Impaired Glymphatic Function in Acute Spontaneous Intracerebral Hemorrhage

ABSTRACT Background and Aims Alterations in glymphatic function during the acute phase of acute spontaneous intracerebral hemorrhage (sICH) remain poorly understood. The aim of this study was to investigate whether, compared to healthy controls (HCs), the glymphatic system is impaired in patients with sICH, and to assess its association with hemorrhage and edema severity and outcome. Methods Fifty‐five sICH patients (including 46 supratentorial sICH and 9 ) and 97 age‐ and sex‐matched HCs underwent conventional MRI and diffusion tensor imaging. The diffusion along the perivascular space (DTI‐ALPS) index, serving as a marker for glymphatic function, was computed, with supratentorial cases being categorized into ipsilateral and contralateral ALPS. Volumes of hemorrhage and edema were evaluated using susceptibility‐weighted imaging (SWI) and T2‐weighted magnetic resonance images, and the relative edema ratio was calculated. Clinical outcomes were categorized as favorable or poor based on a modified Rankin scale score of ≤ 2 or > 2 at 90 days. Results sICH patients showed significantly lower DTI‐ALPS values on the ipsilateral side compared to the average in the HC group (1.34 ± 0.24 vs. 1.46 ± 0.22, p = 0.003), whereas contralateral DTI‐ALPS values in sICH patients did not differ significantly from HCs (1.48 ± 0.21 vs. 1.46 ± 0.22, p = 0.524). The ipsilateral DTI‐ALPS was notably associated with both hemorrhage and relative edema volumes (both p < 0.05). A higher ipsilateral DTI‐ALPS was independently associated with a favorable outcome at 90 days (odds ratio = 1.686 per 0.1 increase, p = 0.038). Conclusions The DTI‐ALPS index, which reflects glymphatic functionality, is notably diminished on the ipsilateral side in acute sICH, correlating significantly with increased volumes of hemorrhage and edema. This study suggests that glymphatic dysfunction may contribute to the severity of clinical outcomes, and highlights the potential role of the glymphatic system in the pathophysiology of sICH.