Impaired glymphatic function in autoimmune glial fibrillary acidic protein astrocytopathy: a prospective analysis

To evaluate the glymphatic dysfunction and its association with disease severity in autoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A) patients, and to determine its clinical predictors.

A total of 20 A-GFAP-A patients and 20 healthy controls (HC) were included. All participants underwent magnetic resonance imaging, and glymphatic function was assessed using the diffusion tensor imaging along the perivascular space (DTI-ALPS) index. Modified Rankin Scale (mRS) scores were recorded at baseline and 4 weeks post-immunotherapy. Multiple linear regression analysis was conducted to identify independent predictors of short-term prognosis.

The baseline DTI-ALPS index was significantly lower in A-GFAP-A patients compared to HC (mean ± SD: 1.50 ± 0.06 vs. 1.62 ± 0.04 [CI -0.16, -0.08], p = 0.003), after adjusting for confounding factors. Four weeks after immunotherapy, the DTI-ALPS index significantly increased (mean ± SD: 1.52 ± 0.14 vs. 1.59 ± 0.17 [CI 0.01, 0.14], p = 0.037). A significant negative correlation was observed between the residuals of the baseline DTI-ALPS index and the baseline mRS scores (r = -0.50 [CI -0.77, -0.07], p = 0.025). The baseline DTI-ALPS index was identified as an independent predictor of short-term prognosis (coefficient = -3.43 [CI -6.68, -0.04], p = 0.048).

This study indicates that A-GFAP-A patients exhibit significant glymphatic dysfunction, as detected by the DTI-ALPS index, which is related to the severity of the disease. The DTI-ALPS index may serve as a biomarker for monitoring disease progression and as a predictor of short-term prognosis in A-GFAP-A patients.