NPHAW Research Blog: The PENS trial

The “PENS trial” (Placebo-Controlled Efficacy in Idiopathic Normal Pressure Hydrocephalus (iNPH) Shunting trial) has provided first-class evidence that shunt surgery can improve NPH symptoms.

Researchers designed a study in which patients were fitted with a shunt with either an open/working valve or a closed/placebo valve. Neither the patients nor most of the doctors knew who received the working shunt and who received a placebo and people were assigned randomly into each group. The study showed that in people with NPH who had shown improvement after a preliminary spinal tap, shunt surgery made a real difference in walking speed.

Nearly 100 people participated, with about half receiving a shunt with an open/working valve and the other half receiving the valve with the placebo setting. For ease, we will refer to these groups as the shunt-treated and placebo groups, respectively. After three months, those in the shunt-treated group walked faster than those in the placebo group. About 8 out of 10 people in the shunt-treated group showed clinically meaningful improvements in walking speed. Balance was also significantly improved, while scores for cognition and bladder function (continence) were unchanged.

There were some other indications of potential improvements in functional independence, cognition, and quality of life, but these were not statistically controlled for multiple comparisons.

So, from the results, we can say that while shunt surgery helped people walk better and steadied their balance, it didn’t make a big difference in memory or bladder control.

Scans showed that the shunt surgery worked by draining excess fluid from the brain, reducing ventricle volume where fluid had built up. Like any surgery, shunt procedures have some risks. There were a few more complications in the shunt-treated group, but the doctors managed them. People in the shunt-treated group actually fell less often than those who didn’t.

Some people in the shunt-treated group had bleeding around the brain, a known risk of the procedure, but this was still relatively uncommon. Headaches, especially when changing positions, were also more common in the shunt-treated group.

Partway through the study, researchers saw such a clear benefit from shunt surgery that they decided to stop enrolling new patients. The remaining participants are being followed for a full year to gather more information about long-term outcomes. Data through 12 months will include neuropsychological, imaging, and biomarker analyses, which may provide insights into the timing, extent, and mechanisms of symptom recovery.

Overall, the PENS trial data at three months clearly support the potential benefits of shunt surgery in eligible NPH patients.