Infant Hemispherectomy for Hemimegalencephaly: Why Early Referral Matters

Hemimegalencephaly can cause drug-resistant epilepsy in infants. Learn when to refer for hemispherectomy and what the evidence shows.

By
November 6, 2026
8 min

Phoenix Children's Medical Connection

At a Glance

Category	Detail
Condition	Hemimegalencephaly (HME), an extremely rare condition estimated to occur in less than 1% of children with epilepsy; most affected children likely develop epilepsy, and many have drug-resistant epilepsy.
Key Mechanisms	Many children with HME and cortical dysplasia have germline or mosaic/somatic variants in genes involved in the PI3K-AKT-mTOR pathway, including DEPDC5. Dr. Hauptman says DEPDC5 mutations can trigger cellular overgrowth and abnormal physiology.
Target Population	Children with epilepsy, especially those with HME; refer as soon as possible when seizures persist despite two appropriately dosed and tolerated medications or when seizures occur with a positive MRI finding.
Care Setting	Specialized pediatric epilepsy and epilepsy-surgery centers; the source says infant hemispherectomy should be considered only at centers experienced with the procedure.

Key Highlights

HME is estimated to occur in less than 1% of children with epilepsy; most affected children likely develop epilepsy, and many have drug-resistant epilepsy.
Brain MRI is the test of choice for babies who develop epilepsy; the article advises imaging and referral as soon as possible.
Refer children for evaluation when seizures persist despite two appropriately dosed and tolerated medications, or when seizures occur with a positive MRI finding.
Hemispherectomy is described as the gold-standard treatment for HME-associated catastrophic epilepsy; timing balances seizure severity with infant surgical risks.
After hemispherectomy, monitor for hydrocephalus; Phoenix Children’s reports a shunt-requiring hydrocephalus rate below 15%.

Guideline-Based Recommendations

Diagnosis

Obtain brain imaging as soon as possible in babies who develop epilepsy; MRI is the test of choice.

Management

Refer as soon as possible for evaluation if seizures persist despite two appropriately dosed and tolerated medications, or if seizures occur with a positive MRI finding.
Consider infant hemispherectomy only at a surgical center experienced with the procedure.
For continuous seizures, surgery may be done as early as the first month of life; when circumstances allow, the team waits until about 2 to 3 months to reduce the need for blood transfusion.
Everolimus and other mTOR inhibitors have been tried for these mutations; the article describes this use as research and off-label. Hemispherectomy remains the gold-standard treatment.

Monitoring & Follow-up

Counsel families about hydrocephalus warning signs after hemispherectomy, including headaches, vomiting, altered mentation, seizure recurrence, or other neurological findings.

Risks

The article identifies intractable epilepsy as an independent risk factor for developmental delay and SUDEP.
Infant hemispherectomy involves risks related to blood loss, abnormal HME anatomy, and prolonged operating time.
Dr. Hauptman says the team worries that genetic involvement may affect the other hemisphere even when it appears normal on MRI or EEG.

Patient & Prescribing Data

Infants and children with HME-associated epilepsy, including those with drug-resistant seizures or seizures and abnormal MRI findings.

Hemispherectomy is described as the gold-standard treatment. The article reports that Phoenix Children’s performs six to 10 hemispherectomies annually and has a shunt-requiring hydrocephalus rate below 15%. mTOR inhibitors such as everolimus have been tried in research and off-label use.

Clinical Best Practices

Refer children with epilepsy early to a specialized pediatric epilepsy center; arrange MRI as soon as possible for babies who develop epilepsy.
Refer as soon as possible for surgical evaluation when seizures persist despite two appropriately dosed and tolerated medications or when MRI is positive.
Use a surgical center experienced with infant hemispherectomy.
Counsel families about postoperative hydrocephalus warning signs.