A novel STXBP1 mutation causes focal seizures with neonatal onset.

Mutations of the syntaxin binding protein 1 (STXBP1) have been associated with severe infantile epileptic encephalopathies (Ohtahara syndrome and West syndrome), but also with moderate to severe cognitive impairment and nonsyndromic epilepsy. We have studied a white infant who presented with focal seizures at age 2 weeks. Brain imaging was unremarkable. The electroencephalograph (EEG) demonstrated normal background frequency content but with multifocal sharp waves and no evidence of the typical patterns associated with Ohtahara or West syndrome. Therapy with levetiracetam and oxcarbazepine effectively managed the seizure episodes. Investigation of genes associated with infantile forms of epilepsy such as SCN1A, SCN1B, and ARX were negative, but we identified a novel single-nucleotide duplication mutation, c.931dupT (p.S311FfsX3), in exon 11 of the STXBP1 gene. This previously unreported STXBP1 mutation in a subject with neonatal-onset focal seizures broadens the spectrum of clinically relevant human disorders caused by STXBP1 mutations.

Heart rate variability during interictal epileptiform discharges.

RATIONALE: Seizures may produce a variety of autonomic alterations. These alterations may occur due to evoked autonomic reflexes or as a direct cortical effect on autonomic control. In animal studies, lock step phenomena of interictal discharges to autonomic output have been repeatedly documented. However, the association of interictal discharges and autonomic output is not as well established in humans. METHODS: RR intervals timely locked to interictal epileptiform discharge (RR(n)) were compared to RR intervals immediately following (RR(n+1)) interictal discharges in 40 patients with focal onset epilepsy and low baseline heart beat variability. RESULTS: In 20 patients with 200 left sided interictal epileptiform discharges, RR(n) shortened in 100 and prolonged in 31 when compared to RR(n+1) intervals. While in 20 patients with 200 right sided interictal epileptiform discharges RR(n) intervals shortened in 17 and prolonged in 116 (Chi square P<0.001). No consistent differences in RR(n) intervals variability between frontal versus temporal localization of the interictal discharges from the same side was found. CONCLUSIONS: Interictal discharges, may influence autonomic control over the cardiac cycle and agree with animal studies. Further study of the relationship of interictal discharges to autonomic output is needed to delineate the potential lateralized influences over autonomic nervous system.