Multiple Sclerosis International

The Clinical Relevance of Force Platform Measures in Multiple Sclerosis: A Review

Luca Prosperini and Carlo Pozzilli — Sun, 19 May 2013 11:55:35 +0000

Balance impairment and falls are frequent in patients with multiple sclerosis (PwMS), and they may occur even at the earliest stage of the disease and in minimally impaired patients. The introduction of computer-based force platform measures (i.e., static and dynamic posturography) has provided an objective and sensitive tool to document both deficits and improvements in balance. By using more challenging test conditions, force platform measures can also reveal subtle balance disorders undetectable by common clinical scales. Furthermore, posturographic techniques may also allow to reliably identify PwMS who are at risk of accidental falls. Although force platform measures offer several theoretical advantages, only few studies extensively investigated their role in better managing PwMS. Standardised procedures, as well as clinical relevance of changes detected by static or dynamic posturography, are still lacking. In this review, we summarized studies which investigated balance deficit by means of force platform measures, focusing on their ability in detecting patients at high risk of falls and in estimating rehabilitation-induced changes, highlighting the pros and the cons with respect to clinical scales.

Hospitalization Rates and Discharge Status in Multiple Sclerosis

Sanober Nusrat, David Levinthal, and Klaus Bielefeldt — Mon, 13 May 2013 16:58:23 +0000

Management of multiple sclerosis (MS) has shifted from supportive to disease modifying therapy. Considering the increasingly widespread adoption of this approach in managing MS patients, we hypothesized that hospitalizations and surrogates of disease-related complications should have declined during the last decade. Methods. Using the Nationwide Inpatient Sample, hospitalizations for MS and associated secondary diagnoses and procedures as well as discharge status were examined. Time trends were examined for different age cohorts focusing on the period from 2001 to 2010. Results. During the preceding decade, annual hospitalizations for MS increased by 40%, with stable rates in all age groups except geriatric patients, who accounted for a significantly higher fraction of admissions. Nursing home transfers as a surrogate marker of disability remained unchanged for all age groups. Similarly, urinary tract infections, the need for skin debridement, or gastrostomy tube placement did not vary during the decade. Conclusion. During a time of increased adoption of disease modifying therapy, MS-related hospitalizations continued to increase and surrogate measures of disability in admitted patients remained stable, demonstrating the still significant impact of the disease on affected individuals.

Morphostructural MRI Abnormalities Related to Neuropsychiatric Disorders Associated to Multiple Sclerosis

Simona Bonavita, Gioacchino Tedeschi, and Antonio Gallo — Tue, 16 Apr 2013 11:21:10 +0000

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS.

The Evidence for Hypoperfusion as a Factor in Multiple Sclerosis Lesion Development

Bernhard H. J. Juurlink — Thu, 04 Apr 2013 10:54:01 +0000

The evidence that hypoxia is a precipitating factor in causing early MS lesions includes increased protein levels of hypoxia-inducible factor-1α; presence of the D-110 hypoxia-inducible protein; increased expression of hypoxia-inducible genes in lesions as well as in adjacent normal-appearing white matter (NAWM); loss of myelin-associated glycoprotein in myelin of early MS lesions; a 50% reduction of blood flow through NAWM with areas of lowest blood flow having the greatest probability of lesion development. Why MS-like lesions develop following hypoxemic insults in some individuals but not in others is likely dependent upon the presence of immune predisposing factors that are governed genetically. Hypoperfusion may be due to decreased arterial supply, restricted venous return, or a combination of these. There are clinical trials ongoing or planned to treat chronic cerebrospinal venous insufficiency (CCSVI) through angioplasty. I suggest that it is important that clinical trials addressing vascular issues in MS should examine how the vascular intervention affects white matter perfusion and determine whether the extent of perfusion recovery and maintenance of this recovery is related to functional recovery and maintenance of functional recovery. Consideration should also be given to the possibility of arterial problems playing a role in hypoperfusion in some MS patients.

DTI Measurements in Multiple Sclerosis: Evaluation of Brain Damage and Clinical Implications

Emilia Sbardella, Francesca Tona, Nikolaos Petsas, and Patrizia Pantano — Sun, 31 Mar 2013 16:11:10 +0000

Diffusion tensor imaging (DTI) is an effective means of quantifying parameters of demyelination and axonal loss. The application of DTI in Multiple Sclerosis (MS) has yielded noteworthy results. DTI abnormalities, which are already detectable in patients with clinically isolated syndrome (CIS), become more pronounced as disease duration and neurological impairment increase. The assessment of the microstructural alterations of white and grey matter in MS may shed light on mechanisms responsible for irreversible disability accumulation. In this paper, we examine the DTI analysis methods, the results obtained in the various tissues of the central nervous system, and correlations with clinical features and other MRI parameters. The adoption of DTI metrics to assess the outcome of prognostic measures may represent an extremely important step forward in the MS research field.

Factors for Lower Walking Speed in Persons with Multiple Sclerosis

Sun, 31 Mar 2013 15:20:04 +0000

Objective. The purpose of this study was to analyze factors related to lower walking speed in persons with multiple sclerosis (PwMS). Methods. A cross-sectional survey was conducted. The study participants were 120 consecutive PwMS, who were able to walk, even with device assistance. Demographic and clinical data were collected. Walking speed was measured in 10 m walk test. Possible factors were assessed: disability, fatigue, visual functioning, balance confidence, physical activity level, walking impact, cognitive interference, and motor planning. A forward linear multiple regression analysis examined the correlation with lower speed. Results. Lower walking speed was observed in 85% of the patients. Fatigue (41%), recurrent falls (30%), and balance problems were also present, even with mild disability (average ). A good level of physical activity was noted in most of the subjects. Dual-task procedure revealed 11.58% of walking speed reduction. Many participants (69.57%) imagined greater walking speed than motor execution (mean ≥ 28.42%). Physical activity level was the only characteristic that demonstrated no significant difference between the groups (lower versus normal walking speed). Many mobility measures were correlated with walking speed; however, disability, balance confidence, and motor planning were the most significant. Conclusions. Disability, balance confidence, and motor planning were correlated with lower walking speed.

Assessment of Definitions of Sustained Disease Progression in Relapsing-Remitting Multiple Sclerosis

Sun, 10 Mar 2013 18:29:10 +0000

Sustained progression on the expanded disability status scale (EDSS) is a common outcome measure of disease progression in clinical studies of MS. Unfortunately, this outcome may not accurately measure long-term and irreversible disease progression. To assess the performance of definitions of sustained progression, patients with relapsing-remitting MS (RRMS) or a clinically isolated syndrome with evidence of lesions on a brain MRI were included in our study. Fifteen definitions of sustained progression using both the EDSS and the functional system (FS) scales were investigated. The impact of both relapses and changes in provider on the probability of maintaining progression was also evaluated. Although the provider scoring the EDSS sometimes changed during followup, the provider had access to previous EDSS scores. Between 15.8% and 42.2% of patients experienced sustained progression based on the definitions using EDSS as the outcome, but nearly 50% of these patients failed to maintain sustained progression for the duration of followup. When FS scales were used, progression was most common on the pyramidal and sensory scales. Unfortunately, progression on specific FS scales failed to be more sensitive to irreversible disability. Relapses or changes in provider did not explain the poor performance of the measures. Short-term changes in the EDSS or FS scores may not be an accurate marker of irreversible change in RRMS.

Gait Variability and Multiple Sclerosis

Michael J. Socie and Jacob J. Sosnoff — Sun, 03 Mar 2013 16:14:50 +0000

Gait variability, that is, fluctuations in movement during walking, is an indicator of walking function and has been associated with various adverse outcomes such as falls. In this paper, current research concerning gait variability in persons with multiple sclerosis (MS) is discussed. It is well established that persons with MS have greater gait variability compared to age and gender matched controls without MS. The reasons for the increase in gait variability are not completely understood. Evidence indicates that disability level, assistive device use, attentional requirement, and fatigue are related to gait variability in persons with MS. Future research should address the time-evolving structure (i.e., temporal characteristics) of gait variability, the clinical importance of gait variability, and underlying mechanisms that drive gait variability in individuals with MS.

Measuring the Quality of Life in Patients with Multiple Sclerosis in Clinical Practice: A Necessary Challenge

Thu, 28 Feb 2013 09:46:49 +0000

While the physical disability aspect of multiple sclerosis (MS) is of great importance, quality of life (QoL) measurements are being considered increasingly important with regard to evaluating disease progression, treatment, and the management of care provided to MS patients. Despite the acknowledged need to consider QoL issues, QoL assessment remains underutilized in clinical practice. These issues should be explored and understood to promote the use of measuring QoL in MS clinical practice. We explore the difficulties for clinicians: choosing and determining the most appropriate QoL measure and how to best integrate QoL measurements into clinical practice. This paper discusses several avenues to provide to clinicians arguments of the clinical relevance and accuracy of QoL instruments and ultimately to enhance the use of QoL measures in clinical practice for MS patients.

Quantitative MRI Demonstrates Abnormality of the Fornix and Cingulum in Multiple Sclerosis

Sat, 16 Feb 2013 14:41:51 +0000

Objective. To characterize MR signal changes associated with tissue damage in the fornix and cingulum in multiple sclerosis (MS) using quantitative MRI measures and to determine associations with cognitive dysfunction. Background. The fornix and cingulum are white-matter bundles that carry information related to cognition. While cognitive dysfunction is reported in 40–60% of MS patients, the neuroanatomical correlates of cognitive impairment remain incompletely understood. Methods. The cingulum, pillars of the fornix, and corticospinal tract were segmented by fiber tracking via diffusion tensor imaging. Average tract-specific fractional anisotropy (FA), mean diffusivity (MD), and magnetization transfer ratio (MTR) were compared in MS cases and healthy volunteers. Associations with clinical measures and neuropsychological tests were derived by multivariate linear regression. Results. Fornix FA () and MTR () were decreased, and fornix MD () and cingulum MD () increased, in MS cases () relative to healthy volunteers () after adjustment for age and sex. Lower fornix FA and MTR, and higher fornix MD and , were correlated with lower PASAT-3 scores, but not with slower 25FTW times. Lower PASAT-3 scores were associated with lower cingulum FA and higher MD and . Conclusions. Cognitive dysfunction in MS may involve damage to a widespread network of brain structures, including white-matter pathways within the limbic system.

The Gap in the Current Research on the Link between Health Locus of Control and Multiple Sclerosis: Lessons and Insights from a Systematic Review

Nicola Luigi Bragazzi — Thu, 14 Feb 2013 10:11:48 +0000

Multiple sclerosis (MS) is a chronic neurological disease whose etiology has not been fully understood yet in detail. Empirical findings show how psychosocial symptoms are very important features of the clinical presentation of MS, having a deep impact on patient's quality of life, and thus psychological coping strategies may play a central role in reducing the burden of the disease and improving patient's satisfaction of life. MS progression and relapses/exacerbations are unpredictable and may depend on factors such as stressor chronicity, frequency, severity, type, and individual patient characteristics such as depression, personality, locus of control (LOC), optimism, and perceived social support. Due to its importance for health-care delivery, rehabilitation, and nursing, here, we make a systematic review on the current state-of-the-art studies concerning the relationship between LOC and MS, according to the PRISMA guidelines, and we assess the quality and the completeness of the studies using the CONSORT instrument, underpinning their limitations, and suggesting how to fill the gap in this research field.

Ultrahigh-Field MR (7 T) Imaging of Brain Lesions in Neuromyelitis Optica

Ilya Kister, Joseph Herbert, Yongxia Zhou, and Yulin Ge — Sun, 27 Jan 2013 07:55:04 +0000

Background. Brain lesions are common in neuromyelitis optica spectrum disorder (NMOsd) and may resemble lesions of multiple sclerosis (MS). Objectives. To describe the imaging characteristics of supratentorial lesions in NMOsd on ultrahigh-field (7 T) MRI with special attention to vessel-lesion relationship. Methods. Ten NMOsd patients, all women and all seropositive for NMO IgG, with mean age of 51.3 ± 15.4 years and disease duration of 9.2 ± 6.4 years, were scanned at a 7 T whole-body human MR system with high-resolution 2D gradient echo sequence optimized to best visualize lesions and venous structures, T2- and T1-weighted imaging. Results. In 10 patients with NMOsd, a total of 92 lesions were observed (mean: 9.2 ± 8.8; range: 2–30), but only 8 lesions (9%) were traversed by a central venule. All lesions were <5 mm in diameter, and 83% were located in subcortical white matter. There were no lesions in the cortex or basal ganglia. Two patients exhibited diffuse periependymal abnormalities on FLAIR. Conclusions. Small, subcortical lesions without a central venule are the most consistent finding of NMOsd on 7 T MRI of the brain. Ultrahigh-field imaging may be useful for differentiating between NMOsd and MS.

Biomarkers in Multiple Sclerosis: An Up-to-Date Overview

Serafeim Katsavos and Maria Anagnostouli — Tue, 22 Jan 2013 07:46:47 +0000

During the last decades, the effort of establishing satisfactory biomarkers for multiple sclerosis has been proven to be very difficult, due to the clinical and pathophysiological complexities of the disease. Recent knowledge acquired in the domains of genomics-immunogenetics and neuroimmunology, as well as the evolution in neuroimaging, has provided a whole new list of biomarkers. This variety, though, leads inevitably to confusion in the effort of decision making concerning strategic and individualized therapeutics. In this paper, our primary goal is to provide the reader with a list of the most important characteristics that a biomarker must possess in order to be considered as reliable. Additionally, up-to-date biomarkers are further divided into three subgroups, genetic-immunogenetic, laboratorial, and imaging. The most important representatives of each category are presented in the text and for the first time in a summarizing workable table, in a critical way, estimating their diagnostic potential and their efficacy to correlate with phenotypical expression, neuroinflammation, neurodegeneration, disability, and therapeutical response. Special attention is given to the “gold standards” of each category, like HLA-DRB1* polymorphisms, oligoclonal bands, vitamin D, and conventional and nonconventional imaging techniques. Moreover, not adequately established but quite promising, recently characterized biomarkers, like TOB-1 polymorphisms, are further discussed.

Bimonthly Evolution of Cortical Atrophy in Early Relapsing-Remitting Multiple Sclerosis over 2 Years: A Longitudinal Study

Thu, 10 Jan 2013 15:15:21 +0000

We investigated the evolution of cortical atrophy in patients with early relapsing-remitting (RR) multiple sclerosis (MS) and its association with lesion volume (LV) accumulation and disability progression. 136 of 181 RRMS patients who participated in the Avonex-Steroids-Azathioprine study were assessed bimonthly for clinical and MRI outcomes over 2 years. MS patients with disease duration (DD) at baseline of ≤24 months were classified in the early group (DD of 1.2 years, ), while patients with DD > 24 months were classified in the late group (DD of 7.1 years, ). Mixed effect model analysis was used to investigate the associations. Significant changes in whole brain volume (WBV) (), cortical volume (CV) (), and in T2-LV () were detected. No significant MRI percent change differences were detected between early and late DD groups over 2 years, except for increased T2-LV accumulation between baseline and year 2 in the early DD group (). No significant associations were found between changes in T2-LV and CV over the followup. Change in CV was related to the disability progression over the 2 years, after adjusting for DD (). Significant cortical atrophy, independent of T2-LV accumulation, occurs in early RRMS over 2 years, and it is associated with the disability progression.

Fatigue, Tiredness, Lack of Energy, and Sleepiness in Multiple Sclerosis Patients Referred for Clinical Polysomnography

Tiffany J. Braley, Ronald D. Chervin, and Benjamin M. Segal — Thu, 20 Dec 2012 10:47:44 +0000

Objectives. To assess the relationship between nocturnal polysomnographic (PSG) findings and a group of key self-reported symptoms—fatigue, tiredness, lack of energy, and sleepiness—among sleep-laboratory referred patients with and without multiple sclerosis (MS). Methods. PSG and questionnaire data from MS patients and matched controls were analyzed retrospectively. Associations between symptoms of fatigue, tiredness, lack of energy, sleepiness, and PSG variables of interest were examined among MS patients and controls. Results. More MS patients than controls reported fatigue, tiredness, and lack of energy to occur often or almost always (Chi-square for each), but sleepiness was reported similarly by both groups (). Among MS patients, tiredness correlated with sleepiness (Spearman correlation ), and a trend emerged toward correlation between fatigue and sleepiness (Spearman correlation ). Decreased sleep efficiency on PSGs correlated with fatigue, tiredness, and lack of energy in MS patients (Spearman correlation , 0.029, and 0.048, resp.), but not sleepiness or any symptom among controls. Conclusion. In comparison to controls, MS patients report more fatigue, tiredness, and lack energy, but not sleepiness. Fatigue and related symptoms may arise from MS itself or in relation to reduced sleep efficiency.

The Diagnostic and Prognostic Value of Neurofilament Heavy Chain Levels in Immune-Mediated Optic Neuropathies

Axel Petzold and Gordon T. Plant — Mon, 17 Dec 2012 13:03:24 +0000

Background. Loss of visual function differs between immune-mediated optic neuropathies and is related to axonal loss in the optic nerve. This study investigated the diagnostic and prognostic value of a biomarker for neurodegeneration, the neurofilament heavy chain (NfH) in three immune-mediated optic neuropathies. Methods. A prospective, longitudinal study including patients with optic neuritis due to multiple sclerosis (MSON, ), chronic relapsing inflammatory optic neuritis (CRION, ), neuromyelitis optica (NMO, ), and healthy controls (). Serum NfH-SMI35 levels were quantified by ELISA. Findings. Serum NfH-SMI35 levels were highest in patients with NMO (mean ng/mL) compared to patients with CRION ( ng/mL, ), MSON (, ), and healthy controls ( ng/mL, ). High serum NfH-SMI35 levels were related to poor visual outcome. Conclusions. Blood NfH-SMI35 levels are of moderate diagnostic and more important prognostic value in immune-mediated optic neuropathies. We speculate that longitudinal blood NfH levels may help to identify particular disabling events in relapsing conditions.

Brain Abnormalities in Neuromyelitis Optica Spectrum Disorder

Woojun Kim, Su-Hyun Kim, So-Young Huh, and Ho Jin Kim — Mon, 03 Dec 2012 14:40:23 +0000

Neuromyelitis optica (NMO) is an idiopathic inflammatory syndrome of the central nervous system that is characterized by severe attacks of optic neuritis (ON) and myelitis. Until recently, NMO was considered a disease without brain involvement. However, since the discovery of NMO-IgG/antiaqaporin-4 antibody, the concept of NMO was broadened to NMO spectrum disorder (NMOSD), and brain lesions are commonly recognized. Furthermore, some patients present with brain symptoms as their first manifestation and develop recurrent brain symptoms without ON or myelitis. Brain lesions with characteristic locations and configurations can be helpful in the diagnosis of NMOSD. Due to the growing recognition of brain abnormalities in NMOSD, these have been included in the NMO and NMOSD diagnostic criteria or guidelines. Recent technical developments such as diffusion tensor imaging, MR spectroscopy, and voxel-based morphometry reveal new findings related to brain abnormalities in NMOSD that were not identified using conventional MRI. This paper focuses on the incidence and characteristics of the brain lesions found in NMOSD and the symptoms that they cause. Recent studies using advanced imaging techniques are also introduced.

Ipsilateral Uveitis and Optic Neuritis in Multiple Sclerosis

Mon, 19 Nov 2012 14:40:34 +0000

Background. Uveitis is 20 times more frequent in multiple sclerosis (MS) patients than in the general population. Methods. A retrospective study of local multiple sclerosis and uveitis cohorts described the ophthalmological and neurological characteristics of patients with multiple sclerosis and uveitis. Results. Uveitis and multiple sclerosis were associated in seven patients. The time intervals between diagnoses of MS and uveitis ranged from 6 months to 15 years. Analysis of the patients’ characteristics revealed that multiple sclerosis was associated with an older age of onset than usually expected, that is, 39 years. Uveitis was bilateral in three cases and mainly posterior (5/10). Five patients presented with acute optic neuritis (two in one eye and three in both eyes). All eyes presenting with acute optic neuritis were also affected by uveitis , though not simultaneously. Conclusion. The ipsilateral association between optic neuritis and uveitis in this series of patients with multiple sclerosis may suggest a reciprocal potentiation between optic neuritis and uveitis in multiple sclerosis.

Quantitative Magnetic Resonance Imaging of Cortical Multiple Sclerosis Pathology

Sun, 18 Nov 2012 17:19:17 +0000

Although significant improvements have been made regarding the visualization and characterization of cortical multiple sclerosis (MS) lesions using magnetic resonance imaging (MRI), cortical lesions (CL) continue to be under-detected in vivo, and we have a limited understanding of the causes of GM pathology. The objective of this study was to characterize the MRI signature of CLs to help interpret the changes seen in vivo and elucidate the factors limiting their visualization. A quantitative 3D high-resolution (350 μm isotropic) MRI study at 3 Tesla of a fixed post mortem cerebral hemisphere from a patient with MS is presented in combination with matched immunohistochemistry. Type III subpial lesions are characterized by an increase in T1, T2 and M0, and a decrease in MTR in comparison to the normal appearing cortex (NAC). All quantitative MR parameters were associated with cortical GM myelin content, while T1 showed the strongest correlation. The histogram analysis showed extensive overlap between CL and NAC for all MR parameters and myelin content. This is due to the poor contrast in myelin content between CL and NAC in comparison to the variability in myelo-architecture throughout the healthy cortex. This latter comparison is highlighted by the representation of T1 times on cortical surfaces at several laminar depths.

“Calcitriol” Is Not Synonymous with “Vitamin D”

Samantha M. Kimball and Heather E. Hanwell — Tue, 23 Oct 2012 10:41:09 +0000

Induced Brain Plasticity after a Facilitation Programme for Autobiographical Memory in Multiple Sclerosis: A Preliminary Study

Thu, 18 Oct 2012 13:24:30 +0000

This preliminary study tackles the assessment and treatment of autobiographical memory (AbM) in relapsing-remitting multiple sclerosis (RR-MS) patients. Our aim was to investigate cerebral activation changes, following clinical improvement of AbM due to a cognitive training based on mental visual imagery (MVI). We assessed AbM using the Autobiographical Interview (AI) in eight patients and 15 controls. The latter subjects established normative data. The eight patients showed selective defective performance on the AI. Four patients were trained cognitively and underwent pre- and post-AI and fMRI. The remaining four patients took a second AI, at the same interval, but with no intervention in between. Results showed a significant improvement of AbM performance after the facilitation programme that could not be explained by learning effects since the AI scores remained stable between the two assessments in the second group of patients. As expected, AbM improvement was accompanied by an increased cerebral activity in posterior cerebral regions in post-facilitation fMRI examination. We interpret this activation changes in terms of reflecting the emphasis made on the role of MVI in memory retrieval through the facilitation programme. These preliminary significant clinical and neuroimaging changes suggest the beneficial effects of this technique to alleviate AbM retrieval deficit in MS patients.

Cortical Pathology in RRMS: Taking a Cue from Four Sisters

Thu, 27 Sep 2012 09:53:26 +0000

Background. Although grey matter pathology is a relevant aspect of multiple sclerosis (MS) both with physical and cognitive rebounds, its pathogenesis is still under investigation. To what extent the familial and sporadic cases of MS differ in cortical pathology has not been elucidated yet. Here we present a multiple case report of four sisters affected by MS, all of them having a very high burden of cortical pathology. Methods. The clinical and grey matter MRI parameters of the patients were compared with those of twenty-five-aged matched healthy women and 25 women affected by sporadic MS (matched for age, disease duration, EDSS, and white matter lesion load). Results. Despite their short disease duration (<5 years), the four sisters showed a significant cortical thinning compared to healthy controls () and sporadic MS () and higher CLs number () and volume () compared to sporadic MS. Discussion. Although limited to a single family, our observation is worth of interest since it suggests that familial factors may account for a peculiar involvement of the cortex in MS pathology. This hypothesis should be further evaluated in a large number of multiplex MS families.

Absence of Multiple Sclerosis and Demyelinating Diseases among Lacandonians, a Pure Amerindian Ethnic Group in Mexico

Wed, 29 Aug 2012 10:06:40 +0000

Multiple Sclerosis (MS) is a highly polymorphic disease characterized by different neurologic signs and symptoms. In MS, racial and genetic factors may play an important role in the geographic distribution of this disease. Studies have reported the presence of several protective alleles against the development of autoimmune disorders. In the case of MS, however, they help define MS as a complex disease, and confirm the importance of environmental agents as an independent variable not associated with ethnicity. We carried out an on-site epidemiological study to confirm the absence of MS or NMO among Lacandonians, a pure Amerindian ethnic group in Mexico. We administered a structured interview to 5,372 Lacandonians to assess by family background any clinical data consistent with the presence of a prior demyelinating event. Every participating subject underwent a comprehensive neurological examination by a group of three members of the research team with experience in the diagnosis and treatment of demyelinating disorders to detect clinical signs compatible with a demyelinating disease. We did not find any clinical signs compatible with multiple sclerosis among study participants.

Falls and Physical Activity in Persons with Multiple Sclerosis

J. J. Sosnoff, B. M. Sandroff, J. H. Pula, S. M. Morrison, and R. W. Motl — Thu, 23 Aug 2012 17:43:26 +0000

Objectives. To examine the association between fall history and physical activity using an objective measure of physical activity (i.e., accelerometry) in persons with multiple sclerosis. Design. A community-based sample of 75 ambulatory persons with multiple sclerosis volunteered for the investigation. Participants self-reported fall history in the last year, underwent a neurological exam to determine Expanded Disability Status Scale (EDSS) score, and wore an accelerometer around the waist for 7 consecutive days to determine physical activity. Results. Overall, 37 persons (49.3% of the sample) reported falling in the last year with 28 of the 37 falling more than once. Persons who fell in the last year had a significantly lower number of steps/day than nonfallers (3510 versus 4940 steps/day; 𝑃<.05). However, when controlling for disability status there was no statistically significant difference between fallers and nonfallers (4092 versus 4373 steps/day; 𝑃>.05). Conclusions. Collectively, the findings suggest that fall history may have little impact on current physical activity levels in persons with multiple sclerosis.

Combination Therapy of Interferon Beta-1b and Tacrolimus: A Pilot Safety Study

F. Jacques, I. Gaboury, S. Christie, and F. Grand'Maison — Wed, 15 Aug 2012 09:08:44 +0000

Tacrolimus is a calcineurin inhibitor which works to induce immune suppression by preventing cytokine transcription and lymphocyte activation. Combining the immunomodulator interferon beta-1b (Betaseron) with the immunosuppressant tacrolimus (Prograf) may have the potential of additive therapeutic benefit through the complementary mechanisms of action of these two therapeutics. In this randomized, open-label, multicenter, two-arm pilot study, the authors examined the safety and tolerability of the combination of interferon beta-1b and tacrolimus in relapsing remitting (RRMS) and secondary progressive (SPMS) multiple sclerosis patients who have failed one or more immunomodulatory therapies. Patients (𝑛=25) received a combination of interferon beta-1b subcutaneously every other day and oral tacrolimus (low blood level tacrolimus, 1–5 ng/mL, or high blood level tacrolimus, 5–10 ng/mL) for a period of 38 weeks. The combination therapy of interferon beta-1b and tacrolimus over the 10-month period of the study was shown to be safe and relatively well tolerated. There were no unexpected adverse events occurring as the result of the combination therapy. Further study of this combination therapy in patients with multiple sclerosis unresponsive to conventional therapy is warranted.

Activities-Specific Balance Confidence in People with Multiple Sclerosis

Ylva Nilsagård, Anna Carling, and Anette Forsberg — Tue, 07 Aug 2012 09:39:34 +0000

Objective. To evaluate the validity of the Activities-specific Balance Confidence scale (ABC) in people with multiple sclerosis (PwMS). Design. A multicentre, cross-sectional study. Setting. Six rural and urban Swedish sites, including specialized units at hospitals and primary care centers. Participants. A sample of 84 PwMS with subjective gait and balance impairment but still able to walk 100 m (comparable with EDSS 1–6). Outcome Measures. Timed Up and Go, Timed Up and Gocog, 25-foot Timed Walk Test, Four Square Step Test, Dynamic Gait Index, Chair Stand Test, 12-item MS Walking Scale, self-reported falls, and use of assistive walking device were used for validation. Results. The concurrent convergent validity was moderate to good (0.50 to −0.75) with the highest correlation found for the 12-item MS Walking Scale. The ABC discriminated between multiple fallers and nonfallers but not between men and women. Ecological validity is suggested since ABC discriminated between users of assistive walking device and nonusers. The internal consistency was high at 𝛼=0.95, and interitem correlations were between 0.30 and 0.83. Conclusion. This study supports the validity of the ABC for persons with mild-to-moderate MS. The participants lacked balance confidence in many everyday activities, likely restricting their participation in society.

A Randomised, Double-Blind, Placebo-Controlled Trial with Vitamin D3 in MS: Subgroup Analysis of Patients with Baseline Disease Activity Despite Interferon Treatment

J. Åivo, B.-M. Lindsröm, and M. Soilu-Hänninen — Sun, 05 Aug 2012 10:53:52 +0000

We present a subgroup analysis of the first double-blind, placebo-controlled, randomised trial with vitamin D3 in MS. In the overall study population, there were 34 patients in the vitamin D arm and 32 patients in the placebo arm. All the patients were using interferon-β-1b (IFNB) therapy. The subgroup consisted of 15 patients in the vitamin D arm and 15 patients in the placebo arm, who had either at least one relapse during the year preceding the study or enhancing T1 lesions at the baseline MRI scan. We measured the total number of MRI T1 enhancing lesions, the number of new/enlarging T2 lesions and T2 lesion volume (BOD) (mm3), EDSS (Expanded Disability Status Scale), annual relapse Rate (ARR), timed 25-foot walk (T25FW), and timed 10-foot tandem walk (TT10W) at baseline and at 12 months in the vitamin D-treated and in the placebo-treated patients. There was a statistically significant reduction in the number of T1 enhancing lesions, a smaller T2 lesion volume growth and less new/enlarging T2 brain MRI lesions in the vitamin D3-treated than in the placebo-treated subgroup patients. The MRI results were slightly more pronounced in the subgroup than in the overall study population.

Retinal Damage in Multiple Sclerosis Disease Subtypes Measured by High-Resolution Optical Coherence Tomography

Wed, 25 Jul 2012 09:27:14 +0000

Background. Optical coherence tomography (OCT) has facilitated characterisation of retinal alterations in MS patients. Only scarce and in part conflicting data exists on different MS subtypes. Objective. To analyse patterns of retinal changes in different subtypes of MS with latest spectral-domain technology. Methods. In a three-centre cross-sectional study 414 MS patients and 94 healthy controls underwent spectral-domain OCT examination. Results. Eyes of MS patients without a previous optic neuritis showed a significant reduction of both retinal nerve fibre layer (RNFL) thickness and total macular volume (TMV) compared to healthy controls independent of the MS subtype (𝑃<0.001 for all subtypes). RNFL thickness was lower in secondary progressive MS (SPMS) eyes compared to relapsing-remitting MS (RRMS) eyes (𝑃=0.007), and TMV was reduced in SPMS and primary progressive MS (PPMS) eyes compared to RRMS eyes (SPMS: 𝑃=0.039, PPMS: 𝑃=0.005). Independent of the subtype a more pronounced RNFL thinning and TMV reduction were found in eyes with a previous optic neuritis compared to unaffected eyes. Conclusion. Analysis of this large-scale cross-sectional dataset of MS patients studied with spectral-domain OCT confirmed and allows to generalize previous findings. Furthermore it carves out distinct patterns in different MS subtypes.

1st International Symposium on Gait and Balance in MS: Gait and Balance Measures in the Evaluation of People with MS

Michelle Cameron, Joanne Wagner, Kathleen Zackowski, and Rebecca Spain — Sun, 17 Jun 2012 09:38:05 +0000

Gait and balance measures have particular potential as outcome measures in Multiple Sclerosis (MS) because, of the many hallmarks of MS disability, gait and balance dysfunction are present throughout the course of the disease, impact many aspects of a person’s life, and progress over time. To highlight the importance and relevance of gait and balance measures in MS, explore novel measurements of gait and balance in MS, and discuss how gait, balance, and fall measures can best be used and developed in clinical and research settings, the 1st International Symposium on Gait and Balance in Multiple Sclerosis was held in Portland, Oregon, USA on October 1, 2011. This meeting brought together nearly 100 neurologists, physiatrists, physical therapists, occupational therapists, nurses, engineers, and others to discuss the current status and recent advances in the measurement of gait and balance in MS. Presentations focused on clinician-administered, self-administered, and instrumented measures of gait, balance, and falls in MS.

Overall Memory Impairment Identification with Mathematical Modeling of the CVLT-II Learning Curve in Multiple Sclerosis

Igor I. Stepanov, Charles I. Abramson, Marietta Hoogs, and Ralph H. B. Benedict — Wed, 13 Jun 2012 15:49:30 +0000

The CVLT-II provides standardized scores for each of the List A five learning trials, so that the clinician can compare the patient's raw trials 1–5 scores with standardized ones. However, frequently, a patient's raw scores fluctuate making a proper interpretation difficult. The CVLT-II does not offer any other methods for classifying a patient's learning and memory status on the background of the learning curve. The main objective of this research is to illustrate that discriminant analysis provides an accurate assessment of the learning curve, if suitable predictor variables are selected. Normal controls were ninety-eight healthy volunteers (78 females and 20 males). A group of MS patients included 365 patients (266 females and 99 males) with clinically defined multiple sclerosis. We show that the best predictor variables are coefficients 𝐵3 and 𝐵4 of our mathematical model 𝐵3∗exp(−𝐵2∗(𝑋−1))+𝐵4∗(1−exp(−𝐵2∗(𝑋−1))) because discriminant functions, calculated separately for 𝐵3 and 𝐵4, allow nearly 100% correct classification. These predictors allow identification of separate impairment of readiness to learn or ability to learn, or both.