When blood hits the brain: altered glymphatic and dural lymphatic function after surface bleeds.
Per Kristian Eide, Markus Hovd, Lars Magnus Valnes, Are Pripp, Geir Ringstad
Abstract
Open AccessBACKGROUND: The impact of acute subdural hematoma (aSDH) on measures of glymphatic-meningeal lymphatic function has not previously been reported. We present a descriptive observational study including a small case series-one patient following unilateral aSDH, three following unilateral subarachnoid hemorrhage (SAH), and three control subjects-providing new insights into the differential effects of surface intracranial bleeds. METHODS: The magnetic resonance imaging (MRI) contrast agent gadobutrol (0.5 mmol), administered intrathecally, was used as a cerebrospinal fluid (CSF) tracer. Multiphase contrast-enhanced MRI was performed to assess glymphatic tracer enrichment. CSF tracer clearance to blood, serving as a proxy for dural lymphatic function, was estimated using population pharmacokinetic modeling. All hemorrhagic cases involved unilateral bleeds, allowing within-subject comparison between affected and unaffected hemispheres. RESULTS: The series included one patient with aSDH (2.8 months post-event), three patients with unilateral SAH (mean 5.8 months post-event), and three age-matched, near-healthy reference subjects. Compared with controls, glymphatic tracer enrichment 24 h post-injection was slightly increased on the affected hemisphere in the aSDH case, whereas SAH patients showed markedly reduced enrichment on the affected side. Tracer distribution in controls was symmetrical. CSF clearance to blood was notably reduced in the aSDH case compared with references, suggesting impaired dural lymphatic function. CONCLUSION: This small descriptive series suggests that aSDH and SAH may differentially affect glymphatic and dural lymphatic functions. While glymphatic enrichment appeared only modestly altered after aSDH, it was severely impaired following SAH. In contrast, CSF clearance to blood was markedly reduced in the aSDH case, potentially reflecting compromised dural lymphatic drainage. The limited number of cases prevent broad generalization, but these findings offer novel hypothesis-generating observations that may inform future studies on the effects of surface intracranial hemorrhages on brain clearance pathways.