and Liberty Fajutrao Copyright © 2014 Marianne Svensson and Liberty Fajutrao. All rights reserved. Does Fatigue Complaint Reflect Memory Impairment in Multiple Sclerosis? Sun, 02 Mar 2014 00:00:00 +0000 Background and Purpose. Fatigue and memory impairment are common symptoms in multiple sclerosis (MS) and both may interact with cognition. This can contribute to making a complaint misrepresentative of the objective disorder. We sought to determine whether fatigue complaint in MS reflects memory impairment and investigated whether patients’ subjective fatigue is associated with memory complaint. Methods. Fifty MS patients complaining of fatigue underwent subjective assessment of fatigue and memory complaint measured using self-assessment scales. Cognitive functions were assessed using a battery of neuropsychological tests, including a test of verbal episodic memory, the selective reminding test (SRT). Correlations were studied between subjective fatigue, memory complaint, and performance in verbal episodic memory. Results. Depression score, psychotropic and/or antiepileptic drug use, Expanded Disability Status Scale (EDSS) score, and MS form were confounding factors. After adjusting for these confounding factors, neither fatigue complaint nor memory complaint was correlated with SRT performance. Subjective fatigue was significantly associated with memory complaint. Conclusion. Although complaint of fatigue in MS was correlated with memory complaint, subjective fatigue was not the expression of memory impairment. Caroline Jougleux-Vie, Emeline Duhin, Valerie Deken, Olivier Outteryck, Patrick Vermersch, and Hélène Zéphir Copyright © 2014 Caroline Jougleux-Vie et al. All rights reserved. Spatial Analysis of Global Prevalence of Multiple Sclerosis Suggests Need for an Updated Prevalence Scale Sun, 16 Feb 2014 15:25:45 +0000 Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with an unknown aetiology. MS has a geographic pattern of prevalence with high prevalence rates between 45 degrees and 65 degrees north. In much of the northern hemisphere, there exists a prevalence gradient, with increasing prevalence from south to north. While genetics may partially explain the latitudinal gradient, it is not strong enough to exclude exogenous variables. Kurtzke initially came up with a three-zone scale for low, medium, and high prevalence zones. He defined high as 30 or more per 100,000, medium as 5–29 per 100,000, and low as less than 5 per 100,000. In this study, 131 geographic datasets (geocases) were spatially analyzed to determine whether the existing global prevalence scale needed to be updated. The mean prevalence rate was 67.83/100,000 with rates ranging from 350/100,000 to 0/100,000. The results of this study suggest that the commonly referenced scale for global MS prevalence needs to be updated with added zones to reflect significantly higher prevalence rates in some areas of the world. We suggest a five-zone scale: very high (170–350), high (70–170), medium (38–70), low (13–38), and very low (0–13). Brett J. Wade Copyright © 2014 Brett J. Wade. All rights reserved. Periventricular Lesions Help Differentiate Neuromyelitis Optica Spectrum Disorders from Multiple Sclerosis Sun, 09 Feb 2014 12:17:25 +0000 Objective. To compare periventricular lesions in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOsd). Materials and Methods. Sagittal and axial fluid attenuated inversion recovery (FLAIR) sequences of 20 NMOsd and 40 group frequency-matched MS patients were evaluated by two neuroradiologists. On axial FLAIR, periventricular area was characterized as free of lesions/smooth-bordered (“type A”) or jagged-bordered (“type B”) pattern. On sagittal FLAIR, the images were evaluated for presence of “Dawson’s fingers.” Results. Type A pattern was observed in 80% of NMOsd patients by Reader 1 and 85% by Reader 2 but only in 5% MS patients by either Reader. Type B was seen in 15% NMOsd patients by Reader 1 and 20% by Reader 2 and in 95% MS patients by either Reader. Dawson’s fingers were observed in no NMOsd patients by Reader 1 and 5% by Reader 2. In MS, Dawson’s fingers were seen in 92.5% patients by Reader 1 and 77.5% by Reader 2. The differences in periventricular patterns and Dawson’s finger detection between NMOsd and MS were highly significant (). Conclusions. Dawson’s fingers and “jagged-bordered” periventricular hyperintensities are typical of MS and almost never seen in NMOsd, which suggests a practical method for differentiating the two diseases. Eytan Raz, John P. Loh, Luca Saba, Mirza Omari, Joseph Herbert, Yvonne Lui, and Ilya Kister Copyright © 2014 Eytan Raz et al. All rights reserved. Comparisons of Costs between Black Caribbean and White British Patients with Advanced Multiple Sclerosis in the UK Wed, 05 Feb 2014 06:31:27 +0000 Background. Multiple sclerosis (MS) is now more common among black and minority ethnic groups in the UK but little is known about the costs of care amongst different ethnic groups. Objective. This study examined and compared service use and costs for people severely affected with MS from Black Caribbean (BC) and White British (WB) backgrounds in the UK and identified predictors of cost for both groups. Method. Population-based cross-sectional study of 43 BC and 43 WB patients with MS (EDSS ≥ 6) and their informal caregivers recruited from an MS service in southeast London. Interviews collected data on health and social service use and informal care support. Costs were calculated using UK unit cost data. Using regression analyses we compared costs between the ethnic groups and identified possible predictors of cost. Results. The mean (SD) costs for the WB and BC groups were £25,778 (£39,387) and £23,186 (£30,433), respectively. Results identified no significant difference in total cost between the two ethnic groups. The EDSS score alone was a significant predictor of cost. Conclusion. Similar costs between ethnic groups indicate that with regard to this MS service and geographical area, access to care was not affected by ethnicity. Wayne Smith, Paul McCrone, Cassie Goddard, Wei Gao, Rachel Burman, Diana Jackson, Irene Higginson, Eli Silber, and Jonathan Koffman Copyright © 2014 Wayne Smith et al. All rights reserved. The Prevalence of Familial Multiple Sclerosis in Saskatoon, Saskatchewan Mon, 03 Feb 2014 09:29:43 +0000 Background. A population-based prevalent cohort of 150 clinical definite multiple sclerosis (MS) cases (102 women; 48 men) ascertained on January 1, 1977, Saskatoon, Saskatchewan, was found to have a familial rate of MS as 17.3%. Objectives. To determine the occurrence of familial MS cases and the frequency of MS among the biological relatives of the study cohort. Methods. The search for new familial cases MS affected relatives continued for 35 years until 2012. The natural history of the disease of sporadic cases is compared with that of the familial cases. SPSS V19 and Kaplan-Meier survival analysis were used for data analysis. Results. Of the 150 unrelated MS patients, 49 cases (32.7%) (36 women and 13 men) were reported of having at least one family member with MS. There were a total of 86 affected relatives, 26 (30.2%) first-degree relatives, 15 (17.4%) second-degree relatives, 20 (23.3%) third-degree relatives, and 25 (29.1%) distant relatives. The average age of MS onset for men with sporadic MS was 33.9 (SD = 10) years and 27.6 (SD = 8.4) years for familial cases and 29.3 (SD = 8.3) years and 26.8 (SD = 8.5) years for women. Conclusion. This 35-year longitudinal natural history study reveals a high frequency of cases with family members developing MS and supports a genetic influence in the etiology of MS. Walter J. Hader and Irene M. Yee Copyright © 2014 Walter J. Hader and Irene M. Yee. All rights reserved. Is Walking Capacity in Subjects with Multiple Sclerosis Primarily Related to Muscle Oxidative Capacity or Maximal Muscle Strength? A Pilot Study Wed, 29 Jan 2014 09:43:30 +0000 Background and Purpose. Walking capacity is reduced in subjects with multiple sclerosis (MS). To develop effective exercise interventions to enhance walking capacity, it is important to determine the impact of factors, modifiable by exercise intervention (maximal muscle strength versus muscle oxidative capacity), on walking capacity. The purpose of this pilot study is to discriminate between the impact of maximal muscle strength versus muscle oxidative capacity on walking capacity in subjects with MS. Methods. From 24 patients with MS, muscle oxidative capacity was determined by calculation of exercise-onset oxygen uptake kinetics (mean response time) during submaximal exercise bouts. Maximal muscle strength (isometric knee extension and flexion peak torque) was assessed on dynamometer. All subjects completed a 6-minute walking test. Relationships between walking capacity (as a percentage of normal value) and muscle strength (of knee flexors and extensors) versus muscle oxidative capacity were assessed in multivariate regression analyses. Results. The expanded disability status score (EDSS) showed a significant univariate correlation (, ) with walking capacity. In multivariate regression analyses, EDSS and mean response time, but not muscle strength, were independently related to walking capacity (). Conclusions. Walking distance is, next to disability level and not taking neurologic symptoms/deficits into account, primarily related to muscle oxidative capacity in subjects with MS. Additional study is needed to further examine/verify these findings. Dominique Hansen, Peter Feys, Inez Wens, and Bert O. Eijnde Copyright © 2014 Dominique Hansen et al. All rights reserved. Gray Matters in Multiple Sclerosis: Cognitive Impairment and Structural MRI Wed, 22 Jan 2014 12:25:39 +0000 Multiple sclerosis (MS) is an immune-mediated disease affecting central nervous system (CNS). Although MS is classically considered a white matter (WM) disease, the involvement of gray matter (GM) in the pathogenic process has been confirmed by pathology studies and MRI studies. Impairment of cognitive domains such as memory, mental processing speed, attention, and executive function can occur from the early stage of the disease and tends to worsen over time, despite stable physical symptoms. WM demyelination is moderately correlated with CI, suggesting that probably WM abnormalities alone cannot fully explain the extent of clinical symptoms in MS, including CI. Several MRI techniques have shown the involvement of GM in MS and the association between GM damage, physical disability, and CI. The aim of this review is to provide an overview of CI and GM damage assessed by structural brain MRI. Silvia Messina and Francesco Patti Copyright © 2014 Silvia Messina and Francesco Patti. All rights reserved. The Effect of Community Exercise Interventions for People with MS Who Use Bilateral Support for Gait Thu, 02 Jan 2014 15:26:34 +0000 Background. Mobility limitations are a key feature of MS and 25% will require the use of a walking aid 15 years after diagnosis. Few studies have specifically evaluated the effectiveness of physiotherapy and exercise interventions delivered in the community for those with significant disability. Methods. An assessor blind, block randomised, and controlled study recruited participants who required bilateral assistance for gait and who occasionally used wheelchairs for longer distances. They were randomised to 10 weeks of group physiotherapy (balance and strengthening exercises), individual physiotherapy, yoga group, or a control group. Results. Repeated measures ANOVA found significant time effects for physical component of MSIS-29v2 (, ) and MFIS (, ). The group × time interaction was significant for the BBS (, ). Post hoc analysis revealed no difference between group and individual physiotherapy for BBS. There was no significant difference between groups but the 6MWT improved for individual physiotherapy () and MSIS-29v2 psychological score for group physiotherapy (). Discussion. This study found that balance and strengthening exercises, delivered in the community to those with significant mobility limitations, improve balance. The effect on walking endurance and patient-reported outcomes are unclear and warrants further investigation with a larger control group with similar baseline characteristics to the intervention groups. Neasa Hogan, Maria Kehoe, Aidan Larkin, and Susan Coote Copyright © 2014 Neasa Hogan et al. All rights reserved. Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics Thu, 26 Dec 2013 09:46:10 +0000 Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country. Objectives. To investigate the spectrum of multiple sclerosis in Malaysia. Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia. Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald’s criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders. Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here. S. Viswanathan, N. Rose, A. Masita, J. S. Dhaliwal, S. D. Puvanarajah, M. H. Rafia, and S. Muda Copyright © 2013 S. Viswanathan et al. All rights reserved. Future of Management of Multiple Sclerosis in the Middle East: A Consensus View from Specialists in Ten Countries Tue, 17 Dec 2013 13:19:37 +0000 The prevalence of multiple sclerosis (MS) is now considered to be medium-to-high in the Middle East and is rising, particularly among women. While the characteristics of the disease and the response of patients to disease-modifying therapies are generally comparable between the Middle East and other areas, significant barriers to achieving optimal care for MS exist in these developing nations. A group of physicians involved in the management of MS in ten Middle Eastern countries met to consider the future of MS care in the region, using a structured process to reach a consensus. Six key priorities were identified: early diagnosis and management of MS, the provision of multidisciplinary MS centres, patient engagement and better communication with stakeholders, regulatory body education and reimbursement, a commitment to research, and more therapy options with better benefit-to-risk ratios. The experts distilled these priorities into a single vision statement: “Optimization of patient-centred multidisciplinary strategies to improve the quality of life of people with MS.” These core principles will contribute to the development of a broader consensus on the future of care for MS in the Middle East. Mohammed Aljumah, Raed Alroughani, I. Alsharoqi, Saeed A. Bohlega, Maurice Dahdaleh, Dirk Deleu, Khaled Esmat, Ahmad Khalifa, Mohammad A. Sahraian, Miklós Szólics, Abdulrahman AlTahan, Bassem I. Yamout, Peter Rieckmann, and Abdulkader Daif Copyright © 2013 Mohammed Aljumah et al. All rights reserved. Diffusion Tensor Imaging in NAWM and NADGM in MS and CIS: Association with Candidate Biomarkers in Sera Tue, 17 Dec 2013 11:26:41 +0000 The aim of this study was to evaluate diffusion tensor imaging (DTI) indices in the corpus callosum and pyramidal tract in normal-appearing white matter (NAWM) and the caudate nucleus and thalamus in deep grey matter (NADGM) in all MS subtypes and clinically isolated syndrome (CIS). Furthermore, it was determined whether these metrics are associated with clinical measures and the serum levels of candidate immune biomarkers. Apparent diffusion coefficients (ADC) values were significantly higher than in controls in all six studied NAWM regions in SPMS, 4/6 regions in RRMS and PPMS and 2/6 regions in CIS. In contrast, decreased fractional anisotropy (FA) values in comparison to controls were detected in 2/6 NAWM regions in SPMS and 1/6 in RRMS and PPMS. In RRMS, the level of neurological disability correlated with thalamic FA values (, ). In chronic progressive subtypes and CIS, ADC values of NAWM and NADGM were associated with the levels of MIF, sFas, and sTNF-α. Our data indicate that DTI may be useful in detecting pathological changes in NAWM and NADGM in MS patients and that these changes are related to neurological disability. Renuka Natarajan, Sanna Hagman, Xingchen Wu, Ullamari Hakulinen, Minna Raunio, Mika Helminen, Maija Rossi, Prasun Dastidar, and Irina Elovaara Copyright © 2013 Renuka Natarajan et al. All rights reserved. Increased Female MS Incidence and Differences in Gender-Specific Risk in Medium- and High-Risk Regions in Finland from 1981–2010 Sun, 10 Nov 2013 13:11:10 +0000 Background. MS incidence has increased among females, suggesting the presence of environmental effect. Object. Regional differences and temporal changes in gender-specific MS incidence were studied in Finland. Methods. Cases from Jan 1, 1981 to Dec 31, 2010 in Pirkanmaa, Seinäjoki and Vaasa districts were included. The standardized incidence rates (SIR), incidences per 105 person years with 95% confidence intervals (CI), and female-to-male ratios (F/M) were determined by district. Results. 1617 cases were included. Compared to Pirkanmaa, the MS risk was 1.9-fold (95% CI: 1.7–2.0) greater in Seinäjoki and 1.2-fold (95% CI: 1.1–1.4) in Vaasa, and the risk was high for both genders. The incidence trend stabilized in Seinäjoki and Vaasa, accompanied by an increase in the F/M ratio. A steady increase in Pirkanmaa was accompanied by a high F/M ratio. Conclusion. A high female preponderance accompanied a general increase in incidence since the 1990s, suggesting the influence of environmental factors. In high-risk districts, increased MS risk prevailed in both genders. High risk reflects both genetic and environmental effects. These effects may be shared with autoimmune diseases such as type 1 diabetes mellitus; the incidence of which follows MS in Finland. Population-based case-control studies are needed to identify these factor effects. Markus Holmberg, Annukka Murtonen, Irina Elovaara, and Marja-Liisa Sumelahti Copyright © 2013 Markus Holmberg et al. All rights reserved. Autoimmune T-Cell Reactivity to Myelin Proteolipids and Glycolipids in Multiple Sclerosis Thu, 07 Nov 2013 18:02:30 +0000 Central nervous system (CNS) myelin, the likely major target of autoimmune attack in multiple sclerosis (MS), contains a number of unique components that are potential targets of the attack. Two classes of molecules that are greatly enriched in CNS myelin compared to other parts of the body are certain types of proteolipids and glycolipids. Due to the hydrophobic nature of both of these classes of molecules, they present challenges for use in immunological assays and have therefore been somewhat neglected in studies of T-cell reactivity in MS compared to more soluble molecules such as the myelin basic proteins and the extracellular domain of myelin oligodendrocyte glycoprotein. This review firstly looks at the makeup of CNS myelin, with an emphasis on proteolipids and glycolipids. Next, a retrospective of what is known of T-cell reactivity directed against proteolipids and glycolipids in patients with MS is presented, and the implications of the findings are discussed. Finally, this review considers the question of what would be required to prove a definite role for autoreactivity against proteolipids and glycolipids in the pathogenesis of MS. Judith M. Greer Copyright © 2013 Judith M. Greer. All rights reserved. The Contribution of Resting State Networks to the Study of Cortical Reorganization in MS Thu, 31 Oct 2013 08:25:33 +0000 Resting State fMRI (RS-fMRI) represents an emerging and powerful tool to explore brain functional connectivity (FC) changes associated with neurologic disorders. Compared to activation/task-related fMRI, RS-fMRI has the advantages that (i) BOLD fMRI signals are self-generated and independent of subject’s performance during the task and (ii) a single dataset is sufficient to extract a set of RS networks (RSNs) that allows to explore whole brain FC. According to these features RS-fMRI appears particularly suitable for the study of FC changes related to multiple sclerosis (MS). In the present review we will first give a brief description of RS-fMRI methodology and then an overview of most relevant studies conducted so far in MS by using this approach. The most interesting results, in particular, regard the default-mode network (DMN), whose FC changes have been correlated with cognitive status of MS patients, and the visual RSN (V-RSN) whose FC changes have been correlated with visual recovery after optic neuritis. The executive control network (ECN), the lateralized frontoparietal network (FPN), and the sensory motor network (SMN) have also been investigated in MS, showing significant FC rearrangements. All together, RS-fMRI studies conducted so far in MS suggest that prominent RS-FC changes can be detected in many RSNs and correlate with clinical and/or structural MRI measures. Future RS-fMRI studies will further clarify the dynamics and clinical impact of RSNs changes in MS. Rosaria Sacco, Simona Bonavita, Fabrizio Esposito, Gioacchino Tedeschi, and Antonio Gallo Copyright © 2013 Rosaria Sacco et al. All rights reserved. Growth Hormone and Disease Severity in Early Stage of Multiple Sclerosis Wed, 23 Oct 2013 09:17:47 +0000 Evidence suggests that neurohormones such as GH and IGF-I are involved in the neuroreparative processes in multiple sclerosis (MS). GH and IGF-I blood levels in naïve MS patients with different disease courses were investigated in this study. Serum GH and IGF-I in untreated MS patients (), healthy controls (HC, ), and patients affected by other neurological diseases (OND, ) were evaluated with a solid-phase-enzyme-labeled-chemiluminescent-immunometric assay. No differences were detected in GH across MS, OND, and HC ( ng/mL; ; and ; ) when considering gender, disease duration, and disease course. However, GH was lower () in patients with more severe disease (expanded disability scale score, ) compared with milder forms (). IGF-I l did not differ across the 3 groups (), as far as concern disease course, disability, and gender were. Lower IGF-I levels were detected in subjects older than 50 years compared to younger ones for all 3 groups. Lower GH was detected in patients with more severe MS, and age was confirmed as the main factor driving IGF-I levels in all subjects. These findings, relying on the natural course of the disease, could help in shedding lights on the mechanisms involved in autoreparative failure associated with poorer prognosis in MS. M. Gironi, C. Solaro, C. Meazza, M. Vaghi, L. Montagna, M. Rovaris, A. P. Batocchi, R. Nemni, R. Albertini, M. Zaffaroni, and M. Bozzola Copyright © 2013 M. Gironi et al. All rights reserved. Fatigue and Sleep-Disordered Breathing in Multiple Sclerosis: A Clinically Relevant Association? Tue, 22 Oct 2013 11:57:55 +0000 Background. Fatigue in patients with multiple sclerosis (MS) is highly prevalent and severely impacts quality of life. Recent studies suggested that sleep-disordered breathing (SDB) significantly contributes to fatigue in MS. Study Objective. To evaluate the importance of routine respirography in MS patients with severe fatigue and to explore the effects of treatment with continuous positive airway pressure (CPAP). Patients and Methods. We prospectively assessed the presence of severe fatigue, as defined by a score of ≥5.0 on the Fatigue Severity Scale (FSS), in 258 consecutive MS patients. Ninety-seven patients (38%) suffered from severe fatigue, whereof 69 underwent overnight respirography. Results. We diagnosed SDB in 28 patients (41%). Male sex was the only independent associate of SDB severity (). CPAP therapy in 6 patients was associated with a significant reduction of FSS scores ( versus , ), but the scores remained pathological (≥4.0) in all patients. Conclusion. Respirography in MS patients with severe fatigue should be considered in daily medical practice, because SDB frequency is high and CPAP therapy reduces fatigue severity. However, future work is needed to understand the real impact of CPAP therapy on quality of life in this patient group. Ulf Kallweit, Christian R. Baumann, Michael Harzheim, Hildegard Hidalgo, Dieter Pöhlau, Claudio L. Bassetti, Michael Linnebank, and Philipp O. Valko Copyright © 2013 Ulf Kallweit et al. All rights reserved. Effects of Walking Direction and Cognitive Challenges on Gait in Persons with Multiple Sclerosis Mon, 07 Oct 2013 09:45:58 +0000 Declines in walking performance are commonly seen when undergoing a concurrent cognitive task in persons with multiple sclerosis (MS). The purpose of this study was to determine the effect of walking direction and simultaneous cognitive task on the spatiotemporal gait parameters in persons with MS compared to healthy controls. Ten persons with MS (Median EDSS, 3.0) and ten healthy controls took part in this pilot study. Participants performed 4 walking trials at their self-selected comfortable pace. These trials included forward walking, forward walking with a cognitive task, backward walking, and backward walking with a cognitive task. Walking performance was indexed with measures of velocity, cadence, and stride length for each testing condition. The MS group walked slower with significantly reduced stride length compared to the control group. The novel observation of this investigation was that walking differences between persons with MS and healthy controls were greater during backward walking, and this effect was further highlighted during backward walking with added cognitive test. This raises the possibility that backward walking tests could be an effective way to examine walking difficulties in individuals with MS with relatively minimal walking impairment. Douglas A. Wajda, Brian M. Sandroff, John H. Pula, Robert W. Motl, and Jacob J. Sosnoff Copyright © 2013 Douglas A. Wajda et al. All rights reserved. Predicting Falls in People with Multiple Sclerosis: Fall History Is as Accurate as More Complex Measures Thu, 26 Sep 2013 09:04:38 +0000 Background. Many people with MS fall, but the best method for identifying those at increased fall risk is not known. Objective. To compare how accurately fall history, questionnaires, and physical tests predict future falls and injurious falls in people with MS. Methods. 52 people with MS were asked if they had fallen in the past 2 months and the past year. Subjects were also assessed with the Activities-specific Balance Confidence, Falls Efficacy Scale-International, and Multiple Sclerosis Walking Scale-12 questionnaires, the Expanded Disability Status Scale, Timed 25-Foot Walk, and computerized dynamic posturography and recorded their falls daily for the following 6 months with calendars. The ability of baseline assessments to predict future falls was compared using receiver operator curves and logistic regression. Results. All tests individually provided similar fall prediction (area under the curve (AUC) 0.60–0.75). A fall in the past year was the best predictor of falls (AUC 0.75, sensitivity 0.89, specificity 0.56) or injurious falls (AUC 0.69, sensitivity 0.96, specificity 0.41) in the following 6 months. Conclusion. Simply asking people with MS if they have fallen in the past year predicts future falls and injurious falls as well as more complex, expensive, or time-consuming approaches. Michelle H. Cameron, Emily Thielman, Rajarshi Mazumder, and Dennis Bourdette Copyright © 2013 Michelle H. Cameron et al. All rights reserved. Olfactory Dysfunction in Patients with Neuromyelitis Optica Wed, 25 Sep 2013 14:24:40 +0000 Background. Neuromyelitis optica (NMO) is a severely disabling autoimmune disorder of the CNS, which mainly affects the optic nerves and spinal cord. However, recent studies have shown that extra-opticospinal are more common in NMO than previously thought. Objective. To investigate olfactory function (OF) in patients with neuromyelitis optica (NMO) versus healthy controls (HC). Methods. Psychophysical testing of the orthonasal OF was performed using the Threshold-Discrimination-Identification test (TDI), measuring different qualities of olfaction, in 10 unselected NMO patients and 10 HC. Results. Five of 10 NMO patients (50%) showed hyposmia, while all 10 HC were normosmic. Moreover, NMO patients had significantly lower mean TDI-scores compared to HC, based on a poorer performance in both the Discrimination and the Identification subtests. Conclusions. Our results suggest that hyposmia might be part of the expanding clinical spectrum of NMO. Felix Schmidt, Önder Göktas, Sven Jarius, Brigitte Wildemann, Klemens Ruprecht, Friedemann Paul, and Lutz Harms Copyright © 2013 Felix Schmidt et al. All rights reserved. Adding to the Burden: Gastrointestinal Symptoms and Syndromes in Multiple Sclerosis Tue, 17 Sep 2013 11:15:35 +0000 Background. Multiple sclerosis (MS) patients often suffer from gastrointestinal (GI) symptoms. However, the full extent and prevalence of such symptoms are not clearly established. Thus, we sought to define the prevalence of GI symptoms and syndromes in those with MS. Methods. 218 MS patients completed self-reported demographic and clinical data questionnaires as well as several standardized surveys probing MS severity and GI health. Results. Nearly two thirds (65.6%) of patients endorsed at least one persistent GI symptom. Constipation (36.6%), dysphagia (21.1%), and fecal incontinence (15.1%) were common. Surprisingly, nearly 30% (28.4%) of the patients reported dyspeptic symptoms. Using validated diagnostic algorithms, patients met criteria for functional dysphagia (14.7%), functional dyspepsia (16.5%), functional constipation (31.7%), and IBS (19.3%), among others. Functional dysphagia, functional dyspepsia, and IBS were significantly more common in those with self-identified mood disorders. Conclusions. Constipation, fecal incontinence, and dysphagia are indeed frequent symptoms seen in MS patients. We also noted a ~30% prevalence of dyspepsia in this population. The mechanisms driving this association are not clear and require further study. However, due to this high prevalence, dyspeptic symptoms should be incorporated into the routine assessment of MS patients and, if found, may warrant collaborative referral with a GI specialist. David J. Levinthal, Ambreen Rahman, Salman Nusrat, Margie O’Leary, Rock Heyman, and Klaus Bielefeldt Copyright © 2013 David J. Levinthal et al. All rights reserved. Is There Extra Cost of Institutional Care for MS Patients? Sat, 14 Sep 2013 12:42:17 +0000 Throughout life, patients with multiple sclerosis (MS) require increasing levels of support, rehabilitative services, and eventual skilled nursing facility (SNF) care. There are concerns that access to SNF care for MS patients is limited because of perceived higher costs of their care. This study compares costs of caring for an MS patient versus those of a typical SNF patient. We merged SNF cost report data with the 2001–2006 Nursing Home Minimum Data Set (MDS) to calculate percentage of MS residents-days and facility case-mix indices (CMIs). We estimated the average facility daily cost using hybrid cost functions, adjusted for facility ownership, average facility wages, CMI-adjusted number of SNF days, and percentage of MS residents-days. We describe specific characteristics of SNF with high and low MS volumes and examine any sources of variation in cost. MS patients were no longer more costly than typical SNF patients. A greater proportion of MS patients had no significant effect on facility daily costs (). MS patients were more likely to receive care in government-owned facilities (OR = 1.904) located in the Western (OR = 2.133) and Midwestern (OR = 1.3) parts of the USA (). Cost of SNF care is not a likely explanation for the perceived access barriers that MS patients face. Katia Noyes, Alina Bajorska, Bianca Weinstock-Guttman, and Dana B. Mukamel Copyright © 2013 Katia Noyes et al. All rights reserved. Infodemiology and Infoveillance of Multiple Sclerosis in Italy Tue, 20 Aug 2013 12:03:33 +0000 Multiple Sclerosis (MS) is a chronic debilitating disease of probable autoimmune inflammatory nature, whose aetiology is not fully understood, despite the many efforts and investigations. In this manuscript, we review the concept of “Multiple Sclerosis 2.0”, that is to say the Internet usage by MS patients, for seeking health and disease-related material for self-care and self-management purposes, and we introduce a Google Trends-based approach for monitoring MS-related Google queries and searches, called MS infodemiology and infoveillance. Google Trends has already proven to be reliable for infectious diseases monitoring, and here we extend its application and potentiality in the field of neurological disorders. Nicola Luigi Bragazzi Copyright © 2013 Nicola Luigi Bragazzi. All rights reserved. Gray Matter Pathology in MS: Neuroimaging and Clinical Correlations Tue, 25 Jun 2013 16:36:09 +0000 It is abundantly clear that there is extensive gray matter pathology occurring in multiple sclerosis. While attention to gray matter pathology was initially limited to studies of autopsy specimens and biopsies, the development of new MRI techniques has allowed assessment of gray matter pathology in vivo. Current MRI techniques allow the direct visualization of gray matter demyelinating lesions, the quantification of diffuse damage to normal appearing gray matter, and the direct measurement of gray matter atrophy. Gray matter demyelination (both focal and diffuse) and gray matter atrophy are found in the very earliest stages of multiple sclerosis and are progressive over time. Accumulation of gray matter damage has substantial impact on the lives of multiple sclerosis patients; a growing body of the literature demonstrates correlations between gray matter pathology and various measures of both clinical disability and cognitive impairment. The effect of disease modifying therapies on the rate accumulation of gray matter pathology in MS has been investigated. This review focuses on the neuroimaging of gray matter pathology in MS, the effect of the accumulation of gray matter pathology on clinical and cognitive disability, and the effect of disease-modifying agents on various measures of gray matter damage. Justin Morris Honce Copyright © 2013 Justin Morris Honce. All rights reserved.