Stroke and brain atrophy in chronic Chagas disease patients: A new theory proposition

Oliveira-Filho, Jamary

doi:10.1590/S1980-57642009DN30100005

Abstract

Chagas disease (CD) remains a major cause of cardiomyopathy and stroke in developing countries. Brain damage in CD has been attributed exclusively to the effects of structural heart disease on the brain, including cardioembolism and low cardiac output symptoms. However, CD patients also develop stroke and brain atrophy independently of cardiac disease severity. Chronic inflammation directed against T. cruzi may act as a trigger for endothelial damage, platelet activation, acceleration of atherosclerosis and apoptosis, all of which lead to stroke and brain atrophy. In the present article, evidence supporting this new theory is presented, along with considerations towards mechanistically-based targeted treatment.

Key words:
Chagas disease; American trypanosomiasis; cognition; cerebrovascular disorders; pathogenesis.

Resumo

A doença de Chagas (DC) permanence uma causa importante de cardiomiopatia e acidente vascular cerebral em países em desenvolvimento. A lesão cerebral na DC tem sido atribuída aos efeitos da doença cardíaca estrutural no cérebro, incluindo cardioembolia e sintomas de baixo débito cardíaco. No entanto, pacientes com DC desenvolvem acidente vascular cerebral e atrofia cerebral independentemente da gravidade da cardiomiopatia. Inflamação crônica direcionada contra o T. cruzi pode agir como desencadeante de lesão endotelial, ativação plaquetária, aceleração de aterosclerose e apoptose, todos predispondo a acidente vascular cerebral e atrofia cerebral. Nesse artigo, as evidências que dão suporte a esta nova teoria são apresentadas, juntamente com argumentos direcionados a um tratamento baseado no mecanismo do dano cerebral.

Palavras-chave:
doença de Chagas; Tripanossomíase americana; cognição; doenças cerebrovasculares; patogênese.

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References

¹
Control of Chagas disease. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser 1991;811:1-95.
²
Anez N, Crisante G, Rojas A. Update on Chagas disease in Venezuela: a review. Mem Inst Oswaldo Cruz 2004;99:781-787.
³
Aras R, Gomes I, Veiga M, Melo A. Vectorial transmission of Chagas' disease in Mulungu do Morro, Northeastern of Brazil. Rev Soc Bras Med Trop 2003;36:359-363.
⁴
Aras R, Veiga M, Gomes I, et al. Prevalence of Chagas' disease in Mulungu do Morro northeastern Brazil. Arq Bras Cardiol 2002;78:441-443.
⁵
Oliveira-Filho J, Viana LC, Vieira-de-Melo RM, et al. Chagas disease is an independent risk factor for stroke: baseline characteristics of a chagas disease cohort. Stroke 2005;36:2015-2017.
⁶
Navin TR, Roberto RR, Juranek DD, et al. Human and sylvatic Trypanosoma cruzi infection in California. Am J Public Health 1985;75:366-369.
⁷
Frank M, Hegenscheid B, Janitschke K, Weinke T. Prevalence and epidemiological significance of Trypanosoma cruzi infection among Latin American immigrants in Berlin, Germany. Infection 1997;25:355-358.
⁸
Reesink HW. European strategies against the parasite transfusion risk. Transfus Clin Biol 2005;12:1-4.
⁹
Cordova E, Boschi A, Ambrosioni J, Cudos C, Corti M. Reactivation of Chagas disease with central nervous system involvement in HIV-infected patients in Argentina, 1992-2007. Int J Infect Dis 2008;12:587-592.
¹⁰
Sartori AM, Ibrahim KY, Nunes Westphalen EV, et al. Manifestations of Chagas disease (American trypanosomiasis) in patients with HIV/AIDS. Ann Trop Med Parasitol 2007;101:31-50.
¹¹
Chagas C. Nova entidade mórbida do homem. Rezumo geral de estudos etiolojicos e clinicos. Mem Inst Oswaldo Cruz 1911;3:219-275.
¹²
Pittella JE, Meneguette C, Barbosa AJ. Histopathological and immunohistochemical study of the brain and heart in the chronic cardiac form of Chagas' disease. Arq Neuropsiquiatr 1993;51:8-15.
¹³
de Queiroz AC, Ramos EA. [Anatomo-pathological study of the brain in idiopathic cardiomegaly]. Arq Neuropsiquiatr 1979;37:405-411.
¹⁴
Pitella JE. Ischemic cerebral changes in the chronic chagasic cardiopathy. Arq Neuropsiquiatr 1984;42:105-115.
¹⁵
de Queiroz AC. Estudo anatomopatológico do encéfalo na forma crônica da doença de Chagas. Rev Pat Trop 1978;7:135-145.
¹⁶
Alencar A. Atrofia cerebral cortical na cardiopatia crônica Chagásica. O Hospital 1964;66:807-815.
¹⁷
Alencar A. Atrofia do cérebro e anóxia na cardiopatia crônica da doença de Chagas. An Acad Bras Cien 1964;36:193-197.
¹⁸
Alencar A. Alterações cerebelares em pacientes com cardiopatia crônica Chagásica. Arq Neuropsiquiatr 1967;25:191-198.
¹⁹
Andrade Z, Sadigursky, M. Tromboembolismo em chagásicos sem insuficência cardíaca. Gazeta Medica 1971:59-64.
²⁰
Samuel J, Oliveira M, Correa De Araujo RR, Navarro MA, Muccillo G. Cardiac thrombosis and thromboembolism in chronic Chagas' heart disease. Am J Cardiol 1983;52:147-151.
²¹
Rocha HP, Andrade ZA. Pulmonary thrombo-embolic phenomena in subjects of chronic Chagas' myocarditis. Arq Bras Med 1955;45:355-364.
²²
Nunes MC, Barbosa MM, Rocha MO. Peculiar aspects of cardiogenic embolism in patients with Chagas' cardiomyopathy: a transthoracic and transesophageal echocardiographic study. J Am Soc Echocardiogr 2005;18:761-767.
²³
Jesus PAP, Vieira-de-Melo RM, Lacerda AM, et al. Chagas disease and microembolic signals on transcranial doppler are predictors of death in patients with congestive heart failure. Neurology 2007;68(suppl):394.
²⁴
Carod-Artal FJ, Vargas AP, Horan TA, Nunes LG. Chagasic cardiomyopathy is independently associated with ischemic stroke in Chagas disease. Stroke 2005;36:965-970.
²⁵
Carod-Artal FJ, Vargas AP, Melo M, Horan TA. American trypanosomiasis (Chagas' disease): an unrecognised cause of stroke. J Neurol Neurosurg Psychiatry 2003;74:516-518.
²⁶
Oliveira-Filho J, Camargo ECS, Oliveira LMB, et al. Genomic response profile in cardiomyopathy and stroke associated with Chagas disease: A microarray analysis study. Cerebrovasc Dis 2008;25 (suppl. 2):107.
²⁷
Oliveira-Filho J, Vieira-de-Melo RM, Reis PSO, et al. Chagas disease is independently associated with brain atrophy. J Neurol (in press).
²⁸
Jefferson AL, Massaro JM, Wolf PA, et al. Inflammatory biomarkers are associated with total brain volume: the Framingham Heart Study. Neurology 2007;68:1032-1038.
²⁹
Abel LC, Rizzo LV, Ianni B, et al. Chronic Chagas' disease cardiomyopathy patients display an increased IFN-gamma response to Trypanosoma cruzi infection. J Autoimmun 2001;17:99-107.
³⁰
Cunha-Neto E, Rizzo LV, Albuquerque F, et al. Cytokine production profile of heart-infiltrating T cells in Chagas' disease cardiomyopathy. Braz J Med Biol Res 1998;31:133-137.
³¹
Ferreira RC, Ianni BM, Abel LC, et al. Increased plasma levels of tumor necrosis factor-alpha in asymptomatic/"indeterminate" and Chagas disease cardiomyopathy patients. Mem Inst Oswaldo Cruz 2003;98:407-411.
³²
Mangone CA, Sica RE, Pereyra S, et al. Cognitive impairment in human chronic Chagas' disease. Arq Neuropsiquiatr 1994;52:200-203.
³³
Wackermann PV, Fernandes RM, Elias J, Jr., Dos Santos AC, Marques W, Jr., Barreira AA. Involvement of the central nervous system in the chronic form of Chagas' disease. J Neurol Sci 2008;269:152-157.
³⁴
Dias JS, Lacerda AM, Vieira-de-Melo RM, et al. Cognitive dysfunction in chronic Chagas disease cardiomyopathy. Dement Neuropsychol 2009;3:27-33.
³⁵
Costa GC, Rocha MO, Moreira PR, et al. Functional IL-10 Gene Polymorphism Is Associated with Chagas Disease Cardiomyopathy. J Infect Dis 2009;199:451-454.

Publication Dates

Publication in this collection
Jan-Mar 2009

History

Received
11 Jan 2009
Accepted
12 Feb 2009

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] ¹
Control of Chagas disease. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser 1991;811:1-95.

[2] ²
Anez N, Crisante G, Rojas A. Update on Chagas disease in Venezuela: a review. Mem Inst Oswaldo Cruz 2004;99:781-787.

[3] ³
Aras R, Gomes I, Veiga M, Melo A. Vectorial transmission of Chagas' disease in Mulungu do Morro, Northeastern of Brazil. Rev Soc Bras Med Trop 2003;36:359-363.

[4] ⁴
Aras R, Veiga M, Gomes I, et al. Prevalence of Chagas' disease in Mulungu do Morro northeastern Brazil. Arq Bras Cardiol 2002;78:441-443.

[5] ⁵
Oliveira-Filho J, Viana LC, Vieira-de-Melo RM, et al. Chagas disease is an independent risk factor for stroke: baseline characteristics of a chagas disease cohort. Stroke 2005;36:2015-2017.

[6] ⁶
Navin TR, Roberto RR, Juranek DD, et al. Human and sylvatic Trypanosoma cruzi infection in California. Am J Public Health 1985;75:366-369.

[7] ⁷
Frank M, Hegenscheid B, Janitschke K, Weinke T. Prevalence and epidemiological significance of Trypanosoma cruzi infection among Latin American immigrants in Berlin, Germany. Infection 1997;25:355-358.

[8] ⁸
Reesink HW. European strategies against the parasite transfusion risk. Transfus Clin Biol 2005;12:1-4.

[9] ⁹
Cordova E, Boschi A, Ambrosioni J, Cudos C, Corti M. Reactivation of Chagas disease with central nervous system involvement in HIV-infected patients in Argentina, 1992-2007. Int J Infect Dis 2008;12:587-592.

[10] ¹⁰
Sartori AM, Ibrahim KY, Nunes Westphalen EV, et al. Manifestations of Chagas disease (American trypanosomiasis) in patients with HIV/AIDS. Ann Trop Med Parasitol 2007;101:31-50.

[11] ¹¹
Chagas C. Nova entidade mórbida do homem. Rezumo geral de estudos etiolojicos e clinicos. Mem Inst Oswaldo Cruz 1911;3:219-275.

[12] ¹²
Pittella JE, Meneguette C, Barbosa AJ. Histopathological and immunohistochemical study of the brain and heart in the chronic cardiac form of Chagas' disease. Arq Neuropsiquiatr 1993;51:8-15.

[13] ¹³
de Queiroz AC, Ramos EA. [Anatomo-pathological study of the brain in idiopathic cardiomegaly]. Arq Neuropsiquiatr 1979;37:405-411.

[14] ¹⁴
Pitella JE. Ischemic cerebral changes in the chronic chagasic cardiopathy. Arq Neuropsiquiatr 1984;42:105-115.

[15] ¹⁵
de Queiroz AC. Estudo anatomopatológico do encéfalo na forma crônica da doença de Chagas. Rev Pat Trop 1978;7:135-145.

[16] ¹⁶
Alencar A. Atrofia cerebral cortical na cardiopatia crônica Chagásica. O Hospital 1964;66:807-815.

[17] ¹⁷
Alencar A. Atrofia do cérebro e anóxia na cardiopatia crônica da doença de Chagas. An Acad Bras Cien 1964;36:193-197.

[18] ¹⁸
Alencar A. Alterações cerebelares em pacientes com cardiopatia crônica Chagásica. Arq Neuropsiquiatr 1967;25:191-198.

[19] ¹⁹
Andrade Z, Sadigursky, M. Tromboembolismo em chagásicos sem insuficência cardíaca. Gazeta Medica 1971:59-64.

[20] ²⁰
Samuel J, Oliveira M, Correa De Araujo RR, Navarro MA, Muccillo G. Cardiac thrombosis and thromboembolism in chronic Chagas' heart disease. Am J Cardiol 1983;52:147-151.

[21] ²¹
Rocha HP, Andrade ZA. Pulmonary thrombo-embolic phenomena in subjects of chronic Chagas' myocarditis. Arq Bras Med 1955;45:355-364.

[22] ²²
Nunes MC, Barbosa MM, Rocha MO. Peculiar aspects of cardiogenic embolism in patients with Chagas' cardiomyopathy: a transthoracic and transesophageal echocardiographic study. J Am Soc Echocardiogr 2005;18:761-767.

[23] ²³
Jesus PAP, Vieira-de-Melo RM, Lacerda AM, et al. Chagas disease and microembolic signals on transcranial doppler are predictors of death in patients with congestive heart failure. Neurology 2007;68(suppl):394.

[24] ²⁴
Carod-Artal FJ, Vargas AP, Horan TA, Nunes LG. Chagasic cardiomyopathy is independently associated with ischemic stroke in Chagas disease. Stroke 2005;36:965-970.

[25] ²⁵
Carod-Artal FJ, Vargas AP, Melo M, Horan TA. American trypanosomiasis (Chagas' disease): an unrecognised cause of stroke. J Neurol Neurosurg Psychiatry 2003;74:516-518.

[26] ²⁶
Oliveira-Filho J, Camargo ECS, Oliveira LMB, et al. Genomic response profile in cardiomyopathy and stroke associated with Chagas disease: A microarray analysis study. Cerebrovasc Dis 2008;25 (suppl. 2):107.

[27] ²⁷
Oliveira-Filho J, Vieira-de-Melo RM, Reis PSO, et al. Chagas disease is independently associated with brain atrophy. J Neurol (in press).

[28] ²⁸
Jefferson AL, Massaro JM, Wolf PA, et al. Inflammatory biomarkers are associated with total brain volume: the Framingham Heart Study. Neurology 2007;68:1032-1038.

[29] ²⁹
Abel LC, Rizzo LV, Ianni B, et al. Chronic Chagas' disease cardiomyopathy patients display an increased IFN-gamma response to Trypanosoma cruzi infection. J Autoimmun 2001;17:99-107.

[30] ³⁰
Cunha-Neto E, Rizzo LV, Albuquerque F, et al. Cytokine production profile of heart-infiltrating T cells in Chagas' disease cardiomyopathy. Braz J Med Biol Res 1998;31:133-137.

[31] ³¹
Ferreira RC, Ianni BM, Abel LC, et al. Increased plasma levels of tumor necrosis factor-alpha in asymptomatic/"indeterminate" and Chagas disease cardiomyopathy patients. Mem Inst Oswaldo Cruz 2003;98:407-411.

[32] ³²
Mangone CA, Sica RE, Pereyra S, et al. Cognitive impairment in human chronic Chagas' disease. Arq Neuropsiquiatr 1994;52:200-203.

[33] ³³
Wackermann PV, Fernandes RM, Elias J, Jr., Dos Santos AC, Marques W, Jr., Barreira AA. Involvement of the central nervous system in the chronic form of Chagas' disease. J Neurol Sci 2008;269:152-157.

[34] ³⁴
Dias JS, Lacerda AM, Vieira-de-Melo RM, et al. Cognitive dysfunction in chronic Chagas disease cardiomyopathy. Dement Neuropsychol 2009;3:27-33.

[35] ³⁵
Costa GC, Rocha MO, Moreira PR, et al. Functional IL-10 Gene Polymorphism Is Associated with Chagas Disease Cardiomyopathy. J Infect Dis 2009;199:451-454.

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