Download PDF
Semin Neurol 2019; 39(04): 448-455
DOI: 10.1055/s-0039-1688942
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neurosyphilis

Hemil Gonzalez
1   Division of Infectious Diseases, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois
,
Igor J. Koralnik
2   Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois
,
Christina M. Marra
3   Harborview Medical Center, University of Washington School of Medicine, Seattle, Washington
› Author Affiliations
Further Information

Publication History

Publication Date:
18 September 2019 (online)

    Permissions and Reprints

Abstract

Neurosyphilis is caused by the bacterium Treponema pallidum subspecies pallidum (T. pallidum). The organism gains entry into the central nervous system (CNS) early (primary syphilis or chancre phase) in the course of infection. While most patients are able to mount an immune response that effectively clears CNS invasion without long-term complications, a minority go on to develop asymptomatic or symptomatic neurosyphilis. Neurosyphilis has been divided into early and late stages. The early stages include asymptomatic meningitis, symptomatic meningitis, gumma, and meningovascular syphilis, while the late stages include dementia paralytica and tabes dorsalis. Ocular and otologic syphilis can occur at any time but often accompany the acute meningitis of early neurosyphilis. The diagnosis of symptomatic neurosyphilis requires meeting clinical, serologic, and cerebrospinal fluid (CSF) criteria, while the diagnosis of asymptomatic neurosyphilis relies on serologic and CSF criteria alone. In the last several decades, a persistent rise in syphilitic meningitis and other forms of early neurosyphilis have been seen in the human immunodeficiency virus-positive population, principally in men who have sex with men. This article reviews the clinical presentation, diagnosis, and treatment of neurosyphilis, and it addresses the controversy regarding the role of lumbar puncture early in the course of infection.

Keywords

neurosyphilis - asymptomatic neurosyphilis - syphilitic meningitis
 

  • References

  • 1 Edmondson DG, Hu B, Norris SJ. Long-term in vitro culture of the syphilis spirochete Treponema pallidum subsp. pallidum . MBio 2018; 9 (03) e01153-18
    CrossrefPubMedGoogle Scholar
  • 2 Thomas DD, Navab M, Haake DA, Fogelman AM, Miller JN, Lovett MA. Treponema pallidum invades intercellular junctions of endothelial cell monolayers. Proc Natl Acad Sci U S A 1988; 85 (10) 3608-3612
    CrossrefPubMedGoogle Scholar
  • 3 Lukehart SA, Hook III EW, Baker-Zander SA, Collier AC, Critchlow CW, Handsfield HH. Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment. Ann Intern Med 1988; 109 (11) 855-862
    PubMedGoogle Scholar
  • 4 Baker-Zander SA, Lukehart SA. Macrophage-mediated killing of opsonized Treponema pallidum. J Infect Dis 1992; 165 (01) 69-74
    CrossrefPubMedGoogle Scholar
  • 5 Marra CM, Tantalo LC, Sahi SK, Dunaway SB, Lukehart SA. Reduced treponema pallidum-specific opsonic antibody activity in HIV-infected patients with syphilis. J Infect Dis 2016; 213 (08) 1348-1354
    CrossrefPubMedGoogle Scholar
  • 6 Leader BT, Godornes C, VanVoorhis WC, Lukehart SA. CD4+ lymphocytes and gamma interferon predominate in local immune responses in early experimental syphilis. Infect Immun 2007; 75 (06) 3021-3026
    CrossrefPubMedGoogle Scholar
  • 7 Giacani L, Molini BJ, Kim EY. , et al. Antigenic variation in Treponema pallidum: TprK sequence diversity accumulates in response to immune pressure during experimental syphilis. J Immunol 2010; 184 (07) 3822-3829
    CrossrefPubMedGoogle Scholar
  • 8 Reid TB, Molini BJ, Fernandez MC, Lukehart SA. Antigenic variation of TprK facilitates development of secondary syphilis. Infect Immun 2014; 82 (12) 4959-4967
    CrossrefPubMedGoogle Scholar
  • 9 Rolfs RT, Joesoef MR, Hendershot EF. , et al; The Syphilis and HIV Study Group. A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. N Engl J Med 1997; 337 (05) 307-314
    CrossrefPubMedGoogle Scholar
  • 10 Moore JE, Hopkins HH. Asymptomatic neurosyphilis VI. The prognosis of early and late asymptomatic neurosyphilis. JAMA 1930; 95 (22) 1637-1641
    CrossrefPubMedGoogle Scholar
  • 11 Marra CM, Maxwell CL, Smith SL. , et al. Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features. J Infect Dis 2004; 189 (03) 369-376
    CrossrefPubMedGoogle Scholar
  • 12 Keidel A. Studies in asymptomatic neurosyphilis I: a tentative classification of early asymptomatic neurosyphilis. Arch Neurol Psychiatry 1921; 6: 286-291
    CrossrefPubMedGoogle Scholar
  • 13 O'Leary PA, Cole HA, Moore JE. , et al. Cooperative clinical studies in the treatment of syphilis: asymptomatic neurosyphilis. Arch Derm Syphilol 1937; 35: 387-401
    CrossrefPubMedGoogle Scholar
  • 14 Marra CM, Castro CD, Kuller L. , et al. Mechanisms of clearance of Treponema pallidum from the CSF in a nonhuman primate model. Neurology 1998; 51 (04) 957-961
    CrossrefPubMedGoogle Scholar
  • 15 Firlag-Burkacka E, Swiecki P, Cielniak I. , et al. High frequency of neurosyphilis in HIV-positive patients diagnosed with early syphilis. HIV Med 2016; 17 (05) 323-326
    CrossrefPubMedGoogle Scholar
  • 16 Taylor MM, Aynalem G, Olea LM, He P, Smith LV, Kerndt PR. A consequence of the syphilis epidemic among men who have sex with men (MSM): neurosyphilis in Los Angeles, 2001-2004. Sex Transm Dis 2008; 35 (05) 430-434
    CrossrefPubMedGoogle Scholar
  • 17 Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA. Neurosyphilis in a clinical cohort of HIV-1-infected patients. AIDS 2008; 22 (10) 1145-1151
    CrossrefPubMedGoogle Scholar
  • 18 Dumaresq J, Langevin S, Gagnon S. , et al. Clinical prediction and diagnosis of neurosyphilis in HIV-infected patients with early syphilis. J Clin Microbiol 2013; 51 (12) 4060-4066
    CrossrefPubMedGoogle Scholar
  • 19 Marra CM, Sahi SK, Tantalo LC. , et al. Toll-like receptor polymorphisms are associated with increased neurosyphilis risk. Sex Transm Dis 2014; 41 (07) 440-446
    CrossrefPubMedGoogle Scholar
  • 20 Tramont EC. Persistence of Treponema pallidum following penicillin G therapy. Report of two cases. JAMA 1976; 236 (19) 2206-2207
    CrossrefPubMedGoogle Scholar
  • 21 Centers for Disease Control and Prevention (CDC). Symptomatic early neurosyphilis among HIV-positive men who have sex with men--four cities, United States, January 2002-June 2004. MMWR Morb Mortal Wkly Rep 2007; 56 (25) 625-628
    PubMedGoogle Scholar
  • 22 Dibbern Jr DA, Ray SC. Recrudescence of treated neurosyphilis in a patient with human immunodeficiency virus. Mayo Clin Proc 1999; 74 (01) 53-56
    CrossrefPubMedGoogle Scholar
  • 23 Zenilman JM, Rand S, Barditch P, Rompalo AM. Asymptomatic neurosyphilis after doxycycline therapy for early latent syphilis. Sex Transm Dis 1993; 20 (06) 346-347
    CrossrefPubMedGoogle Scholar
  • 24 Walter T, Lebouche B, Miailhes P. , et al. Symptomatic relapse of neurologic syphilis after benzathine penicillin G therapy for primary or secondary syphilis in HIV-infected patients. Clin Infect Dis 2006; 43 (06) 787-790
    CrossrefPubMedGoogle Scholar
  • 25 Malone JL, Wallace MR, Hendrick BB. , et al. Syphilis and neurosyphilis in a human immunodeficiency virus type-1 seropositive population: evidence for frequent serologic relapse after therapy. Am J Med 1995; 99 (01) 55-63
    PubMedGoogle Scholar
  • 26 Gordon SM, Eaton ME, George R. , et al. The response of symptomatic neurosyphilis to high-dose intravenous penicillin G in patients with human immunodeficiency virus infection. N Engl J Med 1994; 331 (22) 1469-1473
    CrossrefPubMedGoogle Scholar
  • 27 Marra C, Sahi S, Tantalo L. , et al. Enhanced molecular typing of treponema pallidum: geographical distribution of strain types and association with neurosyphilis. J Infect Dis 2010; 202 (09) 1380-1388
    CrossrefPubMedGoogle Scholar
  • 28 Carlson JA, Dabiri G, Cribier B, Sell S. The immunopathobiology of syphilis: the manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity. Am J Dermatopathol 2011; 33 (05) 433-460
    CrossrefPubMedGoogle Scholar
  • 29 Gyori E, Lew EO. Unsuspected central nervous system gummas in a case of “cerebral infarct” associated with cocaine use. Am J Forensic Med Pathol 2007; 28 (03) 208-211
    CrossrefPubMedGoogle Scholar
  • 30 Yoon YK, Kim MJ, Chae YS, Kang SH. Cerebral syphilitic gumma mimicking a brain tumor in the relapse of secondary syphilis in a human immunodeficiency virus-negative patient. J Korean Neurosurg Soc 2013; 53 (03) 197-200
    CrossrefPubMedGoogle Scholar
  • 31 Brightbill TC, Ihmeidan IH, Post MJ, Berger JR, Katz DA. Neurosyphilis in HIV-positive and HIV-negative patients: neuroimaging findings. AJNR Am J Neuroradiol 1995; 16 (04) 703-711
    PubMedGoogle Scholar
  • 32 Peters M, Gottschalk D, Boit R, Pohle HD, Ruf B. Meningovascular neurosyphilis in human immunodeficiency virus infection as a differential diagnosis of focal CNS lesions: a clinicopathological study. J Infect 1993; 27 (01) 57-62
    CrossrefPubMedGoogle Scholar
  • 33 Pathology of tabes dorsalis and general paralysis. JAMA 1900; XXXIV (10) 630
    PubMedGoogle Scholar
  • 34 Freeman W. Malaria treatment of general paralysis, histopathologic observations in fifteen cases. JAMA 1927; 88 (14) 1064-1068
    CrossrefPubMedGoogle Scholar
  • 35 Gager WE, Israel CW, Smith JL. Presence of spirochaetes in paresis despite penicillin therapy. Br J Vener Dis 1968; 44 (04) 277-282
    PubMedGoogle Scholar
  • 36 Mao C, Gao J, Jin L, Peng B, Guo Y. Postmortem histopathologic analysis of neurosyphilis: a report of 3 cases with clinicopathologic correlations. J Neuropathol Exp Neurol 2018; 77 (04) 296-301
    CrossrefPubMedGoogle Scholar
  • 37 Noguchi H, Moore JW. A demonstration of Treponema pallidum in the brain in cases of general paralysis. J Exp Med 1913; 17 (02) 232-238
    CrossrefPubMedGoogle Scholar
  • 38 Hassin G. Tabes dorsalis, pathology and pathogenesis; a preliminary report. Arch Neurol Psychiatry 1928; 21: 311-341
    PubMedGoogle Scholar
  • 39 Brush A. The etiology of tabes dorsalis. JAMA 1904; XLII (14) 870-872
    PubMedGoogle Scholar
  • 40 CDC. Sexually transmitted disease surveillance, 2001. Available at: https://www.cdc.gov/std/stats01/All-Surv-2001.pdf . Accessed April 27, 2019
    PubMedGoogle Scholar
  • 41 Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2017. Atlanta: U.S. Department of Health and Human Services; 2018
    Google Scholar
  • 42 de Voux A, Kidd S, Torrone EA. Reported cases of neurosyphilis among early syphilis cases-United States, 2009 to 2015. Sex Transm Dis 2018; 45 (01) 39-41
    CrossrefPubMedGoogle Scholar
  • 43 Merritt HH. The early clinical and laboratory manifestations of syphilis of the central nervous system. N Engl J Med 1940; 223 (12) 446-450
    CrossrefPubMedGoogle Scholar
  • 44 Merritt HH. Acute syphilitic meningitis. Medicine (Baltimore) 1935; 14 (01) 119-183
    CrossrefPubMedGoogle Scholar
  • 45 Merritt HH, Adams RD, Solomon HC. Neurosyphilis. New York, NY: Oxford University Press; 1946
    Google Scholar
  • 46 Gállego J, Soriano G, Zubieta JL, Delgado G, Villanueva JA. Magnetic resonance angiography in meningovascular syphilis. Neuroradiology 1994; 36 (03) 208-209
    CrossrefPubMedGoogle Scholar
  • 47 Lachaud S, Suissa L, Mahagne MH. Stroke, HIV and meningovascular syphilis: study of three cases [in French]. Rev Neurol (Paris) 2010; 166 (01) 76-82
    CrossrefPubMedGoogle Scholar
  • 48 Lee JP, Koo SH, Jin SY, Kim TH. Experience of meningovascular syphilis in human immunodeficiency virus infected patient. J Korean Neurosurg Soc 2009; 46 (04) 413-416
    CrossrefPubMedGoogle Scholar
  • 49 Harrigan EP, McLaughlin TJ, Feldman RG. Transverse myelitis due to meningovascular syphilis. Arch Neurol 1984; 41 (03) 337-338
    CrossrefPubMedGoogle Scholar
  • 50 Lowenstein DH, Mills C, Simon RP. Acute syphilitic transverse myelitis: unusual presentation of meningovascular syphilis. Genitourin Med 1987; 63 (05) 333-338
    PubMedGoogle Scholar
  • 51 Matijosaitis V, Vaitkus A, Pauza V, Valiukeviciene S, Gleizniene R. Neurosyphilis manifesting as spinal transverse myelitis. Medicina (Kaunas) 2006; 42 (05) 401-405
    PubMedGoogle Scholar
  • 52 Feng W, Caplan M, Matheus MG, Papamitsakis NI. Meningovascular syphilis with fatal vertebrobasilar occlusion. Am J Med Sci 2009; 338 (02) 169-171
    CrossrefPubMedGoogle Scholar
  • 53 Jiménez JA, Ladino LD, Uribe CS. , et al. Meningovascular neurosyphilis with basilar artery thrombosis, a case report and literature review [in Spanish]. Biomedica 2012; 32 (01) 7-12
    PubMedGoogle Scholar
  • 54 Bourazza A, Kerouache A, Reda R, Mounach J, Mosseddaq R. Meningovascular syphilis: study of five cases [in French]. Rev Neurol (Paris) 2008; 164 (04) 369-373
    CrossrefPubMedGoogle Scholar
  • 55 Balba GP, Kumar PN, James AN. , et al. Ocular syphilis in HIV-positive patients receiving highly active antiretroviral therapy. Am J Med 2006; 119 (05) 448.e21-448.e25
    CrossrefPubMedGoogle Scholar
  • 56 Bollemeijer JG, Wieringa WG, Missotten TO. , et al. Clinical manifestations and outcome of syphilitic uveitis. Invest Ophthalmol Vis Sci 2016; 57 (02) 404-411
    CrossrefPubMedGoogle Scholar
  • 57 Cope AB, Mobley VL, Oliver SE. , et al. Ocular syphilis and human immunodeficiency virus coinfection among syphilis patients in North Carolina, 2014–2016. Sex Transm Dis 2018; 46 (02) 80-85
    PubMedGoogle Scholar
  • 58 Woolston S, Cohen SE, Fanfair RN, Lewis SC, Marra CM, Golden MR. ; Centers for Disease C. A cluster of ocular syphilis cases - Seattle, Washington, and San Francisco, California, 2014-2015. MMWR Morb Mortal Wkly Rep 2015; 64 (40) 1150-1151
    CrossrefPubMedGoogle Scholar
  • 59 CDC. Clinical advisory: ocular syphilis in the United States. Available at: https://www.cdc.gov/std/syphilis/clinicaladvisoryos2015.htm . Accessed April 27, 2019
    PubMed
  • 60 Oliver SE, Aubin M, Atwell L. , et al. Ocular syphilis - eight jurisdictions, United States, 2014-2015. MMWR Morb Mortal Wkly Rep 2016; 65 (43) 1185-1188
    CrossrefPubMedGoogle Scholar
  • 61 Yimtae K, Srirompotong S, Lertsukprasert K. Otosyphilis: a review of 85 cases. Otolaryngol Head Neck Surg 2007; 136 (01) 67-71
    CrossrefPubMedGoogle Scholar
  • 62 Hughes GB, Rutherford I. Predictive value of serologic tests for syphilis in otology. Ann Otol Rhinol Laryngol 1986; 95 (3, Pt 1): 250-259
    CrossrefPubMedGoogle Scholar
  • 63 Fargen KM, Alvernia JE, Lin CS, Melgar M. Cerebral syphilitic gummata: a case presentation and analysis of 156 reported cases. Neurosurgery 2009; 64 (03) 568-575 , 575–576
    CrossrefPubMedGoogle Scholar
  • 64 Shao X, Qiang D, Liu Y, Yuan Q, Tao J, Ji B. Diagnosis and treatment of cerebral syphilitic gumma: a report of three cases. Front Neurosci 2018; 12: 100
    CrossrefPubMedGoogle Scholar
  • 65 Li JC, Mahta A, Kim RY, Saria M, Kesari S. Cerebral syphilitic gumma: a case report and review of the literature. Neurol Sci 2012; 33 (05) 1179-1181
    CrossrefPubMedGoogle Scholar
  • 66 Dewhurst K. The neurosyphilitic psychoses today. A survey of 91 cases. Br J Psychiatry 1969; 115 (518) 31-38
    CrossrefPubMedGoogle Scholar
  • 67 Merritt HH. The Argyll-Robertson pupil: an anatomic-physiologic explanation of the phenomenon, with a survey of its occurrence in neurosyphilis. Arch Neurol Psyc 1933; 30 (02) 357-373
    PubMedGoogle Scholar
  • 68 Yin L, Zou S, Huang Y. Neurosyphilis with psychotic symptoms and parkinsonism in a young girl. Neuropsychiatr Dis Treat 2015; 11: 375-377
    PubMedGoogle Scholar
  • 69 McAuley J, Hughes G. Neurosyphilis presenting as parkinsonism. BMJ Case Rep 2015; 2015: bcr2015210277
    CrossrefPubMedGoogle Scholar
  • 70 Sabre L, Braschinsky M, Taba P. Neurosyphilis as a great imitator: a case report. BMC Res Notes 2016; 9: 372
    CrossrefPubMedGoogle Scholar
  • 71 Tong ML, Chen YY, Zhu XZ. , et al. Comparison of clinical and laboratory characteristics of general paresis and non-neurosyphilis dementia. Eur Neurol 2018; 80 (1–2): 82-86
    CrossrefPubMedGoogle Scholar
  • 72 Holmes G. A British Medical Association lecture on some clinical manifestations of tabes dorsalis: delivered to the Harrogate Branch, October 7th, 1922. BMJ 1923; 1 (3237): 47-51
    CrossrefPubMedGoogle Scholar
  • 73 Romberg E. Pupillary disturbances in tabes. Arch Psychiatr Nervenkr Z Gesamte Neurol Psychiatr 1939; 165: 369-372
    PubMedGoogle Scholar
  • 74 Schaller WF. Early diagnosis of tabes dorsalis. JAMA 1917; LXVIII (03) 190-194
    PubMedGoogle Scholar
  • 75 Rodgers CA, Murphy S. Diagnosis of neurosyphilis: appraisal of clinical caseload. Genitourin Med 1997; 73 (06) 528-532
    PubMedGoogle Scholar
  • 76 Centers for Disease C. Prevention. Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Morb Mortal Wkly Rep 2015; 64 (RR-03): 1-137
    PubMedGoogle Scholar
  • 77 Binnicker MJ, Jespersen DJ, Rollins LO. Treponema-specific tests for serodiagnosis of syphilis: comparative evaluation of seven assays. J Clin Microbiol 2011; 49 (04) 1313-1317
    CrossrefPubMedGoogle Scholar
  • 78 Morshed MG, Singh AE. Recent trends in the serologic diagnosis of syphilis. Clin Vaccine Immunol 2015; 22 (02) 137-147
    CrossrefPubMedGoogle Scholar
  • 79 Marra CM, Tantalo LC, Maxwell CL, Ho EL, Sahi SK, Jones T. The rapid plasma reagin test cannot replace the Venereal Disease Research Laboratory test for neurosyphilis diagnosis. Sex Transm Dis 2012; 39 (06) 453-457
    CrossrefPubMedGoogle Scholar
  • 80 Seña AC, Wolff M, Martin DH. , et al. Predictors of serological cure and Serofast State after treatment in HIV-negative persons with early syphilis. Clin Infect Dis 2011; 53 (11) 1092-1099
    CrossrefPubMedGoogle Scholar
  • 81 Seña AC, Zhang XH, Li T. , et al. A systematic review of syphilis serological treatment outcomes in HIV-infected and HIV-uninfected persons: rethinking the significance of serological non-responsiveness and the serofast state after therapy. BMC Infect Dis 2015; 15: 479
    CrossrefPubMedGoogle Scholar
  • 82 Zhou P, Gu X, Lu H, Guan Z, Qian Y. Re-evaluation of serological criteria for early syphilis treatment efficacy: progression to neurosyphilis despite therapy. Sex Transm Infect 2012; 88 (05) 342-345
    CrossrefPubMedGoogle Scholar
  • 83 Cai SN, Long J, Chen C, Wan G, Lun WH. Incidence of asymptomatic neurosyphilis in serofast Chinese syphilis patients. Sci Rep 2017; 7 (01) 15456
    CrossrefPubMedGoogle Scholar
  • 84 Wang C, Zhu L, Gao Z. , et al. Increased interleukin-17 in peripheral blood and cerebrospinal fluid of neurosyphilis patients. PLoS Negl Trop Dis 2014; 8 (07) e3004
    CrossrefPubMedGoogle Scholar
  • 85 Davis LE, Schmitt JW. Clinical significance of cerebrospinal fluid tests for neurosyphilis. Ann Neurol 1989; 25 (01) 50-55
    CrossrefPubMedGoogle Scholar
  • 86 Zhu L, Gu X, Peng RR. , et al. Comparison of the cerebrospinal fluid (CSF) toluidine red unheated serum test and the CSF rapid plasma reagin test with the CSF venereal disease research laboratory test for diagnosis of neurosyphilis among HIV-negative syphilis patients in China. J Clin Microbiol 2014; 52 (03) 736-740
    CrossrefPubMedGoogle Scholar
  • 87 Castro R, Prieto ES, da Luz Martins Pereira F. Nontreponemal tests in the diagnosis of neurosyphilis: an evaluation of the Venereal Disease Research Laboratory (VDRL) and the rapid plasma reagin (RPR) tests. J Clin Lab Anal 2008; 22 (04) 257-261
    CrossrefPubMedGoogle Scholar
  • 88 Gu W, Yang Y, Wu L, Yang S, Ng LK. Comparing the performance characteristics of CSF-TRUST and CSF-VDRL for syphilis: a cross-sectional study. BMJ Open 2013; 3 (02) e002204
    CrossrefPubMedGoogle Scholar
  • 89 Pettit DE, Larsen SA, Harbec PS. , et al. Toluidine red unheated serum test, a nontreponemal test for syphilis. J Clin Microbiol 1983; 18 (05) 1141-1145
    CrossrefPubMedGoogle Scholar
  • 90 Marra CM, Maxwell CL, Dunaway SB, Sahi SK, Tantalo LC. Cerebrospinal fluid treponema pallidum particle agglutination assay for neurosyphilis diagnosis. J Clin Microbiol 2017; 55 (06) 1865-1870
    CrossrefPubMedGoogle Scholar
  • 91 Castro R, Prieto ES, Aguas MJ. , et al. Evaluation of the Treponema pallidum particle agglutination technique (TP.PA) in the diagnosis of neurosyphilis. J Clin Lab Anal 2006; 20 (06) 233-238
    CrossrefPubMedGoogle Scholar
  • 92 Harding AS, Ghanem KG. The performance of cerebrospinal fluid treponemal-specific antibody tests in neurosyphilis: a systematic review. Sex Transm Dis 2012; 39 (04) 291-297
    CrossrefPubMedGoogle Scholar
  • 93 Marra CM, Boutin P, McArthur JC. , et al. A pilot study evaluating ceftriaxone and penicillin G as treatment agents for neurosyphilis in human immunodeficiency virus-infected individuals. Clin Infect Dis 2000; 30 (03) 540-544
    CrossrefPubMedGoogle Scholar
  • 94 Fathilah J, Choo MM. The Jarisch-Herxheimer reaction in ocular syphilis. Med J Malaysia 2003; 58 (03) 437-439
    PubMedGoogle Scholar
  • 95 Davis LE, Oyer R, Beckham JD, Tyler KL. Elevated CSF cytokines in the Jarisch-Herxheimer reaction of general paresis. JAMA Neurol 2013; 70 (08) 1060-1064
    CrossrefPubMedGoogle Scholar
  • 96 Anshu A, Cheng CL, Chee SP. Syphilitic uveitis: an Asian perspective. Br J Ophthalmol 2008; 92 (05) 594-597
    CrossrefPubMedGoogle Scholar
  • 97 Hoogewoud F, Frumholtz L, Loubet P. , et al. Prognostic factors in syphilitic uveitis. Ophthalmology 2017; 124 (12) 1808-1816
    CrossrefPubMedGoogle Scholar
  • 98 Tucker JD, Li JZ, Robbins GK. , et al. Ocular syphilis among HIV-infected patients: a systematic analysis of the literature. Sex Transm Infect 2011; 87 (01) 4-8
    CrossrefPubMedGoogle Scholar
  • 99 Tuddenham S, Ghanem KG. Ocular syphilis: opportunities to address important unanswered questions. Sex Transm Infect 2016; 92 (08) 563-565
    CrossrefPubMedGoogle Scholar
  • 100 Marra CM, Maxwell CL, Tantalo L. , et al. Normalization of cerebrospinal fluid abnormalities after neurosyphilis therapy: does HIV status matter?. Clin Infect Dis 2004; 38 (07) 1001-1006
    CrossrefPubMedGoogle Scholar
  • 101 Marra CM, Maxwell CL, Tantalo LC, Sahi SK, Lukehart SA. Normalization of serum rapid plasma reagin titer predicts normalization of cerebrospinal fluid and clinical abnormalities after treatment of neurosyphilis. Clin Infect Dis 2008; 47 (07) 893-899
    CrossrefPubMedGoogle Scholar