Utility of cortical tissue analysis in normal pressure hydrocephalus

Abstract

Clinical improvement following neurosurgical cerebrospinal fluid shunting for presumed idiopathic normal pressure hydrocephalus is variable. Idiopathic normal pressure hydrocephalus patients may have undetected Alzheimer's disease-related cortical pathology that confounds diagnosis and clinical outcomes. In this study, we sought to determine the utility of cortical tissue immuno-analysis in predicting shunting outcomes in idiopathic normal pressure hydrocephalus patients. We performed a pooled analysis using a systematic review as well as analysis of a new, original patient cohort. Of the 2707 screened studies, 3 studies with a total of 229 idiopathic normal pressure hydrocephalus patients were selected for inclusion in this meta-analysis alongside our original cohort. Pooled statistics of shunting outcomes for the 229 idiopathic normal pressure hydrocephalus patients and our new cohort of 36 idiopathic normal pressure hydrocephalus patients revealed that patients with Aβ + pathology were significantly more likely to exhibit shunt nonresponsiveness than patients with negative pathology. Idiopathic normal pressure hydrocephalus patients with Alzheimer's disease -related cortical pathology may be at a higher risk of treatment facing unfavorable outcomes following cerebrospinal fluid shunting. Thus, cortical tissue analysis from living patients may be a useful diagnostic and prognostic adjunct for patients with presumed idiopathic normal pressure hydrocephalus and potentially other neurodegenerative conditions affecting the cerebral cortex.

Keywords: Amyloid Beta; Biomarker; Dementia; Shunt Outcome; Tau.

Fig. 1

Graphical study overview. Abstract workflow depicting our original cohort study and meta-analysis. Figure created with BioRender.com. Abbreviations: Aβ = amyloid-beta, HPτ = hyperphosphorylated tau, iNPH = idiopathic normal pressure hydrocephalus.

Fig. 2

Groups for statistical comparison organized by tissue neuropathology. Abstract graphic depicting the tissue neuropathology groupings for each statistical comparison. Figure created with BioRender.com. Abbreviations: Aβ = amyloid-beta, HPτ = hyperphosphorylated tau.

Fig. 3

Distribution of the pooled study cohort (A, left; B) and original cohort (A, right; C). (A, left) preliminary synthesis of pooled study cohort by biopsy pathology and shunt responsiveness; (A, right) patient numbers for original cohort by biopsy pathology and shunt responsiveness; (B) distribution of pooled study cohort by biopsy pathology and shunt responsiveness; (C) distribution of original cohort by biopsy pathology and shunt responsiveness. Abbreviations: SR = shunt responsive, NR = shunt nonresponsive, Aβ = amyloid-beta, HPτ = hyperphosphorylated tau. Any + group = combination of pathology groups with Aβ + and/or HPτ+. Aβ + group = combination of pathology groups with Aβ + regardless of presence of HPτ.

Fig. 4

ORs and M-H tests. Forest plots for each biopsy group comparison, positive pathology versus negative pathology groups. ORs are calculated for the non-event (for the odds of a shunt nonresponsive outcome). Abbreviations and notes: Aβ = amyloid-beta, HPτ = hyperphosphorylated tau, M-H = Mantel Haenszel; events = shunt responsive outcomes, non-events = shunt nonresponsive outcomes. Any + group = combination of pathology groups with Aβ + and/or HPτ+. Aβ + group = combination of pathology groups with Aβ + regardless of presence of HPτ.