Myoclonus and seizures in progressive myoclonus epilepsies: pharmacology and therapeutic trials

Abstract

Generalized motor seizures, usually tonic‐clonic, tonic‐vibratory, myoclonic or clonic, and stimulus‐sensitive/action myoclonus are typical features of progressive myoclonus epilepsies (PMEs). Despite the introduction of many anticonvulsants, the treatment of these symptoms, particularly myoclonus, remains challenging, due to the incomplete and often transitory effects of most drugs. Moreover, treatment is only symptomatic, since therapy targeting the underlying aetiology for these genetic conditions is in its infancy. Traditional antiepileptic drugs for the treatment of PMEs are valproate, clonazepam, and phenobarbital (or primidone). These drugs may improve the overall performance of PME patients by decreasing their generalized seizures and, to a lesser extent, their myoclonic jerks. Newer drugs which have been shown to be effective include piracetam, levetiracetam, topiramate, zonisamide, and possibly perampanel for Lafora disease. The potential of other drugs (such as L‐triptophan and N‐acetylcysteine) and procedures (such as vagal and deep brain stimulation) has also been discussed. The available data on the efficacy of drugs are mainly based on small series or anecdotal reports. Two prospective, randomized, double blind studies investigating the novel SV2A ligand, brivaracetam, in genetically confirmed Unverricht‐Lundborg patients have been performed with disappointing results. When treating PMEs, particular care should be paid to avoid drugs known to aggravate myoclonus or myoclonic seizures, such as phenytoin, carbamazepine, oxcarbazepine, lamotrigine, vigabatrin, tiagabine, gabapentin, and pregabalin. The emergency treatment of motor status, which often complicates the course of PMEs, consists of intravenous administration of benzodiazepines, valproate, or levetiracetam.

Perampanel: Does it have broad‐spectrum potential?

“…Progressive myoclonus epilepsies are typically associated with generalized motor seizures, usually tonic–clonic, tonic vibratory, myoclonic or clonic, and stimulus‐sensitive or action myoclonus . Treatment is challenging, as some AEDs can aggravate myoclonus and myoclonic seizures, including vigabatrin, carbamazepine, phenytoin, and gabapentin.…”

Perampanel, an AMPA receptor antagonist: From clinical research to practice in clinical settings

“…71,72 In a study of 10 patients with Lafora disease, addition of perampanel (mean dose 6.7 mg/d) resulted in a significant reduction in seizures of ≥74% from baseline for four patients and an improvement of myoclonus for seven patients (from 7.01 at baseline to 5.67 and 5.18 at 2-3 and 9-10 months, respectively). 71,72 In a study of 10 patients with Lafora disease, addition of perampanel (mean dose 6.7 mg/d) resulted in a significant reduction in seizures of ≥74% from baseline for four patients and an improvement of myoclonus for seven patients (from 7.01 at baseline to 5.67 and 5.18 at 2-3 and 9-10 months, respectively).…”

Update on Pharmacological Treatment of Progressive Myoclonus Epilepsies

“…Due to the possible development of tolerance, some patients may need dose adjustments after a few weeks or months. Alternatively, in case of reduced efficacy, a shift with other BDZ, such as CLB or nitrazepam, can be attempted [13]. Of note, ULD patients who abruptly withdraw a long-lasting treatment with CNZ may experience myoclonic status epilepticus (personal observation by one of the authors, EF).…”

“…Of note, clinical trials are difficult to perform in PMEs due to the rarity of these conditions and to the lack of specific instruments for the evaluation of disease severity and evolution [12,13]. Moreover, the progression of symptoms makes challenging to assess patients initially responding to AEDs.…”

“…Alternative treatments (such as vagus nerve stimulation, deep brain stimulation, ketogenic diet) have been reviewed elsewhere [13] and will not be treated herein.…”