Reperfusion therapy for acute ischemic stroke: where are we in 2023? / Terapia de reperfusão para o acidente vascular isquêmico agudo: onde estamos em 2023?

Abstract Over the last three decades, stroke care has undergone significant transformations mainly driven by the introduction of reperfusion therapy and the organization of systems of care. Patients receiving treatment through a well-structured stroke service have a much higher chance of favorable outcomes, thereby decreasing both disability and mortality. In this article, we reviewed the scientific evidence for stroke reperfusion therapy, including thrombolysis and thrombectomy, and its implementation in the public health system in Brazil.

Resumo Nas últimas três décadas, o tratamento do AVC sofreu transformações significativas, impulsionadas principalmente pela introdução das terapias de reperfusão e pela organização dos serviços de AVC. Os pacientes que recebem tratamento em um serviço de AVC bem estruturado têm uma probabilidade muito maior de resultados favoráveis, diminuindo assim a incapacidade funcional e a mortalidade. Neste artigo, revisamos as evidências científicas para as terapias de reperfusão do AVC, incluindo trombólise e trombectomia e sua implementação no sistema público de saúde no Brasil.

Reperfusion therapy for acute ischemic stroke: where are we in 2023?

Over the last three decades, stroke care has undergone significant transformations mainly driven by the introduction of reperfusion therapy and the organization of systems of care. Patients receiving treatment through a well-structured stroke service have a much higher chance of favorable outcomes, thereby decreasing both disability and mortality. In this article, we reviewed the scientific evidence for stroke reperfusion therapy, including thrombolysis and thrombectomy, and its implementation in the public health system in Brazil.

Nas últimas três décadas, o tratamento do AVC sofreu transformações significativas, impulsionadas principalmente pela introdução das terapias de reperfusão e pela organização dos serviços de AVC. Os pacientes que recebem tratamento em um serviço de AVC bem estruturado têm uma probabilidade muito maior de resultados favoráveis, diminuindo assim a incapacidade funcional e a mortalidade. Neste artigo, revisamos as evidências científicas para as terapias de reperfusão do AVC, incluindo trombólise e trombectomia e sua implementação no sistema público de saúde no Brasil.

Improving door-to-reperfusion time in acute ischemic stroke during the COVID-19 pandemic: experience from a public comprehensive stroke center in Brazil.

Background: The global COVID-19 pandemic has had a devastating effect on global health, resulting in a strain on healthcare services worldwide. The faster a patient with acute ischemic stroke (AIS) receives reperfusion treatment, the greater the odds of a good functional outcome. To maintain the time-dependent processes in acute stroke care, strategies to reorganize infrastructure and optimize human and medical resources were needed. Methods: Data from AIS patients who received thrombolytic therapy were prospectively assessed in the emergency department (ED) of Hospital de Clínicas de Porto Alegre from 2019 to 2021. Treatment times for each stage were measured, and the reasons for a delay in receiving thrombolytic therapy were evaluated. Results: A total of 256 patients received thrombolytic therapy during this period. Patients who arrived by the emergency medical service (EMS) had a lower median door-to-needle time (DNT). In the multivariable analysis, the independent predictors of DNT >60 min were previous atrial fibrillation (OR 7) and receiving thrombolysis in the ED (OR 9). The majority of patients had more than one reason for treatment delay. The main reasons were as follows: delay in starting the CT scan, delay in the decision-making process after the CT scan, and delay in reducing blood pressure. Several actions were implemented during the study period. The most important factor that contributed to a decrease in DNT was starting the bolus and continuous infusion of tPA on the CT scan table (decreased the median DNT from 74 to 52, DNT ≤ 60 min in 67% of patients treated at radiology service vs. 24% of patients treated in the ED). The DNT decreased from 78 min to 66 min in 2020 and 57 min in 2021 (p = 0.01). Conclusion: Acute stroke care continued to be a priority despite the COVID-19 pandemic. The implementation of a thrombolytic bolus and the start of continuous infusion on the CT scan table was the main factor that contributed to the reduction of DNT. Continuous monitoring of service times is essential for improving the quality of the stroke center and achieving better functional outcomes for patients.

Disparities in Stroke Patient-Reported Outcomes Measurement Between Healthcare Systems in Brazil.

Introduction: Acute stroke interventions, such as stroke units and reperfusion therapy, have the potential to improve outcomes. However, there are many disparities in patient characteristics and access to the best stroke care. Thus, we aim to compare patient-reported outcome measures (PROMs) after stroke in two stroke centers representing the public and private healthcare systems in Brazil. Methods: PROMs through the International Consortium for Health Outcomes Measures (ICHOM) were assessed at 90 days after the stroke to compare two Brazilian hospitals in southern Brazil: a public university and a private stroke center, both with stroke protocols and stroke units. Results: When compared with the private setting (n = 165), patients from the public hospital (n = 175) were younger, had poorer control of risk factors, had more frequent previous strokes, and arrived with more severe strokes. Both hospitals had a similar percentage of IV thrombolysis treatment. Only 5 patients received mechanical thrombectomy (MT), all in the private hospital. Public hospital patients presented significantly worse outcomes at 3 months, including worse quality of life and functional dependence (60 vs. 48%, p = 0.03). Poor outcome, as measured by the mRS score, was significantly associated with older age, higher NIHSS score, and the presence of heart failure. However, the public practice was a strong predictor of any self-reported disability. Conclusion: Patients assisted at a good quality public stroke center with the same protocol used in the private hospital presented worse disability as measured by mRS and patient-reported outcome measures, with greater inability to communicate, dress, toilet, feed, and walk.

Home-Based Transcranial Direct Current Stimulation for the Treatment of Symptoms of Depression and Anxiety in Temporal Lobe Epilepsy: A Randomized, Double-Blind, Sham-Controlled Clinical Trial.

We conducted a double-blind randomized clinical trial in order to examine the effects and the safety of home-based transcranial direct current stimulation (tDCS) on depressive and anxious symptoms of patients with temporal lobe epilepsy (TLE). We evaluated 26 adults with TLE and depressive symptoms randomized into two different groups: active tDCS (tDCSa) and Sham (tDCSs). The patients were first submitted to 20 sessions of tDCS for 20 min daily, 5 days a week for 4 weeks and then received a maintenance tDCS application in the research laboratory once a week for 3 weeks. The intensity of the current was 2 mA, applied bilaterally over the dorsolateral prefrontal cortex, with the anode positioned on the left side and the cathode on the right side. Participants were evaluated on days 1, 15, 30, and 60 of the study using the Beck Depression Inventory II (BDI). A follow-up evaluation was performed 1 year after the end of treatment. They were also evaluated for quality of life and for anxious symptoms as secondary outcomes. The groups did not differ in clinical, socioeconomic or psychometric characteristics at the initial assessment. There was no statistically significant difference between groups regarding reported adverse effects, seizure frequency or dropouts. On average, between the 1st and 60th day, the BDI score decreased by 43.93% in the active group and by 44.67% in the Sham group (ΔBDIfinal - initial = -12.54 vs. -12.20, p = 0.68). The similar improvement in depressive symptoms observed in both groups was attributed to placebo effect and interaction between participants and research group and not to tDCS intervention per se. In our study, tDCS was safe and well tolerated, but it was not effective in reducing depressive or anxiety symptoms in patients with temporal lobe epilepsy. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT03871842].

Methylation of BDNF and SLC6A4 Gene Promoters in Brazilian Patients With Temporal Lobe Epilepsy Presenting or Not Psychiatric Comorbidities.

The relationship between epilepsy and psychiatric comorbidities has been recognized for centuries, but its pathophysiological mechanisms are still misunderstood. It is biologically plausible that genetic or epigenetic variations in genes that codify important neurotransmitters involved in epilepsy as well as in psychiatric disorders may influence the development of the latter in patients with epilepsy. However, this possibility remains poorly investigated. The aim of this study was to evaluate the methylation profile of the BDNF and SLC6A4, two genes importantly involved in neuroplasticity, in patients with temporal lobe epilepsy (TLE) regarding the development or not of psychiatric comorbidities. One hundred and thirty-nine patients with TLE, 90 females and 45 males, were included in the study. The mean age of patients was 44.0 (+12.0) years, and mean duration of epilepsy was 25.7 (+13.3) years. The Structured Clinical Interview for DSM-IV shows that 83 patients (59.7%) had neuropsychiatric disorders and 56 (40.3%) showed no psychiatric comorbidity. Mood disorders were the most common psychiatric disorder observed, being present in 64 (46.0%) of all 139 patients. Thirty-three (23.7%) patients showed anxiety disorders, 10 (7.2%) patients showed history of psychosis and 8 (5.8%) patients showed history of alcohol//drug abuse. Considering all 139 patients, 18 (12.9%) demonstrated methylation of the promoter region of both BDNF and SLC6A4 genes. A significant decreased methylation profile was observed only in TLE patients with mood disorders when compared with TLE patients without a history of mood disorders (O.R. = 3.45; 95% C.I. = 1.08-11.11; p = 0.04). A sub-analysis showed that TLE patients with major depressive disorder mostly account for this result (O.R. = 7.20; 95% C.I. = 1.01-56.16; p = 0.042). A logistic regression analysis showed that the independent factors associated with a history of depression in our TLE patients was female sex (O.R. = 2.30; 95% C.I. = 1.02-5.18; p = 0.044), not controlled seizures (O.R. = 2.51; 95% C.I. = 1.16-5.41; p = 0.019) and decreased methylation in BDNF and SLC6A4 genes (O.R. = 5.32; 95% C.I. = 1.14-25.00; p = 0.033). Our results suggest that BDNF or SLC6A4 genes profile methylation is independently associated with depressive disorders in patients with epilepsy. Further studies are necessary to clarify these matters.

Fighting Against Stroke in Latin America: A Joint Effort of Medical Professional Societies and Governments.

Introduction: Stroke is one of the leading causes of death in Latin America, a region with countless gaps to be addressed to decrease its burden. In 2018, at the first Latin American Stroke Ministerial Meeting, stroke physician and healthcare manager representatives from 13 countries signed the Declaration of Gramado with the priorities to improve the region, with the commitment to implement all evidence-based strategies for stroke care. The second meeting in March 2020 reviewed the achievements in 2 years and discussed new objectives. This paper will review the 2-year advances and future plans of the Latin American alliance for stroke. Method: In March 2020, a survey based on the Declaration of Gramado items was sent to the neurologists participants of the Stroke Ministerial Meetings. The results were confirmed with representatives of the Ministries of Health and leaders from the countries at the second Latin American Stroke Ministerial Meeting. Results: In 2 years, public stroke awareness initiatives increased from 25 to 75% of countries. All countries have started programs to encourage physical activity, and there has been an increase in the number of countries that implement, at least partially, strategies to identify and treat hypertension, diabetes, and lifestyle risk factors. Programs to identify and treat dyslipidemia and atrial fibrillation still remained poor. The number of stroke centers increased from 322 to 448, all of them providing intravenous thrombolysis, with an increase in countries with stroke units. All countries have mechanical thrombectomy, but mostly restricted to a few private hospitals. Pre-hospital organization remains limited. The utilization of telemedicine has increased but is restricted to a few hospitals and is not widely available throughout the country. Patients have late, if any, access to rehabilitation after hospital discharge. Conclusion: The initiative to collaborate, exchange experiences, and unite societies and governments to improve stroke care in Latin America has yielded good results. Important advances have been made in the region in terms of increasing the number of acute stroke care services, implementing reperfusion treatments and creating programs for the detection and treatment of risk factors. We hope that this approach can reduce inequalities in stroke care in Latin America and serves as a model for other under-resourced environments.

Evaluating the Association of Calcified Neurocysticercosis and Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis in a Large Cohort of Patients With Epilepsy.

BACKGROUND: Neurocysticercosis (NCC) is a parasitic infection of the central nervous system that has been associated with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). However, this association has not been completely established. OBJECTIVE: To evaluate the prevalence of calcified NCC (cNCC), its characteristics and a possible association between cNCC and MTLE-HS in a cohort of 731 patients with epilepsy. METHODS: We review clinical, EEG and neuroimaging findings of 731 patients with epilepsy. From these, 659 had CT-scans and 441 patients had complete neuroimaging with CT-scans and MRI. In these patients, we review the prevalence and characteristic of epilepsy in cNCC and in MTLE-HS patients. RESULTS: Forty-two (6.4%) of the 659 patients studied with CT-scans had cNCC. cNCC lesions were more frequent in women than in men (n = 33-78.6% vs. n = 09-21.4%, respectively; OR = 3.64;(95%CI = 1.71-7.69); p < 0.001). cNCC was more often in patients who developed epilepsy later in life, in older patients, in patients who had a longer history of epilepsy, and in those with a lower educational level. MTLE-HS was observed in 93 (21.1%) of 441 patients that had complete neuroimaging, and 25 (26.9%) of these 93 patients also had cNCC. Calcified NCC was observed in only 17 (4.9%) of the remaining 348 patients that had other types of epilepsy rather than MTLE-HS. Thus, in our cohort, cNCC was more frequently associated with MTLE-HS than with other forms of epilepsy, O.R. = 11.90;(95%CI = 6.10-23.26); p < 0.0001). CONCLUSIONS: As expected, in some patients the epilepsy was directly related to cNCC lesional zone, although this was observed in a surprisingly lower number of patients. Also, cNCC lesions were observed in other forms of epilepsy, a finding that could occur only by chance, with epilepsy probably being not related to cNCC at all. In this cohort, cNCC was very commonly associated with MTLE-HS, an observation in agreement with the hypothesis that NCC can contribute to or directly cause MTLE-HS in many patients. Given the broad world prevalence of NCC and the relatively few studies in this field, our findings add more data suggesting a possible and intriguing frequent interplay between NCC and MTLE-HS, two of the most common causes of focal epilepsy worldwide.

Coma irreversível em paciente portadora de esquizofrenia paranóide: encefalopatia de Wernicke após síndrome de realimentação: um relato de caso / Irreversible coma in a patient with paranoid schizophrenia: Wernicke encephalopathy after refeeding syndrome: a case report

Encefalopatia de Wernicke (EW) e síndrome de realimentação (SR) são duas condições frequentemente coexistentes, subdiagnosticadas e que podem implicar prognóstico reservado após sua instalação. Sua identificação precoce representa um desafio para os intensivistas, haja vista a falta de sensibilidade e especificidade das manifestações clínicas. Apresenta-se um relato de caso de uma paciente portadora de esquizofrenia paranoide, sem histórico de abuso de álcool, que desenvolveu quadro de coma irreversível após greve de fome, sendo feito diagnóstico tardio de EW associada a SR. Descreve-se a evolução clínica e neuropsiquiátrica com o intuito de enfatizar a necessidade crucial de alta suspeição diagnóstica, com reposição vitamínica imediata, vigilância de distúrbios eletrolíticos e progressão parcimoniosa do aporte nutricional. (AU)

Wernicke encephalopathy (WE) and refeeding syndrome (RFS) are two often coexisting, underdiagnosed conditions that may involve a poor prognosis after their onset. Early identification represents a challenge for intensivists, given the lack of sensitivity and specificity of clinical manifestations. We report a case of a patient with paranoid schizophrenia, without a history of alcohol abuse, who developed irreversible coma after a hunger strike, with a late diagnosis of WE associated with RFS. The clinical and neuropsychiatric outcomes are described herein in order to emphasize the crucial need for a high diagnostic suspicion, with immediate vitamin replacement, monitoring of electrolyte disorders, and gradual progression of nutritional support. (AU)

Risk Factors for Epilepsy After Thrombolysis for Ischemic Stroke: A Cohort Study.

The effects of thrombolysis in seizure and epilepsy after acute ischemic stroke have been poorly explored. In this study, we examine risk factors and consequences of intravenous rt-PA for treatment of acute ischemic stroke. In a retrospective cohort study we evaluate risk factors for seizure and epilepsy after stroke thrombolysis, as well as the impact of seizures and epilepsy in outcome of stroke patients. In our cohort, mean age of patients was 67.2 years old (SD = 13.1) and 79 of them (51.6%) were male and. Initial NIHSS mean score were 10.95 (SD = 6.25). Three months NIHSS mean score was 2.09 (SD = 3.55). Eighty seven (56.9%) patients were mRS of 0-1 after thrombolysis. Hemorrhagic transformation was observed in 22 (14.4%) patients. Twenty-one (13.7%) patients had seizures and 15 (9.8%) patients developed epilepsy after thrombolysis. Seizures were independently associated with hemorrhagic transformation (OR = 3.26; 95% CI = 1.08-9.78; p = 0.035) and with mRS ≥ 2 at 3 months after stroke (OR = 3.51; 95% CI = 1.20-10.32; p = 0.022). Hemorrhagic transformation (OR = 3.55; 95% CI = 1.11-11.34; p = 0.033) and mRS ≥ 2 at 3 months (OR = 5.82; 95% CI = 1.45-23.42; p = 0.013) were variables independently associated with post-stroke epilepsy. In our study, independent risks factors for poor outcome in stroke thrombolysis were age (OR = 1.03; 95% CI = 1.01-1.06; p = 0.011), higher NIHSS (OR = 1.08; 95% CI = 1.03-1.14; p = 0.001), hemorrhagic transformation (OR = 2.33; 95% CI = 1.11-4.76; p = 0.024), seizures (OR = 3.07; 95% CI = 1.22-7.75; p = 0.018) and large cortical area (ASPECTS ≤ 7) (OR = 2.04; 95% CI = 1.04-3.84; p = 0.036). Concluding, in this retrospective cohort study, the neurological impairment after thrombolysis (but not before) and hemorrhagic transformation remained independent risk factors for seizures or post-stroke epilepsy after thrombolysis. Moreover, we observed that seizures emerged as an independent risk factor for poor outcome after thrombolysis therapy in stroke patients (OR = 3.07; 95% CI = 1.22-7.75; p = 0.018).