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Background: Aneurysmal subarachnoid haemorrhage (SAH) is a complex form of stroke affecting approximately 10 per 100,000 individuals in Western populations. In addition to the damage caused by the initial haemorrhage, secondary complications such as rebleeding, hydrocephalus and delayed cerebral ischemia may further contribute to the overall extentof brain injury. Long-term outcomes range widely, from death to full recovery. Predicting functional outcomes during theacute phase of the disease remains challenging, and currently, no blood-based biomarkers are routinely used in clinical practice.

Aim: This thesis investigates whether the biochemical biomarkers myo-inositol (MI), neurofilament light chain (NFL), and S100-beta (S100B) measured in venous blood are associated with secondary complications and long-term functional outcomes. The focus is also on characterizing their trajectories during the acute phase of SAH. The main hypothesis is that levels of the biomarkers are associated with functional outcome 12 months after the haemorrhage.

Method: This work is based on four studies; all derived from a single observational cohort. The cohort included patients aged 18 years or older who were treated for SAH at Umeå University Hospital between 2014 and 2018. Serum samples were collected at multiple time points during hospitalization. Demographic and clinical data were recorded, including neurological status upon admission according to the World Federation of Neurosurgical Societies and Hunt and Hessscores, the amount of subarachnoid blood on the initial CT scan as classified by the Fisher grade, the presence of delayed cerebral ischemia and angiographic vasospasm, as well as the treatment modality used for aneurysm occlusion. Functional status was assessed one year after disease onset using the Glasgow Outcome Scale Extended and the modified Rankin Scale. Outcomes were dichotomized into favourable (Glasgow Outcome Scale 5-8, modified Rankin Scale 0-3) and unfavourable (Glasgow Outcome Scale 1-4, modified Rankin Scale 4-6) groups. In one study, health-related quality of life was also evaluated using the EuroQoL 5-Dimension Index. Biomarker levels were compared between groups, and multivariable logistic regression was applied to assess their predictive value for long-term outcomes.

Results: For MI, levels at admission did not correlate with World Federation of Neurosurgical Societies score, nor did they differ between favourable and unfavourable outcome groups. However, by day seven, significant differences in MI levels emerged between outcome groups, and the change in MI levels over this period also differed significantly. For NFL, levelswere significantly associated with both World Federation of Neurosurgical Societies score at admission and outcome group,with differences observed at admission and throughout follow-up. S100B values obtained during the first days after SAH onset correlated significantly with both modified Rankin Scale and EuroQoL 5-Dimension Index with peak S100B levels showing the strongest association with functional outcome. All three biomarkers were significant predictors of long-termfunctional outcome in univariate analyses. When combined with established predictors, these biomarkers improved the performance of multivariable regression models.

Conclusions: The biomarkers MI, NFL, and S100B are associated with long-term functional outcomes in patients with SAH. Incorporating them into predictive models may provide a valuable tool for outcome prognostication. However, external validation in larger cohorts is required before these biomarkers can be considered for routine clinical implementation. The main hypothesis of this thesis has therefore to be accepted.