Number needed to treat with intravenous tenecteplase to reduce the need for mechanical thrombectomy in large vessel occlusion acute ischemic stroke patients: A retrospective look at real-world experience data.

OBJECTIVE: We sought to describe short term outcomes in patients with large vessel occlusion acute ischemic stroke (LVOAIS) who were treated with intravenous tenecteplase (TNK) as compared to alteplase (tPA), focusing on reduction in the need for mechanical thrombectomy (MT). BACKGROUND: In LVOAIS, TNK has shown improved reperfusion and outcomes with a similar safety profile to tPA. Ultra-early reperfusion has been described with TNK which would prevent the need for MT. We analyze the magnitude of this effect in a "real-world" setting. DESIGN/METHODS: In this retrospective study, demographic, clinical, and imaging information from patients with LVOAIS treated with intravenous thrombolysis was collected. Data was compared between the group treated with TNK and tPA. RESULTS: One hundred eighty-six patients met the criteria for the study. Of these,144patients received tPA and 42 received TNK. Nine had clinical improvement prior to groin puncture and did not require angiography. When combining the number of patients who had recanalization on angiography before MT and those who had clinical improvement prior to angiography, there were a total of 23 patients. This was noted in 9.7 % of patients who received tPA and 21.4 % of those who received TNK (p = 0.043). For patients treated with TNK we observed a rapid clinical improvement, improved NIHSS, improved functional outcomes and decreased length of stay compared to patients treated with tPA. For patients with spontaneous recanalization either angiographically or with clinical improvement from intravenous thrombolysis, MT may not be required. CONCLUSIONS: Intravenous TNK in patients with LVOAIS decreases the need for MT, and is associated with improved outcomes and reduced length of stay.

Intravenous thrombolysis prior to mechanical thrombectomy does not affect clinical or procedural outcomes in patients with large vessel occlusion acute ischemic stroke.

Mechanical thrombectomy (MT) has revolutionized the care of large vessel occlusion acute ischemic strokes (LVOAIS). However, the benefit of intravenous thrombolysis prior to MT remains unproven. Two recent trials showed equivocal results regarding the benefits of pre-MT intravenous thrombolysis in predominantly Asian populations. We evaluated clinical outcomes and procedural metrics for patients with LVOAIS who were treated with MT alone compared to those who were treated with both intravenous tPA and MT. In a retrospective study, LVOAIS patients treated with MT, with or without preceding intravenous thrombolysis, between January of 2017 and December of 2019 were identified. Patients were treated according to contemporary guidelines. Baseline demographic and clinical characteristics, procedural metrics, and clinical outcomes were collected. Among LVOAIS patients, those treated with intravenous thrombolysis and MT did not differ from those with MT alone on clinical outcomes at three months. Further, the two groups did not differ on thrombectomy procedure times, recanalization rates, and symptomatic intracranial hemorrhage rates. In our patients with LVOAIS, intravenous thrombolysis combined with MT offered no advantage compared to MT alone in clinical outcomes or recanalization rates. Our results are consistent with earlier studies in other populations. In addition, our results suggest that IV tPA does not impact the ease of clot removal by MT. Further studies will evaluate how newly available thrombolytic agents may benefit patients eligible for MT.

Maternal allergic inflammation in rats impacts the offspring perinatal neuroimmune milieu and the development of social play, locomotor behavior, and cognitive flexibility.

Maternal systemic inflammation increases risk for neurodevelopmental disorders like autism, ADHD, and schizophrenia in offspring. Notably, these disorders are male-biased. Studies have implicated immune system dysfunction in the etiology of these disorders, and rodent models of maternal immune activation provide useful tools to examine mechanisms of sex-dependent effects on brain development, immunity, and behavior. Here, we employed an allergen-induced model of maternal inflammation in rats to characterize levels of mast cells and microglia in the perinatal period in male and female offspring, as well as social, emotional, and cognitive behaviors throughout the lifespan. Adult female rats were sensitized to ovalbumin (OVA), bred, and challenged intranasally on gestational day 15 of pregnancy with OVA or saline. Allergic inflammation upregulated microglia in the fetal brain, increased mast cell number in the hippocampus on the day of birth, and conferred region-, time- and sex- specific changes in microglia measures. Additionally, offspring of OVA-exposed mothers subsequently exhibited abnormal social behavior, hyperlocomotion, and reduced cognitive flexibility. These data demonstrate the long-term effects of maternal allergic challenge on offspring development and provide a basis for understanding neurodevelopmental disorders linked to maternal systemic inflammation in humans.