Efficacy, safety and patient reported outcomes in patients with active relapsing multiple sclerosis treated with ocrelizumab: Final results from the PRO-MSACTIVE study.

Background: Ocrelizumab, a humanized anti-CD20 monoclonal antibody, has been approved in Europe for the treatment of adult patients with active relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS), on the basis of previous phase III studies. However, limited data were available on ocrelizumab efficacy in RMS according to the Lublin definition of activity (clinical and/or imaging features) used in the current drug label. The PRO-MSACTIVE study was thus designed to provide additional data on ocrelizumab efficacy according to this definition, and also on safety and patient reported outcomes (PROs).

The effectiveness of natalizumab vs fingolimod-A comparison of international registry studies.

Background: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening.

Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs.

Digital biomarkers can highlight subtle clinical differences in radiologically isolated syndrome compared to healthy controls.

Objective: To explore the use of digital biomarkers to distinguish healthy controls (HC) from subjects with a radiologically isolated syndrome (RIS).

Methods: We developed a smartphone application called MS Screen Test (MSST) to explore several dimensions of the neurological exam such as finger tapping speed, agility, hand synchronization, low contrast vision and cognition during a short evaluation. This app was tested on a cohort of healthy volunteers including a subset of subjects who underwent two evaluations on the same day to assess reproducibility.

Cerebellar volume loss in radiologically isolated syndrome.

Radiologically isolated syndrome (RIS), in which asymptomatic demyelinating-appearing lesions are detected incidentally on MRI, can be a pre-clinical form of multiple sclerosis (MS). In this study, we measured cerebellar volumes on 3D T1-weighted 3T MR images in 21 individuals with RIS and 38 age- and sex-matched healthy controls (HC). Normalized cerebellar white matter volume and the anterior cerebellar gray matter volume were significantly decreased in RIS compared to HC ( = 0.

Immunization and multiple sclerosis: Recommendations from the French multiple sclerosis society.

Objectives: To establish recommendations on immunization for patients with multiple sclerosis (MS) BACKGROUND: Vaccines have been suspected in the past to trigger MS and relapses. With the extension of the immunoactive treatment arsenal, other concerns have been raised more recently about an increased risk of infection or a decreased effectiveness of immunization in immunosuppressed patients.

Methods: The French Group for Recommendations into Multiple Sclerosis (France4MS) performed a systematic search of papers in Medline and other university databases (January 1975-June 2018).

Oligoclonal bands increase the specificity of MRI criteria to predict multiple sclerosis in children with radiologically isolated syndrome.

Background: Steps towards the development of diagnostic criteria are needed for children with the radiologically isolated syndrome to identify children at risk of clinical demyelination.

Objectives: To evaluate the 2005 and 2016 MAGNIMS magnetic resonance imaging criteria for dissemination in space for multiple sclerosis, both alone and with oligoclonal bands in cerebrospinal fluid added, as predictors of a first clinical event consistent with central nervous system demyelination in children with radiologically isolated syndrome.

Methods: We analysed an international historical cohort of 61 children with radiologically isolated syndrome (≤18 years), defined using the 2010 magnetic resonance imaging dissemination in space criteria (Ped-RIS) who were followed longitudinally (mean 4.

Multiple sclerosis with atypical MRI presentation: Results of a nationwide multicenter study in 57 consecutive cases.

Background: The recent 2017 modification have increased the sensitivity of McDonald criteria for MS. Nevertheless, some MS patients with atypical MRI findings have been identified, leading to prolonged delay to diagnosis and high costs to look for alternative diagnoses.

Objective: To describe a series of MS patients with atypical MRI presentation.

De novo convulsive status epilepticus in patients with multiple sclerosis treated with dalfampridine.

Background: Dalfampridine extended release (DAL) is a broad-spectrum voltage-gated potassium channel blocker that is indicated in multiple sclerosis to improve the nerve conduction of demyelinated axons. Seizures are a known side effect of DAL, which is contraindicated in patients with a history of epilepsy.

Objective: Three cases of multiple sclerosis (MS) with de novo convulsive status epilepticus (CSE) probably related to dalfampridine administration are described.

Cancer Risk in Patients with Multiple Sclerosis: Potential Impact of Disease-Modifying Drugs.

In the 1990s, the first disease-modifying therapies (DMTs) for multiple sclerosis (MS) were injectable immunomodulatory (IM) drugs, including four different interferon-β preparations and glatiramer acetate. Since 2000, more than 15 immunosuppressant (IS) drugs have been used, with a more or less specific action on inflammation. These include monoclonal antibodies targeting CTL4, the integrin receptor, the interleukin (IL)-2 receptor, CD19, CD20, CD52, and the sphingosine 1 phosphate family.

Only Follow-Up of Memory B Cells Helps Monitor Rituximab Administration to Patients with Neuromyelitis Optica Spectrum Disorders.

Introduction: Neuromyelitis optica spectrum disorders (NMOSD) are identified as a spectrum of inflammatory demyelinating disorders involving the brain, spinal cord and optic nerves. These disorders require early diagnosis and highly active immunosuppressive treatment. Rituximab (RTX) has demonstrated efficacy in limiting relapse in NMOSD when using several administration schedules.

Cerebrospinal fluid chitinase-3-like protein 1 level is not an independent predictive factor for the risk of clinical conversion in radiologically isolated syndrome.

Background: Younger age, male sex and presence of spinal cord lesion(s) increase the risk of conversion from radiologically isolated syndrome (RIS) to relapsing-remitting multiple sclerosis (RRMS). Elevated cerebrospinal fluid (CSF) chitinase-3-like protein 1 (CHI3L1) levels predict conversion from clinically isolated syndrome (CIS) to RRMS.

Objective: To evaluate the prognostic value of CSF CHI3L1 in RIS patients for conversion to RRMS.

Anomalies Characteristic of Central Nervous System Demyelination: Radiologically Isolated Syndrome.

Radiologically isolated syndrome (RIS) was defined in 2009 for asymptomatic patients who presented incidentally identified white matter anomalies within the central nervous system suggestive of multiple sclerosis (MS). Approximately one-third of RIS subjects will have a seminal clinical demyelinating event within 5 years of the identification of their abnormal MRI. Clinical evolution mirrors relapsing remitting or progressive forms of MS.

Cognition and quality of life in clinically isolated syndrome patients starting a disease modifying therapy in the QUALICIS study may not predict treatment response at one year.

Cognition and health-related quality of life (HRQoL) are early involved in multiple sclerosis (MS). The aim of QUALICIS study was to monitor cognition and HRQoL prospectively in a cohort of clinically isolated syndrome (CIS) patients starting a treatment with subcutaneous beta-1b interferon as a first disease modifying treatment (DMT), and to assess their correlation with the clinical outcome 6years later. Relapse history, EDSS and yearly standardized brain MRI data were also collected.

Radiologically isolated syndrome in children: Clinical and radiologic outcomes.

Objective: To describe clinical and radiologic outcomes of children with incidental findings on neuroimaging suggestive of CNS demyelination (termed "radiologically isolated syndrome" or RIS).

Methods: Clinical and radiologic data were obtained from a historical cohort of children with no symptoms of demyelinating disease who had MRI scans that met the 2010 MRI criteria for dissemination in space for MS.

Results: We identified 38 children (27 girls and 11 boys) with RIS now being prospectively followed at 16 sites in 6 countries.

A Case Report of Solitary Sclerosis: This is Really Multiple Sclerosis.

Progressive solitary sclerosis is characterized by an isolated central nervous system demyelinating lesion arising in the spinal cord and brainstem, responsible for progressive motor impairment. We describe the case of a 40-year-old patient treated for more than 2 years with high doses of biotin (CERENDAY) for progressive symptoms of solitary sclerosis, who presented asymptomatic new T2 white matter lesions on brain magnetic resonance imaging (MRI). As there is no treatment option for solitary sclerosis, high doses of biotin were proposed, but had no impact on the progression of motor deficit.

Natalizumab-PML survivors with subsequent MS treatment: Clinico-radiologic outcome.

Objective: To describe the clinico-radiologic outcome of MS patients with natalizumab-related progressive multifocal leukoencephalopathy (Nz-PML) surviving and receiving disease-modifying therapy (DMT).

Methods: We describe clinical and radiologic evolution of Nz-PML survivors in an observational retrospective multicenter cohort to clarify the effect of different subsequent MS DMT strategies. Twenty-three patients from 11 centers were analyzed.

Double-Blind Controlled Randomized Trial of Cyclophosphamide versus Methylprednisolone in Secondary Progressive Multiple Sclerosis.

Background: Therapeutic options are limited in secondary progressive multiple sclerosis (SPMS). Open-label studies suggested efficacy of monthly IV cyclophosphamide (CPM) without induction for delaying progression but no randomized trial was conducted so far.

Objective: To compare CPM to methylprednisolone (MP) in SPMS.

Therapeutic target of memory B cells depletion helps to tailor administration frequency of rituximab in myasthenia gravis.

Rituximab (RTX) has demonstrated efficacy in limiting relapses in myasthenia gravis (MG). We investigated the interest of CD27+ memory B cell monitoring in patients as a biological marker of clinical relapse. Twenty-four patients have been treated with RTX (375mg/m(2)/week-month as an induction treatment).

Interleukin 17 alone is not a discriminant biomarker in early demyelinating spectrum disorders.

Background: Radiologically isolated syndrome (RIS) is a sub clinical demyelinating neurological disorder and to date no biomarker that triggers the seminal event has been identified. As for multiple sclerosis (MS), disease activity and clinical course are unpredictable. In MS, exploratory studies reported increased IL-17 levels in CSF but results in detecting IL-17 in serum at different stage of the disease are controversial.

False positivity of anti aquaporin-4 antibodies in natalizumab-treated patients.

Background: Neuromyelitis optica spectrum disorders (NMOSD) represent a differential diagnosis of multiple sclerosis (MS). Detection of anti-aquaporin-4 antibodies (AQP4-Ab) is the strongest argument to confirm NMOSD. Diagnosing NMOSD is a major concern because specific MS disease modifying drugs can lead to neurological worsening.

Primary Progressive Multiple Sclerosis Evolving From Radiologically Isolated Syndrome.

Objective: The aim of this work was to evaluate the preprogressive phase in subjects with radiologically isolated syndrome (RIS) who evolve to primary progressive multiple sclerosis (PPMS).

Methods: A multicenter RIS cohort was previously established. Demographic, clinical, and radiological characteristics of subjects with RIS that evolved directly to PPMS were compared to those that developed a relapsing disease course from onset (clinically isolated syndrome [CIS] or relapsing-remitting MS) and were also compared to two other population- and clinic-based PPMS cohorts.

Rituximab as first-line therapy in neuromyelitis optica: efficiency and tolerability.

Neuromyelitis optica (NMO) is a life-threatening disease without any validated treatment strategy. Recent retrospective studies suggested the efficacy of B cell depletion without any distinction between first-line or rescue therapy. To assess whether rituximab as first-line therapy in NMO could efficiently control the occurrence of relapses.

Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): a randomised, controlled, double-blind, non-inferiority trial.

Background: 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.