Hemimegalencephaly is a rare malformation of cortical development in which one cerebral hemisphere is abnormally enlarged and structurally disorganised. It is strongly associated with early-onset epilepsy, which is frequently drug-resistant.
What happens in the brain?
The affected hemisphere can show abnormal cortical thickness, abnormal gyration, altered white matter and enlarged ventricular or hemispheric structures. The degree and distribution vary between individuals.
Seizure onset
Seizures often begin in infancy and may be frequent, multiple in type and difficult to control with medication. Epileptic spasms, focal seizures and other severe seizure patterns can occur.
Development
Developmental outcome is influenced by the severity of the malformation, seizure burden, underlying genetic or mosaic cause and associated neurological impairment. Motor deficits are common.
Genetics and mosaicism
Hemimegalencephaly is increasingly understood as a disorder of abnormal brain growth pathways, often involving somatic mosaic variants affecting the PI3K–AKT–mTOR pathway. A variant may be present in affected brain tissue even when blood testing is negative.
Why surgery is considered early
When seizures are severe and drug-resistant, disconnective hemispheric surgery can be considered. The aim is to disconnect the epileptogenic hemisphere from the rest of the brain rather than trying to remove every abnormal cortical area.
Outcomes and risks
A large 2024 single-centre series reported meaningful seizure control after hemispheric surgery, but outcomes were variable and complications such as hydrocephalus and the need for revision surgery occurred. Surgery is therefore undertaken in specialist centres after detailed evaluation.
Newer approaches
Some highly specialised centres have investigated endovascular approaches in very young infants with severe disease, but these are not standard treatment everywhere and evidence remains limited to specialist series.
Related reading
- Structural and Acquired Epilepsies
- Epilepsy Surgery
- Drug-Resistant Epilepsy
- Epilepsy in Children and Young People
Functional trade-offs of hemispheric surgery
Hemispheric surgery can carry major expected neurological consequences, including loss of fine hand function and visual-field change on the opposite side. Presurgical assessment therefore weighs existing function, seizure burden and developmental harm from ongoing seizures.
Sources and further reading
- Hemispheric epilepsy surgery for hemimegalencephaly: The UCLA experience. Epilepsia. 2024. PMID: 37873610.
- Transarterial embolization for infants under 3 months with refractory seizures due to hemimegalencephaly. 2025. PMID: 40425282.
Evidence checked: September 2026.