Lennox-Gastaut syndrome: Comorbidities and clinical implications

Lennox-Gastaut syndrome (LGS) is a rare, severe developmental and epileptic encephalopathy marked by drug-resistant seizures, abnormal EEG patterns, and a broad spectrum of comorbidities. In this review we provide an overview of the main neurodevelopmental, psychiatric, motor, systemic, and epilepsy-related comorbidities in LGS, and their impact on patients and caregivers. Cognitive impairment and intellectual disability are nearly universal, often accompanied by behavioral disturbances such as hyperactivity, irritability, anxiety, and autism spectrum disorder. Motor impairments, including cerebral palsy, spasticity, and gait difficulties, are common. Epilepsy-related complications, such as recurrent status epilepticus, seizure-related injuries, and sudden unexpected death, add to the disease's burden. Systemic comorbidities, including sleep and gastrointestinal disturbances, further contribute to long-term care. Collectively, these comorbidities often impact patients and families more than seizures themselves, underscoring the need for comprehensive, multidisciplinary care and targeted interventions. In this review, we highlight comorbidities in LGS across neurodevelopmental, psychiatric, motor, systemic, and epilepsy-related domains, emphasizing their contribution to disease burden, functional impairment, and quality of life.