Diagnostic value of CSF biomarker profile in idiopathic normal pressure hydrocephalus; leucine-rich α-2-glycoprotein is a potential biological marker

Abstract

Cerebrospinal fluid (CSF) shunting can improve symptoms of elderly patients idiopathic normal pressure hydrocephalus (iNPH). However, adjunctive means for confirming the diagnosis remain unavailable. We have previously reported specific increase of leucine-rich alpha-2-glycoprotein (LRG) in iNPH CSF, and present study investigates its potential clinical applications. We performed CSF tap test (TT) on 90 patients and shunting in 52 patients (mean age 73.5 years), evaluating symptom improvement and higher cerebral functions-MMSE and Frontal Assessment Battery (FAB) before and twelve months after shunting. LRG and tau protein concentrations in TT CSF were simultaneously measured using ELIZA. Then we compared the predictive value of these concentrations with TT results regarding successful shunting outcomes. Positive combinations of TT and LRG concentrations of 67 ng/mL or higher, gave 81.6% sensitivity and 78.6% specificity. Therefore we used LRG (67 ng/mL) and tau (200 pg/mL) cutoff values, LRG ≥ 67 ng/ml and tau < 200 pg/ml, 31 of 34 patients (91.2%) had a positive TT and all operated 22 patients were shunt responders. Dementia MMSE and FAB scores in them increased from a baseline of 22.05 to 25.65 and 11.38 to 13.08 respectively. A combination of positive TT and biomarkers quantification such as LRG and tau protein, can reliably predict shunting outcome in iNPH patients.