The press release was modified with permission from Johns Hopkins University.
Idiopathic normal pressure hydrocephalus (iNPH) is a treatable condition caused by a buildup of cerebrospinal fluid in the brain that leads to walking and balance problems, memory decline, and bladder control issues. The disorder affects up to 1.5% of people in their late 60s and as many as one in 13 over age 86. Left untreated, iNPH can cause falls, loss of independence, and progressive disability.
A new international study led by Johns Hopkins University School of Medicine in collaboration with the University of Utah and 10 additional institutions, and published September 16 in The New England Journal of Medicine, has provided definitive proof that shunt surgery restores mobility and safety in older adults with iNPH. The Placebo-Controlled Effectiveness in iNPH Shunting (PENS) Trial is the first large, double-blind, placebo-controlled study to resolve decades of debate on whether shunts truly help patients.
"The findings favoring the effectiveness of shunting were so compelling that the independent board reviewing the trial stopped it early and directed all participants with the 'placebo' shunts to immediately have them opened," said Richard Holubkov, Ph.D., senior author of the study and faculty with the Utah Data Coordinating Center (DCC) at the University of Utah. The DCC led the planning, implementation, data management and statistics on the study.
"This trial will greatly increase awareness of idiopathic normal pressure hydrocephalus among physicians and their patients, and improve the lives of many older Utahns and others suffering the effects of this now demonstrably treatable condition," said Holubkov, who is also a professor of pediatric critical care medicine at the university's the Spencer Fox Eccles School of Medicine.
The trial enrolled 99 patients across 17 centers in the U.S., Canada, and Sweden. All underwent shunt surgery and received a functioning shunt. However, in half the shunt was initially adjusted to a placebo setting that temporarily blocked drainage. Neither patients nor their doctors knew which group they were in.
After three months, results indicated patients with functioning shunts walked significantly faster than before surgery, while the placebo group showed virtually no change. On average, walking speed in the open shunt group improved by 0.23 meters per second-more than double the threshold considered a meaningful change in older adults. Eighty percent of patients with a functioning shunt achieved meaningful improvement compared to just 24% of those in the placebo group.
"Although shunts have been used for 50 years, skepticism persisted because of the powerful placebo effect and the risks of operating in frail, elderly patients," said Mark Luciano, M.D., Ph.D., principal investigator and Director of the Cerebral Fluid Center at Johns Hopkins. "This study shows surgery is both effective and has an acceptable safety profile. We've proven this treatment works, definitively and safely, in the most rigorous type of study possible."
Patients in the treatment group also displayed improved balance and reported fewer falls. Forty-six percent of patients in the placebo group reported falling during the trial, compared with just 25% of those who received a functioning shunt. These gains are especially meaningful for older adults, as poor mobility and frequent falls are directly tied to loss of independence, nursing home placement, and higher mortality risk.
Despite its potential for treatment, iNPH is often overlooked. Researchers report only about 20% of patients who could benefit from surgery are referred for evaluation because their symptoms are dismissed as normal signs of aging. That said, diagnosis can be simple.
"If there appears to be imbalance that's increasing, or memory loss that's increasing, it's a diagnosis that can be explored with a routine brain scan," said Luciano. "If the ventricles are enlarged and the symptoms are there, then patients can be referred to specialists who can further evaluate and treat."
Looking ahead, the PENS Trial will continue to follow participants for 12 months to measure long-term outcomes, including cognition, daily functioning, and quality of life. Early findings already suggest gains beyond walking.
"The 99 patients in the trial are being followed for another year to establish the longer-term durability of the shunting benefit, said Holubkov. "As is the case after many trials with positive findings, the researchers are designing additional studies to determine whether a more wide-ranging population of patients with this condition can also have improved lives from shunting."
The research team is also working to develop non-invasive diagnostic methods that could replace current spinal fluid drainage trials, making it easier for clinicians to diagnose patients with iNPH and connect them to treatment.
