Collaterals Are a Major Determinant of the Core but Not the Penumbra Volume in Acute Ischemic Stroke

Purpose: Determinants of early loss of ischemic tissue (core) or its prolonged survival (penumbra) in acute ischemic stroke (AIS) are poorly understood. We aimed to identify radiological associations of core and penumbra volumes on CT perfusion (CTP) in a large cohort of AIS.

Methods: In the ASTRAL registry (2003-2016), we identified consecutive AIS patients with proximal middle cerebral artery (MCA) occlusion. We calculated core and penumbra volumes using established thresholds and the mismatch ratio (MR). We graded collaterals into three categories on CT-angiography. We used clot burden score (CBS) to quantify the clot length. We related CTP volumes to radiological variables in multivariate regression analyses, adjusted for time from stroke onset to first imaging.

Results: The median age of the 415 included patients was 69 years (IQR = 21) and 49% were female. Median admission NIHSS was 16 (11) and median delay to imaging 2.2 h (1.9). Lower core volumes were associated with higher ASPECTS (hazard ratio = 1.08), absence of hyperdense MCA sign (HR = 0.70), higher CBS (i.e., smaller clot, HR = 1.10), and better collaterals (HR = 1.95). Higher penumbra volumes were related to lower CBS (i.e., longer clot, HR = 1.08) and proximal intracranial occlusion (HR = 1.47), but not to collaterals. Higher MR was found in absence of hyperdense MCA sign (HR = 1.28), absence of distal intracranial occlusion (HR = 1.39), and with better collaterals (HR = 0.52).

Conclusions: In AIS, better collaterals were associated with lower core volumes, but not with higher penumbra volumes. This suggests a major role of collaterals in early tissue loss and their limited significance as marker of salvageable tissue.