Impaired glymphatic system in cryptococcal meningitis: DTI-ALPS index as a novel biomarker for clinical severity and treatment response.

OBJECTIVE: To assess perivascular-aligned diffusion in patients with cryptococcal meningitis (CM) by means of the Diffusion Tensor Imaging Along the Perivascular Space (DTI-ALPS) parameter and investigate its relationship with clinical results. METHODS: Thirty CM patients and thirty healthy controls underwent 3 T MRI-DTI to calculate the ALPS index. Clinical measures included intracranial pressure (ICP), cerebrospinal fluid parameters, and modified Rankin Scale (mRS) scores. RESULTS: CM patients had significantly lower ALPS indices than controls (1.28 ± 0.13 vs. 1.49 ± 0.09, p < 0.001). Lower ALPS correlated with higher ICP (r = -0.72, p < 0.001) and worse mRS scores (r = -0.65, p = 0.001). A moderate inverse correlation was found with CSF protein (r = -0.45, p = 0.013), but not with CSF WBC. Patients with an unfavorable four-week response showed lower ALPS indices than those with a favorable response. CONCLUSION: The DTI-ALPS index suggests altered perivascular diffusion, which may reflect glymphatic dysfunction in CM and correlates with disease severity. Exploratory findings suggest a possible link with four-week treatment outcome, though prospective validation is needed. The ALPS index shows promise as a severity biomarker and supports impaired brain clearance as a therapeutic target for further study.