Search

New multiple sclerosis (MS) disease-modifying therapies (DMTs), which exert beneficial effects through prevention of relapse, limitation of disability progression, and improvement of patients’ quality of life, have recently emerged. Nonetheless, these DMTs are not without associated complications (severe adverse events like. progressive multifocal leukoencephalopathy). Patient follow-up requires regular clinical evaluations and close monitoring with magnetic resonance imaging (MRI). Detection of new T2 lesions and potential brain atrophy measurements contribute to the evaluation of treatment effectiveness. Current MRI protocols for MS recommend the acquisition of an annual gadolinium (Gd) enhanced MRI, resulting in administration of high volume of contrast agents over time and Gd accumulation in the brain.

Although relatively common in children, severe acute lactic acidosis is rare in adults with mitochondrial myopathies. We report here three cases, aged 27, 32 and 32 years, who developed life-threatening metabolic crisis with severe lactic acidosis, requiring hospitalisation in intensive care unit. Plasma lactates were elevated 10 to 15 fold normal values, necessitating extra-renal dialysis. By contrast CK levels were moderately increased (3 to 5N). No triggering factor was identified, but retrospectively all patients reported long-lasting mild muscle fatigability and weakness before their acute metabolic crisis. All of them recovered after prolonged intensive care but resting lactate levels remained elevated. Muscle biopsy showed ragged-red and COX-negative fibers in two patients and mild lipidosis in the third one. Heteroplasmic pathogenic point mutations were detected in MT-TL1(m.3280G>A;m.3258C>T) and MT-TK(m.8363A>G). Life-threatening lactic acidosis may thus be a major inaugural clinical manifestation in adults with mitochondrial myopathies. Prolonged intensive care may lead to a dramatic and sustained improvement and is mandatory in such cases.

La maladie de Paget extramammaire (MPEM) est une prolifération de cellules intra épithéliales touchant préférentiellement la région périnéale. Elle peut devenir invasive (MPEMi) avec un risque évolutif mal connu. Le but de cette étude était de déterminer les caractéristiques cliniques et évolutives des MPEMi.

In genetically complex diseases, the search for missing heritability is focusing on rare variants with large effect. Thanks to next generation sequencing technologies, genome-wide characterization of these variants is now feasible in every individual. However, a lesson from current studies is that collapsing rare variants at the gene level is often insufficient to obtain a statistically significant signal in case–control studies, and that network-based analyses are an attractive complement to classical approaches. In Alzheimer disease (AD), according to the prevalent amyloid cascade hypothesis, the pathology is driven by the amyloid beta (Aß) peptide. In past years, based on experimental studies, several hundreds of proteins have been shown to interfere with Aß production, clearance, aggregation or toxicity. Thanks to a manual curation of the literature, we identified 335 genes/proteins involved in this biological network and classified them according to their cellular function. The complete list of genes, or its subcomponents, will be of interest in ongoing AD genetic studies.

Le lymphome T sous-cutané à type de panniculite (LTSP) est un lymphome primitif cutané rare, de diagnostic difficile. La clinique comporte des nodules et placards infiltrés essentiellement localisés aux membres et au tronc, plus rarement au visage. En l’absence d’hémophagocytose, le pronostic est en général favorable. En 2018, des formes sévères à risque d’hémophagocytose ont été associées à des mutations germinales du gène HAVCR2,codant la protéine TIM3 (T-cell immunoglobulin mucin3), récepteur des cellules immunitaires impliqué dans la régulation de la réponse immune. Nous rapportons un cas de LTSP se présentant comme une sévère infiltration œdémateuse isolée de la face, dont le diagnostic a nécessité plusieurs biopsies et confrontations anatomocliniques ; le traitement par corticothérapie et méthotrexate a permis une réponse rapide et complète.

Le Teriflunomide (TRF) et le Dimethyl-Fumarate (DMF) sont deux traitements approuvés de 1religne pour la forme rémittente de sclérose en plaques (SEP). Cependant, à ce jour, il n’existe aucun essai randomisé ni aucune étude observationnelle comparant leur efficacité relative.