The current European Stroke Organisation expedited recommendation on tenecteplase (TNK) for acute ischemic stroke (AIS) advocates that TNK 0.25 mg/kg can be used alternatively to alteplase (tissue plasminogen activator [TPA]) for AIS of <4.5 hours duration, based on a meta-analytical approach establishing noninferiority. Since the publication of these guidelines, 4 additional randomized controlled clinical trials (RCTs) have provided further insight. We conducted an updated systematic review and meta-analysis including all available RCTs that investigated efficacy and safety of TNK 0.25 mg/kg compared with TPA for the treatment of AIS within 4.5 hours of onset. The primary outcome was defined as the excellent functional outcome at 3 months (modified Rankin Scale [mRS] score 0-1), whereas good functional outcome (mRS score 0-2), reduced disability at 3 months (≥1-point reduction across all mRS scores), symptomatic intracranial hemorrhage (sICH), and 3-month mortality were evaluated as secondary outcomes. Pooled estimates were calculated with random-effects model. A prespecified subgroup analysis was performed stratifying for TNK formulation, that is, original TNK vs biocopy: recombinant human TNK tissue-type plasminogen activator that is available in China and has a different production process. Eleven RCTs were included comprising a total of 3,788 patients treated with TNK vs 3,757 patients treated with TPA. TNK was associated with higher likelihood of excellent functional outcome (risk ratio [RR] 1.05, 95% CI 1.01-1.10; p = 0.012; I² = 0%; risk difference 2.95%; 95% CI 0.76%-5.14%; p = 0.008; I² = 0%) and reduced disability at 3 months (common odds ratio 1.10, 95% CI 1.01-1.19; p = 0.034; I² = 0%) compared with TPA while good functional outcome (RR 1.03, 95% CI 0.99-1.07; p = 0.142; I² = 28%) was similar between the groups. Regarding safety outcomes, similar rates of sICH (RR 1.12, 95% CI 0.83-1.53; p = 0.456; I² = 0%) and 3-month mortality (RR 0.97, 95% CI 0.82-1.15; p = 0.727; I² = 12%) were observed. When stratified for TNK regimen (original vs biocopy), statistical significance in achieving an excellent functional outcome at 3 months was retained for the original TNK (RR 1.05, 95% CI 1.00-1.10; p = 0.044; I² = 0%). The updated meta-analysis confirms similar safety between TNK 0.25 mg/kg and TPA, while showing that TNK is superior to TPA regarding excellent functional outcome and reduced disability at 3 months. These findings support transitioning to TNK in clinical practice.

BACKGROUND AND PURPOSE: Transcranial Doppler is a useful ancillary test for brain death confirmation because it is safe, noninvasive, and done at the bedside. Transcranial Doppler confirms brain death by evaluating cerebral circulatory arrest. Case series studies have generally reported good correlations between transcranial Doppler confirmation of cerebral circulatory arrest and clinical confirmation of brain death. The purpose of this study is to evaluate the utility of transcranial Doppler as an ancillary test in brain death confirmation. MATERIALS AND METHODS: We conducted a systematic review of the literature and a diagnostic test accuracy meta-analysis to compare the sensitivity and specificity of transcranial Doppler confirmation of cerebral circulatory arrest, by using clinical confirmation of brain death as the criterion standard. RESULTS: We identified 22 eligible studies (1671 patients total), dating from 1987 to 2014. Pooled sensitivity and specificity estimates from 12 study protocols that reported data for the calculation of both values were 0.90 (95% CI, 0.87–0.92) and 0.98 (95% CI, 0.96–0.99), respectively. Between-study differences in the diagnostic performance of transcranial Doppler were found for both sensitivity (I² = 76%; P < .001) and specificity (I² = 74.3%; P < .001). The threshold effect was not significant (Spearman r = −0.173; P = .612). The area under the curve with the corresponding standard error (SE) was 0.964 ± 0.018, while index Q test ± SE was estimated at 0.910 ± 0.028. CONCLUSIONS: The results of this meta-analysis suggest that transcranial Doppler is a highly accurate ancillary test for brain death confirmation. However, transcranial Doppler evaluates cerebral circulatory arrest rather than brain stem function, and this limitation needs to be taken into account when interpreting the results of this meta-analysis.

Ischemic strokes related to atrial fibrillation are highly prevalent, presenting with severe neurologic syndromes and associated with high risk of recurrence. Although advances have been made in both primary and secondary stroke prevention for patients with atrial fibrillation, the long-term risks for stroke recurrence and bleeding complications from antithrombotic treatment remain substantial. We summarize the major advances in stroke prevention for patients with atrial fibrillation during the past 30 years and focus on novel diagnostic and treatment approaches currently under investigation in ongoing clinical trials. Non–vitamin K antagonist oral anticoagulants have been proven to be safer and equally effective compared with warfarin in stroke prevention for patients with nonvalvular atrial fibrillation. Non–vitamin K antagonist oral anticoagulants are being investigated for the treatment of patients with atrial fibrillation and rheumatic heart disease, for the treatment of patients with recent embolic stroke of undetermined source and indirect evidence of cardiac embolism, and in the prevention of vascular-mediated cognitive decline in patients with atrial fibrillation. Multiple clinical trials are assessing the optimal timing of non–vitamin K antagonist oral anticoagulant initiation after a recent ischemic stroke and the benefit:harm ratio of non–vitamin K antagonist oral anticoagulant treatment in patients with atrial fibrillation and history of previous intracranial bleeding. Ongoing trials are addressing the usefulness of left atrial appendage occlusion in both primary and secondary stroke prevention for patients with atrial fibrillation, including those with high risk of bleeding. The additive value of prolonged cardiac monitoring for subclinical atrial fibrillation detection through smartphone applications or implantable cardiac devices, together with the optimal medical management of individuals with covert paroxysmal atrial fibrillation, is a topic of intensive research interest. Colchicine treatment and factor XIa inhibition constitute 2 novel pharmacologic approaches that might provide future treatment options in the secondary prevention of cardioembolic stroke attributable to atrial fibrillation.

Vertebral artery hypoplasia is not currently considered an independent risk factor for stroke. Emerging evidence suggest that vertebral artery hypoplasia may contribute to posterior circulation ischemic events, especially when other risk factors coexist. In the present literature review, we present published data to discuss the relationship between a hypoplastic vertebral artery and posterior circulation cerebral ischemia. Despite difficulties and controversies in the accurate definition and prevalence estimation of vertebral artery hypoplasia, ultrasound studies reveal that the reduced blood flow observed ipsilateral to the hypoplastic vertebral artery may result in local cerebral hypoperfusion and subsequent focal neurological symptomatology. That risk of cerebral ischemia is related to the severity of the hypoplasia, suggesting that the smaller of paired arteries are more vulnerable to occlusion. Existing cohort studies further support clinical observations that hypoplastic vertebral artery enhances synergistically the vascular risk for posterior circulation ischemic events and is closely associated with both atherosclerotic and prothrombotic processes.