Tenecteplase (TNK) is a promising alternative to alteplase (ALT) as the thrombolytic agent for acute ischemic stroke (AIS). However, its clinical outcomes in certain populations remain unclear. This study aimed to compare the efficacy and safety among different doses of TNK in AIS patients. We searched PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Embase for studies comparing at least one dose of TNK to another dose of TNK or ALT 0.90 mg/kg. We conducted Bayesian network meta-analyses to estimate the relative risks (RRs) and 95% credible intervals (CrIs) for all outcomes using ALT 0.90 mg/kg as the reference. The treatments were ranked according to their surface under the cumulative ranking (SUCRA) values. We included 11 trials from 16 publications comprising 5423 participants. There were no significant differences between any doses of TNK and ALT for reperfusion, 3-month modified Rankin Score (mRS) 0-1 (rank 1st: TNK 0.25 mg/kg; SUCRA = 0.68), mRS 0-2 (rank 1st: TNK 0.25 mg/kg; SUCRA = 0.86), mortality (rank 1st: TNK 0.25 mg/kg; SUCRA = 0.82), intracranial hemorrhage (ICH) (rank 1st: TNK 0.25 mg/kg; SUCRA = 0.88), symptomatic ICH (sICH) (rank 1st: TNK 0.10 mg/kg; SUCRA = 0.70), and parenchymal hematoma (rank 1st: TNK 0.10 mg/kg; SUCRA = 0.68). TNK 0.40 mg/kg had a significantly higher sICH rate compared to TNK 0.25 mg/kg (RR = 2.39, 95% CrI = 1.00-7.92). Among elderly patients, TNK 0.25 mg/kg had a significantly lower rate of sICH than ALT 0.9 mg/kg (RR = 3.0 × 10^-13, 95% CrI = 3.4 × 10^-40-0.07). TNK has efficacy and safety outcomes comparable to those of ALT. TNK 0.25 mg/kg may be the optimal dose of TNK for patients with AIS.

Although most spontaneous intracerebral hemorrhages (ICHs) are due to cerebral small vessel diseases (SVDs), between 1 in 7 and 1 in 10 are due to a macrovascular cause. Rapid diagnosis has important therapeutic and prognostic implications but sometimes requires digital subtraction angiography (DSA), an invasive procedure which cannot be performed in all patients. MRI provides optimal sensitivity for markers of SVD but was not included in previous risk stratification scores. We aimed to create and validate a risk stratification score for macrovascular causes of ICH including MRI findings to guide diagnosis and further investigations. We pooled data from 2 large observational study cohorts (London/United Kingdom and Graz/Austria) of consecutive patients with ICH who had brain MRI and at least 1 angiographic modality within 90 days of symptom onset. The primary outcome was a macrovascular cause of ICH (arteriovenous malformation/dural arteriovenous fistula, aneurysm, cavernoma, or cerebral venous thrombosis), with the diagnosis based on neurovascular multidisciplinary meetings. Using lasso logistic regression, we built the MRI Assessment of the Causes of intRacerebral haemOrrhage (MACRO) score to assess the probability of a macrovascular cause. We performed internal validation using bootstrapping and external validation in an independent cohort (Bern/Switzerland). We included 1,043 patients with ICH (mean age 66 years, 42% female), 78 of whom had a macrovascular cause (7.5%). The final score includes age (0-39, 40-69, or ≥70), location of ICH (lobar, deep, or infratentorial), and SVD markers on MRI (≥1 microbleed, ≥1 lacune, presence of cortical superficial siderosis, or white matter hyperintensities using the Fazekas scale). The MACRO score showed an optimism-adjusted c-statistic of 0.90 (95% CI 0.88-0.93), superior to existing CT-based scores (p < 0.001). In external validation, the c-statistic was 0.87 (95% CI 0.80-0.94). MACRO scores ≥6 (59.5% of patients) indicated a very low risk of a macrovascular cause (0.2%), while scores ≤2 (9% of patients) indicated a high risk (48.9%). The MRI-based MACRO score shows excellent performance in predicting the likelihood of macrovascular causes of spontaneous intracerebral hemorrhage, making it useful in guiding further investigations. Important limitations include the observational study design and the performance of DSA in a minority of patients.

Intracranial hemorrhage (ICH) is the most devastating complication of recombinant tissue plasminogen activator (rtPA) treatment in acute ischemic stroke patients. Data on rtPA-associated asymptomatic ICH (aICH) are limited. To determine the incidence, risk factors, characteristics, management, and clinical outcome of rtPA-associated aICH. The data were retrieved from the Chiang Mai University Hospital Stroke Registry between 1995 and 2019. Consecutive ischemic stroke patients were included if they were 18 or older and received rtPA. Study outcomes were the incidence and characteristics of aICH, management, 90-day modified Rankin scale (mRS), National Institute of Health Stroke Scale (NIHSS), Barthel index, and all-cause mortality. Of 725 rtPA treated patients, 166 (16.0%, 95% confidence interval [CI] 13.4–18.9) had aICH, 50 (6.9%, 95% CI 5.2–9.0) had symptomatic ICH (sICH). Patients with aICH had more hemorrhagic infarctions (HI) compared to sICH (81.9% vs 2.0%, P-value < 0.001). Fresh Frozen Plasma and cryoprecipitate were the most common blood products used to reverse the anticoagulant effect in sICH. Craniotomy was performed in 1% and 60% of patients who had aICH and sICH. At 90 days, patients who had aICH had poorer clinical outcomes (mRS, NIHSS and Barthel index) as compared to those without ICH. Compared to non-ICH patients, aICH patients were associated with increased risk of 90-day mortality, the hazard ratio (HR), 3.7, 95% CI 1.6–8.9. The rtPA-associated aICH increased the risk of morbidity and mortality outcomes. Further treatment consensus, guideline generation, or clinical trials focusing on the treatment of rtPA-associated aICH may be required.

Purpose: Preseptal and pretarsal botulinum toxin injections are approved for treatment of hemifacial spasm and blepharospasm. However, the long-term data is limited. We compared the efficacy, safety, and costs between preseptal and pretarsal injection in hemifacial spasm and blepharospasm. Patients and Methods: The data were retrieved between 2011 and 2021. Consecutive hemifacial spasm and blepharospasm botulinum toxin patients were categorized as preseptal or pretarsal. Study outcomes were the difference in pre-and post-treatment modified Jankovic scale, self-reporting scales, time-related treatment, safety, and cost. Results: Of 152 botulinum toxin-injected patients, 117 (77.0%) patients had hemifacial spasm and 35 (33.0%) patients had blepharospasm. Analysis included data pertinent to 1665 injections in hemifacial spasm (920 preseptal and 745 pretarsal) and 527 injections in blepharospasm (210 preseptal and 317 pretarsal). The difference between pre-and post-treatment modified Jankovic scale was lower in the preseptal group than in the pretarsal group in both hemifacial spasm and blepharospasm (1.5± 0.8 vs 1.8± 0.6, P-value < 0.001 and 1.8± 0.8 vs 3.1± 0.9, P-value < 0.001). There was no difference in duration of maximum response in hemifacial spasm between groups, while the blepharospasm with preseptal had a longer duration than blepharospasm with pretarsal. The preseptal injection was associated with more adverse events overall than the pretarsal (9.4% vs 5.2%, P-value < 0.001). The total dose and cost per session in the preseptal group is lower for onabotulinum toxin but higher for abobotulinum toxin. Conclusion: Pretarsal injections reduced symptom severity with fewer side effects. Further studies on the pharmacoeconomics of both techniques are required.