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INTRODUCTION: Dravet Syndrome (DS) is a rare epileptiform disorder typically presenting within the first year of life of a normally developing infant. It is characterized by several prolonged seizures that are often resistant to current anti-epileptic drug (AED) regimens. This paper outlines the history and clinical trials of the drug fenfluramine, a drug that when used in addition to AED regimens may provide hope to children affected by DS. BODY: Fenfluramine (3-trifulormethyl-N-ethylamphetamine) is an amphetamine derivative that primarily affects serotonin neurotransmitter levels. It was initially prescribed in the 1960s as an appetite suppressant marketed as a weight loss drug. However, it was removed from the markets due to its association with cardiac valvopathies. It continued to by studied in epilepsy by Gastaut in the 1980s in children with self-induced syncope and irretractable epilepsy. In 2012, Ceulemans et al. studied the use of fenfluramine in patients with DS. Following the success of that retrospective case study, Nabbout et al. and Legae et al. conducted two randomized control trials leading to the FDA approval of fenfluramine under its trade name Fintepla in 2020. DISCUSSION: The success of the randomized control trials suggests the addition of fenfluramine to current AED regimens may lead to better control of seizures in patients with DS. The side effects of fenfluramine prove to be manageable and the concern for valvopathies has not been reproducible with low dose fenfluramine.
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BACKGROUND: Despite the availability of several immunomodulatory therapies, about 20% of myasthenia gravis (MG) patients remain refractory to conventional treatments. There is limited evidence to support the use of maintenance therapeutic plasma exchange (TPE) therapy for refractory generalized MG. METHODS: Retrospective chart review of 14 patients with refractory generalized MG treated for 12 months with maintenance TPE therapy. Outcome measures were myasthenia gravis composite (MGC) score, myasthenia gravis activities of daily living (MG-ADL), number of acute exacerbations, medication changes, and adverse events. Data were collected at 3 monthly intervals for 12 months before and after initiation of TPE therapy. RESULTS: Clinically meaningful reductions in mean MG-ADL (>2 points) (mean MG-ADL score: 9.9 ± 0.5; 12-month pre-TPE to 5.2 ± 0.9; 12-month post-TPE) and MGC (>3 points) (mean MGC score: 25.2 ± 1.6; 12-month pre-TPE to 11.7 ± 1.4; 12-month post-TPE) were observed at 3 months following initiation of TPE and were maintained up to 12 months in all patients. After 12 months of TPE therapy, all patients had a significant reduction in daily prednisone and pyridostigmine use. Patients previously on IVIG or rituximab therapy were successfully weaned off both treatments. There was a significant reduction in acute MG exacerbations; 7.8 ± 1.1 mean exacerbations/patient (12-month pre-TPE) to 2 ± 1.1 mean exacerbations/patient (12-month post-TPE). CONCLUSION: Over a period of 12 months, maintenance TPE therapy improved MG-ADL, and MGC with decreased immunosuppressant requirement, while being well-tolerated.