Epilepsy in Menkes disease: Analysis of clinical stages

Purpose: Epilepsy is one of the main features of Menkes disease ( MD), although it is not described in depth. To determine the spectrum of epilepsy, we studied its main characteristics. Methods: Based on clinical charts, we retrospectively analyzed the evolution of electroclinical features of 12 patients with confirmed MD. Results: Epilepsy could be divided into three periods: ( a) an early stage ( median age, 3 months), characterized by focal clonic status epilepticus, usually triggered by fever ( 10 patients). Ictal EEG showed runs of slow spike-waves and slow waves in the posterior regions, and interictal EEG multifocal and polymorphic slow waves ( three cases), or mixed slow spike-waves and slow waves ( seven cases). Partial seizure control was obtained in nine patients during 5.9 months; ( b) an intermediate stage ( median age, 10 months) with intractable infantile spasms ( 11 patients) in which interictal EEG demonstrated modified hypsarrhythmia ( seven cases), diffuse irregular slow waves and spike-waves ( four cases). Six patients died at the median age of 15 months; and ( c) a late stage in the six remaining patients ( median age, 25 months), with multifocal seizures, tonic spasms, and myoclonus in four patients, whereas two patients became seizure free. Interictal EEG showed multifocal high-amplitude activity, mixed with irregular slow waves in all six cases. These patients died at the median age of 3.6 years. Conclusions: Based on a relatively large series of MD patients with a quite prolonged survival, we individualized three successive periods in the course of epilepsy: early focal status, then infantile spasms, and then myoclonic and multifocal epilepsy after age 2 years.