Learning disability and poor academic performance in epilepsy patients are multidependent, and their treatment requires a polypragmatic approach

Dear Editor,

We read with interest the article by Babikir et al. on a prospective, cross-sectional case-control study of the learning abilities and school performance of children with epilepsy [1]. Intelligence quotient (IQ) was measured using the Stanford–Binet Intelligence Scale, and knowledge, quantitative reasoning, visual-spatial processing, working memory, and logical reasoning were tested by an experienced psychologist [1]. Patients with epilepsy had lower IQs and more learning difficulties compared to the control group [1]. The study is noteworthy, but some points require further discussion.

The first point is that the patients included were not tested for the genetic cause of epilepsy [1]. Since many of the mutations manifest phenotypically not only through epilepsy but also through cognitive impairments, developmental delays, and retardation, it would have been useful to search for pathogenic variants using whole-exome sequencing or other techniques.

The second point is that family history was not included in the analysis [1]. Since only patients with idiopathic epilepsy were included in the study and there was no possibility of genetic testing, it would have been useful to investigate how many relatives of the index patients had a positive family history of epilepsy or a multisystem disorder with epilepsy as one of the clinical manifestations.

The third point is that learning abilities and school performance before the onset of epilepsy were not assessed. Since it is conceivable that at least some of the included patients had impaired learning abilities before the onset of epilepsy, it would have been crucial to examine the cognitive functions of the included patients before epilepsy. We should also know about the early development of the included patients. How many patients had developmental delays or regressions?

The fourth point is that learning ability and academic performance can also depend heavily on sleep quality [2]. However, sleep hygiene and sleep quality were not assessed and were not included in the analysis. Sleep can be disturbed not only by nocturnal seizures but also by current medication or the underlying genetic defect. Levetiracetam and gabapentin, in particular, are known to cause insomnia in a small proportion of patients who take them [3]. Carbamazepine can also cause sleep disturbances. Other medications such as benzodiazepines, barbiturates, and some older antiepileptic drugs can impair sleep quality by potentially reducing rapid eye movement (REM) sleep or increasing sleep interruptions [3].

The fifth point is that several other factors that influence school and learning performance were not included in the analysis. Was there a difference in school performance and learning ability between patients with only focal seizures and patients with generalized seizures? Patients with generalized seizures are known to have poorer school performance compared to patients with focal seizures [4]. We should also know to what extent the frequency of seizures, the frequency of status epilepticus, and the frequency of absences have affected school performance and learning ability.

Before attributing reduced IQ and learning disorders in pediatric patients to epilepsy, all factors that influence intelligence and learning ability must be considered and included in the analysis.