A clinical and biochemical analysis in the differential diagnosis of idiopathic normal pressure hydrocephalus

Abstract

Introduction: Idiopathic normal pressure hydrocephalus (iNPH) can be misdiagnosed with other neurodegenerative diseases, especially in the early disease stages. Considering the opportunity of the shunt surgery, iNPH should be diagnosed with accuracy. Here, we evaluate the utility of CSF biomarkers and their relationship with clinical features in the diagnosis of iNPH.

Methods: We performed a multivariate analysis of the CSF levels of Aβ42, t-tau, and p-tau collected from four groups of patients: 14 iNPH, 14 progressive supranuclear palsy (PSP), 14 Alzheimer's disease (AD), 14 controls (CTL). Diagnostic accuracy of biomarkers was determined by the receiver operating characteristic curve analysis. Statistical correlation was calculated between each CSF biomarker and single clinical items of iNPH.

Results: Aβ42 levels in iNPH were lower than controls, although not as low as in AD. Likewise, CSF t-tau and p-tau were lower in iNPH than in controls. Of interest, t-tau and p-tau were higher in AD than in controls and hence both t-tau and p-tau were significantly lower in iNPH than in AD. No differences were found between iNPH and PSP. CSF biomarkers levels did not correlate to clinical features of iNPH, whereas two significant correlations emerged within clinical parameters: cognitive impairment was related to gait difficulties, while ventricular enlargement correlated with continence disturbances.

Conclusion: Measurement of CSF biomarker levels may be helpful in the differential diagnosis between iNPH and AD but not between iNPH and PSP. Both Aβ42 and tau levels appear unrelated to main clinical features of iNPH.

Keywords: CSF biomarkers; idiopathic normal pressure hydrocephalus; progressive supranuclear palsy.

Figure 1

Demographical and biochemical profiles of groups. (A) No statistical differences exist regarding the distribution of age and gender among the groups. Aβ42/p-tau ratio was calculated considering ratio values <6.43 as AD, ≥6.43 as non-AD (14). Aβ42/p-tau ratio of AD group is significantly different (p < 0.01) from other groups. (B) Statistical differences of biomarkers concentrations among the groups. Asterisks indicate p < 0.05.