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

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). 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. 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. 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. 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 .