Association of early-onset epileptic encephalopathy with involuntary movements - Case series and literature review

Abstract

Epileptic-dyskinetic encephalopathies are rare epilepsies characterized by early-onset epileptic encephalopathies (EOEEs) with involuntary movement. Herein, we investigated the impact of gene variants in epileptic-dyskinetic encephalopathies. Four independent patients from four families who exhibited involuntary movements were recruited from Tokyo Metropolitan Neurological Hospital. The inclusion criteria were as follows: onset within 1 year after birth, frequent seizures, severe developmental delay and accompanying involuntary movements. We detected four genetic mutations, including STXBP1, GNAO1, CYFIP2, and SCN8A variants. The involuntary movements were drug-resistant. However, pallidal electrocoagulation followed by gabapentin were partially effective in treating chorea and ballismus of the extremities in patients with GNAO1 variants, and perampanel partially suppressed seizures and involuntary movements in one patient with a SCN8A variant. Movement disorders are common to many neurodevelopmental disorders, including a variety of EOEEs. Although we could not establish a definitive correlation using genetic variants in patients with EOEE and movement disorders, involuntary movements in patients with EOEEs may be a key diagnostic finding. The usage of genetic variants could prove beneficial in the future as more patients are investigated with epileptic-dyskinetic encephalopathies.

Keywords: ACTH, adrenocorticotropic hormone; EEG, electroencephalography; EMG, electromyography; EOEE; EOEEs, early-onset epileptic encephalopathies; Early-onset epileptic encephalopathy; Epileptic seizure; Epileptic-dyskinetic encephalopathy; Genetic variant; Involuntary movement; MRI, magnetic resonance imaging.

Fig. 1

Interictal electroencephalography (EEG) findings. Patient 1 (STXBP1 variant); interictal EEG showed continuous, generalized irregular spike-and-wave complexes while awake (A-1) and during sleep (A-2). Patient 2 (GNAO1 variant); multifocal spikes, spikes and waves during waking (B-1), and generalized polyspikes and waves during sleep (B-2). Patient 3 (CYFIP2 variant); multifocal spikes and spike-and-waves during waking (C-1) and bilateral independent focal spikes and spike-and-waves during sleep (C-2). Patient 4 (SCN8A variant); posterior dominant theta rhythm while awake (D-1) and bilateral independent focal spikes during sleep (D-2).