The PENS Trial: Breakthrough Evidence for Treating Idiopathic Normal Pressure Hydrocephalus (iNPH)

What is iNPH?

Idiopathic normal pressure hydrocephalus (iNPH) is a treatable neurological condition caused by a buildup of cerebrospinal fluid in the brain. This buildup leads to walking and balance problems, memory decline, and bladder control issues.

Normal pressure hydrocephalus is one of the few reversible causes of dementia. The disorder affects up to 1.5% of people in their late 60s and as many as 7.7% of adults over age 86. If left untreated, iNPH can cause progressive impairment, loss of independence, and even earlier death.

Diagnosis of iNPH is typically based on three key factors:

1. Symptoms – including impaired gait and balance, cognitive decline, and urinary incontinence.
2. Neurological exam – which helps rule out other potential causes in older adults.
3. Brain imaging – showing characteristic enlargement of the ventricles.

The decision to perform shunt surgery is usually guided by how a patient’s gait responds after temporary removal of cerebrospinal fluid (CSF). Currently, the only effective treatment for iNPH is the surgical implantation of a shunt to continuously drain excess CSF.

What is the PENS Trial for iNPH?

The Placebo-Controlled Effectiveness in iNPH Shunting (PENS) Trial is the first large, randomized, double-blind, placebo-controlled study to demonstrate that shunt surgery significantly improves gait and reduces falls in older adults with iNPH.

This landmark study resolves decades of debate about whether shunts truly help patients.

Key details:

• The iNPH multicenter trial was led by Johns Hopkins University School of Medicine and the Adult Hydrocephalus Clinical Research Network (AHCRN).
• Results were published online September 16, 2025, in the New England Journal of Medicine.
• Joint first authors include Mark G. Luciano, MD, PhD (Johns Hopkins University); Michael A. Williams, MD (University of Washington); and Mark G. Hamilton, MD, CM (University of Calgary, Alberta, Canada).
• The trial enrolled 99 patients across 17 centers in the U.S., Canada, and Sweden.
• Pacific Neuroscience Institute’s Hydrocephalus Center was proud to serve as one of the participating trial centers. Center director, Garni Barkhoudarian, MD, was the Local Site Principal Investigator for the study and the Pacific Brain Health Center’s Verna Porter, MD, was a co-investigator.

All participants underwent shunt surgery. However, in half of the patients, the shunt was programmed to a placebo setting that prevented it from functioning. In the other half, the shunt was open and functioning. Importantly, neither the patients nor their doctors knew which group they were in.

What Were the Results?

The primary outcome of the study was gait speed.

• After three months, gait velocity in the open-shunt group improved significantly, while gait speed in the placebo group remained virtually unchanged.
  • Open-shunt group: walking speed increased by 0.23 meters per second, more than double the threshold considered clinically meaningful in older adults.
  • Placebo group: change was only 0.03 meters per second.
  • 80% of patients in the open-shunt group achieved meaningful improvement, compared to just 24% in the placebo group.
• Patients with open shunts also had better balance and fewer falls.
  • 25% of open-shunt patients reported falling during the trial.
  • 46% of placebo patients reported falls.

Why is This Important?

Despite being a treatable condition, iNPH is often overlooked or misdiagnosed. Researchers estimate that only about 20% of patients who could benefit from shunt surgery are ever referred for evaluation. Too often, symptoms are dismissed as “normal aging.”

For more than 30 years, experts have debated whether iNPH is a distinct disorder and whether shunt surgery makes a difference. The PENS trial provides definitive proof: shunts work, and they dramatically improve mobility and quality of life.

These gains are particularly critical for older adults. Poor mobility and frequent falls are directly linked to loss of independence, nursing home placement, and increased mortality.

Looking ahead, the research team is working on noninvasive diagnostic methods to replace current spinal fluid drainage trials. This could make it easier for clinicians to identify iNPH and connect patients to life-changing treatment sooner.

The PENS trial confirms what patients and clinicians have long hoped: shunt surgery is effective for iNPH, offering renewed independence and better quality of life for older adults living with this condition.

Study Background

• Funding: National Institute of Neurological Disorders and Stroke (U01NS122764).
• ClinicalTrials.gov: NCT05081128.
• Support: Trial Innovation Network (funded by NIH awards U24TR001597 and U24TR004440).
• Collaborators: Hydrocephalus Association and AHCRN.

Take the Next Step

If you or a loved one are experiencing symptoms of iNPH — such as walking and balance problems, memory decline, or bladder control issues — it’s important to seek expert evaluation.

At the Pacific Hydrocephalus Center at Pacific Neuroscience Institute, our specialists provide comprehensive diagnosis and advanced treatments, including shunt surgery.

To learn more or request an appointment, contact the Pacific Hydrocephalus Center.

About Dr. Garni Barkhoudarian

Garni Barkhoudarian, MD, FAANS, is a board certified, fellowship-trained neurosurgeon with a focus on skull base and minimally invasive endoscopic surgery. Dr. Barkhoudarian has particular interest and expertise in pituitary and parasellar tumors, brain tumors, skull base tumors, intra-ventricular brain tumors, colloid cysts, trigeminal neuralgia, hemifacial spasm and other vascular compression syndromes. Among his numerous appointments, he is the director of the Pacific Hydrocephalus Center.

About Dr. Verna Porter

Verna R. Porter MD, FAAN, FANA, is a board certified, fellowship trained adult and geriatric neurologist.  She is the Director of Dementia, Alzheimer’s disease, and Neurocognitive Disorders at the Pacific Brain Health Center. Dr. Porter’s clinical and research interests focus on the intersection between immunological, genetic, and biomarker characteristics of neurodegenerative diseases and the impact of health lifestyle and dietary practices on optimizing brain health and cognitive vitality in the context of aging.