Miller School Neurology Researcher Contributes to NEJM Study Analyzing Shunting for Idiopathic Normal-Pressure Hydrocephalus
Summary
- Idiopathic normal-pressure hydrocephalus is a neurological disorder that primarily affects older adults, causing difficulties with walking, balance, cognition and bladder control.
- A new New England Journal of Medicine multicenter trial provides robust evidence that shunt surgery improves gait and reduces falls in older adults with iNPH.
- The study’s lead investigator, the Miller School’s Heather Katzen, Ph.D., says the work shows shunt surgery can deliver substantial improvements in mobility and balance but must be weighed against procedural risks and realistic expectations for other symptoms.
Idiopathic normal-pressure hydrocephalus (iNPH) is a neurological disorder that primarily affects older adults, causing difficulties with walking, balance, cognition and bladder control. The disorder affects up to 1.5% of individuals in their late 60s and as many as 7.7% older than 86. Left untreated, iNPH can cause progressive impairment and disability, loss of independence and earlier death.
While shunt surgery—implanting a device to drain excess cerebrospinal fluid (CSF)—has long been used to treat iNPH, its true effectiveness has remained uncertain due to variable study results and concerns about placebo effects and surgical risks.
A new multicenter trial published in the New England Journal of Medicine provides robust evidence that shunt surgery improves gait and reduces falls in older adults with iNPH. The University of Miami Miller School of Medicine’s Heather Katzen, Ph.D., a voluntary assistant professor of neurology, is a lead investigator of the study.
Research Overview: Does Shunting Work?
The Placebo-Controlled Effectiveness in iNPH Shunting (PENS) trial is the first large, randomized, double-blind, placebo-controlled study examining shunt outcomes in iNPH. This NIH-funded study enrolled 99 participants across the United States, Canada and Sweden, all selected for shunt surgery based on a positive response to temporary CSF drainage.
All participants received programmable shunts and were randomly assigned to one of two groups:
• Open-shunt group: Shunt set to an opening pressure allowing CSF to drain (110 millimeters of water).
• Placebo group: Shunt set at pressure effectively preventing CSF drainage (greater than 400 millimeters of water).
Key Findings
• Gait and balance improvements: After three months, gait velocity in the open shunt group was significantly faster than before surgery. Gait speed in the placebo group was virtually unchanged. 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 in the open shunt group achieved meaningful improvement, compared to just 24% of those in the placebo group. Patients in the open shunt group also had improved balance and reported fewer falls. Twenty-five percent of patients in the open shunt group reported falling during the trial, compared with 46% of those in the placebo group.
• Cognition and incontinence: While there was a small improvement on a cognitive screening tool and bladder symptom questionnaire in the open shunt group, these changes were not statistically significant.
• Functional outcomes: Patients in the open-shunt group reported notable improvements in functional independence and quality of life, as well as tertiary measures of cognitive functioning, as assessed by standardized scales. All of these outcomes will be examined more extensively in follow-up studies.
• Imaging findings: The open shunt valve setting appeared to reduce lateral ventricular volume, which is consistent with a functioning shunt.
• Safety and adverse events: The trial carefully monitored complications. Notably, the placebo group experienced more falls (46% vs. 25%) while the open-shunt group had higher rates of cerebral or subdural bleeding (14% vs. 4%) and positional headaches (59% vs. 28%). Most serious complications were managed successfully by adjusting the shunt valve settings.
Implications for Clinical Care
This study conducted by Dr. Katzen and colleagues provides compelling evidence that shunt surgery, when performed according to international guidelines and after confirming a patient’s responsiveness to CSF drainage, leads to meaningful improvements in gait and balance for individuals with iNPH. These improvements can reduce the risk of falls, a major concern for older adults, and enhance overall quality of life.
Clinicians and patients facing the challenges of idiopathic normal-pressure hydrocephalus now have clear guidance. Shunt surgery can deliver substantial improvements in mobility and balance but must be weighed against procedural risks and realistic expectations for other symptoms.
“Despite the potential for treatment, iNPH had often been overlooked,” said Dr. Katzen. “In fact, only about 20% of patients who could benefit from surgery are referred, as symptoms are dismissed as normal aging and doubts have persisted about shunt effectiveness. We hope this study will encourage clinicians to carefully evaluate patients with symptoms, neurologic findings and imaging consistent with iNPH, and consider surgery, when appropriate.”
Moving forward, the PENS researchers are following patients out to 12 months of open shunting to examine longer-term outcomes. Dr. Katzen and her colleagues are also conducting detailed neuropsychological testing in about two-thirds of study participants to better understand cognitive outcomes.
“We have suspected for some time that cognition takes longer to improve after shunting,” Dr. Katzen said. “At the end of the 12-month period we will have more to say about the expected time course of cognitive recovery, as well as the extent to which patients are improving in their activities of daily living and independence.”
Tags: Department of Neurology, Dr. Heather Katzen, neurology, The New England Journal of Medicine