Abstract

An imbalance of production and reabsorption of cerebrospinal fluid might be an aetiological factor in normal pressure hydrocephalus (NPH) and pseudotumor cerebri (PTC), but so far several studies have not been conclusive. As the dynamic of the cerebrospinal fluid (CSF) is partly regulated by the water channels (aquaporins) AQP1 and AQP4, their detection and quantification in CSF represents a new approach in the diagnostic research of NPH and PTC which was analysed in this study. A pilot study using a specific ELISA found a significantly higher concentration of AQP4 in the CSF of patients with bacterial meningitis compared to healthy controls. We analysed the CSF concentration of AQP4 and AQP1 of 49 NPH- and 34 PTC-patients and 28 control subjects. Due to a high inter-assay variance of the AQP-ELISA, the AQP1 and AQP4 concentrations of NPH patients were corrected to z-values according to the results of the control samples. Significant differences of AQP4 concentration of NPH patients in comparison to the healthy control group could not be found (p = 0.201). The z-values of AQP1 in CSF of NPH patients was one standard deviation higher than within the control group (z = 1.2 ± 1.8 NPH vs. 0.0 ± 1.0 (control group), p < 0.01), which might be the result of a higher AQP1 expression within the ependymal cells of the plexus choroideus of NPH patients followed by a higher metabolic rate of transmembraneous channel with increased shedding into the CSF. Furthermore, this indicates that a decrease of AQP1 expression as an adaptive mechanism is missing within the group of NPH patients. The concentration of AQP4 in the CSF of PTC patients showed a tendency to lower values when compared to the control group (p = 0.077). None of the analysing methods used in this study showed a significant difference of AQP4 between PTC patients and controls. A significant role of AQP1 in the diagnosis of PTC was not expected, as current radiological and neuropathological studies have already dismissed an overproduction of cerebrospinal fluid as the main cause of PTC. Accordingly, we found no difference of AQP1 concentration of PTC patients in comparison to the control group. As expected, all neuropsychological tests yielded a significant difference between NPH patients and the control group. The NPH patients showed a significantly better improvement in MMSE and the visoconstructive function from the test before to one day after lumbar puncture (spinal tap) when compared to their control group. In all other domains the result was not significantly different. Hence, we recommend the use of the MMSE and tests for the visoconstructive function as useful addition to the gait analysis for the diagnosis of NPH.

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