Multiple Sclerosis International The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Cytokines as Biomarkers of Treatment Response to IFNβ in Relapsing-Remitting Multiple Sclerosis Tue, 22 Jul 2014 12:38:14 +0000 Background. MS patients show a remarkable heterogeneity in their response to disease modifying treatments. Given the need for early treatment initiation and the diversity of available options, a predictive marker that indicates good or poor response to treatment is highly desirable. Objective. To find a biomarker for treatment response to IFNβ among pro- and anti-inflammatory cytokines. Materials and Methods. IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, IL-17A, and TGF-β1 levels were measured in serum and CSF of 43 patients with RR-MS who were followed up for a mean period of 5.3 years. Thirty-five patients received IFNβ treatment and were divided into good responders (GR, n = 19) and poor responders (PR, n = 16). The remaining 8 patients showed a very favorable outcome and remained untreated (noRx). Results. GR had significantly higher serum baseline levels of IL-17A than PR and significantly higher serum levels of IL-17A, IFN-γ, TNF-α, and IL-2 than noRx. PR had significantly higher IFN-γ serum levels than noRx. No significant differences were observed in serum levels of IL-6, IL-4, IL-10, and TGF-β1 or the levels of all cytokines measured in CSF between the 3 groups of patients. Conclusions. Baseline serum levels of IL-17A can be used as a biomarker of IFNβ treatment response. Nikolaos Dimisianos, Maria Rodi, Dimitra Kalavrizioti, Vasileios Georgiou, Panagiotis Papathanasopoulos, and Athanasia Mouzaki Copyright © 2014 Nikolaos Dimisianos et al. All rights reserved. Sound Lateralization Test Distinguishes Unimpaired MS Patients from Healthy Controls Tue, 15 Jul 2014 13:58:02 +0000 There is an urgent need to develop a practical and reliable clinical measure of disease progression in early and mild MS. We hypothesized that a test of sound lateralization, which is exquisitely sensitive to transmission delays in auditory brainstem, could be more useful for detecting processing speed deficits in mildly impaired MS subjects than standard cognitive tasks. Objective. To develop a practical test of sound lateralization for the clinic and to compare performance of MS subjects with variable disability and healthy subjects on Sound Lateralization Test (SLT) and two speed-of-processing tasks. Design. 42 healthy controls and 90 subjects with clinically definite MS, divided into no, mild, and moderate disability strata, were administered the Symbol Digit Modalities Test (SDMT), and 3-second Paced Auditory Serial Addition Test (PASAT). Results. All of the tests showed an overall difference in performance between controls and the three MS groups, but only the SLT measured a significant difference between controls and the no disability group. Conclusion. SLT is rapidly applied, technically simple, and superior to standard processing speed tests for discriminating between healthy controls and nondisabled MS subjects. SLT should be investigated as an outcome measure in early-phase trials and for monitoring early disease progression in the clinic. Joshua H. Bacon, Ilya Kister, Tamar E. Bacon, Eliana Pasternak, Yael Strauchler, and Joseph Herbert Copyright © 2014 Joshua H. Bacon et al. All rights reserved. Leg Spasticity and Ambulation in Multiple Sclerosis Wed, 04 Jun 2014 07:36:31 +0000 Background. Spasticity of the legs is common in multiple sclerosis (MS), but there has been limited research examining its association with ambulatory outcomes. Objective. This study examined spasticity of the legs and its association with multiple measures of ambulation in persons with MS. Methods. The sample included 84 patients with MS. Spasticity of the legs was measured using a 5-point rating scale ranging between 0 (normal) and 4 (contracted). Patients completed the 6-minute walk (6 MW), timed 25 foot walk (T25FW), and timed up-and-go (TUG), and O2 cost of walking was measured during the 6 MW. The patients undertook two walking trials on a GAITRite (CIR systems, Inc.) for measuring spatial and temporal parameters of gait. The patients completed the Multiple Sclerosis Walking Scale-12 (MSWS-12) and wore an accelerometer over a seven-day period. Results. 52% () of the sample presented with spasticity of the legs. Those with leg spasticity had significantly worse ambulation as measured by 6 MW (, ), T25FW (), TUG (, ), MSWS-12 (), O2 cost of walking (, ), average steps/day (, ), and walking velocity (, ) and cadence (, ). Conclusion. Leg spasticity was associated with impairments in ambulation, including alterations in spatiotemporal parameters and free-living walking. Swathi Balantrapu, Jacob J. Sosnoff, John H. Pula, Brian M. Sandroff, and Robert W. Motl Copyright © 2014 Swathi Balantrapu et al. All rights reserved. Impact of a 5-Day Expedition to Machu Picchu on Persons with Multiple Sclerosis Wed, 21 May 2014 06:34:41 +0000 Persons with multiple sclerosis (MS) are less physically active than nondiseased persons and often report low self-efficacy levels. In the context of an awareness project to promote physical activity and participation in MS, we addressed the impact of training for and participation in a unique expedition. Medical events, relapses, and self-reported neurological worsening were followed from 6 months before and up to 4 months afterwards. Validated patient-reported outcome measures were used to assess fatigue, self-efficacy in exercising, walking abilities, and illness perception. Nine participants completed the training, expedition, and observational study. Minor events, relapses, and/or neurological worsening were reported in six participants. The three participants with mild disability and no cardiovascular risk factors or comorbidities were free of medical and neurological events. We found a significant reduction of motor fatigue at last when compared with the first assessment. The reduction tended to be more evident in participants with mild disability (Expanded Disability Status Scale (EDSS) at baseline). Cognitive fatigue, self-efficacy, and self-reported walking abilities did not change significantly. Illness perceptions tended to be reduced over time in the domains of consequences, identity, and concerns. Overall, no major adverse events occurred. Marie Beatrice D’hooghe, Peter Feys, Sam Deltour, Isabelle Van de Putte, Jan De Meue, Daphne Kos, Bert O Eijnde, and Paul Van Asch Copyright © 2014 Marie Beatrice D’hooghe et al. All rights reserved. Meta-Analysis of Three Different Types of Fatigue Management Interventions for People with Multiple Sclerosis: Exercise, Education, and Medication Wed, 14 May 2014 07:58:52 +0000 Fatigue is a common symptom of multiple sclerosis (MS) with negative impacts extending from general functioning to quality of life. Both the cause and consequences of MS fatigue are considered multidimensional and necessitate multidisciplinary treatment for successful symptom management. Clinical practice guidelines suggest medication and rehabilitation for managing fatigue. This review summarized available research literature about three types of fatigue management interventions (exercise, education, and medication) to provide comprehensive perspective on treatment options and facilitate a comparison of their effectiveness. We researched PubMed, Embase, and CINAHL (August 2013). Search terms included multiple sclerosis, fatigue, energy conservation, Amantadine, Modafinil, and randomized controlled trial. The search identified 230 citations. After the full-text review, 18 rehabilitation and 7 pharmacological trials targeting fatigue were selected. Rehabilitation interventions appeared to have stronger and more significant effects on reducing the impact or severity of patient-reported fatigue compared to medication. Pharmacological agents, including fatigue medication, are important but often do not enable people with MS to cope with their existing disabilities. MS fatigue affects various components of one’s health and wellbeing. People with MS experiencing fatigue and their healthcare providers should consider a full spectrum of effective fatigue management interventions, from exercise to educational strategies in conjunction with medication. Miho Asano and Marcia L. Finlayson Copyright © 2014 Miho Asano and Marcia L. Finlayson. All rights reserved. Multiple Sclerosis: Evaluation of Purine Nucleotide Metabolism in Central Nervous System in Association with Serum Levels of Selected Fat-Soluble Antioxidants Tue, 06 May 2014 08:08:34 +0000 In the pathogenesis of demyelinating diseases including multiple sclerosis (MS) an important role is played by oxidative stress. Increased energy requirements during remyelination of axons and mitochondria failure is one of the causes of axonal degeneration and disability in MS. In this context, we analyzed to what extent the increase in purine catabolism is associated with selected blood lipophilic antioxidants and if there is any association with alterations in serum levels of coenzyme Q10. Blood serum and cerebrospinal fluid (CSF) samples from 42 patients with diagnosed MS and 34 noninflammatory neurologic patients (control group) were analyzed. Compared to control group, MS patients had significantly elevated values of all purine nucleotide metabolites, except adenosine. Serum lipophilic antioxidants γ-tocopherol, β-carotene, and coenzyme Q10 for the vast majority of MS patients were deficient or moved within the border of lower physiological values. Serum levels of TBARS, marker of lipid peroxidation, were increased by 81% in the MS patients. The results indicate that the deficit of lipophilic antioxidants in blood of MS patients may have a negative impact on bioenergetics of reparative remyelinating processes and promote neurodegeneration. Ľubomír Kuračka, Terézia Kalnovičová, Jarmila Kucharská, and Peter Turčáni Copyright © 2014 Ľubomír Kuračka et al. All rights reserved. Outcome Measures in Multiple Sclerosis Mon, 05 May 2014 08:11:14 +0000 Robert Bermel, Amy Waldman, and Ellen M. Mowry Copyright © 2014 Robert Bermel et al. All rights reserved. Outcome Measures in Relapsing-Remitting Multiple Sclerosis: Capturing Disability and Disease Progression in Clinical Trials Sun, 04 May 2014 14:02:31 +0000 Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease that manifests as acute relapses and progressive disability. As a primary endpoint for clinical trials in MS, disability is difficult to both characterize and measure. Furthermore, the recovery from relapses and the rate of disability vary considerably among patients. Given these challenges, investigators have developed and studied the performance of various outcome measures and surrogate endpoints in MS clinical trials. This review defines the outcome measures and surrogate endpoints used to date in MS clinical trials and presents challenges in the design of both adult and pediatric trials. Amy M. Lavery, Leonard H. Verhey, and Amy T. Waldman Copyright © 2014 Amy M. Lavery et al. All rights reserved. Bedside Tested Ocular Motor Disorders in Multiple Sclerosis Patients Wed, 30 Apr 2014 07:16:10 +0000 Background/Aims. Ocular motor disorders (OMDs) are a common feature of multiple sclerosis (MS). In clinical practice, if not reported by patients, OMDs are often underdiagnosed and their prevalence is underestimated. Methods. We studied 163 patients (125 women, 76.7%, 38 men, 23.3%; median age 45.0 years; median disease duration 10 years; median EDSS 3.5) with definite MS (, 92%) or clinically isolated syndrome (, 8%) who underwent a thorough clinical examination of eye movements. Data on localization of previous relapses, MS subtype, and MRI findings were collected and analyzed. Results. Overall, 111/163 (68.1%) patients showed at least one abnormality of eye movement. Most frequent OMDs were impaired smooth pursuit (42.3%), saccadic dysmetria (41.7%), unilateral internuclear ophthalmoplegia (14.7%), slowing of saccades (14.7%), skew deviation (13.5%), and gaze evoked nystagmus (13.5%). Patients with OMDs had more severe disability and showed more frequently infratentorial MRI lesions . Localization of previous relapses was not associated with presence of OMDs. Conclusion. OMDs are frequent in patients with stable (no relapses) MS. A precise bedside examination of eye motility can disclose abnormalities that imply the presence of subclinical MS lesions and may have a substantial impact on definition of the diagnosis and on management of MS patients. G. Servillo, D. Renard, G. Taieb, P. Labauge, S. Bastide, M. Zorzon, and G. Castelnovo Copyright © 2014 G. Servillo et al. All rights reserved. Factors Associated with Neurologists’ Provision of MS Patient Care Thu, 24 Apr 2014 09:18:09 +0000 Neurologists are central to providing quality care for individuals with MS. However, neurologist shortages may restrict access to care for MS patients. To examine factors influencing neurologists’ provision of MS care, we surveyed 1,700 US neurologists to assess demographic/practice characteristics, training, and attitudes toward MS care. The study population consisted of 573 respondents: 87 (15.2%) MS subspecialists and 486 (84.8%) “other neurologists,” including subspecialists in other neurology areas (i.e., non-MS) and general neurologists. MS subspecialists indicating they “enjoy interacting with MS patients” had a significantly greater rate of MS patients seen per week. In separate analyses of the “other neurologists” group, the rate of MS patients seen was lower among neurologists in university-based groups or those practicing in major cities; female neurologists; and neurologists who indicated lack of sufficient knowledge regarding MS patient care. Rates of MS patients seen were significantly greater for other neurologists who agreed that MS care involved “ability to improve patient outcomes and quality of life”; “dynamic area with evolving treatment options”; and “enjoy interacting with MS patients.” Understanding factors influencing MS patient care by neurologists and developing policies for appropriate access to care is critical for optimal outcomes among this population. Michael T. Halpern, Stephanie M. Teixeira-Poit, Heather Kane, Corey Frost, Michael Keating, and Murrey Olmsted Copyright © 2014 Michael T. Halpern et al. All rights reserved. Association between Smoking and Health Outcomes in Postmenopausal Women Living with Multiple Sclerosis Tue, 22 Apr 2014 12:18:43 +0000 Background. In multiple sclerosis (MS), symptom management and improved health-related quality of life (HrQOL) may be modified by smoking. Objective. To evaluate the extent to which smoking is associated with worsened health outcomes and HrQOL for postmenopausal women with MS. Methods. We identified 251 Women’s Health Initiative Observational Study participants with a self-reported MS diagnosis. Using a linear model, we estimated changes from baseline to 3 years for activities of daily living, total metabolic equivalent tasks (MET) hours per week, mental and physical component scales (MCS, PCS) of the SF-36, and menopausal symptoms adjusting for years since menopause and other confounders. Results. Nine percent were current and 50% past smokers. Age at smoking initiation was associated with significant changes in MCS during menopause. PCS scores were unchanged. While women who had ever smoked experienced an increase in physical activity during menopause, the physical activity levels of women who never smoked declined. Residual confounding may explain this finding. Smoking was not associated with change in menopausal symptoms during the 3-year follow-up. Conclusion. Smoking was not associated with health outcomes among post-menopausal women with MS. Rachel Jawahar, Unsong Oh, Charles Eaton, Nicole Wright, Hilary Tindle, and Kate L. Lapane Copyright © 2014 Rachel Jawahar et al. 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.