American Heart Association


The Reversibly Stunned Brain After Successful Endovascular Reperfusion in Acute Anterior Circulation Ischemic Stroke

Tolga D. Dittrich, MD

Talavera B, Gómez-Vicente B, Martínez-Galdámez M, López-Cancio E, García-Cabo C, Castellanos M, Roel A, Tejada-Meza H, Marta-Moreno J, Pérez-Lázaro C, et al. Delayed Neurological Improvement After Full Endovascular Reperfusion in Acute Anterior Circulation Ischemic Stroke. Stroke. 2021;52:2210-2217.

Endovascular thrombectomy (EVT) is an essential part of acute therapy for ischemic stroke due to large vessel occlusion. As early clinical improvement after successful reperfusion therapy is a reliable predictor of long-term independence, the absence of such clinical progress can discourage the treating stroke team. But does this necessarily mean that the long-term prognosis in such patients is unfavorable? This is one of the questions addressed by Talavera et al. in their paper.

A total of 628 patients with proximal occlusions of the anterior circulation, all of whom received successful EVT (i.e., mTICI 3), were included in the study. After EVT, 142 (22.6%) showed no early neurological improvement. However, 32 (22.5%) still had a favorable long-term outcome. In contrast, 323 (66.5%) of a total of 486 patients with early neurological improvement demonstrated a favorable long-term outcome. Baseline predictors of delayed neurological improvement were male sex (OR 6.4 [95% CI, 2.1-22.3] p=.002), lower baseline NIHSS score (OR 1.4 [95% CI, 1.2-1.5]. p=<.001) and treatment with rtPA (OR 9.1, [95% CI, 2.7-30.9], p=<.001).

Article Commentary: “Dual Antiplatelet Therapy Versus Aspirin in Patients With Stroke or Transient Ischemic Attack”

Wern Yew Ding, MBChB

Bhatia K, Jain V, Aggarwal D, Vaduganathan M, Arora S, Hussain Z, Uberoi G, Tafur A, Zhang C, Ricciardi M, Qamar A. Dual Antiplatelet Therapy Versus Aspirin in Patients With Stroke or Transient Ischemic Attack: Meta-Analysis of Randomized Controlled Trials. Stroke. 2021;52:e217–e223.

Transient ischemic attack (TIA)/cerebral vascular accident (CVA) and acute coronary syndrome share many similarities. An integral element to the management of patients with either condition includes the use of antiplatelet therapy to reduce the risk of recurrent events. In acute coronary syndrome, the administration of dual antiplatelet therapy (DAPT) has been established, while this is less certain in TIA/CVA. Recently, several trials have investigated this issue. In this meta-analysis by Bhatia and colleagues, they sought to compare the safety and efficacy of aspirin plus a P2Y12 inhibitor against aspirin alone for the prevention of recurrent stroke in patients with minor ischemic stroke or high-risk TIA.

The authors performed a thorough literature search to identify a total of 8,211 citations, of which, 4 were eventually included in this article with a total of 21,459 patients. Patients with presumed cardioembolic stroke, who received thrombolysis, were planned for endovascular therapy and had underlying indications for anticoagulation were excluded. Compared to aspirin alone, DAPT was associated with a lower risk of recurrent stroke (ischemic and hemorrhagic), major adverse cardiovascular event and recurrent ischemic event but with greater risk of major bleeding. There was no difference in the risk of hemorrhagic stroke or all-cause death between DAPT vs. aspirin alone. Overall, the authors surmised that current data supports the use of DAPT in patients with minor ischemic stroke or TIA.

When to Call It Quits: Number of EVT Passes is Associated With Increased ICH Risk

Lauren Peruski, DO

Maros ME, Brekenfeld C, Broocks G, Leischner H, McDonough R, Deb-Chatterji M, Alegiani A, Thomalla G, Fiehler J, Flottmann F, for the GSR Investigators. Number of Retrieval Attempts Rather Than Procedure Time Is Associated With Risk of Symptomatic Intracranial Hemorrhage. Stroke. 2021;52:1580–1588.

Endovascular therapies used to treat acute ischemic stroke are becoming increasingly common and effective. As more of these procedures are being conducted, we are becoming aware of the potential risks and complications associated with such treatments. Established adverse events include vessel dissection and/or perforation, cerebral vasospasm, clot migration with distal ischemia, and symptomatic intracerebral hemorrhage (sICH), among others. Of these, sICH in particular has been associated with poor outcomes and high mortality rates. Prior studies have concluded that >3 device passes correlates to increased sICH risk; however, procedure time was not properly adjusted for. Therefore, the data previously presented was confounded by time. This study was designed around the hypothesis that the number of retrieval attempts is positively associated with sICH regardless of procedure time.

The cohort described in this paper was collected from the German Stroke Registry – Endovascular Treatment (GSR-ET); this registry was created between 2015 and 2018. The adult patients included were required to have undergone endovascular therapy to treat an acute ischemic stroke caused by a large vessel occlusion of the anterior circulation. Those selected needed to have pre-specified data points within their chart (for example, Alberta Stroke Program Early CT Score, NIH Stroke Scale, Thrombolysis in Cerebral Infarction [TICI] score, 90-day Modified Rankin Scale [mRS], etc.). Patients were not included if they had an occlusion of the extracranial internal carotid artery (ICA), or an ICA occlusion proximal to the carotid terminus. Patients were also excluded if they required stent placement at the time of endovascular therapy, or if they experienced spontaneous recanalization at the time of angiography.

Frequency and Clinical Impact of Procedural Complications During Early Versus Late Endovascular Treatment in Acute Stroke

Tolga D. Dittrich, MD

Maslias E, Nannoni S, Ricciardi F, Bartolini B, Strambo D, Puccinelli F, Hajdu SD, Eskandari A, Saliou G, Michel P. Procedural Complications During Early Versus Late Endovascular Treatment in Acute Stroke: Frequency and Clinical Impact. Stroke. 2021;52:1079–1082.

The efficacy of endovascular treatment (EVT) for patients with acute ischemic stroke due to proximal vessel occlusion is well established. This holds for patients in the early (<6 hours after symptom onset) and radiologically preselected patients in the late time window (6-24 hours). Randomized controlled trials showed a reasonable overall safety profile, with a relatively wide range (2.4-7%) of reported intraprocedural cerebrovascular complications. These complications include embolization in the non-ischemic territory, arterial dissections, and perforations.

In their monocenter retrospective analysis of 695 stroke patients receiving EVT, Maslias and colleagues examined the incidence of intraprocedural complications and their implications for short-term outcomes in the early (N=493) and late time window (N=202). The overall proportion of patients with at least one intraprocedural complication was relatively high across both groups (16.2% in the early, 16.3% in the late window, Padj=0.90). This might be surprising given the intuitive concern of increased intraprocedural complication rates in the late time window (e.g., due to increased permeability of the vessel walls with longer-lasting ischemia). Still, the occurrence of intraprocedural complications was associated with a worse outcome, at least in the short term (i.e., within the first 24 hours), at comparable recanalization rates in the late time window.

MR CLEAN and Mechanical Thrombectomy in Children

Kevin O’Connor, MD

van Es ACGM, Hunfeld MAW, van den Wijngaard I, Kraemer U, Engelen M, van Hasselt BAAM, Fransen PSS, Dippel DWJ, Majoie CBLM, van der Lugt A, et al.; MR CLEAN Registry Investigators. Endovascular Treatment for Acute Ischemic Stroke in Children: Experience From the MR CLEAN Registry. Stroke. 2021;52:781-788.

Although there have been no large, robust, randomized trials of endovascular mechanical thrombectomy (EVT) in children with acute ischemic stroke, there is growing evidence indicating that the approach may be safe and effective.

van Es et al. performed EVT on 9 children between March 2014 and July 2017 (4 boys and 5 girls, aged 13 months-16 years, median 14 years) with an anterior circulation large vessel occlusion. Four of these children had a left ventricular assist device (ages 13 months, 18 months, 3 years, and 10 years). The median initial Pediatric National Institutes of Health Stroke Scale score (PedNIHSS) was 17 (IQR, 9.5-19.5). Four of 9 children received IV alteplase; four children with LVAD did not because they were therapeutically anticoagulated. Younger children with smaller vessels necessitated the use of smaller catheters and stent retrievers. The six children ages >10-year, however, underwent EVT with a stent retriever commonly employed for M1 occlusions in adults.

Is There a Magic Number for Thrombectomy Retrieval Attempts?

Melanie R. F. Greenway, MD

Flottmann F, Brekenfeld C, Broocks G, Leischner H, McDonough R, Faizy T, Deb-Chatterji M, Alegiani A, Thomalla G, Mpotsaris A, et al. Good Clinical Outcome Decreases With Number of Retrieval Attempts in Stroke Thrombectomy: Beyond the First-Pass Effect. Stroke. 2021;52:482-490.

Between discussion of the “First Pass Effect”1,2 and wondering “When to Stop,”3 finding a magic number of retrieval attempts that optimizes potential good outcome and minimizes risk of adverse events continues to be an important clinical question. 

Utilizing the German Stroke Registry-Endovascular Treatment section, the authors focused on reviewing number of retrieval attempts as it correlates with final TICI score and modified Rankin Score (mRS) at 90 days.  They analyzed 2611 patients from 2015-2018, 1225 of which met inclusion and exclusion criteria. All patients included were 18 years of age or older, underwent endovascular therapy of the intracranial anterior circulation, and had a complete set of data needed for the study. A successful reperfusion was defined as TICI 2b or 3, and a “good clinical outcome” was defined as mRS 0-2.

Endovascular Stroke Therapy in the Extended Time Window: Beneficial Even in the Absence of Perfusion Imaging?

Tolga Daniel Dittrich, MD

Nogueira RG, Haussen DC, Liebeskind D, Jovin TG, Gupta R, Jadhav A, Budzik RF, Baxter B, Krajina A, Bonafe A, et al. Stroke Imaging Selection Modality and Endovascular Therapy Outcomes in the Early and Extended Time Windows. Stroke. 2021;52:491-497.

Perfusion imaging currently represents a key selection tool for endovascular therapy (EVT) in stroke patients with large vessel occlusions in the extended time window. However, the extent to which imaging modality influences clinical outcome in EVTs remains unclear in this context.

Nogueira et al. tackled this question by comparing the functional outcome of patients with intracranial carotid, M1-, or M2-occlusions of the middle cerebral artery with modified Rankin Scale score from 0 to 2 and time to treatment between early (i.e., 0-6 hours) and extended time windows (i.e., 6-24 hours) depending on the imaging modality received. These were either non-contrast computed tomography (NCCT)±CT angiography (CTA) or NCCT±CTA with CT perfusion (CTP).

Managing Tandem Occlusions From Carotid Dissection: To Stent or Not to Stent?

Setareh Salehi Omran, MD

Marnat G, Lapergue B, Sibon I, Gariel F, Bourcier R, Kyheng M, Labreuche J, Dargazanli C, Consoli A, Blanc R, et al. Safety and Outcome of Carotid Dissection Stenting During the Treatment of Tandem Occlusions: A Pooled Analysis of TITAN and ETIS. Stroke. 2020;51:3713–3718.

Intracranial occlusions with an ipsilateral cervical internal carotid artery (ICA) stenosis/occlusion, so-called tandem occlusions, are a frequent cause of anterior circulation strokes. Tandem occlusions can be treated with endovascular therapy, although the best technical strategy for treating the ICA stenosis/occlusion component is unclear.1 In particular, there is great variability in practice with performing carotid artery stenting (CAS) in addition to intracranial thrombectomy.2 It is also unknown whether the etiology of the ICA stenosis/occlusion, either from dissection or atherosclerosis, should impact the decision to perform CAS. While data supports thrombectomy with CAS in tandem occlusions due to atherosclerosis, there is limited data on its safety and efficacy in tandem occlusions from carotid dissection.3

Marnat et al4 examined the safety and outcome of CAS during the treatment of tandem occlusions from carotid dissections using pooled data from two prospectively maintained, multicenter databases (Endovascular Treatment in Ischemic Stroke and Thrombectomy in Tandem Lesion). The analysis included patients who received endovascular therapy for tandem occlusions related to acute cervical carotid dissection between January 2012 and January 2019. The endovascular strategy, stenting protocol, and antithrombotic regimens were chosen by the interventionalist and treating team. Patients were divided in two groups depending on whether they did or did not undergo CAS. The main outcomes of favorable neurological outcome (defined as 90-day mRS 0-2) and successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3) were assessed in both groups. The rates of procedural complications, 90-day mortality, and symptomatic intracerebral hemorrhage were also compared between patients who did and did not undergo CAS. In order to minimize potential bias due to endovascular strategy, the authors performed a sensitivity analysis comparing main clinical outcomes (favorable outcome and overall degree of disability) in the subgroup of patients with successful reperfusion.

Interventions for Medium Vessel Occlusions

Kevin O’Connor, MD

Pérez-García C, Moreu M, Rosati S, Simal P, Egido JA, Gomez-Escalonilla C, Arrazola J. Mechanical Thrombectomy in Medium Vessel Occlusions: Blind Exchange With Mini-Pinning Technique Versus Mini Stent Retriever Alone. Stroke. 2020;51:3224-3231.

Although mechanical thrombectomy (MT) is routinely performed for patients with acute stroke due to large vessel occlusions, interventions for those with medium vessel occlusions (MeVO) are increasing. Techniques for MT for MeVOs include the use stent retrievers and distal aspiration catheters (DACs). A recently developed approach is the blind exchange/mini-pinning (BEMP) technique, which combines a mini stent retriever with a DAC (see Figure 1 below).

Figure 1. Illustrations depicting the blind exchange with mini-pinning technique.
Figure 1. Illustrations depicting the blind exchange with mini-pinning technique.

Pérez-García et al. retrospectively compared mini stent retrievers alone (initial standard institutional MeVO procedure, n=50) versus the BEMP technique (later standard institutional MeVO procedure, n=56) for effectiveness and safety using a prospective database of MT patients. Aside from the DACs, the devices used for the two groups were comparable. The BEMP technique group had a higher rate of expanded Thrombolysis in Cerebral Ischemia (eTICI) 2c/3 recanalization scores after first pass (n=32, 57% versus n=17, 34%; P=0.017) and at procedure conclusion (n=37, 66% versus n=23, 46%; P=0.037). The rate of eTICI ≥ 2b recanalization scores was comparable between the groups after first pass (n=36, 64% versus n=25, 50%; P=0.137) and at procedure end (n=44, 78.5% versus n=39, 78%; P=0.856). A rescue therapy (other than the initial technique) was used less often in the BEMP group (n=4, 7.1% versus n=11, 22%; P=0.028). The BEMP technique was an independent predictor of eTICI 2c/3 recanalization (OR 2.72 [95% CI, 1.19-6.22]; P=0.018).

The Benefit of Targeting LDL Cholesterol <70 mg/dL Even at Expense of Adding Second Lipid-Lowering Agent

Manya Khrlobyan, DO, MS

Amarenco P, Kim JS, Labreuche J, Charles H, Giroud M, Lee BC, Mahagne MH, Nighoghossian N, Steg PG, Vicaut E, et al. Benefit of Targeting a LDL (Low-Density Lipoprotein) Cholesterol <70 mg/dL During 5 Years After Ischemic Stroke. Stroke. 2020;51:1231–1239.

The most recent American Heart Association/American Stroke Association guidelines recommend high intensity statin therapy for patients with ischemic stroke or TIA presumed to be of atherosclerotic origin and a Low-Density Lipoprotein (LDL) level >100 mg/dL. These recommendations are largely based on the results of the 2006 SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Level). With these recommendations in mind, patients are typically started on Atorvastatin 80 mg daily, though often times without a specific LDL target in mind.

The TST trial (Treat Stroke to Target) was a randomized, event driven trial which investigated the benefit of targeting an LDL of <70 mg/dL in ischemic stroke patients in a French and Korean population to reduce the risk of cardiovascular events. Patients were eligible if they had an ischemic stroke <3 months previously or a TIA within the previous 15 days, atherosclerotic stenosis of cerebral vasculature (extra or intracranial), aortic arch plaque >4 mm, or known history of coronary artery disease. Patients were randomly assigned in a 1:1 ratio to target LDL of < 70 mg/dL or target LDL of 100 + 10 mg/dL. Investigators were free to use any type and dose of statin to reach the target LDL and, at 3 weeks follow-up, had an option of adjusting the statin dose or adding other lipid lowering agents such as ezetimibe to achieve the target LDL. The primary endpoint was the composite of ischemic stroke, myocardial infarction, need for carotid or coronary revascularization, and unexplained sudden death.