Tms-evoked potentials: Neurophysiological biomarkers for diagnosis and prediction of response to ventriculoperitoneal shunt in normal pressure hydrocephalus

Background: Current practice for normal pressure hydrocephalus (NPH) relies upon clinical presentation, imaging and invasive clinical procedures for indication of treatment with ventriculoperitoneal shunt (VPS). We aimed to assess the utility of a TMS-evoked potential (TEP)-based evaluation, for prediction of response to VPS in NPH, as an alternative for the cerebrospinal fluid tap test (CTT). Methods: 37 “possible iNPH” patients and 16 age-matched healthy controls (HC) were included. All subjects performed Delphi (TMS-EEG and automated analysis of TEP), in response to primary motor cortex (M1) and dorsolateral prefrontal (DLPFC) stimulations. Sixteen patients underwent VPS and response was evaluated with change in modified Rankin Scale (MRS), clinical global impression of change (CGIC) regarding gait and the change on a repeated 3-meter timed up and Go (TUG) after 3 months. Results: TEP Delphi-NPH index was most successful in discrimination of iNPH responders to VPS (ROC-AUC of 0.91, p = 0.006) compared to other imaging (AUC_EI = 0.58, p = 0.58; AUC_TH = 0.65, p = 0.32; AUC_CA = 0.83, p = 0.03) and TUG tests (AUC_TUG = 0.63, p = 0.42; AUC_CTT = 0.65, p = 0.35). The TEP M1 P60 and P180 latencies were earlier in responders compared to controls (p_{M1 P60} = 0.016, p_{M1 P180} = 0.009, respectively). Also, significant correlations of TEP Delphi measures were registered in comparison to the rank CGIC and magnitude of change in TUG times. Conclusions: These initial results suggest that TEPs, may be an alternative for CTT, in prediction of response to VPS in patients suspected as iNPH, exhibiting higher efficacy with reduced patient discomfort and risks, given replication of results in a larger sample and longer follow up times.