The objective of this study was to characterize the population of multiple sclerosis (MS) patients suffering from spasticity and to evaluate treatment patterns, including intrathecal baclofen (ITB) delivery, related to patient quality of life (QOL). We conducted a cross-sectional, two-level study using data from the Patient Registry of the North American Research Committee on MS (NARCOMS). In addition, we surveyed a subgroup of 198 preselected patients who are using ITB (ITBG) and a random sample of 315 oral drug users (ORALG). Among the registrants, 16% reported no spasticity, 31% minimal, 19% mild, 17% moderate (frequently affects activities), 13% severe (daily forced to modify activities) and 4% total (prevents daily activities). Patients experiencing greater severity included by proportion males, and those older and with longer duration of MS. QOL scores decreased inversely with severity. In the focused survey, ITBG reported lower levels of spasticity than ORALG, less stiffness in the legs, less pain and fewer spasms at any time. They scored significantly lower in the SF-36 physical component, yet reported less fatigue on the MFIS scale. Prevalence data reveal that one third of MS patients modify or eliminate daily activities as a result of spasticity. Treatment of spasticity can significantly impact QOL parameters by reducing spasms, pain and fatigue.

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Background: Most of Multiple Sclerosis (MS) patients without previous optic neuritis (ON) show

The ongoing US Glatiramer Acetate (GA) Trial is the longest evaluation of continuous immunomodulatory therapy in relapsing-remitting multiple sclerosis (RRMS). The objective of this study was to evaluate up to 15 years of GA as a sole disease-modifying therapy. Two hundred and thirty-two patients received at least one GA dose since study initiation in 1991 (mITT cohort), and 100 (43%, Ongoing cohort) continued as of February 2008. Patients were evaluated every 6 months using the Expanded Disability Status Scale (EDSS). Mean GA exposures were 8.6 ±5.2, 4.81 ±3.69, and 13.6 ± 1.3 years and mean disease durations were 17, 13, and 22 years for mITT, Withdrawn and Ongoing cohorts, respectively. For Ongoing patients, annual relapse rates (ARRs) maintained a decline from 1.12±0.82 at baseline to 0.25 ± 0.34 per year; 57% had stable/improved EDSS scores (change ± 0.5 points); 65% had not transitioned to secondary progressive multiple sclerosis (SPMS); 38%, 18%, and 3% reached EDSS 4, 6, and 8. For all patients on GA therapy (the mITT cohort), ARRs declined from 1.18 ± 0.82 to 0.43 ± 0.58 per year; 54% had stable/improved EDSS scores; 75% had not transitioned to SPMS; 39%, 23%, and 5% reached EDSS 4, 6, and 8. In conclusion, multiple sclerosis patients with mean disease duration of 22 years administering GA for up to 15 years had reduced relapse rates, and decreased disability progression and transition to SPMS. There were no long-term safety issues.

Objective:To update the consensus recommendations for reporting of quantitative optical coherence tomography (OCT) study results, thus revising the previously published Advised Protocol for OCT Study Terminology and Elements (APOSTEL) recommendations.Methods:To identify studies reporting quantitative OCT results, we performed a PubMed search for the terms “quantitative” and “optical coherence tomography” from 2015 to 2017. Corresponding authors of the identified publications were invited to provide feedback on the initial APOSTEL recommendations via online surveys following the principle of a modified Delphi method. The results were evaluated and discussed by a panel of experts, and changes to the initial recommendations were proposed. A final survey was recirculated among the corresponding authors to obtain a majority vote on the proposed changes.Results:One hundred sixteen authors participated in the surveys, resulting in 15 suggestions, of which 12 were finally accepted and incorporated into an updated 9-point-checklist. We harmonized the nomenclature of the outer retinal layers, added the exact area of measurement to the description of volume scans; we suggested reporting device-specific features. We advised to address potential bias in manual segmentation or manual correction of segmentation errors. References to specific reporting guidelines and room light conditions were removed. The participants’ consensus with the recommendations increased from 80% for the previous APOSTEL version to greater than 90%.Conclusions:The modified Delphi method resulted in an expert-led guideline (evidence class III, GRADE criteria) concerning study protocol, acquisition device, acquisition settings, scanning protocol, fundoscopic imaging, post-acquisition data selection, post-acquisition analysis, nomenclature and abbreviations, and statistical approach. It will still be essential to update these recommendations to new research and practices regularly.

Schwann cells derived from human sural nerve may provide a valuable source of tissue for a cell-based therapy in multiple sclerosis. However, it is essential to show that transplanted human Schwann cells can remyelinate axons in adult CNS and improve axonal conduction. Sections of sural nerve were removed from amputated legs of patients with vascular disease or diabetes, and Schwann cells were isolated and cryopreserved. Suspensions of reconstituted cells were transplanted into the X-irradiation/ethidium bromide lesioned dorsal columns of immunosuppressed Wistar rat. After 3-5 weeks of extensive remyelination, a typical Schwann cell pattern was observed in the lesion zone. Many cells in the lesion were immunopositive for an anti-human nuclei monoclonal antibody. The dorsal columns were removed and maintained in an in vitro recording chamber; the conduction properties were studied using field potential and intra-axonal recording techniques. The transplanted dorsal columns displayed improved conduction velocity and frequency-response properties, and action potentials conducted over a greater distance into the lesion, suggesting that conduction block was overcome. These data support the conclusion that transplantation of human Schwann cells results in functional remyelination of a dorsal column lesion.

BackgroundGait impairment represents one of the most common and disabling symptom of multiple sclerosis. Quantification of the gait is an important aspect of clinical trials. In order to identify which temporal or spatial parameters of gait could be used as outcome measures in interventional studies of patients with different levels of disability, we evaluated characteristics of these parameters in MS patients across the whole spectrum of mobility from EDSS 0 to 6.5.MethodsThis is a cross-sectional study of spatial and temporal parameters of gait at self selected speed and at fast speed of walking in 284 patients with multiple sclerosis (108 men, mean age 38 years ± SD 10.8 years, range 18–64) divided into seven levels of disability (EDSS 0 to 1.5, EDSS 2.0 to 2.5, EDSS 3.0 to 3.5, EDSS 4.0 to 4.5, EDSS 5.0 to 5.5, EDSS 6.0, EDSS 6.5).ResultsThe velocity of gait decreases with increasing EDSS levels. Hovewer, the spatio-temporal parameters of gait that are involved in this process differ across the EDSS levels. The step length is decreased at higher EDSS levels up to the EDSS 6.0, but was not different between EDSS 6.0 and 6.5. The step time is significantly longer at EDSS 6.0 and 6.5, while the step length remains the same at those levels. The increase in percentage of double support time becomes statistically significant at EDSS 3.0-3.5 and continues to increase until EDSS 6.5. Variability of step time, step length or step width did not show significant difference between studied EDSS levels.ConclusionsThere is no single spatio-temporal parameter of gait (other than velocity of gait) that would show significant differences among all levels of EDSS. The step length reflects shortening of steps at lower EDSS levels (2.0 to 6.0), and percentage of double support time better reflects changes at higher EDSS levels 3.0 – 6.5. Gait variability is not associated with disability in MS and therefore would not be a suitable outcome measure. These observations have to be considered when designing gait experiments with temporal and spatial parameters of gait as outcomes.

References 30 (max is 30) * > 0•5% patients per system organ class and > 1% patients per preferred term (MedDRA Version 19•1 System Organ Class Preferred Term; MedDRA = Medical Dictionary for Regulatory Activities) TEAE = Treatment Emergent Adverse Event * Based on Safety population; MD1003 n=331 and placebo n=311. ^ T2 imaging analysis at M6 is M0-M6 and at M15 is M6-M15. DMT = disease modifying treatment; Gd+ = gadolinium enhanced; MRI = Magnetic Resonance Imaging