Ammad Mahmood, MBChB, BMedSci

A joint symposium between ESO and ESMINT discussed the challenges faced in acute reperfusion therapies, including patient selection and therapeutic targets.

Endovascular thrombectomy for mid-sized artery occlusions – Raul Nogueira

The importance of IV thrombolysis (IVT) therapy in this patient population was highlighted, and what constitutes mid-sized arteries considered. The anatomical variation of the M2 segment of the MCA makes this definition critical — there is generally agreement on EVT for clots in the proximal portion of larger M2 vessels. The terminology of DMVO — distal medium vessel occlusions — separates proximal dominant M2 occlusions from non-dominant M2 occlusions, as well as M3, ACA, and PCA territories. The literature suggests DMVOs cause 25-40% of acute ischemic stroke either as the primary finding or a secondary embolization complicating mechanical thrombectomy. Although IVT for this population is advocated, only half achieve reperfusion and around 25-33% have functional independence after DMVO stroke, highlighting the room for improvement potentially with EVT. Registry data showed DMVO stroke had moderately high baseline NIHSS with similar rates of reperfusion and complication with EVT compared with more proximal occlusions and up to two-thirds of patients achieving functional independence at 90 days. Patient selection in DMVO stroke needs to take into consideration many factors, including correlation of imaging and clinical findings to determine the eloquence of the area of brain involved, as well as technical considerations of the EVT procedure, such as tortuosity of the vessel, which can making procedures higher risk.

New thrombolytics for the treatment of acute ischemic stroke – Georgios Tsivgoulis

Given tenecteplase trials were the hot topic at ESOC 2022, this presentation focused on tenecteplase as the potential successor to alteplase. A brief summary of the evidence for tenecteplase in AIS prior to ESOC 2022, including meta-analysis data of previous trials, was presented, which argued that the non-inferiority of tenecteplase was established by existing data. The AcT, TASTE-A, and NOR-TEST2 results presented earlier in the day were summarized, including establishment of non-inferiority in the AcT trial, improved reperfusion rates with tenecteplase in the pre-hospital setting in the TASTE-A study, and poor safety outcomes with higher dose 0.4mg/kg tenecteplase in the NOR-TEST2 study. Observational registry data showing real-world experience of using tenecteplase suggests improved safety and efficacy of tenecteplase compared with alteplase. Ongoing trials of tenecteplase provide an opportunity to examine its potential superiority to alteplase, particularly in LVO patients, and recruitment to these trials is strongly encouraged.

Endovascular thrombectomy for mild stroke syndromes – Christos Krogias

Minor stroke (NIHSS<6) accounts for the majority of stroke presentations (two-thirds); up to 30% of presentations with large vessel occlusion (LVO) have NIHSS<6, of whom up to 30% will have early neurological deterioration. The outcomes of patients treated with best medical therapy in this group are good, and in the HERMES EVT trials, the subgroup of NIHSS<10 did not meet statistical significance for functional benefit for EVT over medical therapy, largely because these patients were small in number as they were usually excluded from the trials. Patient selection for EVT needs to be carefully thought out as the risk benefit ratio is more finely balanced. Studies suggest neurological deterioration occurs early after presentation, though its prediction is challenging. Guidelines currently state it may be reasonable to treat with EVT in minor stroke, particularly if NIHSS is low but disabling, though also encourage enrolment in clinical trials. Meta-analysis of patients from EVT trials and data from prospective observational data suggest no benefit of EVT over best medical therapy and possibly a higher risk of ICH, though in more proximal occlusions, there may be benefit of EVT. The take-home message was that benefit of EVT in mild stroke is not proven, but EVT is potentially beneficial in those with proximal occlusions, large clot burden and insufficient collateral circulation. Further RCTs of patients with mild stroke presentation and proximal LVO are ongoing, and recruitment is encouraged.

Reperfusion therapies in patients with unfavorable imaging features (low ASPECTS, poor collaterals): who, when and how? – Jens Fiehler

Imaging and clinical outcomes for patients with low ASPECTS score 0-5 vary depending upon collateral circulation. Low ASPECTS score cases with evidence of good collaterals have been shown to have better 90-day functional outcome. Good collateral status can be determined by collateral scoring or mismatch ratio on perfusion imaging. Net water uptake studies show oedema formation may be improved by reperfusion, and in patients with low ASPECTS, low net water uptake can be associated with better outcome. ESO guidelines recommend on the basis of expert opinion that patients with radiological evidence of infarction can be considered for IVT on an individual basis taking into consideration factors such as EVT eligibility, perfusion imaging, time from onset, and pre-stroke disability. In these patients, rates of ICH may be higher with EVT with bridging IVT, and study of direct EVT in this patient group is warranted. In the HERMES analysis, patients over the age of 75 showed no benefit of EVT when ASPECTS was 0-5, though a benefit was maintained in those aged under 75. The recently published RESCUE-Japan LIMIT study showed benefit of EVT in this patient group over medical therapy, though the generalizability of the results is unclear, as the majority of patients were included on the basis of MRI and only 60% of patients in the medical therapy arm had IVT. Further trials are ongoing.

Acute stroke reperfusion treatment in the elderly and those with multiple co-morbidities –evidence, and how I do it – Keith Muir

Evidence from the alteplase trials showed that benefit of IVT in those aged over 80 was studied in small numbers other than the IST-3 trial, and in meta-analysis, benefit was only seen in the first 3 hours in those aged over 80. Functional outcome after IVT also depended on stroke severity and time to treatment. In severe strokes (NIHSS>15) given IVT after 3 hours, the absolute increase in proportions with symptomatic ICH exceeded that of those achieving mRS 0-1. Patients with very mild or very severe stroke were generally excluded from clinical trials. Considering the evidence in EVT, the average age in the HERMES trials was 65-70. Age and baseline NIHSS were both correlated with outcome in the EVT and control groups. Pre-stroke mRS was the most predictive factor of functional outcome followed by baseline NIHSS, occurrence of symptomatic ICH, and age, respectively. Individual co-morbidities or measures of frailty may not be predictive of outcome, but the cumulative effect of these must be considered. Imaging parameters can be helpful in stratifying risk. A ‘three strikes’ rule was advocated, with each relative contraindication constituting a ‘strike’ and decreasing the likelihood of pursuing reperfusion therapy.