Postoperative changes in ventricular cerebrospinal fluid biomarkers with correlation to clinical outcome in...

BackgroundVentricular cerebrospinal fluid (CSF) was analysed peri- and postoperatively to elucidate the pathophysiology of Idiopathic normal pressure hydrocephalus (iNPH).ObjectiveTo capture the dynamics of biomarkers and their relation to clinical symptoms.MethodsIn 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, Aβ₄₀, sAβPPα, sAβPPβ, GAP43, Alzheimer's disease biomarkers Aβ₄₂, Aβ_42/40, total tau (T-tau), phosphorylated tau (P-tau), and neurogranin.ResultsConcentrations increased postoperatively for Aβ₄₀ (134%), Aβ₄₂ (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 Aβ₄₀ (R_s 0.27 (0.05-0.46)), Aβ₄₂ (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 Aβ₄₀ (R_s 0.36 (0.05-0.60)) was associated with improvement in urinary continence (p 0.01-0.05).ConclusionsCSF 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.