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CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2021; 79(02): 103-106
DOI: 10.1590/0004-282X-anp-2020-0178
Article

Small vessel occlusion and syphilis in patients with first-ever ischemic stroke

Oclusão de pequenos vasos e sífilis em pacientes com o primeiro acidente vascular cerebral isquêmico
Matheus Gomes Ferreira 
1   Universidade Federal do Paraná, Hospital de Clínicas, Departamento de Neurologia, Curitiba PR, Brazil.
,
Valeria Cristina Scavasine 
1   Universidade Federal do Paraná, Hospital de Clínicas, Departamento de Neurologia, Curitiba PR, Brazil.
,
Giovanni Luís Breda 
2   Universidade Federal do Paraná, Hospital de Clínicas, Departamento de Doenças Infecciosas, Curitiba PR, Brazil.
,
Bernardo Montesanti Machado de Almeida 
2   Universidade Federal do Paraná, Hospital de Clínicas, Departamento de Doenças Infecciosas, Curitiba PR, Brazil.
,
Viviane de Hiroki Flumignan Zétola 
1   Universidade Federal do Paraná, Hospital de Clínicas, Departamento de Neurologia, Curitiba PR, Brazil.
,
Marcos Christiano Lange 
1   Universidade Federal do Paraná, Hospital de Clínicas, Departamento de Neurologia, Curitiba PR, Brazil.
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ABSTRACT

Background: Syphilis is an endemic disease, particularly in low- and middle-income countries, with vascular involvement in large vessels (aortitis), but no clear relationship with stroke patients, except for those who presented with meningovascular neurosyphilis. Objective: To investigate the relationship between a positive history of syphilis determined by serological testing and ischemic stroke etiology, particularly small vessel disease (SVD). Methods: In total, 269 first-ever ischemic stroke patients admitted to the stroke unit were tested for syphilis. Patients with neurosyphilis were excluded. All patients were classified according to the ASCOD phenotyping as SVD — when SVD was the potential causal mechanism (S1) — or non-SVD — when SVD was uncertain (S2), unlike (S3), or not detected (S0). Results: Syphilis was positive in 32 (12%) patients. When comparing patients with positive and negative serology, the only significant difference was SVD as the causal mechanism (S1) in patients with positive results: 9 (28%) vs. 22 (9%), p<0.01. Conclusion: The current study showed that the frequency of positive syphilis serological test was higher in patients with first-ever ischemic stroke and SVD as the potential causal mechanism. This finding could be related to the endothelial dysfunction occurring in syphilis.

RESUMO

Introdução: A sífilis é uma doença endêmica, especialmente em países de baixa e média renda, com acometimento vascular descrito em grandes vasos (aortite), porém nenhuma relação clara foi reconhecida em paciente com acidente vascular cerebral, exceto para aqueles com sífilis meningovascular. Objetivos: Investigar a relação entre história positiva de sífilis determinada pelo status sorológico e o mecanismo do acidente vascular cerebral isquêmico, particularmente doença de pequenos vasos. Métodos: Ao todo, 269 pacientes com AVC isquêmico foram testados para sífilis. Pacientes com diagnóstico de neurossífilis foram excluídos. Todos os pacientes foram classificados segundo o fenótipo ASCOD quando a doença de pequenos vasos era o mecanismo causal provável (S1) ou não-pequenos vasos quando este mecanismo era incerto (S2), pouco provável (S3) ou não detectado (S0). Resultados: O teste para sífilis foi positivo em 32 (12%) pacientes. Quando comparados, pacientes com sorologia positiva e o grupo com teste não reagente, a única diferença significativa foi a doença de pequenos vasos como mecanismo causal (S1) em pacientes com sorologia positiva: 9 (28%) vs. 22 (9%), p<0.01. Conclusão: O presente estudo mostra que o teste sorológico positivo para sífilis tem maior ocorrência em pacientes com o primeiro AVC isquêmico com a doença de pequenos vasos como um mecanismo causal possível. Tal achado pode estar relacionado à disfunção endotelial que ocorre durante a sífilis.

Keywords:

Syphilis - Stroke - Cerebral Small Vessel Diseases

Palavras-chave:

Sífilis - Acidente Vascular Cerebral - Doenças de Pequenos Vasos Cerebrais

Authors’ contribution:

MGF: data collection, study design, literature review, manuscript draft. VCS: manuscript review, data collection. BMMA: study design, data collection. GLB: study design, data collection. VHFZ: study design, manuscript review. MCL: study design, manuscript review, statistical analysis.




Publication History

Received: 26 April 2020

Accepted: 07 July 2020

Article published online:
04 July 2023

© 2021. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Halperin JJ. Spirochetal Infections of the Nervous System. In: Aminoff MJ, Josephson SA. Aminoff's Neurology and General Medicine. 5th ed. London. Elsevier Inc.; 2014. p.817-31.
  • 2 Arora N, Schuenemann VJ, Jäger G, Peltzer A, Seitz A, Herbig A, et al. Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster. Nat Microbiol. 2016 Dec;2:16245. https://doi.org/10.1038/nmicrobiol.2016.245
  • 3 Kojima N, Klausner JD. An update on the global epidemiology of syphilis. Curr Epidemiol Rep. 2018 Mar;5(1):24-38 https://doi.org/10.1007/s40471-018-0138-z
  • 4 French P, Gomberg M, Janier M, Schmidt B, van Voorst Vader P, Young H, et al. IUSTI: 2008 European Guidelines on the Management of Syphilis. Int J STD AIDS. 2009 May;20(5):300-9. https://doi.org/10.1258/ijsa.2008.008510
  • 5 Kelley RE, Bell L, Kelley SE, Lee SC. Syphilis detection in cerebrovascular disease. Stroke. 1989 Feb;20(2):230-4. https://doi.org/10.1161/01.str.20.2.230
  • 6 Macaron NC, Cohen C, Chen SC, Arbiser JL. Cutaneous lesions of secondary syphilis are highly angiogenic. J Am Acad Dermatol. 2003 Jun;48(6):878-81. https://doi.org/10.1067/mjd.2003.504
  • 7 Brazil. Ministério da Saúde. Technical manual for diagnosis of syphilis. Brasília: Ministério da Saúde; 2016.
  • 8 Adams Jr. HP, Bendizen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993 Jan;24(1):35-41. https://doi.org/10.1161/01.str.24.1.35
  • 9 Amarenco P, Bogousslavsky J, Caplan LR, Donnan GA, Wolf ME, Hennerici MG. The ASCOD phenotyping of ischemic stroke (Updated ASCO Phenotyping). Cerebrovasc Dis. 2013;36(1):1-5. https://doi.org/10.1159/000352050
  • 10 Borges CR, Almeida SM, Sue K, Koslyk JLA, Sato MT, Shiokawa N, et al. Neurosyphilis and ocular syphilis clinical and cerebrospinal fluid characteristics: a case series. Arq Neuro-Psiquiatr. 2018 Jun;76(6):373-80. https://doi.org/10.1590/0004-282X20180054
  • 11 Cordato DJ, Djekic S, Taneja SR, Maley M, Beran RG, Cappelen-Smith C, et al. Prevalence of positive syphilis serology and meningovascular neurosyphilis in patients admitted with stroke and TIA from a culturally diverse population (2005-09). J Clin Neurosci. 2013 Jul;20(7):943-7. https://doi.org/10.1016/j.jocn.2012.08.011
  • 12 Dharmasaroja PA, Dharmasaroja P. Serum and cerebrospinal fluid profiles for syphilis in Thai patients with acute ischemic stroke. Int J STD AIDS. 2012 May;23(5):340-5. https://doi.org/10.1258/ijsa.2011.011207
  • 13 Zhang RL, Zhang PJ, Wang QQ. Recombinant Treponema pallidum protein Tp0965 activates endothelial cells and increase the permeability of endothelial cell monolayer. PLoS One. 2014 Dec;9(12):e115134. https://doi.org/10.1371/journal.pone.0115134
  • 14 Zhang RL, Wang QQ, Zhang JP, Yang JL. Tp17 membrane protein of Treponema pallidum activates endothelial cells in vitro. Int Immunopharmacol. 2015 Apr;25(2):538-44. https://doi.org/10.1016/j.intimp.2015.02.028
  • 15 Carlson JA, Dabiri G, Cribier B, Sell S. The immunopathobiology of syphilis: manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity. Am J Dermatopathol. 2011 Jul;33(5):433-60. https://doi.org/10.1097/DAD.0b013e3181e8b587
  • 16 Wiseman SJ, Doubal FN, Chappell FM, Valdés-Hernández MC, Wang X, Rumley A, et al. Plasma biomarkers of inflammation, endothelial function and hemostasis in cerebral small vessel disease. Cerebrovasc Dis. 2015;40(3-4):157-64. https://doi.org/10.1159/000438494
  • 17 Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P. Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med. 2004 Dec;351(25):2611-8. https://doi.org/10.1056/NEJMoa041747
  • 18 Musher DM, Abers MS, Corrales-Medina VF. Acute infection and myocardial infarction. N Engl J Med. 2019 Jan;380(2):171-6. https://doi.org/10.1056/NEJMra1808137