Eide Per Kristian, Undseth Ragnhild Marie, Pripp Are, Lashkarivand Aslan, Nedregaard Bård, Sletteberg Ruth, Rønning Pål Andre, Sorteberg Angelika G, Ringstad Geir, Valnes Lars Magnus
Department of Neurosurgery, Oslo University Hospital-Rikshospitalet, Norway (P.K.E., A.L., P.A.R., A.G.S., L.M.V.).
Institute of Clinical Medicine, Faculty of Medicine (P.K.E., A.L., A.G.S., G.R.), University of Oslo, Norway.
Stroke. 2025 Mar;56(3):678-691. doi: 10.1161/STROKEAHA.124.047739. Epub 2025 Jan 9.
Subarachnoid hemorrhage (SAH) is associated with significant mortality and morbidity. The impact of SAH on human glymphatic function remains unknown.
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.
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.
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.
蛛网膜下腔出血（SAH）与显著的死亡率和发病率相关。SAH对人体类淋巴功能的影响尚不清楚。
这项前瞻性对照研究调查了SAH后人体类淋巴功能是否改变、随时间如何变化以及可能的潜在机制。通过鞘内注射对比增强磁共振成像（MRI，类淋巴MRI）检查类淋巴富集情况，使用磁共振造影剂钆布醇（佳迪显，拜耳公司，通用电气；0.50 mmol）作为脑脊液（CSF）示踪剂。使用标准化的多期MRI T1序列评估示踪剂在脑内以及蛛网膜下腔和脑室CSF间隙中的分布，并通过线性混合模型分析随时间标准化T1信号单位比率变化百分比的组间差异。
该研究纳入了27例SAH患者（19例女性/8例男性；59.3±10.2岁），分别在出血后<3个月（n = 5）、3至6个月（n = 10）、6至12个月（n = 5）或>12个月（n = 7）接受检查。一个由22名个体组成的性别和年龄匹配的对照组（15例女性/7例男性；55.5±10.5岁）接受了相同的类淋巴MRI检查方案，但无神经或CSF疾病。SAH患者在整个脑内（特别是大脑皮层和皮层下白质）显示出类淋巴富集的明显受损，尤其是在24小时后。类淋巴功能受损伴随着CSF示踪剂从蛛网膜下腔向脑室的重新分布。这些改变在3至6个月后最为明显，12个月后减轻，尽管存在个体差异。血管周围蛛网膜下腔内的CSF示踪剂转运受损，且与类淋巴富集受损同时出现。
SAH会严重损害人体类淋巴功能，尤其是在事件发生后不久。类淋巴功能衰竭与CSF从蛛网膜下腔向脑室的重新分布有关。SAH相关的血管周围蛛网膜下腔内液体转运受损可能导致类淋巴流入减少。由于患者组规模较小，在得出时间对类淋巴功能影响的结论时应谨慎。
