Cognitive outcomes following epilepsy in infancy: A longitudinal community‐based study

Abstract

Objective: Onset of epilepsy before 2 years of age is associated with poor cognitive outcome; however, the natural course of the range of epilepsies that occur at this age is unknown. The aim of this prospective community-based study was to investigate the neuropsychological development of infants with newly diagnosed epilepsy longitudinally and to identify the clinical factors that predict long-term impairment. Methods: Sixty-six infants <24 months of age were enrolled in the baseline phase of this study; 40 were seen again at 1-year follow-up and 40 at 3-year follow-up. Children underwent a neurological and neuropsychological assessment at each time point. Results: More than 55% of children demonstrated impaired cognitive functioning at each assessment, with a similar percentage showing impaired memory and attention at 3-year follow-up. Cognitive scores obtained at each time point were correlated. More than 20 seizures/seizure clusters prior to assessment and an abnormal neurologic examination predicted poor cognitive functioning at baseline, whereas continuing seizures and baseline cognitive score predicted 3-year intelligence quotient (IQ)/cognitive score. Significance: These findings demonstrate the following: (1) infants who are performing poorly at baseline continue to display impaired development at follow-up, (2) these children are delayed across a range of neuropsychological functions, and (3) a high number of seizures close to initial diagnosis and continuing seizures at follow-up independently predict cognitive impairment. These findings help to identify those infants with new-onset epilepsy who are most at risk for poor developmental outcome and suggest that multimodal interventions should be instituted early in the course of the disorder to improve outcomes. K E Y W O R D S cognitive development, cognitive outcome, epilepsy in infancy, neurologic predictors

Visuospatialskills and Antiseizure Medicationsin Chi

“…The worst performance in visuospatial memory in our sample was linked to an earlier onset and longer duration of epilepsy and executive functions, while there was no significant association with non-verbal intelligence. The data collected, support the evidence that an early onset of seizures can lead to a worse deterioration of cognitive functions, affect the development of the neuronal system still in development (Kellermann et al, 2015;O'Reilly et al, 2018). In this study there is a positive relationship between visuospatial memory skills and executive functions at baseline, not in visuospatial perception skills.…”

Improved everyday executive functioning following profound reduction in seizure frequency with fenfluramine: Analysis from a phase 3 long-term extension study in children/young adults with Dravet syndrome

“…Children with DS experience early-onset developmental delays across cognitive, adaptive, motor, and behavioral domains [1,3,12,13]. The degree of intellectual disability varies widely, from mild to severe [14][15][16], with most people with DS requiring lifelong care due to limitations in their ability to conduct normal activities of daily living [1,6,[17][18][19][20][21][22][23].…”

“…Individuals with DS almost always require polytherapy [33], which significantly increases the likelihood of adverse cogni-tive drug effects [30,32,34,35]. Children and young adults with DS represent a particularly vulnerable population because multi-ASM combinations can have negative additive effects on cognition [29,31], especially if seizures are poorly controlled, during their most developmentally sensitive time period [22,23]. To our knowledge, no studies have evaluated the long-term impact of ASMs on EF in children and young adults with DS.…”

Raising the bar: Fenfluramine sets new treatment standards for Dravet syndrome

“…Fenfluramine is currently labeled for treatment at a minimum age of 2 years [21], with pivotal trials conducted in patients at a mean age of 9 years [8]. However, disease onset most often occurs before 1 year of age, and minimizing seizure burden from an early stage in the disease could result in a better long-term prognosis for cognitive outcomes and other non-seizure comorbidities (1) as a direct result of seizure control [8,29,[39][40][41][42][43], (2) as the result of better engagement in other early intervention and education programs to support cognitive and social development [23,26,27], and (3) due to the inherent pharmacological activity of fenfluramine [30,31,33]. As Dravet is diagnosed earlier and earlier, the question arises as to whether fenfluramine could be utilized in younger patients (before the age of 2 years).…”