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Show © 1989 Raven Press, Ltd., New York Editorial Comment Diagnosing Neurosyphilis The Value of the Cerebrospinal Fluid VDRL or Lack Thereof In their description of a patient with AIDS, herpes zoster ophthalmicus and recurrent ocular toxoplasmosis, Pillai and colleagues ( 1) state that their neurological consultant did not feel that the patient required intravenous penicillin for neurosyphilis because his cerebrospinal fluid ( CSF) venereal disease research laboratory test ( VORL) was negative. This belief regarding the CSF VORL, though widely held, is mistaken. The VORL is a nontreponemal reaginic test in which serum or CSF is tested for its ability to flocculate a suspension of cardiolipin- cholesterol- lecithin. The immunoglobulirls responsible for a positive response are directed against a lipoidal antigen that results from an irlteraction of Treponema pallidum with host tissues and/ or T. pallidum itself. In the serum, a positive VORL is neither sensitive nor specific for syphilis and requires confirmation with specific treponemal tests, such as the fluorescent treponemal antibody- absorption test ( FTA- abs), microhemagglutination assay for antibodies to T. pallidum hemagglutination assay ( MHA- TP), or the T. pallidum immobilization ( TPI) test. The serum VORL is positive in 72% of patients with primary syphilis, in nearly 100% of patients with secondary syphilis, in 73% of patients with latent syphilis, and in 77% of patients with tertiary syphilis ( 2). Therefore, one- quarter of patients with neurosyphilis have a negative serum VORL. In the presence of concomitant HIV infection, the likelihood of a false- negative serum VORL may be even higher. For instance, Hicks and colleagues ( 3) reported a HIV- seropositive patient with secondary syphilis and negative serological studies. The diagnosis of syphilis was established by dark- field examination of the patients skin biopsy. The nontreponemal reaginic test widely used before the development of the VORL slide test was the Wasserman test. Merritt et al. reported that the incidence of a positive CSF Wasserman test in the 234 face of neurosyphilis varied from 81% in meningovascular syphilis to 100% in tabes dorsalis and spinal pachymeningitis ( 4). However, tabes dorsalis has been clinically diagnosed irl patients with a nonreactive CSF Wasserman test ( 5). Additionally, pathologically confirmed neurosyphilis has been reported in a patient with a nonreactive CSF VORL test ( 6). In a study by the Centers for Oisease Control, the CSF VORL was positive in 90% of patients with symptomatic neurosyphilis, but only irl 10% of patients with asymptomatic neurosyphilis ( 7). However, the insensitivity of the VORL in the latter group may have reflected their definition of asymptomatic neurosyphilis. Recently, Lukehart and colleagues cultured CSF from patients with untreated syphilis in rabbit testicles ( 8). This test is the " gold standard" for establishing the presence of T. pallidlllll infection in the central nervous system; however, it is impractical to perform and available in only a handful of medical centers. Treponemes were demonstrated in the CSF of 12 ( 30%) of 40 patients with primary and secondary syphilis ( 8). The CSF VORL was positive in only 4 ( 33%) of the 12 patients from whom CSF treponemes were isolated ( 8). Therefore, measures other than a positive CSF VORL must be relied on to establish a diagnosis of neurosyphilis. Unfortunately, no consensus exists regarding the diagnostic criteria for neurosyphilis. At one end of the spectrum, a diagnosis of neurosyphilis has been recommended in patients with serological evidence of syphilis and one or more of the following abnormalities in their CSF: a pleoctyosis, an elevated protein level, a decreased glucose concentration, or a positive VORL ( 9). In the presence of concomitant human immunodeficiency virus irlfection, however, a CSF pleocytosis and elevated CSF protein are frequently observed ( 10). Furthermore, other useful clues for neurosyphilis, such as elevated CSF immunoglobulins or the presence of EDITORIAL COMMENT 235 CSF oligoclonal bands, are often detected ( 10), which seriously detracts from their diagnostic utility. At the other extreme, a reactive CSF with increased cell count and protein level and a positive CSF VORL have been the diagnostic requirements for neurosyphilis proposed by others ( 11). Clearly, the appropriate answer lies somewhere between these two extremes. A reliable CSF test that exhibits both a high degree of sensitivity and specificity for neurosyphilis would be ideal. The currently available treponemal tests are hardly ideal for this purpose ( 12), and the physician must refrain from dogma in making this diagnosis. Perhaps the development of newer generation tests, such as polymerase chain reaction or monoclonal antibodies for syphilis, may solve our current dilemma. Joseph R. Berger, M. D., F. A. C. P. Department of Neurology University of Miami School of Medicine Miami, Florida, U. S. A. REFERENCES 1. Pillai 5, Mahmood MA, Limaye SR. Herpes zoster ophthalmicus, contralateral hemiplegia and recurrent ocular toxoplasmosis in a patient with acquired immunodeficiency syndrome related complex. I Clin Neuro- ophthalmol 1989; 9: 229- 33. 2. Holmes KA. Syphilis. In: Petersdorf RG, Adams RD, Braunwald E, Isselbacher KJ, Martin JB, Wilson JD, eds. Harrison's principles of internal medicine, 10th ed. New York: McGraw- Hill, 1983, 1034- 1045. 3. Hicks CB, Benson PM, Lupton GP, Tramont EC Seronegative secondary syphilis in a patient infected with the human immunodeficiency virus ( HIV) with KapOSi sarcoma. Ann Intern Med 1987; 107: 492- 495. 4. Merritt HH, Adams RD, Solomon HC Neurosyphilis. New York: Oxford University Press, 1946. 5. Merritt HH. A textbook of neurology, 5 ed. Philadelphia: Lea & Febiger, 1973: 123. 6. Burke AW. Syphilis in a Jamaican psychiatric hospital: a review of 52 cases including 17 of neurosyphilis. Br I Vener Dis 1972; 48: 249- 253. 7. Larsen SA, Hambie EA, Wobig GH, Kennedy EJ. Cerebrospinal fluid serologic test for syphilis: treponemal and nontreponemaI tests. In: Morisset R, Kurstak E, eds. Advances in sexually transmitted diseases. Utrecht: VNU Science Press, 1986: 157- 162. 8. Lukehart SA, Hook 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: 855- 862. 9. Tramont EC Treponema pallidum ( syphilis). In: Mandell GL, Douglas RG, Bennett JE, eds. Infectious diseases, 5th ed. New York: John Wiley & Sons, 1985: 1323-- 1333. 10. Marshall OW, Brey RL, Cahill WT, Houk RW, Zajac RA, Boswell RN. Spectrum of cerebrospinal fluid findings in various states of human immunodeficiency virus infection. Arch NeuroI1988; 45: 954- 958. 11. Simon RP. Neurosyphilis. Arch Neurol 1985; 42: 606- 613. 12. Jaffe HW, Kabins SA. Examination of cerebrospinal fluid in patients with syphilis. Rev Infect Dis 1982; 4: 5842- 5847. I Clin Neuro- ophthalmol, Vol. 9, No. 4, 1989 |
