Cerebrospinal fluid and venous biomarkers of shunt‐responsive idiopathic normal pressure hydrocephalus: a systematic review and meta‐analysis

Acta Neurochirurgica (2022) 164:1719–1746

Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease and dementia subtype involving disturbed cerebrospinal fluid (CSF) homeostasis. Patients with iNPH may improve clinically following CSF diversion through shunt surgery, but it remains a challenge to predict which patients respond to shunting. It has been proposed that CSF and blood biomarkers may be used to predict shunt response in iNPH.

Objective To conduct a systematic review and meta-analysis to identify which CSF and venous biomarkers predict shunt- responsive iNPH most accurately.

Methods Original studies that investigate the use of CSF and venous biomarkers to predict shunt response were searched using the following databases: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR. Included studies were assessed using the ROBINS-I tool, and eligible studies were evaluated utilising univariate meta-analyses.

Results The study included 13 studies; seven addressed lumbar CSF levels of amyloid-β 1–42, nine studies CSF levels of Total-Tau, six studies CSF levels of Phosphorylated-Tau, and seven studies miscellaneous biomarkers, proteomics, and genotyping. A meta-analysis of six eligible studies conducted for amyloid-β 1–42, Total-Tau, and Phosphorylated-Tau demonstrated significantly increased lumbar CSF Phosphorylated-Tau (− 0.55 SMD, p = 0.04) and Total-Tau (− 0.50 SMD, p = 0.02) in shunt-non-responsive iNPH, though no differences were seen between shunt responders and non-responders for amyloid-β 1–42 (− 0.26 SMD, p = 0.55) or the other included biomarkers.

Conclusion This meta-analysis found that lumbar CSF levels of Phosphorylated-Tau and Total-Tau are significantly increased in shunt non-responsive iNPH compared to shunt-responsive iNPH. The other biomarkers, including amyloid-β 1–42, did not significantly differentiate shunt-responsive from shunt-non-responsive iNPH. More studies on the Tau proteins examining sensitivity and specificity at different cut-off levels are needed for a robust analysis of the diagnostic efficiency of the Tau proteins.

Feasibility of radiological markers in idiopathic normal pressure hydrocephalus

Feasibility of radiological markers in idiopathic normal pressure hydrocephalus

Acta Neurochir (2015) 157:1709–1719

Various radiological markers have been proposed for diagnostics in idiopathic normal pressure hydrocephalus (iNPH).We examined the usefulness of radiological markers in the diagnostics and prediction of shunt response in iNPH.

Method In this retrospective cohort study, we evaluated brain CTor MRI scans of 390 patients with suspected iNPH. Based on a 24-h intraventricular pressure monitoring session, patients were classified into a non-NPH (n=161) or probable iNPH (n=229) group. Volumes of cerebrospinal fluid compartments (lateral ventricles, sylvian and suprasylvian subarachnoid spaces and basal cisterns) were visually assessed. Disproportionally enlarged subarachnoid spaces, flow void, white matter changes, medial temporal lobe atrophy and focally dilated sulci were evaluated. Moreover, we measured quantitative markers: Evans’ index (EI), the modified cella media index, mean width of the temporal horns and callosal angle.

Results iNPH was more likely in patients with severe volumetric disproportion between the suprasylvian and sylvian subarachnoid spaces than in those without disproportion (OR 7.5, CI 95 % 4.0–14.1, P<0.0001). Mild disproportion (OR 2.6, CI 95 % 1.4–4.6, P=0.001) and narrow temporal horns (OR per 1mm0.91, CI 95%0.84–0.98, P=0.014)were also associated with an iNPH diagnosis. Other radiological markers had little association with the iNPH diagnosis in the final combined multivariate model. Interestingly, EI was higher in non-NPH than iNPH patients (0.40 vs. 0.38, P= 0.039). Preoperative radiological markers were not associated with shunt response.

Conclusions Visually evaluated disproportion was the most useful radiological marker in iNPH diagnostics. Narrower temporal horns also supported an iNPH diagnosis, possibly since atrophy was more pronounced in the non-NPH than iNPH group.

Diagnostic Intracranial Pressure Monitoring and Surgical Management in Idiopathic Normal Pressure Hydrocephalus: A 6-Year Review of 214 Patients

Neurosurgery 66:80-91, 2010 DOI: 10.1227/01.NEU.0000363408.69856.B8

OBJECTIVE: To review our experience of managing idiopathic normal pressure hydrocephalus (iNPH) during the 6-year period from 2002 to 2007, when intracranial pressure (ICP) monitoring was part of the diagnostic workup.

METHODS: The review includes all iNPH patients undergoing diagnostic ICP monitoring during the years 2002 to 2007. Clinical grading was done prospectively using a normal pressure hydrocephalus (NPH) grading scale (scores from 3 to 15). The selection of patients for surgery was based on clinical symptoms, enlarged cerebral ventricles, and findings on ICP monitoring. The median follow-up time was 2 years (range, 0.3-6 years). Both static ICP and pulsatile ICP were analyzed.

RESULTS: A total of 214 patients underwent the diagnostic workup, of whom 131 went on to surgery. Although 1 patient died shortly after treatment, 103 of the 130 patients (79%) improved clinically. This improvement lasted throughout the observation period. The static ICP observed during ICP monitoring was a poor predictor of the response to surgery. In contrast, among 109 of 130 patients with increased ICP pulsatility (ie, ICP wave amplitude >4 mm Hg on average and >5 mm Hg in >10% of recording time), 101 (93%) were responders (ie, increase in the NPH score of >2). Correspondingly, only 2 of 21 (10%) without increased ICP pulsatility were responders. Superficial wound infection was the only complication of ICP monitoring and occurred in 4 (2%) patients.

CONCLUSION: Surgical results in iNPH were good with almost 80% of patients improving after treatment. The data indicate that improvement after surgery can be anticipated in 9 of 10 iNPH patients with abnormal ICP pulsatility, but in only 1 of 10 with normal ICP pulsatility. Diagnostic ICP monitoring had a low complication rate