BALTIMORE – About one in 4,000 children are born with hemimegalencephaly, meaning one brain hemisphere is abnormally formed and larger than the other.
Dr. Taeun Chang
The abnormal hemisphere causes seizures, and when they become intractable, the standard of care is to remove it as soon as possible; the longer the abnormal hemisphere is left in, the worse children do developmentally, and the less likely hemispherectomy will stop the seizures.
A problem comes up, however, when children become intractable before they’re 3 months old: “Neurosurgeons won’t touch them,” said Taeun Chang, MD, a neonatal neurointensivist at Children’s National Medical Center in Washington.
Newborns’ coagulation systems aren’t fully developed, and the risk of fatal hemorrhage is too high, she explained.
Out of what she said was a sense of “desperation” to address the situation, Dr. Chang has spearheaded a new approach for newborns at Children’s National, serial glue embolization to induce targeted strokes in the affected hemisphere. She reported on the first five cases at the American Epilepsy Society annual meeting.
At this point, “I feel like we’ve pretty much figured out the technique in terms of minimizing the complications. There’s no reason to wait anymore” for surgery as newborns get worse and worse, she said.
The technique
In two or three stages over several days, the major branches of the affected hemisphere’s anterior, middle, and posterior cerebral arteries are embolized. “You have to glue a long area and put in a lot of glue and glue up the secondary branches because [newborns] are so good at forming collaterals,” Dr. Chang said.
Fresh frozen plasma is given before and after each embolization session to boost coagulation proteins. Nicardipine is given during the procedure to prevent vasospasms. The one death in the series, case four, was in an 11-day old girl who vasospasmed, ruptured an artery over the tip of the guidewire, and hemorrhaged.
After the procedure, body temperature is kept at 36° C to prevent fever; sodium is kept high, and ins and outs are matched, to reduce brain edema; and blood pressure is tightly controlled. Children are kept on EEG during embolization and for days afterwards, and seizures, if any, are treated. The next embolization comes after peak swelling has passed in about 48-72 hours.
“The reason we can get away with this without herniation is that newborns’ skulls are soft, and their sutures are open,” so cerebral edema is manageable, Dr. Chang said.
Learning curve and outcomes
“What we learned in the first two cases” – a 23-day-old boy and 49-day-old girl – “was to create effective strokes. That’s not something any of us are taught to do,” she said.
“We were not trying to destroy the whole hemisphere, just the area that was seizing on EEG.” That was a mistake, she said: Adjacent areas began seizing and both children went on to anatomical hemispherectomies and needed shunts.
They are 5 years old now, and both on four seizure medications. The boy is in a wheelchair, fed by a G-tube, and has fewer than 20 words. The girl has a gait trainer, is fed mostly by G-tube, and has more than 50 words.
The third patient had her middle and posterior cerebral arteries embolized beginning when she was 43 days old. She was seizure free when she left the NICU, but eventually had a functional hemispherectomy. She’s 2 years old now, eating by mouth, in a gait trainer, and speaks in one- or two-word sentences. She’s on three seizure medications.
Outcomes have been best for patient five. Her posterior, middle, and anterior cerebral arteries were embolized starting at 14 days. She’s 1 year old now, seizure free on three medications, eating by G-tube and mouth, and has three-five words.
Dr. Chang said that newborns with hemimegalencephaly at Children’s National aren’t lingering as long on failing drug regimens these days. “We go to intervention now that we have this option” after they fail just two or three medications.
Given that the fifth patient, treated at 2 weeks old, is the only one who has been seizure free, she suspects it’s probably best to do embolization sooner rather than later, just as with anatomical hemispherectomy in older children. “We’ve got the sense that even a couple of weeks makes a difference. People need to come to us sooner,” Dr. Chang said.
It’s possible embolization could be a sound alternative to surgery even after 3 months of age. Focal embolization might also be a viable alternative to surgery to knock out epileptogenic lesions in children with tuberous sclerosis. Dr. Chang and her colleagues are interested in those and other possibilities, and plan to continue to develop the approach, she said.
There was no funding, and the investigators didn’t have any relevant disclosures.
SOURCE: Chang T et al. AES 2019, Abstract 1.225.