Brain atrophy and endovascular treatment effect in acute ischemic stroke: a secondary analysis of the MR CLEAN trial

Abstract

Background: Brain atrophy is suggested to impair the potential for functional recovery after acute ischemic stroke. We assessed whether the effect of endovascular treatment is modified by brain atrophy in patients with acute ischemic stroke due to large vessel occlusion.

Methods: We used data from MR CLEAN, a multicenter trial including patients with acute ischemic stroke due to anterior circulation large vessel occlusion randomized to endovascular treatment plus medical care (intervention) versus medical care alone (control). We segmented total brain volume (TBV) and intracranial volume (ICV) on baseline non-contrast computed tomography (n = 410). Next, we determined the degree of atrophy as the proportion of brain volume in relation to head size (1 - TBV/ICV) × 100%, analyzed as continuous variable and in tertiles. The primary outcome was a shift towards better functional outcome on the modified Rankin Scale expressed as adjusted common odds ratio. Treatment effect modification was tested using an interaction term between brain atrophy (as continuous variable) and treatment allocation.

Results: We found that brain atrophy significantly modified the effect of endovascular treatment on functional outcome (P for interaction = 0.04). Endovascular treatment led to larger shifts towards better functional outcome in the higher compared to the lower range of atrophy (adjusted common odds ratio, 1.86 [95% CI: 0.97-3.56] in the lowest tertile vs. 1.97 [95% CI: 1.03-3.74] in the middle tertile vs. 3.15 [95% CI: 1.59-6.24] in the highest tertile).

Conclusion: Benefit of endovascular treatment is larger in the higher compared to the lower range of atrophy, demonstrating that advanced atrophy should not be used as an argument to withhold endovascular treatment.

Keywords: CT scan; Ischemic stroke; acute stroke therapy.

Figure 1.

Assessment of brain atrophy. Examples of axial non-contrast CT images of two patients with total brain volume (TBV) masks shown in red and intracranial volume (ICV) masks shown in blue. (a) A 43-year-old female patient presenting with a left M2 middle cerebral artery occlusion. (b) An 81-year-old male patient presenting with a left intracranial carotid artery occlusion.

Figure 2.

Association of brain atrophy with functional outcome and effect of endovascular treatment. Association of brain atrophy with functional outcome expressed as the log odds for better functional outcome (modified Rankin Scale [mRS], 0–6) with corresponding 95% confidence intervals (shading) stratified by treatment allocation (a). Effect of endovascular treatment with brain atrophy expressed as the adjusted common odds ratio (acOR) for a shift towards better functional outcome (mRS, 0–6) with corresponding 95% confidence interval (dashed lines) (b). Graphs were created using the fully adjusted models with all covariates fixed at their respective mean or mode.

Figure 3.

Association of brain atrophy with secondary outcomes. Association of brain atrophy with National Institutes of Health Stroke Scale (NIHSS) score at 24 h (a), recanalization grade on CTA with arterial occlusive lesion (AOL) score at 24 h (b), and final infarct volume (FIV, in milliliters [mL]) at 5–7 days (c) with corresponding 95% intervals (shading) stratified by treatment allocation. For illustration purposes, non-transformed FIV was used. Graphs were created using the fully adjusted models with all covariates fixed at their respective mean or mode.