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Mutations Cause Massive Brain Swelling, UCSD Doctor Finds

Hemimegalencephaly, a rare condition that causes asymmetrical brain growth.
UC San Diego School of Medicine
Hemimegalencephaly, a rare condition that causes asymmetrical brain growth.

Hemimegalencephaly is a rare brain condition that creates a dramatic problem: half of the brain swells to an abnormal size. And the treatment is even more dramatic: removing the entire swollen half of the brain.

But Dr. Joseph Gleeson, a professor at UC San Diego, published research this week that he hopes could eventually change that. He said the condition causes severe seizures that start in childhood and right now the only treatment—removing the swollen half of the brain—is shocking to parents.

Mutations Cause Massive Brain Swelling, UCSD Doctor Finds
Hemimegalencephaly is a rare brain condition that creates a dramatic problem: half of the brain swells to an abnormal size. And the treatment is even more dramatic: removing the entire swollen half of the brain.

A rare brain condition creates a dramatic problem: half of the brain swells to an abnormal size. And the treatment is even more dramatic: removing the entire swollen half of the brain. But KPBS reporter Claire Trageser (tra-GUESS-er) tells us a researcher at U-C San Diego has made a discovery that could eventually change that. ________________________ BRAIN1 (ct) Hemimegalencephaly (hemmi-megan-ceff-oly) causes severe seizures that start in childhood. Dr. Joseph Gleeson, a professor at U-C San Diego, said right now the only treatment—removing the swollen half of the brain—is shocking to parents. BRAIN1A 0:19 “Well you can imagine when you hear your child has this condition and then you hear the treatment is to remove half the brain, it is absolutely devastating to these families. It’s kind of counterintuitive that removing half the brain would be the treatment for any disease, but in fact once the hemisphere is removed the patients can do much better because the seizures stop.” Gleeson said because brain cells come from the same place, it doesn’t make sense that half would cause swelling and half wouldn’t. He studied samples from swollen brains that were removed and found surprising results. BRAIN1B 0:21 “These mutations are the same exact mutations found in cancers. The mutations that we found are not inherited from either parent, so these came about spontaneously as the cells were dividing during brain development, yet the diseased brain never takes the form of cancer in these patients.” Gleeson hopes his research could lead to medicine to treat the condition without removing the brain. He also hopes it could help explain why certain cell types don’t form cancer, even though they have the same mutations found in cancer.

Study Published in Nature Genetics
The study on hemimegalencephaly published in Nature Genetics.
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“You can imagine when you hear your child has this condition and then you hear the treatment is to remove half the brain, it is absolutely devastating to these families," he said. "It’s kind of counterintuitive that removing half the brain would be the treatment for any disease, but in fact once the hemisphere is removed the patients can do much better because the seizures stop.”

Gleeson said the fact that only half the brain develops this swelling condition is a mystery to scientists. Because brain cells have the same origin, it doesn’t make sense that half would cause swelling and half wouldn’t.

"With everything we know about how the brain develops, we don’t think of the two hemispheres as coming from different populations of cells, so it didn’t make sense to anybody," he said.

Gleeson worked with Dr. Gary Mathern, a neurosurgeon at UC Los Angeles' Mattel Children's Hospital, who treats children with hemimegalencephaly. Gleeson took samples from the half of swollen brains Mathern had removed and compared those samples with the patient's blood.

When he looked at the genetic makeup of the blood and brain, he found surprising mutations.

"We found that patients have developed a new mutation in a specific set of genes that regulate cell growth and cell size," he said. "These are some of the same genes that are known to underlie many forms of cancer.

“These mutations are the same exact mutations found in cancers. The mutations that we found are not inherited from either parent, so these came about spontaneously as the cells were dividing during brain development, yet the diseased brain never takes the form of cancer in these patients.”

Gleeson said this finding raises the question of why the exact same mutations don’t cause cancer in hemimegalencephaly patients, but instead cause asymmetrical brain growth.

"Maybe patients are lacking the mutations to develop cancer, or maybe neurons are not capable of forming cancer like other rapidly dividing cells are," he said.

Gleeson hopes his research could lead to medicine to treat hemimegalencephaly without removing the brain. He also hopes it could help explain why certain cell types don’t form cancer, even though they have the same mutations found in cancer.