Effect of inflammation on neurovascular coupling, microperfusion, and clinical outcomes in ischemic stroke patients: a case series report

Astrid Cancino^1*Pablo Munoz¹Pablo Cox^1,2Lilian Acevedo²Sebastián Castillo²Aldo Letelier²Alejandro Veloz¹Maria Rodriguez-Fernandez³Steren Chabert^1*

• ¹Universidad de Valparaiso, Valparaíso, Chile
• ²Hospital Carlos Van Buren, Valparaíso, Chile
• ³Pontificia Universidad Catolica de Chile, Santiago, Chile

Ischemic stroke leads to a range of sequelae that affect daily functioning. In many cases, such as wake-up strokes or late hospital arrivals, the therapeutic window for reperfusion is missed for the patient, and functional outcomes remain uncertain. The inflammatory response to ischemia plays a pivotal role in the initiation, progression, and recovery phase of stroke. Yet, a gap remains in understanding its impact on neuroimaging and clinical outcomes. This prospective case series investigates the relationship between inflammation, neuroimaging findings in the first 48 hours after stroke onset, and six-month clinical outcomes. Biomarkers of inflammation, such as C-reactive protein (CRP) and Interleukin 6 (IL-6), as well as oxidative stress (OS), were measured. Additionally, advanced neuroimaging techniques were used to assess neurovascular coupling, cerebrovascular reactivity, and intravoxel incoherent motion (IVIM) for microperfusion. After six months, outcomes were evaluated using the modified Rankin Scale (mRS), and participants were categorized into two groups: those with good outcomes (mRS 1 to 3) and those with poor outcomes (mRS 4 to 6). A total of 23 wake-up stroke patients not eligible for reperfusion therapy were included: 11 with cortical ischemic lesions and 12 with subcortical or deep ischemic lesions, involving the thalamus, basal ganglia, brainstem, or cerebellum. Significant differences were observed in pseudodiffusion (D*) and delayed neurovascular coupling between patients with normal and elevated inflammatory markers. CRP levels showed a positive correlation with these imaging findings. Additionally, when stratified by six-month outcomes, patients with poor recovery had higher CRP levels and altered contralateral cerebrovascular reactivity within the first 48 hours of admission. These preliminary findings suggest that combining inflammatory and neuroimaging markers across cortical and subcortical stroke subtypes could enhance understanding of inflammation's role in early hemodynamic responses and long-term effects outcomes. Further research is needed to explore the broader implications of these case series representations.