European Multicenter Study on the Prediction of Outcome in Patients With Idiopathic Normal Pressure Hydrocephalus

Study background:

The selection of patients with idiopathic normal pressure hydrocephalus (INPH) for shunting remains difficult. The upcoming guidelines for the diagnosis and management of INPH state that there is no accepted standard for the clinical presentation, the results of imaging and the various tests that provide information on CSF dynamics 1. Hebb and Cusiamo could not find a single test that reliably predicts outcome after shunting in their systematic review of INPH 2. To properly evaluate the predictive value of diagnostic tests for the outcome of shunting all patients should receive a shunt irrespective of the test results. Only a few studies set up to examine the diagnostic reliability of tests of CSF dynamics fulfilled this condition. The common finding of these studies was that the predictive value of a positive test was high but the negative predictive values were disappointingly low.

In the Dutch Normal Pressure Hydrocephalus Study, containing 101 patients, the positive and negative predictive values of lumbar constant flow infusion were 92% and 34% for an Rout of 18 mmHg/ml/min and 100% and 27% for an Rout of 24 3. External lumbar CSF drainage for 4 days resulted in positive and negative predictive values of 87% and 36% 4. The predictive value of the cerebrospinal fluid tap test reported by Wikkelso et al in 1986 was 100% for a positive and 45% for a negative test 5 Another parameter of CSF dynamics is elastance that can be expressed by the pressure volume-index (PVI). In a group of 30 patients with NPH high elastance, i.e low PVI was the best predictor of a marked and rapid reduction of ventricular size after shunting 6.

One of the major issues is whether the false negative tests mostly occur in the same population. In these patients the INPH might be caused not so much by a CSF circulation disorder but by parenchymal disease. From our clinical experience we think that different patients have false negative tests, we frequently encounter cases with a positive tap test and a negative infusion test or the reverse. This is also shown in a study by Kahlon et al. who performed an infusion test and a tap test in 68 patients suspected of NPH. Both tests agreed in only 45% and they were both negative in 31% of patients 7.

An important drawback of all INPH studies so far is the rather limited number of patients and, the "mixing" of idiopathic NPH patients (primary NPH) with those of known cause (secondary NPH) such as trauma, subarachnoid hemorrhage and stroke.INPH is considered a multfactorial condition with a disturbance of CSF circulation as well as parenchymal abnormalities in a vulnerable population with much comorbidity. Because of the many outcome variables a study on the prediction of outcome needs large numbers of INPH patients. With a few exceptions, previous studies on CSF dynamics in INPH were conducted in single high quality institutions. We also have to demonstrate that the same or even better results can be obtained with international cooperation providing higher patients numbers. Therefore we intend to conduct a large European multicentre study on INPH including at least 200 patients. All these patients will receive the same shunt system and will be followed-up by a standardized protocol using primary and secondary NPH outcome measures. Because of the continuing controversy with respect to the appropriate shunt opening pressure and the many problems of over- and underdrainage after insertion of the shunt, we chose the Codman Hakim programmable valve 8.