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Neurology India
Medknow Publications on behalf of the Neurological Society of India
ISSN: 0028-3886 EISSN: 1998-4022
Vol. 57, Num. 3, 2009, pp. 233-234

Neurology India, Vol. 57, No. 3, May-June, 2009, pp. 233-234

Editorial

Neurosyphilis

Ananthapuri Hospital and Research Institute, Trivandrum, Kerala

Correspondence Address: Mr. Mohan Madhusudhan, Deepam, Kanjikunzhy, Kottayam, India.
neuromadhu@yahoo.com

Date of Acceptance: 04-Jun-2009

Code Number: ni09075

PMID: 19587460

DOI: 10.4103/0028-3886.53259

Neurosyphilis remains a clinical problem, especially when it presents in an unfamiliar and bizarre fashion. Several recent reports suggest a worldwide increase in the incidence of this condition. [1],[2] One should keep a close vigilance as not to miss this treatable condition, since its presentation can reflect affection of different parts of the neuraxis. Neurosyphilis now rarely presents in its classical form of tabes or general paresis, but presents atypically with subtle signs and symptoms. [3] For example, neurosyphilis can masquerade as a stroke-like syndrome, [4],[5] intracranial space-occupying lesion, [6],[7] dementia, [8],[9] psychosis or as movement disorders apart from its classical presentation of chronic meningitis. Cases presenting as dementia with magnetic resonance imaging showing findings suggestive of herpes simplex encephalitis have been reported. [10],[11] In this issue cases presenting with stroke secondary to subclavian artery aneurysm [12] and chorea [13] have been presented. Spinal presentations can mimic amyotrophic lateral sclerosis, spinal cord compression or transverse myelitis. [14]

Since the antibiotic era, the spectrum of neurosyphilis is reported to have changed. Of the 241 new cases of neurosyphilis studied by Hooshmand et al ., [15] the majority were asymptomatic and the remainder had atypical syndromes, with only 49% having a reactive non-treponemal serological test for syphilis. A study from South Africa [16] reported that the majority of patients with neurosyphilis presented with subtle clinical signs and with weakly positive or even negative serology. The atypical presentation has been emphasized in an editorial in the British Medical Journal. [17] However, a study from the United Kingdom [18] in 1979 reported 17 cases of neurosyphilis and found that the presentations were not atypical.

Human immunodeficiency virus (HIV) and syphilis affect similar patient groups and co-infection is common. Patients with HIV are at increased risk for neurosyphilis. [19] All patients presenting with syphilis should be offered HIV testing and all HIV-positive patients should be regularly screened for syphilis. Detection and treatment of syphilis can, therefore, help to reduce HIV transmission. Syphilis may present with non-typical features in the HIV-positive patients: there is a higher rate of non-symptomatic primary syphilis and proportionately more HIV-positive patients present with secondary disease. Secondary infection may be more aggressive and there is an increased rate of early neurological involvement. Relapse of infection is more likely in the HIV-positive patient and careful follow-up is required. [20]

The diagnosis of neurosyphilis, or more often the definite exclusion of neurosyphilis as a clinical possibility, remains a difficult problem. Treponema pallidum , the causative agent, cannot be cultured in vitro and microscopic techniques are laborious. Thus, diagnosis depends on serologic tests and cerebrospinal fluid (CSF) examination. The diagnosis of neurosyphilis can be made with reasonable certainty if there is an appropriate neuropsychiatric syndrome associated with a positive CSF Venereal Disease Research Laboratory (VDRL) test. [21] The CSF VDRL when reactive, and in the absence of substantial contamination of CSF with blood, is diagnostic of neurosyphilis. The VDRL will be falsely positive only if blood contamination is sufficient to tinge the CSF pink. [22] What if the CSF VDRL is negative? CSF studies are reactive in only approximately 70-75% of neurosyphilis cases. [23] CSF fluorescent treponemal antibody absorption (FTA-AB) test may be the only serological evidence of neurosyphilis, and carries the advantage of being highly sensitive. However, a high proportion of cases with a positive FTA-AB in the CSF did not have neurosyphilis. The primary value of the FTA test in CSF may be to exclude the possibility of neurosyphilis if the test result is negative. If the CSF VDRL is negative, a positive FTA-ABS in an appropriate clinical setting, associated with raised CSF cell count, protein or IgG index, is a useful method of identifying neurosyphilis. [22]

Penicillin remains the drug of choice for the treatment of syphilis. Although several studies have suggested that azithromycin may have clinical efficacy, macrolide resistance has been widely documented among strains of Treponema pallidum, and treatment failures have been reported. Ceftriaxone is effective for the treatment of syphilis when used in multiple-dose regimens. [24]

References

1.St Louis ME, Farley TA, Aral SO. Untangling the persistence of syphilis in the South. Sex Transm Dis 1996;23:1-4.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Fenton KA, Breban R, Vardavas R, Okano JT, Martin T, Aral S, et al . Syphilis in high-income settings in the 21st century. Lancet Infect Dis 2008;8:244-53.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Mitsonis CH. Incidence and clinical presentation of neurosyphilis: A retrospective study of 81 cases. Int J Neurosci 2008;118:1251-7.  Back to cited text no. 3    
4.Flint AC, Liberato BB, Anziska Y, Schantz-Dunn J, Wright CB. Meningovascular syphilis as a cause of basilar artery stenosis. Neurology 2005;64:391-2.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Bourazza A. Meningovascular syphilis: Study of five cases. Rev Neurol (Paris) 2008;164:369-73.  Back to cited text no. 5    
6.Weinert LS. Cerebral syphilitic gumma in HIV-infected patients: case report and review. Int J STD 2008;19:62-4.  Back to cited text no. 6    
7.Fargen KM. Cerebral syphilitic gummata: a case presentation and analysis of 156 reported cases. Neurosurgery 2009;64:568-75.  Back to cited text no. 7    
8.Lee CH. Initially unrecognized dementia in a young man with neurosyphilis. Neurologist 2009;15:95-7.  Back to cited text no. 8    
9.Teixeira AL. Rapid progressive dementia associated with neurosyphilis. Rev Soc Bras Med Trop 2006;39:390-1.  Back to cited text no. 9    
10.Lessig S, Tecoma E. Perils of the prozone reaction: Neurosyphilis presenting as an RPR negative subacute dementia. Neurology 2006;66:777.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Otto B. Neurosyphilis: Important differential diagnosis of herpes simplex encephalitis. Nervenarzt 2007;78:944-7.  Back to cited text no. 11    
12.Lin CM. Left subclagian artery aneurysm secondary to shypilitic arteritis presenting with a right ischemic cerebellar infarction. Neurol India 2009;57:344-6.  Back to cited text no. 12  [PUBMED]  Medknow Journal
13.Ozben S, Erol C, Ozer F, Tiras R. Chorea as the presentation of neurosyphilis. Neurol India 2009;347-9.   Back to cited text no. 13    
14.Chilver-Stainer L, Fischer U, Hauf M, Fux CA, Sturzenegger M. Syphilitic myelitis: Rare, nonspecific, but treatable. Neurology 2009;72:673-4.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
15.Hooshmand H, Escobar MR, Kopf SW. Neurosyphilis: A study of 241 patients. JAMA 1972;219:726-9   Back to cited text no. 15  [PUBMED]  
16.Joyce CN, Molteno AC. Modified neurosyphilis in the Cape Peninsula. S Afr Med J 1978;53:10-4.  Back to cited text no. 16    
17.Modified neurosyphilis [editorial]. BMJ 1978;2:647-8.  Back to cited text no. 17    
18.Wolters EC. Neurosyphilis: a changing diagnostic problem? Eur Neurol 1987;26:23-8.  Back to cited text no. 18  [PUBMED]  
19.Marra CM, Maxwell CL, Smith SL, Lukehart SA, Rompalo AM, Eaton M, et al . Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features. J Infect Dis 2004;189:369-76.  Back to cited text no. 19  [PUBMED]  [FULLTEXT]
20.Lynn WA, Lightman S. Syphilis and HIV: a dangerous combination. Lancet Infect Dis 2004;7:456-66.  Back to cited text no. 20    
21. Hart G. Syphilis tests in diagnostic and therapeutic decision making. Ann Intern Med 1986;104:368-76.  Back to cited text no. 21  [PUBMED]  
22.Hook EW, Marra CM. Acquired syphilis in adults. N Engl J Med 1992;326:1060-9.  Back to cited text no. 22    
23.Hart G. Syphilis tests in diagnostic and therapeutic decision making. Ann Intern Med 1986;104:368-7.  Back to cited text no. 23  [PUBMED]  
24.Stoner BP. Current controversies in the management of adult syphilis. Clin Infect Dis 2007;44:S130-46.  Back to cited text no. 24  [PUBMED]  [FULLTEXT]

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