Biomarker changes in suspected idiopathic normal-pressure hydrocephalus patients undergoing external lumbar drainage: a pilot study

Abstract

Aim: To examine whether changes in biomarker concentrations in patients with idiopathic normal-pressure hydrocephalus (iNPH) during 72 h of external lumbar drainage (ELD) can differentiate between responders and non-responders.

Methods: Twenty patients with clinical and neuroradiological signs of iNPH underwent ELD over a period of 72 h. During this period, changes in cerebrospinal fluid (CSF) concentrations of biomarkers (amyloid-β, total and phosphorylated tau proteins) and intracranial pressure were monitored, and the volume of drained CSF was measured. Changes in the concentrations of selected biomarkers at three time points (0, 36, and 72 h) during ELD were tested for association with changes in clinical condition.

Results: Ten patients showed significant clinical improvement after ELD, quantified as a difference of two or more points on the Mini-Mental State Examination and/or Japanese iNPH grading scale. The concentration of all tested biomarkers increased during the first 36 h. Respondents had higher Aβ 1-42 at all time points, with a significant difference seen after 72 h. They also had a significantly higher Aβ1-42/Aβ1-40 ratio at all time points.

Conclusion: A gradual increase in Aβ 1-42 concentration during three-day ELD represents a possible positive prognostic factor for the placement of permanent CSF drainage in patients with iNPH.

Figure 1

Flow diagram of patient selection. MRI – magnetic resonance imaging; iNPH – idiopathic normal-pressure hydrocephalus; MMSE – Mini-mental State Examination; JiNPHS – Japanese iNPH Scale; CSF – cerebrospinal fluid.

Figure 2

Concentrations of different biomarkers in the responder and non-responder groups: (A) amyloid Aβ1-42, (B) Aβ1-40, (C) total tau protein (t-tau), (D) phosphorylated tau protein (pT181) (expressed in pg/mL), and (E) Aβ1-42 /Aβ1-40 ratio in cerebrospinal fluid at time points: 0`– immediately after external lumbar drainage placement, after 36 hours, and after 72 hours of drainage; * significant difference.