Key Takeaways

• Hemimegalencephaly (HME) is extremely rare; it is estimated to occur in less than 1% of children with epilepsy. Most affected children likely develop epilepsy, and many have drug-resistant epilepsy.
• Phoenix Children’s currently performs six to 10 hemispherectomies a year, and the rate of hydrocephalus requiring a shunt after surgery is less than 15%.
• Children whose seizures persist despite two appropriately dosed and tolerated medications, or who have seizures and a positive finding on MRI, should be referred for evaluation as soon as possible.

Hemimegalencephaly (HME) typically causes catastrophic epilepsy involving most of the affected hemisphere. Intractable epilepsy is an independent risk factor for developmental delay and sudden unexpected death in epilepsy (SUDEP), which makes early imaging and early referral critical.

Jason S. Hauptman, MD, PhD

“For HME, early referral, diagnosis and surgery can lead to the best possible outcomes,” said Jason S. Hauptman, MD, PhD, division chief of neurosurgery and Caroline Hoeye Endowed Chair in neurosurgery at Phoenix Children’s, where the team performs six to 10 hemispherectomies a year.

Case: Seizures in the First Days of Life

Gunnar began having seizures in his first days of life. He was evaluated at another hospital for 22 days and sent home. His seizures continued, eventually reaching more than 100 a day, and his family brought him to the Phoenix Children’s Emergency Department for a second opinion.

At Phoenix Children’s, Gunnar was diagnosed with HME of the right hemisphere, and genetic testing identified a DEPDC5 variant. He underwent a hemispherectomy at the age of 2 months and became the youngest patient to have the procedure at Phoenix Children’s. He has been seizure-free since surgery. His family reported that his medications were reduced from five or six to one. He receives physical therapy for gross motor skills and occupational therapy for weakness in his left hand.

The Genetic Picture

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 described DEPDC5 as “a very well-described genetic mutation that leads to HME and intractable epilepsy.”

“DEPDC5 mutations lead to the mTOR complex being stuck ‘on’ – triggering cellular overgrowth and abnormal physiology,” he said. A genetic cause also shapes the long-term outlook.

“We worry in children with genetic mutations that the ‘good’ hemisphere can be involved sometimes – even when the hemisphere can look ‘normal’ on MRI or on EEG,” Dr. Hauptman said. “That said, the catastrophic epilepsy associated with the ‘bad’ hemisphere outweighs that risk by orders of magnitude, and many kids can have an excellent quality of life if the seizures are controlled early on.”

mTOR inhibitors such as everolimus have been tried in children with these mutations. This use is considered research and is an off-label indication, though Dr. Hauptman said the team has had success in some cases. Hemispherectomy remains the gold standard treatment. As we learn more about the biology and develop more biological therapeutics, Dr. Hauptman said he hopes that “one day this can be treated medically.”

Timing and Technique

Hemispherectomy is a technically complex, long operation that requires experience and training. In small babies, the risk of blood loss, the abnormal anatomy of HME and prolonged surgical time make infant hemispherectomy more involved than surgery in older children.

“Hemispherectomy in infants should only be considered in surgical centers that have a lot of experience in doing this surgery, mainly for safety reasons,” Dr. Hauptman said.

The team balances the safety of surgery with the severity and intensity of the epilepsy. When a child is having continuous seizures, surgery may be done as early as the first month of life. When there is time, the team waits until babies are about 2 to 3 months old to reduce the need for blood transfusion.

The team performs the lateral (peri-insular) functional hemispherectomy, which Dr. Hauptman described as “considered by many to be one of the gold standards for this surgery with 80-90%+ success rates.” Through experience, the team has adapted several techniques specific to infants that enhance healing and reduce blood transfusion requirements.

What the Evidence Shows

Published research supports surgery for infants in the first year of life. Dr. Hauptman co-authored a retrospective chart review in the Journal of Neurosurgery: Pediatrics on hemispherectomy in children younger than 1 year.

“That series, which was a pooled patient experience between myself and my esteemed colleagues, Drs. Jeff Ojemann and Rich Ellenbogen, showed that the surgery can be done safely and effectively,” Dr. Hauptman said. “We firmly believe the earlier the intervention, the better the long-term outcomes in these cases.”

At Phoenix Children’s, the rate of hydrocephalus requiring a shunt after hemispherectomy is less than 15%.

“Our seizure freedom rates are extremely high,” Dr. Hauptman said.

When to Refer

Early referral of all children with epilepsy to a specialized pediatric epilepsy center is critical. When epilepsy is intractable, early surgical evaluation and imaging are mandatory. Refer for evaluation as soon as possible any child with:

• Refractory epilepsy – seizures persisting despite trials of two appropriately dosed and tolerated medications
• Seizures and a positive finding on MRI

“Time is brain – both literally and figuratively,” Dr. Hauptman said. Seizures that persist can lead to lifelong cognitive and developmental consequences, along with the risk of death from SUDEP.

“Every child has a surgical option – we have many options even for children who are not candidates for resective brain surgery,” he said.

Clinical Implications for Your Practice

• Get brain imaging as soon as possible in babies who develop epilepsy. MRI is the test of choice. In HME, one hemisphere may appear overgrown, asymmetric and abnormal.
• Refer children with seizures that persist despite two appropriately dosed and tolerated medications, or with seizures and a positive MRI finding, for evaluation as soon as possible.
• After hemispherectomy, watch for signs of hydrocephalus, including headaches, vomiting, altered mentation, seizure recurrence or other neurological findings. The team counsels families on these signs and often follows children with MRIs in the years after surgery.

A Coordinated Team

The epilepsy surgery team brings together expertise in radiology, neurology, neuropsychology and neurosurgery, with highly experienced anesthesia, surgical and hospital staff and a seamless transition to rehabilitation. The team cares for children of all ages and at all levels of medical and surgical complexity.

A standard presurgical evaluation includes a visit with an epilepsy neurologist and a neuropsychologist. A comprehensive evaluation may include structural and functional MRI, video EEG, genetic testing and PET. The pediatric epilepsy surgery team meets every week to confer on surgical patients and agree on next steps.

Phoenix Children’s actively participates in the Pediatric Epilepsy Research Consortium and offers many clinical trials for children with epilepsy. 

How to Refer

MRIs and any prior studies help if sent in advance to streamline the process. Epilepsy Surgery Coordinator Diane Laroque, RN, is a resource for referring providers. If you have a patient who may be a candidate for a clinical trial, call the team.

“When in doubt, reach out! We are here to help,” Dr. Hauptman said. Call (602) 933-KIDS (5437) or make a referral online. 

About the Author

Jason S. Hauptman, MD, PhD, is a pediatric neurosurgeon, division chief of neurosurgery and the Caroline Hoeye Endowed Chair in Neurosurgery at Phoenix Children’s. He specializes in epilepsy and functional neurosurgery, and his surgical expertise includes functional hemispherectomy, robotic stereo-EEG, responsive neurostimulation and laser interstitial thermal therapy. His research focuses on brain mapping, the genetics of pediatric epilepsy and clinical trials of novel drug therapies for children with epilepsy. Before joining Phoenix Children’s, he helped direct the surgical epilepsy program at Seattle Children’s Hospital. He has authored or co-authored more than 100 peer-reviewed articles.

Citation

Nistal D, et al. Hemispherectomy in infants: an institutional experience with 21 patients. J Neurosurg Pediatr. 2026;37(3):220–226. PMID: 41569724.