Cerebrospinal fluid shunting for idiopathic normal pressure hydrocephalus: a comprehensive meta‑analysis with trial sequential analysis of randomized controlled trials.

backgroundIdiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurocognitive disorder causing severe functional decline in the elderly. Cerebrospinal fluid (CSF) shunting aims to relieve ventricular stress and restore perfusion; however, high-quality placebo-controlled evidence has historically been limited.

methodsThis PRISMA-compliant systematic review and meta-analysis (PROSPERO: CRD420261372290) evaluated adults aged 60 years or older with iNPH. We included randomized controlled trials (RCTs) comparing immediate active CSF shunting against placebo or no shunting. The primary outcome was the change in gait speed using standardized timed assessments. Data were pooled using a restricted maximum-likelihood random-effects model, supplemented by Trial Sequential Analysis (TSA) and GRADE assessment to control for random error.

resultsFour RCTs comprising 224 patients were included. Shunting significantly improved the primary outcome of gait velocity (SMD 0.73, 95% CI 0.45 to 1.01; P < 0.0001). Significant secondary improvements were observed in qualitative gait function (SMD 0.81, P = 0.007), functional independence (OR 3.92, P < 0.0001), continuous modified Rankin Scale reduction (MD - 0.73, P < 0.0001), Mini-Mental State Examination or Montreal Cognitive Assessment scores (SMD 0.37, P = 0.009), and Symbol Digit Test performance (SMD 0.47, P = 0.002). TSA confirmed conclusive evidence for functional disability reduction before reaching the required information size. Shunting increased the incidence of positional headaches (OR 5.62, 95% CI 1.16 to 27.18). The pooled estimate for subdural hematoma was imprecise and did not reach statistical significance (OR 4.07, 95% CI 0.62 to 26.94) and should not be interpreted as evidence of an absence of risk given the small number of events. No significant difference was observed for ischemic stroke (OR 0.64, 95% CI 0.18 to 2.33), also based on few events.

conclusionCerebrospinal fluid shunting appears to provide meaningful clinical benefit in patients with idiopathic normal pressure hydrocephalus, particularly through improvement in gait velocity and functional independence. However, the evidence suggests a more limited or uncertain effect on cognitive and urinary symptoms. Importantly, the available randomized evidence is too imprecise to rule out an increase in major complications such as surgically treated subdural hematoma; positional headaches were significantly more frequent with shunting, and the largest included trial independently reported a significant excess of subdural bleeding. These safety signals warrant careful discussion with patients considering shunt surgery. These findings support shunting as an effective therapeutic option for appropriately selected patients with iNPH, while emphasizing the need for careful patient selection, standardized outcome assessment, and further high-quality, large-scale trials with longer follow-up.