Abstracts

Rationale: In our large study of infantile-onset epileptic encephalopathies, we identified a new genetic focal epileptic encephalopathy of severe infantile multifocal epilepsy (SIMFE) defined as infantile onset epileptic encephalopathy with multifocal seizures and subsequent developmental slowing. We aimed to confirm that SIMFE is a recognizable electroclinical syndrome due to sodium channel gene (SCN1A) mutations. Methods: Clinical and electrophysiological findings in 7 SIMFE patients were characterized. Sanger sequencing of SCN1A was performed and copy number variations were excluded by multiplex ligation-dependent probe amplification. Results: Median age of seizure onset was 6 mths(5-19 mths). All 7 patients were female (3 briefly reported previously). Initial seizures were brief and afebrile in 57%(4/7) and comprised generalized tonic-clonic (TCS)(3/7), focal(3/7), and hemiclonic seizures(1/7). The most frequent seizure type was focal in all with a median onset age of 19 mths(4.5 mths - 4.3 yrs). 5(71%) had TCS and 4(57%) had tonic seizures. Myoclonic (5/7), hemiclonic (4/7), or atonic seizures (1/7) were transient. Myoclonic seizures were triggered by vigabatrin or gabapentin in two patients. All patients had multiple types of focal seizures which were often well lateralized but poorly localized. The most common semiology comprised eye and/or head deviation with focal clonic or asymmetric tonic movements with unresponsiveness (4/7, 57%). Focal seizures (20 sec-3 mins) occurred in clusters (71%) and evolved to bilateral convulsive seizures or SE (median onset age 3 yrs; 9 mths-7 yrs). All developed learning difficulties (median onset age, 3.5 yrs; 16 mths-8 yrs) with variable cognitive ability from severe intellectual disability to normal. There is no generalized epilepsy. Early EEGs were normal or showed slowing and 3 patients showed 1 or 2 epileptiform foci. Multifocal epileptiform activity appeared later in 5 (71%)(median onset age 4.3 yr; 3 yrs - 9 yr 10 mth). Photosensitivity was not seen. Ictal EEGs showed multifocal seizures that propagating diffusely but did show a not migrating focal pattern. 6 patients (86%) had SCN1A mutations. Conclusions: SIMFE is due to SCN1A mutations in most cases. SIMFE is distinct from Dravet syndrome as it has multifocal rather than generalized seizures, later developmental slowing and frequent tonic seizures.