Abstract Objective Developmental arrest or regression that results in intellectual disability (ID) is a common neurological sequela of infantile epileptic spasms syndrome. Spindles are the hallmark of non‐rapid eye movement sleep, and their density correlates with cognitive performance. Recent evidence suggests that ictal and interictal epileptic activities hijack the thalamocortical network. Therefore, we aimed to investigate whether thalamocortical dysfunction, as represented by reduced spindle density, is related to cognitive outcomes. Methods We retrospectively recruited patients diagnosed with infantile epileptic spasms syndrome who were treated at Saitama Children's Hospital. Specifically, we included patients with an unknown etiology to minimize the effects of preceding thalamocortical dysfunction induced by various etiologies before the onset of infantile epileptic spasms syndrome. These cohorts were separated into two groups based on the presence or absence of ID, defined as an intelligence quotient (IQ) or developmental quotient (DQ) of <70, during follow‐up. Information concerning patients' background characteristics, treatment response (defined as seizure cessation for at least 3 months), and cognitive performance was extracted. Pre‐ and posttreatment spindle features were derived from quantitative assessment of spindle features performed using automated algorithms, which were validated against expert human annotations. Additionally, logistic regression was used to validate the independent predictors of cognitive outcomes. Results Overall, 45 patients were included (23 and 22 patients in the ID and non‐ID groups, respectively). Posttreatment spindle density was significantly higher in the non‐ID group than in the ID group. Moreover, spindle density was positively correlated with DQ/IQ values across the entire cohort. Finally, a logistic regression model revealed that spindle density and treatment response were independent predictors of cognitive outcomes. Significance Reduced posttreatment spindle density was correlated with cognitive outcome in infantile epileptic spasms syndrome. The thalamocortical network may be a potential treatment target to achieve favorable cognitive outcomes.
Daida et al. (2026) studied this question.