EXPRESS: Cerebral hemodynamic reserve and the prediction of shunt-responsive reversibility in idiopathic normal-pressure hydrocephalus

The placebo-controlled PENS trial showed that shunting improves gait but not cognition or continence in idiopathic normal-pressure hydrocephalus (iNPH). This selective response highlights an unresolved problem: even among patients who respond to temporary cerebrospinal-fluid (CSF) drainage, we cannot predict which deficits will reverse after shunting. Static structural and perfusion markers, including white-matter hyperintensity load, cerebral small-vessel-disease burden, and baseline cerebral blood flow, do not predict shunt response. In contrast, impaired cerebrovascular reactivity is associated with a favorable response, yet cerebral autoregulation has not been measured before and after CSF diversion. I propose that reversibility in iNPH reflects recoverable hemodynamic reserve, and that this hypothesis can be tested within the existing diagnostic pathway.