Multiple Sclerosis International The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Disease-Modifying Drugs Reduce Cortical Lesion Accumulation and Atrophy Progression in Relapsing-Remitting Multiple Sclerosis: Results from a 48-Month Extension Study Mon, 23 Feb 2015 08:11:27 +0000 Cortical lesions (CLs) and atrophy are pivotal in multiple sclerosis (MS) pathology. This study determined the effect of disease modifying drugs (DMDs) on CL development and cortical atrophy progression in patients with relapsing-remitting MS (RRMS) over 48 months. Patients () were randomized to sc IFN β-1a 44 μg, im IFN β-1a 30 μg, or glatiramer acetate 20 mg. The reference population comprised 50 DMD-untreated patients with RRMS. After 24 months, 43 of the untreated patients switched to DMDs. The four groups of patients were followed up for an additional 24 months. At 48 months the mean standard deviation number of new CLs was significantly lower in patients treated with sc IFN β-1a (1.4 ± 1.0, range 0–5) compared with im IFN β-1a (2.3 ± 1.3, range 0–6, ) and glatiramer acetate (2.2 ± 1.5, range 0–7, ). Significant reductions in CL accumulation and new white matter and gadolinium-enhancing lesions were also observed in the 43 patients who switched to DMDs after 24 months, compared with the 24 months of no treatment. Concluding, this study confirms that DMDs significantly reduce CL development and cortical atrophy progression compared with no treatment. Francesca Rinaldi, Paola Perini, Matteo Atzori, Alice Favaretto, Dario Seppi, and Paolo Gallo Copyright © 2015 Francesca Rinaldi et al. All rights reserved. Intrathecal IgG Synthesis: A Resistant and Valuable Target for Future Multiple Sclerosis Treatments Thu, 08 Jan 2015 13:44:03 +0000 Intrathecal IgG synthesis is a key biological feature of multiple sclerosis (MS). When acquired early, it persists over time. A growing body of evidence suggests that intrathecal Ig-secreting cells may be pathogenic either by a direct action of toxic IgG or by locally secreting bystander toxic products. Intrathecal IgG synthesis depends on the presence of CNS lymphoid organs, which are strongly linked at anatomical level to cortical subpial lesions and at clinical level to the impairment slope in progressive MS. As a consequence, targeting CNS lymphoid lesions could be a valuable new target in MS, especially during the progressive phase. As intrathecal IgGs are end-products of these lymphoid lesions, intrathecal IgG synthesis may be considered as a specific marker of the persistence of these inflammatory lesions. Here we review the effect upon intrathecal IgG synthesis of all drugs ever used in MS. Except for steroids, all these therapeutic strategies, including rituximab, failed to decrease intrathecal IgG synthesis, with the exception of a questionable incomplete action of natalizumab. Thus, IgG synthesis is a robust marker of persistent intrathecal inflammation and its complete normalization should be one of the goals in future therapeutic strategies. Mickael Bonnan Copyright © 2015 Mickael Bonnan. All rights reserved. Treatment with Anti-EGF Ab Ameliorates Experimental Autoimmune Encephalomyelitis via Induction of Neurogenesis and Oligodendrogenesis Tue, 30 Dec 2014 06:34:23 +0000 Background. The neural stem cells (NSCs) migrate to the damaged sites in multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAE). However, the differentiation into neurons or oligodendrocytes is blocked. Epidermal growth factor (EGF) stimulates NSC proliferation and mobilization to demyelinated lesions but also induces astrogenesis and glial scar. Objective. To examine the clinical and histopathological effects of EGF neutralization on EAE. Methods. EAE-induced SJL mice were intravenously treated with either anti-EGF neutralizing antibody (Ab) or isotype control or PBS. On day 9 after immunization, 3 mice of each group were daily treated for 9 days with BrdU and then sacrificed for immunohistochemical analysis. Results. Treatment with anti-EGF Ab significantly ameliorated EAE symptoms during the second relapse. Anti-EGF Ab induced a shift from BrdU+GFAP+ NSCs to BrdU+DCX+ neuroblasts in the subventricular zone (SVZ), increased BrdU+NeuN+ neurons in the granular cell layer of the dentate gyrus, and increased BrdU+O4+ oligodendrocytes in the SVZ. There was no change in the inflammatory infiltrates in response to anti-EGF Ab. Conclusions. Therapy with anti-EGF Ab ameliorates EAE via induction of neurogenesis and oligodendrogenesis. No immunosuppressive effect was found. Further investigation is needed to support these notions of beneficial effect of anti-EGF Ab in MS. Yifat Amir-Levy, Karin Mausner-Fainberg, and Arnon Karni Copyright © 2014 Yifat Amir-Levy et al. All rights reserved. A Pilot Study of an Exercise-Based Patient Education Program in People with Multiple Sclerosis Sun, 21 Dec 2014 12:47:23 +0000 There is increasing evidence that physical exercise leads to numerous positive effects in PwMS. However, long-term effects of exercise may only be achievable if training is implemented in daily routine. Enabling patients to exercise regularly, we developed a patient education program focused on evidence-based information of training. PwMS were educated in neurophysiological effects of physical exercise, exercise-induced benefits for PwMS, and risk factors (e.g., weather). Fifteen PwMS were analyzed before () and after () a 12-week patient education. Afterwards, participants performed their exercises autonomously for 32 weeks and were tested in sustainability tests (). Guided interviews were carried out, additionally. Significant improvements from to were found in 6MWT, gait velocity, TUG, fatigue, and quality of life. Significant results of TUG and gait velocity from to demonstrated that participants kept few effects after the 32-week training phase. Qualitative analyses showed improved self-confidence and identified training strategies and barriers. This pilot study provides evidence that PwMS are able to acquire good knowledge about physical exercise and apply this knowledge successfully in training management. One might conclude that this exercise-based patient education seems to be a feasible option to maintain or improve patients’ integral constitution concerning physical and mental health. Stephanie Kersten, Mohammed Mahli, Julia Drosselmeyer, Christina Lutz, Magnus Liebherr, Patric Schubert, and Christian T. Haas Copyright © 2014 Stephanie Kersten et al. All rights reserved. The Frequency of Anti-Aquaporin-4 Ig G Antibody in Neuromyelitis Optica and Its Spectrum Disorders at a Single Tertiary Referral Center in Malaysia Mon, 17 Nov 2014 13:09:36 +0000 Background. In the past the occurrence of neuromyelitis optica in Malaysia was thought to be uncommon and the frequency of anti-aquaporin-4 Ig G antibody was unknown. Objective. To evaluate the frequency of anti-aquaporin-4 Ig G antibody (Anti-AQP4 antibody) amongst patients with neuromyelitis optica (NMO) and its spectrum disorders (NMOSD) and the differences between the seropositive and seronegative groups. Methods. Retrospectively, 96 patients with NMO/high risk syndromes for NMOSD (HRS-NMOSD) were identified out of 266 patients with idiopathic inflammatory demyelinating disease from a single center hospital based registry. Anti-AQP4 seropositivity was found in 38/48 (79.2%) with NMO, 12/21 (57.1%) with brain involvement at high risk for NMOSD, 12/15 (80%) with transverse myelitis (i.e., 11/15 with relapsing transverse myelitis and one with monophasic transverse myelitis), and 3/7 (42.8%) with relapsing optic neuritis. Sixty-five out of 96 patients, that is, 67.7%, with NMO/HRS for NMOSD were seropositive. Seropositivity was significantly associated with female gender, a higher number of mean relapses, that is, 5.15 ± 4.42 versus 2.10 ± 1.68, longer length of spinal cord lesions, that is, 6.6 ± 4.9 versus 2.9 ± 2.5, vertebral bodies, higher EDSS, 4.5 ± 2.4 versus 2.4 ± 2.6, presence of paroxysmal tonic spasms, and blindness (unilateral/bilateral); . Longitudinally extensive cord lesions (contiguous or linear), presence of lesions in the cervical and thoracic regions, and involvement of the central gray matter or holocord regions on axial scans, were also significantly associated with seropositivity; . Conclusion. NMO and HRS for NMOSD are present in larger numbers than previously thought in Malaysia. More than 2/3rds are seropositive. Seropositive and seronegative NMO/NMOSD have differences that are useful in clinical practice. Shanthi Viswanathan, Masita Arip, Norhazlin Mustafa, Jasbir S. Dhaliwal, Norzainie Rose, Sobri Muda, Santhi Datuk Puvanarajah, Mohammad Hanip Rafia, and Mark Cheong Wing Loong Copyright © 2014 Shanthi Viswanathan et al. All rights reserved. Increasing Incidence in Relapsing-Remitting MS and High Rates among Young Women in Finland: A Thirty-Year Follow-Up Sun, 09 Nov 2014 06:49:21 +0000 Object. Gender and disease course specific incidences were studied in high- and medium-risk regions of MS in Finland. Methods. Age- and gender-specific incidences with 95% CIs were calculated in 10-year periods from 1981 to 2010. Poser diagnostic criteria were used and compared with the McDonald criteria from 2001 to 2010. Association between age and diagnostic delay over time was assessed by using the Kruskal-Wallis test. Results. 1419 (89%) RRMS and 198 (11%) PPMS cases were included. RRMS incidence increased with the female to male ratio (F/M) from 4,2/105 (F/M 1.9) to 9,7 (2.3), while that of PPMS decreased from 1,2 (1.6) to 0,7 (1.2). The use of McDonald criteria did not change the conclusion. The decreasing diagnostic delay and age at diagnosis in RRMS were associated within the 10-year periods and contrasted those in PPMS. Increasing female risk in RRMS was observed in the high-risk region. Conclusion. Increasing RRMS incidence and high female ratios shown in each age group indicate gender-specific influences acting already from childhood. A more precise definition of the risk factors and their action in MS is needed to provide a better understanding of underlying pathological processes and a rationale for the development of new preventive and treatment strategies. Marja-Liisa Sumelahti, Markus H. A. Holmberg, Annukka Murtonen, Heini Huhtala, and Irina Elovaara Copyright © 2014 Marja-Liisa Sumelahti et al. All rights reserved. The Contribution of Immune and Glial Cell Types in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis Sun, 12 Oct 2014 11:22:52 +0000 Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterised by widespread areas of focal demyelination. Its aetiology and pathogenesis remain unclear despite substantial insights gained through studies of animal models, most notably experimental autoimmune encephalomyelitis (EAE). MS is widely believed to be immune-mediated and pathologically attributable to myelin-specific autoreactive CD4+ T cells. In recent years, MS research has expanded beyond its focus on CD4+ T cells to recognise the contributions of multiple immune and glial cell types to the development, progression, and amelioration of the disease. This review summarises evidence of T and B lymphocyte, natural killer cell, macrophage/microglial, astrocytic, and oligodendroglial involvement in both EAE and MS and the intercommunication and influence of each cell subset in the inflammatory process. Despite important advances in the understanding of the involvement of these cell types in MS, many questions still remain regarding the various subsets within each cell population and their exact contribution to different stages of the disease. Samuel S. Duffy, Justin G. Lees, and Gila Moalem-Taylor Copyright © 2014 Samuel S. Duffy et al. All rights reserved. Symptoms and Association with Health Outcomes in Relapsing-Remitting Multiple Sclerosis: Results of a US Patient Survey Tue, 23 Sep 2014 05:20:10 +0000 Background. A variety of symptoms have been reported, but the prevalence of specific symptoms in relapsing-remitting multiple sclerosis (RRMS), how they are related to one another, and their impact on patient reported outcomes is not well understood. Objective. To describe how symptoms of RRMS cooccur and their impact on patient-reported outcomes. Methods. Individuals who reported a physician diagnosis of RRMS in a large general health survey in the United States indicated the symptoms they experience because of RRMS and completed validated scales, including the work productivity and activity impairment questionnaire and either the SF-12v2 or SF-36v2. Symptom clusters were identified through hierarchical cluster analysis, and the relationship between clusters and outcomes was assessed through regression. Results. Fatigue, difficulty walking, and numbness were the most commonly reported symptoms. Seven symptom clusters were identified, and several were significantly related to patient reported outcomes. Pain, muscle spasms, and stiffness formed a cluster strongly related to physical quality of life; depression was strongly related to mental quality of life and cognitive difficulty was associated with work impairment. Conclusions. Symptoms in RRMS show a strong relationship with quality of life and should be taken into consideration in treatment decisions and evaluation of treatment success. Angela E. Williams, Jeffrey T. Vietri, Gina Isherwood, and Armando Flor Copyright © 2014 Angela E. Williams et al. All rights reserved. Multiple Sclerosis State of the Art (SMART): A Qualitative and Quantitative Analysis of Therapy’s Adherence, Hospital Reliability’s Perception, and Services Provided Quality Tue, 26 Aug 2014 05:53:56 +0000 The purpose of this study was to assess the adherence to therapy in patients with relapsing remitting multiple sclerosis (RR-MS) and to analyze the possible influence of factors such as hospital care and patients socioeconomic status. Two hundred eighty-five patients with RR-MS according to Mc Donald’s criteria and naïve disease-modifying drugs (DMDs) naïve were enrolled. Two self-administered questionnaires addressing the management of patients at therapy prescription and the personal perception of the daily life changes caused by DMDs were administered at months 3 and 12. Full adherence, considered as correct use of the therapy prescribed, was observed in a very high percentage of subjects (97.3% and 93.9% at 3 and 12 months). The main cause for reduced adherence was single dose forgetfulness, followed by anxiety, pain at the injection site, and tiredness of “doing all injections.” Nurses and neurologists of MS Center were identified as the major resource in coping with the disease at 3 and 12 months by patients. The neurologist was the health professional involved in MS management in 95% of cases and the nurse appeared to play a central role in patient training and drug administration management (50.3%). G. Di Battista, A. Bertolotto, C. Gasperini, A. Ghezzi, D. Maimone, and C. Solaro Copyright © 2014 G. Di Battista et al. All rights reserved. Impaired Object Handling during Bimanual Task Performance in Multiple Sclerosis Wed, 06 Aug 2014 13:10:34 +0000 We investigated the kinetic features of manual dexterity and fine motor control during a task that resembles an activity of daily living in 30 persons with relapsing-remitting multiple sclerosis (PwMS). Specifically, a novel two-transducer system was used to measure time and grip-load forces during a bimanual task that is similar to opening and closing a jar. We hypothesized that PwMS would have increased grip force production, deteriorations in kinetic timing, and preserved grip-load coupling indices compared to healthy controls (i.e., young and older adults). Increased grip force production and deterioration in timing indices were confirmed in PwMS. Abnormal grip-load coupling was exhibited by PwMS, in contrast to healthy participants. The correlation between task time and self-reported disability scores suggests that objective measurement of impaired upper-extremity movements relates to perception of overall function. Stacey L. Gorniak, Matthew Plow, Corey McDaniel, and Jay L. Alberts Copyright © 2014 Stacey L. Gorniak et al. All rights reserved. Autoimmune Disease Prevalence in a Multiple Sclerosis Cohort in Argentina Wed, 06 Aug 2014 06:49:08 +0000 Background. Comorbid autoimmune diseases in MS patients have been studied extensively with controversial results. Moreover, no such data exists for Latin-American MS patients. Methods. We conducted a case-control study aimed to establish the prevalence of autoimmune disorders in a cohort of Argentinean MS patients. Results. There were no significant differences in autoimmune disease prevalence in MS patients with respect to controls. The presence of one or more autoimmune disorders did not increase risk of MS (OR 0.85, 95% CI 0.6–1.3). Discussion. Our results indicate absence of increased comorbid autoimmune disease prevalence in MS patients, as well as of increased risk of MS in patients suffering from other autoimmune disorders. Mauricio F. Farez, María E. Balbuena Aguirre, Francisco Varela, Alejandro A. Köhler, and Jorge Correale Copyright © 2014 Mauricio F. Farez et al. 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.