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.).

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.

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.

Heterozygous HTRA1 nonsense or frameshift mutations are pathogenic.

Heterozygous missense HTRA1 mutations have been associated with an autosomal dominant cerebral small vessel disease (CSVD) whereas the pathogenicity of heterozygous HTRA1 stop codon variants is unclear. We performed a targeted high throughput sequencing of all known CSVD genes, including HTRA1, in 3853 unrelated consecutive CSVD patients referred for molecular diagnosis. The frequency of heterozygous HTRA1 mutations leading to a premature stop codon in this patient cohort was compared with their frequency in large control databases. An analysis of HTRA1 mRNA was performed in several stop codon carrier patients. Clinical and neuroimaging features were characterized in all probands. Twenty unrelated patients carrying a heterozygous HTRA1 variant leading to a premature stop codon were identified. A highly significant difference was observed when comparing our patient cohort with control databases: gnomAD v3.1.1 [P = 3.12 × 10-17, odds ratio (OR) = 21.9], TOPMed freeze 5 (P = 7.6 × 10-18, OR = 27.1) and 1000 Genomes (P = 1.5 × 10-5). Messenger RNA analysis performed in eight patients showed a degradation of the mutated allele strongly suggesting a haploinsufficiency. Clinical and neuroimaging features are similar to those previously reported in heterozygous missense mutation carriers, except for penetrance, which seems lower. Altogether, our findings strongly suggest that heterozygous HTRA1 stop codons are pathogenic through a haploinsufficiency mechanism. Future work will help to estimate their penetrance, an important information for genetic counselling.

Predictors of Early Stroke or Death in Patients Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND/OBJECTIVE: While postoperative stroke is a known complication of Transcatheter Aortic Valve Implantation (TAVI), predictors of early stroke occurrence have not been specifically reviewed. The objective of this study was to estimate the predictors and incidence of stroke during the first 30 days post-TAVI. METHODS: A cohort of 506 consecutive patients having undergone TAVI between January 2017 and June 2019 was extracted from a prospective database. Preoperative, intraoperative and postoperative characteristics were analyzed by univariate analysis followed by logistic regression to find predictors of the occurrence of stroke or death within the first 30 days after the procedure. RESULTS: Incidence of stroke within 30 days post-TAVI was 4.9%, [CI 95% 3.3-7.2], i.e., 25 strokes. Four out of the 25 patients (16%) with a stroke died within 30 days post-TAVI. After logistic regression analysis, the predictors of early stroke related to TAVI were: CHA2Ds2VASc score ≥ 5 (odds ratio [OR] 2.62; 95% CI: 1.06-6.49; p = .037), supra-aortic access vs. femoral access (OR: 9.00, 95%CI: 2.95-27.44; p = .001) and introduction post-TAVI of a single vs. two or three antithrombotic agents (OR: 5.13; CI 95%: 1.99 to 13.19; p = .001). Over the 30-day period, bleeding occurred in 28 patients (5.5%), in 25 of whom, it was associated with femoral or iliac artery access injury. Anti-thrombotic regimen was not associated with bleeding; two patients out of 48 (4.1%) bled with a single anti-thrombotic regimen vs. 26 patients out of 458 (5.6%) with a dual or triple anti-thrombotic regimen (p = 0.94). The overall 30-day mortality rate was 3.9%, [95% CI 2.5-6.0]. Patients with a single post-TAVI antithrombotic agent (OR: 44.07 [CI 95% 13.45-144.39]; p < .0001) and patients with previous coronary artery bypass surgery or coronary artery stenting (OR: 6.16, [CI 95% 1.99-21.29]; p = .002) were at significantly higher risk of death within the 30-day period. CONCLUSION: In this large-scale single-center retrospective study, a single post-TAVI antithrombotic regimen independently predicted occurrence of early stroke or death. Dual or triple antithrombotic regimen was not associated with a higher risk of bleeding and should be considered as an option in patients undergoing TAVI.

Should We Screen for Janus Kinase 2 V617F Mutation in Cerebral Venous Thrombosis?

BACKGROUND: The presence of Janus Kinase 2 (JAK2) V617F mutation represents a major diagnostic criterion for detecting myeloproliferative neoplasms (MPN) and even in the absence of overt MPN, JAK2 V617F mutation is associated with splanchnic vein thrombosis. However, the actual prevalence and diagnostic value of the JAK2 V617F mutation in patients with cerebral venous thrombosis (CVT) are not known. The aims of this study were to assess the prevalence of JAK2 V617F mutation in a large group of consecutive CVT patients, to detect clinical, biological, and radiological features associated with the mutation, and to determine the long-term venous thrombosis recurrence rate in CVT patients with JAK2 mutation but without overt MPN in order to recommend the best preventive treatment. METHODS: This was a prospective study conducted on consecutive patients with a first-ever radiologically confirmed CVT. JAK2 V617F mutation analysis was assessed in all the study subjects. JAK2 V617F-positive patients were followed up to detect new venous thrombotic events. RESULTS: Of the 125 included subjects, 7 were found to have JAK2 V617F mutation (5.6%; 95% CI 2.3-11.2). Older age (p = 0.039) and higher platelet count (p = 0.004) were independently associated with JAK2 V617F positivity in patients without overt MPN. During a mean follow-up period of 59 (SD 46) months, 2 JAK2 V617F-positive patients presented with 4 new venous thromboembolic events. CONCLUSIONS: Screening for the JAK2 V617F mutation in CVT patients seems to be useful even in the absence of overt MPN and/or in the presence of other risk factors for CVT because of its relatively high prevalence and the risk of thrombosis recurrence.

Management of acute central retinal artery occlusion: Intravenous thrombolysis is feasible and safe.

Background Although acute central retinal artery occlusion is as a stroke in the carotid territory (retinal artery), its management remains controversial. The aim of this study was to assess the feasibility and safety of intravenous thrombolysis delivered within 6 h of central retinal artery occlusion in French stroke units. Methods We performed a retrospective analysis of patients treated with intravenous alteplase (recombinant tissue-plasminogen activator), based on stroke units thrombolysis registers from June 2005 to June 2015, and we selected those who had acute central retinal artery occlusion. The feasibility was assessed by the ratio of patients that had received intravenous alteplase within 6 h after central retinal artery occlusion onset among those who had been admitted to the same hospital for acute central retinal artery occlusion. All adverse events were documented. Results Thirty patients were included. Visual acuity before treatment was limited to "hand motion", or worse, in 90% of the cases. The mean onset-to-needle time was 273 min. The individuals treated with intravenous alteplase for central retinal artery occlusion represented 10.2% of all of the patients hospitalized for central retinal artery occlusion in 2013 and 2014. We observed one occurrence of major bleeding, a symptomatic intracerebral hemorrhage. Conclusion When applied early on, intravenous thrombolysis appears to be feasible and safe, provided that contraindications are given due consideration. Whether intravenous thrombolysis is more effective than conservative therapy remains to be determined. In order to conduct a well-designed prospective randomized control trial, an organized network should be in place.

Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome after bilateral carotid paraganglioma resection: A case report.

Background Paraganglioma is a rare neuroendocrine tumour arising anywhere along the paravertebral sympathetic and parasympathetic chains. In the neck, paraganglioma may affect the carotid body (carotid body tumour). Case report We describe a 43-year-old woman who presented with a reversible vasoconstriction syndrome associated with a posterior reversible encephalopathy syndrome following a surgery for a left carotid paraganglioma (with a past medical history of surgery for a right carotid paraganglioma a few months before). Conclusion A consequence of a baroreflex modification is discussed in order to explain the rare occurrence of such symptoms.

Venous Thrombotic Recurrence After Cerebral Venous Thrombosis: A Long-Term Follow-Up Study.

BACKGROUND AND PURPOSE: After cerebral venous thrombosis (CVT), the risk of venous thrombotic events was estimated at 2% to 3% for a new CVT and 3% to 8% for extracranial events. However, because of the paucity of prospective studies, the clinical course of CVT is still largely unknown. We aimed to prospectively evaluate the rate of thrombosis recurrence in a cohort of CVT patients with a long-term follow-up and to detect predisposing factors for recurrence. METHODS: Consecutive CVT patients with complete clinical, radiological, biological, and genetic data were systematically followed up. New venous thrombotic events were detected after hospital readmission and imaging confirmation. RESULTS: One-hundred eighty-seven patients (mean age 45±18 years, 67% women) with angiographically confirmed CVT were included. Cause was found in 73% of patients. Coagulation abnormality and JAK2 gene mutation were detected in 20% and 9%, respectively. Median follow-up length was 73 months (range 1-247 months). Mean duration of the oral anticoagulant treatment was 14 months. Mortality rate was 2.5% per year, with 2% in-hospital mortality. During follow-up, CVT reoccurred in 6 patients, whereas 19 subjects had a symptomatic extracranial venous thrombotic event, with cumulative venous thrombotic recurrence rates of 3% at 1 year, 8% at 2 years, 12% at 5 years, and 18% at 10 years. A previous venous thrombotic event (hazard ratio, 2.8; P=0.018), presence of cancer or malignant hemopathies (hazard ratio, 3.2; P=0.039), and unknown CVT causes (hazard ratio, 2.81; P=0.024) were independently associated with recurrence. CONCLUSIONS: In our cohort of CVT patients followed on average for >6 years, subjects with a previous venous thrombotic event, cancer/malignant hemopathies, and unknown CVT causes were found to be at higher risk of recurrence.

Anti-NMDA Receptor Encephalitis During Pregnancy: A Case Report.

Anti-N-methyl-D-aspartate receptor (anti-MMDAR) encephalitis is an immune-mediated encephalitis mainly affecting young women.We describe the case of a 21-year-old woman who developed a classical form of anti-NMDAR encephalitis during the 10th week of gestation. The patient had been treated with methylpredinsolone and intravenous immunoglobulins. Birth history of the child was normal, with normal APGAR score. The clinical symptoms of the patient have improved after a few months.This rare occurrence during pregnancy (only 9 other cases described) presents an opportunity to highlight the importance of making the earliest possible diagnosis of this treatable and potentially reversible encephalitis, and to educate gynecologists, psychiatrists, anesthetists, and neurologists on this potential cause of psychiatric and neurological manifestations during pregnancy.

Paroxysmal sneezing at the onset of syncopes and transient ischemic attack revealing a papillary cardiac fibroelastoma.

Sneezing can at times be associated with neurological disorders. The "sneeze center" is localized in the lateral medulla. We report the case of a 50-year-old man who presented three episodes of sneezing, two of them followed by an episode of transient gait instability and dizziness and the third one followed by an episode of transient left hemiparesis due to fibroelastoma of the aortic cardiac valve. To the best of our knowledge, this is the first description of a transient ischemic attack due to cardiac papillary fibroelastoma and revealed by violent episodes of sneezing.