Clinical response after cerebrospinal fluid shunting in complex versus pure idiopathic normal pressure hydrocephalus:...

Idiopathic normal pressure hydrocephalus (iNPH) frequently coexists with neurodegenerative or vascular disease, but shunt outcomes in these complex presentations remain poorly synthesized.

We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 systematic review and meta-analysis of shunt outcomes in pure iNPH and complex iNPH. Binary outcomes were global shunt response and urinary improvement. Continuous outcomes were harmonized into cognition, gait, general function, and incontinence and summarized as standardized mean change with raw-score standardization (SMCR). Prespecified primary comparative estimates used random-effects models with Hartung-Knapp confidence intervals (CIs).

Nineteen unique analytical studies were included. In direct head-to-head binary comparisons, global shunt response was directionally lower in complex iNPH but did not reach statistical significance under the prespecified random-effects Hartung-Knapp model (odds ratio [OR] 0.31, 95% CI 0.09-1.10; k = 3). Urinary improvement did not clearly differ between phenotypes (OR 0.85, 95% CI 0.58-1.25; k = 3). Within complex iNPH, continuous pre-post estimates varied by domain and were imprecise: cognition was directionally positive, gait was near null with marked heterogeneity, and incontinence showed a small positive estimate. Direct continuous complex-minus-pure comparisons did not show a consistent deficit across domains. Exploratory time meta-regression suggested a phenotype-by-time interaction for incontinence, but this signal was based on sparse follow-up support and should be considered hypothesis-generating.

Low- to very-low-certainty evidence suggests that complex iNPH is associated with greater uncertainty and possibly lower global response than pure iNPH, but lower odds of response should not be interpreted as absence of response. Counseling should be phenotype-aware and domain-specific, particularly when Alzheimer-related biomarkers, parkinsonism, vascular burden, or other neurodegenerative features coexist with suspected iNPH.