Trial of Thrombectomy for Stroke with a Large Infarct of Unrestricted Size.

BACKGROUND: The use of thrombectomy in patients with acute stroke and a large infarct of unrestricted size has not been well studied. METHODS: We assigned, in a 1:1 ratio, patients with proximal cerebral vessel occlusion in the anterior circulation and a large infarct (as defined by an Alberta Stroke Program Early Computed Tomographic Score of ≤5; values range from 0 to 10) detected on magnetic resonance imaging or computed tomography within 6.5 hours after symptom onset to undergo endovascular thrombectomy and receive medical care (thrombectomy group) or to receive medical care alone (control group). The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). The primary safety outcome was death from any cause at 90 days, and an ancillary safety outcome was symptomatic intracerebral hemorrhage. RESULTS: A total of 333 patients were assigned to either the thrombectomy group (166 patients) or the control group (167 patients); 9 were excluded from the analysis because of consent withdrawal or legal reasons. The trial was stopped early because results of similar trials favored thrombectomy. Approximately 35% of the patients received thrombolysis therapy. The median modified Rankin scale score at 90 days was 4 in the thrombectomy group and 6 in the control group (generalized odds ratio, 1.63; 95% confidence interval [CI], 1.29 to 2.06; P<0.001). Death from any cause at 90 days occurred in 36.1% of the patients in the thrombectomy group and in 55.5% of those in the control group (adjusted relative risk, 0.65; 95% CI, 0.50 to 0.84), and the percentage of patients with symptomatic intracerebral hemorrhage was 9.6% and 5.7%, respectively (adjusted relative risk, 1.73; 95% CI, 0.78 to 4.68). Eleven procedure-related complications occurred in the thrombectomy group. CONCLUSIONS: In patients with acute stroke and a large infarct of unrestricted size, thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone but led to a higher incidence of symptomatic intracerebral hemorrhage. (Funded by Montpellier University Hospital; LASTE ClinicalTrials.gov number, NCT03811769.).

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.

Safety and effectiveness of mechanical thrombectomy for primary isolated distal vessel occlusions: A monocentric retrospective comparative study.

BACKGROUND: Distal vessel occlusions represent about 25-40% of acute ischemic stroke (AIS), either as primary occlusion or secondary occlusion complicating mechanical thrombectomy (MT) for large vessel occlusion. OBJECTIVE: Our aim was to evaluate safety and effectiveness of MT associated with the best medical treatment (BMT) in the management of AIS patients with distal vessel occlusion in comparison with the BMT alone. METHODS: Retrospective analysis was conducted on AIS patients treated by MT+BMT for primary distal vessel occlusion between 2015 and 2020, and were compared with a historic cohort managed by BMT alone between 2006 and 2015 selected based on the same inclusion criteria. A secondary analysis was conducted using propensity score matching (PSM) including the following: NIHSS, age and treatment with intravenous thrombolysis (IVT) as covariates. RESULTS: Of 650 patients screened, 44 patients with distal vessel occlusions treated by MT+BMT were selected and compared with 36 patients who received BMT alone. After PSM, 28 patients in each group were matched without significant difference. Good clinical outcome defined as mRS≤2 was achieved by 53.6% of the MT+BMT group and 57% of the BMT group (OR, 0.87; 95%CI, 0.3-2.4; p = 1.00). The mortality rate was comparable in both groups (7% vs. 10.7% in MT+BMT and BMT patients, respectively; OR=0.64; 95%CI, 0.1-4; p = 1.00). Symptomatic intracranial hemorrhage (ICH) was seen in only one patient treated by MT+BMT (3.6%). CONCLUSION: Mechanical thrombectomy seems to be comparable with the best medical treatment regarding the effectiveness and safety in the management of patients with distal vessel occlusions.

Patent foramen ovale closure in stroke patients with migraine in the CLOSE trial. The CLOSE-MIG study.

BACKGROUND AND PURPOSE: The efficacy of patent foramen ovale (PFO) closure to reduce the frequency of migraine attacks remains controversial. METHODS: This was a planned sub-study in migraine patients enrolled in a randomized, clinical trial designed to assess the superiority of PFO closure plus antiplatelet therapy over antiplatelet therapy alone to prevent stroke recurrence in patients younger than 60 years with a PFO-associated cryptogenic ischaemic stroke. The main outcome was the mean annual number of migraine attacks in migraine patients with aura and in those without aura, as recorded at each follow-up visit by study neurologists. RESULTS: Of 473 patients randomized to PFO closure or antiplatelet therapy, 145 (mean age 41.9 years; women 58.6%) had migraine (75 with aura and 70 without aura). Sixty-seven patients were randomized to PFO closure and 78 to antiplatelet therapy. During a mean follow-up of about 5 years, there were no differences between antiplatelet-only and PFO closure groups in the mean annual number of migraine attacks, both in migraine patients with aura (9.2 [11.9] vs. 12.0 [19.1], p = 0.81) and in those without aura (12.1 [16.1] vs. 11.8 [18.4], p > 0.999). There were no differences between treatment groups regarding cessation of migraine attacks, migraine-related disability at 2 years and use of migraine-preventive drugs during follow-up. CONCLUSIONS: In young and middle-aged adults with PFO-associated cryptogenic stroke and migraine, PFO closure plus antiplatelet therapy did not reduce the mean annual number of migraine attacks compared to antiplatelet therapy alone, in migraine patients both with and without aura.

Primary Sjögren's syndrome: central and peripheral nervous system involvements.

Primary Sjögren's syndrome (pSS) is a common systemic autoimmune disease characterised by exocrinopathy resulting in dryness of the mouth and eyes, unexplained fatigue and diffuse pain. Neurological involvement is uncommon in pSS, involving the central nervous system in 2-5% of cases and more frequently the peripheral nervous system in 5-15% of cases. The diagnosis of pSS is to be considered when confronted with symptoms such as mouth and eye dryness, fatigue and pain, the most frequent of pSS symptoms. Objective measures of oral and eye dryness may help assert the diagnosis of pSS, as well as ACR/EULAR criteria. Differential diagnoses have to be excluded in patients exhibiting neurological symptoms, such as cryoglobulinaemic vasculitis or multiple sclerosis, before considering a neurological involvement specific to pSS. The treatment of these neurological manifestations takes into account different parameters, such as the presence of cryoglobulinaemic vasculitis, the severity of the symptoms, a rapidly progressing evolution and the failure of previous symptomatic treatments.

Rescue stenting versus medical care alone in refractory large vessel occlusions: a systematic review and meta-analysis.

PURPOSE: Mechanical thrombectomy (MT) failure is associated with very poor prognosis. Permanent intracranial stenting (PIS) may be useful in such refractory occlusions. However, this strategy requires an aggressive antithrombotic regimen that may be harmful in extended strokes. The aim of this study was to compare clinical outcomes between patients with refractory acute large vessel occlusions (LVOs) treated by PIS versus patients for whom the procedure was stopped without recanalization. METHODS: We conducted a systematic review by searching for articles in PubMed, the Cochrane Library, and ClinicalTrials.gov from January 2015 to September 2019. Two reviewers independently selected studies comparing PIS after failed MT in addition to usual care versus usual care only. A comparative meta-analysis was performed using random-effects models to estimate odds ratios of favorable clinical outcome at 90 days, defined as a modified Rankin scale 0-2, mortality and symptomatic intracranial hemorrhage (SICH). RESULTS: Four comparative studies were included for a total of 352 patients: 149 in the PIS group versus 203 in the control group. PIS was associated with significantly higher rates of 90-day favorable clinical outcome (odds ratio [OR], 2.87 [95% confidence interval (95% CI), 1.77-4.66]; p < 0.001; I2, 0%) and lower mortality (OR, 0.39 [0.16-0.93]; p = 0.03; I2, 43%), whereas SICH rates did not significantly differ (OR, 0.68 [0.37-1.27]; p = 0.23; I2, 0%). CONCLUSION: From observational study results, attempting PIS after failed MT seems to improve clinical outcomes without increasing the risk of intracranial bleeding. Randomized trials are needed to confirm these results.

Outcome and recanalization rate of tandem basilar artery occlusion treated by mechanical thrombectomy.

BACKGROUND: Tandem basilar artery occlusions (tBAO) are defined as concomitant basilar artery and extracranial dominant vertebral artery occlusions. The prognosis of such tBAO treated by mechanical thrombectomy (MT) has been scantly reported. The purpose of our study was to compare the safety and effectiveness of MT for patients with tBAO compared to those with non-tandem basilar artery occlusions (ntBAO). PATIENTS AND METHODS: Retrospective analysis of a database of patients who underwent MT at two academic centres. All patients treated for BAO were retrieved. Patients with tBAO, defined as a concomitant BAO and extracranial vertebral artery (VA) occlusion or severe stenosis ≥70% (V1 or proximal V2 segment) were compared with patients with ntBAO. RESULTS: A total of 15 patients with tBAO and 74 patients with ntBAO were enrolled. Successful reperfusion (modified thrombolysis in cerebral infarction score ≥2b) was obtained in 73.3% versus 90.5% (OR = 0.29, 95%CI: 0.07-1.15), good clinical outcome (3-months modified Rankin scale ≤2) was reached by 26.7% versus 32.4% (OR = 0.76; 95% CI: 0.24-2.63) and mortality at 3-months was 46.7% versus 31% (OR = 1.94; 95%CI: 0.63-6) of patients with tBAO versus ntBAO, respectively. Two patients (13.3%) with tBAO and three (4%) with ntBAO had symptomatic intracranial haemorrhage (OR = 3.64; 95% CI: 0.55-24). CONCLUSION: Mechanical thrombectomy for patients with tandem basilar artery occlusion tends to be associated with lower rates of successful reperfusion and good clinical outcome, and higher rate of mortality. Larger multicentre studies are warranted to better precise the proper selection and management of such patients.

Ischemic stroke in giant-cell arteritis: French retrospective study.

Acute cerebrovascular ischemic events are a rare and severe complication of giant cell arteritis (GCA). We aimed to determine the prevalence of GCA-related stroke, the overall survival and the relapse-free survival in patients with GCA. A multicentric retrospective analysis was performed on 129 patients with GCA diagnosed between September 2010 and October 2018 in two University Hospitals. Among 129 GCA patients, 18 (16%) presented an acute ischemic cerebrovascular event. Patients with stroke were older (83 [67-96] years versus 76 [58-96]; p = 0.014) and more frequently males (61% versus 30%; p = 0.014) than those without stroke. The frequency of anterior ischemic optic neuropathy was higher in patients with stroke (n = 6, 33%) than patients without stroke (n = 12, 11%)(p = 0.02). Overall survival was significantly decreased in GCA patients with stroke (4.4 months), comparatively to patients without stroke (221.7 months; log rank test = 0.006). The 3-years relapse-free survival was decreased in patients with stroke (8.42 versus78.0 months; log rank = 0.0001), as well as the time with sustained remission (78 versus 139 months; log rank test = 0.0004). This study shows the prevalence and risk factors of ischemic stroke in GCA.

New insights in radiation-induced leukoencephalopathy: a prospective cross-sectional study.

BACKGROUND: Radiation-induced leukoencephalopathy (RIL) is the most threatening delayed complication of cerebral radiotherapy (RT) and remains roughly defined by cognitive dysfunction associated with diffuse FLAIR MRI white matter hyperintensities after brain irradiation. We documented clinical, neuropsychological, and radiological aspects of RI in order to refine diagnostic criteria. METHODS: Patients referred to our center for deterioration in cognitive complaint at least 6 months after completing a focal or whole brain RT underwent a systematic cross-sectional assessment including clinical examination, neuropsychological tests, and a standardized MRI protocol. Patients with progressive tumor were excluded. RESULTS: Forty patients were prospectively enrolled. Of these, 26 had received a focal RT, median dose of 53 Gy (range 50 to 60), and 14 had received a whole brain RT, median dose of 30 Gy. Cognitive complaints, gait apraxia, and urinary troubles were reported in 100, 67, and 38% of cases, respectively. On neuropsychological examination, patients displayed a global and severe cognitive decline through a subcortical frontal mode. The cognitive changes observed were not hippocampic, but related to executive dysfunction. On MRI, 68% of the patients had extensive FLAIR hyperintensities with anterior predominance, 87% had brain atrophy, and 21% had intraparenchymal cysts. T2*-weighted MRI showed small asignal areas in 53% of the patients. These abnormalities are evocative of cerebral small vessel disease. Fractional anisotropy in the corpus callosum correlated with the cognitive evaluation. No differentiation in terms of cognitive and MRI features could be made between patients treated with focal brain RT (glioma) and patients treated with WBRT (for brain metastases or PCNSL). CONCLUSIONS: RIL can be defined by clinical symptoms (subcortical frontal decline, gait apraxia, urinary incontinence) and MRI criteria (cortico-subcortical atrophy, spread FLAIR HI, T2* asignals). This condition mimics a diffuse progressive cerebral small vessel disease triggered by RT, independent of RT protocol.

Mechanical Thrombectomy in Perioperative Strokes: A Case-Control Study.

BACKGROUND AND PURPOSE: Perioperative strokes (POS) are rare but serious complications for which mechanical thrombectomy could be beneficial. We aimed to compare the technical results and patients outcomes in a population of POS versus non-POS (nPOS) treated by mechanical thrombectomy. METHODS: From 2010 to 2017, 25 patients with POS (ie, acute ischemic stroke occurring during or within 30 days after a procedure) who underwent mechanical thrombectomy (POS group) were enrolled and paired with 50 consecutive patients with nPOS (control group), based on the occlusion's site, National Institute of Health Stroke Scale, and age. RESULTS: Respectively, mean age was 68.3±16.6 versus 67.2±16.6 years (P=0.70), and median National Institute of Health Stroke Scale score at admission was 20 (interquartile range, 15-25) versus 19 (interquartile range, 17-25; P=0.79). Good clinical outcome (modified Rankin Scale score of 0-2 at 3 months) was achieved by 33.3% (POS) versus 56.5% (nPOS) of patients (P=0.055). Successful reperfusion (modified Thrombolysis In Cerebral Infarction score of ≥2b) was obtained in 76% (POS) versus 86% (nPOS) of cases (P=0.22). Mortality at 3 months was 33.3% in the POS group versus 4.2% (nPOS) (P=0.002). The rate of major procedural complications was 4% (POS) versus 6% (nPOS); none were lethal. Average time from symptoms' onset to reperfusion was 4.9 hours (±2.0) in POS versus 5.2 hours (±2.6). CONCLUSIONS: Successful reperfusion seems accessible in POS within a reasonable amount of time and with a good level of safety. However, favorable outcome was achieved with a lower rate than in nPOS, owing to a higher mortality rate.

Strokes in Sneddon syndrome without antiphospholipid antibodies.

OBJECTIVE: Sneddon syndrome (SS) is characterized by the association of a livedo reticularis with stroke. Clinicoradiological features of its neurological manifestations, its prognosis, and the frequency of associated cardiac valvulopathy remain poorly known, particularly in the absence of antiphospholipid antibodies (APL). The objectives were to assess the clinicoradiological pattern of SS without APL (SSAPL- ) and its midterm prognosis. METHODS: Clinical data, transthoracic echocardiograms, and brain imaging of 53 consecutive patients (83% women) with SSAPL- , followed up at our institution between 1991 and 2011, were reviewed. RESULTS: Seventy-four strokes were reported; 76% were ischemic strokes (IS), 15% transient ischemic attacks, and 9% hemorrhagic strokes. Heart valve lesions were found in 50% of the cases. Brain imaging showed 177 IS of 3 different types: large territorial (43%), small distal corticosubcortical (14%), and small deep (23%) IS. No significant association was found between the valve involvement and the presence of territorial IS. After a mean follow-up of 7.4 years, 82% of patients had a modified Rankin Scale score ≤ 2. The ischemic event recurrence rate was 20%, with a similar annual rate in the antiplatelet group (3%) compared to the anticoagulation group (2.7%). INTERPRETATION: SSAPL- is not only a neurocutaneous disorder, but is frequently associated with heart valve involvement. The latter does not influence the IS type, which suggests that strokes are caused by vasculopathy of the small and medium-size cerebral arteries. Our results show no progression toward a serious disability in the majority of the cases and a moderate recurrence rate under antiplatelet therapy.

Incidence and predictors of intracranial hemorrhage after intravenous thrombolysis with tenecteplase.

BACKGROUND: Despite its increasing use, there are limited data on the risk of intracranial hemorrhage (ICH) after intravenous thrombolysis with tenecteplase in the setting of acute ischemic stroke. Our aim was to investigate the incidence and predictors of ICH after tenecteplase administration. METHODS: We reviewed data from the prospective ongoing multicenter TETRIS (Tenecteplase Treatment in Ischemic Stroke) registry. Patients with available day-1 imaging were included in this study. Clinical, imaging and biological variables were collected. Follow-up imaging performed 24 h after IVT was locally reviewed by senior neuroradiologists and neurologists. The incidence of parenchymal hematoma (PH) and any ICH were investigated. Potential predictors of PH and any ICH were assessed in multivariable logistic regressions. Subgroup analyses focusing on patients intended for endovascular treatment were performed. RESULTS: PH and any ICH occurred in 126/1321 (incidence rate: 9.5%, 95% CI 8.1-11.2) and 521/1321 (39.4%, 95% CI 36.8-42.1) patients, respectively. Symptomatic ICH was observed in 77/1321 (5.8%; 95% CI 4.7-7.2). PH occurrence was significantly associated with poorer functional outcomes (p < 0.0001) and death (p < 0.0001) after 3 months. Older age (aOR = 1.03; 95% CI 1.01-1.05), male gender (aOR = 2.07; 95% CI 1.28-3.36), a history of hypertension (aOR = 2.08; 95% CI 1.19-3.62), a higher baseline NIHSS (aOR = 1.07; 95% CI 1.03-1.10) and higher admission blood glucose level (aOR = 1.12; 95% CI 1.05-1.19) were independently associated with PH occurrence. Similar associations were observed in the subgroup of patients intended for endovascular treatment. CONCLUSION: We quantified the incidence of ICH after IVT with tenecteplase in a real-life prospective registry and determined independent predictors of ICH. These findings allow to identify patients at high risk of ICH.

Intravenous thrombolysis with tenecteplase versus alteplase combined with endovascular treatment of anterior circulation tandem occlusions: A pooled analysis of ETIS and TETRIS.

BACKGROUND: Tandem occlusions are a singular large vessel occlusion entity involving specific endovascular and perioperative antithrombotic management. In this context, data on safety and efficacy of prior intravenous thrombolysis (IVT) with tenecteplase is scarce. We aimed to compare IVT with tenecteplase or alteplase in patients with acute tandem occlusions intended for endovascular treatment. PATIENTS AND METHODS: A retrospective pooled analysis of two large observational registries (ETIS (Endovascular Treatment of Ischemic Stroke) and TETRIS (Tenecteplase Treatment in Ischemic Stroke)) was performed on consecutive patients presenting with anterior circulation tandem occlusion treated with IVT using either alteplase (ETIS) or tenecteplase (TETRIS) followed by endovascular treatment between January 2015 and June 2022. Sensitivity analyses on atherosclerosis related tandem occlusions and on patient treated with emergent carotid stenting were conducted. Propensity score overlap weighting analyses were performed. RESULTS: We analyzed 753 patients: 124 in the tenecteplase and 629 in the alteplase group. The overall odds of favorable outcome (3-month modified Rankin score 0-2) were comparable between both groups (49.4% vs 47.1%; OR = 1.10, 95%CI 0.85-1.41). Early recanalization, final successful recanalization and mortality favored the use of tenecteplase. The occurrence of any intracranial hemorrhage (ICH) was more frequent after tenecteplase use (OR = 2.24; 95%CI 1.75-2.86). However, risks of symptomatic ICH and parenchymal hematoma remained similar. In atherosclerotic tandems, favorable outcome, mortality, parenchymal hematoma, early recanalization, and final successful recanalization favored the tenecteplase group. In the carotid stenting subgroup, PH were less frequent in the tenecteplase group (OR = 0.18; 95%CI 0.05-0.69). CONCLUSION: In patients with tandem occlusions, IVT with tenecteplase seemed reasonably safe in particular with increased early recanalization rates. These findings remain preliminary and should be further confirmed in randomized trials.

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.

Comparison of rescue intracranial stenting versus best medical treatment alone in acute refractory large vessel occlusion: study protocol for the PISTAR multicenter randomized trial.

BACKGROUND: Mechanical thrombectomy (MT) has become a standard treatment for acute ischemic strokes (AIS). However, MT failure occurs in approximately 10-30% of cases, leading to severe repercussions (with mortality rates up to 40% according to observational data). Among the available rescue techniques, rescue intracranial stenting (RIS) appears as a promising option. OBJECTIVE: This trial is poised to demonstrate the superiority of RIS in addition to the best medical treatment (BMT) in comparison with BMT alone, in improving the functional outcomes at 3 months for patients experiencing an AIS due to a large vessel occlusion refractory to MT (rLVO). METHODS: Permanent Intracranial STenting for Acute Refractory large vessel occlusions (PISTAR) is a multicenter prospective randomized open, blinded endpoint trial conducted across 11 French University hospitals. Adult patients (≥18 years) with an acute intracranial occlusion refractory to standard MT techniques will be randomized 1:1 during the procedure to receive either RIS+BMT (intervention arm) or BMT alone (control arm). RESULTS: The primary outcome is the rate of good clinical outcome at 3 months defined as a modified Rankin Scale score ≤2 and evaluated by an independent assessor blinded to the randomization arm. Secondary outcomes include hemorrhagic complications, all adverse events, and death. The number of patients to be included is 346. Two interim analyses are planned with predefined stopping rules. CONCLUSION: The PISTAR trial is the first randomized controlled trial focusing on the benefit of RIS in rLVOs. If positive, this study will open new insights into the management of AIS. TRIAL REGISTRATION NUMBER: NCT06071091.

Evaluation of mechanical thrombectomy in acute ischemic stroke related to a distal arterial occlusion: A randomized controlled trial.

RATIONALE: Mechanical thrombectomy (MT) associated with the best medical treatment (BMT) has recently shown efficacy for the management of acute ischemic stroke (AIS) secondary to a large vessel occlusion. However, evidence is lacking regarding the benefit of MT for more distal occlusions. AIM: To evaluate the efficacy in terms of good clinical outcome at 3 months of MT associated with the BMT over the BMT alone in AIS related to a distal occlusion. METHODS: The DISCOUNT trial is a multicenter open-label randomized controlled trial involving French University hospitals. Adult patients (⩾18 years) with an AIS involving the anterior or posterior circulation secondary to a distal vessel occlusion within 6 h of symptom onset or within 24 h if no hyperintense signal on fluid attenuation inversion recovery acquisition will be randomized 1:1 to receive either MT associated with the BMT (experimental group) or BMT alone (control group). The number of patients to be included is 488. STUDY OUTCOMES: The primary outcome is the rate of good clinical outcome at 3 months defined as a modified Rankin scale (mRS) ⩽2 and evaluated by an independent assessor blinded to the intervention arm. Secondary outcomes include recanalization of the occluded vessel within 48 h, angiographic reperfusion in the experimental group, 3-month excellent clinical outcome (mRS ⩽ 1), all adverse events, and death. A cost utility analysis will estimate the incremental cost per quality-adjusted life year (QALY) gained. DISCUSSION: If positive, this study will open new insights in the management of AISs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05030142 registered on 1 September 2021.

[Cerebral amyloid angiopathy and atrial fibrillation: anticoagulant dilemma]. / Angiopathie amyloïde cérébrale et fibrillation atriale : le dilemme des anticoagulants.

Cerebral amyloid angiopathy and atrial fibrillation are two frequent comorbidities in older patients, leading to a therapeutic dilemma on the risk-benefit ratio of long-term anticoagulation. These patients both have a risk of cardioembolic complications due to atrial fibrillation, and a risk of cerebral haemorrhage from cerebral amyloid angiopathy. Since there is no therapeutic consensus, the best therapeutic strategy should be discussed during a multidisciplinary staff, based on four risk estimations: 1) the baseline risk of intracerebral haemorrhage without anticoagulation; 2) the risk of ischaemic stroke without anticoagulation; 3) the expected increase of intracerebral haemorrhage with anticoagulation; 4) the expected reduction in ischaemic stroke risk with anticoagulation. The risk of intracerebral haemorrhage varies according to the cerebral amyloid angiopathy phenotype. Patients with transient neurological episode or cortical superficial siderosis have the highest risk of intracerebral haemorrhage. Direct oral anticoagulant should be preferred to vitamin K antagonists, as the risk of intracerebral haemorrhage is lower with direct oral anticoagulants. If anticoagulation is introduced, a close clinical and radiological monitoring should be performed every 6-12 months minimum. If it has been decided not to anticoagulate, left atrial appendage occlusion should be proposed. In all situations, close blood pressure control is essential to reduce the risk of intracerebral haemorrhage.