Alternating hemiplegia of childhood - a systematic review

Alternating hemiplegia of childhood (AHC) is a rare ATP1A3-related neurodevelopmental disorder characterized by recurrent hemiplegic episodes, paroxysmal neurological symptoms, and progressive motor and cognitive impairment. This systematic review summarizes current evidence on its clinical course, comorbidities, diagnostic findings, and treatment options.

A PubMed search (2015-2025) identified 233 records. Following PRISMA-guided screening, 31 original studies on human subjects were included.

Alternating hemiplegia of childhood typically presents in infancy and evolves into persistent interictal motor dysfunction, including impaired balance and reduced coordination. Behavioral and social impairments, such as aggression, self-injury, and severe autism spectrum traits, occur in more than half of patients. Epilepsy affects approximately 50-60%, with p.Glu815Lys variants linked to higher risk of status epilepticus. Sleep disturbances, including frequent arousals and central or obstructive apnea, are common and contribute to morbidity. Neuroimaging frequently demonstrates white matter loss and cerebellar volume reduction, occasionally accompanied by hippocampal or insular atrophy. Cardiac abnormalities, especially QTc shortening in ATP1A3-D801N carriers, represent an emerging risk factor for ventricular arrhythmias and SUDEP. Flunarizine remains the primary treatment, while cannabidiol shows additional benefit for seizures and behavioral symptoms.

Alternating hemiplegia of childhood is a complex multisystem disorder requiring early diagnosis, continuous monitoring, and multidisciplinary care. Disease-modifying treatments remain urgently needed.