Intracranial hypocapnia is associated with parenchymal ischemia and worsened outcomes following stroke

Background: Despite good rates of reperfusion with thrombectomy, rates of moderate to severe post-stroke disability remain high. Even with successful reperfusion, infarct growth occurs, leading to worsened outcomes. Methods: This prospective cohort study integrates cone-beam CT (CBCT) perfusion imaging with intracranial microcatheter sampling during thrombectomy. A prototype CBCT perfusion platform was used to generate real-time perfusion maps, allowing delineation of core, penumbra, and normal perfusion. Sampling sites are co-registered using a 2D-3D fusion program, enabling precise sample localization. Intracranial and systemic blood samples were collected, followed by immediate arterial blood gas analysis. Clinical outcome measures were also assessed. Primary analyses investigated blood gas differences between sampling locations and their association with clinical outcomes. Results: Intracranial samples from 82 patients exhibited lower pO2, pCO2, HCO3-, and base excess relative to systemic blood (P<0.001) with pH remaining stable across locations. When stratified by microcatheter location, intracranial pCO2 was significantly lower in ischemic core (31.5±1.5 mmHg) than penumbra (37±1.2 mmHg, P=0.007). Further, patients with elevated intracranial pCO2 demonstrated significantly lower discharge National Institutes of Health Stroke Scale (NIHSS) score (P=0.028), particularly pronounced within the penumbra (P=0.0093). These relationships were not observed in systemic blood sample analysis. Conclusion: This study is the first of its kind to evaluate the impact of perfusion on intracranial pathophysiology. The intracranial microenvironment during stroke is highly perfusion-specific, and intracranial hypocapnia is associated with parenchymal ischemia and worsened functional outcomes. Whether this implicates the vasodilatory effect of pCO2 or reflects an ischemic metabolic acidosis deserves further study but may provide avenues to reduce stroke injury.