Diagnostic Impasse and Wandering in Patients With Rare Neuromuscular Diseases: Insights Into Patient Characteristics From the French National Network for Rare Neuromuscular Diseases (FILNEMUS) and the French National Rare Disease Database (BNDMR).

Background: Diagnostic wandering and impasse are major challenges for rare disease management. This study describes the characteristics of patients with rare neuromuscular diseases (RNMDs) without a diagnosis being managed by the French national network for RNMDs (FILNEMUS).

Methods: Data for RNMD patients managed by FILNEMUS centers between January 2017 and November 2022 were extracted from the French National Rare Disease Database (BNDMR).

Safety and efficacy of apitegromab in nonambulatory type 2 or type 3 spinal muscular atrophy (SAPPHIRE): a phase 3, double-blind, randomised, placebo-controlled trial.

Background: Approved spinal muscular atrophy therapies greatly improve clinical outcomes; however, substantial motor function deficits persist. Apitegromab, a fully human monoclonal antibody, selectively inhibits myostatin activation, improving muscle function. We aimed to assess the safety and efficacy of apitegromab in patients with nonambulatory type 2 or type 3 spinal muscular atrophy receiving nusinersen or risdiplam.

The Two Faces of Pediatric SCA2.

Introduction: Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurological disease usually described in adults. Expanded CAG repeats in the ATXN2 gene can lead to pediatric onset. This study aims to describe the natural history of SCA2 in children.

REGISTRE SMA FRANCE: A nationwide observational registry of patients with spinal muscular atrophy in France.

BackgroundSpinal muscular atrophy (SMA) is a severe neurodegenerative disease affecting children. Three innovative disease-modifying therapies (DMTs)-nusinersen, risdiplam, and onasemnogene abeparvovec-are available for treatment.ObjectiveTo provide a descriptive overview of patients enrolled in the until July 22, 2024.

Spectrum of Phenotypes in SMA Patients With 4 Copies in the French Population: Registre SMA France.

Background And Objectives: Clinical phenotype and course of individuals with 4 copies of the gene are insufficiently described, and presymptomatic treatment remains controversial.

Methods: This is a cohort study that analyzed data from SMA patients with zero SMN1 and 4 SMN2 copies collected in the "Registre SMA France" to describe epidemiology, clinical presentation, and course.

Results: A total of 140 of 1,112 patients with SMA carried 4 copies (16% of those with available copy number).

STARDEV Study: Neurodevelopmental Trajectory and Long-Term Outcomes of Patients with Startle Disease/Hyperekplexia.

Background: Although initial clinical presentation of hyperekplexia/startle disease is well known, data regarding long-term clinical outcomes is lacking.

Objectives: We provide a long-term evaluation from clinical and pharmacological perspectives, focusing on neurodevelopmental trajectory.

Methods: Twenty-eight patients from nine French hospitals were included based on clinical diagnosis criteria.

Behavioral, neurodevelopmental profile, and epilepsy trajectory in two series of SLC6A1-NDD: A retrospective study with comprehensive assessment, and a participatory database study.

SLC6A1 (Solute Carrier Family 6 Member 1) variants are associated with SLC6A1-neurodevelopmental disorders (SLC6A1-NDD), which manifest as early-onset epilepsy, intellectual developmental disorder, and autism spectrum disorder. There have been over 300 reported cases so far. A retrospective analysis of 14 patients with de novo SLC6A1 variants was conducted to assess their developmental milestones, epilepsy progression, antiseizure medication, and, for some, a comprehensive neurodevelopmental evaluation.

Evaluation of professional practices in the use of mexiletine for the management of childhood myotonia in French pediatric neuromuscular centers (MEXI-PEDI survey).

Background: Myotonia is the main feature of both myotonic dystrophy (DM) and non-dystrophic myotonia (NDM). It is felt as stiffness, pain, fatigue, and weakness. In France, mexiletine, a non-selective voltage-gated sodium channel blocker, is approved for the treatment of myotonia in adults with NDM, and it has a temporary recommendation for use in the symptomatic treatment of DM in adults.

Choice of compound, dosage, and management of side effects for long-term corticosteroid treatment in Duchenne muscular dystrophy: Guidelines from the Neuromuscular Commission of the French Society of Pediatric Neurology.

The French Society of Pediatric Neurology and the FILNEMUS network created a working group on corticosteroid therapy in children with Duchenne muscular dystrophy in order to analyze the literature review and current French practices. The aim of this work was to produce guidelines regarding treatment initiation, pre-therapeutic interventions, choice between available compounds, and treatment monitoring (dosage, duration, and discontinuation). The treatment side effects and their management are also detailed: osteoporosis, endocrinological anomaly (growth delay, weight gain, pubertal delay), cataract, arterial hypertension, behavioral disorders, management of immunosuppression and vaccines, and management of gastrointestinal and metabolic complications.

French National Protocol for diagnosis and care of facioscapulohumeral muscular dystrophy (FSHD).

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common genetically inherited myopathies in adults. It is characterized by incomplete penetrance and variable expressivity. Typically, FSHD patients display asymmetric weakness of facial, scapular, and humeral muscles that may progress to other muscle groups, particularly the abdominal and lower limb muscles.

The Ala1186Val Variant Linked to Cytoplasmic Body Myopathy and Cardiomyopathy Causes Protein Instability.

Filamin C-related disorders include myopathies and cardiomyopathies linked to variants in the gene. Filamin C belongs to a family of actin-binding proteins involved in sarcomere stability. This study investigates the pathogenic impact of the c.

Phosphatidylserine enriched with polyunsaturated n-3 fatty acid supplementation for attention-deficit hyperactivity disorder in children and adolescents with epilepsy: A randomized placebo-controlled trial.

Background: Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity in children with epilepsy, which management mostly relies on the usual treatments of ADHD, especially methylphenidate. Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed as an alternative therapeutic approach in ADHD without epilepsy but has never been evaluated in epilepsy-associated ADHD.

Methods: A multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA, in eicosapentaenoic- and docosahexaenoic-acid form, conjugated to a phospholipid vector (PS-Omega3) in children aged >6 and <16-years old, and suffering from any type of epilepsy and ADHD (inattentive or combined type) according to DSM-V.

Real-life data comparing the efficacy of vigabatrin and oral steroids given sequentially or combined for infantile epileptic spasms syndrome.

Aims: The prognosis of Infantile epileptic spasm syndrome (IESS), relates to the underlying etiology and delay in controlling epileptic spasms. Based on the spasm-free rate, a randomized controlled trial has demonstrated the superiority of combining oral steroids and vigabatrin over oral steroids alone but confirmation in real-life conditions is mandatory.

Methods: We compared two real-life IESS cohorts: a multicenter, retrospective cohort of 40 infants treated with vigabatrin followed by a sequential (ST) addition of steroids, and a prospective, single-center cohort of 58 infants treated with an immediate combination of vigabatrin and steroids (CT).

Confirmatory validation of the french version of the Duchenne Muscular Dystrophy module of the pediatric quality of life inventory (PedsQL3.0DMDfv).

Duchenne Muscular Dystrophy (DMD) is a neuromuscular disease that inevitably leads to total loss of autonomy. The new therapeutic strategies aim to both improve survival and optimise quality of life. Evaluating quality of life is nevertheless a major challenge.

Effects of miglustat therapy on neurological disorder and survival in early-infantile Niemann-Pick disease type C: a national French retrospective study.

Background: Niemann-Pick disease type C (NP-C) is a rare neurovisceral lysosomal lipid storage disease characterized by progressive neurodegeneration and premature death. While miglustat can stabilize neurological manifestations in later onset forms of NP-C, its efficacy in the early-infantile neurological form has not been demonstrated. In this observational retrospective study, we compared long-term neurodevelopmental outcome and survival between an untreated and a treated group of early infantile NP-C patients.

Movement disorders in valine métabolism diseases caused by HIBCH and ECHS1 deficiencies.

Background And Purpose: HIBCH and ECHS1 genes encode two enzymes implicated in the critical steps of valine catabolism, 3-hydroxyisobutyryl-coenzyme A (CoA) hydrolase (HIBCH) and short-chainenoyl-CoA hydratase (ECHS1), respectively. HIBCH deficiency (HIBCHD) and ECHS1 deficiency (ECHS1D) generate rare metabolic dysfunctions, often revealed by neurological symptoms. The aim of this study was to describe movement disorders spectrum in patients with pathogenic variants in ECHS1 and HIBC.

Phenotypical variability and atypical presentations in a French cohort of Andersen-Tawil syndrome.

Background And Purpose: Andersen-Tawil syndrome (ATS) is a skeletal muscle channelopathy caused by KCNJ2 mutations, characterized by a clinical triad of periodic paralysis, cardiac arrhythmias and dysmorphism. The muscle phenotype, particularly the atypical forms with prominent permanent weakness or predominantly painful symptoms, remains incompletely characterized.

Methods: A retrospective clinical, histological, electroneuromyography (ENMG) and genetic analysis of molecularly confirmed ATS patients, diagnosed and followed up at neuromuscular reference centers in France, was conducted.

Rituximab Therapy in the Treatment of Juvenile Myasthenia Gravis: The French Experience.

Background And Objectives: Corticosteroids are the first-line immunosuppressants in the management of juvenile myasthenia gravis despite their adverse effects. The place of new immunosuppressive therapies is not clearly defined by the last international consensus held in March 2019 due to the lack of clinical trials. The aim of this study is to describe the use of rituximab and its efficacy and safety in 8 main pediatric centers of the French neuromuscular reference network to propose a new place in the therapeutic strategy of juvenile myasthenia gravis.

Unexpected Intermediate Nerve Conduction Velocity Findings in Charcot-Marie-Tooth Syndromes Classified as Demyelinated or Axonal in a Pediatric Population.

Introduction: Among the hereditary motor and sensory neuropathies (HMSN), demyelinating forms are the best characterized, with a clear predominance of CMT1A. The axonal and intermediate forms are less described. The aim of this study is to report the genetic diagnosis of Charcot-Marie-Tooth (CMT) according to the nerve conduction velocity (NCV) findings in a pediatric population.