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Johns Hopkins Medicine
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. Researchers report the disorder affects up to 1.5% of people in their late 60s and as many as 1 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 researchers, and published Sept. 16 in The New England Journal of Medicine, has provided definitive proof that shunt surgery restores mobility and physical 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.
“Although shunts have been used for 50 years, skepticism persisted because of the placebo effect and the risks of operating in frail, elderly patients,” says Mark Luciano, M.D., Ph.D., principal investigator and director of the Johns Hopkins Hydrocephalus and Cerebral Fluid Center. “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.”
The National Institutes of Health–supported trial, funded through a $14 million grant from the National Institute of Neurological Disorders and Stroke (NINDS), was conducted by the Johns Hopkins Cerebral Fluid Center in the Department of Neurosurgery. The study enrolled 99 patients across 17 centers in the U.S., Canada, and Sweden. All patients underwent shunt surgery and received a functioning shunt. However, in half, the shunt was initially adjusted to a placebo setting. Neither patients nor their doctors knew which group they were in.
After three months, patients with functioning shunts walked significantly faster than they did before surgery, while the placebo group showed virtually no change. On average, walking speed in the shunt group improved by 0.23 meters per second — more than double the threshold considered by researchers to be a meaningful change in older adults. Eighty percent of patients with a functioning shunt achieved meaningful improvement, compared with just 24% of those in the placebo group.
“When a person walks better and doesn’t fall, everything improves: their independence, their safety and their quality of life,” says Luciano.
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 impactful for older adults, as poor mobility and frequent falls are directly tied to loss of independence, increased injury as well as higher mortality risk.
Despite its potential for treatment, iNPH is often overlooked. Researchers report that 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,” says 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.
“It has always been suspected that cognitive changes take longer to improve and need more detailed testing,” says Luciano. “At the 12-month period, we’ll have more to say not only about cognition, but how much patients are improving in their activities and independence.”
The research team is also working to develop noninvasive 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.
The study was funded by the NINDS U01NS122764; ClinicalTrials.gov number NCT05081128. This work received support from the Trial Innovation Network funded by the National Institutes of Health under awards U24TR001597 and U24TR004440.
Additional researchers involved in this trial are Abhay Moghekar, M.B.B.S., Jun Hua, Ph.D., Jessica Wollett, M.A., and Daniel Hanley, M.D., of the Johns Hopkins University School of Medicine; Michael Williams, M.D., and Nickolas Dasher, Ph.D., of the University of Washington School of Medicine, Seattle, WA; Mark Hamilton, M.D., C.M., of the University of Calgary, Cumming School of Medicine, Calgary, Canada; Heather Katzen, Ph.D., of the University of Miami Miller School of Medicine, Miami, FL; Jan Malm, M.D., Ph.D., and Anders Eklund, Ph.D., of Umeå University, Umeå, Sweden; Naomi Alpert Abel, M.D., of the University of South Florida, Tampa, FL; Ahmed Raslan, M.D., of Oregon Health & Science University, Portland, OR; Benjamin Elder, M.D., Ph.D., of the Mayo Clinic, Rochester, MN; Jesse Savage, M.D., of Adventist Health Bakersfield, Bakersfield, CA; Daniel Barrow, M.D., of Emory University, Atlanta, GA; Kiarash Shahlaie, M.D., of the University of California, Davis, CA; Hailey Jensen, M.Stat. and Richard Holubkov, Ph.D., of the University of Utah, Salt Lake City, UT; and Thomas J. Zwimpfer, M.D., Ph.D., of the University of British Columbia, Vancouver, Canada.
Information source: Johns Hopkins Medicine
