Motor network neurophysiological (TMS-EEG) markers as predictors of outcomes of ventriculoperitoneal shunt sustained for over a year in normal pressure hydrocephalus.

Abstract

Background and objectives: Current practice for normal pressure hydrocephalus (NPH) relies on clinical presentation, imaging, and various clinical procedures to determine the need for neurosurgical intervention, specifically the installation of a ventriculoperitoneal shunt (VPS). This study aimed to evaluate the utility of a TMS-evoked potential (TEP)-based assessment (Delphi-MD) for predicting sustained response (over one year) to VPS, serving as an ancillary test to the cerebrospinal fluid tap test (CTT).

Methods: Forty-one patients with possible iNPH underwent Delphi-MD evaluation of wave form adherence (WFA), a composite measure assessing how closely their TEPs resembled an ideal benchmark TEP. Of these, 18 patients received VPS treatment following a multidisciplinary team decision based on standard practice, blinded to the TEP results. Response to the intervention was evaluated over a period of more than one year using the clinical global impression of change (CGIC) scale, in addition to assessments with a 10-meter timed up and go test and the modified Rankin scale.

Results: Responders had higher M1L WFA values at baseline (prior to VPS) than non-responders (median 0.51 [95% CI 0.36-0.76], median 0.14 [95% CI -0.02-0.38], respectively p = 0.012). M1L WFA was successful in distinguishing responders (11/18) from non-responders (7/18) with an ROC-AUC of 0.935 [bootstrap 95% CI 0.792-1.00], p < 0.0001. M1L WFA cutoff was established with LOOCV and produced 90.9% sensitivity, 85.7% specificity and 88.9% accuracy. In contrast the CTT result was unsuccessful in predicting shunt responsiveness.

Conclusion: This study indicates that higher M1L WFA obtained through Delphi-MD (TMS-EEG), signifies better preservation and functional integrity of the motor network in patients with probable iNPH that had a sustained response to VPS than those that did not. Given replication of results in future independent cohorts, Delphi-MD shows promise as an objective, accurate, and accessible ancillary screening tool for iNPH candidates, prior to referral for VPS treatment.

Trial registration: Registration number: MOH_2021-12-08_010449. Registration date: 11.09.2021. https://clinicaltrial.health.gov.il/clinicaltrials/?sort=experimentapproveddate_tdt+desc&page=1&searchQuery=MOH_2021-12-08_010449 .