Editor’s note: This is one of three articles on Upstate’s “renegade researchers” — scientists who are providing new ways of looking at long-standing medical problems, including hydrocephalus (detailed below), Kaposi sarcoma and schizophrenia.
BY AMBER SMITH
Brain surgery to install a shunt is currently the only solution for hydrocephalus, a buildup of fluid in the brain. Most research on this condition is related to devising a better shunt.
Satish Krishnamurthy, MD, goes a step further.
The Upstate neurosurgeon seeks a better solution — one that could more certainly help a greater number of people, one without so many risks, one that doesn’t even involve surgery.
He thinks in a new way about the enduring problem of hydrocephalus. It’s a condition that can affect anyone. Bleeding in the brain is the most common cause, but 180 disorders can lead to hydrocephalus — in older kids, adults, senior citizens. Sometimes babies are born with it. Any condition that results in the accumulation of cerebrospinal fluid through brain cavities known as ventricles can result in hydrocephalus.
“We really don’t understand how, exactly, this process of extra fluid damages the brain, but we do know that if you don’t treat hydrocephalus it causes both cognitive and physical handicap,” Krishnamurthy says.
Surgical treatments were developed based on the idea that excess fluid accumulates in the ventricles because of a blockage in the pathways that help absorb the fluid. Thisdiscrepancy between the amount of fluid produced and then absorbed in the ventricles results in hydrocephalus.
“There are two different kinds of surgeries that we do,” Krishnamurthy explains. “One is to put a tube into the ventricles and put the other end of the tube elsewhere — the most popular place is the belly — so the extra fluid is diverted through this tube into the belly. This is called a shunt.
“Another way to treat the hydrocephalus is to make a hole in the bottom of the brain, called endoscopic third ventriculostomy,” he says. “But it doesn’t work in everybody. Especially in infants, it doesn’t work very well at all. In adults, it works in two-thirds of people.”
Either operation may require adjustments, and serious and life-threatening complications are possible. Care includes close monitoring, which includes repeated medical imaging to make sure the shunt or ventriculostomy is working properly, and additional surgery for adjustments.
“For the patients and their families, this means that a diagnosis of hydrocephalus condemns them for multiple surgeries,” Krishnamurthy explains. “Since there is little warning before the shunt gets blocked, resulting in deadly hydrocephalus, the patient has to live with the constant fear of shunt blockage or infection.
“All of these issues compel us to seek better solutions that are predictable and more effective.”
Surgery undoubtedly helps most people with this condition. Before shunts were developed in the 1950s, everyone with hydrocephalus died.
Redefining the disorder
Solutions are developed based on what you think the problem is.
If you believe hydrocephalus happens because too much fluid is produced, and the brain is unable to drain the excess, you would envision a plastic bag full of water needing to be drained.
But the brain is actually permeable to water, Krishnamurthy says. Water can pass through the tissue, as it does in other organs. Proteins and other large molecules cannot move out of the brain cavities easily; they draw in water through a process known as osmosis. The surgeon says the brain is not like a plastic bag. Instead, it’s like a saturated tea bag.
Rather than a problem of fluid circulation, he says, “we have to redefine hydrocephalus as a disorder of protein transportation.” This calls for a very different solution.
To understand what Krishnamurthy proposes, you first have to understand a force called osmotic gradients. He has published several scientific papers on his research at Upstate explaining how the osmotic gradient causes hydrocephalus. Basically, it draws water into the ventricles when more proteins are inside the ventricles and pushes water out when there are fewer proteins. (Click here to hear Krishnamurthy explain his work in a radio/podcast interview with Upstate’s “HealthLink on Air.”)
“As osmotic gradients play an important role in the water transport into the ventricles, the transport of osmotically active macromolecules plays a critical role in the genesis of hydrocephalus,” he writes in the medical journal Translational Pediatrics. That means getting rid of the proteins in the ventricles will make the water go away from the ventricles, relieving hydrocephalus.
The surgeon envisions a medication that could coax the proteins and other molecules out of the ventricles and into the venous system, where the body would handle them like other wastes. He is currently working on testing several different medications, along with a new diagnostic test to understand how the proteins are transported in a given patient.
Much of Krishnamurthy’s research has been paid for by the Syracuse nonprofit REaCH Organization, whose name is an acronym for Research, Educate and Cure Hydrocephalus. His research is also sponsored by the hydrocephalus fund at the Upstate Foundation.
The downsides of shunts
Hydrocephalus is often treated surgically with the installation of a shunt, a tube that diverts excess fluid from the ventricles in the brain to the belly or elsewhere in the body. Neurosurgeon Satish Krishnamurthy points out problems with shunts:
- Few medical devices have a higher rate of failure. Shunts often malfunction — 40 percent fail in their first year — and have to be re-implanted. Many new shunts are programmable, but the complication rates have not decreased.
- Once in place, they provide no data and no easy method of determining if they are functioning properly.
- When a patient with suspected shunt problems is treated in the emergency department, he or she faces radiation exposure from X-rays or other imaging scans.
- Repeated shunt operations are common and are disruptive to patients’ lives, as they are usually emergency surgeries.
- Patients face a lifetime of monitoring, including diagnostic tests and surgeries.
Is it hydrocephalus?
Symptoms of fluid on the brain, or hydrocephalus, vary depending on a person’s age. Infants may develop an enlarged head, and their eyes could deviate downward. Older children or adults may experience headaches, nausea, vomiting or blurred vision. Senior citizens may appear to have dementia, difficulty walking and incontinence.
This article appears in the summer 2019 issue of Upstate Health magazine.