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1.
Can J Neurol Sci ; : 1-17, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38826076

RESUMO

The 7th edition of the Canadian Stroke Best Practice Recommendations (CSBPR) is a comprehensive summary of current evidence-based recommendations, appropriate for use by healthcare providers and system planners, and intended to drive healthcare excellence, improved outcomes and more integrated health systems. This edition includes a new module on the management of cerebral venous thrombosis (CVT). Cerebral venous thrombosis is defined as thrombosis of the veins of the brain, including the dural venous sinuses and/or cortical or deep veins. Cerebral venous thrombosis is a rare but potentially life-threatening type of stroke, representing 0.5-1.0% of all stroke admissions. The reported rates of CVT are approximately 10-20 per million and appear to be increasing over time. The risk of CVT is higher in women and often associated with oral contraceptive use and with pregnancy and the puerperium. This guideline addresses care for adult individuals who present to the healthcare system with current or recent symptoms of CVT. The recommendations cover the continuum of care from diagnosis and initial clinical assessment of symptomatic CVT, to acute treatment of symptomatic CVT, post-acute management, person-centered care, special considerations in the long-term management of CVT, including pregnancy and considerations related to CVT in special circumstances such as trauma and vaccination. This module also includes supporting materials such as implementation resources to facilitate the adoption of evidence into practice and performance measures to enable monitoring of uptake and effectiveness of recommendations.

2.
J Stroke Cerebrovasc Dis ; 33(8): 107811, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38866118

RESUMO

OBJECTIVES: Embolic Stroke of Undetermined Source (ESUS) is a distinct stroke entity that disproportionately affects young adults. We sought to describe characteristics, workup and outcomes of young adult ESUS patients who underwent thrombectomy, and compare outcomes to those reported in different age groups. MATERIALS AND METHODS: Young-ESUS is a multicenter longitudinal cohort study that enrolled consecutive patients aged 21-50 years at 41 stroke centers in 13 countries between 2017- 2019. Between-group comparisons were performed using Wilcoxon rank sum test for continuous variables or Fisher's exact test for binary variables. Distribution of functional outcomes after thrombectomy for our young adult cohort versus pediatric and older adult cohorts reported in the literature were described using the Kruskal-Wallis test. RESULTS: Of 535 patients enrolled in Young-ESUS, 65 (12.1%) were treated with endovascular thrombectomy. Patients who underwent thrombectomy were more likely to undergo in-depth cardiac testing than those who did not, but cardiac abnormalities were not detected more often in this group. Among thrombectomy patients, 35/63 (55.6%) had minimal to no functional disability at follow up. When adjusted for age, stroke severity and IV alteplase, the odds of achieving favorable outcome did not differ between treated versus untreated patients. CONCLUSIONS: Thrombectomy is not rare in young adults with ESUS. Despite extensive workup, cardiac abnormalities were not more prevalent in the thrombectomy group. More research to determine optimal workup, etiologic factors and favorable outcome of stroke across the lifespan is needed.


Assuntos
Avaliação da Deficiência , AVC Embólico , Trombectomia , Humanos , Trombectomia/efeitos adversos , Masculino , Feminino , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Resultado do Tratamento , Estudos Longitudinais , AVC Embólico/etiologia , AVC Embólico/diagnóstico , Fatores Etários , Fatores de Risco , Fatores de Tempo , Estado Funcional , Recuperação de Função Fisiológica , Procedimentos Endovasculares/efeitos adversos , Medição de Risco , Europa (Continente)
3.
Stroke ; 54(11): 2724-2736, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37675613

RESUMO

BACKGROUND: Emerging data suggest that direct oral anticoagulants may be a suitable choice for anticoagulation for cerebral venous thrombosis (CVT). However, conducting high-quality trials in CVT is challenging as it is a rare disease with low rates of adverse outcomes such as major bleeding and functional dependence. To facilitate the design of future CVT trials, SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) assessed (1) the feasibility of recruitment, (2) the safety of rivaroxaban compared with standard-of-care anticoagulation, and (3) patient-centered functional outcomes. METHODS: This was a phase II, prospective, open-label blinded-end point 1:1 randomized trial conducted at 12 Canadian centers. Participants were aged ≥18 years, within 14 days of a new diagnosis of symptomatic CVT, and suitable for oral anticoagulation; they were randomized to receive rivaroxaban 20 mg daily, or standard-of-care anticoagulation (warfarin, target international normalized ratio, 2.0-3.0, or low-molecular-weight heparin) for 180 days, with optional extension up to 365 days. Primary outcomes were annual rate of recruitment (feasibility); and a composite of symptomatic intracranial hemorrhage, major extracranial hemorrhage, or mortality at 180 days (safety). Secondary outcomes included recurrent venous thromboembolism, recanalization, clinically relevant nonmajor bleeding, and functional and patient-reported outcomes (modified Rankin Scale, quality of life, headache, mood, fatigue, and cognition) at days 180 and 365. RESULTS: Fifty-five participants were randomized. The rate of recruitment was 21.3 participants/year; 57% of eligible candidates consented. Median age was 48.0 years (interquartile range, 38.5-73.2); 66% were female. There was 1 primary event (symptomatic intracranial hemorrhage), 2 clinically relevant nonmajor bleeding events, and 1 recurrent CVT by day 180, all in the rivaroxaban group. All participants in both arms had at least partial recanalization by day 180. At enrollment, both groups on average reported reduced quality of life, low mood, fatigue, and headache with impaired cognitive performance. All metrics improved markedly by day 180. CONCLUSIONS: Recruitment targets were reached, but many eligible participants declined randomization. There were numerically more bleeding events in patients taking rivaroxaban compared with control, but rates of bleeding and recurrent venous thromboembolism were low overall and in keeping with previous studies. Participants had symptoms affecting their well-being at enrollment but improved over time. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03178864.


Assuntos
Tromboembolia Venosa , Trombose Venosa , Humanos , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Masculino , Rivaroxabana/efeitos adversos , Anticoagulantes/efeitos adversos , Tromboembolia Venosa/induzido quimicamente , Estudos Prospectivos , Estudos de Viabilidade , Qualidade de Vida , Canadá , Hemorragia/induzido quimicamente , Trombose Venosa/tratamento farmacológico , Hemorragias Intracranianas/induzido quimicamente , Cefaleia
4.
Stroke ; 53(1): 45-52, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34538089

RESUMO

BACKGROUND AND PURPOSE: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial. METHODS: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics. RESULTS: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26-115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack (P<0.001), modified Rankin Scale score >0 (P<0.001), and current tobacco use (P=0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS. CONCLUSIONS: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909.


Assuntos
Infarto Encefálico/diagnóstico por imagem , Infarto Encefálico/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/tratamento farmacológico , Rivaroxabana/uso terapêutico , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Estudos de Coortes , Método Duplo-Cego , Feminino , Humanos , Internacionalidade , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico
5.
Can J Neurol Sci ; 48(3): 417-418, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32892767

RESUMO

A 56-year-old woman with Down syndrome presented with right-sided weakness and dysarthria, and was found on CT/CTA to have a left middle cerebral artery infarct secondary to moyamoya disease. Her left posterior inferior cerebellar artery (PICA) was fed both by the left vertebral artery, and the left ascending pharyngeal artery (APA), with a variant origin from the internal carotid artery (ICA), then passing through the jugular foramen (Figure 1). Her right PICA originated exclusively from her right occipital artery, also via the jugular foramen (Figure 2). The left vertebral artery originated directly from the aortic arch, whereas the right vertebral artery originated from the brachiocephalic trunk. In addition, she had a trifurcated anterior cerebral artery (ACA), and just prior to this trifurcation, her left ACA was partially supplied by the left ICA, via a superior hypophyseal artery. This case is noteworthy for several reasons. First, though it is exceedingly rare to have the PICA supplied by the jugular branch of the APA, this is the first reported case with an ICA origin of that APA.1,2 The fact that both PICAs in this patient originate from the anterior circulation should remind clinicians that in unexplained posterior circulation infarctions, vascular anatomy should be explored, as carotid-vertebrobasilar anastomoses such as these are rare, but possible. Lastly, the conjunction of moyamoya disease and anomalies of the vertebrobasilar system in a patient with Down syndrome raises interesting questions about the influence of trisomy 21 on the developing vasculature. Connections from the APA to the vertebrobasilar system are hypothesized to result from a lack of regression of an embryological anastomosis, in line with the more common persistent trigeminal and persistent hypoglossal arteries.1 Patients with moyamoya disease have a significantly higher rate of persistent carotid-vertebrobasilar anastomoses than the general population,3 and are also 26 times more likely to have Down syndrome.4 Correspondingly, patients with Down syndrome have significantly higher levels of moyamoya disease, and are more than 10 times as likely as the general population to have abnormalities of the Circle of Willis5 and vertebral arteries.6 Several genes on chromosome 21 are known to affect angiogenesis, namely collagen XIII/endostatin (COL18A1), DYRK1A, and Down syndrome candidate region 1 (DSCR1), possibly through inhibition of VEGF activity.7 Whether additional copies of these genes are responsible for the anomalous vascular development seen in Down syndrome, in turn predisposing to the development of moyamoya disease, could benefit from further exploration.


Assuntos
Síndrome de Down , Doença de Moyamoya , Artérias Carótidas , Artéria Carótida Interna/diagnóstico por imagem , Síndrome de Down/complicações , Feminino , Humanos , Pessoa de Meia-Idade , Doença de Moyamoya/complicações , Doença de Moyamoya/diagnóstico por imagem , Artéria Vertebral/diagnóstico por imagem
6.
J Stroke Cerebrovasc Dis ; 29(8): 104936, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689594

RESUMO

BACKGROUND: Non-stenotic intracranial and systemic atherosclerosis are associated with ischemic stroke. We report frequency and response to anticoagulant vs. antiplatelet prophylaxis of patients with embolic stroke of undetermined source (ESUS) who have non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis. METHODS: Exploratory analysis of the international NAVIGATE ESUS randomized trial comparing rivaroxaban 15mg daily with aspirin 100mg daily in 7213 patients with recent ESUS. Among participants with results of intracranial arterial imaging with either computed tomographic angiography (CTA) or magnetic resonance angiography (MRA), the frequency and predictors of non-stenotic intracranial and systemic atherosclerosis and responses to antithrombotic therapy were assessed. RESULTS: Among 4723 participants with available intracranial CTA or MRA results (65% of the trial cohort), the prevalence of intracranial atherosclerosis was 16% (n=739). Patient features independently associated with intracranial atherosclerosis included East Asian region (odds ratio 2.7, 95%CI 2.2,3.3) and cervical carotid plaque (odds ratio 2.3, 95%CI 1.9,2.7), among others. The rate of recurrent ischemic stroke averaged 4.8%/year among those with intracranial atherosclerosis vs. 5.0.%/year for those without (HR 0.95, 95%CI 0.65, 1.4). Among those with intracranial atherosclerosis, the recurrent ischemic stroke rate was higher if assigned to rivaroxaban (5.8%/year) vs. aspirin (3.7%/year), but the difference was not statistically significant (HR 1.6, 95%CI 0.78, 3.3). There was trend for the effect of antithrombotic treatments to be different according to the presence or absence of intracranial atherosclerosis (pinteraction=0.09). Among participants with evidence of systemic atherosclerosis by either history or imaging (n=3820), recurrent ischemic stroke rates were similar among those assigned to rivaroxaban (5.5%/year) vs. aspirin (4.9%/year)(HR 1.1, 95%CI 0.84, 1.5). CONCLUSIONS: East Asia region was the strongest factor associated with intracranial atherosclerosis. There were no statistically significant differences between rivaroxaban and aspirin prophylaxis for recurrent ischemic stroke in patients with non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis.


Assuntos
Aspirina/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Fibrinolíticos/administração & dosagem , Arteriosclerose Intracraniana/tratamento farmacológico , Embolia Intracraniana/prevenção & controle , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação Plaquetária/administração & dosagem , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Idoso , Aspirina/efeitos adversos , Método Duplo-Cego , Inibidores do Fator Xa/efeitos adversos , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/epidemiologia , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/epidemiologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/epidemiologia , Inibidores da Agregação Plaquetária/efeitos adversos , Prevalência , Recidiva , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do Tratamento
7.
J Stroke Cerebrovasc Dis ; 28(8): 2273-2279, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31160218

RESUMO

BACKGROUND: Embolic stroke of undetermined source (ESUS) identifies patients with cryptogenic ischemic stroke presumed due to embolism from several unidentified sources. Among patients with recent ESUS, we sought to determine independent predictors of recurrent ischemic stroke during treatment with aspirin or rivaroxaban and to assess the relative effects of these treatments according to risk. METHODS: Exploratory analyses of 7213 participants in the NAVIGATE ESUS international trial who were randomized to aspirin 100 mg/day or rivaroxaban 15 mg/day and followed for a median of 11 months, during which time there were 309 first recurrent ischemic strokes (4.6% per year). Baseline features were correlated with recurrent stroke by multivariate analysis. RESULTS: The 7 independent predictors of recurrent stroke were stroke or transient ischemic attack (TIA) prior to the qualifying stroke (hazard ratio [HR] 2.03 95% confidence internal [CI] 1.58-2.60), current tobacco user (HR 1.62, 95% CI 1.24-2.12), age (HR 1.02 per year increase, 95%CI 1.01-1.03), diabetes (HR 1.28, 95% CI 1.01-1.64), multiple acute infarcts on neuroimaging (HR 1.49, 95% CI 1.09-2.02), aspirin use prior to qualifying stroke (HR 1.34, 95% CI 1.02-1.70), and time from qualifying stroke to randomization (HR .98, 95% CI .97-.99). The rate of recurrent stroke rate was 2.6% per year for participants without any of these risk factors, and increased by an average of 45% for each independent predictor (P < .001). There were no significant interactions between treatment effects and independent stroke predictors or stroke risk status. CONCLUSIONS: In this large cohort of ESUS patients, several features including prior stroke or TIA, advanced age, current tobacco user, multiple acute infarcts on neuroimaging, and diabetes independently identified those with an increased risk of ischemic stroke recurrence. The relative effects of rivaroxaban and aspirin were similar across the spectrum of independent stroke predictors and recurrent stroke risk status.


Assuntos
Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Embolia Intracraniana/tratamento farmacológico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Método Duplo-Cego , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Embolia Intracraniana/diagnóstico , Embolia Intracraniana/etiologia , Masculino , Pessoa de Meia-Idade , Recidiva , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento
8.
Am Heart J ; 201: 160-163, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29764671

RESUMO

BACKGROUND: The Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial (ASSERT) demonstrated that subclinical atrial fibrillation (SCAF) was associated with a 2.5-fold increased risk of stroke. However, the absolute stroke rate was only 1.7% per year and fewer than 20% patients with stroke had SCAF in the preceding 30 days. This raises the possibility that SCAF is merely a risk marker for stroke rather than the cause. Systematic characterization of stroke subtypes among patients with SCAF would help clarify this issue. METHODS: All ischemic strokes that occurred in the ASSERT trial were blindly adjudicated by stroke neurologists, classified as cortical versus subcortical, and subtyped using modified TOAST criteria. Stroke severity was measured using the modified Rankin Score. RESULTS: Of the 44 participants who had an ischemic stroke, 14 had SCAF before stroke. Among patients with SCAF who had stroke, 57% of strokes (n = 8) were judged to be cardioembolic, 36% to be lacunar (n = 5), and 7% (n = 1) to be large artery disease. However, of 5 patients who had SCAF detected within 30 days before their index stroke, 4 patients had a cardioembolic stroke. The average duration of SCAF in these 4 patients was 6.0 ± 6.1 h/d. The modified Rankin score at 30 days was similar between patients with (2.7 ± 2.3) and without SCAF (2.3 ± 2.0; P = .68). CONCLUSIONS: In patients with SCAF and stroke, SCAF seems probably causal in many cases; however, in more than 40%, it seems to be acting only as a risk marker.


Assuntos
Fibrilação Atrial/terapia , Isquemia Encefálica/etiologia , Marca-Passo Artificial , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Fibrilação Atrial/complicações , Isquemia Encefálica/diagnóstico , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Fatores de Risco , Índice de Gravidade de Doença
9.
Stroke ; 48(4): 867-872, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28265016

RESUMO

BACKGROUND AND PURPOSE: Embolic stroke of undetermined source (ESUS) designates patients with nonlacunar cryptogenic ischemic strokes in whom embolism is the likely stroke mechanism. It has been hypothesized that anticoagulation is more efficacious than antiplatelet therapy for secondary stroke prevention in ESUS patients. We review available information about ESUS. METHODS: Systematic literature review to assess the frequency of ESUS, patient features, and prognosis using PubMed from 2014 to present, unrestricted by language. RESULTS: On the basis of 9 studies, the reported frequency of ESUS ranged from 9% to 25% of ischemic strokes, averaging 17%. From 8 studies involving 2045 ESUS patients, the mean age was 65 years and 42% were women; the mean NIH stroke score was 5 at stroke onset (4 studies, 1772 ESUS patients). Most (86%) ESUS patients were treated with antiplatelet therapy during follow-up, with the annualized recurrent stroke rate averaging 4.5% per year during a mean follow-up of 2.7 years (5 studies, 1605 ESUS patients). CONCLUSIONS: ESUS comprises about 1 ischemic stroke in 6. Patients with ischemic stroke meeting criteria for ESUS were relatively young compared with other ischemic stroke subtypes and had, on average, minor strokes, consistent with small emboli. Retrospective methods of available studies limit confidence in stroke recurrence rates but support a substantial (>4% per year) rate of stroke recurrence during (mostly) antiplatelet therapy. There is an important need to define better antithrombotic prophylaxis for this frequently occurring subtype of ischemic stroke.


Assuntos
Anticoagulantes/uso terapêutico , Isquemia Encefálica/epidemiologia , Embolia Intracraniana/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/etiologia , Feminino , Humanos , Embolia Intracraniana/complicações , Embolia Intracraniana/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia
10.
Stroke ; 47(9): 2197-202, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27507860

RESUMO

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is increasingly recognized as the single most important cause of disabling ischemic stroke in the elderly. We undertook an international survey to characterize the frequency of AF-associated stroke, methods of AF detection, and patient features. METHODS: Consecutive patients hospitalized for ischemic stroke in 2013 to 2014 were surveyed from 19 stroke research centers in 19 different countries. Data were analyzed by global regions and World Bank income levels. RESULTS: Of 2144 patients with ischemic stroke, 590 (28%; 95% confidence interval, 25.6-29.5) had AF-associated stroke, with highest frequencies in North America (35%) and Europe (33%) and lowest in Latin America (17%). Most had a history of AF before stroke (15%) or newly detected AF on electrocardiography (10%); only 2% of patients with ischemic stroke had unsuspected AF detected by poststroke cardiac rhythm monitoring. The mean age and 30-day mortality rate of patients with AF-associated stroke (75 years; SD, 11.5 years; 10%; 95% confidence interval, 7.6-12.6, respectively) were substantially higher than those of patients without AF (64 years; SD, 15.58 years; 4%; 95% confidence interval, 3.3-5.4; P<0.001 for both comparisons). There was a strong positive correlation between the mean age and the frequency of AF (r=0.76; P=0.0002). CONCLUSIONS: This cross-sectional global sample of patients with recent ischemic stroke shows a substantial frequency of AF-associated stroke throughout the world in proportion to the mean age of the stroke population. Most AF is identified by history or electrocardiography; the yield of conventional short-duration cardiac rhythm monitoring is relatively low. Patients with AF-associated stroke were typically elderly (>75 years old) and more often women.


Assuntos
Fibrilação Atrial/complicações , Isquemia Encefálica/epidemiologia , Embolia Intracraniana/epidemiologia , Ataque Isquêmico Transitório/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Fatores Etários , Idoso , Isquemia Encefálica/etiologia , Isquemia Encefálica/mortalidade , Eletrocardiografia , Feminino , Humanos , Incidência , Embolia Intracraniana/etiologia , Embolia Intracraniana/mortalidade , Ataque Isquêmico Transitório/etiologia , Ataque Isquêmico Transitório/mortalidade , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores Sexuais , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Taxa de Sobrevida
12.
Int J Stroke ; 19(4): 470-477, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37981572

RESUMO

BACKGROUND: Chronic ischemic lesions (CILs) are frequent findings in patients with acute ischemic stroke, but their phenotypes and relevance in young adults with embolic stroke of undetermined source (Y-ESUS) remains uncertain. We aimed to compare Y-ESUS patients with CIL to those without CIL and assessed the association of CIL and its phenotypes with the presence of patent foramen ovale (PFO). METHODS: This prospective longitudinal, multicenter cohort study enrolled consecutive patients 50 years and younger with ESUS from October 2017 to October 2019 in 41 stroke research centers in 13 countries. Local investigators adjudicated presence and phenotypes of CIL on routine brain imaging (either magnetic resonance imaging (MRI) or computed tomography (CT)). RESULTS: Overall, 535 patients were enrolled (mean age = 40.4 (standard deviation (SD) = 7.3) years, 238 (44%) female). CILs were present in 76/534 (14.2%) patients with a median count CIL count of 1.0 (interquartile range (IQR) = 1-2), 42/76 (55%) had at least one cortical phenotype and 38/76 (50%) at least one non-cortical phenotype. Y-ESUS with CIL were less often female (32% vs 47% in non-CIL Y-ESUS), were older (mean 43 vs 40 years), had more often hypertension (42% vs 19%), diabetes (17% vs 7%), and hyperlipidemia (34% vs 18%). CIL Y-ESUS were independently associated with lower stroke recurrence (relative risk (RR) = 0.17 (0.05-0.61)). In Y-ESUS with PFO, CILs were less frequent in probable pathogenic PFO than with probable non-pathogenic PFO (6.1% vs 30% p< 0.001). CONCLUSION: One in seven Y-ESUS patients has additional CIL. CILs were associated with several vascular risk factors, lower probability of a pathogenic PFO, and lower stroke recurrence.


Assuntos
AVC Embólico , Forame Oval Patente , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Feminino , Adulto Jovem , Adulto , Masculino , Acidente Vascular Cerebral/complicações , Forame Oval Patente/complicações , Forame Oval Patente/diagnóstico por imagem , Forame Oval Patente/epidemiologia , AVC Embólico/complicações , Estudos de Coortes , Estudos Prospectivos , AVC Isquêmico/complicações , Fatores de Risco , Sistema de Registros
13.
Rheumatol Adv Pract ; 7(3): rkad080, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38091383

RESUMO

Primary CNS vasculitis (CNSV) is a rare, idiopathic autoimmune disease that, if untreated, can cause significant morbidity and mortality. It is a challenging diagnosis due to multiple mimics that can be difficult to differentiate, given that the CNS is an immunologically privileged and structurally isolated space. As such, diagnosis requires comprehensive multimodal investigations. Usually, a brain biopsy is required to confirm the diagnosis. Treatment of CNSV involves aggressive immunosuppression, but relapses and morbidity remain common. This expert review provides the reader with a deeper understanding of presentations of CNSV and the multiple parallel diagnostic pathways that are required to diagnose CNSV (and recognize its mimics), highlights the important knowledge gaps that exist in the disease and also highlights how we might be able to care for these patients better in the future.

14.
Can J Cardiol ; 39(2): 187-197, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36179950

RESUMO

BACKGROUND: Clinical trials provide conflicting evidence regarding oral factor Xa inhibitors for prevention of ischemic stroke in patients without a history of atrial fibrillation (AF). METHODS: We performed a critical appraisal of randomized clinical trials that tested oral factor Xa inhibitors in patients without AF that reported ischemic stroke. RESULTS: Considering the 11 trials that reported > 10 ischemic strokes during follow-up (97,578 participants, 1195 ischemic strokes), 1 tested apixaban (57 strokes), 1 betrixaban (52 strokes), and 9 rivaroxaban (1086 strokes). In 7 trials with placebo comparisons, numerically fewer ischemic strokes occurred among those assigned factor Xa inhibitors in 7 of 8 randomized comparisons (range of hazard ratios [HRs], 0.89-0.51), including statistically significant reductions in 2 trials that compared rivaroxaban 2.5 mg twice daily vs placebo on a background of aspirin in patients with cardiovascular disease, COMPASS (HR, 0.51; 95% confidence interval [CI], 0.38-0.68) and COMMANDER-HF (HR, 0.64; 95% CI, 0.43-0.95). Compared with aspirin in 4 trials, oral factor Xa inhibitors were associated with fewer ischemic strokes in 2, with statistically significant reduction in 1 (rivaroxaban 5 mg twice daily in COMPASS; HR, 0.69; 95% CI, 0.53-0.90). Major bleeding was increased by oral factor Xa inhibitors in all 7 placebo-controlled trials (HR range, 1.42-4.08), with statistically significant increases reported in 5 trials, and in all 4 aspirin-controlled trials (all statistically significant increases; HR range, 1.52-2.72). CONCLUSIONS: Aggregate evidence on the basis of placebo comparisons from randomized trials supports the potential for oral factor Xa inhibitors to reduce ischemic stroke in patients without AF, but major bleeding is increased.


Assuntos
Fibrilação Atrial , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Inibidores do Fator Xa/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Rivaroxabana/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/complicações , Hemorragia/tratamento farmacológico , Aspirina , Anticoagulantes/uso terapêutico
15.
Eur Stroke J ; 7(2): 92-98, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35647310

RESUMO

Purpose: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of direct oral anticoagulation (DOAC) compared with antiplatelet therapy for secondary stroke prevention in adult patients with embolic stroke of undetermined source (ESUS). Method: We searched major databases (Embase, MEDLINE, CINAHL, CENTRAL, and Web of Science) for RCTs published until March 2021. The primary outcome was recurrent stroke, and the main safety outcomes were major bleeding and clinically relevant non-major bleeding (CRNB). We assessed risk of bias using the Cochrane Risk of Bias tool. We used a random-effects model to determine pooled risk ratios and 95% confidence intervals in the datasets and key subgroups. Findings: Our search identified two RCTs, involving a total of 12,603 patients with ESUS. Anticoagulation with dabigatran or rivaroxaban compared with aspirin did not reduce the risk of recurrent stroke (RR, 0.96 [0.76-1.20]) or increase major bleeding (RR, 1.77 [0.80-3.89]) but significantly increased the composite of major or clinically relevant non-major bleeding (RR, 1.57 [1.26-1.97]). Prespecified subgroup analysis demonstrated consistent results according to age and sex. Additional post-hoc subgroup analyses demonstrated consistent results according to prior stroke and presence of a patent foramen ovale but suggested that DOACs reduced recurrent stroke in patients with an estimated glomerular filtration rate (eGFR) <50 and 50-80 ml/min but not in those with eGFR >80 ml/min (interaction P = 0.0234). Discussion/conclusion: Direct oral anticoagulations are not more effective than aspirin in preventing stroke recurrence in patients with ESUS and increase bleeding. Registration: PROSPERO ID: CRD42019138593.

16.
Int J Stroke ; 17(7): 799-805, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34791941

RESUMO

BACKGROUND: Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown. AIMS: To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate the effects of antithrombotic therapies. METHODS: At 87 sites in 15 countries, substudy participants were randomly assigned to receive rivaroxaban 15 mg daily or aspirin 100 mg daily and underwent brain MRI near randomization and after study termination. The primary outcome was incident brain infarct (clinical ischemic stroke or covert brain infarct). Brain infarcts and microbleeds were ascertained centrally by readers unaware of treatment. Treatment effects were estimated using logistic regression. RESULTS: Among the 718 substudy participants with interpretable, paired MRIs, the mean age was 67 years and 61% were men with a median of 52 days between the qualifying ischemic stroke and randomization and a median of seven days between randomization and baseline MRI. During the median (IQR) 11 (12) month interval between scans, clinical ischemic strokes occurred in 27 (4%) participants, while 60 (9%) of the remaining participants had an incident covert brain infarct detected by MRI. Assignment to rivaroxaban was not associated with reduction in the incidence of brain infarct (OR 0.77, 95% CI 0.49, 1.2) or of covert brain infarct among those without clinical stroke (OR 0.85, 95% CI 0.50, 1.4). New microbleeds were observed in 7% and did not differ among those assigned rivaroxaban vs. aspirin (HR 0.95, 95% CI 0.52-1.7). CONCLUSIONS: Incident covert brain infarcts occurred in twice as many ESUS patients as a clinical ischemic stroke. Treatment with rivaroxaban compared with aspirin did not significantly reduce the incidence of covert brain infarcts or increase the incidence of microbleeds, but the confidence intervals for treatment effects were wide.Registration: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.


Assuntos
AVC Embólico , Embolia Intracraniana , Acidente Vascular Cerebral , Idoso , Aspirina/uso terapêutico , Infarto Encefálico/diagnóstico por imagem , Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/etiologia , Hemorragia Cerebral/tratamento farmacológico , Método Duplo-Cego , Inibidores do Fator Xa/uso terapêutico , Feminino , Humanos , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/tratamento farmacológico , Embolia Intracraniana/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Estudos Prospectivos , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle
17.
JAMA Neurol ; 79(5): 450-458, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35285869

RESUMO

Importance: Cryptogenic strokes constitute approximately 40% of ischemic strokes in young adults, and most meet criteria for the embolic stroke of undetermined source (ESUS). Two randomized clinical trials, NAVIGATE ESUS and RESPECT ESUS, showed a high rate of stroke recurrence in older adults with ESUS but the prognosis and prognostic factors among younger individuals with ESUS is uncertain. Objective: To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults. Design, Setting, and Participants: This multicenter longitudinal cohort study with enrollment from October 2017 to October 2019 and a mean follow-up period of 12 months ending in October 2020 included 41 stroke research centers in 13 countries. Consecutive patients 50 years and younger with a diagnosis of ESUS were included. Of 576 screened, 535 participants were enrolled after 1 withdrew consent, 41 were found to be ineligible, and 2 were excluded for other reasons. The final follow-up visit was completed by 520 patients. Main Outcomes and Measures: Recurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO). Results: The mean (SD) age of participants was 40.4 (7.3) years, and 297 (56%) participants were male. The most frequent vascular risk factors were tobacco use (240 patients [45%]), hypertension (118 patients [22%]), and dyslipidemia (109 patients [20%]). PFO was detected in 177 participants (50%) who had transthoracic echocardiograms with bubble studies. Following initial ESUS, 468 participants (88%) were receiving antiplatelet therapy, and 52 (10%) received anticoagulation. The recurrent ischemic stroke and death rate was 2.19 per 100 patient-years, and the ischemic stroke recurrence rate was 1.9 per 100 patient-years. Of the recurrent strokes, 9 (64%) were ESUS, 2 (14%) were cardioembolic, and 3 (21%) were of other determined cause. AF was detected in 15 participants (2.8%; 95% CI, 1.6-4.6). In multivariate analysis, the following were associated with recurrent ischemic stroke: history of stroke or transient ischemic attack (hazard ratio, 5.3; 95% CI, 1.8-15), presence of diabetes (hazard ratio, 4.4; 95% CI, 1.5-13), and history of coronary artery disease (hazard ratio, 10; 95% CI, 4.8-22). Conclusions and Relevance: In this large cohort of young adult patients with ESUS, there was a relatively low rate of subsequent ischemic stroke and a low frequency of new-onset AF. Most recurrent strokes also met the criteria for ESUS, suggesting the need for future studies to improve our understanding of the underlying stroke mechanism in this population.


Assuntos
AVC Embólico , Forame Oval Patente , AVC Isquêmico , Acidente Vascular Cerebral , Adulto , Idoso , Estudos de Coortes , Feminino , Forame Oval Patente/complicações , Humanos , Estudos Longitudinais , Masculino , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Adulto Jovem
18.
JAMA Neurol ; 77(1): 43-48, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524941

RESUMO

Importance: The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) randomized clinical trial was stopped early owing to the efficacy of low-dose rivaroxaban plus aspirin in preventing major cardiovascular events. The main reason for early trial termination was the effect of combination therapy on reducing ischemic strokes. Objective: To analyze the association between low-dose rivaroxaban with or without aspirin and different ischemic stroke subtypes. Design, Setting, and Participants: This is a secondary analysis of a multicenter, double-blind, randomized, placebo-controlled study that was performed in 33 countries from March 12, 2013, to May 10, 2016. Patients with stable atherosclerotic vascular disease were eligible, and a total of 27 395 participants were randomized and followed up to February 6, 2017. All first ischemic strokes and uncertain strokes that occurred by this date were adjudicated using TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. The analysis of ischemic stroke subtypes was evaluated using an intention-to-treat principle. Statistical analysis was performed from March 12, 2013, to February 6, 2017. Interventions: Participants received rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban (5 mg twice a day), or aspirin (100 mg once a day). Main Outcomes and Measures: Risk of ischemic stroke subtypes during follow-up. Results: A total of 291 patients (66 women; mean [SD] age, 69.4 [8.5] years; 43 [14.8%] had a previous nonlacunar stroke) experienced an ischemic stroke. During the study, 49 patients (16.8%) received a diagnosis of atrial fibrillation. Applying TOAST criteria, 59 strokes (20.3%) were cardioembolic, 54 strokes (18.6%) were secondary to greater than 50% stenosis of the ipsilateral internal carotid artery, 42 strokes (14.4%) had a negative evaluation that met criteria for embolic stroke of undetermined source, and 21 strokes (7.2%) were secondary to small vessel disease. There were significantly fewer cardioembolic strokes (hazard ratio [HR], 0.40 [95% CI, 0.20-0.78]; P = .005) and embolic strokes of undetermined source (HR, 0.30 [95% CI, 0.12-0.74]; P = .006) in the combination therapy group compared with the aspirin-only group. A trend for reduction in strokes secondary to small vessel disease (HR, 0.36 [95% CI, 0.12-1.14]; P = .07) was not statistically significant. No significant difference was observed between the 2 groups in strokes secondary to greater than 50% carotid artery stenosis (HR, 0.85 [95% CI, 0.45-1.60]; P = .61). Rivaroxaban, 5 mg, twice daily showed a trend for reducing cardioembolic strokes compared with aspirin (HR, 0.57 [95% CI, 0.31-1.03]; P = .06) but was not associated with reducing other stroke subtypes. Conclusions and Relevance: For patients with systemic atherosclerosis, low-dose rivaroxaban plus aspirin was associated with large, significant reductions in cardioembolic strokes and embolic strokes of undetermined source. However, these results of exploratory analysis need to be independently confirmed before influencing clinical practice. Trial Registration: ClinicalTrials.gov identifier: NCT01776424.


Assuntos
Aspirina/administração & dosagem , Embolia Intracraniana/complicações , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Aterosclerose/complicações , Fibrilação Atrial/complicações , Estenose das Carótidas/complicações , Método Duplo-Cego , Quimioterapia Combinada , Inibidores do Fator Xa/administração & dosagem , Cardiopatias/complicações , Humanos
19.
Neurology ; 95(5): e480-e487, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32651298

RESUMO

OBJECTIVE: Subdural hematomas (SDHs) are an uncommon, but important, complication of anticoagulation therapy. We hypothesized that the risks of SDH would be similar during treatment with oral factor Xa inhibitors compared with aspirin. METHODS: We assessed the frequency and the effects of antithrombotic treatments on SDHs in the recent international Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) randomized trial comparing aspirin 100 mg daily, rivaroxaban 5 mg twice daily, and rivaroxaban 2.5 mg twice daily plus aspirin. A systematic review/meta-analysis of randomized trials comparing oral factor Xa inhibitors vs aspirin on SDH risk was undertaken. RESULTS: Among 27,395 COMPASS participants, 28 patients with SDHs were identified (mean age 72 years). SDH-associated mortality was 7%. Incidence was 0.06 per 100 patient-years (11 SDH/17,492 years observation) during the mean 23-month follow-up among aspirin-assigned patients and did not differ significantly between treatments. Three additional randomized controlled trials including 16,177 participants reported a total of 14 SDHs with an incidence ranging from 0.06 to 0.1 per 100 patient-years. Factor Xa inhibitor use was not associated with an increased risk of SDH compared to aspirin (odds ratio, 0.97; 95% confidence interval, 0.52-1.81; I2 = 0%). CONCLUSION: The frequency of SDH was similar in all 3 treatment arms of the COMPASS trial. The COMPASS trial results markedly increase the available evidence from randomized comparisons of oral factor Xa inhibitors with aspirin regarding SDH. From available, albeit limited, evidence from 4 randomized trials, therapeutic dosages of factor Xa inhibitors do not appear to increase the risk of SDH compared with aspirin. CLINICAL TRIAL IDENTIFIER NUMBER: NCT01776424.


Assuntos
Inibidores do Fator Xa/efeitos adversos , Hematoma Subdural Intracraniano/induzido quimicamente , Rivaroxabana/efeitos adversos , Idoso , Aspirina/uso terapêutico , Aterosclerose/tratamento farmacológico , Feminino , Hematoma Subdural Intracraniano/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Am J Cardiol ; 121(5): 584-589, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29291887

RESUMO

The mortality rate of most patients with atrial fibrillation (AF) exceeds the stroke rate, but predictors of mortality have not been well defined. The Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE A) recruited patients with AF who were unsuitable to receive vitamin K-antagonists and were randomized to aspirin alone versus aspirin plus clopidogrel. We investigated independent predictors of all-cause mortality by multivariable Cox regression analysis and explored interactions with assigned antiplatelet therapy. Of the 7,554 patients enrolled with a mean age of 71 years, 1,687 (22%) patients died during the median follow-up of 3.7 years (annualized mortality rate 6.4%/year). Assignment to dual antiplatelet therapy had no effect on mortality (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.90 to 1.1) or on vascular and nonvascular death. Independent predictors of all-cause mortality were advancing age, lower body mass index (HR 1.4 < 25 kg/m2, 95% CI 1.3 to 1.6), diabetes mellitus, Latin American ethnicity (HR 1.4, 95% CI 1.1 to 1.6), previous stroke or transient ischemic attack, peripheral artery disease, increased resting heart rate (HR 1.3, 95% CI 1.1 to 1.4 per 30 bpm), lower diastolic blood pressure, coronary artery disease, heart failure, left ventricular systolic dysfunction, hemoglobin level of <13 mg/dl, and reduced estimated glomerular filtration rate. In conclusion, in this large clinical trial cohort of patients with AF, treatment with clopidogrel plus aspirin versus aspirin monotherapy did not affect all-cause mortality, vascular death, or nonvascular death. Novel independent predictors of increased mortality included lower diastolic blood pressure and Latin American ethnicity.


Assuntos
Aspirina/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Clopidogrel/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Feminino , Humanos , Irbesartana/uso terapêutico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes
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