Stroke in Chagas disease: from pathophysiology to clinical practice

Abstract

Despite substantial progress toward its control, Chagas disease continues to be a major public health problem in Latin America and has become a global health concern. The disease affects approximately 6 million people, of whom 20-40% will develop cardiomyopathy over the years after the initial Trypanosoma cruzi infection. Chagas cardiomyopathy is the most serious and frequent manifestation of Chagas disease. Clinical manifestations vary widely according to the severity of myocardial dysfunction, ranging from asymptomatic to severe forms, including dilated cardiomyopathy with heart failure, arrhythmias, thromboembolism events, and sudden death. Chagas disease is a risk factor for stroke regardless of the severity of cardiomyopathy, which is a leading cause of chronic disability. Classically, stroke etiology in patients with Chagas disease is thought to be cardioembolic and related to apical aneurysm, mural thrombus, and atrial arrhythmias. Although most strokes are thromboembolic, other etiologies have been observed. Small vessel disease, atherosclerosis, and cryptogenic diseases have been reported in patients with Chagas disease and stroke. The potential mechanisms involved in non-embolic strokes include the presence of associated risk factors, pro-inflammatory and prothrombotic disease states, and endothelial dysfunction. However, the contribution of each mechanism to stroke in Chagas disease remains unclear. The review aims to provide an overview of stroke in Chagas disease, highlighting the main pathophysiological mechanisms, clinical presentation, approaches for prevention, and unanswered questions regarding treatment strategies.

Diretriz da SBC sobre Diagnóstico e Tratamento de Pacientes com Cardiomiopatia da Doença de Chagas – 2023

“… 474 , 866 Ademais, as empíricas condutas terapêuticas sugeridas quando de sua formulação 364 idealmente deverão ser lastreadas em estudos aleatorizados de comprovação de eficácia. 474 , 866 , 867 …”

“… 474 , 866 In addition, the empirical therapeutic managements suggested by the time it was formulated 364 should be ideally supported by randomized studies of efficacy. 474 , 866 , 867 …”

Anxiety, depression, and memory loss in Chagas disease: a puzzle far beyond neuroinflammation to be unpicked and solved*

“…Even though the pathophysiological mechanisms are not completely understood, clinical approaches for the prevention of stroke in CD are demanded. 123 Interestingly, in a long-term follow-up benznidazole therapy was associated with a decreased incidence of CD progression from the IND to the CARD form, and with a reduced risk of cardiovascular events, including stroke. 124 Considering the putative effect of benznidazole on biological mechanisms contributing to stroke, our studies in chronically T. cruzi -infected mice showed that benznidazole therapy abrogated atrial fibrillation and reduced the expression of chemokines and cytokines (such as CCL3, TNF, and IFNγ) in the cardiac and the systemic inflammatory profile, as decreased the TNF and nitric oxide serum levels.…”

“…Indeed, stroke is an important neurobehavioural change in CD, leading to chronic disabilities. 121 , 122 , 123 Although most strokes are cardioembolic, related to apical aneurysm, mural thrombus, and atrial fibrillation, small vessel diseases and atherosclerosis may also concur to stroke in CD patients. Thus, endothelial dysfunction, and prothrombotic and inflammatory disorders may represent non-embolic risk factors for stroke in CD.…”

“…Also, the microbiota-gut-brain axis gained attention due the role played by gut-microbiota in a myriad of biological circuits crucial for behavioural and neurocognition processes, 131 including the regulation of tryptophan bioavailability and its conversion to neuroactive metabolites such as serotonin, melatonin, kynurenine and quinolinic acid, 131 , 132 a matter to be explored in T. cruzi infection. In CD, diverse factors may concur to deterioration of the CNS, neurobehavioural changes (such as stroke) 123 and trigger behavioural and neurocognitive alterations. It is also conceivable to consider that in CD patients CNS impairment may have a neuro-hormonal basis involving the renin-angiotensin-aldosterone system, 133 , 134 since systemic and brain renin-angiotensin system may take part in aging and neurodegenerative disorders, through oxidative stress and vascular dysfunction.…”