Pathophysiology of developmental and/or epileptic encephalopathy with spike–wave activation in sleep: A diagnostic framework

Developmental and/or epileptic encephalopathy with spike–wave activation in sleep (D/EE-SWAS) is a rare childhood epilepsy syndrome in which abnormal brain activity during sleep can interfere with learning, language, behaviour, memory, and overall development. This condition can occur either in children with a pre-existing developmental impairment or in those who were previously developing at an expected rate, but their epilepsy syndrome causes the change in development or behaviour. Children may experience developmental slowing or regression even when seizures are infrequent or well controlled, making the condition difficult to recognize. This review summarizes current understanding of how D/EE-SWAS affects the developing brain and proposes a practical framework to help clinicians investigate children with the suspected condition. Emerging evidence suggests that the impact of D/EE-SWAS is not explained simply by the amount of epileptic activity seen on an electroencephalogram (EEG) in sleep. Instead, disruption of normal sleep processes and dysfunction of networks connecting parts of the brain – particularly, the thalamus and cerebral cortex - appear to play an important role in determining cognitive outcomes. The review also highlights that an underlying genetic cause can be identified in many children, with the gene GRIN2A being the most commonly implicated. A structured review of 293 published cases with D/EE-SWAS found that language, cognitive, and behavioural difficulties are common and may sometimes appear before obvious seizures, emphasizing the need to consider sleep EEG in children with unexplained developmental regression. Based on these findings, we propose a diagnostic framework that combines careful clinical assessment with sleep EEG, high-resolution brain MRI, genetic testing, and ongoing neuropsychological assessment. This approach aims to identify affected children earlier, understand the underlying cause, and better monitor their development over time.