Reference: N Engl J Med. 2025 Sep 16 early online
Practice Point: Ventriculoperitoneal shunts likely offer both appreciable benefits and risk for patients with symptomatic NPH.
EBM Pearl: Primary outcomes are sometimes chosen by authors because they are the most important outcome and sometimes chosen because they are expedient.
NPH can cause memory loss, falling, and incontinence in older people. A standard treatment for years has been the placement of a ventriculoperitoneal shunt. Because it’s difficult to ethically perform a double-blind placebo-controlled trial of brain surgery, it has been difficult to ascertain exactly what is the benefit of shunting cerebrospinal fluid into the abdominal cavity. This month, researchers from Johns Hopkins reported on a method to do just that with a clever use of technology for blinding that might be a model for future surgical interventions.
They enrolled ninety-nine patients with moderate symptoms of idiopathic NPH who all underwent shunt placement. Newer shunts, now standard for this indication, can be open and closed through noninvasive adjustments. In this trial, half the patients were randomized to have their shunts effectively closed after placement and half had their shunts set to properly drain. Investigators compared baseline and 3-month values for a mix of clinical and disease-oriented outcomes, including the chosen primary outcome for this study, performance on a 10-meter walk test. Three months postoperatively, patients with a functional shunt walked faster, had fewer falls, and had better overall quality of life. Unfortunately, they didn’t end up with improved cognitive or bladder function, and they also had significantly more subdural hematomas and positional headaches. The authors state they will publish again once 12-month follow-up is complete.
Many academic papers don’t just state facts—they tell a story. The difficulty for authors is balancing the need to tell a story while sticking to the evidence. The choice of a primary outcome is part of telling a story. To that end, a paper on research methodology by Vetter and Mascha recommends restricting the number of primary and secondary outcomes for focus and clarity of communication. Yet, this NPH paper has a total of 4 secondary outcomes, 7 tertiary outcomes, and 2 radiologic outcomes! Why would the authors choose to report an artificial measure such as gait speed as their primary outcome over more patient-centered symptoms like cognitive or bladder function? One reason may be that although gait speed is a surrogate marker, it also has a history of predicting more important outcomes such as falling, balance, and quality of life in research studies. In addition, gait speed is easy to measure, and there is evidence that improvements in symptoms such as mental status may take longer to occur after shunt placement. Perhaps most importantly, gait speed, even if it probably isn’t as important as remembering the name of a grandchild, is an easily understood and precisely measured hard outcome. We’ll go out on a limb and hypothesize that this was a consideration when these authors designed their study with this as the primary outcome. Separate from the primary outcome, the 14 reported outcomes give us a very nice list of the relative likelihood of benefits and adverse effects of the shunt flow rate, distinct from outcomes associated with the surgical procedure itself. These secondary and tertiary outcomes serve their own purpose and may be just as helpful as the primary one. Overall, this study is an important step forward to help clinicians counsel patients on what outcomes (good and bad) are likely after shunt placement.
For more information, see the topic Normal-Pressure Hydrocephalus (NPH) in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Dan Randall, MD, MPH, FACP, Senior Deputy Editor at DynaMed. Edited by Alan Ehrlich, MD, FAAFP, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Katharine DeGeorge, MD, MS, Senior Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia; Claire Symanski, PhD, Medical Editor and Team Lead for ENT at DynaMed; McKenzie Ferguson, PharmD, BCPS, Senior Clinical Writer at DynaMed; Rich Lamkin, MPH, MPAS, PA-C, Clinical Writer at DynaMed; Matthew Lavoie, BA, Senior Medical Copyeditor at DynaMed; Hannah Ekeh, MA, Senior Associate Editor II at DynaMed; and Jennifer Wallace, BA, Senior Associate Editor at DynaMed.