Evolution of neurodegeneration in patients with normal pressure hydrocephalus: a monocentric follow up study.

BACKGROUND: The aim of this study was to examine in patients with idiopathic and neurodegenerative normal pressure hydrocephalus (NPH) if motor and cognitive performance as well as changes in biomarkers in cerebrospinal fluid (CSF) evolve differently. METHODS: 41 patients with a typical clinical and MR-/CT-morphological presentation of NPH divided into an Alzheimer-negative (AD-, n = 25) and an Alzheimer-positive (AD+, n = 16) group according to neurodegenerative biomarkers (S100 protein, neuron-specific enolase, ß-amyloid 1-42, Tau protein, phospho-Tau, protein-level and CSF pressure) in CSF. Follow-up of cognitive and gait functions before and after a spinal tap of 40-50 ml CSF of up to 49 months. Clinical, motor, neuropsychological and CSF biomarkers were analyzed using a repeated multifactorial analysis of variance (ANOVA) with post-hoc testing. RESULTS: Gait and neuropsychological performance and CSF biomarkers evolved differently between the AD- and AD+ patients. In particular, the AD+ patients benefited from the spinal tap regarding short-term memory. In contrast, gait parameters worsened over time in the AD+ patients, although they showed a relevant improvement after the first tap. CONCLUSIONS: The results substantiate the recently reported association between a tap-responsive NPH and CSF changes of Alzheimer disease. Furthermore, they suggest that the AD changes in CSF manifest in an age-related fashion in AD- patients presenting with NPH.

Deficient visuomotor hand coordination in normal pressure hydrocephalus.

OBJECTIVE: To investigate if visuomotor coordination of hand movements is impaired in patients with normal pressure hydrocephalus (NPH) identified by dedicated testing procedures. METHODS: Forty-seven patients admitted for diagnostic workup for suspected NPH were studied prospectively with MRI, testing of cognitive and motor functions, lumbar puncture, and visuomotor coordination of hand movements using the PABLOR-device before and after a spinal tap of 40-50 ml CSF. Statistical analyses were carried out with repeated measures ANOVA and non-parametric correlation analyses. RESULTS: Fourteen patients were found to suffer from ideopathic NPH. They were severely impaired in visuomotor control of intermittent arm movements in comparison to patients who were found not to be affected by NPH (n = 18). In the patients with NPH the deficient arm control was improved after the spinal tap in proportion to the improvement of gait. There was no improvement of cognitive and motor functions in the patients not affected by NPH, while the patients with possible NPH (n = 15) showed intermediate deficit and improvement patterns. INTERPRETATION: Our data underline the importance of a multiparametric assessment of NPH and provide evidence for a motor control deficit in idiopathic NPH involving leg and arm movements. It is suggested that this motor control deficit resulted from an affection of the output tracts from the supplementary motor area in the periventricular vicinity.

Normal Pressure Hydrocephalus Associated with Alzheimer's Disease.

OBJECTIVE: The aim was to investigate whether neurodegenerative biomarkers in cerebrospinal fluid (CSF) differentiate patients with suspected normal pressure hydrocephalus (NPH) who respond to CSF drainage from patients who do not respond. METHODS: Data from 62 consecutive patients who presented with magnetic resonance imaging changes indicative of NPH were studied with regard to cognitive and gait functions before and after drainage of 40-50ml of CSF. Additionally, S100 protein, neuron-specific enolase, ß-amyloid protein, tau protein and phospho-tau were determined in CSF. Statistical analyses were carried out with ANOVA and multiple linear regression. RESULTS: Patients with CSF constellations typical for Alzheimer's disease (n = 28) improved significantly in cognitive and gait-related functions after CSF drainage. In contrast, those patients without a CSF constellation typical for Alzheimer's disease (n = 34) did not improve in cognitive and gait-related functions after CSF drainage. In addition, positive CSF biomarkers for Alzheimer's disease predicted these improvements. INTERPRETATION: Our data suggest an association between Alzheimer's disease and NPH changes, supporting the recently suggested dichotomy of a neurodegenerative NPH and a true idiopathic NPH, with the latter appearing to be rare. ANN NEUROL 2020;88:703-711.