Novel Parameters for the Prediction of Ventriculoperitoneal Shunting Efficacy in Patients With iNPH

Overview

INPH is a chronic, progressive disease characterised by enlarged ventricles in the absence of elevated intracranial pressure. Patients often present with the Hakim triad comprising gait disturbance, dementia and urinary incontinence. Treatment consists of ventriculoperitoneal (VP) shunting reducing the cerebrospinal fluid (CSF) volume in the central nervous system (CNS); a generally safe and well tolerated procedure nevertheless invasive in nature and associated with surgical risk. The currently used diagnostic algorithms to predict surgery outcome by testing patients before and after a diagnostic spinal tap temporarily reducing the CSF volume in the CNS are of wide variability and limited validity. Developing measures to accurately diagnose and select patients for intervention is thus of great importance. The objective of this study is to define and validate a diagnostic algorithm for the selection of patients with symptoms compatible with iNPH for shunt surgery.

Idiopathic normal pressure hydrocephalus (iNPH) is an important differential diagnosis of dementia in the elderly patients. It is characterised by an enlargement of the ventricular system and can lead to cognitive deficits, gait disturbance and incontinence. Treatment consists of a ventriculoperitoneal shunt. A major challenge is the identification of patients who suffer from iNPH and who will benefit from shunt surgery. Typically, cerebrospinal fluid (CSF) is withdrawn by a spinal tap, and walking speed and steps per distance are measured before and thereafter. In patients who benefit from the test tap the diagnosis iNPH is made and the indication for shunt surgery is ascertained. The diagnostic procedure is not standardised. Little is known about the examinations and time-points suited best to predict surgery outcome. Thus, patients may undergo surgery who do not benefit, and patients who would benefit may be missed. This study aims at defining a diagnostic algorithm to improve the prediction of surgery outcome in patients supposed to suffer from iNPH. In 25 serial patients, motor function will be analysed in detail by functional tests and a treadmill-based analysis before and after the test tap at different time-points. In addition, neuropsychological tests and MRI investigations (DWI and pw) will be done, and patients will fill-out a micturition diary. Patients who do not respond to the test tap will be offered a lumbar drainage for continuous CSF release as diagnostic escalation with repeated tests thereafter. Patients who finally undergo shunt surgery will be re-assessed to identify those who responded to surgery. Thereby, post-hoc analyses will identify those parameter(s) that had the best predictive value for surgery outcome. To confirm the parameters derived from such exploratory analyses, these parameters will be validated in another series of 25 patients. The results of this study have the potential to improve the clinical routine and to provide a strategic advantage for the University Hospital Zurich.