Ischaemic stroke in chagasic patients
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《神经病学神经外科学杂志》
1 Universidade Federal de Minas Gerais (UFMG), Instituto de Ciências Biológicas, Belo Horizonte, Brazil
Correspondence to:
A L Teixeira Jr
Universidade Federal de Minas Gerais (UFMG), Departamento de Morfologia, Instituto de Ciências Biológicas, Av. Ant?nio Carlos, 6627, Pampulha, Belo Horizonte MC 31270-901, Brazil; altexjr@hotmail.com
Keywords: Chagas; disease; stroke
We read with interest the paper by Carod-Artal et al1 that showed the relevance of Chagas’ disease as a stroke risk factor in patients of South American origin. They also confirmed a textbook view2 (not hitherto demonstrated) that cardioembolism is the main cause of stroke in Chagas’ disease, in 52% of cases. This reflects in part the underlying chagasic cardiomyopathy, characterised by congestive heart failure and arrhythmias, present in 46% of chagasic patients as compared with 25% of non-chagasic patients.
Despite the lack of comparison of stroke characteristics between both groups, one very interesting finding was the significant percentage of chagasic patients who developed stroke without any known vascular risk factors or cardiopathy. As the authors stated, undetected cardiovascular disease could account for at least part of this finding. The indeterminate form of the disease is defined by the presence of infection confirmed by serological tests, in the absence of symptoms or of electrocardiographic or radiological abnormalities. Twenty five % of subjects with the indeterminate form of the disease may present significant structural and/or functional abnormalities when they are fully evaluated by more sensitive methods, such as ergometry and autonomic tests.3
Another possible explanation proposed by the authors would be the vasculitis phenomenon. Although there is good experimental evidence to suggest that changes in the microvasculature may contribute to chagasic heart disease,4 much less is known about the possible involvement of central nervous system microvasculature in Chagas’ disease. Indeed, most studies point to an important role for endothelin in the pathogenesis of microvascular changes in the chagasic heart, but we are unaware of any similar studies of the central nervous system.
The authors also suggest the need for primary prevention in all patients with Chagas’ disease cardiomyopathy. This is a strong recommendation, as most chagasic patients derive from poor social economic backgrounds and have poor access to the health system.1 Chronic oral anticoagulant therapy is known to cause frequent clinical complications, especially bleeding; an alternative approach could be use of the low dose anticoagulant therapy that has been recently suggested for the treatment of deep vein thrombosis.6 However, further studies are still needed to investigate this possibility specifically in Chagas’ disease.
References
Carod-Artal FJ, Vargas AP, Melo M, et al. American trypanosomiasis (Chagas’ disease): an unrecognised cause of stroke. J Neurol Neurosurg Psychiatry 2003;74:516–18.
Kirchhoff LV. Trypanosoma species (American trypanosomiasis, Chagas’ disease). In: Mandell GL, Bennet JE, Dolin R, eds. Principles and practice of infectious disease. New York: Churchill Livingstone, 1995:2442–9.
Rocha MOC, Ribeiro ALP, Teixeira MM. Clinical management of chronic Chagas cardiomyopathy. Front Biosci 2003;8:44–54.
Petkova SB, Huang H, Factor SM, et al. The role of endothelin in the pathogenesis of Chagas’ disease. Int J Parasitol 2001;31:499–511.
Camargos ERS, Machado CRS, Teixeira AL Jr, et al. Role of endothelin during experimental Trypanosoma cruzi infection in rats. Clin Sci 2002;103(suppl):64S–67S.
Ridker PM, Goldhaber SZ, Danielson E, et al. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003;348:1425–34.
Authors’ reply
F J Carod-Artal2, A P Vargas2, M Melo2 and T A Horan2
2 Neurology Department, Sarah Hospital, Brasilia, Brazil
Correspondence to:
Dr F J Carod-Artal
Neurology Department, Sarah Hospital, SMHS quadra 501 conjunto A, CEP 7330-150, Brasilia DF, Brazil; javier@bsb.sarah.br/FJCarod@aol.com
Keywords: anti; thrombotic therapy; stroke
In our recent study, we demonstrated that at least 52.2% of chagasic strokes are due to cardioembolism and 36.8% are of undetermined cause.1 A significant proportion of these cryptogenic chagasic strokes may also be cardioembolic in origin.2,3 We therefore encourage the use of transoesophageal echocardiography in all patients with chagasic stroke, especially for the better definition of aetiology in the 36% having strokes of undetermined cause.
The monitored administration of warfarin is remarkably effective in the reduction of stroke recurrence in persons with cardioembolic stroke.4,5 Thus, we recommend oral anticoagulation for all individuals with chagasic stroke, who have demonstrated risk factors for cardioembolism. To our knowledge, no case control study analysing these factors has yet been carried out.
Stroke of arterial origin in Chagas’ disease seems much less common than in the general population of stroke patients.1 Evidence for secondary prevention of stroke of arterial origin with oral anticoagulation as in the Warfarin-Aspirin Recurrent Stroke Study (WARSS)6 and European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT)7 clinical trials is controversial. Our follow up experience with the administration of secondary anticoagulation to persons with chagasic stroke, whether cardioembolic or not, has been encouraging in the lack of significant complications. We are therefore currently investigating the efficacy of antithrombotic therapy in chagasic stroke patients, using either low or moderate dosages of anticoagulants. Until the results of this or similar investigations are available, antithrombotic prophylaxis should be individualised in persons with chagasic stroke of undetermined cause, on the basis of the estimated risk of recurrent stroke v the risk of complications during anticoagulation.
We thank M M Teixeira and A L Teixeira for their comments and interest in our article.
References
Carod-Artal FJ, Vargas AP, Melo M, et al. American trypanosomiasis (Chagas’ disease): an unrecognised cause of stroke. J Neurol Neurosurg Psychiatry 2003;74:516–18.
Del Brutto OH, Carod-Artal FJ, Román GC, et al. Stroke in the tropics. In: American Academy of Neurology, ed. Tropical neurology. Philadelphia: Lippincott Williams & Wilkins, 2002:11–35.
Carod-Artal FJ, Vargas AP, Melo M, et al. Síndrome de la oclusión rostral de la arteria basilar y enfermedad de Chagas. Rev Neurol 2002;35:337–41.
Albers G, Amarenco P, Easton D, et al. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest 2001;119:300S–320S.
Hart RG, Halperin JL, Pearce LA, et al. Lessons from the Stroke Prevention in Atrial Fibrillation trials. Ann Intern Med 2003;138:831–8.
Mohr J, Thomson JLP, Lazar RM, et al. For the Warfarin-Aspirin Recurrent Stroke Study Group. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 2001;345:1444–51.
The European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT) Study Group. Oral anticoagulation in patients after cerebral ischemia of arterial origin and risk of intracranial hemorrhage. Stroke 2003;34:e45–7.(A L Teixeira, Jr1 and M M)
Correspondence to:
A L Teixeira Jr
Universidade Federal de Minas Gerais (UFMG), Departamento de Morfologia, Instituto de Ciências Biológicas, Av. Ant?nio Carlos, 6627, Pampulha, Belo Horizonte MC 31270-901, Brazil; altexjr@hotmail.com
Keywords: Chagas; disease; stroke
We read with interest the paper by Carod-Artal et al1 that showed the relevance of Chagas’ disease as a stroke risk factor in patients of South American origin. They also confirmed a textbook view2 (not hitherto demonstrated) that cardioembolism is the main cause of stroke in Chagas’ disease, in 52% of cases. This reflects in part the underlying chagasic cardiomyopathy, characterised by congestive heart failure and arrhythmias, present in 46% of chagasic patients as compared with 25% of non-chagasic patients.
Despite the lack of comparison of stroke characteristics between both groups, one very interesting finding was the significant percentage of chagasic patients who developed stroke without any known vascular risk factors or cardiopathy. As the authors stated, undetected cardiovascular disease could account for at least part of this finding. The indeterminate form of the disease is defined by the presence of infection confirmed by serological tests, in the absence of symptoms or of electrocardiographic or radiological abnormalities. Twenty five % of subjects with the indeterminate form of the disease may present significant structural and/or functional abnormalities when they are fully evaluated by more sensitive methods, such as ergometry and autonomic tests.3
Another possible explanation proposed by the authors would be the vasculitis phenomenon. Although there is good experimental evidence to suggest that changes in the microvasculature may contribute to chagasic heart disease,4 much less is known about the possible involvement of central nervous system microvasculature in Chagas’ disease. Indeed, most studies point to an important role for endothelin in the pathogenesis of microvascular changes in the chagasic heart, but we are unaware of any similar studies of the central nervous system.
The authors also suggest the need for primary prevention in all patients with Chagas’ disease cardiomyopathy. This is a strong recommendation, as most chagasic patients derive from poor social economic backgrounds and have poor access to the health system.1 Chronic oral anticoagulant therapy is known to cause frequent clinical complications, especially bleeding; an alternative approach could be use of the low dose anticoagulant therapy that has been recently suggested for the treatment of deep vein thrombosis.6 However, further studies are still needed to investigate this possibility specifically in Chagas’ disease.
References
Carod-Artal FJ, Vargas AP, Melo M, et al. American trypanosomiasis (Chagas’ disease): an unrecognised cause of stroke. J Neurol Neurosurg Psychiatry 2003;74:516–18.
Kirchhoff LV. Trypanosoma species (American trypanosomiasis, Chagas’ disease). In: Mandell GL, Bennet JE, Dolin R, eds. Principles and practice of infectious disease. New York: Churchill Livingstone, 1995:2442–9.
Rocha MOC, Ribeiro ALP, Teixeira MM. Clinical management of chronic Chagas cardiomyopathy. Front Biosci 2003;8:44–54.
Petkova SB, Huang H, Factor SM, et al. The role of endothelin in the pathogenesis of Chagas’ disease. Int J Parasitol 2001;31:499–511.
Camargos ERS, Machado CRS, Teixeira AL Jr, et al. Role of endothelin during experimental Trypanosoma cruzi infection in rats. Clin Sci 2002;103(suppl):64S–67S.
Ridker PM, Goldhaber SZ, Danielson E, et al. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003;348:1425–34.
Authors’ reply
F J Carod-Artal2, A P Vargas2, M Melo2 and T A Horan2
2 Neurology Department, Sarah Hospital, Brasilia, Brazil
Correspondence to:
Dr F J Carod-Artal
Neurology Department, Sarah Hospital, SMHS quadra 501 conjunto A, CEP 7330-150, Brasilia DF, Brazil; javier@bsb.sarah.br/FJCarod@aol.com
Keywords: anti; thrombotic therapy; stroke
In our recent study, we demonstrated that at least 52.2% of chagasic strokes are due to cardioembolism and 36.8% are of undetermined cause.1 A significant proportion of these cryptogenic chagasic strokes may also be cardioembolic in origin.2,3 We therefore encourage the use of transoesophageal echocardiography in all patients with chagasic stroke, especially for the better definition of aetiology in the 36% having strokes of undetermined cause.
The monitored administration of warfarin is remarkably effective in the reduction of stroke recurrence in persons with cardioembolic stroke.4,5 Thus, we recommend oral anticoagulation for all individuals with chagasic stroke, who have demonstrated risk factors for cardioembolism. To our knowledge, no case control study analysing these factors has yet been carried out.
Stroke of arterial origin in Chagas’ disease seems much less common than in the general population of stroke patients.1 Evidence for secondary prevention of stroke of arterial origin with oral anticoagulation as in the Warfarin-Aspirin Recurrent Stroke Study (WARSS)6 and European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT)7 clinical trials is controversial. Our follow up experience with the administration of secondary anticoagulation to persons with chagasic stroke, whether cardioembolic or not, has been encouraging in the lack of significant complications. We are therefore currently investigating the efficacy of antithrombotic therapy in chagasic stroke patients, using either low or moderate dosages of anticoagulants. Until the results of this or similar investigations are available, antithrombotic prophylaxis should be individualised in persons with chagasic stroke of undetermined cause, on the basis of the estimated risk of recurrent stroke v the risk of complications during anticoagulation.
We thank M M Teixeira and A L Teixeira for their comments and interest in our article.
References
Carod-Artal FJ, Vargas AP, Melo M, et al. American trypanosomiasis (Chagas’ disease): an unrecognised cause of stroke. J Neurol Neurosurg Psychiatry 2003;74:516–18.
Del Brutto OH, Carod-Artal FJ, Román GC, et al. Stroke in the tropics. In: American Academy of Neurology, ed. Tropical neurology. Philadelphia: Lippincott Williams & Wilkins, 2002:11–35.
Carod-Artal FJ, Vargas AP, Melo M, et al. Síndrome de la oclusión rostral de la arteria basilar y enfermedad de Chagas. Rev Neurol 2002;35:337–41.
Albers G, Amarenco P, Easton D, et al. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest 2001;119:300S–320S.
Hart RG, Halperin JL, Pearce LA, et al. Lessons from the Stroke Prevention in Atrial Fibrillation trials. Ann Intern Med 2003;138:831–8.
Mohr J, Thomson JLP, Lazar RM, et al. For the Warfarin-Aspirin Recurrent Stroke Study Group. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 2001;345:1444–51.
The European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT) Study Group. Oral anticoagulation in patients after cerebral ischemia of arterial origin and risk of intracranial hemorrhage. Stroke 2003;34:e45–7.(A L Teixeira, Jr1 and M M)