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Predictors of unfavorable outcome in neurosyphilis: Multicenter ID-IRI Study

  • Derya Ozturk-Engin
  • Hakan Erdem
  • Rodrigo Hasbun
  • Shu-Hua Wang
  • Hulya Tireli
  • Pierre Tattevin
  • Xavier Argemi
  • Enora Ouamara-Digue
  • Andrea Gombos
  • Botond Lakatos
  • Fatma Sırmatel
  • Yasemin Cag
  • Abdullah Umut Pekok
  • Seniha Senbayrak
  • Ilker Inanç Balkan
  • Marie Gheno
  • Nuray Uzun
  • Selçuk Kaya
  • Gönül Cicek-Senturk
  • Gönül Şengöz
  • Recep Tekin
  • Mustafa Kemal Çelen
  • Saygın Nayman-Alpat
  • Pınar Ergen
  • Alper Şener
  • Canan Agalar
  • Sükran Köse
  • Ahmet Çagkan Inkaya
  • Figen Kaptan
  • Fahad Al-majid
  • Umit Savasci
  • Haluk Vahaboglu
Original Article

Abstract

Neurosyphilis (NS) has different clinical manifestations and can appear during any stage of syphilis. We aimed to identify the factors affecting poor outcome in NS patients. Patients with positive cerebrospinal fluid Venereal Disease Research Laboratory test, and positive serological serum treponemal or nontreponemal tests were classified as definite NS. The data of 141 patients with definite NS were submitted from 22 referral centers. Asymptomatic NS, syphilitic meningitis, meningovascular syphilis, tabes dorsalis, general paresis, and taboparesis were detected in 22 (15.6%), 67 (47.5%), 13 (9.2%), 10 (7%), 13 (9.2%), and 16 patients (11.3%), respectively. The number of HIV-positive patients was 43 (30.4%). The most common symptoms were headache (n = 55, 39%), fatigue (n = 52, 36.8%), and altered consciousness (50, 35.4%). Tabetic symptoms were detected in 28 (19.8%), paretic symptoms in 32 (22.6%), and vascular symptoms in 39 patients (27.6%). Eye involvement was detected in 19 of 80 patients (23.7%) who underwent eye examination and ear involvement was detected in eight of 25 patients (32%) who underwent ear examination. Crystallized penicillin was used in 109 (77.3%), procaine penicillin in seven (4.9%), ceftriaxone in 31 (21.9%), and doxycycline in five patients (3.5%). According to multivariate regression analysis, while headache was a protective factor in NS patients, double vision was significantly associated to poor outcome. We concluded that double vision indicated unfavorable outcome among NS patients. A high clinical suspicion is needed for the diagnosis NS. As determined in our study, the presence of headache in syphilitic patients can help in early diagnosis of central nervous system disease.

Keywords

Syphilis Neurosyphilis Outcome Cerebrospinal fluid VDRL 

Notes

Funding information

We haven’t received support financial for this study.

Compliance with ethical standards

We have no competing interests to declare. The neurosyphilis study protocol was approved by Fatih Sultan Mehmet Training and Research Hospital in Istanbul.

References

  1. 1.
    Bhai S, Lyons JL (2015) Neurosyphilis update: atypical is the new typical. Curr Infect Dis Rep 17(5):481CrossRefGoogle Scholar
  2. 2.
    Stamm LV (2016) Syphilis: re-emergence of an old foe. Microb Cell 3(9):363–370CrossRefGoogle Scholar
  3. 3.
    Jantzen SU, Ferrea S, Langebner T, Gaebel W, Griese M, Arendt G, Dihne M (2012) Late-stage neurosyphilis presenting with severe neuropsychiatric deficits: diagnosis, therapy, and course of three patients. J Neurol 259(4):720–728CrossRefGoogle Scholar
  4. 4.
    Zhang HL, Lin LR, Liu GL, Zeng YL, Wu JY, Zheng WH, Tong ML, Dong J, Su YH, Liu LL et al (2013) Clinical spectrum of neurosyphilis among HIV-negative patients in the modern era. Dermatology 226(2):148–156CrossRefGoogle Scholar
  5. 5.
    Nyatsanza F, Tipple C (2016) Syphilis: presentations in general medicine. Clin Med (Lond) 16(2):184–188CrossRefGoogle Scholar
  6. 6.
    Brightbill TC, Ihmeidan IH, Post MJ, Berger JR, Katz DA (1995) Neurosyphilis in HIV-positive and HIV-negative patients: neuroimaging findings. AJNR Am J Neuroradiol 16(4):703–711Google Scholar
  7. 7.
    Hooshmand H, Escobar MR, Kopf SW (1972) Neurosyphilis. A study of 241 patients. JAMA 219(6):726–729CrossRefGoogle Scholar
  8. 8.
    Erdem H, Inan A, Guven E, Hargreaves S, Larsen L, Shehata G, Pernicova E, Khan E, Bastakova L, Namani S et al (2017) The burden and epidemiology of community-acquired central nervous system infections: a multinational study. Eur J Clin Microbiol Infect Dis 36(9):1595–1611CrossRefGoogle Scholar
  9. 9.
    Vanhaecke C, Grange P, Benhaddou N, Blanche P, Salmon D, Parize P, Lortholary O, Caumes E, Pelloux I, Epaulard O et al (2016) Clinical and biological characteristics of 40 patients with neaAurosyphilis and evaluation of Treponema pallidum nested polymerase chain reaction in cerebrospinal fluid samples. Clin Infect Dis 63(9):1180–1186Google Scholar
  10. 10.
    Drago F, Merlo G, Ciccarese G, Agnoletti AF, Cozzani E, Rebora A, Parodi A (2016) Changes in neurosyphilis presentation: a survey on 286 patients. J Eur Acad Dermatol Venereol 30(11):1886–1900Google Scholar
  11. 11.
    Control CfD (2014) Prevention: STD surveillance case definitions. Centers for Disease Control and Prevention, Atlanta: http://www.cdc.gov/std/stats/casedefinitions-2014.pdf Google Scholar
  12. 12.
    Lafond RE, Lukehart SA (2006) Biological basis for syphilis. Clin Microbiol Rev 19(1):29–49CrossRefGoogle Scholar
  13. 13.
  14. 14.
    Ghanem KG (2010) Review: neurosyphilis: a historical perspective and review. CNS Neurosci Ther 16(5):e157–e168CrossRefGoogle Scholar
  15. 15.
    Wong T, Fonseca K, Chernesky MA, Garceau R, Levett PN, Serhir B (2015) Canadian public health laboratory network laboratory guidelines for the diagnosis of neurosyphilis in Canada. Can J Infect Dis Med Microbiol 26(Suppl A):18A–22ACrossRefGoogle Scholar
  16. 16.
    cdc.gov/std/syphilis/Syphilis-Pocket-Guide-FINAL-508.pdf: Syphilis: a provider’s guide to treatment and prevention. November 30, 2017
  17. 17.
    Amarenco P CLR, Pessin M (1998) Vertebrobasilar occlusive diseases. In: Barnett HJM, Mohr JP, Stein BM (eds) Stroke Pathophysiology, diagnosis and management, 3rd edn. Churchill Livingstone, pp 513–527Google Scholar
  18. 18.
    Khamaysi Z, Bergman R, Telman G, Goldsher D (2014) Clinical and imaging findings in patients with neurosyphilis: a study of a cohort and review of the literature. Int J Dermatol 53(7):812–819CrossRefGoogle Scholar
  19. 19.
    Conde-Sendin MA, Amela-Peris R, Aladro-Benito Y, Maroto AA (2004) Current clinical spectrum of neurosyphilis in immunocompetent patients. Eur Neurol 52(1):29–35CrossRefGoogle Scholar
  20. 20.
    Mitsonis CH, Kararizou E, Dimopoulos N, Triantafyllou N, Kapaki E, Mitropoulos P, Sfagos K, Vassilopoulos D (2008) Incidence and clinical presentation of neurosyphilis: a retrospective study of 81 cases. Int J Neurosci 118(9):1251–1257CrossRefGoogle Scholar
  21. 21.
    de Fatima MAMM, Bezerra PC, Guedes DL, Cabral DB, de Barros Miranda-Filho D (2013) Prognostic indicators in bacterial meningitis: a case-control study. Braz J Infect Dis 17(5):538–544CrossRefGoogle Scholar
  22. 22.
    Qu J, Zhou T, Zhong C, Deng R, Lu X (2017) Comparison of clinical features and prognostic factors in HIV-negative adults with cryptococcal meningitis and tuberculous meningitis: a retrospective study. BMC Infect Dis 17(1):51CrossRefGoogle Scholar
  23. 23.
    Dinkin M (2014) Diagnostic approach to diplopia. Continuum (Minneap Minn) 20(4 Neuro-ophthalmology):942–965Google Scholar
  24. 24.
    Control CD (2015) Prevention: sexually transmitted diseases treatment guidelines, 2015. Ann Emerg Med 66(5):526–528CrossRefGoogle Scholar
  25. 25.
    Shann S, Wilson J (2003) Treatment of neurosyphilis with ceftriaxone. Sex Transm Infect 79(5):415–416CrossRefGoogle Scholar
  26. 26.
    Kang-Birken SL, Castel U, Prichard JG (2010) Oral doxycycline for treatment of neurosyphilis in two patients infected with human immunodeficiency virus. Pharmacotherapy 30(4):119e–122eCrossRefGoogle Scholar
  27. 27.
    Pratas AC, Goldschmidt P, Lebeaux D, Aguilar C, Ermak N, Benesty J, Charlier C, Benveniste E, Merabet L, Sedira N et al (2018) Increase in ocular syphilis cases at ophthalmologic reference center, France, 2012-2015. Emerg Infect Dis 24(2):193–200CrossRefGoogle Scholar
  28. 28.
    Karsan N, Barker R, O'Dwyer JP (2014) Clinical reasoning: the “great imitator”. Neurology 83(22):e188–e196CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Derya Ozturk-Engin
    • 1
  • Hakan Erdem
    • 2
  • Rodrigo Hasbun
    • 3
  • Shu-Hua Wang
    • 4
  • Hulya Tireli
    • 5
  • Pierre Tattevin
    • 6
  • Xavier Argemi
    • 7
  • Enora Ouamara-Digue
    • 6
  • Andrea Gombos
    • 8
  • Botond Lakatos
    • 8
  • Fatma Sırmatel
    • 9
  • Yasemin Cag
    • 10
  • Abdullah Umut Pekok
    • 11
  • Seniha Senbayrak
    • 12
  • Ilker Inanç Balkan
    • 13
  • Marie Gheno
    • 6
  • Nuray Uzun
    • 14
  • Selçuk Kaya
    • 15
  • Gönül Cicek-Senturk
    • 16
  • Gönül Şengöz
    • 17
  • Recep Tekin
    • 18
  • Mustafa Kemal Çelen
    • 18
  • Saygın Nayman-Alpat
    • 19
  • Pınar Ergen
    • 10
  • Alper Şener
    • 20
  • Canan Agalar
    • 1
  • Sükran Köse
    • 21
  • Ahmet Çagkan Inkaya
    • 22
  • Figen Kaptan
    • 23
  • Fahad Al-majid
    • 24
  • Umit Savasci
    • 25
  • Haluk Vahaboglu
    • 10
  1. 1.Department of Infectious Diseases and Clinical MicrobiologyFatih Sultan Mehmet Training and Research HospitalIstanbulTurkey
  2. 2.Principal Coordinator of ID-IRIAnkaraTurkey
  3. 3.Department of Infectious DiseasesUT Health McGovern Medical SchoolHoustonUSA
  4. 4.Division of Infectious Diseases, Deparment of Internal MedicineThe Ohio State UniversityColumbusUSA
  5. 5.Department of NeurologyHaydarpasa Numune Training and Research HospitalIstanbulTurkey
  6. 6.Infectious Diseases and Intensive Care UnitPontchaillou University HospitalRennesFrance
  7. 7.Department of Infectious Diseases and Clinical MicrobiologyNouvel Hôpital CivilStrasbourgFrance
  8. 8.Department of Infectious Disease and Clinical MicrobiologySaint Laszlo Hospital BudapestBudapestHungary
  9. 9.Department of Infectious Disease and Clinical MicrobiologyIzzet Baysal University School of MedicineBoluTurkey
  10. 10.Department of Infectious Diseases and Clinical MicrobiologyMedeniyet University, Goztepe Training and Research HospitalIstanbulTurkey
  11. 11.Department of Infectious Diseases and Clinical MicrobiologyPrivate Erzurum Sifa HospitalErzurumTurkey
  12. 12.Department of Infectious Diseases and Clinical MicrobiologyHaydarpasa Numune Training and Research HospitalIstanbulTurkey
  13. 13.Department of Infectious Diseases and Clinical Microbiology, Cerrahpasa Medical FacultyIstanbul UniversityIstanbulTurkey
  14. 14.Department of Infectious Diseases and Clinical MicrobiologySisli Hamidiye Etfal Training and Research HospitalIstanbulTurkey
  15. 15.Department of Infectious Diseases and Clinical MicrobiologyKaradeniz Technical University School of MedicineTrabzonTurkey
  16. 16.Department of Infectious Disease and Clinical MicrobiologyDiskapi Yildirim Beyazit Training and Research HospitalAnkaraTurkey
  17. 17.Department of Infectious Diseases and Clinical MicrobiologyHaseki Training and Research HospitalIstanbulTurkey
  18. 18.Department of Infectious Diseases and Clinical MicrobiologyDicle University Faculty of MedicineDiyarbakırTurkey
  19. 19.Department of Infectious Disease and Clinical Microbiology, Faculty of MedicineEskisehir Osmangazi UniversityEskisehirTurkey
  20. 20.Department of Infectious Diseases and Clinical MicrobiologyOnsekiz Mart University School of MedicineCanakkaleTurkey
  21. 21.Department of Infectious Diseases and Clinical MicrobiologyTepecik Training and Education HospitalİzmirTurkey
  22. 22.Department of Infectious Disease and Clinical MicrobiologyHacettepe University Faculty of MedicineAnkaraTurkey
  23. 23.Department of Infectious Diseases and Clinical MicrobiologyAtatürk Training and Research Hospital, İzmir Kâtip Çelebi UniversityİzmirTurkey
  24. 24.Department of Medicine, Infectious Diseases DivisionKing Saud University HospitalRiyadhSaudi Arabia
  25. 25.Department of Infectious Diseases and Clinical MicrobiologyGulhane Medical AcademyAnkaraTurkey

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