Exploring the Chagas disease-Stroke 'Connection': Findings from a Large Multicenter Study.

INTRODUCTION: Strokes are traditionally attributed to risk factors like aging, hypertension, diabetes, and atherosclerosis. Chagas disease has emerged as an important risk factor for stroke in Latin American. Our study aims at describing the largest cohort of patients with Chagas disease and ischemic stroke and determining variables associated with stroke recurrence and cardioembolic cause. METHODS: This study is the result of a national multicenter cohort study conducted in Brazil. The study spanned from January 2009 to December 2016 and involved a comprehensive retrospective analysis of medical records of patients with both Chagas disease and stroke. This cohort comprised 499 individuals from diverse Brazilian regions, focusing on vascular risk factors and the epidemiological variables associated with Chagas disease and stroke. RESULTS: Our findings underscore the significant prevalence of traditional vascular risk factors among Chagas disease patients who had stroke. 81% of patients had hypertension, 56% dyslipidemia and 25% diabetes. We observed a 29.7% recurrence rate, especially within the cardioembolic subgroup. 56% of the patients had embolic stroke of undetermined source (ESUS). Specific EKG abnormalities were associated with an increased risk of cardioembolic etiology (with three altered results increasing 81fold the chance of the stroke being of cardioembolic nature). Age emerged as a protective factor (OR:0.98, CI 0.970 - 0.997) against cardioembolic etiology. Anticoagulation therapy was associated with reduced risk (OR:0.221 |CI 0.104 - 0.472), highlighting the importance of accurate etiological classification. Conversely, female gender(OR:1.83 CI 1.039 - 3.249) emerged as a significant risk factor for stroke recurrence. CONCLUSION: This study significantly advances our epidemiological understanding of the intersection between Chagas disease and stroke. It emphasizes the critical need for extensive epidemiological investigations, a deeper comprehension of stroke recurrence determinants, and accurate etiological classification to reduce the ESUS population. Our findings have substantial clinical implications, suggesting the need of control of vascular risk factors and comorbidities and hold promise for improving patient care and reducing the burden of Chagas disease and stroke worldwide.

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.

Trends in Intensive Care Admissions and Outcomes of Stroke Patients Over 10 Years in Brazil: Impact of the COVID-19 Pandemic.

BACKGROUND: The coronavirus 2019 (COVID-19) pandemic affected stroke care worldwide. Data from low- and middle-income countries are limited. RESEARCH QUESTION: What was the impact of the pandemic in ICU admissions and outcomes of patients with stroke, in comparison with trends over the last 10 years? STUDY DESIGN AND METHODS: Retrospective cohort study including prospectively collected data from 165 ICUs in Brazil between 2011 and 2020. We analyzed clinical characteristics and mortality over a period of 10 years and evaluated the impact of the pandemic on stroke outcomes, using the following approach: analyses of admissions for ischemic and hemorrhagic strokes and trends in in-hospital mortality over 10 years; analysis of variable life-adjusted display (VLAD) during 2020; and a mixed-effects multivariable logistic regression model. RESULTS: A total of 17,115 stroke admissions were analyzed, from which 13,634 were ischemic and 3,481 were hemorrhagic. In-hospital mortality was lower after ischemic stroke as compared with hemorrhagic (9% vs 24%, respectively). Changes in VLAD across epidemiological weeks of 2020 showed that the rise in COVID-19 cases was accompanied by increased mortality, mainly after ischemic stroke. In logistic regression mixed models, mortality was higher in 2020 compared with 2019, 2018, and 2017 in patients with ischemic stroke, namely, in those without altered mental status. In hemorrhagic stroke, the increased mortality in 2020 was observed in patients 50 years of age or younger, as compared with 2019. INTERPRETATION: Hospital outcomes of stroke admissions worsened during the COVID-19 pandemic, interrupting a trend of improvements in survival rates over 10 years. This effect was more pronounced during the surge of COVID-19 ICU admissions affecting predominantly patients with ischemic stroke without coma, and young patients with hemorrhagic stroke.

Clinical and radiological features of severe acute respiratory syndrome coronavirus 2 meningo-encephalitis.

BACKGROUND AND PURPOSE: This case illustrates for the first time the clinical and radiological evolution of SARS-CoV-2 meningo-encephalitis. METHODS: A case of a SARS-CoV-2 meningo-encephalitis is reported. RESULTS: A 65-year-old man with COVID-19 presenting with meningo-encephalitis without respiratory involvement is described. He had fever, diarrhea and vomiting, followed by diplopia, urinary retention and sleepiness. Examination disclosed a convergence strabismus and ataxia. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis, oligoclonal bands and increased interleukin 6 level. SARS-CoV-2 was detected in the CSF through reverse transcriptase polymerase chain reaction, but not in nasopharyngeal, tracheal secretion and rectal samples. Brain magnetic resonance imaging showed lesions on white matter hemispheres, the body and splenium of the corpus callosum and resembling the projection of corticospinal tract, remarkably on cerebellar peduncles. CONCLUSIONS: This demonstrates the challenges in diagnosing COVID-19 in patients with neurological presentations.

Artificial Inteligence-Based Decision for the Prediction of Cardioembolism in Patients with Chagas Disease and Ischemic Stroke.

BACKGROUND: Chagas disease (CD) and ischemic stroke (IS) have a close, but poorly understood, association. There is paucity of evidence on the ideal secondary prophylaxis and etiological determination, with few cardioembolic patients being identified. AIMS: This study aimed to describe a multicenter cohort of patients with concomitant CD and IS admitted in tertiary centers and to create a predictive model for cardioembolic embolism in CD and IS. MATERIALS AND METHODS: We retrospectively studied data obtained from electronic medical and regular medical records of patients with CD and IS in several academic, hospital-based, and university hospitals across Brazil. Descriptive analyses of cardioembolic and non-cardioembolic patients were performed. A prediction model for cardioembolism was proposed with 70% of the sample as the derivation sample, and the model was validated in 30% of the sample. RESULTS: A total of 499 patients were analyzed. The median age was similar in both groups; however, patients with cardioembolic embolism were younger and tended to have higher alcoholism, smoking, and death rates. The predictive model for the etiological classification showed close relation with the number of abnormalities detected on echocardiography and electrocardiography as well as with vascular risk factors. CONCLUSIONS: Our results replicate in part those previously published, with a higher prevalence of vascular risk factors and lower median age in patients with cardioembolic etiology. Our new model for predicting cardioembolic etiology can help identify patients with higher recurrence rate and therefore allow an optimized strategy for secondary prophylaxis.

Stroke Care during the COVID-19 Pandemic: International Expert Panel Review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions. SUMMARY: The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. Key Messages: Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.

Randomization of endovascular treatment with stent-retriever and/or thromboaspiration versus best medical therapy in acute ischemic stroke due to large vessel occlusion trial: Rationale and design.

BACKGROUND: RESILIENT is a prospective, multicenter, randomized phase III trial to test the safety, efficacy, and cost-effectiveness of mechanical thrombectomy as compared to medical treatment alone in patients treated under the less than ideal conditions typically found in the public healthcare system of a developing country. METHODS: Subjects must fulfill the following main inclusion criteria: symptom onset ≤8 h, age ≥18 years, baseline NIHSS ≥8, evidence of intracranial ICA or proximal MCA (M1 segment) occlusion, ASPECTS ≥6 on CT or >5 on DWI-MRI and be either ineligible for or unresponsive to intravenous alteplase. The primary end-point is the distribution of disability levels (on the modified Rankin Scale, mRS) at 90 days under the intention-to-treat principle. RANDOMIZATION: Randomization is performed under a minimization process using age, baseline NIHSS, intravenous alteplase use, occlusion site and center. DESIGN: The trial is designed with an expectation of a 10% difference in the proportion of favorable outcome (mRS 0-2 at 90 days) common odds ratio of 1.615. PRIMARY OUTCOME: Projected sample size is 690 subjects with pre-planned interim analyses at 174, 346, and 518 subjects. SECONDARY OUTCOMES: Secondary end-points include: 90-day functional independence (mRS ≤2), mRS shift stratified for treatment with IV rt-PA at 90 days, infarct volume on 24 h CT or MRI, early dramatic response (NIHSS 0-2 or improvement ≥8 points) at 24 h, vessel recanalization evaluated by CTA or MRA at 24 h, and the post-procedure rate of successful reperfusion (defined as a modified Treatment in Cerebral Infarction 2b or greater). Safety variables are mortality at 90 days, symptomatic intracranial hemorrhage at 24 h and procedure-related complications.

Latin American Consensus Statement for the Use of Contrast-Enhanced Transcranial Ultrasound as a Diagnostic Test for Detection of Right-to-Left Shunt.

BACKGROUND: The role of patent foramen ovale is a field of debate and current publications have increasing controversies about the patients' management in young undetermined stroke. Work up with echocardiography and transcranial Doppler (TCD) can aid the decision with better anatomical and functional characterization of right-to-left shunt (RLS). Medical and interventional strategy may benefit from this information. SUMMARY: a group of experts from the Latin American participants of the Neurosonology Research Group (NSRG) of World Federation of Neurology created a task force to review literature and describe the better methodology of contrast TCD (c-TCD). All signatories of the present consensus statement have published at least one study on TCD as an author or co-author in an indexed journal. Two meetings were held while the consensus statement was being drafted, during which controversial issues were discussed and voted on by the statement signatories. The statement paper was reviewed and approved by the Executive Committee of the NSRG of the World Federation of Neurology. The main objective of this consensus statement is to establish a standardization of the c-TCD technique and its interpretation, in order to improve the informative quality of the method, resulting in expanding the application of TCD in the clinical setting. These recommendations optimize the comparison of different diagnostic methods and encourage the use of c-TCD for RLS screening and complementary diagnosis in multicenter studies.

Epidemiology of concurrent Chagas disease and ischemic stroke in a population attending a multicenter quaternary rehabilitation network in Brazil.

BACKGROUND AND PURPOSE: Chagas disease and ischemic stroke (IS) have a close but poorly understood correlation. In endemic settings, continued transmission over time has resulted in increasing prevalence of both asymptomatic infection and cardiomyopathy with increasing age. Latin America has made substantial progress towards Chagas disease control. Although several epidemiological studies have been conducted, information regarding epidemiology and distribution of IS in Chagas disease is still lacking. METHODS: We retrospectively studied the electronic medical record data of all patients with both IS and Chagas disease admitted at SARAH Hospitals across Brazil from 2009 to 2013 to make epidemiological quantifications and statistical inferences. RESULTS: A total of 279 patients with Chagas disease and IS were analyzed from 7729 IS-related admissions, indicating a median prevalence of 3.6% of Chagas disease in IS patients in our cohort. Mean age was 60 years, with female predominance (65%). Most of the cases were from Bahia (61%), followed by Minas Gerais (19%) and Goiás (9.7%). Low-income cities, with decreased access to healthcare, showed the highest number of cases. Distribution of vascular risk factors and outcome after stroke differed among the units. According to current guidelines, secondary prevention was inadequate in 60% of patients. CONCLUSIONS: Chagas disease was common in IS patients; prevalence of concurrent Chagas disease and IS was high in some regions of the country. However, the infection frequency seems to be reduced in the last few years. Public health issues for improving the treatment of Chagas disease and IS are urgently needed.

Cerebral infarct topography of atrial fibrillation and Chagas disease.

BACKGROUND: Chagas disease (CD) and ischemic stroke (IS) have a significant but poorly understood correlation. There is paucity of evidence regarding secondary prophylaxis of IS and etiological causes. OBJECTIVES: To compare arterial stroke topography and the respective morbidities and mortality in patients with CD of undetermined and cardioembolic etiologies and with cardioembolic IS (atrial fibrillation [AF]). METHODS: We compared vascular topography and outcomes using data obtained from the electronic medical records of all patients with IS with either CD (with cardioembolic or undetermined etiology) or AF, admitted to SARAH Hospital Brasilia between 2009 and 2013. RESULTS: A total of 115 patients were investigated: 49 involving AF, 23 involving CD of unclear etiology, and 43 involving CD of cardioembolic etiology. Middle cerebral artery stroke was predominant in all groups, although more frequent in patients with CD of undetermined etiology. No significant difference was found in the arterial territories. Hemodynamic stroke was predominant among CD patients who experienced cardioembolic events. AF patients had worse modified Rankin scale scores upon admission and a higher mortality rate than CD patients in both categories. CONCLUSIONS: Stroke topography is not useful in determining the etiological diagnosis. Patients with AF and IS are more likely to have worse outcomes than are those with CD and IS. The autonomic nervous system could be affected in patients with CD.

Machado de Assis' Original Sin.

Machado de Assis (1839-1908) suffered from temporal lobe epilepsy, probably with origin in the non-dominant hemisphere. The evidence for this is provided by the detailed reports of the characteristics of his seizures by his contemporaries and by his correspondence with other writers. He was treated with bromides and homeopathy. It is unclear whether his neurological disorder influenced his artistic performance. What is evident is that he was deeply ashamed of the disease - he avoided the word "epilepsy" and just wrote about it in his personal correspondence with friends in the last years of his life. Though controversial, he had no clear traces of personality disorders linked to his temporal lobe epilepsy. Despite all his adversities, including being "mulatto," having a stutter, being of humble origins, and epileptic in a period when there was no efficacious therapy and a profound stigma associated with the disease, Machado de Assis became one of the most important Brazilian writers of all times.

Mortality and Stroke Recurrence in a Rehabilitation Cohort of Patients with Cerebral Infarcts and Chagas Disease.

BACKGROUND: Chagas disease is related to ischemic stroke (IS), although few epidemiological studies have evaluated the associated mortality and recurrence. Our objective is to determine factors associated with mortality and recurrence of IS in patients with IS and Chagas disease. METHODS: We retrospectively studied data obtained from electronic medical records of patients admitted at SARAH Hospitals across Brazil between 2009 and 2013. Using Cox regression analysis for mortality and logistic regression for recurrence, we assessed primary population characteristics and statistical associations between risk factors and outcomes. RESULTS: We analyzed 279 patients who were followed up until 2016. The mean age at stroke onset was 61 with a 10% frequency of death. Multivariate analysis assessing mortality demonstrated that the associated factors were age at stroke (hazard ratio [HR] 1.04), initial modified Rankin Scale (mRS; HR 20.91), bladder dysfunction (HR 2.51), diabetes mellitus (DM; HR 3.64), and alcoholism (HR 3.37). Multivariate analysis assessing recurrence demonstrated that the associated factors were age at ictus (OR 0.96), cognitive deficit (OR 0.44), initial mRS (OR 1.84), cardioembolic etiology (OR 2.47), and female sex (OR 2.73). CONCLUSIONS: Cardiac conditions did not correlate with mortality or recurrence. Age was a protective factor against recurrence, probably due to cumulative risk of IS over time, while initial mRS was associated with both outcomes. Treating diseases such as DM and bladder dysfunction, and early treatment to reduce the initial mRS could potentially prevent both outcomes; also, establishing a correct etiological diagnosis is important.

Early Cyclical Neuromuscular Electrical Stimulation Improves Strength and Trophism by Akt Pathway Signaling in Partially Paralyzed Biceps Muscle After Spinal Cord Injury in Rats.

Background: Electrical stimulation is often used to treat weakness in people with spinal cord injury (SCI); however its efficacy for increasing strength and trophism is weak, and the mechanisms underlying the therapeutic benefits are unknown. Objective: The purpose of this study was to analyze the effects of neuromuscular electrical stimulation (NMES) on muscle function, trophism, and the Akt pathway signaling involved in muscular plasticity after incomplete SCI in rats. Design: This was an experimental study. Methods: Twenty-one adult female Wistar rats were divided into sham, SCI, and SCI plus NMES groups. In injured animals, SCI hemisection was induced by a surgical procedure at the C5-C7 level. The 5-week NMES protocol consisted of biceps brachii muscle stimulation 5 times per week, initiated 48 h after injury. Forepaw function and strength, biceps muscle trophism, and the expression of phosphorylated Akt, p70S6K, and GSK-3ß cellular anabolic pathway markers in stimulated muscle tissue were assessed. Results: There was an increase in bicep muscle strength in the NMES group compared with the untreated SCI group, from postoperative day 21 until the end of the evaluation period. Also, there was an increase in muscle trophism in the NMES group compared with the SCI group. Forelimb function gradually recovered in both the SCI group and the NMES group, with no differences between them. Regarding muscle protein expression, the NMES group had higher values for phospho-Akt, phospho-p70S6K, and phospho-GSK-3ß than did the SCI group. Limitations: The experimental findings were limited to an animal model of incomplete SCI and may not be fully generalizable to humans. Conclusions: Early cyclical NMES therapy was shown to increase muscle strength and induce hypertrophy after incomplete SCI in a rat model, probably by increasing phospho-Akt, phospho-p70S6K, and phospho-GSK-3ß signaling protein synthesis.

Corrigendum to "Increasing Dose of Autologous Bone Marrow Mononuclear Cells Transplantation Is Related to Stroke Outcome: Results from a Pooled Analysis of Two Clinical Trials".

[This corrects the article DOI: 10.1155/2016/8657173.].

Next generation sequencing analysis of patients with familial cervical artery dissection.

BACKGROUND: The cause of cervical artery dissection is not well understood. We test the hypothesis that mutations in genes associated with known arterial connective tissue disorders are enriched in patients with familial cervical artery dissection. PATIENTS AND METHODS: Patient duos from nine pedigrees with familial cervical artery dissection were analyzed by whole exome sequencing. Single nucleotide variants in a panel of 11 candidate genes (ACTA2, MYH11, FBN1, TGFBR1, TGFBR2, TGFB2, COL3A1, COL4A1, SMAD3, MYLK and SLC2A10) were prioritized according to functionality (stop-loss, nonsense, and missense variants with polyphen-2 score ≥0.95). Variants classified as "benign" or "likely benign" in the ClinVar database were excluded from further analysis. For comparison, non-benign stop-loss, nonsense and missense variants with polyphen-2 score ≥0.95 in the same panel of candidate genes were identified in the European non-Finnish population of the ExAC database (n = 33,370). RESULTS: Non-benign Single nucleotide variants in both affected patients were identified in four of the nine cervical artery dissection families (COL3A1; Gly324Ser, FBN1: Arg2554Trp, COL4A1: Pro116Leu, and TGFBR2: Ala292Thr) yielding an allele frequency of 22.2% (4/18). In the comparison group, 1782 variants were present in 33,370 subjects from the ExAC database (allele frequency: 1782/66,740 = 2.7%; p = 0.0008; odds ratio = 14.2; 95% confidence interval = 3.8-52.9). CONCLUSION: Cervical artery dissection families showed enrichment for non-benign variants in genes associated with arterial connective tissue disorders. The observation that findings differed across families indicates genetic heterogeneity of familial cervical artery dissection.

Ischemic stroke classification and risk of embolism in patients with Chagas disease.

Ischemic stroke (IS) and Chagas disease are strongly related. Nevertheless, little attention has been paid to this association and its natural history. The current guidelines concerning the management and secondary prevention of IS are largely based on the incomplete information or extrapolation of knowledge from other stroke etiologies. We performed a retrospective study which compared stroke etiologies among a cohort of hospitalized patients with IS and Chagas disease. The Instituto de Pesquisa Evandro Chagas/Fundação Oswaldo Cruz (IPEC/FIOCRUZ) embolic score was also used to identify and evaluate the risk of embolism in this population. A total of 86 patients were included in the analysis. The mean age of the study population was 58 years, and 60 % were men. According to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) Classification, 45 % of the strokes were of undetermined etiology and 45 % of cardioembolic origin, while the Stop Stroke Study/Causative Classification System (SSS/CCS) TOAST indicated that 34 % were undetermined and 50 % cardioembolic (p < 0.01); 44 % of these patients were classified as having a high embolic risk according to the IPEC/FIOCRUZ score. Among the undetermined causes, 83.3 % fulfilled the criteria for embolic stroke of undetermined source (ESUS). The SSS/CCS TOAST etiological classification system was superior to the classical TOAST criteria in identifying a cardioembolic etiology in patients with ischemic stroke and Chagas disease. The IPEC/FIOCRUZ score did not correlate with the number of patients who were determined to have cardioembolic stroke etiologies. The current guidelines for stroke prevention should be reviewed in this population.

Prodromal Transient Ischemic Attack or Minor Stroke and Outcome in Basilar Artery Occlusion.

BACKGROUND: The presence of prodromal transient ischemic attacks (TIAs) has been associated with a favorable outcome in anterior circulation stroke. We aimed to determine the association between prodromal TIAs or minor stroke and outcomes at 1 month, in the Basilar Artery International Cooperation Study, a registry of patients presenting with an acute symptomatic and radiologically confirmed basilar artery occlusion. METHODS: A total of 619 patients were enrolled in the registry. Information on prodromal TIAs was available for 517 patients and on prodromal stroke for 487 patients. We calculated risk ratios and corresponding 95% confidence intervals (CIs) for poor clinical outcome (modified Rankin Scale score ≥4) according to the variables of interest. RESULTS: Prodromal minor stroke was associated with poor outcome (crude risk ratio [cRR], 1.26; 95% CI, 1.12-1.42), but TIAs were not (cRR, .93; 95% CI, .79-1.09). These associations remained essentially the same after adjustment for confounding variables. CONCLUSIONS: Prodromal minor stroke was associated with an unfavorable outcome in patients with basilar artery occlusion, whereas prodromal TIA was not.