Frailty reduces penumbral volumes and attenuates treatment response in hyperacute ischemic stroke

Frailty-the loss of physiological reserve to withstand a stressor event-is associated with poorer outcomes following acute stroke reperfusion therapies. However, the mechanisms underlying this relationship are poorly understood. This study investigated the association between frailty and penumbral volumes in hyperacute ischemic stroke.

Total ischemic lesion volumes (comprising infarct core and penumbral volumes) were measured using computed tomography (CT) perfusion imaging to give the penumbral fraction within the ischemic lesion. Pre-stroke frailty was measured using a validated frailty index. The relationship between frailty and penumbral fraction was adjusted for age, onset-to-CT interval, collateral scores, small vessel disease burden and vascular comorbidities. Stroke severity was measured using the National Institutes of Health Stroke Scale at baseline and after 24 h.

In 55 individuals receiving thrombolysis for ischemic stroke, increasing frailty was associated with a reduction in penumbral fraction (rs = -0.36, P < 0.01). This remained significant after adjustment for age, onset-to-imaging time and collateral score (beta = -1.16, P < 0.001). Correspondingly, frailty was independently negatively associated with proportional improvement in stroke severity following treatment (beta = -2.00, P < 0.01). C-reactive protein (CRP) on presentation was associated with frailty index (rs = 0.38, P < 0.01) and penumbral fraction (rs = -0.30, P = 0.02).

A reduction in salvageable penumbra in frailty may explain the treatment-attenuating effects of frailty on reperfusion therapies. The association with CRP motivates further research into a possible inflammatory component of this relationship.

Frailty is independently associated with reduced penumbra and poorer neurological recovery in acute stroke. These findings may explain the attenuated response to stroke reperfusion therapies seen in frailer individuals.