Elena Zapata-Arriaza, MD

Campbell BCV, Majoie CBLM, Albers GW, Menon BK, Yassi N, Sharma G, et al. Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data. Lancet Neurol. 2019;18:46-55.

Image selection in acute stroke involves a radiological prognostic marker in patients with large vessel occlusion. Ischemic penumbra is defined as hypoperfused tissue, which is at risk for irreversible damage (i.e., infarction) if blood flow is not rapidly restored and can widen the treatment time window for selected patients as seen in recent positive endovascular trials. The possibility of increasing target population that would experience clinical benefit after performing mechanical thrombectomy motivates the assessment of influence of ischaemic core volume and mismatch volume on functional outcome after endovascular treatment.

The HERMES collaboration performed a systematic review and meta-analysis from all randomized controlled trials published in PubMed from January 2010 to May 2017, assessing endovascular thrombectomy predominantly performed with stent retrievers versus medical therapy in patients with anterior circulation ischaemic stroke, according to PRISMA guidelines. For CTP, irreversibly injured ischaemic core was defined as a relative cerebral blood flow of less than 30% of normal brain blood flow. For diffusion MRI, ischaemic core was defined as an apparent diffusion coefficient of less than 620 μm²/s. The association of ischaemic core and penumbral volumes with 90-day mRS score (functional independence, defined as mRS score 0–2) and functional improvement by at least one mRS category in all patients and in a subset of those with more than 50% endovascular reperfusion was evaluated as highlights among other issues. Symptomatic intracerebral haemorrhage was assessed as a safety outcome.

Among 1764 patients included, CTP was available and accessible for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Increasing ischaemic core volume was associated with reduced likelihood of functional independence, but there was no interaction between imaging modality (CTP or MRI) and treatment effect.

Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion, age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. However, the odds of improved functional outcome and absolute benefit (i.e., number needed to treat to benefit) from treatment with thrombectomy were maintained in patients over a wide range of ischaemic core volumes. In terms of safety, patients with large ischaemic core volumes,  symptomatic intracerebral haemorrhage was not increased in them.

Study limitations include that CTP was not required in all trials, so imaging acquisition protocols varied. Overestimation of the actual ischaemic core volume could potentially explain good functional outcomes in some patients with a large ischaemic core volume.

As the authors argued, despite large core volumes being related to reduced likelihood of functional independence, good outcomes were more likely with thrombectomy than with medical therapy alone, when patients underwent endovascular therapy within 6 hours after stroke onset, at every ischaemic core volume level. Given the independent association of age, ischaemic core volume, and imaging-to-reperfusion time with functional improvement in patients with CTP with more than 50% endovascular reperfusion, it seems logical not to exclude patients for thrombectomy within the first six hours only based on perfusion results, since these patients possibly need reperfusion as early as possible to increase the chances of clinical improvement. Finally, besides endovascular treatment efficacy in large core infarcts, its safety doesn’t act as excluding criteria due to symptomatic intracerebral haemorrhage rates between groups. However, further studies are needed to prove the safety and efficacy of endovascular treatment in patients in whom the large size of the infarction constitutes an inclusion criterion from the beginning.