Juvenile myoclonic epilepsy: when will it end.

Commentary Juvenile myoclonic epilepsy (JME) has long been considered to be the most common chronic idiopathic generalized epilepsy syndrome, requiring lifelong antiepileptic drug (AED) therapy (1–4). Long-term seizure freedom on appropriate AED medication has been reported between 75 and 90 percent diagnosed with JME (5–7). Janz (1985) reported seizure recurrence in 91% of patients studied when AED dosages were lowered or withdrawn completely (6). More recent patient datasets are emerging supporting the notion that the seizures seen in JME do not tend to recur following discontinuation of AED medications (5, 8). The recent review by Geithner et al. (2012) is a retrospective study summarizing the natural history of JME in 31 patients followed over several decades (mean follow-up, 39.1 years) in the northeast region of Germany. The study is unique in that it establishes several predictors of seizure remission and reaffirms that JME is a heterogeneous syndrome. As a brief review, semiological criteria required to diagnose JME must include, at least, bilateral myoclonic seizures that typically occur upon awakening. JME often includes generalized tonic-clonic seizures and, less commonly, absence seizures. Geithner et al. complements recently published studies demonstrating that the natural course of JME depends on its semiology frequency. For example, Martinez-Juarez et al. (2006) , subclassi-fied JME into four subtypes or subsyndromes: 1) classic JME, 2) childhood absence epilepsy (CAE) persisting as JME, 3) JME with adolescent onset pyknoleptic absences, and 4) JME with astatic seizures. Classic JME demonstrated the most favorable outcomes: 58% were completely controlled on AED therapy, and 5% remitted following discontinuation of medications. CAE evolving to JME has been shown to exhibit the worst clinical outcome. Such clinical classifications may complement linkage studies demonstrating JME has a high genetic predisposition. Seven loci have so far been associated with JME. These loci include 1) CACNB4 encoding a calcium channel β subunit, 2) GABRA1 encoding an α subunit of the GABA-A receptor, 3) CLCN2 encoding a chloride channel densely expressed in brain regions inhibited by GABA, 4) GABRD encoding the δ subunit of the GABA receptor, and 5) a poorly understood EFHC1 gene associated with JME; in addition, 6) chromosome 15q14, and 7) the BRD2 gene on chromosome 6p21 have also been linked to JME. Geithner et al. reported that 21 of the 31 patients identified in the study became seizure free with an appropriate AED regi-men, predominantly monotherapy. AED therapy was withdrawn (initiated by either patient …