New Directions in Infection-Associated Ischemic Stroke.

The relationship between infections and stroke has not been fully characterized, probably delaying the development of specific treatments. This narrative review addresses mechanisms of stroke linked to infections, including hypercoagulability, endothelial dysfunction, vasculitis, and impaired thrombolysis. SARS-CoV-2, the virus that causes COVID-19, may promote the development of stroke, which may represent its most severe neurological complication. The development of specific therapies for infection-associated stroke remains a profound challenge. Perhaps the most important remaining issue is the distinction between infections that trigger a stroke versus infections that are truly incidental. This distinction likely requires the establishment of appropriate biomarkers, candidates of which are elevated levels of fibrin D-dimer and anticardiolipin/antiphospholipid antibodies. These candidate biomarkers might have potential use in identifying pathogenic infections preceding stroke, which is a precursor to establishing specific therapies for this syndrome.

Safety and efficacy of factor XIa inhibition with milvexian for secondary stroke prevention (AXIOMATIC-SSP): a phase 2, international, randomised, double-blind, placebo-controlled, dose-finding trial.

BACKGROUND: People with factor XI deficiency have lower rates of ischaemic stroke than the general population and infrequent spontaneous bleeding, suggesting that factor XI has a more important role in thrombosis than in haemostasis. Milvexian, an oral small-molecule inhibitor of activated factor XI, added to standard antiplatelet therapy, might reduce the risk of non-cardioembolic ischaemic stroke without increasing the risk of bleeding. We aimed to estimate the dose-response of milvexian for recurrent ischaemic cerebral events and major bleeding in patients with recent ischaemic stroke or transient ischaemic attack (TIA). METHODS: AXIOMATIC-SSP was a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial done at 367 hospitals in 27 countries. Eligible participants aged 40 years or older, with acute (<48 h) ischaemic stroke or high-risk TIA, were randomly assigned by a web-based interactive response system in a 1:1:1:1:1:2 ratio to receive one of five doses of milvexian (25 mg once daily, 25 mg twice daily, 50 mg twice daily, 100 mg twice daily, or 200 mg twice daily) or matching placebo twice daily for 90 days. All participants received clopidogrel 75 mg daily for the first 21 days and aspirin 100 mg daily for the first 90 days. Investigators, site staff, and participants were masked to treatment assignment. The primary efficacy endpoint was the composite of ischaemic stroke or incident covert brain infarct on MRI at 90 days, assessed in all participants allocated to treatment who completed a follow-up MRI brain scan, and the primary analysis assessed the dose-response relationship with Multiple Comparison Procedure-Modelling (MCP-MOD). The main safety outcome was major bleeding at 90 days, assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov (NCT03766581) and the EU Clinical Trials Register (2017-005029-19). FINDINGS: Between Jan 27, 2019, and Dec 24, 2021, 2366 participants were randomly allocated to placebo (n=691); milvexian 25 mg once daily (n=328); or twice-daily doses of milvexian 25 mg (n=318), 50 mg (n=328), 100 mg (n=310), or 200 mg (n=351). The median age of participants was 71 (IQR 62-77) years and 859 (36%) were female. At 90 days, the estimates of the percentage of participants with either symptomatic ischaemic stroke or covert brain infarcts were 16·8 (90·2% CI 14·5-19·1) for placebo, 16·7 (14·8-18·6) for 25 mg milvexian once daily, 16·6 (14·8-18·3) for 25 mg twice daily, 15·6 (13·9-17·5) for 50 mg twice daily, 15·4 (13·4-17·6) for 100 mg twice daily, and 15·3 (12·8-19·7) for 200 mg twice daily. No significant dose-response was observed among the five milvexian doses for the primary composite efficacy outcome. Model-based estimates of the relative risk with milvexian compared with placebo were 0·99 (90·2% CI 0·91-1·05) for 25 mg once daily, 0·99 (0·87-1·11) for 25 mg twice daily, 0·93 (0·78-1·11) for 50 mg twice daily, 0·92 (0·75-1·13) for 100 mg twice daily, and 0·91 (0·72-1·26) for 200 mg twice daily. No apparent dose-response was observed for major bleeding (four [1%] of 682 participants with placebo, two [1%] of 325 with milvexian 25 mg once daily, two [1%] of 313 with 25 mg twice daily, five [2%] of 325 with 50 mg twice daily, five [2%] of 306 with 100 mg twice daily, and five [1%] of 344 with 200 mg twice daily). Five treatment-emergent deaths occurred, four of which were considered unrelated to the study drug by the investigator. INTERPRETATION: Factor XIa inhibition with milvexian, added to dual antiplatelet therapy, did not substantially reduce the composite outcome of symptomatic ischaemic stroke or covert brain infarction and did not meaningfully increase the risk of major bleeding. Findings from our study have informed the design of a phase 3 trial of milvexian for the prevention of ischaemic stroke in patients with acute ischaemic stroke or TIA. FUNDING: Bristol Myers Squibb and Janssen Research & Development.

Perspectiva neurológica en la elección del anticoagulante oral directo para la prevención del accidente cerebrovascular en fibrilación auricular / Neurological perspective in the choice of direct oral an ticoagulants for prevention of stroke in atrial fibrillation

Resumen La fibrilación auricular no valvular (FA) es la arritmia con potencial embolígeno más prevalente y una de las principales y crecientes causas de accidente cerebrovas cular isquémico (ACVi). El principal objetivo del uso de la anticoagulación en pacientes con FA es la prevención del ACVi. Hasta hace poco tiempo, la anticoagulación con antagonistas de la vitamina K (AVKs) era la única opción disponible. Los anticoagulantes orales directos (DOACs) como el inhibidor directo de la trombina, dabigatrán, o los inhibidores directos del factor Xa, rivaroxabán, apixa bán y edoxabán, tienen un perfil de efectividad/seguridad más favorable en comparación con los AVKs. No existen estudios que comparen la efectividad de los DOACs entre sí. La elección del DOAC depende de múltiples factores específicos del paciente, preferencias del médico, costos y accesibilidad. Entre 1-2% de los pacientes correctamente tratados con un DOAC intercurre con un ACVi cada año. La posibilidad de contar con un agente reversor debería ser tenida en cuenta al momento de la elección del DOAC, especialmente por el riesgo residual de ocurrencia de ACVi. En la actualidad, en nuestro país solo el dabigatrán cuenta con un agente reversor disponible y lo convierte en el único DOAC que no contraindica el uso de trombolisis intraveno sa con rtPA. Esta situación debería ser considerada en el momento de la elección del DOAC para la prevención de eventos tromboembólicos en pacientes con FA.

Abstract Non-valvular atrial fibrillation (AF) is the most preva lent arrhythmia with high embolic potential, and one of the main and growing causes of stroke. The main objec tive of anticoagulation in patients with AF is prevention of stroke. Until recently, anticoagulation with vitamin K antagonists (VKAs) was the only available option. Direct oral anticoagulants (DOACs), such as the direct thrombin inhibitor dabigatran, or the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, have a more favor able effectiveness/safety profile compared to VKAs. There are no studies comparing the efficacy of DOACs with each other. The choice of a DOAC arose from patient car achterictis, physician preferences, cost, and accessibility. Between 1-2% of patients correctly treated with a DOAC experience a stroke each year. The possibility of having a reversal agent should be taken into account when choos ing a DOAC, especially due to the residual risk of stroke occurrences even under DOACs. Currently, in our country only dabigatran has a reversing agent available, making it the only DOAC that does not contraindicate the use of intravenous thrombolysis. This should be taken into account when choosing the DOAC for the prevention of thromboembolic events in patients with AF.

[Neurological perspective in the choice of direct oral anticoagulants for prevention of stroke in atrial fibrillation]. / Perspectiva neurológica en la elección del anticoagulante oral directo para la prevención del accidente cerebrovascular en fibrilación auricular.

Non-valvular atrial fibrillation (AF) is the most prevalent arrhythmia with high embolic potential, and one of the main and growing causes of stroke. The main objective of anticoagulation in patients with AF is prevention of stroke. Until recently, anticoagulation with vitamin K antagonists (VKAs) was the only available option. Direct oral anticoagulants (DOACs), such as the direct thrombin inhibitor dabigatran, or the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, have a more favorable effectiveness/safety profile compared to VKAs. There are no studies comparing the efficacy of DOACs with each other. The choice of a DOAC arose from patient carachterictis, physician preferences, cost, and accessibility. Between 1-2% of patients correctly treated with a DOAC experience a stroke each year. The possibility of having a reversal agent should be taken into account when choosing a DOAC, especially due to the residual risk of stroke occurrences even under DOACs. Currently, in our country only dabigatran has a reversing agent available, making it the only DOAC that does not contraindicate the use of intravenous thrombolysis. This should be taken into account when choosing the DOAC for the prevention of thromboembolic events in patients with AF.

La fibrilación auricular no valvular (FA) es la arritmia con potencial embolígeno más prevalente y una de las principales y crecientes causas de accidente cerebrovascular isquémico (ACVi). El principal objetivo del uso de la anticoagulación en pacientes con FA es la prevención del ACVi. Hasta hace poco tiempo, la anticoagulación con antagonistas de la vitamina K (AVKs) era la única opción disponible. Los anticoagulantes orales directos (DOACs) como el inhibidor directo de la trombina, dabigatrán, o los inhibidores directos del factor Xa, rivaroxabán, apixabán y edoxabán, tienen un perfil de efectividad/seguridad más favorable en comparación con los AVKs. No existen estudios que comparen la efectividad de los DOACs entre sí. La elección del DOAC depende de múltiples factores específicos del paciente, preferencias del médico, costos y accesibilidad. Entre 1-2% de los pacientes correctamente tratados con un DOAC intercurre con un ACVi cada año. La posibilidad de contar con un agente reversor debería ser tenida en cuenta al momento de la elección del DOAC, especialmente por el riesgo residual de ocurrencia de ACVi. En la actualidad, en nuestro país solo el dabigatrán cuenta con un agente reversor disponible y lo convierte en el único DOAC que no contraindica el uso de trombolisis intravenosa con rtPA. Esta situación debería ser considerada en el momento de la elección del DOAC para la prevención de eventos tromboembólicos en pacientes con FA.

Incidence and case-fatality rate of stroke in General Villegas, Buenos Aires, Argentina. The EstEPA population study.

OBJECTIVES: Stroke epidemiology varies among different populations. The burden of stroke is high in low- and middle-income countries. Reliable population data is needed to assess the impact of stroke and to develop policies aimed to improve stroke care in our region. EstEPA is a population-based project assessing prevalence, incidence, mortality and burden of stroke in General Villegas Department, Buenos Aires, Argentina (pop=30,864 inhabitants). We determined incidence of stroke (first-ever and recurrent stroke) and stroke case-fatality rate from 2017 to 2020. METHODS: First-ever strokes, recurrent strokes and transient ischemic attacks were ascertained and case-fatality rate was obtained. Diagnoses were based on standard AHA/WHO definitions. Study population included all persons residing in General Villegas during the three-year period. Hospitals, households, nursing homes, death certificates and several overlapping sources were surveyed. RESULTS: We assessed 92,592 person-years. There were 155 cerebrovascular events aged 70 years (SD ± 13 years), of which 115 were first-ever strokes (74%), 21 recurrent strokes (13.5%) and 19 transient ischemic attacks (12.5%). The crude overall incidence rate of first-ever strokes was 124.2 per 100,000 population (86.9 per 100,000 [95% CI 58.5-115.2] when standardized by WHO World population and 109.7 per 100,000 [95% CI 89.7-129.8] when standardized by Argentine population) and 317.0 per 100,000 population in subjects older than 40 years. Case fatality rate at 30 days of first-ever strokes was 27%. CONCLUSION: In this population-based comprehensive stroke epidemiological study in Argentina, first-ever stroke incidence in an urban population was 124.2 per 100,000 population (86.9 per 100,000 adjusted by the WHO World population). This is lower than the incidence in other countries in the region and similar to a recent incidence study in Argentina. It is also comparable to reported incidence in most middle- and high-income countries. Stroke case-fatality rate was comparable to other population-based Latin-American studies.

Predictive factors for the development of epilepsy after ischemic stroke.

OBJECTIVES: Ischemic stroke is one of the most common causes of epilepsy in adults. The incidence of post-stroke epilepsy (PSE) is approximately 7%. Risk factors are higher stroke severity, cortical localization, higher National Institute of Health Stroke Scale (NIHSS) upon admission and acute symptomatic seizures. We analyzed the predictive factors of PSE development in our population. MATERIALS AND METHODS: Retrospective observational cohort of adult patients (age ≥ 18 years) with ischemic stroke assessed between January 2012 and June 2020. Patients with personal history of epilepsy and potentially epileptogenic structural injury other than acute or chronic stroke were excluded. Demographic, clinical and imaging variables were evaluated in a multivariate analysis for independent risk factors associated with PSE. RESULTS: Medical records of 1586 stroke patients were reviewed, 691 met the inclusion criteria and had at least one year of follow-up. Of them, 428 (61.9%) were males. During follow-up, 6.2% had diagnosis of PSE (42/691) with a higher frequency of: previous ischemic stroke, higher NIHSS upon admission, treatment with rt-PA, higher Fazekas scale grade, cortical involvement, hemorrhagic transformation, acute symptomatic seizures, longer hospitalization and higher modified Rankin Scale (mRS) at discharge compared to the group without PSE. In a multivariate analysis, acute symptomatic seizures (OR=3.22, p: 0.033), cortical involvement (OR=0.274, p < 0.05), Fazekas scale score (OR=0.519, p < 0.05) and mRS at discharge (OR=1.33, p: 0.043) were independent risk factors. CONCLUSIONS: The variables related to higher risk of PSE were similar to those reported in the literature, highlighting the importance of neuroimaging findings, acute symptomatic seizures during hospitalization and neurological deficit at discharge. The data obtained will serve as the basis for construction of predictive models, allowing to individualize PSE probability in our population.

Control of Vascular Risk Factors and Response to Stroke Symptoms in Argentina During the COVID-19 Quarantine. The SIFHON-COVID Population Survey.

Background and Objectives: In preparation for the suspected influx of COVID-19 patients, many healthcare systems reduced or discontinued provision of "non-urgent" care. This decision had potential impact on stroke prevention and management. We conducted a large population survey to assess the effect of mandatory social isolation on routine health controls, emergency consultations and other stroke care-related behaviors of the population during the pandemic. Methods: We distributed multiple-choice anonymous questionnaires through the institutional email database and through the email database of clients of a beverage delivery company. Most respondents resided in the metropolitan area of Buenos Aires. This is the area where the infection rates were highest and restriction measures were hardest. The survey assessed demographic characteristics and actual and potential behaviors of people regarding medical checkups, risk factors control, medication provision and response to onset of symptoms consistent with stroke or TIA. Surveys were sent during May 2020, the strictest period of the quarantine in Argentina. Results: A total of 10,303 questionnaires were completed. Thirty-seven percent of the respondents were older than 60 years, 74% were women and 16% lived alone. Vascular risk factors were present in 39% of the individuals. Seventy-six percent did not continue with their regular medical checkups during the mandatory social and preventive isolation, 21% had difficulty obtaining medical prescriptions and only 38% considered that health institutions had implemented reliable safety measures to avoid exposure to COVID-19. When asked about response in case of onset of stroke symptoms, 9% would not consult given the context of the pandemic. Six percent reported having had symptoms consistent with stroke or TIA but only 35% went to a hospital. The vast majority of the respondents said they were awaiting for the end of the quarantine to resume their usual medical care. Conclusions: The implementation of a quarantine may have some serious adverse effects on the prevention, diagnosis and treatment of stroke. These undesirable aspects should be taken into consideration in the planning, communication and implementation of health policies.

Evaluating Rates of Recurrent Ischemic Stroke Among Young Adults With Embolic Stroke of Undetermined Source: The Young ESUS Longitudinal Cohort Study.

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.

Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy.

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.

Frequency and Patterns of Brain Infarction in Patients With Embolic Stroke of Undetermined Source: NAVIGATE ESUS Trial.

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.

Changes in the Care of Neurological Diseases During the First Wave of the COVID-19 Pandemic: A Single Private Center Study in Argentina.

Introduction: Healthcare systems are struggling to cope with the rapid evolution of the COVID-19 pandemic. In Argentina, the pandemic is advancing despite prolonged lockdown measures. We aim to analyze the impact of the easing of lockdown measures in the number of visits to the emergency department (ED), and outpatient consultations (OC) to a tertiary neurological center. Methods: We compared the number of ED visits with the social mobility overtime. We also compared the number of OC, and the geographic distribution of patients' addresses between 2019 and 2020. Results: ED visits decreased 48.33% (n = 14,697 in 2019 vs. n = 7,595 in 2020). At the beginning of the lockdown, the social mobility decreased in pharmacies/groceries, and workplaces, along with a reduction in the number of ED visits. With the easing of lockdown restrictions, the social mobility decreased in residential places, slightly increased in workplaces and almost return to normal in pharmacies/groceries. Variations in ED visits correlate better with social mobility in workplaces (coef. =0.75, p < 0.001) than in groceries/pharmacies (coef. =0.68, p < 0.001). OC decreased 43%. Fourteen percent of OC were tele consults. This was associated with an increase of the geographical area of influence of our center (standard distance of 109 km in 2019 and 127 km in 2020). Conclusions: Despite an increase in social mobility, the number of ED visits and OC to an Argentinian tertiary neurological center remain worrisomely low. The pandemic catalyzed the introduction of telemedicine in our country. This has also allowed patients from distant zones to gain access to specialized neurological care.

COVID-19 Lockdown Effects on Acute Stroke Care in Latin America.

OBJECTIVES: COVID-19 pandemic has forced important changes in health care worldwide. Stroke care networks have been affected, especially during peak periods. We assessed the impact of the pandemic and lockdowns in stroke admissions and care in Latin America. MATERIALS AND METHODS: A multinational study (7 countries, 18 centers) of patients admitted during the pandemic outbreak (March-June 2020). Comparisons were made with the same period in 2019. Numbers of cases, stroke etiology and severity, acute care and hospitalization outcomes were assessed. RESULTS: Most countries reported mild decreases in stroke admissions compared to the same period of 2019 (1187 vs. 1166, p = 0.03). Among stroke subtypes, there was a reduction in ischemic strokes (IS) admissions (78.3% vs. 73.9%, p = 0.01) compared with 2019, especially in IS with NIHSS 0-5 (50.1% vs. 44.9%, p = 0.03). A substantial increase in the proportion of stroke admissions beyond 48 h from symptoms onset was observed (13.8% vs. 20.5%, p < 0.001). Nevertheless, no differences in total reperfusion treatment rates were observed, with similar door-to-needle, door-to-CT, and door-to-groin times in both periods. Other stroke outcomes, as all-type mortality during hospitalization (4.9% vs. 9.7%, p < 0.001), length of stay (IQR 1-5 days vs. 0-9 days, p < 0.001), and likelihood to be discharged home (91.6% vs. 83.0%, p < 0.001), were compromised during COVID-19 lockdown period. CONCLUSIONS: In this Latin America survey, there was a mild decrease in admissions of IS during the COVID-19 lockdown period, with a significant delay in time to consultations and worse hospitalization outcomes.

Uso y resultados de la fibrinolisis intravenosa en una unidad cerebrovascular / Use and results of intravenous fibrinolysis in a stroke unit

Resumen La fibrinólisis intravenosa con activador del plasminógeno tisular recombinante (rTPA) y la utilización de unidades cerradas, demostraron disminuir sustancialmente la morbimortalidad en pacientes con accidente cerebrovascular isquémico (ACVi). Sin embargo, los datos publicados en Argentina son escasos. Describimos la experiencia en la utilización de fibrinólisis en pacientes con ACVi agudo antes y después de la implementación de una unidad cerebrovascular (UCV) en un Centro Integral de Neurología Vascular de la Ciudad de Buenos Aires durante 17 años. Se realizó un análisis retrospectivo de pacientes consecutivos tratados con rTPA entre enero 2003 y diciembre 2019. Se evaluaron tiempos de tratamiento, de internación, complicaciones post tratamiento y discapacidad a 3 meses. Para su análisis se evaluaron los períodos pre y post apertura de la UCV, período 1 (P1 de 2003-2011) y P2 (2012 -2019). Se realizó fibrinolisis intravenosa en 182 pacientes. La apertura de UCV resultó en aumento del porcentaje de fibrinólisis sobre el total de los ACVi ingresados (4% en P1 vs. 10% en P2, p < 0.001), acortamiento del tiempo puerta-aguja (75 minutos en P1 vs. 53 minutos en P2, p < 0.00001) y mayor proporción de pacientes tratados dentro de los 60 minutos del ingreso hospitalario (36% en P1 vs. 76% en P2, p < 0.00001). Además, hubo reducción de la mediana de internación de 9 días en P1 a 5 días en P2 (p < 0.00001). En conclusión, la UCV parece optimizar la utilización de fibrinólisis en el ACVi agudo, aumentando el porcentaje de pacientes tratados, reduciendo el tiempo puerta-aguja y disminuyendo el de internación.

Abstract Intravenous fibrinolysis with recombinant tissue plasminogen activator (rTPA) and use of stroke units improve morbidity and mortality in patients with acute ischemic stroke (AIS). However, data published in Argentina are scarce. We describe the experience in the use of fibrinolysis in patients with acute ischemic stroke (AIS) before and after the implementation of a stroke unit in a Comprehensive Stroke Center in Buenos Aires during the last 17 years. Retrospective analysis of consecutive patients treated with rTPA between January 2003 and December 2019. Treatment times, hospitalization time, post-treatment complications and disability at 3 months were evaluated. For the analysis, the pre and post opening periods of the stroke unit were evaluated, Period 1 (P1, from 2003 to 2011) and Period 2 (P2, from 2012 to 2019). Intravenous fibrinolysis was performed in 182 patients. Opening of the stroke unit resulted in an increase in the percentage of fibrinolysis over the total number of admitted strokes (4% in P1 vs. 10% in P2, p < 0.001), shortening of the door-to-needle time (75 minutes in P1 vs. 53 minutes in P2, p < 0.00001) and higher proportion of patients treated within 60 minutes of hospital admission (36% in P1 vs. 76% in P2, p < 0.00001). In addition, there was a reduction in the median hospital stay from 9 days in P1 to 5 days in P2 (p < 0.00001). In conclusion, stroke units seem to optimize the use of fibrinolysis in acute stroke, increasing the percentage of patients treated, reducing door-to-needle time, and reducing hospitalization time.

Neurologic complications of rheumatic fever.

Sydenham chorea, also known as St. Vitus dance, is a major clinical criterion for the diagnosis of acute rheumatic fever. Clinically, it results in a combination of movement disorders and complex neuropsychiatric symptoms. Cardiac damage due to rheumatic fever may also predispose to neurologic complications later in life. Rheumatic heart disease (RHD) is associated with heart remodeling, cardiac arrhythmias, and ischemic stroke. Furthermore, chronically damaged heart valves are predisposed to infection. Septic brain embolism, a known complication of infective endocarditis, may result in brain ischemia, hemorrhage, and spread of the infection to the brain.

[Use and results of intravenous fibrinolysis in a stroke unit]. / Uso y resultados de la fibrinolisis intravenosa en una unidad cerebrovascular.

Intravenous fibrinolysis with recombinant tissue plasminogen activator (rTPA) and use of stroke units improve morbidity and mortality in patients with acute ischemic stroke (AIS). However, data published in Argentina are scarce. We describe the experience in the use of fibrinolysis in patients with acute ischemic stroke (AIS) before and after the implementation of a stroke unit in a Comprehensive Stroke Center in Buenos Aires during the last 17 years. Retrospective analysis of consecutive patients treated with rTPA between January 2003 and December 2019. Treatment times, hospitalization time, post-treatment complications and disability at 3 months were evaluated. For the analysis, the pre and post opening periods of the stroke unit were evaluated, Period 1 (P1, from 2003 to 2011) and Period 2 (P2, from 2012 to 2019). Intravenous fibrinolysis was performed in 182 patients. Opening of the stroke unit resulted in an increase in the percentage of fibrinolysis over the total number of admitted strokes (4% in P1 vs. 10% in P2, p < 0.001), shortening of the door-to-needle time (75 minutes in P1 vs. 53 minutes in P2, p < 0.00001) and higher proportion of patients treated within 60 minutes of hospital admission (36% in P1 vs. 76% in P2, p < 0.00001). In addition, there was a reduction in the median hospital stay from 9 days in P1 to 5 days in P2 (p < 0.00001). In conclusion, stroke units seem to optimize the use of fibrinolysis in acute stroke, increasing the percentage of patients treated, reducing door-to-needle time, and reducing hospitalization time.

La fibrinólisis intravenosa con activador del plasminógeno tisular recombinante (rTPA) y la utilización de unidades cerradas, demostraron disminuir sustancialmente la morbimortalidad en pacientes con accidente cerebrovascular isquémico (ACVi). Sin embargo, los datos publicados en Argentina son escasos. Describimos la experiencia en la utilización de fibrinólisis en pacientes con ACVi agudo antes y después de la implementación de una unidad cerebrovascular (UCV) en un Centro Integral de Neurología Vascular de la Ciudad de Buenos Aires durante 17 años. Se realizó un análisis retrospectivo de pacientes consecutivos tratados con rTPA entre enero 2003 y diciembre 2019. Se evaluaron tiempos de tratamiento, de internación, complicaciones post tratamiento y discapacidad a 3 meses. Para su análisis se evaluaron los períodos pre y post apertura de la UCV, período 1 (P1 de 2003-2011) y P2 (2012 -2019). Se realizó fibrinolisis intravenosa en 182 pacientes. La apertura de UCV resultó en aumento del porcentaje de fibrinólisis sobre el total de los ACVi ingresados (4% en P1 vs. 10% en P2, p < 0.001), acortamiento del tiempo puerta-aguja (75 minutos en P1 vs. 53 minutos en P2, p < 0.00001) y mayor proporción de pacientes tratados dentro de los 60 minutos del ingreso hospitalario (36% en P1 vs. 76% en P2, p < 0.00001). Además, hubo reducción de la me diana de internación de 9 días en P1 a 5 días en P2 (p < 0.00001). En conclusión, la UCV parece optimizar la utilización de fibrinólisis en el ACVi agudo, aumentando el porcentaje de pacientes tratados, reduciendo el tiempo puerta-aguja y disminuyendo el de internación.

Regional, sex, and age differences in diagnostic testing among participants in the NAVIGATE-ESUS trial.

BACKGROUND AND AIM: The diagnosis of embolic stroke of undetermined source (ESUS) is based on excluding other more likely stroke etiologies, and therefore diagnostic testing plays an especially crucial role. Our objective was to compare the diagnostic testing by region, sex, and age among the participants of NAVIGATE-ESUS trial. METHODS: Participants were grouped according to five global regions (North America, Latin America, Western Europe, Eastern Europe and East Asia), age (<60, 60-74, and >75 years), and sex. Frequencies of each diagnostic test within areas of echocardiography, cardiac rhythm monitoring, and arterial imaging were described and compared across groups. A multivariable logistic regression model for each diagnostic test was fit to assess the independent influence of each of region, age, and sex and likelihood of testing. RESULTS: We included 6985 patients in the analysis (918 from North America; 746 from Latin America; 2853 from Western Europe; 1118 from Eastern Europe; 1350 from East Asia). Average age (highest in Western Europe (69 years), lowest in Eastern Europe (65 years)), % females (highest in Latin America (44%) and lowest in East Asia (31%)), and use of each diagnostic test varied significantly across regions. Region, but not sex, was independently associated with use of each diagnostic test examined. Transesophageal echocardiography and either CT or MR angiogram were more often used in younger patients. CONCLUSION: Diagnostic testing differed by region, and less frequently by age, but not by sex. Our findings reflect the existing variations in global practice in diagnostic testing in ESUS patients.