Altered glymphatic system in idiopathic normal pressure hydrocephalus

Objective: To assess the glymphatic activity in patients with idiopathic normal pressure hydrocephalus (NPH) using the Diffusion Tensor Image-Analysis aLong the Perivascular Space (DTI-ALPS) method, and determine the feasibility of non-invasive MRI for the evaluation of the glymphatic function. Methods: Between April 2017 and March 2019, 16 patients diagnosed with NPH and 16 ageand sex-matched controls were included. On 3T DTI-MRI, the diffusivities along x-, y-, and z-axes were measured, and the ALPS-index - a ratio that accentuated water diffusion along the perivascular space - was calculated by two independent readers. The inter-observer agreement was tested using the interclass correlation coefficient. The differences in the diffusivities and the ALPS-index between the NPH and control groups were compared using the Mann-Whitney test. The values were also compared according to the treatment response to the cerebrospinal fluid drainage and correlated with the callosal angle using a correlation coefficient. Results: The inter-observer agreements were excellent for the diffusivities and the ALPS-index. The diffusivity along the x-axis in the projection fibers area and the ALPS-index were significantly lower in patients with NPH (median, 0.556/1.181) than in the controls (0.610/1.540), respectively (P = 0.032/< 0.0001). The ALPS-index was significantly lower in the NPH group who did not show treatment response than those who showed symptomatic relief (0.987/1.329; P < 0.0001). The ALPS-index showed a significant positive correlation with the callosal angle (r = 0.82, P = 0.0001). Conclusions: The DTI-ALPS method can be a useful imaging tool for identifying glymphatic dysfunction and for individually quantifying glymphatic activity in patients with NPH.

Automated summary

The study assessed glymphatic activity in patients with idiopathic normal pressure hydrocephalus using DTI-ALPS method, which proved to be a useful tool for identifying glymphatic dysfunction and quantifying activity in individual patients.