Distal Medium Vessel Occlusion Strokes: Understanding the Present and Paving the Way for a Better Future.

Distal medium vessel occlusions (DMVOs) are thought to cause as many as 25% to 40% of all acute ischemic strokes and may result in substantial disability amongst survivors. Although intravenous thrombolysis (IVT) is more effective for distal than proximal vessel occlusions, the overall efficacy of IVT remains limited in DMVO with less than 50% of patients achieving reperfusion and about 1/3 to 1/4 of the patients failing to achieve functional independence. Data regarding mechanical thrombectomy (MT) among these patients remains limited. The smaller, thinner, and more tortuous vessels involved in DMVO are presumably associated with higher procedural risks whereas a lower benefit might be expected given the smaller amount of tissue territory at risk. Recent advances in technology have shown promising results in endovascular treatment of DMVOs with room for future improvement. In this review, we discuss some of the key technical and clinical considerations in DMVO treatment including the anatomical and clinical terminology, diagnostic modalities, the role of IVT and MT, existing technology, and technical challenges as well as the contemporary evidence and future treatment directions.

Intraoperative neuromonitoring as real-time diagnostic for cerebral ischemia in endovascular treatment of ruptured brain aneurysms.

OBJECTIVE: To evaluate the diagnostic accuracy of intraoperative neurophysiological monitoring (IONM) during endovascular treatment (EVT) of ruptured intracranial aneurysms (rIA). METHODS: IONM and clinical data from 323 patients who underwent EVT for rIA from 2014-2019 were retrospectively reviewed. Significant IONM changes and outcomes were evaluated based on visual review of data and clinical documentation. RESULTS: Of the 323 patients undergoing EVT, significant IONM changes were noted in 30 patients (9.29%) and 46 (14.24%) experienced postprocedural neurological deficits (PPND). 22 out of 30 (73.33%) patients who had significant IONM changes experienced PPND. Univariable analysis showed changes in somatosensory evoked potential (SSEP) and electroencephalogram (EEG) were associated with PPND (p-values: <0.001 and <0.001, retrospectively). Multivariable analysis showed that IONM changes were significantly associated with PPND (Odd ratio (OR) 20.18 (95%CI:7.40-55.03, p-value: <0.001)). Simultaneous changes in both IONM modalities had specificity of 98.9% (95% CI: 97.1%-99.7%). While sensitivity when either modality had a change was 47.8% (95% CI: 33.9%-62.0%) to predict PPND. CONCLUSIONS: Significant IONM changes during EVT for rIA are associated with an increased risk of PPND. SIGNIFICANCE: IONM can be used confidently as a real time neurophysiological diagnostic guide for impending neurological deficits during EVT treatment of rIA.

Optical Coherence Tomography in the Evaluation of Suspected Carotid Webs.

BACKGROUND: Carotid web (CaW) is a subtype of fibromuscular dysplasia that predominantly involves the intimal layer of the arterial wall and is commonly overlooked as a separate causative entity for recurrent strokes. CaW is defined as a shelf-like lesion at the carotid bulb, although different morphological features have been reported. Optical coherence tomography (OCT) has been described in the literature as a useful microscopic and cross-sectional tomographic imaging tool. This study aimed to evaluate the potential utility of OCT in characterizing the wall structure features of patients with suspected CaW. METHODS: Retrospective analysis of patients with suspected CaW who underwent digital subtraction angiography (DSA) coupled with OCT of the carotid bulb from 2018 to 2021 in a single comprehensive stroke center. RESULTS: Sixteen patients were included. The median age was 56 years (IQR 46-61) and 50% were women. OCT corroborated the diagnosis of CaW in 12/16 (75%) cases and ruled it out in 4/16 (25%) patients in whom atherosclerotic disease was demonstrated. Five of the 12 lesions demonstrated a thick fibrotic ridge consistent with CaW but also showed atherosclerotic changes in the vicinity of the carotid bulb (labeled as "CaW+"). In 4/16 (25%) patients, microthrombi adhered to the vessel wall were noted on OCT (inside the CaW pocket or just distal to the web), none of which were observed on CT angiography or DSA. CONCLUSIONS: OCT may have value as a complementary imaging tool in the investigation of patients with suspected CaW and atypical morphological features. Further studies are warranted.

Intracranial stenting versus aggressive medical therapy for symptomatic intracranial stenosis: A meta-analysis of multicenter randomized controlled trials and an expert assessment of the current data.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is associated with high risk of recurrent strokes despite best medical management (MM). We aimed to synthesize the evidence from randomized studies comparing intracranial stenting plus MM versus MM alone. METHODS: Comprehensive search of MEDLINE database was performed until May 2023. The data were extracted and pooled as risk ratio (RR) with 95% confidence interval (95% CI). RESULTS: We included three multicenter RCTs totaling 919 patients. As compared to MM alone, intracranial stenting was associated with statistically significant higher risks of any stroke or death (RR = 2.93, 95%CI [1.80-4.78], p < 0.0001), stroke in the same territory of qualifying artery (RR = 3.56, 95%CI [1.97-6.44], p < 0.0001), any ischemic stroke (RR = 2.22, 95%CI [1.27-3.87], p = 0.005), hemorrhagic stroke (RR = 13.49, 95%CI [2.59-70.15], p = 0.0002), and death (RR = 5.43, 95%CI [1.21-24.40], p = 0.003) within 30 days of randomization. There was a persistent lack of benefit and signals of harm at the last follow up within 1-3 years: any stroke or death (RR = 1.57, 95%CI [0.92-2.67], p = 0.1), stroke in the same territory of qualifying artery (RR = 1.84, 95%CI [0.97-3.50], p = 0.06), any ischemic stroke (RR = 1.56, 95%CI [1.11-2.20], p = 0.01), death (RR = 1.61, 95%CI [0.77-3.38], p = 0.2). The cumulative rate of stroke in the same territory of qualified artery with MM alone within the 1-3-year follow up was lower than expected, with only 47 out of the 450 (10.4%) MM alone patients suffering such events. CONCLUSION: The findings from this meta-analysis do not recommend stenting as a routine care option for the broader symptomatic ICAS patient population. The rates of recurrent strokes in ICAS patients managed with aggressive MM do not seem to be as high as anticipated. Additional multicenter RCTs including safer devices, larger sample sizes, and patients at higher risk of recurrent events are warranted.

Clot composition and recanalization outcomes in mechanical thrombectomy.

BACKGROUND: Mechanical thrombectomy (MT) has become standard for large vessel occlusions, but rates of complete recanalization are suboptimal. Previous reports correlated radiographic signs with clot composition and a better response to specific techniques. Therefore, understanding clot composition may allow improved outcomes. METHODS: Clinical, imaging, and clot data from patients enrolled in the STRIP Registry from September 2016 to September 2020 were analyzed. Samples were fixed in 10% phosphate-buffered formalin and stained with hematoxylin-eosin and Martius Scarlett Blue. Percent composition, richness, and gross appearance were evaluated. Outcome measures included the rate of first-pass effect (FPE, modified Thrombolysis in Cerebral Infarction 2c/3) and the number of passes. RESULTS: A total of 1430 patients of mean±SD age 68.4±13.5 years (median (IQR) baseline National Institutes of Health Stroke Scale score 17.2 (10.5-23), IV-tPA use 36%, stent-retrievers (SR) 27%, contact aspiration (CA) 27%, combined SR+CA 43%) were included. The median (IQR) number of passes was 1 (1-2). FPE was achieved in 39.3% of the cases. There was no association between percent histological composition or clot richness and FPE in the overall population. However, the combined technique resulted in lower FPE rates for red blood cell (RBC)-rich (P<0.0001), platelet-rich (P=0.003), and mixed (P<0.0001) clots. Fibrin-rich and platelet-rich clots required a higher number of passes than RBC-rich and mixed clots (median 2 and 1.5 vs 1, respectively; P=0.02). CA showed a trend towards a higher number of passes with fibrin-rich clots (2 vs 1; P=0.12). By gross appearance, mixed/heterogeneous clots had lower FPE rates than red and white clots. CONCLUSIONS: Despite the lack of correlation between clot histology and FPE, our study adds to the growing evidence supporting the notion that clot composition influences recanalization treatment strategy outcomes.

Changes in the care of acute cerebrovascular and cardiovascular conditions during the first year of the covid-19 pandemic in 746 hospitals in the USA: retrospective analysis.

Objective: To measure the impact of the covid-19 pandemic on admissions to hospital and interventions for acute ischemic stroke and acute myocardial infarction. Design: A retrospective analysis. Setting: 746 qualifying hospitals in the USA from the Premier Healthcare Database. Participants: Patients aged 18 years and older who were admitted to hospital with a primary diagnosis of acute ischemic stroke or acute myocardial infarction between 1 March 2019 and 28 February 2021. Main outcome measures: Relative changes in volumes were assessed for acute ischemic stroke and acute myocardial infarction hospital admissions as well as intravenous thrombolysis, mechanical thrombectomy, and percutaneous coronary intervention (overall and for acute myocardial infarction only) across the first year of the pandemic versus the prior year. Mortality in hospital and length of stay in hospital were also compared across the first year of the pandemic versus the corresponding period the year prior. These metrics were explored across the different pandemic waves. Results: Among 746 qualifying hospitals, admissions to hospital were significantly reduced after the covid-19 pandemic compared with before the pandemic for acute ischemic stroke (-13.59% (95% confidence interval-13.77% to -13.41%) and acute myocardial infarction (-17.20% (-17.39% to -17.01%)), as well as intravenous thrombolysis (-9.47% (-9.99% to -9.02%)), any percutaneous coronary intervention (-17.89% (-18.06% to -17.71%)), and percutaneous coronary intervention for acute myocardial infarction (-14.36% (-14.59% to -14.12%)). During the first year of the pandemic versus the previous year, the odds of mortality in hospital for acute ischemic stroke were 9.00% higher (3.51% v 3.16%; ratio of the means 1.09 (95% confidence interval (1.03 to 1.15); P=0.0013) and for acute myocardial infarction were 18.00% higher (4.81% v 4.29%; ratio of the means 1.18 (1.13 to 1.23); P<0.0001). Conclusions: We observed substantial decreases in admissions to hospital with acute ischemic stroke and acute myocardial infarction, but an increase in mortality in hospital throughout the first year of the pandemic. Public health interventions are needed to prevent these reductions in future pandemics.

From therapeutic nihilism to armamentarium: A meta-analysis of randomized clinical trials assessing safety and efficacy of endovascular therapy for acute large ischemic strokes.

BACKGROUND: Three recent randomized clinical trials (RCTs) investigated the potential benefit of endovascular therapy (EVT) in acute ischemic stroke patients presenting with large infarcts. We aimed to confirm the safety and efficacy of EVT in patients presenting with large infarcts and provide more precise estimations of the treatment effects using study-level meta-analysis. METHODS: Comprehensive search of MEDLINE database through PubMed till February 2023 was performed including RCTs only. The data were then extracted from the selected studies and pooled as risk ratio (RR) with 95% confidence interval (95% CI). RESULTS: There were a total of 1005 patients across the three qualifying RCTs. Regarding the functional outcomes assessed by modified Rankin Scale (mRS) score, the analyzed data demonstrated statistically significant differences in favor of thrombectomy for both independent ambulatory status (mRS 0-3: RR = 1.78, 95% CI [1.28, 2.48], p = 0.0006) and functional independence (mRS 0-2: RR = 2.54, 95% CI [1.85, 3.48], p < 0.001). The analyzed data did not demonstrate any statistically significant differences between EVT and medical management alone in terms of 90-day mortality (RR = 0.95, 95% CI [0.78, 1.16], p = 0.61), symptomatic intracranial hemorrhage (RR = 1.83, 95% CI [0.95, 3.55], p = 0.07), and need for hemicraniectomy (RR = 1.22, 95% CI [0.43, 3.41], p = 0.71). CONCLUSION: This study confirms the benefit of EVT on functional outcomes of patients presenting with large ischemic infarcts without significant differences in the rates of symptomatic intracranial hemorrhage, hemicraniectomy, or 90-day mortality.

Characterizing Fast and Slow Progressors in Anterior Circulation Large Vessel Occlusion Strokes.

BACKGROUND AND PURPOSE: Infarct growth rate (IGR) in acute ischemic stroke is highly variable. We sought to evaluate impact of symptom-reperfusion time on outcomes in patients undergoing mechanical thrombectomy (MT). METHODS: A prospectively maintained database from January,2012-August,2020 was reviewed. All patients with isolated MCA-M1 occlusion who achieved complete reperfusion(mTICI2C-3), had a witnessed symptom onset and follow-up MRI were included. IGR was calculated as final infarct volume (FIV)(ml)/symptom onset to reperfusion time(hours) and was dichotomized according to the median value into slow-(SP) versus fast-progressors (FP). The primary analysis aimed to evaluate the impact of symptom-reperfusion time on 90-day mRS in SP and FP. Secondary analysis was performed to identify predictors of IGR. RESULTS: A total of 137 patients were eligible for analysis. Mean age was 63 ± 15.4 years and median IGR was 5.13ml/hour. SP(n = 69) had higher median ASPECTS, lower median rCBF<30% lesion volume, higher proportion of favorable collaterals and hypoperfusion intensity ratio (HIR)<0.4, higher minimal mean arterial blood pressure before reperfusion, and lower rates of general anesthesia compared to FP(n = 68). Symptom-reperfusion time was comparable between both groups. SP had higher rates of 90-day mRS0-2(71.9%vs.38.9%,aOR;7.226,95%CI[2.431-21.482],p < 0.001) and lower median FIV. Symptom-reperfusion time was associated with 90-day mRS0-2 in FP (aOR;0.541,95%CI[0.309-0.946],p = 0.03) but not in SP (aOR;0.874,95%CI[0.742-1.056],p = 0.16). On multivariable analysis, high ASPECTS and favorable collaterals in the NCCT/CTA model, and low rCBF<30% and HIR<0.4 in the CTP model were independent predictors of SP. CONCLUSIONS: The impact of symptom-reperfusion time on outcomes significantly varies across slow-versus fast-progressors. ASPECTS, collateral score, rCBF<30%, and HIR define stroke progression profile.

In Search of the Optimal Antithrombotic Regimen for Intracerebral Hemorrhage Survivors with Atrial Fibrillation.

Spontaneous intracerebral hemorrhage (ICH) constitutes 10-15% of all strokes, and is a significant cause of mortality and morbidity. Survivors of ICH, especially those with atrial fibrillation (AF), are at risk for both recurrent hemorrhagic and ischemic cerebrovascular events. A conundrum in the field of vascular neurology, neurosurgery, and cardiology has been the decision to initiate or resume versus withhold anticoagulation in survivors of ICH with AF. To initiate anticoagulation would decrease the risk of ischemic stroke but may increase the risk of hemorrhage. To withhold anticoagulation maintains a lower risk of hemorrhage but does not decrease the risk of ischemic stroke. In this narrative review, we discuss the evidence for and against the use of antithrombotics in ICH survivors with AF, focusing on recently completed and ongoing clinical trials.

Direct to Angiosuite Versus Conventional Imaging in Suspected Large Vessel Occlusion: A Systemic Review and Meta-Analysis.

BACKGROUND: There is growing evidence to suggest that the direct transfer to angiography suite (DTAS) approach for patients with suspected large vessel occlusion stroke potentially requiring mechanical thrombectomy shortens treatment times and improves outcomes compared with the direct transfer to conventional imaging (DTCI) model. Therefore, we conducted this meta-analysis to compare both approaches to build more concrete evidence to support this innovative treatment concept. METHODS: All potentially relevant studies published in 4 electronic databases/search engines (PubMed, Web of Science, Cochrane Library, and Scopus) from inception to November 2021 were reviewed. Eligible studies were included if they enrolled ≥10 patients in both groups, were published in English, and reported baseline and procedural characteristics and outcomes. Relevant data were then extracted and analyzed. RESULTS: Among 4514 searched studies, 7 qualified for the analysis with 1971 patients (DTAS=675, DTCI=1296). Times from door to puncture (mean difference, -30.76 minutes [95% CI, -43.70 to -17.82]; P<0.001) as well as door-to-reperfusion (mean difference=-33.24 minutes [95% CI, -51.82 to -14.66]; P<0.001) were significantly shorter and the rates of functional independence (modified Rankin Scale score, 0-2: risk ratio [RR], 1.25 [95% CI, 1.02-1.53]; P=0.03) at 90 days were higher in the DTAS versus the DTCI approach. There was no difference across the DTAS and DTCI groups in terms of the rates of successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2B-3: RR, 1.03 [95% CI, 0.95-1.12]; P=0.42), near-complete/full reperfusion (modified Thrombolysis in Cerebral Infarction 2C-3: RR, 0.89 [95% CI, 0.74-1.08]; P=0.23), symptomatic intracranial hemorrhage (RR, 0.81 [95% CI, 0.56-1.17]; P=0.26), or fair outcomes (modified Rankin Scale score, 0-3: RR, 1.14 [95% CI, 0.88-1.47]; P=0.32) or mortality (RR, 0.98 [95% CI, 0.67-1.44]; P=0.93) at 90 days. Subgroup analysis showed no significant difference in 90-day functional independence across approaches in transfer patients (RR, 1.20 [95% CI, 0.96-1.51]; P=0.11). CONCLUSIONS: Our meta-analysis showed that the DTAS approach seems to be associated with improved time metrics and functional outcomes with comparable safety to the DTCI approach. Ongoing multicenter randomized clinical trials will hopefully provide more definite data about this promising approach.

Impact of Intravenous Alteplase Door-to-Needle Times on 2-Year Mortality in Patients With Acute Ischemic Stroke.

Objective: We sought to determine whether administration of Intravenous Thrombolysis (IVT) to patients with Acute Ischemic Stroke (AIS) within 60 min from hospital arrival is associated with lower 2-year mortality. Methods: This retrospective study was conducted among patients receiving IVT in hospitals participating in the Georgia Coverdell Acute Stroke Registry (GCASR) from January 1, 2008 through June 30, 2018. Two-year mortality data was obtained by linking the 2008-2018 Georgia Discharge Data System data and the 2008-2020 Georgia death records. We analyzed the study population in two groups based on the time from hospital arrival to initiation of IVT expressed as Door to Needle time (DTN) in a dichotomized (DTN ≤ 60 vs. > 60 min) fashion. Results: The median age of patients was 68 years, 49.4% were females, and the median NIHSS was 9. DTN ≤60 min was associated with lower 30-day [odds ratio (OR), 0.62; 95% CI, 0.52-0.73; P < 0.0001], 1-year (OR, 0.71; 95% CI, 0.61-0.83; P < 0.0001) and 2-year (OR, 0.76; 95% CI, 0.65-0.88; P = 0.001) mortality as well as lower rates of sICH at 36 h (OR, 0.57; 95% CI, 0.43-0.75; P = 0.0001), higher rates of ambulation at discharge (OR, 1.38; 95% CI, 1.25-1.53; P < 0.0001) and discharge to home (OR, 1.36; 95% CI, 1.23-1.52; P < 0.0001). Conclusion: Faster DTN in patients with AIS was associated with lower 2-year mortality across all age, gender and race subgroups. These findings reinforce the need for intensifying quality improvement measures to reduce DTN in AIS patients.

Reliability of Field Assessment Stroke Triage for Emergency Destination Scale Use by Paramedics: Mobile Stroke Unit First-Year Experience.

Background and Purpose: Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scale is a helpful tool to triage patients with stroke in the field. However, data on its reliability in the prehospital setting are lacking. We aim to test the reliability of FAST-ED scale when used by paramedics in a mobile stroke unit covering a metropolitan area. Methods: As part of standard operating mobile stroke unit procedures, paramedics initially evaluated patients. If the event characterized a stroke alert, the FAST-ED score was determined by the paramedic upon patient contact (in-person) and then independently by a vascular neurologist (VN) immediately after paramedic evaluation (remotely/telemedicine). This allowed testing of the interrater agreement of the FAST-ED scoring performance between on-site prehospital providers and remotely located VN. Results: Of a total of 238 patients transported in the first 15 months of the mobile stroke unit's activity, 173 were included in this study. Median age was 63 (interquartile range, 55.5­75) years and 52.6% were females. A final diagnosis of ischemic stroke was made in 71 (41%), transient ischemic attack in 26 (15%), intracranial hemorrhage in 15 (9%), whereas 61 (35%) patients were stroke mimics. The FAST-ED scores matched perfectly among paramedics and VN in 97 (56%) instances, while there was 0 to 1-point difference in 158 (91.3%), 0 to 2-point difference in 171 (98.8%), and 3 or more point difference in 2 (1.1%) patients. The intraclass correlation between VN and paramedic FAST-ED scores showed excellent reliability, intraclass correlation coefficient 0.94 (95% CI, 0.92­0.96; P<0.001). When VN recorded FAST-ED score ≥3, paramedics also scored FAST-ED≥3 in majority of instances (63/71 patients; 87.5%). A large vessel occlusion was identified in 16 (9.2%) patients; 13 occlusions were identified with a FAST-ED≥3 while 3 were missed. All of the latter patients had National Institutes of Health Stroke Scale score ≤5. Conclusions: We demonstrate excellent reliability of FAST-ED scale performed by paramedics when compared with VN, indicating that it can be accurately performed by paramedics in the prehospital setting.

Safety of Ticagrelor in Moderate and Severe Acute Ischemic Stroke: A Single-Center Retrospective Review.

OBJECTIVES: Ticagrelor may be superior to aspirin after minor ischemic stroke or TIA, particularly in patients with symptomatic atherosclerotic disease. However, there may be an increased risk of intracerebral hemorrhage in patients with moderate to severe ischemic stroke, and ticagrelor has not been studied in this patient population. Therefore, we sought to evaluate the safety of ticagrelor after moderate or severe ischemic stroke. MATERIALS AND METHODS: Retrospective chart review of all patients admitted with acute ischemic stroke and NIHSS 6 or greater who were discharged on ticagrelor between January 2016 and December 2019. Patients who underwent angioplasty, stenting or carotid revascularization during the hospitalization were excluded. RESULTS: Of 183 patients discharged on ticagrelor, 61 patients were included. Median age was 61 (IQR 52-68); 33 (54%) patients were men. Median NIHSS was 11 (IQR 8-15). Fourteen (23%) patients received IV alteplase and 35 (57%) patients received mechanical thrombectomy. Stroke mechanism was large artery atherosclerosis in 53 (87%) of patients, of which 40 (71%) were deemed intracranial atherosclerosis. Final infarct volume was greater than 10 mL in 32 (52%) patients. Follow-up information was available for 53 (87%) patients; median length of follow-up was 3 (IQR 2-6) months. Six (10%) patients experienced recurrent ischemic stroke. No patients experienced symptomatic intracerebral hemorrhage after initiation of ticagrelor. One (2%) patient experienced major bleeding. CONCLUSIONS: This study provides preliminary evidence supporting the potential safety of ticagrelor following moderate or severe acute ischemic stroke. These findings support the need for future prospective studies.