Utility of cortical tissue analysis in normal pressure hydrocephalus

Author:

Greenberg Ana B W12,Mekbib Kedous Y12,Mehta Neel H1,Kiziltug Emre2,Duy Phan Q2,Smith Hannah R1,Junkkari Antti3,Leinonen Ville4,Hyman Bradley T5,Chan Diane5,Curry Jr William T1,Arnold Steven E5,Barker II Frederick G1,Frosch Matthew P6,Kahle Kristopher T137

Affiliation:

1. Department of Neurosurgery, Massachusetts General Hospital , Boston, MA 02114 , United States

2. Department of Neurosurgery, Yale School of Medicine , New Haven, CT 06510 , United States

3. Broad Institute of MIT and Harvard , Cambridge, MA 02142 , United States

4. Department of Neurosurgery, Kuopio University Hospital , Kuopio 70211 , Finland

5. Department of Neurology, Massachusetts General Hospital , Boston, MA 02114 , United States

6. Department of Pathology, Massachusetts General Hospital , Boston, MA 02114 , United States

7. Harvard Center for Hydrocephalus and Neurodevelopmental Disorders, Massachusetts General Hospital , Boston, MA 02114 , United States

Abstract

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.

Funder

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Cellular and Molecular Neuroscience,Cognitive Neuroscience

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