Novel Parameters for the Prediction of Ventriculoperitoneal Shunting Efficacy in Patients With iNPH
Novel Parameters for the Prediction of Ventriculoperitoneal Shunting Efficacy in Patients With iNPH
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 (CSF) is withdrawn by a spinal tap, and walking speed and steps per distance are measured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.
Inclusion Criteria:

 -  Informed consent.

 -  Age 50 years or above

 -  Impaired walking function for at least 3 months, onset at/ after 40 years of age.

 -  MRI or CT with enlarged ventricular system (Evans' index ≥0.30) without evidence of
 moderate or severe cortical atrophy.

 -  Eligible for shunt surgery.

 -  Eligible for analysis of gait, neuropsychological and urological function.

 -  Subjects must be able to understand the patient information sheet and comply with the
 requirements of the protocol.

 Exclusion Criteria:

 -  Previous intracranial disorder or surgery.

 -  Contraindications to surgery or MRI

 -  Contraindications to the testing of gait, bladder or neuropsychological function.

 -  Presence of concomitant disease which might reasonably account for the clinical
 symptoms or radiological findings.

 -  Worsening of walking function secondary to any other condition occurring during the
 study.