Researchers in the Department of Neurological Surgery at the Indiana University School of Medicine are leading efforts to develop new, safe therapies for children and adults living with hydrocephalus, a life-threatening condition in which cerebrospinal fluid builds up in the brain.
More than 1 million people in the United States are living with hydrocephalus, and one out of every 770 American babies will develop the condition, according to the Hydrocephalus Association.
"There are natural fluid spaces or ventricles in the brain, and when there is extra spinal fluid, the ventricles enlarge and cause high pressure in the brain," said Jason Chu, MD, MSc, pediatric neurosurgeon and associate professor of neurological surgery.
"Untreated hydrocephalus can impair neurodevelopmental progress, and that is critical in babies as they are going through this phase from newborn to infant. Their brain is growing and trying to achieve its maximum potential, but the high pressure will prevent that from happening."
There are currently no pharmaceutical treatments for hydrocephalus, and the only standard of care for patients of all ages involves surgery — the most common being the placement of a ventriculoperitoneal shunt, a small silastic tube that is placed through incisions on the scalp and abdomen. The tube goes into brain ventricles where extra fluid is built up and runs under the skin to the abdomen, where it is absorbed back into the body.
While shunts have revolutionized the treatment for hydrocephalus and are "responsible for saving countless infants' lives," Chu said they can fail for a variety of reasons including equipment malfunction and infection, predisposing the patient to multiple brain surgeries.
"Data suggests if you have a baby that had a shunt placed early on in life, in about 10 years-time, 50% of those patients will have had a second surgery because the shunt stopped working properly," Chu said. "Every year, that risk is pretty low, but over time as that child grows into an adult, it does add up."
Chu is investigating whether a different treatment approach may lead to better, long-term developmental outcomes for young patients with hydrocephalus.
He is the primary investigator for the Endoscopic vs Shunt Treatment of Hydrocephalus in Infants, or ESTHI, in Indianapolis at Riley Children’s Health, one of 19 sites participating in the randomized controlled clinical trial for children less than 2 years of age with hydrocephalus.
The purpose of the study is to compare the placement of a shunt with a newer technique called endoscopic third ventriculostomy with choroid plexus cauterization (ETV+CPC).
The technique manages hydrocephalus in two steps. First, surgeons use an endoscope to create a small opening in the brain's third ventricle, allowing fluid to escape and be reabsorbed into a different area of the brain. Second, choroid plexus tissue is cauterized to slow down the production of cerebrospinal fluid.
"The biggest advantage is that we're able to treat hydrocephalus without needing a permanent device in the brain," Chu said. "That helps eliminate the worry of having trouble with the shunt in the future and needing additional operations."
Within the first six months of the operation, Chu said surgeons will know if the ETV+CPC technique worked or if a second operation is needed.
Children participating in the trial will undergo neurodevelopmental testing for five years. These results will help researchers determine the impact of each treatment on the brain's development, Chu said.
Trial enrollment will continue until 2027.
"We understand participating in clinical trials can be intimidating, but I always explain to families that their child, regardless of participation or not, will receive the same level of high-quality care that every single baby with hydrocephalus does at Riley," Chu said. "It's hard to know if participating in this trial will directly help your baby, but the results will certainly help others in the future who may be in similar situation as yourself by potentially giving them two different treatments for hydrocephalus."
Chu is not alone in his pursuit of better treatment options for patients with hydrocephalus.
Bradley Bohnstedt, MD, associate professor of neurological surgery, is the primary investigator for Evaluation of the Safety and Effectiveness of the CereVasc eShunt System in Normal Pressure Hydrocephalus or STRIDE, which is currently enrolling patients aged 60 years or older.
Angela Richardson, MD, PhD, assistant professor of neurological surgery, was the local site primary investigator for the A Placebo-Controlled Effectiveness in INPH Shunting or PENS. Primary results of the clinical trial were published in the New England Journal of Medicine.
And Scott Mitchell, MD, a PGY 6 neurosurgery resident, is studying the development of large animal models of post-hemorrhagic hydrocephalus alongside Bonnie Blazer-Yost, PhD, director of the Hydrocephalus Research Center at the IU School of Medicine.
"Everyone is working to achieve the same goal and that is to make our patients feel better and help give them the best quality of life," Chu said. "We're doing that through cutting-edge, frontline care and by participating in these innovative research studies to better understand the best way to treat hydrocephalus. That’s what sets IU School of Medicine apart — there are very few centers around the country that are achieving what we are for our patients."
