Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP)

International audienceSummaryBackground High doses of intravenous methylprednisolone are recommended to treat relapses in patients with multiple sclerosis, but can be inconvenient and expensive. We aimed to assess whether oral administration of high-dose methylprednisolone was non-inferior to intravenous administration. Methods We did this multicentre, double-blind, randomised, controlled, non-inferiority trial at 13 centres for multiple sclerosis in France. We enrolled patients aged 18–55 years with relapsing-remitting multiple sclerosis who reported a relapse within the previous 15 days that caused an increase of at least one point in one or more scores on the Kurtzke Functional System Scale. With use of a computer-generated randomisation list and in blocks of four, we randomly assigned (1:1) patients to either oral or intravenous methylprednisolone, 1000 mg, once a day for 3 days. Patients, treating physicians and nurses, and data and outcome assessors were all masked to treatment allocation, which was achieved with the use of saline solution and placebo capsules. The primary endpoint was the proportion of patients who had improved by day 28 (decrease of at least one point in most affected score on Kurtzke Functional System Scale), without need for retreatment with corticosteroids, in the per-protocol population. The trial was powered to assess non-inferiority of oral compared with intravenous methylprednisolone with a predetermined non-inferiority margin of 15%. This trial is registered with ClinicalTrials.gov, number NCT00984984. Findings Between Jan 29, 2008, and June 14, 2013, we screened 200 patients and enrolled 199. We randomly assigned 100 patients to oral methylprednisolone and 99 patients to intravenous methylprednisolone with a mean time from relapse onset to treatment of 7·0 days (SD 3·6) and 7·4 days (3·9), respectively. In the per-protocol population, 66 (81%) of 82 patients in the oral group and 72 (80%) of 90 patients in the intravenous group achieved the primary endpoint (absolute treatment difference 0·5%, 90% CI −9·5 to 10·4). Rates of adverse events were similar, but insomnia was more frequently reported in the oral group (77 [77%]) than in the intravenous group (63 [64%]). Interpretation Oral administration of high-dose methylprednisolone for 3 days was not inferior to intravenous administration for improvement of disability scores 1 month after treatment and had a similar safety profile. This finding could have implications for access to treatment, patient comfort, and cost, but indication should always be properly considered by clinicians. Funding French Health Ministry, Ligue Française contre la SEP, Tev

MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.

BACKGROUND: Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. OBJECTIVE: To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. METHODS: Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. RESULTS: A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. CONCLUSION: MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated.journal article2016 Nov2016 09 01importe

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Laboratory running test vs. field roller skiing test in cross-country skiers : a longitudinal study

Does social-media usage (e.g. Twitter) influence candidates' number of votes? Recent studies have shown that a modest impact might exist. However, these studies used data on elections in which only a limited group of politicians used Twitter. In such a context it was easy for a candidate to stand out. It remains to be seen whether the effect holds in times of widespread usage. This study compares a low-usage with a widespread-usage election, the Dutch 2010 and 2012 national elections respectively. It utilizes unique data on all 1024 candidates of the 'large' parties. Interestingly, even in the context of widespread Twitter usage we still find a positive association between Twitter use and preference votes

Immuno-Guided Laser-Capture Microdissection of Glial Cells for mRNA Analysis

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The Rise of Connected Tools in Medicine : Evaluating Neurological Deficits in Lower Limbs With The MYO Armband in Multiple Sclerosis Patients

International audienceObjective: Analysing simple biomechanistics and kinetics parameters of the non invasive, easy-to-use, biosensor MYO Armband can help assessing and monitoring neurological disabilities, especially motor and gait impairments and progression in Multiple Sclerosis (MS) patients.Background: Because of the high variability of MS clinical onset, evolution, phenotypes and mechanisms, the longitudinal assessment of this disease and its progression remain to this date a challenge for Neurologists worldwide.Design/Methods: We included 20 MS patients followed at the Nantes University Hospital(France) and included in the {\textquotedblleft}Myo Project{\textquotedblright} study, from January to December 2018. While wearing the MYO armband, patients performed several clinical tests, including clinical EDSS, Timed 25-foot Walk test, Romberg maneuver, Heel-Knee test and filled auto-questionnaires including a patient EDSS (pEDSS). We analysed data from the 3 dimension inertial measurement unit (gyroscope and accelerometer) and the surface electromyogram (sEMG) included in the MYO.Results: 20 patients presenting with remitting-recurring MS and 5 healthy controls matched with sex and age were included in this study. The mean rotation speed measured with the gyroscope sensor, increased with the severity of the disease along the X, Y and Z axis; r(x)=0.558, r(y)=0.328, r(z)=0.443 and respectively p=0.00029, p=0.000298, p=0.0003 for the Romberg maneuver. There was a significant negative correlation between the linear acceleration measured with the accelerometer along the X-axis, r(x)=-0.731 (p=0.030) and Y-axis, r(y)=-0.273 (p=0.0002) and a positive correlation along the Z axis, r(z)=0.792 (p=10-4) for the 25-foot walk test. The pEDSS responses were correlated with the cEDSS. A big data analytics approach of raw data obtained with the sEMG allows to differentiate MS patients from healthy controls.Conclusions: There is a correlation between certain measures obtained with the MYO Armband and MS severity and progression. The MYO can also differentiate the muscle contraction profile of the lower limbs of MS patients and healthy controls

B cell differentiation is defective in Multiple Sclerosis patients

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Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic

International audienceThe immune system plays a significant role in multiple sclerosis. While MS was historically thought to be T cell-mediated, multiple pieces of evidence now support the view that B cells are essential players in multiple sclerosis pathogenic processes. High-efficacy disease-modifying therapies that target the immune system have emerged over the past two decades. Anti-CD20 monoclonal antibodies selectively deplete CD20+ B and CD20+ T cells and efficiently suppress inflammatory disease activity. These monotherapies prevent relapses, reduce new or active magnetic resonance imaging brain lesions, and lessen disability progression in patients with relapsing multiple sclerosis. Rituximab, ocrelizumab, and ofatumumab are currently used in clinical practice, while phase III clinical trials for ublituximab have been recently completed. In this review, we compare the four anti-CD20 antibodies in terms of their mechanisms of action, routes of administration, immunological targets, and pharmacokinetic properties. A deeper understanding of the individual properties of these molecules in relation to their efficacy and safety profiles is critical for their use in clinical practice

Increased IGM and IGG anti-NEU5GC antibodies in infectious mononucleosis (IMN): link with multiple sclerosis (MS)?

International audienceIntroduction: Multiple Sclerosis (MS) is a chronic inflammatory and demyelinating disease which displays an autoimmune component at its overt clinical stage. Among etiological hypotheses, the potential initiating role of EBV in the disease has been raised following works linking EBNA levels and the risk of MS occurrence [1] showing a linkage between the occurrence of IMN and MS. Our hypothesis is that a vigorous production of anti-Neu5Gc in IMN (as indirectly measured by Paul-Bunnell Davidson reaction) may induce brain blood barrier alterations when the EBV primo-infection is contemporary of an extraordinary high frequency of EBV committed T cells and of circulating EBV+ memory B cells[2]. Our aim was to measure anti-Neu5Gc IgG and IgM levels during the IMN and to investigate whether levels of anti-NeuGc could be also increased in MS. Material and Methods: Sera from 49 patients with overt IMN were collected from the University Hospital of Grenoble and Nantes. The gender ratio was 22F/ 27M. The age average was 24 years (range: 7- 65). Two cohorts of EBV negative individuals (n= 45) and healthy individuals (n= 120) were used as controls. A second cohort of 46 patients with proven MS was collected from the University Hospital of Nantes. The gender ratio was 30F/ 16M. The age average was 48 years (range: 22-73). This cohort contained 30 patients presenting a Remitting Relapsing (RR) form (65.2%) and 16 with a Secondary or Primary Progressive (SP-PP) one (34.7%). A cohort of healthy individuals (n= 37) matched for gender and age was used as controls. On these samples, we performed two Elisa [3][4] to quantify anti-Neu5Gc IgG and IgM antibodies. Results: We showed a highly significant increase in anti-Neu5Gc IgM in IMN patients in comparison to EBV negative controls (0.82±0.16 vs. 0.15±0.05 ng/ul; p<0.0001). Anti-Neu5Gc IgG were also, though less dramatically, increased (3.64±0.6 vs. 2.78±0.57ng/ul; p=0.04). The values obtained in IMN differed significantly to healthy individuals (0.82±0.16 vs. 0.2±0.03 ng/ul;p<0.0001 for IgM and 3.63±0.6 vs. 2.74±0.3 ng/ul; p= 0.01 for IgG). The levels of anti-α1-3Gal epitopes, an other type of «xeno» antibody against a sugar not synthesized by normal individuals were also increased during IMN (12.4±1.1 vs. 9.67±1.46 ng/ul for EBV negative controls and vs. 11.7±3.4 ng/ul for healthy individuals; p<0.0001 for both). We found neither increase in anti-Neu5gc antibodies in this small MS patient cohort (p=0.8 for IgM and p=0.84 for IgG), nor in RR or SP-PP subgroups. We found no correlation between the anti-Neu5Gc titers and age or gender of IMN or MS patients, or of healthy individuals. Conclusion: Despite the fact that EVB does not express Neu5Gc, anti-Neu5Gc antibodies are strongly increased in IMN patients, suggesting that uptake of Neu5Gc from dietary sources by EBV infected cells induces them to become more immunogenic during the acute disease. However our data did not evidence higher anti-Neu5Gc antibodies in established MS

CD161 intermediate expression defines a novel activated, inflammatory and pathogenic subset of CD8+ T cells involved in multiple sclerosis

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