Association of immune cells with early and late vasospasm and the need for repeat endovascular therapy after subarachnoid hemorrhage

Introduction: Spontaneous subarachnoid hemorrhage (SAH) accounts for 30% of hemorrhagic strokes and carries a high morbidity and mortality rate, for which vasospasm and associated delayed cerebral ischemia are major causes. The etiology of vasospasm is not well-understood but likely related to aberrant sympathetic nervous system (SNS) activation and immune cell activity. This study focused on assessing the relationship between vasospasm, inflammation, and hospital course of SAH patients.

Methods: Between 1/1/2018 to 8/6/2023, 57 patients with spontaneous SAH were enrolled in this prospective observational study conducted at Maine Medical Center. Peripheral blood samples were obtained at post-bleed days (PBDs) 1, 3, 5, 7, and 10. Flow cytometry was used to quantify sub-populations of immune cells. Inflammatory lab values, CTA and DSA, transcranial doppler (TCD) results, interventions, and mortality rates were obtained by chart review.

Results: The cohort included 57 patients (58.4 [19-81] years old, 36 [63.2%] female) with median Hunt Hess 4 and hospital mortality rate of 12.3% (7/57). 49 patients (85%) had aneurysmal SAH. 31 patients had symptomatic vasospasm (54.4%) with 30 confirmed on CTA, and 25 received intra-arterial (IA) therapy for vasospasm. A high neutrophil to lymphocyte ratio (NLR) on PBD 5 correlated with a more severe course of vasospasm in the early phase of the vasospasm window (PBD3-17) as tracked by TCD. A lower NLR and higher absolute lymphocyte count on PBD10 was associated with a more severe course in the late phase of the vasospasm window (PBD3-17). Higher lymphocyte counts later in hospitalization were more common with symptomatic vasospasm and associated with a greater need for repeat IA vasodilator therapy.

Conclusion : While others have demonstrated NLR at admission as a predictor of vasospasm, our findings delineate the association of neutrophils and lymphocytes with early versus late vasospasm. We also identify late lymphocytosis as a possibly more accurate predictor of repeat endovascular therapy than NLR at admission. A better understanding of SNS interaction with immune cell populations in vasospasm could provide novel therapeutic targets to improve outcomes.