Floating aortic arch thrombus involving the left common carotid artery complicated with ischemic stroke associated with cocaine use.

BACKGROUND: Floating aortic thrombi (FLOAT) are rare, with very few cases attributed to cocaine use. We report a new case of FLOAT involving the left common carotid artery due to cocaine use, for the first time, complicated with acute ischemic stroke. METHODS: We present in detail our case report, and then, a literature search in PubMed and Scopus was performed up to March 20, 2022, to review the reported cases of aortic thrombus associated with cocaine use. RESULTS: A 39-year-old man with a history of smoking and daily cocaine use was admitted to our stroke unit for acute left-hemispheric symptoms due to carotid-Sylvian occlusion. CT angiography of the supra-aortic trunks showed FLOAT involving the left common carotid artery. The thrombus was removed successfully by endovascular thrombectomy with recanalization of carotid-Sylvian occlusion. Our literature search yielded seven reported cases of aortic thrombus due to cocaine use revealed by lower limb ischemia (3 patients), renal infarction (1 patient), abdominal pain (1 patient), bowel ischemia (1 patient), and lower limb ischemia with renal infarction (1 patient). CONCLUSION: Aortic thrombus should be suspected in patients without overt cardiovascular risk factors but with a recent history of cocaine use who presents with acute ischemic stroke.

Stroke Prevention by Anticoagulants in Daily Practice Depending on Atrial Fibrillation Pattern and Clinical Risk Factors.

Background and Purpose: The objective of the study was to assess the effectiveness of individual direct oral anticoagulants versus vitamin K antagonists for primary prevention of stroke (ischemic and hemorrhagic) in routine clinical practice in patients with various clinical risk factors depending on their atrial fibrillation (AF) patterns. Methods: A nested case-referent study was conducted using data from 2 national registries of patients with stroke and AF. Stroke cases with previous history of AF were matched to up to 2 randomly selected referent patients with AF and no stroke. The association of individual anticoagulant use with ischemic or hemorrhagic stroke was studied in patients with or without permanent AF using multivariable conditional logistic models, controlled for clinically significant risk factors and multiple other cardiovascular risk factors. Results: In total, 2586 stroke cases with previous AF and 4810 nonstroke referent patients with AF were retained for the study. Direct oral anticoagulant users had lower odds of stroke of any type than vitamin K antagonist users: the adjusted-matched OR for ischemic stroke were 0.70 (95% CI, 0.50­0.98) for dabigatran, 0.68 (95% CI, 0.53­0.86) for rivaroxaban, and 0.73 (95% CI, 0.52­1.02) for apixaban while for hemorrhagic stroke they were 0.31 (95% CI, 0.14­0.68), 0.64 (95% CI, 0.39­1.06), and 0.70 (95% CI, 0.33­1.49), respectively. The effects of individual direct oral anticoagulants relative to vitamin K antagonists were similar in permanent AF and nonpermanent AF patients. Conclusions: Similar results were observed for each direct oral anticoagulant in real life as those observed in the pivotal clinical trials. The pattern of AF did not affect the outcome.

Reversal of Vitamin K Antagonist Therapy Before Thrombolysis for Acute Ischemic Stroke.

Background and Purpose- Acute ischemic strokes under vitamin K antagonist (VKA) treatment are not uncommon, but intravenous thrombolysis (IVT) is not recommended for international normalized ratio (INR) >1.7 because of the excess bleeding risk. However, VKA-induced anticoagulation can be easily reversed by IV infusions of 4-factor prothrombin complex concentrate bolus and vitamin K. Our pilot study aimed to determine whether IVT immediately after anticoagulation reversal could be feasible and safe in acute ischemic stroke patients under VKA with INR >1.7. Methods- Consecutive acute ischemic stroke patients, otherwise eligible for IVT except for VKA intake and INR >1.7, were given IVT after infusing 4-factor prothrombin complex concentrate and vitamin K. Safety and efficacy were assessed clinically and by cerebral imaging at 24 hours. Results- Twenty-six patients (age, 77.8±12.8 years; atrial fibrillation, 84.6%; initial National Institutes of Health Stroke Scale, 11.6±5.6) were prospectively included. INR values were 2.3±0.6 initially and 1.3±0.2, 5 minutes postreversal. No symptomatic intracranial hemorrhage or thrombotic events occurred during the first 3 days. One patient developed major systemic hemorrhoidal bleeding that required blood transfusion; 61.5% of the patients were independent (modified Rankin Scale score of ≤2) at 3 months. Conclusions- A reversal strategy of 4-factor prothrombin complex concentrate bolus and vitamin K before IVT could be feasible and safe in acute ischemic stroke patients under VKA with INR >1.7. Well-designed, randomized controlled trials are warranted to confirm these preliminary findings.

Symptomatic Carotid-Bulb Atypical Fibromuscular Dysplasia.

Fibromuscular dysplasia (FMD) is known as rare cause ischemic stroke and usually involves the internal carotid or vertebral arteries in middle age women. A poorly known type of FMD located at the carotid bulb is called atypical fibromuscular dysplasia. We present the case of 3 young black patients suffering from recurrent ischemic strokes in the same middle cerebral artery territory. Computed tomographic angiography and arteriography showed a moderate diaphragmatic stenosis of the carotid bulb. After surgical removal of the dysplasia, postoperative course was uneventful without any recurrence. Pathologic examination confirmed atypical FMD. Carotid-bulb atypical FMD is a rare cause of stroke and concerns mostly young black patients. Surgical approach should be recommended to avoid recurrent stroke.

Association Between Carotid Bulb Diaphragm and Ischemic Stroke in Young Afro-Caribbean Patients: A Population-Based Case-Control Study.

BACKGROUND AND PURPOSE: Carotid bulb diaphragm (CBD) has been described in young carotid ischemic stroke (CIS) patients, especially in blacks. However, the prevalence of CBD in CIS patients is unknown, and whether CBD is a risk factor for CIS remains unclear. We assessed the association between CBD and incident CIS in a population-based study. METHODS: We selected all young (<55 years) CIS patients from a 1-year population-based cohort study in the Afro-Caribbean population of Martinique in 2012. All patients had a comprehensive work-up including a computed tomographic angiography. We calculated CIS associated with ipsilateral CBD incidence with 95% confidence intervals using Poisson distribution. We then selected age- and sex-matched controls among young (<55 years) Afro-Caribbean stroke-free patients admitted for a road crash who routinely had computed tomographic angiography. Odds ratio (ORs) were calculated by conditional logistic regression adjusted for hypertension, dyslipidemia, diabetes and smoking. RESULTS: CIS associated with ipsilateral CBD incidence was 3.8 per 100 000 person-years (95% confidence interval, 1.4-6.1). Prevalence of ipsilateral CBD was 23% in all CIS and 37% in undetermined CIS patients. When restricted to undetermined CIS, CBD prevalence was 24 times higher than that in controls (adjusted OR, 24.1; 95% confidence interval, 1.8-325.6). CONCLUSIONS: CBD is associated with an increased risk of ipsilateral CIS in young Afro-Caribbean population.

Endovascular Management of Acute Ischemic Strokes with Tandem Occlusions.

BACKGROUND: Ischemic strokes with tandem occlusions are associated with a poor prognosis. Recent studies demonstrating the effectiveness of endovascular treatment for large vessel occlusions have shown less impressive results in patients with tandem occlusions than in those with isolated intracranial occlusions. Also, the indications and effects of carotid stenting remain unclear. METHODS: From a prospectively gathered registry, we analyzed data of 70 consecutive patients who underwent mechanical endovascular treatment for acute stroke with tandem occlusions from November 2011 to August 2014. Clinical (including demographics, National Institutes of Health Stroke Scale (NIHSS), and stroke etiology), imaging (including diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score), and endovascular treatment data were assessed and reviewed in consensus by 2 observers. Good clinical outcome was defined as a modified Rankin Scale of ≤2 at 3-month follow-up. RESULTS: At 3-month follow-up, 50.8% had a poor clinical outcome, including death in 13.4%. Lower NIHSS (initial, at day 1, and at discharge) and successful recanalization (thrombolysis in cerebral infarction 2b-3) were associated with a good clinical outcome (p < 0.05). There were no statistically significant differences between patients with a good or poor clinical outcome in terms of intravenous (IV) tissue plasminogen activator use, delay between symptom onset and recanalization, and endovascular technique including the carotid stenting. CONCLUSIONS: Despite the recent randomized control trials demonstrating the effectiveness of thrombectomy, there is still a research gap about tandem occlusions. This subtype of stroke, which usually responds poorly to IV thrombolysis, is also difficult to treat by endovascular means. Guidelines for the endovascular management of tandem occlusions are needed.

Carotid-bulb atypical fibromuscular dysplasia in young Afro-Caribbean patients with stroke.

BACKGROUND AND PURPOSE: An atypical form of fibromuscular dysplasia located in the internal carotid-bulb (CaFMD) is thought to be uncommon and is poorly described as a cause of ischemic stroke in the young. This study aimed to obtain a better description of CaFMD in Afro-Caribbean population, who could be particularly affected by it. METHODS: This study included consecutive patients <55 years consulting at Fort-de-France University Hospital Stroke Center (Martinique, FWI) found to have CaFMD as the only cause after a comprehensive work-up. CaFMD was diagnosed when computed tomographic angiography showed a bulbar spur without calcification. RESULTS: Twenty-five patients with stroke and CaFMD were identified. Computed tomographic angiography showed 2 CaFMD patterns: a thin (n=15) or thick (n=10) spur. Three patients initial computed tomographic angiography images showed a mural thrombus overlying the CaFMD. CaFMD was surgically removed from 7 of 25 and 20 of 25 patients who received antiplatelet therapy; after mean follow-up of 25.3±19.5 months, their respective recurrence rates were 0% and 30%. CONCLUSIONS: CaFMD could be a common condition in young Afro-Caribbeans with carotid-territory ischemic stroke. Recurrences were frequent under antiplatelet treatment, while surgical CaFMD removal seemed more effective.

Trends in incidence and early outcomes in a Black Afro-Caribbean population from 1999 to 2012: Etude Réalisée en Martinique et Centrée sur l'Incidence des Accidents Vasculaires Cérébraux II Study.

BACKGROUND AND PURPOSE: Seldom studies are available on trends in stroke incidence in blacks. We aimed to evaluate whether stroke risk prevention policies modified first-ever stroke incidence and outcomes in the black Afro-Caribbean population of Martinique. METHODS: Etude Réalisée en Martinique et Centrée sur l'Incidence des Accidents Vasculaires Cérébraux (ERMANCIA) I and II are 2 sequential prospective population-based epidemiological studies. There have assessed temporal trends in first-ever stroke incidence, risk factors, pathological types, and early outcomes in the black Afro-Caribbean population of Martinique comparing two 12-month periods (1998-1999 and 2011-2012). Crude and age-standardized incidence and 30-day outcomes for stroke in the 2 study periods were compared using Poisson regression. RESULTS: We identified 580 and 544 first-ever strokes in the 2 studies. World age-standardized incidence rates decreased by 30.6% in overall (111 [95% confidence interval, 102-120] versus 77 [95% confidence interval, 70-84]). Rate decline was greater in women than in men (34% versus 26%) particularly in women aged 65 to 74 years (-69%) and 75 to 84 years (-43%). Frequencies of hypertension and diabetes mellitus were unchanged, whereas dyslipidemia, smoking, and atrial fibrillation significantly increased. Only ischemic stroke types showed significant rate reduction in overall and in women, incidence rate ratio (95% confidence intervals) of 0.69 (0.50-0.97) and 0.61 (0.42-0.88), respectively. The overall 30-day case-fatality ratio remained stable (19.3%/17.6%), whereas a better 30-day outcome was found (modified Rankin Score, ≤2 in 47%/37.6%; P=0.03). CONCLUSIONS: Over 13 years, there has been a significant decrease (30.6%) in the age-specific first-ever stroke incidence in our Afro-Carribean population. Although prevention policies seem effective, we need to focus on new risk factors limitation and on male population adherence to prevention program.

Safety of standard-dose (.9-mg/kg) alteplase intravenous thrombolysis for acute ischemic stroke in Afro-Caribbeans, French West Indies.

BACKGROUND: Pharmacobiologic data suggested that people of African ancestry were more sensitive to the recombinant tissue plasminogen activator, alteplase, than Caucasians. Furthermore, the higher incidences of hypertension and diabetes mellitus in black populations could contribute to a higher cerebral bleeding risk. However, standard-dose (.9-mg/kg) alteplase safety for stroke has never been evaluated in blacks. This study was undertaken to evaluate standard-dose alteplase safety to treat strokes in an Afro-Caribbean population. METHODS: Parenchymal hemorrhage and symptomatic intracerebral hemorrhage rates in Afro-Caribbean Martinicans given standard-dose alteplase for acute stroke were evaluated based on prospectively collected data from 2007 to 2010 and compared with those from studies on predominantly Caucasian stroke victims. RESULTS: Parenchymal hemorrhage type 2 and symptomatic intracerebral hemorrhages, as defined by the third European Cooperative Acute Stroke Study, respectively, occurred in 15 (10.1%) and 12 (8.1%) of the 148 thrombolyzed Afro-Caribbeans, respectively. This excess bleeding risk (parenchymal hemorrhage type 2) concerned more patients >70 than those 70 years of age or lesser (respectively, 17.6% [13 of 74] vs. 2.7% [2 of 74]). Older age was the only factor significantly associated with a higher parenchymal hemorrhage type 2 risk (P = .02). CONCLUSIONS: The excess hemorrhagic risk after standard-dose alteplase infusion into older Afro-Caribbean patients warrants further study to determine the possible role of cerebral microangiopathy and should be evaluated in different black populations.

Infarction in the anterior choroidal artery territory: clinical progression and prognosis factors.

This study was undertaken to describe the still poorly known evolving profile of anterior choroidal artery (AChA) infarctions, identify their prognosis factors, and evaluate responses to intravenous (IV) thrombolysis. During 42 months, we prospectively enrolled patients with an isolated AChA stroke. Clinical and radiologic parameters were compared between patients with or without progression, defined as any clinical worsening. Factors associated with poor outcome (dependence or death) were tested, and IV thrombolysis responses were assessed. For the 100 of 1234 (8.1%) analyzed patients with AChA stroke (predominantly lacunar syndrome [88%]), mean admission and maximum National Institutes of Health Stroke Scale (NIHSS) scores were 4.4 and 5.2, respectively. Arterial hypertension (78%) and diabetes (30%) were the main vascular risk factors. Despite low 3-month mortality (3%), 26% of the patients were dependent; 46 patients with progressive stroke (over 56 ± 56 hours, 1.6 mean successive plateaus) had higher risks of dependence (P < .0001). An acute-phase NIHSS score of 6 or more significantly increased the risk of poor outcome (P < .0001). Maximum NIHSS score and progression were independently associated with poor outcome. Among 21 patients given IV thrombolysis, 12 AChA strokes continued to progress, leaving 8 disabled at 3 months. Almost half of AChA strokes progress during the first 2 to 3 days. Maximum acute-phase NIHSS scores and progression were independently associated with poor outcome, also strongly predicted by an NIHSS score of 6 or more at any time. Our unconvincing experience with IV thrombolysis means new therapeutic options and trials are needed, especially for patients with clinical progression and/or NIHSS score of 6 or more.

Detection of moderate to severe middle cerebral artery atherosclerotic stenosis in stroke patients: Transcranial color-coded duplex sonography versus computed tomography angiography.

Background: Intracranial atherosclerotic stenosis is a common cause of ischemic cerebrovascular events and is associated with a high risk of stroke recurrence. This study aimed to assess the diagnostic accuracy of transcranial color-coded duplex sonography for moderate-to-severe middle cerebral artery stenosis in stroke patients. Methods: A retrospective analysis was carried out, including 31 patients aged ⩾18 years hospitalized for ischemic cerebrovascular event in whom middle cerebral artery stenosis ⩾30% was identified on computed tomography angiography. Transcranial color-coded duplex sonography findings were compared to the degree of stenosis blindly identified on the computed tomography angiography used as the reference method. Results: Overall, 27 patients had M1 stenosis and the other 4 had M2 stenosis. To detect M2 stenosis ⩾ 50% and ⩾ 70%, stenotic to pre-stenotic ratio ⩾ 2 and ⩾ 3 had a sensitivity of 100%, respectively. To detect M1 stenosis ⩾ 70%, peak systolic velocity ⩾ 300 cm/s had a sensitivity of 53.8% and specificity of 85.7% with area under the receiver-operating characteristic curve of 0.753 (95% confidence interval: 0.568-0.938; p = 0.026), and stenotic to pre-stenotic ratio ⩾ 3 had a sensitivity of 84.6% and a specificity of 78.6% (area under the curve = 0.854; 95% confidence interval: 0.707-1; p = 0.002). Middle cerebral artery/anterior cerebral artery velocity ratio < 0.7 had a sensitivity of 57.1% and specificity of 90% to detect dampened pre-stenotic flow in middle cerebral artery secondary to downstream M1 stenosis ⩾ 70% (area under the curve = 0.800; 95% confidence interval: 0.584-1; p = 0.040). Conclusion: This study showed that stenotic to pre-stenotic ratio ⩾ 3 was more sensitive than peak systolic velocity ⩾ 300 cm/s to screen M1 stenosis ⩾ 70%. Middle cerebral artery/anterior cerebral artery ratio < 0.7 was a good indirect sign to detect dampened pre-stenotic flow due to M1 stenosis ⩾ 70%.

Transient recurrent episodes of abducens nerve palsy and cheiro-oral syndrome in a sub-occlusive carotid bulb atherosclerotic stenosis.

We report the case of a male in his 50s with a history of smoking admitted to our hospital for three transient recurrent episodes of less than 60 min of cheiro-oral paresthesias and binocular horizontal diplopia with convergent strabismus. On admission, his neurological examination was normal. Cerebral magnetic resonance imaging showed no cerebral lesion. Computed tomography angiography showed a sub-occlusive right carotid bulb atherosclerotic stenosis, the absence of abnormality of the subclavian arteries and the origin of the vertebral arteries, and no stenosis of the basilar artery or posterior cerebral arteries. Routine blood tests were normal with glycated hemoglobin of 6.5%. The patient underwent right carotid endarterectomy. One year after carotid endarterectomy, the patient has had no other cerebrovascular events.

A Simple Score for Predicting Paroxysmal Atrial Fibrillation in Patients with Embolic Stroke of Undetermined Source in a Tunisian Cohort Study.

BACKGROUND: The annualized recurrent stroke rate in patients with Embolic Stroke of Undetermined Source (ESUS) under antiplatelet therapy is around 4.5%. Only a fraction of these patients will develop atrial fibrillation (FA), to which a stroke can be attributed retrospectively. The challenge is to identify patients at risk of occult AF during follow-up. OBJECTIVE: This work aims to determine clinical factors and electrocardiographic and ultrasound parameters that can predict occult AF in patients with ESUS and build a simple predictive score applicable worldwide. METHODS: This is a single-center, registry-based retrospective study conducted at the stroke unit of Sahloul University Hospital, Sousse, Tunisia, between January 2016 and December 2020. Consecutive patients meeting ESUS criteria were monitored for a minimum of one year, with a standardized follow-up consisting of outpatient visits, including ECG every three months and a new 24-hour Holter monitoring in case of palpitations. We performed multivariate stepwise regression to identify predictors of new paroxysmal AF among initial clinical, electrocardiographic (ECG and 24-hour Holter monitoring) and echocardiographic parameters. The coefficient of each independent covariate of the fitted multivariable model was used to generate an integerbased point-scoring system. RESULTS: Three hundred patients met the criteria for ESUS. Among them, 42 (14%) patients showed at least one episode of paroxysmal AF during a median follow-up of two years. In univariate analysis, age, gender, coronary artery disease, history of ischemic stroke, higher NIHSS at admission and lower NIHSS at discharge, abnormal P-wave axis, prolonged P-wave duration, premature atrial contractions (PAC) frequency of more than 500/24 hours, and left atrial (LA) mean area of more than 20 cm2 were associated with the risk of occurrence of paroxysmal AF. We proposed an AF predictive score based on (1.771 x NIHSS score at admission) + (10.015 x P-wave dispersion; coded 1 if yes and 0 if no) + (9.841x PAC class; coded 1 if ≥500 and 0 if no) + (9.828x LA class surface; coded 1 if ≥20 and 0 if no) + (0.548xNIHSS score at discharge) + 0.004. A score of ≥33 had a sensitivity of 76% and a specificity of 93%. CONCLUSION: In this cohort of patients with ESUS, NIHSS at both admission and discharge, Pwave dispersion, PAC≥500/24h on a 24-hour Holter monitoring, and LA surface area≥20 cm2 provide a simple AF predictive score with very reasonable sensitivity and specificity and is applicable almost worldwide. An external validation of this score is ongoing.

First-ever acute ischemic strokes in HIV-infected persons: A case-control study from stroke units.

OBJECTIVE: The stroke risk for persons living with human immunodeficiency virus (PLHIVs) doubled compared to uninfected individuals. Stroke-unit (SU)-access, acute reperfusion therapy-use and outcome data on PLHIVs admitted for acute ischemic stroke (AIS) are scarce. METHODS: AIS patients admitted (01 January 2017 to 31 January 2021) to 10 representative Paris-area SUs were screened retrospectively from the National Hospitalization Database. PLHIVs were compared to age-, initial NIHSS- and sex-matched HIV-uninfected controls (HUCs). Outcome was the 90-day modified Rankin Scale score. RESULTS: Among 126 PLHIVs with confirmed first-ever AIS, ~80% were admitted outside the thrombolysis-administration window. Despite antiretrovirals, uncontrolled plasma HIV loads exceeded 50 copies/mL (26% of all PLHIVs; 38% of those ≤55 years). PLHIVs' stroke causes by decreasing frequency were large artery atherosclerosis (LAA), undetermined, other cause, cerebral small-vessel disease (CSVD) or cardioembolism. No stroke etiology was associated with HIV duration or detectable HIVemia. MRI revealed previously unknown AIS in one in three PLHIVs, twice the HUC rate (p = 0.006). Neither group had optimally controlled modifiable cardiovascular risk factors (CVRFs): 20%-30% without specific hypertension, diabetes, and/or dyslipidemia treatments. Their stroke outcomes were comparable. Multivariable analyses retained good prognosis associated solely with initial NIHSS or reperfusion therapy. Older age and hypertension were associated with CSVD/LAA for all PLHIVs. Standard neurovascular care and reperfusion therapy were well-tolerated. INTERPRETATION: The high uncontrolled HIV-infection rate and suboptimal CVRF treatment support heightened vigilance to counter suboptimal HIV suppression and antiretroviral adherence, and improve CVRF prevention, mainly for younger PLHIVs. Those preventive, routine measures could lower PLHIVs' AIS risk.

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.

Second-dose intravenous thrombolysis with tenecteplase in alteplase-resistant medium-vessel-occlusion strokes: A retrospective and comparative study.

INTRODUCTION: In intracranial medium-vessel occlusions (MeVOs), intravenous thrombolysis (IVT) shows inconsistent effectiveness and endovascular interventions remains unproven. We evaluated a new therapeutic strategy based on a second IVT using tenecteplase for MeVOs without early recanalization post-alteplase. PATIENTS AND METHODS: This retrospective, comparative study included consecutively low bleeding risk MeVO patients treated with alteplase 0.9 mg/kg at two stroke centers. One center used a conventional single-IVT approach; the other applied a dual-IVT strategy, incorporating a 1-h post-alteplase MRI and additional tenecteplase, 0.25 mg/kg, if occlusion persisted. Primary outcomes were 24-h successful recanalization for efficacy and symptomatic intracranial hemorrhage (sICH) for safety. Secondary outcomes included 3-month excellent outcomes (modified Rankin Scale score of 0-1). Comparisons were conducted in the overall cohort and a propensity score-matched subgroup. RESULTS: Among 146 patients in the dual-IVT group, 103 failed to achieve recanalization at 1 h and of these 96 met all eligible criteria and received additional tenecteplase. Successful recanalization at 24 h was higher in the 146 dual-IVT cohort patients than in the 148 single-IVT cohort patients (84% vs 61%, p < 0.0001), with similar sICH rate (3 vs 2, p = 0.68). Dual-IVT strategy was an independent predictor of 24-h successful recanalization (OR, 2.7 [95% CI, 1.52-4.88]; p < 0.001). Dual-IVT cohort patients achieved higher rates of excellent outcome (69% vs 44%, p < 0.0001). Propensity score matching analyses supported all these associations. CONCLUSION: In this retrospective study, a dual-IVT strategy in selected MeVO patients was associated with higher odds of 24-h recanalization, with no safety concerns. However, potential center-level confounding and biases seriously limit these findings' interpretation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05809921.

Clinical, imaging, and management features of symptomatic carotid web: Insight from CAROWEB registry.

BACKGROUND: Although carotid web (CaW) is increasingly diagnosed as a cause of cryptogenic stroke, data are still limited to monocentric small sample cohort. To broaden knowledge on symptomatic CaW, CAROWEB registry has been recently implemented. AIMS: In a large cohort of symptomatic CaW patients, we described epidemiologic characteristics, admission clinical and imaging features, and the current management including the secondary preventive strategy choice made in comprehensive French Stroke Units. METHODS: CAROWEB is an ongoing French observational multicenter registry enrolling consecutive CaW patients diagnosed after an ipsilateral ischemic stroke (IS) or transient ischemic attack (TIA). Submitted cases were validated by two experienced neurologist and neuroradiologist. Clinical, imaging, and management features were collected for this study. RESULTS: Between June 2019 and December 2021, 244 cases were submitted by 14 centers, 42 rejected, and 202 included (IS, 91.6%; TIA, 7.9%; retinal infarction, 0.5%; mean age, 50.8 ± 12.2 years; female, 62.9%; Caucasian, 47.5%; Afro-Caribbean, 20.3%). IS patients showed median (interquartile range (IQR)) admission National Institutes of Health Stroke Scale (NIHSS) score, 8 (2-15); intracranial artery occlusion, 71.8%; ipsilateral chronic cerebral infarction (CCI), 16.3%; and reperfusion treatment, 57.3%. CaW was not identified during the mechanical thrombectomy procedure in 30 of 85 (35.3%) patients. Secondary prevention was invasive in 55.6% (stenting, n = 80; surgery, n = 30). In multivariable analysis, the invasive therapeutic option was associated with ipsilateral CCI (odds ratio (OR): 4.24 (1.27-14.2), p = 0.019) and inversely associated with risk factors (OR: 0.47 (0.24-0.91), p = 0.025) and admission NIHSS score (OR: 0.93 (0.89-0.97), p = 0.001). CONCLUSION: CaW must be considered in all ethnic groups including Caucasians. Secondary prevention is heterogeneous in large French Stroke Centers. The absence of risk factors, milder severity strokes, and ipsilateral CCI were predictive variables of secondary invasive treatment. The high rate of invasive treatment suggests that medical treatment alone is deemed ineffective to avoid recurrence and emphasize the need of 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.

Safety of long-term treatment of HAM/TSP patients with valproic acid.

HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease of the central nervous system induced by human T-lymphotropic virus type 1. As a potential therapeutic approach, we previously suggested reducing the proviral load by modulating lysine deacetylase activity using valproic acid (VPA) and exposing virus-positive cells to the host immune response. We conducted a single-center, 2-year, open-label trial, with 19 HAM/TSP volunteers treated with oral VPA. Proviral load, CD38/HLA-DR expression, and CD8(+) lysis efficiency were not significantly affected by VPA. Mean scores of HAM/TSP disability did not differ between baseline and final visit. Walking Time Test increased significantly (> 20%) in 3 patients and was in keeping with minor VPA side effects (drowsiness and tremor). Walking Time Test improved rapidly after VPA discontinuation. We conclude that long-term treatment with VPA is safe in HAM/TSP.