Epidemiology of myasthenia gravis in France: Incidence, prevalence, and comorbidities based on national healthcare insurance claims data.

BACKGROUND: The European literature has reported high variability in the incidence and prevalence rates of myasthenia gravis (MG), but no specific epidemiological data for France have been published. This study aimed to assess the incidence and prevalence rates of myasthenia gravis in France based on data extracted from the French National Health Insurance Claims Database (the SNIIRAM database). METHODS: We conducted a retrospective repeated cross-sectional population study from 2008 to 2018 using a representative sample of the French population (Échantillon généraliste des bénéficiaires) covered by health insurance. We calculated the incidence, prevalence, and sex ratio of MG and screened for comorbidities associated with MG (standardized to the general population). RESULTS: In total, 331 MG patients were identified between 2008 and 2018. The average incidence of MG in France was 50 per million person-years, while the mean prevalence was 465 per million people. The female-to-male ratio was 1.33. The Incidence of MG gradually increased from 40years of age for women and 60 for men. Thymoma was present for 5.1% of MG patients and a thymectomy was performed for 4.7%. Thyroid disease was the most prevalent autoimmune comorbidity, affecting approximately 8.5% of cases. MG patients had an increased cancer risk, with a standardized rate ratio of 2.38 (95% CI: 1.64-3.46). CONCLUSION: The incidence and prevalence rates of MG are significantly higher than those previously reported in the literature and the incidence increases with age. The excess risk of cancer raises concerns for MG patients, in particular, concerning the management of immunosuppressive drugs.

Prospective study of the additional benefit of plexus magnetic resonance imaging in the diagnosis of chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND PURPOSE: Hypertrophy/signal hyperintensity and/or gadolinium enhancement of plexus structures on magnetic resonance imaging (MRI) are observed in two-thirds of cases of typical chronic inflammatory demyelinating polyneuropathy (CIDP). The objective of our study was to determine the additional benefit of plexus MRI in patients referred to tertiary centers with baseline clinical and electrophysiological characteristics suggestive of typical or atypical CIDP. METHODS: A total of 28 consecutive patients with initial suspicion of CIDP were recruited in nine centers and followed for 2 years. Plexus MRI data from the initial assessment were reviewed centrally. Physicians blinded to the plexus MRI findings established the final diagnosis (CIDP or neuropathy of another cause). The proportion of patients with abnormal MRI was analyzed in each group. RESULTS: Chronic inflammatory demyelinating polyneuropathy was confirmed in 14 patients (50%), as were sensorimotor CIDP (n = 6), chronic immune sensory polyradiculoneuropathy (n = 2), motor CIDP (n = 1) and multifocal acquired demyelinating sensory and motor neuropathy (n = 5). A total of 37 plexus MRIs were performed (17 brachial, 19 lumbosacral and 8 in both localizations). MRI was abnormal in 5/37 patients (14%), all of whom were subsequently diagnosed with CIDP [5/14(36%)], after an atypical baseline presentation. With plexus MRI results masked, non-invasive procedures confirmed the diagnosis of CIDP in all but one patient [1/14 (7%)]. Knowledge of the abnormal MRI findings in the latter could have prevented nerve biopsy being performed. CONCLUSION: Systematic plexus MRI in patients with initially suspected CIDP provides little additional benefit in confirming the diagnosis of CIDP.

Implication of the SH3TC2 gene in Charcot-Marie-Tooth disease associated with deafness and/or scoliosis: Illustration with four new pathogenic variants.

The autosomal recessive demyelinating form of Charcot-Marie-Tooth can be due to SH3TC2 gene pathogenic variants (CMT4C, AR-CMTde-SH3TC2). We report on a series of 13 patients with AR-CMTde-SH3TC2 among a French cohort of 350 patients suffering from all type of inheritance peripheral neuropathy. The SH3TC2 gene appeared to be the most frequently mutated gene for demyelinating neuropathy in this series by NGS. Four new pathogenic variants have been identified: two nonsense variants (p.(Tyr970*), p.(Trp1199*)) and two missense variants (p.(Leu1126Pro), p.(Ala1206Asp)). The recurrent variant p.Arg954* was present in 62%, and seems to be a founder mutation. The phenotype is fairly homogeneous, as all these patients, except the youngest ones, presented scoliosis and/or hearing loss.

Dimethyl fumarate and teriflunomide for multiple sclerosis in a real-life setting: a French retrospective cohort study.

BACKGROUND AND PURPOSE: Dimethyl fumarate (DMF) and teriflunomide are approved oral disease-modifying treatments for relapsing-remitting multiple sclerosis (MS). Phase 3 trials established these agents to be effective and generally well tolerated, although comparative efficacy and discontinuation rates are still unknown. The aim of this study was to assess real-world efficacy and discontinuation of DMF and teriflunomide in patients with relapsing-remitting MS. METHODS: This retrospective observational cohort study was carried out in a French administrative region between March 2014 and July 2017. Patients who were followed by private or hospital neurologists were included. Efficacy and tolerance of the two treatments were assessed and compared by multivariate analysis, considering the duration of MS, annualized relapse rate and Expanded Disability Status Scale score at treatment initiation, treatment duration, type of prescriber and tobacco use. RESULTS: We identified 189 DMF- and 157 teriflunomide-treated patients who had been treated for 22 ± 10 months. After correction for confounders, DMF more efficiently reduced the annualized relapse rate after 2 years than teriflunomide (0.06 vs. 0.21; P = 0.03). DMF-treated patients had more clinical and biological adverse events, resulting in a higher rate of treatment discontinuation (28% vs. 12%, P = 0.03). CONCLUSION: In this retrospective cohort study, DMF demonstrated significantly better efficacy over 2 years than teriflunomide, but tolerance to teriflunomide was better.

Fixed 50:50 mixture of nitrous oxide and oxygen to reduce lumbar-puncture-induced pain: a randomized controlled trial.

BACKGROUND AND PURPOSE: Lumbar puncture (LP) has been frequently performed for more than a century. This procedure is still stressful and often painful. The aim of the study was to evaluate the efficacy of a fixed 50% nitrous oxide-oxygen mixture compared to placebo to reduce immediate procedural pain and anxiety during LP. METHODS: A randomized controlled trial was conducted involving adults who needed a cerebrospinal fluid analysis. Patients were randomly assigned to inhale either a fixed 50% nitrous oxide-oxygen mixture (50% N2 O-O2 ) or medical air (22% O2 -78% N2 ). Cutaneous application of a eutectic mixture of local anaesthetics was systematically done and all LPs were performed with pencil point 25G needles (20G introducer needle). The primary end-point was the maximal pain level felt by the patient during the procedure, the maximal anxiety level being a secondary outcome, both measured using a numerical rating scale (0-10). RESULTS: A total of 66 consecutive patients were randomized. The analysis was intention to treat. The maximal pain was 4.9 ± 2.7 for the 33 patients receiving air and 2.7 ± 2.7 for the 33 receiving 50% N2 O-O2 (P = 0.002). Similarly, the maximal LP-induced anxiety was 4.5 ± 3.1 vs. 2.6 ± 2.6 (P = 0.009), respectively. The number needed to treat to avoid one patient undergoing significant pain (pain score ≥ 4/10) was 2.75. Body mass index >25 kg/m2 was significantly associated with higher pain intensity (P = 0.03). No serious adverse events were attributable to 50% N2 O-O2 inhalation. CONCLUSIONS: Inhalation of a fixed 50% N2 O-O2 mixture is efficient to reduce LP-induced pain and anxiety.

A novel autosomal dominant leukodystrophy with specific MRI pattern.

Etiologic diagnosis of adulthood leukodystrophy is challenging in neurologic practice. We describe here the clinico-radiological features of a novel autosomal dominant leukodystrophy in a single family. Clinical and MRI features were recorded in a three generation family. Exome sequencing was performed in two affected relatives and one healthy member. Four total relatives (3 women and 1 man, mean age at onset: 45, range 32-59) were followed: 2 for migraine and 2 for cognitive loss. MRI features were homogeneous in the four affected relatives: extensive and symmetrical white matter hyperintensities on T2-weighted images, with a posterior predominance, involvement of the middle cerebellar peduncles, corpus callosum and the posterior limb of the internal capsules. An extensive metabolic screening was negative. In addition, sequencing of pathogenic genes involved in dominant leukodystrophies (NOTCH3, LMNB1, GFAP, CSF1R) was negative. No mutation has been identified yet with exome sequencing. This report is peculiar because of dominant inheritance, adult onset, highly homogeneous white matter hyperintensities on T2-weighted MR images, predominant in the middle cerebellar peduncles and posterior part of internal capsule and absence of mutation of the genes involved in dominant leukodystrophies.

[Unilateral Creutzfeld-Jakob disease: report of a probable case on electroclinical, MRI and biological criteria]. / Maladie de Creutzfeld-Jakob unilatérale: à propos d'un cas probable sur les critères électrocliniques, IRM et biologiques.

We report the case of a 70-year-old man who developed probable unilateral Creutzfeldt-Jakob disease. Clinically, he presented with right hemiparesis, progressive aphasia, temporospatial disorientation and cerebellar ataxia and later on, myoclonia. The MRI showed a hypersignal from the left caudate in DWI with decreased ADC. Repeated electroencephalograms showed a slow background rhythm in the left hemisphere with superimposed periodic, biphasic and triphasic sharp-wave complexes in the left temporal region. Death occurred after 5weeks. Although exceptional, unilateral Creutzfeldt-Jakob disease was retained as possible.

Home administration of intravenous methylprednisolone for multiple sclerosis relapses: the experience of French multiple sclerosis networks.

BACKGROUND: One single center study has provided support for a home-based approach to the therapeutic management of multiple sclerosis (MS) relapse. OBJECTIVE: To report a multicenter series of patients with MS who were treated at home for a relapse with a 3-day course of intravenous methylprednisolone. METHODS: The home administration of intravenous methylprednisolone was coordinated by four MS networks in France; patients with MS with a relapse were referred by their neurologists, and treatment was administered by a local nurse. We analyzed the safety and efficiency of this approach and estimated the related cost savings. Patients completed a patient satisfaction questionnaire. RESULTS: Eight hundred and seven patients received intravenous methylprednisolone at home. The mean disease duration was 10.3 +/- 7.9 years. Treatment was often prescribed by community-based neurologists. The delay between prescription and treatment was 2.8 +/- 0.5 days if treatment was initiated at home and 1.9 +/- 3.0 days if treatment was initiated in hospital (the subsequent two injections were always administered at home). Home treatment was well tolerated; three serious side effects requiring hospital transfer were observed (anxiety, thoracic oppression, and arrhythmia), which were fully reversible. Overall, 93.8% of patients were satisfied with the treatment approach, and 98% wished to receive future treatment courses at home. The overall cost savings of home-based treatment versus hospital-based treatment were evaluated at EUR1,091,482. CONCLUSION: Safety data, patient satisfaction, and economic considerations support home-based treatment of MS relapses with intravenous methylprednisolone, provided strict patient selection criteria are observed and the process is coordinated and closely monitored by an MS network.

[Quality of life in multiple sclerosis]. / La qualité de vie des patients souffrant de sclérose en plaques.

Multiple sclerosis is responsible for impairment and disability, which play a major role in the personal burden of the disease. Health-related quality of life (HRQoL) has been intensively studied in this medical condition, more intensively than in other chronic neurological disorders, perhaps because of the limitations of the conventional disability instruments, which seem less sensitive to change. Moreover, HRQoL measurements can summarize all sources of patient satisfaction and dissatisfaction. Instead of relying on motor limitations, many psychological, social, and neuropsychological factors, such as cognitive impairment and fatigue, are predictors of a reduced quality of life, even in the early stages, more than conventional radiological MRI. The analysis of self-administered HRQoL questionnaires, generic or mixed (specific and generic), can help clinicians advance toward the best therapeutic approach for the patient.

[Steroid responsive encephalopathy associated with auto-immune thyroiditis]. / Encéphalopathie corticosensible associée à une thyroidite auto-immune: données actuelles.

Since the first description of encephalopathy associated with Hashimoto's thyroiditis in 1966, more than 100 cases of this entity called Hashimoto's encephalopathy or SREAT [steroid-responsive encephalopathy associated with auto-immune thyroiditis] have been reported. The two cases reported here illustrate different diagnostic criteria and offer the opportunity to discuss the many pathophysiological hypotheses based on particularly pertinent biological data, especially the activity of anti-TPO and anti-TG antibodies present in serum and cerebrospinal fluid and the recent discovery of anti-alpha-enolase antibody. Different treatment options are also discussed, in particular corticosteroid therapy.

[Diffuse lower motor neuron disease in a carcinomatous meningitis]. / Atteinte diffuse du deuxième motoneurone révélant une méningite carcinomateuse.

INTRODUCTION: Between 4 and 15% of solid cancers are associated with carcinomatous meningitis ant its unfavorable prognosis. The clinical presentation of neoplastic meningitis typically associates cerebral signs, cranial nerve involvement, and medullary or radicular symptoms. OBSERVATION: We report a case of a 58-year-old woman, with a history of breast cancer in remission since 8 years, who presented an acute paraparesia and a pure motor deficit of the left arm. This diffuse lower motor neuron disease was the inaugural sign of carcinomatous meningitis. CONCLUSION: The diagnosis of cacinomatous meningitis is based on medullar MRI and lumbar puncture. In same cases, clinical signs are limited to a pure diffuse lower motor neuron disease.