Multiple Sclerosis International The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. The Efficacy of Functional Electrical Stimulation of the Abdominal Muscles in the Treatment of Chronic Constipation in Patients with Multiple Sclerosis: A Pilot Study Wed, 20 Apr 2016 07:01:20 +0000 Chronic constipation in patients with multiple sclerosis (MS) is common and the current methods of treatment are ineffective in some patients. Anecdotal observations suggest that functional electrical stimulation (FES) of the abdominal muscles may be effective in the management of constipation in these patients. Patients and Methods. In this exploratory investigation we studied the effects of FES on the whole gut transit time (WGTT) and the colonic transit time (CTT). In addition, we evaluated the treatment effect on the patients’ constipation-related quality of life and on the use of laxatives and the use of manual bowel evacuation. FES was given for 30 minutes twice a day for a period of six weeks. Four female patients were studied. Results. The WGTT and CTT and constipation-related quality of life improved in all patients. The patients’ use of laxatives was reduced. No adverse effects of FES treatment were reported. Conclusion. The findings of this pilot study suggest that FES applied to the abdominal muscles may be an effective treatment modality for severe chronic constipation in patients with MS. Christine Singleton, Abdel Magid Bakheit, and Carla Peace Copyright © 2016 Christine Singleton et al. All rights reserved. Management of Multiple Sclerosis in the Breastfeeding Mother Thu, 04 Feb 2016 08:21:29 +0000 Multiple Sclerosis (MS) is an autoimmune neurological disease characterized by inflammation of the brain and spinal cord. Relapsing-Remitting MS is characterized by acute attacks followed by remission. Treatment is aimed at halting these attacks; therapy may last for months to years. Because MS disproportionately affects females and commonly begins during the childbearing years, clinicians treat pregnant or nursing MS patients. The intent of this review is to perform an in-depth analysis into the safety of drugs used in breastfeeding women with MS. This paper is composed of several drugs used in the treatment of MS and current research regarding their safety in breastfeeding including immunomodulators, immunosuppressants, monoclonal antibodies, corticosteroids, and drugs used for symptomatic treatment. Typically, some medications are large polar molecules which often do not pass into the milk in clinically relevant amounts. For this reason, interferon beta is likely safe for the infant when given to a breastfeeding mother. However, other drugs with particularly dangerous side effects may not be recommended. While treatment options are available and some data from clinical studies does exist, there continues to be a need for investigation and ongoing review of the medications used in breastfeeding mothers. Saneea Almas, Jesse Vance, Teresa Baker, and Thomas Hale Copyright © 2016 Saneea Almas et al. All rights reserved. Lack of Association between Pulse Steroid Therapy and Bone Mineral Density in Patients with Multiple Sclerosis Thu, 04 Feb 2016 06:41:40 +0000 Multiple sclerosis (MS) has been associated with reduced bone mineral density (BMD). The purpose of this study was to determine the possible factors affecting BMD in patients with MS. We included consecutive 155 patients with MS and 90 age- and sex-matched control subjects. Patients with MS exhibited significantly lower T-scores and Z-scores in the femoral neck and trochanter compared to the controls. Ninety-four (61%) patients had reduced bone mass in either the lumbar spine or the femoral neck; of these, 64 (41.3%) had osteopenia and 30 (19.4%) had osteoporosis. The main factors affecting BMD were disability, duration of MS, and smoking. There was a negative relationship between femoral BMD and EDSS and disease duration. No association with lumbar BMD was determined. There were no correlations between BMD at any anatomic region and cumulative corticosteroid dose. BMD is significantly lower in patients with MS than in healthy controls. Reduced BMD in MS is mainly associated with disability and duration of the disease. Short courses of high dose steroid therapy did not result in an obvious negative impact on BMD in the lumbar spine and femoral neck in patients with MS. Serap Zengin Karahan, Cavit Boz, Sevgi Kilic, Nuray Can Usta, Mehmet Ozmenoglu, Vildan Altunayoglu Cakmak, and Sibel Gazioglu Copyright © 2016 Serap Zengin Karahan et al. All rights reserved. Stride-Time Variability and Fall Risk in Persons with Multiple Sclerosis Wed, 30 Dec 2015 11:28:21 +0000 Gait variability is associated with falls in clinical populations. However, gait variability’s link to falls in persons with Multiple Sclerosis (PwMS) is not well established. This investigation examined the relationship between stride-time variability, fall risk, and physiological fall risk factors in PwMS. 17 PwMS ( years) and 17 age-matched controls ( years) performed the 6-minute walk test. Stride-time was assessed with accelerometers attached to the participants’ shanks. Stride-time variability was measured by interstride coefficient of variation (CV) of stride-time. The participant’s fall risk was measured by the short form physiological profile assessment (PPA). A Spearman correlation analysis was used to determine the relationship between variables. Increased fall risk was strongly associated with increased stride-time CV in both PwMS (, ) and the controls (, ). Fall risk was not correlated with average stride-time (). In PwMS, stride-time CV was related to postural sway (, ) while in the control group, it was related to proprioception (, ) and postural sway (, ). Current observations suggest that gait variability is maybe more sensitive marker of fall risk than average gait parameters in PwMS. It was also noted that postural sway may be potentially targeted to modify gait variability in PwMS. Yaejin Moon, Douglas A. Wajda, Robert W. Motl, and Jacob J. Sosnoff Copyright © 2015 Yaejin Moon et al. All rights reserved. The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis Tue, 29 Dec 2015 11:39:23 +0000 Until recently, multiple sclerosis has been viewed as an entirely inflammatory disease without acknowledgment of the significant neurodegenerative component responsible for disease progression and disability. This perspective is being challenged by observations of a dissociation between inflammation and neurodegeneration where the neurodegenerative component may play a more significant role in disease progression. In this review, we explore the relationship between mitochondrial dysfunction and neurodegeneration in multiple sclerosis. We review evidence that the ketogenic diet can improve mitochondrial function and discuss the potential of the ketogenic diet in treating progressive multiple sclerosis for which no treatment currently exists. Mithu Storoni and Gordon T. Plant Copyright © 2015 Mithu Storoni and Gordon T. Plant. All rights reserved. The Communication of Multiple Sclerosis Diagnosis: The Patients’ Perspective Tue, 15 Dec 2015 11:05:16 +0000 Background. Multiple sclerosis (MS) is the leading cause of nontraumatic neurological disability in young adults in Europe and in the United States. The uncertainty regarding its evolution makes the diagnosis disclosure a difficult process. Objective. The aim of the study was to provide patients’ global perspective towards MS diagnosis communication. Methods. 150 consecutive patients, recently diagnosed with CIS or MS, were asked to complete a 17-item questionnaire assessing factors influencing their satisfaction with the information provided. Results. Eighty-six patients fulfilled diagnostic criteria for MS and 64 for CIS. Diagnosis disclosure took place in a private setting and required in most cases (87.3%) less than 30 minutes. Most patients reported being moderately or highly satisfied with the information provided (75%). The degree of satisfaction seems significantly related to patients’ younger age, a longer time dedicated to disclose the diagnosis, a CIS diagnosis, and, above all, tailored information and an adequate emotional support. Conclusion. Most patients reported a good degree of satisfaction about the communication of MS or CIS diagnosis. A fruitful relationship between patient and neurologist is essential to obtain a better acceptance of the disease, patients’ compliance with chronic treatments and to improve patients’ quality of life. Maria Josè Messina, Gloria Dalla Costa, Mariaemma Rodegher, Lucia Moiola, Bruno Colombo, Giancarlo Comi, and Vittorio Martinelli Copyright © 2015 Maria Josè Messina et al. All rights reserved. Comparing Three Dual-Task Methods and the Relationship to Physical and Cognitive Impairment in People with Multiple Sclerosis and Controls Mon, 23 Nov 2015 10:00:11 +0000 Dual-tasking (DT) is a measure to detect impairments in people with multiple sclerosis (MS). We compared three DT methods to determine whether cognitive (Montreal Cognitive Assessment (MoCA)) or physical disability (Expanded Disease Severity Scale; EDSS) was related to DT performance. We recruited MS participants with low disability (<3 EDSS, ) and high disability (≥3 EDSS, ) and matched controls (). Participants walked at self-selected (SS) speed on an instrumented walkway (Protokinetics, Havertown, USA), followed by DT walks in randomized order: DT ABC (reciting every second letter of the alphabet), DT 7 (serially subtracting 7’s from 100), and DT 3 (counting upwards, leaving out multiples and numbers that include 3). DT 7 resulted in the most consistent changes in performance. Both MS and control groups reduced velocity and cadence and shortened step length during DT with no significant differences between groups. Control subjects widened stride width by about 1 cm while MS subjects (collapsed as one group) did not. MS subjects with higher disability significantly increased percentage time in double support during DT compared to SS (, ). The change in DS was related to cognitive and not physical disability (,). Megan C. Kirkland, Elizabeth M. Wallack, Samantha N. Rancourt, and Michelle Ploughman Copyright © 2015 Megan C. Kirkland et al. All rights reserved. Adipsin Is Associated with Multiple Sclerosis: A Follow-Up Study of Adipokines Sun, 08 Nov 2015 12:28:40 +0000 Background and Objective. The role of adipokines in regulation of immune responses has been recognized, but very little is known about their impact on multiple sclerosis (MS). In this study, we analysed whether the major adipokines are differentially expressed in plasma of patients with different MS subtypes and clinically isolated syndrome (CIS) and explored their association with major disease characteristics. Methods. The levels of adiponectin, adipsin, leptin, and resistin in the plasma of 80 patients with different subtypes of MS and CIS were followed up annually over the two years. The data obtained were correlated with disease activity, EDSS and volumes of T1-weighted lesions (T1-LV), and fluid attenuation inversion recovery lesions (FLAIR-LV) on MRI. Results. In MS group, a correlation was found between the level of adipsin and EDSS score at baseline (, ). In RRMS, the levels of adipsin correlated with EDSS scores (, ), T1-LV (, ), and FLAIR-LV (, ) at baseline and an increase in the T1-LV over the follow-up (, ). Associations with other adipokines were not detected. Conclusion. Our exploratory study provides novel insights on the impact of adipokines in MS and suggests that adipsin exerts predictive potential as a biomarker of neurodegeneration. Renuka Natarajan, Sanna Hagman, Mari Hämälainen, Tiina Leppänen, Prasun Dastidar, Eeva Moilanen, and Irina Elovaara Copyright © 2015 Renuka Natarajan et al. All rights reserved. Neuroimaging of Natalizumab Complications in Multiple Sclerosis: PML and Other Associated Entities Mon, 21 Sep 2015 12:00:37 +0000 Natalizumab (Tysabri) is a monoclonal antibody (α4 integrin antagonist) approved for treatment of multiple sclerosis, both for patients who fail therapy with other disease modifying agents and for patients with aggressive disease. Natalizumab is highly effective, resulting in significant decreases in rates of both relapse and disability accumulation, as well as marked decrease in MRI evidence of disease activity. As such, utilization of natalizumab is increasing, and the presentation of its associated complications is increasing accordingly. This review focuses on the clinical and neuroimaging features of the major complications associated with natalizumab therapy, focusing on the rare but devastating progressive multifocal leukoencephalopathy (PML). Associated entities including PML associated immune reconstitution inflammatory syndrome (PML-IRIS) and the emerging phenomenon of rebound of MS disease activity after natalizumab discontinuation are also discussed. Early recognition of neuroimaging features associated with these processes is critical in order to facilitate prompt diagnosis, treatment, and/or modification of therapies to improve patient outcomes. Justin M. Honce, Lidia Nagae, and Eric Nyberg Copyright © 2015 Justin M. Honce et al. All rights reserved. Fingolimod Treatment in Relapsing-Remitting Multiple Sclerosis Patients: A Prospective Observational Multicenter Postmarketing Study Wed, 22 Jul 2015 11:24:23 +0000 Objective. The aim of this prospective observational multicenter postmarketing study was to evaluate fingolimod efficacy in a real world clinical setting. Methods. One hundred forty-two subjects with relapsing-remitting multiple sclerosis (RRMS) were enrolled in three multiple sclerosis centers throughout Central and Southern Italy between January 2011 and September 2013. After enrollment, regular visits and EDSS assessment were scheduled every 3 months, and MRI scan was obtained every 12 months. Patients were followed up from 1 to 33 months (mean 14.95 ± 9.15 months). The main efficacy endpoints included the proportion of patients free from clinical relapses, from disability progression, from magnetic resonance imaging activity, and from any disease activity. Results. Out of 142 patients enrolled in the study, 88.1% were free from clinical relapse and 69.0% were free from disability progression; 68.5% of patients remained free from new or newly enlarging T2 lesions and 81.7% of patients were free from gadolinium enhancing lesions. Overall the proportion of patients free from any disease activity was 41.9%. Conclusions. Our data in a real world cohort are consistent with previous findings that yield convincing evidence for the efficacy of fingolimod in patients with RRMS. Rocco Totaro, Caterina Di Carmine, Gianfranco Costantino, Roberta Fantozzi, Paolo Bellantonio, Aurora Fuiani, Ciro Mundi, Stefano Ruggieri, Carmine Marini, and Antonio Carolei Copyright © 2015 Rocco Totaro et al. All rights reserved. Prevalence of Depression and Anxiety among Patients with Multiple Sclerosis Attending the MS Clinic at Sheikh Khalifa Medical City, UAE: Cross-Sectional Study Thu, 09 Jul 2015 11:42:22 +0000 Depression and anxiety are reported to be prevalent in patients with MS, with prevalence rates ranging from 20% to 50%. Unfortunately, the rates, patterns, and risk factors are not well studied in our Middle East region, and, to our knowledge, not at all in UAE. Using standardized screening tools, we observed that 17% and 20% of 80 patients seen in MS clinic had scores consistent with major depression and anxiety disorders, respectively, at a rate that was not statistically different when compared to age and sex matched controls. None of the studied variables including duration of the disease, EDSS scores, age, gender, and the level of education had any significant correlation with the rates of both disorders. Almost two-thirds of the patients with scores consistent with major depression and anxiety were not on antidepressant and antianxiety medications. Taoufik Alsaadi, Khadija El Hammasi, Tarek M. Shahrour, Mustafa Shakra, Lamya Turkawi, Abdulla Mudhafar, Lina Diab, and Mufeed Raoof Copyright © 2015 Taoufik Alsaadi et al. All rights reserved. EDSS Change Relates to Physical HRQoL While Relapse Occurrence Relates to Overall HRQoL in Patients with Multiple Sclerosis Receiving Subcutaneous Interferon β-1a Sun, 05 Jul 2015 09:49:20 +0000 Objective. To compare patterns of associations of changes in mental and physical health dimensions of health-related quality of life (HRQoL) over time with relapse occurrence and changes in Expanded Disability Status Scale (EDSS) scores in patients with relapsing multiple sclerosis (RMS). Methods. This 24-month, phase IV, observational study enrolled 334 patients with RMS who received interferon β-1a 44 μg or 22 μg subcutaneously three times weekly. At each 6-month visit, patients completed the Multiple Sclerosis Quality of Life-54 (MSQOL-54) and site investigators assessed EDSS and recorded relapse occurrence. A generalized linear model procedure was used for multivariable analyses (per protocol) that explored unique associations of EDSS score change and relapse occurrence with MSQOL-54 physical health composite score (PCS) and mental health composite score (MCS). Results. HRQoL improved over 2 years among those who completed the study. Occurrence of ≥1 relapse was significantly associated with lower MSQOL-54 PCS and MCS. Changes in EDSS score were significantly associated with MSQOL-54 PCS, but not MCS. Conclusions. HRQoL assessments, particularly those that examine mental health, may provide information on the general health status of patients with RMS that would not be recognized using traditional clinician-assessed measures of disease severity and activity. This trial is registered with; identifier: NCT01141751. Barbara G. Vickrey, Liesly Lee, Fraser Moore, and Patrick Moriarty Copyright © 2015 Barbara G. Vickrey et al. All rights reserved. Antiepileptic and Antidepressive Polypharmacy in Patients with Multiple Sclerosis Mon, 29 Jun 2015 09:42:19 +0000 Objective. Patients with multiple sclerosis (MS) are often suffering from neuropathic pain. Antiepileptic drugs (AEDs) and tricyclic antidepressants (TCAs) are commonly used and are susceptible to be involved in drug interactions. The aim of this retrospective study was to investigate the prevalence of use of antiepileptic and antidepressive drugs in MS patients and to discuss the theoretical potential for interactions. Methods. Review of the medical records from all patients treated at a dedicated MS rehabilitation centre in Norway between 2009 and 2012. Results. In total 1090 patients attended a rehabilitation stay during the study period. Of these, 342 (31%; 249 females) with mean age of 53 (±10) years and EDSS 4.8 (±1.7) used at least one AED (gabapentin 12.7%, pregabalin 7.7%, clonazepam 7.8%, and carbamazepine 2.6%) or amitriptyline (9.7%). Polypharmacy was widespread (mean 5.4 drugs) with 60% using additional CNS-active drugs with a propensity to be involved in interactions. Age, gender, and EDSS scores did not differ significantly between those using and not using AED/amitriptyline. Conclusion. One-third of MS patients attending a rehabilitation stay receive AED/amitriptyline treatment. The high prevalence of polypharmacy and use of CNS-active drugs calls for awareness of especially pharmacodynamic interactions and possible excessive adverse effects. Georg Anton Giæver Beiske, Trygve Holmøy, Antonie Giæver Beiske, Svein I. Johannessen, and Cecilie Johannessen Landmark Copyright © 2015 Georg Anton Giæver Beiske et al. All rights reserved. Development of Activity-Related Muscle Fatigue during Robot-Mediated Upper Limb Rehabilitation Training in Persons with Multiple Sclerosis: A Pilot Trial Sun, 24 May 2015 10:13:22 +0000 Robot-assisted rehabilitation facilitates high-intensity training of the impaired upper limb in neurological rehabilitation. It has been clinically observed that persons with Multiple Sclerosis (MS) have difficulties in sustaining the training intensity during a session due to the development of activity-related muscle fatigue. An experimental observational pilot study was conducted to examine whether or not the muscle fatigue develops in MS patients during one session of robot-assisted training within a virtual learning environment. Six MS patients with upper limb impairment (motricity index ranging from 50 to 91/100) and six healthy persons completed five training bouts of three minutes each performing lifting tasks, while EMG signals of anterior deltoid and lower trapezius muscles were measured and their subjective perceptions on muscle fatigue were registered. Decreased performance and higher subjective fatigue perception were present in the MS group. Increased mean EMG amplitudes and subjective perception levels on muscle fatigue were observed in both groups. Muscle fatigue development during 15′ training has been demonstrated in the arm of MS patients, which influences the sustainability of training intensity in MS patients. To optimize the training performance, adaptivity based on the detection of MS patient’s muscle fatigue could be provided by means of training program adjustment. Johanna Renny Octavia, Peter Feys, and Karin Coninx Copyright © 2015 Johanna Renny Octavia et al. All rights reserved. Applying an Open-Source Segmentation Algorithm to Different OCT Devices in Multiple Sclerosis Patients and Healthy Controls: Implications for Clinical Trials Mon, 18 May 2015 12:34:13 +0000 Background. The lack of segmentation algorithms operative across optical coherence tomography (OCT) platforms hinders utility of retinal layer measures in MS trials. Objective. To determine cross-sectional and longitudinal agreement of retinal layer thicknesses derived from an open-source, fully-automated, segmentation algorithm, applied to two spectral-domain OCT devices. Methods. Cirrus HD-OCT and Spectralis OCT macular scans from 68 MS patients and 22 healthy controls were segmented. A longitudinal cohort comprising 51 subjects (mean follow-up: 1.4 ± 0.9 years) was also examined. Bland-Altman analyses and interscanner agreement indices were utilized to assess agreement between scanners. Results. Low mean differences (−2.16 to 0.26 μm) and narrow limits of agreement (LOA) were noted for ganglion cell and inner and outer nuclear layer thicknesses cross-sectionally. Longitudinally we found low mean differences (−0.195 to 0.21 μm) for changes in all layers, with wider LOA. Comparisons of rate of change in layer thicknesses over time revealed consistent results between the platforms. Conclusions. Retinal thickness measures for the majority of the retinal layers agree well cross-sectionally and longitudinally between the two scanners at the cohort level, with greater variability at the individual level. This open-source segmentation algorithm enables combining data from different OCT platforms, broadening utilization of OCT as an outcome measure in MS trials. Pavan Bhargava, Andrew Lang, Omar Al-Louzi, Aaron Carass, Jerry Prince, Peter A. Calabresi, and Shiv Saidha Copyright © 2015 Pavan Bhargava et al. All rights reserved. The Lived Experience of Multiple Sclerosis Relapse: How Adults with Multiple Sclerosis Processed Their Relapse Experience and Evaluated Their Need for Postrelapse Care Wed, 13 May 2015 09:50:15 +0000 Background. Multiple sclerosis (MS) relapses can take a toll on individuals’ health and quality of life. Given such consequences of relapses, postrelapse care beyond pharmacological approaches may play an important role in recovery. Nevertheless, how individuals with MS process their relapse experience and manage the consequences is still uncertain. Purpose. We conducted a qualitative study to understand relapse experiences and postrelapse care need from perspectives of adults with MS and identify relapse management patterns. Methods. We interviewed 17 adults with MS. Results. By examining combinations of three categories related to relapse experience, we identified four relapse management patterns: (i) Active Relapse Manager, (ii) Early-Stage Proactive Relapse Monitor, (iii) Adapted Passive Relapse Manager, and (iv) Passive Relapse Monitor. The relapse management patterns appear to associate strongly with the appraisal of the experience. Conclusions. The results of this study suggest the importance of understanding each patient beyond their functional limitations and the potential need for multidisciplinary postrelapse care which goes past restoring functional limitations at the acute phase. Future research to further understand the relapse management process at all stages of the healthcare continuum is a crucial step toward developing strategies to advance the current postrelapse care and to facilitate optimal recovery. Miho Asano, Karli Hawken, Merrill Turpin, Abby Eitzen, and Marcia Finlayson Copyright © 2015 Miho Asano et al. All rights reserved. Does Self-Efficacy Affect Cognitive Performance in Persons with Clinically Isolated Syndrome and Early Relapsing Remitting Multiple Sclerosis? Wed, 29 Apr 2015 09:35:51 +0000 In persons with multiple sclerosis (MS) a lowered self-efficacy negatively affects physical activities. Against this background we studied the relationship between self-efficacy and cognitive performance in the early stages of MS. Thirty-three patients with Clinically Isolated Syndrome (CIS) and early Relapsing Remitting MS (eRRMS) were assessed for self-efficacy (MSSES-18), cognition (CDR System), fatigue (MFIS-5), depressive symptoms (BDI), disease impact (MSIS-29), and disability (EDSS). Correlative analyses were performed between self-efficacy and cognitive scores, and stepwise regression analyses identified predictors of cognition and self-efficacy. Good correlations existed between total self-efficacy and Power of Attention (; ), Reaction Time Variability (; ), and Speed of Memory (; ), and between control self-efficacy and Reaction Time Variability (; ). Total self-efficacy predicted 40% of Power of Attention, 34% of Reaction Time Variability, and 40% of Speed of Memory variabilities. Disease impact predicted 65% of total self-efficacy and 58% of control self-efficacy variabilities. The findings may suggest that in persons with CIS and eRRMS self-efficacy may positively affect cognitive performance and that prevention of disease activity may preserve self-efficacy. Peter Joseph Jongen, Keith Wesnes, Björn van Geel, Paul Pop, Hans Schrijver, Leo H. Visser, H. Jacobus Gilhuis, Ludovicus G. Sinnige, and Augustina M. Brands Copyright © 2015 Peter Joseph Jongen et al. All rights reserved. Epidemiology of Neuromyelitis Optica in the World: A Systematic Review and Meta-Analysis Mon, 20 Apr 2015 12:17:09 +0000 Background. Neuromyelitis optica (Devic’s disease) is a severe autoimmune inflammatory disorder of the central nervous system. Epidemiological aspects of NMO have not been systemically reviewed. In this study we systematically reviewed and assessed the quality of studies reporting the incidence and/or prevalence of NMO across the world. Methods. A comprehensive literature search using MEDLINE, EMBASE, and Web of Science for the terms “Neuromyelitis optica,” “devic disease,” “incidence,” “prevalence,” and “epidemiology” was conducted on January 31, 2015. Study quality was assessed using an assessment tool based on recognized guidelines and designed specifically for this study. Results. A total of 216 studies were initially identified, with only 9 meeting the inclusion criteria. High level of heterogeneity amongst studies precluded a firm conclusion. Incidence data were found in four studies and ranged from 0.053 per 100,000 per year in Cuba to 0.4 in Southern Denmark. Prevalence was reported in all studies and ranged from 0.51 per 100,000 in Cuba to 4.4 in Southern Denmark. Conclusion. This review reveals the gaps that still exist in the epidemiological knowledge of NMO in the world. Published studies have different qualities and methodology precluding a robust conclusion. Future researches focusing on epidemiological features of NMO in different nations and different ethnic groups are needed. Masoud Etemadifar, Zahra Nasr, Behrang Khalili, Maryam Taherioun, and Reza Vosoughi Copyright © 2015 Masoud Etemadifar et al. All rights reserved. Italian Validation of the 12-Item Multiple Sclerosis Walking Scale Thu, 26 Mar 2015 07:34:07 +0000 Objective. Gait impairment is commonly in people with multiple sclerosis (MS). The 12-item MS walking scale (MSWS-12) assesses patients’ measurement of walking quality. The aim of this study was to cross-culturally adapt and validate the MSWS-12 for the Italian population with MS. Methods. Six MS out-patient clinics across Italy enrolled subjects between June 2013 and December 2013. Construct validity of MSWS-12 was determined by examining correlations with the Italian version of the EDSS, the timed 25-foot walk (T25FW), and the Fatigue Severity Scale (FSS). Results. 321 MS subjects were enrolled. Mean age was 47.55 years and mean disease duration was 13.8 years. Mean EDSS score was 4.46. 185 subjects had a relapsing-remitting course, 92 were secondary progressive, 43 were primary progressive, and 1 had a clinically isolated syndrome. The mean total score of the MSWS-12 was 49.6 (SD: 31) with values ranging between 0 and 100. Correlations between the MSWS-12 with age, disease duration, and disease course were found but not with gender. Values of the MSWS-12/IT were significantly related to EDSS (0.71), to the T25FW (0.65), and to the FSS (0.51). Conclusion. MSWS-12/IT has been adapted and validated, it is a reliable and reproducible scale for Italian patients with MS. C. Solaro, E. Trabucco, A. Signori, M. Cella, M. Messmer Uccelli, G. Brichetto, P. Cavalla, M. Gironi, F. Patti, and L. Prosperini Copyright © 2015 C. Solaro et al. 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.