Thrombolysis for Cerebral Ischemia

The care for patients with acute ischemic stroke has been revolutionized by the clinical application of fibrinolysis. Intravenous recombinant tissue plasminogen activator (rt-PA) has been proven to improve functional outcomes following acute ischemic stroke and can be administered to a select group of patients up to 4.5 h after symptom onset. Time from symptom onset to thrombolysis is the most important determinant of the success of treatment, with greatest efficacy if given within 90 min. Hospitals should implement standardized processes and protocols for acute stroke to guide immediate patient assessment, brain imaging, drug administration, and post-thrombolysis care. In this article we review the clinical application of thrombolysis, care of acute stroke patients, current evidence regarding fibrinolysis, and future direction of penumbral imaging to select candidates for reperfusion therapies

A Disclosure About Death Disclosure: Variability in Circulatory Death Determination

Introduction. Circulatory-respiratory death declaration is a common duty of physicians, but little is known about the amount of education and physician practice patterns in completing this examination. Methods. We conducted an online survey of physicians evaluating the rate of formal training and specific examination techniques used in the pronouncement of circulatory-respiratory death. Data, including level of practice, training received in formal death declaration, and examination components were collected. Results. Respondents were attending physicians (52.4%), residents (30.2%), fellows (10.7%), and interns (6.7%). The majority of respondents indicated they had received no formal training in death pronouncement, however, most reported self-perceived competence. When comparing examination components used by our cohort, 95 different examination combinations were used for death pronouncement. Conclusions. Formal training in death pronouncement is uncommon and clinical practice varies. Implementation of formal training and standardization of the examination are necessary to improve physician competence and reliability in death declarations

Cardioembolic but Not Other Stroke Subtypes Predict Mortality Independent of Stroke Severity at Presentation

Introduction. Etiology of acute ischemic stroke (AIS) is known to significantly influence management, prognosis, and risk of recurrence. Objective. To determine if ischemic stroke subtype based on TOAST criteria influences mortality. Methods. We conducted an observational study of a consecutive cohort of patients presenting with AIS to a single tertiary academic center. Results. The study population consisted of 500 patients who resided in the local county or the surrounding nine-county area. No patients were lost to followup. Two hundred and sixty one (52.2%) were male, and the mean age at presentation was 73.7 years (standard deviation, SD = 14.3). Subtypes were as follows: large artery atherosclerosis 97 (19.4%), cardioembolic 144 (28.8%), small vessel disease 75 (15%), other causes 19 (3.8%), and unknown 165 (33%). One hundred and sixty patients died: 69 within the first 30 days, 27 within 31–90 days, 29 within 91–365 days, and 35 after 1 year. Low 90-, 180-, and 360-day survival was seen in cardioembolic strokes (67.1%, 65.5%, and 58.2%, resp.), followed for cryptogenic strokes (78.0%, 75.3%, and 71.1%). Interestingly, when looking into the cryptogenic category, those with insufficient information to assign a stroke subtype had the lowest survival estimate (57.7% at 90 days, 56.1% at 180 days, and 51.2% at 1 year). Conclusion. Cardioembolic ischemic stroke subtype determined by TOAST criteria predicts long-term mortality, even after adjusting for age and stroke severity

Prophylaxis of venous thrombosis in patients with spontaneous intracerebral bleeding

Spontaneous intracerebral haemorrhage (SIH) represents a severe clinical event that is associated with high rates of mortality and morbidity. Only a minority of SIH patients receive surgical treatment, whereas the majority are treated conservatively. Venous thromboembolism (VTE) is one of the most common complications in SIH patients and a potential cause of death. Because of the lack of adequate evidences from the literature, the risk to benefit ratio of pharmacologic prophylaxis of VTE, represented on the one hand by hematoma enlargement and/or rebleeding and on the other hand by an expected reduction of the risk of VTE, remains controversial. Mechanical prophylaxis is a potentially safer alternative, but the efficacy of this approach is uncertain. In the absence of specific clinical guidelines containing clear-cut recommendations, physicians have insufficient tools to assist their therapeutic decisions

Tenecteplase vs. alteplase for treatment of acute ischemic stroke: A systematic review and meta-analysis of randomized trials

Background and objectivesSeveral randomized controlled trials (RCTs) have compared tenecteplase to alteplase for treatment of acute ischemic stroke (AIS). Yet, there is no meta-analysis that includes the latest published RCTs of 2022. We sought to compare the safety and efficacy of tenecteplase vs. alteplase for the treatment of AIS through a meta-analysis of all published RCTs.MethodsA systematic literature review of the English language literature was conducted using PubMed, Web of Science, Scopus, and Embase. We included RCTs that focused on patients with AIS treated with tenecteplase and alteplase. Multiple reviewers screened through potential studies to identify the final papers included in our analysis. Following PRISMA guidelines, multiple authors extracted data to ensure accuracy. Data were pooled using a random-effects model.ResultsNine trials, with 3,706 patients, compared outcomes of patients treated with tenecteplase and alteplase for AIS. Both treatments resulted in comparable rates of modified Rankin Scale (mRS) 0–1 at 90 days (RR = 1.03; 95% CI = 0.97–1.10; P-value = 0.359) and mRS 0–2 at 90 days (RR = 1.03; 95% CI = 0.87–1.22; P-value = 0.749). There was no heterogeneity among included studies regarding mRS 0–1 rates (I2 = 26%; P-value = 0.211); however, there was significant heterogeneity in mRS 0–2 rates (I2 = 71%; P-value = 0.002). Similarly, rates of mortality (RR = 0.97; 95% CI = 0.81–1.16; P-value = 0.746) and symptomatic intracranial hemorrhage (sICH) rates (RR = 1.10; 95% CI = 0.75–1.61; P-value = 0.622) were comparable in both treatment groups. There was no significant heterogeneity among included studies in either mortality (I2 = 30%; P-value = 0.181) or sICH (I2 = 0%; P-value = 0.734) rates. Further analysis comparing dosing of tenecteplase (0.1, 0.25, 0.32, and 0.4 mg/kg) yielded no significant differences for any of the endpoints (mRS 0–1, mRS 0–2, sICH, and mortality) compared to alteplase.DiscussionBased on available evidence from completed RCTs, tenecteplase has proven similar safety and efficacy to alteplase for treatment of AIS

Silent cerebral infarcts in patients with atrial fibrillation: Clinical implications of an imaging-adjusted CHA2DS2-VASc score

Background: The CHA2DS2-VASc score does not include silent infarcts on neuroimaging in stroke risk estimation for patients with atrial fibrillation (AF). The inclusion of silent infarcts into CHA2DS2-VASc scoring and its impact on stroke prophylaxis recommendations in patients with AF has not been previously studied. The present study sought to quantify the prevalence of silent infarcts in patients with AF and describe potential changes in management based on magnetic resonance imaging (MRI) findings. Methods: Participants from the Mayo Clinic Study of Aging with AF and brain MRI were included. Silent infarcts were identified. “Standard” CHA2DS2-VASc scores were calculated for each subject based on clinical history alone and “imaging-adjusted” CHA2DS2-VASc scores based on evidence of cerebral infarction on MRI. Standard and imaging-adjusted scores were compared. Results: 147 participants (average age 77, 28% female) were identified with AF, MRI, and no clinical history of stroke. Overall, 41 (28%) patients had silent infarcts on MRI, corresponding with a 2-point increase in CHA2DS2-VASc score. Of these participants, only 39% (16/41) with silent infarct were on anticoagulation despite that standard CHA2DS2-VASc scores supportive of anticoagulation. After incorporating silent infarcts, 13% (19/147) would have an indication for periprocedural bridging compared to 0.6% (1/147) at baseline. Conclusions: Incorporation of silent infarcts into the CHA2DS2-VASc score may change the risk-benefit ratio of anticoagulation. It may also increase the number of patients who would benefit from periprocedural bridging. Future research should examine whether an anticoagulation strategy based on imaging-adjusted CHA2DS2-VASc scores could result in a greater reduction of stroke and cognitive decline

External validation of the Ottawa subarachnoid hemorrhage clinical decision rule in patients with acute headache ☆

We aim to externally validate the Ottawa subarachnoid hemorrhage (OSAH) clinical decision rule. This rule identifies patients with acute nontraumatic headache who require further investigation. We conducted a medical record review of all patients presenting to the emergency department (ED) with headache from January 2011 to November 2013. Per the OSAH rule, patients with any of the following predictors require further investigation: age 40 years or older, neck pain, stiffness or limited flexion, loss of consciousness, onset during exertion, or thunderclap. The rule was applied following the OSAH rule criteria. Patients were followed up for repeat visits within 7 days of initial presentation. Data were electronically harvested from the electronic medical record and manually abstracted from individual patient charts using a standardized data abstraction form. Calibration between trained reviewers was performed periodically. A total of 5034 ED visits with acute headache were reviewed for eligibility. There were 1521 visits that met exclusion criteria, and 3059 had headache of gradual onset or time to maximal intensity greater than or equal to 1 hour. The rule was applied to 454 patients (9.0%). There were 9 cases of subarachnoid hemorrhage (SAH), yielding an incidence of 2.0% (95% confidence interval [CI], 1.0%-3.9%) in the eligible cohort. The sensitivity for SAH was 100% (95% CI, 62.9%-100%); specificity, 7.6% (95% CI, 5.4%-10.6%); positive predictive value, 2.1% (95% CI 1.0%-4.2%); and negative predictive value, 100% (95% CI, 87.4%-100%). The OSAH rule was 100% sensitive for SAH in the eligible cohort. However, its low specificity and applicability to only a minority of ED patients with headache (9%) reduce its potential impact on practice