The natural history of seizures and neuropsychiatric symptoms in childhood epilepsy with centrotemporal spikes (CECTS)

Abstract

Objective: Childhood epilepsy with centrotemporal spikes (CECTS) (formally benign epilepsy with centrotemporal spikes, BECTS) is a common childhood epilepsy syndrome characterized by psychiatric, behavioral, and cognitive abnormalities and self-limited seizures. Although CECTS is one of the most well-characterized electroclinical epilepsy syndromes, the natural history of neuropsychiatric outcomes is poorly understood. We report the psychiatric, behavioral, and cognitive profiles over the course of disease from a large, prospectively-enrolled, longitudinal cohort of children with CECTS. We further characterize the detailed seizure course and test the relationship between several proposed risk factors and neuropsychiatric and seizure outcomes in these children.

Methods: Patients diagnosed with CECTS were enrolled as part of a community-based study and followed from diagnosis through disease resolution (16.0 ± 3.1 years, N = 60). Twenty sibling controls were also recruited. We report the natural history of premorbid neuropsychiatric concerns, postmorbid neuropsychiatric diagnoses, long-term neuropsychological performance, seizure course, antiseizure medication (ASM) treatment response, and the relationship between duration seizure-free and remission. Age at onset and premorbid neuropsychiatric concerns were tested as predictors of seizure count, epilepsy duration, postmorbid neuropsychiatric diagnoses, and long-term neuropsychological performance. Antiseizure medication treatment duration, seizure count, and epilepsy duration were tested as predictors of postmorbid neuropsychiatric diagnoses and long-term neuropsychological performance.

Results: Children with CECTS had a high incidence of ADD/ADHD symptoms (18.3%) or learning difficulties (21.7%) before diagnosis. New or persistent ADHD (20%), mood disorders (23.6%), learning difficulties (14.5%), and behavioral disorders (7.3%) were common after CECTS diagnosis. At 9-year follow-up, performance on formal neuropsychological testing was comparable to population statistics and sibling controls. More than two-thirds of treated children experienced at least one seizure during treatment. Most children (61.7%) had entered terminal resolution after 12 months seizure-free. Among all children, for each month seizure-free, there was a 6-7% increase in the probability of achieving terminal remission (p < 1e-10). The presence of a premorbid neurodevelopmental concern predicted a longer epilepsy duration (p = 0.02), higher seizure count (p = 0.02), and a postmorbid psychiatric or neurodevelopmental diagnosis (p = 0.002). None of the tested features predicted long-term neuropsychological performance.

Significance: Children are at high risk of neuropsychiatric symptoms along the course of the disease in CECTS, however, long-term cognitive performance is favorable. The majority of children had a seizure while being treated with ASMs, suggesting that CECTS is not as pharmacoresponsive as assumed or that treatment approaches are not optimized. Among treated and untreated children, future seizure-risk can be estimated from duration seizure-free. The presence of a premorbid neuropsychiatric concern predicted a more severe disease course in CECTS.

Keywords: Behavior; Cognitive; Mood; Outcome; Rolandic; Treatment.

Figure 1.

There is a high burden of neuropsychiatric and behavioral diagnoses in CECTS. (A) Premorbid symptoms of learning disorders and ADHD. (B) Postmorbid diagnoses of learning disorders, ADHD, psychiatric disorders, and behavioral disorders. (C) Scores on formal neuropsychological testing after 9 years. The blue dashed line represents population mean scores on each test. The black bar and diamond in the middle of the box and whisker plot represent the median and mean respectively. The first 10 scores are standardized to a mean of 100 and standard deviation of 15. The last 4 scores are standardized to a mean of 50 and standard deviation of 10. FSIQ=Full Scale IQ; VIQ=Verbal IQ; PIQ=Performance IQ; Verbal comp=Verbal comprehension subtest; Organize=Perceptual Organization subtest; Distract=Freedom from Distractibility subtest; Process Speed=Processing Speed; WRAT-R=Wide Range Achievement Test (WRAT)-Reading; WRAT-S=WRAT-Spelling; WRAT-A=WRAT-Arithmetic; TONI=Test of Nonverbal Intelligence; CPT-Om=Continuous Performance Test (CPT)-Omissions; CPT-Com=CPT Commissions; CPT-RT=CPT Reaction Time

Figure 2.

Age of onset and termination of disease in CECTS. (A) Kernel density estimates of age of first and last seizure in all subjects. (B) Empirical histograms of age of first and last seizure in all subjects. (C) Kernel density estimates of age of first and last seizure in untreated children, and (D) treated children. Age at medication end is also shown.

Figure 3.

Age of onset does not predict disease course. (A) Scatter plot of age of onset versus duration of disease. (B) Scatter plot of age of onset versus total number of seizures.

Figure 4:

The number of patients with a seizure decreases with time. The number of patients at each month (asterisks) and model fit (solid curve is mean estimate, and dashed curve is 95% confidence interval) decreases similarly for (A) all patients, (B) patients not treated with ASMs and (C) patients treated with ASMs. Among all children, after 9.1 months seizure-free, there is a 50% chance of having a subsequent seizure. After 15.1 months seizure-free, there is a 33% chance of having a subsequent seizure. After 2 years seizure-free, there is an 18.3% chance of having a subsequent seizure. After 3 years seizure-free, there is an 8.1% chance of having a subsequent seizure.