A tale of two cohorts: Differing outcomes in infantile‐onset focal epilepsy

Abstract

Objective: Infants with focal-onset epilepsy are an understudied population, requiring additional evaluation for clinical assessment and prognostication. Our goal was to characterize the etiology and natural history of infantile-onset focal epilepsy. Methods:We retrospectively identified all infants (0-24 months) with onset of focal epilepsy while resident in Olmsted County, Minnesota, between 1980 and 2018, using the Rochester Epidemiology Project Database. We assessed the impact of etiology on both seizure and neurodevelopmental outcome, and mortality.Results: Of 686 children with epilepsy onset <18 years, 125 (18.2%) presented with focal-onset seizures in infancy. Median follow-up for this group was 10.9 years (interquartile range [IQR] 6.2, 19.3). Etiology was identified in 65.6% (structural N = 62, genetic N = 13, both structural and genetic N = 3, metabolic N = 4). Of 107 patients followed >2 years, 38 (35.5%) developed drug-resistant epilepsy (DRE). DRE was more likely with younger age at onset, known etiology, and presence of epileptic spasms. Sixty-eight (63.0% of those with follow-up)were developmentally delayed at last follow-up, and known etiology, DRE, and presence of epileptic spasms were significantly associated with delay (p < .001 for all). Fifteen patients (12.0%) died at a median age of 7.1 years (IQR 1.7, 21.7), but only one death was seizure related (suspected sudden unexpected death in epilepsy [SUDEP]). Of 20 infants with normal development at onset and no known etiology with >2 years follow-up, none developed DRE, all were seizure-free at last follow-up (95% off antiseizure medications [ASMs]), and all remained developmentally normal.

Outcome at age 7 of epilepsy presenting in the first 2 years of life. A population‐based study

“…Mortality at 9.5% in our study is in line with previous data, as is the observation that mortality is related mainly to severe underlying etiology and impairments, with pneumonia being a common fatal complication 10–12 . Cases of aspiration due to seizures 10,11 and SUDEP 9,12 add to mortality.…”

“…12 Mortality at 9.5% in our study is in line with previous data, as is the observation that mortality is related mainly to severe underlying etiology and impairments, with pneumonia being a common fatal complication. [10][11][12] Cases of aspiration due to seizures 10,11 and SUDEP 9,12 add to mortality. Mortality after first-year seizure onset is somewhat lower in previous studies than the 11% in our cohort, possibly due to their shorter follow-up time 9 and inclusion of milder cases.…”

“…In addition, hospital‐based reports of outcomes in infantile‐onset epilepsy often show worse outcomes in terms of seizure freedom and cognition due to selection bias 13–16 . Recurrently reported prognostic factors include seizure‐onset age, developmental delay at onset, and etiology 1,4,8–12 . Etiology appears to be the main independent prognostic factor but it is often unknown 1,9,10 …”

“…[13][14][15][16] Recurrently reported prognostic factors include seizure-onset age, developmental delay at onset, and etiology. 1,4,[8][9][10][11][12] Etiology appears to be the main independent prognostic factor but it is often unknown. 1,9,10 We recently described epilepsy syndromes and etiologies in a population-based prospective incidence cohort of 116 children presenting with epilepsy during the first 2 years of life.…”

A Muddy Crystal Ball for Infantile-Onset Epilepsy Outcomes

“…Let’s enjoy the good news first. 4 After at least 2 years of follow-up, 57% of patients were seizure-free for at least a year, and almost one-third were able to stop taking anti-seizure medication. Normal cognition at diagnosis, normal neurological examination, normal MRI, absence of EEG background slowing, and an unknown etiology predict seizure freedom.…”