Postoperative changes in ventricular cerebrospinal fluid biomarkers with correlation to clinical outcome in idiopathic normal pressure hydrocephalus

Background Ventricular cerebrospinal fluid (CSF) was analysed peri- and postoperatively to elucidate the pathophysiology of Idiopathic normal pressure hydrocephalus (iNPH). Objective To capture the dynamics of biomarkers and their relation to clinical symptoms. Methods In 113 consecutively diagnosed patients, the Hellström iNPH scale was used to quantify symptom burden pre- and postoperatively. CSF was collected at shunt insertion and postoperatively by shunt reservoir puncture, and analyzed for concentrations of GFAP, YKL40, MCP-1, NfL, Aβ 40 , sAβPPα, sAβPPβ, GAP43, Alzheimer's disease biomarkers Aβ 42 , Aβ 42/40 , total tau (T-tau), phosphorylated tau (P-tau), and neurogranin. Results Concentrations increased postoperatively for Aβ 40 (134%), Aβ 42 (106%), sAβPPα (112%), sAβPPβ (83%), NfL (128%), YKL40 (86%), GAP43 (124%), and MCP-1 (5%) (p < 0.001, MCP-1 (p = 0.03)), while mean concentration reductions were seen in T-tau (32%), GFAP (31%), neurogranin (49%), and Aβ 42/40 (10%) (p < 0.001). A higher perioperative concentration of AβPPβ correlated with less pronounced gait disturbance (R p 0.20 (0.01–0.38) (95% CI)), whereas higher levels of NfL (−0.23 (−0.41–(−)0.04) and MCP-1 (−0.21 (−0.37–(−)0.01)) correlated with impaired cognition. Higher MCP-1 correlated with a lower balance domain score (−0.20 (−0.37–(−)0.01)). Postoperative increases in levels of Aβ 40 (R s 0.27 (0.05–0.46)), Aβ 42 (R s 0.24 (0.02–0.44)) and YKL40 (R s 0.22 (−0.00–0.43)) correlated with gait improvement, and a postoperative increase in Aβ 40 (R s 0.36 (0.05–0.60)) was associated with improvement in urinary continence (p 0.01–0.05). Conclusions CSF biomarker concentrations change after shunt insertion. These changes, seen as increased concentrations for some biomarkers and decreased concentrations for others, are associated with improvement in core clinical symptoms and may illustrate reversibility of pathophysiological mechanisms in iNPH.