Case series of intravenous thrombolysis for acute ischemic stroke in confirmed COVID-19 patients: single-centre experience

Background Coronavirus disease 2019 (COVID-19) not only caused a large surge of respiratory infections, it also had a potential association with and increases the risk of stroke. The pandemic has certainly provided new challenges and opportunities in the management of acute ischemic stroke (AIS); however, data regarding outcomes of intravenous tissue plasminogen activator (IV TPA) administration in stroke patients with COVID-19 remains limited. Case presentation Three AIS patients with confirmed COVID-19 treated using IV tPA. One case had excellent outcome, while the other cases showed unfavorable results. The risk–benefit ratio of IV TPA in COVID-19 remains unclear. Conclusion In this article, we discuss the possible explanation behind these different outcomes. Although IV tPA could not cure COVID-19, we suggest that its administration should not be delayed in AIS patients with COVID-19.

Exploring the Unmet Need in Acute Ischemic Stroke Patients Not Treated With Intravenous Alteplase: The Get With The Guidelines‐Stroke Registry

BACKGROUND Early administration of intravenous tissue plasminogen activator (IV alteplase) improves functional outcomes in patients with acute ischemic stroke, yet many patients are not treated with IV alteplase. There is a need to understand the reasons for nontreatment and the short‐ and long‐term outcomes in this patient population. METHODS We analyzed patients ≥65 years old with a primary diagnosis of acute ischemic stroke presenting within 24 hours of time last known well (LKW) but not treated with IV alteplase from 1630 Get With The Guidelines‐Stroke hospitals in the United States between January 2016 and December 2016. We report clinical characteristics, reasons for withholding treatment, in‐hospital mortality, and 90‐day and 1‐year outcomes including costs, stratified by time from LKW to presentation (≤4.5, >4.5–6, and >6–24 hours). RESULTS Of 39 760 patients (median age 80 [25th–75th quartiles: 73–87], 56.7% female), 19 391 (48.8%) presented within 4.5 hours of LKW. In those with documented reasons for withholding IV alteplase, the most common reasons were rapid improvement of symptoms (3985/14 782, 27.0%) and mild symptoms (3791/14 782, 25.6%). In 1100 out of 1174 (93.7%) patients presenting in the >3.0‐ to 4.5‐hour time window, the most common reason for not treating was a delay in patient arrival. The most common discharge location for those presenting ≤4.5 hours since LKW was home (8660/19 391, 44.7%). The 90‐day mortality and readmission rates were 18.9% and 23.0% in those presenting ≤4.5 hours since LKW, 19.0% and 22.2% in those presenting between 4.5 and 6 hours, and 19.1% and 23.2% in those presenting between 6 and 24 hours. Median 90‐day total in‐hospital costs remained relatively high at $9471 (Q25–Q75: $5622–$21 356) in patients presenting ≤4.5 hours since LKW. CONCLUSIONS Patients within the Get With The Guidelines‐Stroke registry not treated with IV alteplase have a high risk of readmission and mortality and have high total in‐hospital and postdischarge costs. This study may inform future efforts to address the unmet need to improve the scope of IV alteplase delivery along with other aspects of acute ischemic stroke care and, consequently, outcomes in this patient population.

Mobile stroke care expedites intravenous thrombolysis and endovascular thrombectomy

BackgroundThe number of mobile stroke programmes has increased with evidence, showing they expedite intravenous thrombolysis. Outstanding questions include whether time savings extend to patients eligible for endovascular therapy and impact clinical outcomes.ObjectiveOur mobile stroke unit (MSU), based at an academic medical centre in upstate New York, launched in October 2018. We reviewed prospective observational data sets over 26 months to identify MSU and non-MSU emergency medical service (EMS) patients who underwent intravenous thrombolysis or endovascular thrombectomy for comparison of angiographic and clinical outcomes.ResultsOver 568 days in service, the MSU was dispatched 1489 times (2.6/day) and transported 300 patients (20% of dispatches). Intravenous tissue plasminogen activator (tPA) was administered to 57 MSU patients and the average time from 911 call-to-tPA was 42.5 min (±9.2), while EMS transported 73 patients who received tPA at 99.4 min (±35.7) (p<0.001). Seven MSU patients (12%) received tPA from 3.5 hours to 4.5 hours since last known well and would likely have been outside the window with EMS care. Endovascular thrombectomy was performed on 21 MSU patients with an average 911 call-to-groin puncture time of 99.9 min (±18.1), while EMS transported 54 patients who underwent endovascular thrombectomy (ET) at 133.0 min (±37.0) (p=0.0002). There was no difference between MSU and traditional EMS in modified Rankin score at 90-day clinic follow-up for patients undergoing intravenous thrombolysis or endovascular thrombectomy, whether assessed as a dichotomous or ordinal variable.ConclusionsMobile stroke care expedited both intravenous thrombolysis and endovascular thrombectomy. There is an ongoing need to show improved functional outcomes with MSU care.

Mechanical Thrombectomy With and Without Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis Using Nested Knowledge

Background: Mechanical thrombectomy (MT) is now the standard-of-care treatment for acute ischemic stroke (AIS) of the anterior circulation and may be performed irrespective of intravenous tissue plasminogen activator (IV-tPA) eligibility prior to the procedure. This study aims to understand better if tPA leads to higher rates of reperfusion and improves functional outcomes in AIS patients after MT and to simultaneously evaluate the functionality and efficiency of a novel semi-automated systematic review platform.Methods: The Nested Knowledge AutoLit semi-automated systematic review platform was utilized to identify randomized control trials published between 2010 and 2021 reporting the use of mechanical thrombectomy and IV-tPA (MT+tPA) vs. MT alone for AIS treatment. The primary outcome was the rate of successful recanalization, defined as thrombolysis in cerebral infarction (TICI) scores ≥2b. Secondary outcomes included 90-day modified Rankin Scale (mRS) 0–2, 90-day mortality, distal embolization to new territory, and symptomatic intracranial hemorrhage (sICH). A separate random effects model was fit for each outcome measure.Results: We subjectively found Nested Knowledge to be highly streamlined and effective at sourcing the correct literature. Four studies with 1,633 patients, 816 in the MT+tPA arm and 817 in the MT arm, were included in the meta-analysis. In each study, patient populations consisted of only tPA-eligible patients and all imaging and clinical outcomes were adjudicated by an independent and blinded core laboratory. Compared to MT alone, patients treated with MT+tPA had higher odds of eTICI ≥2b (OR = 1.34 [95% CI: 1.10; 1.63]). However, there were no statistically significant differences in the rates of 90-day mRS 0-2 (OR = 0.98 [95% CI: 0.77; 1.24]), 90-day mortality (OR = 0.94 [95% CI: 0.67; 1.32]), distal emboli (OR = 0.94 [95% CI: 0.25; 3.60]), or sICH (OR = 1.17 [95% CI: 0.80; 1.72]).Conclusions: Administering tPA prior to MT may improve the rates of recanalization compared to MT alone in tPA-eligible patients being treated for AIS, but a corresponding improvement in functional and safety outcomes was not present in this review. Further studies looking at the role of tPA before mechanical thrombectomy in different cohorts of patients could better clarify the role of tPA in the treatment protocol for AIS.

Quantification of clot spatial heterogeneity and its impact on thrombectomy

BackgroundCompositional and structural features of retrieved clots by thrombectomy can provide insight into improving the endovascular treatment of ischemic stroke. Currently, histological analysis is limited to quantification of compositions and qualitative description of the clot structure. We hypothesized that heterogeneous clots would be prone to poorer recanalization rates and performed a quantitative analysis to test this hypothesis.MethodsWe collected and did histology on clots retrieved by mechanical thrombectomy from 157 stroke cases (107 achieved first-pass effect (FPE) and 50 did not). Using an in-house algorithm, the scanned images were divided into grids (with sizes of 0.2, 0.3, 0.4, 0.5, and 0.6 mm) and the extent of non-uniformity of RBC distribution was computed using the proposed spatial heterogeneity index (SHI). Finally, we validated the clinical significance of clot heterogeneity using the Mann–Whitney test and an artificial neural network (ANN) model.ResultsFor cases with FPE, SHI values were smaller (0.033 vs 0.039 for grid size of 0.4 mm, P=0.028) compared with those without. In comparison, the clot composition was not statistically different between those two groups. From the ANN model, clot heterogeneity was the most important factor, followed by fibrin content, thrombectomy techniques, red blood cell content, clot area, platelet content, etiology, and admission of intravenous tissue plasminogen activator (IV-tPA). No statistical difference of clot heterogeneity was found for different etiologies, thrombectomy techniques, and IV-tPA administration.ConclusionsClot heterogeneity can affect the clot response to thrombectomy devices and is associated with lower FPE. SHI can be a useful metric to quantify clot heterogeneity.

The History of Neurosurgical Management of Ischemic Stroke

Stroke remains a major public health issue and the second leading cause of death worldwide. The Hippocratic Corpus used the word apoplexy to describe a person collapsing while retaining pulse and respiration. This is believed to be the first written description of stroke. The theories of what caused stroke evolved over the years. When autopsies were performed stroke was attributed to emboli and thrombi formation. Carotid endarterectomies (CEA) were then performed for the treatment of stroke. Originally CEA were seen with skepticism but the North American Symptomatic Carotid Endarterectomy trial (NASCET) and the European Carotid Surgery trial (ECS) helped restore their efficacy in the management of ischemic stroke. A milestone in the management of ischemic stroke was the use of intravenous tissue plasminogen activator (tPA). Secondary to the limitations of the use of tPA other avenues were sought which included intraarterial recombinant prourokinase and mechanical thrombectomy. The field of mechanical thrombectomy continues to be rapidly changing and evolving. Various randomized controlled trials and meta-analysis have been conducted in order to evaluate who will benefit from mechanical thrombectomies, the timing, the best device to use and the role of combining this intervention with the administration of intravenous tPA.

Effect of COVID‐19 on Acute Ischemic Stroke Hospitalizations and Treatments: Population‐Level Experience

BACKGROUND Several studies have reported changes in the volume and type of acute ischemic stroke (AIS) hospitalizations during the early stage of the COVID‐19 pandemic. However, population‐based assessments, which include lower volume centers and more comprehensive geographic areas, are limited. Here, we evaluate an entire state‐level experience during the first peak COVID pandemic and compare against a 1‐year prior historical period. METHODS We conducted a retrospective population‐based study using the Texas Inpatient Public Use Data File, capturing all discharges from hospitals in the State of Texas, except federal hospitals. AIS admission volumes, patient characteristics, proportions of large vessel occlusion (LVO), admission rates to comprehensive stroke centers, use of intravenous tissue plasminogen activator and endovascular treatment, and patient outcomes were compared between April 1, 2019 and June 30, 2019 (historical control period) and April 1, 2020 and June 30, 2020 (pandemic period). RESULTS A total of 9277 hospitalized AIS cases were identified during the pandemic period, a decrease of 12% (10 524) compared with the control period. Cases without LVO dropped by 15%, whereas LVO cases dropped by only 5%. There were no significant differences in age or race and ethnicity of patients. While admission rates to comprehensive stroke centers (39.6% versus 39.4%, P =0.81) and endovascular treatment use in LVO (17.0% versus 16.3%, P =0.45) were not different between the 2 periods, the use of intravenous tissue plasminogen activator (15.0% versus 13.6%, relative risk [RR], 0.90; 95% CI, 0.84–0.97; P =0.004) decreased. The percentage of patients who died or were discharged to hospice increased from 7.2% to 8.25% (RR, 1.17; 95% CI. 1.06–1.29; P =0.001). CONCLUSIONS This study from a statewide population‐level analysis confirms smaller hospital‐based cohorts observing decreasing numbers of milder AIS admissions, and lower use of thrombolysis. Although LVO admissions and endovascular treatment use were largely unchanged, these findings suggest missed treatment opportunities for patients with AIS in the pandemic.

Mechanical thrombectomy versus intravenous alteplase alone in acute isolated posterior cerebral artery occlusion: a systematic review

BackgroundAcute isolated posterior cerebral artery occlusions (aPCAOs) were excluded or under-represented in major randomized trials of mechanical thrombectomy (MT). The benefit of MT in comparison to intravenous tissue plasminogen activator (alteplase; IV-tPA) alone in these patients remains controversial and uncertain.MethodsWe performed a systematic search of PubMed, MEDLINE, and EMBASE databases for articles comparing MT with or without bridging IV-tPA and IV-tPA alone for aPCAO using keywords (‘posterior cerebral artery’, ‘thrombolysis’ and ‘thrombectomy’) with Boolean operators. Extracted data from patients reported in the studies were pooled into groups (MT vs IV-tPA alone) for comparison. Estimated rates for favorable outcome (modified Rankin scale score 0–2), symptomatic intracranial hemorrhage (sICH), and mortality were extracted.ResultsSeven articles (201 MT patients, 64 IV-tPA) were included, all retrospective. There was no statistically significant difference between pooled groups in median age, median presentation National Institutes of Health Stroke Scale (NIHSS) score, PCAO segment, and median time from symptom onset to puncture or needle. The recanalization rate was significantly higher in the MT group than the IV-tPA group (85.6% vs 53.1%, p<0.00001). Odds ratios for favorable outcome (OR 1.5, 95% CI 0.8 to 2.5), sICH (OR 1.1, 95% CI 0.2 to 5.5), and mortality (OR 1.4, 95% CI 0.5 to 3.6) did not significantly favor any modality.ConclusionsWe found no significant differences in odds of favorable outcome, sICH, and mortality in MT and IV-tPA in comparable aPCAO patients, despite superior MT recanalization rates. Equipoise remains regarding the optimal treatment modality for these patients.

Intravenous Thrombolysis for a Stroke Mimic Patient

The authors present the case of a young woman on phentermine and herbal supplements who presented as an acute stroke alert with right-sided facial droop and numbness. She was treated acutely with intravenous tissue plasminogen activator (tPA). However, the workup did not reveal any evidence of cerebrovascular disease or cerebral infarct. The authors discuss plausible stroke mimics and the safety of administering tPA to such patients.

Intracranial non-occlusive intraluminal thrombus may indicate underlying etiology of large vessel occlusion in patients undergoing endovascular therapy

BackgroundThe underlying etiology of intracranial non-occlusive intraluminal thrombus (iNOT) remains unknown. This study aimed to investigate whether the presence of iNOT can indicate the underlying etiology of large vessel occlusion (LVO) in patients undergoing endovascular therapy (EVT).MethodsAmong patients who underwent EVT at three comprehensive stroke centers, we included those with intracranial LVO in the anterior circulation. The presence of iNOT was determined by pretreatment DSA. We investigated the association between iNOT and intracranial atherosclerotic stenosis (ICAS) related LVO.ResultsOf 546 patients, 44 (8.1%) had iNOT. Patients with iNOT were younger, had less hypertension, atrial fibrillation, and a history of antiplatelet use. In addition, the involvement of the M1 segment of the middle cerebral artery (MCA) was more frequent. However, they had a lower National Institutes of Health Stroke Scale (NIHSS) score on admission and longer onset to recanalization time compared with patients with no iNOT. In a logistic regression model adjusting for age, sex, atrial fibrillation, smoking, prior antiplatelet and anticoagulant use, intravenous tissue plasminogen activator, NIHSS on admission, number of technical trials, intraprocedural re-occlusion, and the location of LVO (p<0.10 in the univariate analysis), the presence of iNOT was significantly associated with ICAS related LVO (adjusted OR 3.04; 95% CI 1.33 to 6.90; p=0.007).ConclusionsThe presence of iNOT may reflect an underlying ICAS related LVO in patients undergoing EVT.