[Novel immunomodulatory therapies in myasthenia gravis]. / Myasthénie grave : nouvelles thérapies immunosuppressives.

Myasthenia gravis (MG) is an autoimmune disease characterized by fluctuating weakness of skeletal muscles. Despite current treatments, a significant percentage of patients remain symptomatic. This review explores new immunosuppressive therapies and ongoing clinical trials in MG, including depletion of B lymphocytes with agents such as rituximab and inebilizumab, as well as the use of eculizumab, efgartigimod, satralizumab, tocilizumab, and CAR-T (Chimeric Antigen Receptor-T) cell therapy. These advancements aim to improve disease control and patients' quality of life.

La myasthénie grave (MG) est une maladie auto-immune caractérisée par une faiblesse fluctuante des muscles squelettiques. Malgré les traitements classiques, un pourcentage significatif de patients reste symptomatique. Cet article explore les nouvelles thérapies immunosuppressives et les essais cliniques en cours pour la MG, notamment la déplétion des lymphocytes B avec des agents tels que le rituximab et l'inébilizumab, ainsi que l'utilisation de l'éculizumab, de l'efgartigimod, du satralizumab, du tocilizumab et de la thérapie par cellules CAR-T (Chimeric Antigen Receptor-T). Ces avancées visent à améliorer le contrôle de la maladie et la qualité de vie des patients.

[Management of chronic inflammatory demyelinating polyradiculoneuropathy]. / Prise en charge de la polyradiculoneuropathie inflammatoire démyélinisante chronique.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common chronic autoimmune neuropathy. Its management has considerably evolved over the last decade. In 2021, the diagnostic guidelines for CIDP were updated and the diagnostic criteria simplified. They enable better characterization of the electro-clinical phenotype of the disease, and emphasize supportive criteria, in particular neuro-muscular imaging. In terms of pathophysiology, the discovery of antibodies directed against antigens in the nodal and paranodal regions has given rise to the concept of autoimmune nodopathy. Finally, the preliminary results of the ADHERE study on efgartigimod have rekindled hopes of a new, effective therapy for CIDP.

La polyradiculoneuropathie inflammatoire démyélinisante chronique (PIDC) est la neuropathie auto-immune chronique la plus fréquente. Sa prise en charge a largement évolué durant la dernière décennie. En 2021, les recommandations diagnostiques de la PIDC ont été mises à jour et les critères diagnostiques simplifiés. Ils permettent une meilleure caractérisation du phénotype électroclinique de la maladie et mettent en avant les critères de support diagnostiques, en particulier l'imagerie neuromusculaire. Sur le plan physiopathologique, la découverte d'anticorps dirigés contre des antigènes des régions nodale et paranodale a fait naître le concept de nodopathie auto-immune. Enfin, les résultats préliminaires de l'étude ADHERE sur l'efgartigimod font émerger l'espoir d'une nouvelle thérapie efficace dans la PIDC.

Patisiran exposure in early pregnancy: a case report.

We describe here the first case of exposure to patisiran treatment, a small interfering RNA molecule, during early pregnancy of a 36-year-old woman with symptomatic hereditary transthyretin-related amyloidosis. There were no major complications during pregnancy and delivery, except for a postpartum hemorrhage due to uterine atony. Vitamin A levels had to be closely monitored during pregnancy, and vitamin A substitution adapted accordingly. There was no sign of minor or major congenital abnormalities of the baby. One month after delivery, the patient showed slight clinical and electrophysiological signs of neuropathy progression due to patisiran treatment withdrawal. Patisiran infusions were resumed 3 months after delivery. Due to the unknown teratogenic potential of patisiran, the risk of neuropathy worsening associated with withholding treatment must of course be weighed against a potential teratogenic risk of treatment during pregnancy. Vitamin A levels need to be closely assessed, and substitution must be adapted accordingly, to avoid embryofetal adverse outcome due to vitamin A deficiency or toxicity.

Acute Valproate-Induced Encephalopathy in Status Epilepticus: A Registry-Based Assessment.

BACKGROUND: Valproate-induced encephalopathy (VIE) affects between 0.1% and 2.5% of patients under long-term epilepsy treatment. Its frequency and characteristics in adults with status epilepticus (SE) is, however, unknown. OBJECTIVE: The aim of this study was to characterize the frequency and the clinico-biological characteristics of VIE in adult SE patients. METHODS: We reviewed all patients included in our institutional SE registry who were treated for an SE episode between November 2021 and February 2023 and identified 39 patients who received valproate for their SE treatment. Acute VIE was defined by worsening of consciousness having led to the discontinuation of valproate, and improvement of consciousness within 96 hours after discontinuation of valproate during acute hospital treatment. RESULTS: Patients had a mean valproate intravenous loading dose of 34.5 mg/kg and a mean maintenance dose of 15.3 mg/kg/d (1078 mg/d). Four out of 29 patients with measured ammonium had hyperammonemia. We identified four (10%) patients fulfilling acute VIE criteria. Median time from administration of valproate to the occurrence of VIE, and to resolution of VIE after cessation of valproate treatment, was 2 days for each. Three of the four VIE patients had no associated hyperammonemia. Patients who developed VIE more frequently had a history of liver disease (p = 0.023), and tended to be younger, but other clinical variables did not differ significantly from patients without VIE, including valproate loading or maintenance doses, SE cause, duration or severity, other concomitant antiseizure medications (none received topiramate, phenobarbital, or primidone). CONCLUSION: Pending larger studies, VIE in SE seems relatively frequent and difficult to foresee; clinical alertness to symptoms is mandatory, even without hyperammonemia, and valproate withdrawal should be considered in suspected cases.

Serum neurofilament light chain as a reliable biomarker of hereditary transthyretin-related amyloidosis-A Swiss reference center experience.

Hereditary transthyretin-related (hATTR) amyloidosis is a rare disease, causing a disabling and life-threatening axonal length-dependent polyneuropathy. Monitoring of disease progression and treatment response is difficult. We aimed to determine if serum neurofilament light chain (sNfL) is a reliable and early biomarker of peripheral neuropathy in hATTR amyloidosis. We prospectively included 20 hATTR patients, 14 symptomatic and 6 asymptomatic. Patients were assessed at baseline and 1 year, including a full clinical examination with disease severity and functional scores, electrochemical skin conductance measurement with Sudoscan and nerve conduction studies, and sNfL level. hATTR patient sNfL were also compared with sNfL of 4532 healthy controls of a reference database by calculating age and BMI-adjusted Z scores. At baseline, median sNfL concentration was 3.6-fold higher in symptomatic than asymptomatic hATTR patients (P = .003), and this difference was also found in our under 60-years-old patients (P = .003). There was no significant difference of sNfL concentration between asymptomatic patients and healthy controls (Z-score of -0.29), but a significant difference between symptomatic patients and healthy controls (Z-score of 2.52). We found a significant correlation between sNfL levels and most clinical and electrophysiological disease severity scores, the strongest correlation being with the NIS score. sNfL seems to be a reliable biomarker of peripheral neuropathy severity in hATTR amyloidosis and can distinguish between asymptomatic and symptomatic patients. sNfL could also become a reliable biomarker to establish disease onset and treatment response.

Clinical Reasoning: A 39-Year-Old Man With Asymmetric Distal Weakness and Loss of Sensitivity.

A 39-year-old man presented with an asymmetric distal weakness and loss of sensitivity sequentially affecting both lower extremities and the left upper limb. Nerve conduction studies showed a multifocal sensory and motor axonal neuropathy, and a pseudo-conduction block of the right fibular nerve, the whole being consistent with a mononeuropathy multiplex. An uncommon etiology was found after an extensive workup. Axonal loss was severe, with only partial response to treatment with corticosteroids and IV immunoglobulins.