Functional Outcome and Hemorrhage Rates After Bridging Therapy With Tenecteplase or Alteplase in Patients With Large Ischemic Core.

BACKGROUND AND OBJECTIVES: IV tenecteplase is an alternative to alteplase before mechanical thrombectomy (MT) in patients with large-vessel occlusion (LVO) ischemic stroke. Little data are available on its use in patients with large ischemic core. We aimed to compare the efficacy and safety of both thrombolytics in this population. METHODS: We conducted a retrospective analysis of patients with anterior circulation LVO strokes and diffusion-weighed imaging Alberta Stroke Program Early CT Score (DWI-ASPECTS) ≤5 treated with tenecteplase or alteplase before MT from the TETRIS (tenecteplase) and ETIS (alteplase) French multicenter registries. Primary outcome was reduced disability at 3 months (ordinal analysis of the modified Rankin scale [mRS]). Safety outcomes were 3-month mortality, parenchymal hematoma (PH), and symptomatic intracranial hemorrhage (sICH). We used propensity score overlap weighting to reduce baseline differences between treatment groups. RESULTS: We analyzed 647 patients (tenecteplase: n = 194; alteplase: n = 453; inclusion period 2015-2022). Median (interquartile range) age was 71 (57-81) years, with NIH Stroke Scale score 19 (16-22), DWI-ASPECTS 4 (3-5), and last seen well-to-IV thrombolysis and puncture times 165 minutes (130-226) and 260 minutes (203-349), respectively. After MT, the successful reperfusion rate was 83.1%. After propensity score overlap weighting, all baseline variables were well balanced between both treatment groups. Compared with patients treated with alteplase, patients treated with tenecteplase had better 3-month mRS (common odds ratio [OR] for reduced disability: 1.37, 1.01-1.87, p = 0.046) and lower 3-month mortality (OR 0.52, 0.33-0.81, p < 0.01). There were no significant differences between thrombolytics for PH (OR 0.84, 0.55-1.30, p = 0.44) and sICH incidence (OR 0.70, 0.42-1.18, p = 0.18). DISCUSSION: Our data are encouraging regarding the efficacy and reassuring regarding the safety of tenecteplase compared with that of alteplase in bridging therapy for patients with LVO strokes and a large ischemic core in routine clinical care. These results support its consideration as an alternative to alteplase in bridging therapy for patients with large ischemic cores. TRIALS REGISTRATION INFORMATION: NCT03776877 (ETIS registry) and NCT05534360 (TETRIS registry). CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that patients with anterior circulation LVO stroke and DWI-ASPECTS ≤5 treated with tenecteplase vs alteplase before MT experienced better functional outcomes and lower mortality at 3 months.

Becoming a thrombectomy-capable stroke center: Clinical and medico-economical effectiveness at the hospital level.

INTRODUCTION: Too few patients benefit from endovascular therapy (EVT) in large vessel occlusion acute stroke (LVOS), and various acute stroke care paradigms are currently investigated to reduce these inequalities in health access. We aimed to investigate whether newly set-up thrombectomy-capable stroke centers (TSC) offered a safe, effective and cost-effective procedure. PATIENTS AND METHODS: This French retrospective study compared the outcomes of LVOS patients with an indication for EVT and treated at the Perpignan hospital before on-site thrombectomy was available (Primary stroke center), and after formation of local radiology team for neurointervention (TSC). Primary endpoints were 3-months functional outcomes, assessed by the modified Rankin scale. Various safety endpoints for ischemic and hemorragic procedural complications were assessed. We conducted a medico-economic analysis to estimate the cost-benefit of becoming a TSC for the hospital. RESULTS: The differences between 422 patients in the PSC and 266 in the TSC were adjusted by the means of weighted logistic regression. Patients treated in the TSC had higher odds of excellent functional outcome (aOR 1.77 [1.16-2.72], p = 0.008), with no significant differences in the rates of procedural complications. The TSC setting shortened onset-to-reperfusion times by 144 min (95% CI [131-155]; p < 0.0001), and was cost-effective after 21 treated LVOS patients. On-site thrombectomy saves 10.825€ per patient for the hospital. DISCUSSION: Our results demonstrate that the TSC setting improves functional outcomes and reduces intra-hospital costs in LVOS patients. TSCs could play a major public health role in acute stroke care and access to EVT.

Early Recanalization Among Patients Undergoing Bridging Therapy With Tenecteplase or Alteplase.

BACKGROUND: Intravenous thrombolysis (IVT) with alteplase or tenecteplase before mechanical thrombectomy is the recommended treatment for large-vessel occlusion acute ischemic stroke. There are divergent data on whether these agents differ in terms of early recanalization (ER) rates before mechanical thrombectomy, and little data on their potential differences stratified by ER predictors such as IVT to ER evaluation (IVT-to-EReval) time, occlusion site and thrombus length. METHODS: We retrospectively compared the likelihood of ER after IVT with tenecteplase or alteplase in anterior circulation large-vessel occlusion acute ischemic stroke patients from the PREDICT-RECANAL (alteplase) and Tenecteplase Treatment in Ischemic Stroke (tenecteplase) French multicenter registries. ER was defined as a modified Thrombolysis in Cerebral Infarction score 2b-3 on the first angiographic run, or noninvasive vascular imaging in patients with early neurological improvement. Analyses were based on propensity score overlap weighting (leading to exact balance in patient history, stroke characteristics, and initial management between groups) and confirmed with adjusted logistic regression (sensitivity analysis). A stratified analysis based on pre-established ER predictors (IVT-to-EReval time, occlusion site, and thrombus length) was conducted. RESULTS: Overall, 1865 patients were included. ER occurred in 156/787 (19.8%) and 199/1078 (18.5%) patients treated with tenecteplase or alteplase, respectively (odds ratio, 1.09 [95% CI, 0.83-1.44]; P=0.52). A differential effect of tenecteplase versus alteplase on the probability of ER according to thrombus length was observed (Pinteraction=0.003), with tenecteplase being associated with higher odds of ER in thrombi >10 mm (odds ratio, 2.43 [95% CI, 1.02-5.81]; P=0.04). There was no differential effect of tenecteplase versus alteplase on the likelihood of ER according to the IVT-to-EReval time (Pinteraction=0.40) or occlusion site (Pinteraction=0.80). CONCLUSIONS: Both thrombolytics achieved ER in one-fifth of patients with large-vessel occlusion acute ischemic stroke without significant interaction with IVT-to-EReval time and occlusion site. Compared with alteplase, tenecteplase was associated with a 2-fold higher likelihood of ER in larger thrombi.

Association between altered cognition and Loa loa microfilaremia: First evidence from a cross-sectional study in a rural area of the Republic of Congo.

BACKGROUND: Individuals with high Loa loa microfilarial densities are at risk of developing severe encephalopathy after administration of antiparasitic drugs. Apart from this finding, loiasis is considered benign with no effect on brain function. However, recent epidemiological data suggest an increased mortality and morbidity in L. loa infected individuals, underscoring the importance of studies on the possible neurological morbidity associated with loiasis. METHODOLOGY: Using MoCA tests and neurological ultrasounds, we conducted a cross-sectional study to assess cognitive alteration in a population living in a rural area endemic for loiasis in the Republic of Congo. Fifty individuals with high microfilarial densities (MFD) were matched on sex, age and residency with 50 individuals with low MFD and 50 amicrofilaremic subjects. Analyses focused on individuals with MoCA scores indicating an altered cognition (i.e. < 23/30) and on the total MoCA score according to Loa loa MFD, sociodemographic characteristics and neurological ultrasound results. PRINCIPAL FINDINGS: MoCA scores were very low in the studied population (mean of 15.6/30). Individuals with more than 15,000 microfilariae per milliliter of blood (mean predicted score:14.0/30) are more than twenty times more likely to have an altered cognition, compared to individuals with no microfilaremia (mean predicted score: 16.3/30). Years of schooling were strongly associated with better MoCA results. Extracranial and intracranial atheroma were not associated with L. loa MFD. CONCLUSION/SIGNIFICANCE: Loaisis microfilaremia is probably involved in cognitive impairment, especially when the MFD are high. These results highlight the urgent need to better understand loaisis-induced morbidity. Further studies investigating neurological morbidity of loiasis are needed.

Blood Flow Velocity: a Decision Tool for Stenting Indication in Venous Pulsatile Tinnitus.

BACKGROUND AND PURPOSE: Lateral sinus stenosis is the most common cause of venous pulsatile tinnitus (VPT). Stenting is an effective treatment after demonstration of a trans-stenotic pressure gradient; however, pressure measurement has many technical limitations. In 2018, a study showed that a combined approach with intravascular velocity measurement could be effective in identifying most appropriate candidates for stenting. The aim of the present study was to evaluate a new strategy using this biomarker for the indication of stenting even without a significant pressure gradient. MATERIAL AND METHODS: Consecutive patients with disabling VPT were included from 2016 to 2019 and analyzed retrospectively. Intrasinusal pressures were measured and blood flow velocities (with a dual-sensor guidewire) were used for the indication of stenting independent of the pressure gradient. We evaluated the clinical outcome after stenting based on this new biomarker. RESULTS: A total of 41 patients were treated according to this strategy. At last follow-up (mean = 30.2 months), 32/33 patients (97%) treated by stenting showed complete resolution or a significant decrease in VPT intensity. The use of velocity as the threshold for indicating stenting identified 8 patients (24%) missed by the pressure gradient. Their clinical outcome after stenting was excellent and no complications occurred. CONCLUSION: Measurement of sinus blood flow velocity provides a hemodynamic explanation of disease and may be a better tool than pressure gradient for the indication of stenting in VPT.

Treatment times, functional outcome, and hemorrhage rates after switching to tenecteplase for stroke thrombolysis: Insights from the TETRIS registry.

Introduction: The encouraging efficacy and safety data on intravenous thrombolysis with tenecteplase in ischemic stroke and its practical advantages motivated our centers to switch from alteplase to tenecteplase. We report its impact on treatment times and clinical outcomes. Methods: We retrospectively analyzed clinical and procedural data of patients treated with alteplase or tenecteplase in a comprehensive (CSC) and a primary stroke center (PSC), which transitioned respectively in 2019 and 2018. Tenecteplase enabled in-imaging thrombolysis in the CSC. The main outcomes were the imaging-to-thrombolysis and thrombolysis-to-puncture times. We assessed the association of tenecteplase with 3-month functional independence and parenchymal hemorrhage (PH) with multivariable logistic models. Results: We included 795 patients, 387 (48.7%) received alteplase and 408 (51.3%) tenecteplase. Both groups (tenecteplase vs alteplase) were similar in terms of age (75 vs 76 years), baseline NIHSS score (7 vs 7.5) and proportion of patients treated with mechanical thrombectomy (24.1% vs 27.5%). Tenecteplase patients had shorter imaging-to-thrombolysis times (27 vs 36 min, p < 0.0001) mainly driven by patients treated in the CSC (22 vs 38 min, p < 0.001). In the PSC, tenecteplase patients had shorter thrombolysis-to-puncture times (84 vs 95 min, p = 0.02), reflecting faster interhospital transfer for MT. 3-month functional independence rate was higher in the tenecteplase group (62.8% vs 53.4%, p < 0.01). In the multivariable analysis, tenecteplase was significantly associated with functional independence (ORa 1.68, 95% CI 1.15-2.48, p < 0.01), but not with PH (ORa 0.68, 95% CI 0.41-1.12, p = 0.13). Conclusion: Switch from alteplase to tenecteplase reduced process times and may improve functional outcome, with similar safety profile.