Impact of Subarachnoid Hemorrhage on Human Glymphatic Function: A Time-Evolution Magnetic Resonance Imaging Study

BACKGROUND: Subarachnoid hemorrhage (SAH) is associated with significant mortality and morbidity. The impact of SAH on human glymphatic function remains unknown. METHODS: This prospective, controlled study investigated whether human glymphatic function is altered after SAH, how it differs over time, and possible underlying mechanisms. Glymphatic enrichment was examined by intrathecal contrast-enhanced magnetic resonance imaging (MRI, glymphatic MRI), utilizing the MRI contrast agent gadobutrol (Gadovist, Bayer AG, GE; 0.50 mmol) as a cerebrospinal fluid (CSF) tracer. The distribution of the tracer in the brain and the subarachnoid and ventricular CSF spaces was assessed using standardized multi-phase MRI T1 sequences, and between-group differences in percentage change of standardized T1 signal unit ratios over time were analyzed by linear mixed models. RESULTS: The study comprised 27 patients with SAH (19 female/8 male; 59.3±10.2 years) who were examined <3 months (n=5), 3 to 6 months (n=10), 6 to 12 months (n=5), or >12 months (n=7) after bleed. A sex- and age-matched control group of 22 individuals (15 female/7 male; 55.5±10.5 years) underwent the same glymphatic MRI protocol but had no neurological or CSF disease. The patients with SAH showed a marked impairment of glymphatic enrichment throughout the brain (particularly addressing the cerebral cortex and subcortical white matter), especially after 24 hours. The glymphatic impairment was accompanied by redistribution of CSF tracer from subarachnoid spaces toward ventricles. These alterations were most pronounced after 3 to 6 months and less after 12 months, though with interindividual variation. CSF tracer transport within perivascular subarachnoid spaces was impaired and coincided with impaired glymphatic enrichment. CONCLUSIONS: Human glymphatic function is severely impaired by SAH, particularly shortly after the event. Glymphatic failure is associated with redistribution of CSF from subarachnoid spaces toward ventricles. SAH-related impairment of fluid transport within perivascular subarachnoid spaces may contribute to reduced glymphatic influx. Since patient groups are small, care should be made when concluding about the impact of time on glymphatic function.