LETTERS
Neurosyphrlis in Patients Infected with Human Immunodeficiency Virus
These findings suggest serious limitations to the use of the CSF FTA-ABS test as a screening test for neurosyphilis. We recommend caution in its interpretation and agree vigorously with Davis and Schmitt that clinical judgment remains the cornerstone in establishing this diagnosis.
Joseph R. Berger, MD, and Micheline McCarthy, PhD, M D
Department of Neurology University of Miami School of Medicine Miami, FL
We wish to share some observations concerning Davis and Schmitt’s article on the significance of cerebrospinal fluid (CSF) tests for neurosyphilis {I). As part of an ongoing study of the development of neurological disease in asymptomatic, human immunodeficiency virus (HIV)-seropositive subjects, we query all participants for a history of syphilis, perform serum rapid plasma reagin (RPR) and fluorescent treponemal antibody absorption (FTA-ABS) tests, and examine the CSF by Venereal Disease Research Laboratory (VDRL) and FTA-ABS tests. In the first 81 subjects, the serum FTA-ABS test was positive in 32 (39.5%). The CSF ETA-ABS test was positive in 5 of the 81 subjects, and in 3 of these 5 subjects, the CSF VDRL test was negative. Two of these 3 subjects had neither a history of syphilis nor serological evidence of syphilis as indicated by a positive serum RPR or FTA-ABS test. In the other 2 subjects with a positive CSF ETA-ABS test, the CSF VDRL test was also positive. Both had a history of prior syphilis and a positive serum FTA-ABS test. These 2 neurologically asymptomatic subjects would be categorized as unlikely to have active neurosyphilis by the criteria of Davis and Schmitt {I). Our observations in this HIV-seropositive population are similar to those of others that predate the AIDS era. For instance, in 1970 Escobar and colleagues {2) reported finding 3 reactive and 3 weakly reactive ETA-ABS tests in CSF samples from 67 patients with neither clinical nor serological evidence of syphilis. Lower rates of falsely positive CSF ETA-ABS tests have been reported by other investigators [3-57. The nonspecificity qf the CSF FTA-ABS test raises concern about its value in diagnosing neurosyphilis. Davis and Schmitt suggest that other CSF measures (e.g., elevated IgG index and oligoclonal bands) can help to distinguish the “truly positive” CSF FTA-ABS from falsely positive tests, but many of the CSF abnormalities commonly found in neurosyphilis, such as increased protein, increased immunoglobulins, and oligoclonal bands are also found in asymptomatic HIV infection {67. The sensitivity of the CSF ETA-ABS test has also been questioned by a number of investigators. Duncan and coworkers {37 reported that 19 (50%) of 38 patients with clinical neurosyphilis had a negative CSF ETA-ABS test. Similarly, Wilkinson { 7) noted false-negative results for CSF ETA-ABS tests in 16 (33%) of 49 patients with neurosyphilis, and Mahoney and associates 181 reported false-negative results in 5 (25%) of 20 with the disease. Importantly, false-negative results of serological studies for syphilis have been reported in the setting of HIV infection [9, 10). In one recent study, 43% of patients with AIDSrelated complex had “seroreversion” of their treponemal tests (i.e., serum FTA-ABS andor MHA-TP) {lo}. HOWever, the sensitivity of the CSF ETA-ABS test in the HIVinfected patient with neurosyphilis awaits further investigation.
Editor’s Note Please see the editorial by D r Davis on this topic on page 2 11 of this issue. A.K.A. Supported by National Institute of Neurological Disorders and Stroke grant Pol-NS-25569-01.
References 1. Davis LE, Schmitt JW. Clinical significance of cerebrospinal fluid tests for neurosyphilis. Ann Neurol 1989;25:50-55 2. Escobar MR, Dalton HP, Allison MJ. Fluorescent antibody test for syphilis using cerebrospinal fluid: clinical correlation in 150 cases. Am J Clin Pathol 1970;53:886-890 3. Duncan WP, Jenkins TW, Parham CE. Fluorescent treponemal antibody cerebrospinal fluid (ETA-ABS) tests. Br J Vener Dis 1972;48:97-101 4. Jaffe HW, Larsen SA, Peters M, et al. Tests for treponemal antibody in CSF. Arch Intern Med 1978;138:252-255 5. Harris A, Bossak HM, Deacon WE, Bunch W. Comparison of the fluorescent treponemal antibody test with other tests for syphilis on cerebrospinal fluids. Br J Vener Dis 1960;36:178180 6. Marshall DW, Brey RL,Cahill WT, et al. Spectrum of cerebrospinal fluid findings in various states of human immunodeficiency virus infection. Arch Neurol 1988;45:954-958 7. Wilkinson AE. Fluorescent treponemal antibody tests on cerebrospinal fluid. Br J Vener Dis 1973;49:346-349 8. Mahoney JDH, Harris JRW, Sydney-McCannJ, et al. Evaluation of the CSF ETA-ABS test in latent and tertiary treated syphilis. Acta Derm Venereol (Stockh) 1972;52:71-74 9. Hicks CB, Benson PM, Lupton GP, Tramont EC. Seronegative secondary syphilis in a patient infected with the human immunodeficiency virus (HIV) with Kaposi sarcoma. A diagnostic dilemma. Ann Intern Med 1987;107:492-495 10. Haas JS, Bolan G, Larsen S, et al. “Seroreversion” of treponemal tests during HIV infection. Fifth International Conference on AIDS, Montreal, June, 1989: 360 (Abstract)
Obercular Sign: S&nlficance Beyond Cerebral Dysgenesis Naomi Amir, MD, Orly El-Peleg, MD, and Varda Gross. M D Tatum and co-workers [l) reported 4 children in whom magnetic resonance imaging disclosed bilaterally enlarged sylvian fissures. They concluded that the pathogenesis is a
Copyright 0 1990 by the American Neurological Association 213
Neurosyphrlis in Patients Infected with Human Immunodeficiency Virus
These findings suggest serious limitations to the use of the CSF FTA-ABS test as a screening test for neurosyphilis. We recommend caution in its interpretation and agree vigorously with Davis and Schmitt that clinical judgment remains the cornerstone in establishing this diagnosis.
Joseph R. Berger, MD, and Micheline McCarthy, PhD, M D
Department of Neurology University of Miami School of Medicine Miami, FL
We wish to share some observations concerning Davis and Schmitt’s article on the significance of cerebrospinal fluid (CSF) tests for neurosyphilis {I). As part of an ongoing study of the development of neurological disease in asymptomatic, human immunodeficiency virus (HIV)-seropositive subjects, we query all participants for a history of syphilis, perform serum rapid plasma reagin (RPR) and fluorescent treponemal antibody absorption (FTA-ABS) tests, and examine the CSF by Venereal Disease Research Laboratory (VDRL) and FTA-ABS tests. In the first 81 subjects, the serum FTA-ABS test was positive in 32 (39.5%). The CSF ETA-ABS test was positive in 5 of the 81 subjects, and in 3 of these 5 subjects, the CSF VDRL test was negative. Two of these 3 subjects had neither a history of syphilis nor serological evidence of syphilis as indicated by a positive serum RPR or FTA-ABS test. In the other 2 subjects with a positive CSF ETA-ABS test, the CSF VDRL test was also positive. Both had a history of prior syphilis and a positive serum FTA-ABS test. These 2 neurologically asymptomatic subjects would be categorized as unlikely to have active neurosyphilis by the criteria of Davis and Schmitt {I). Our observations in this HIV-seropositive population are similar to those of others that predate the AIDS era. For instance, in 1970 Escobar and colleagues {2) reported finding 3 reactive and 3 weakly reactive ETA-ABS tests in CSF samples from 67 patients with neither clinical nor serological evidence of syphilis. Lower rates of falsely positive CSF ETA-ABS tests have been reported by other investigators [3-57. The nonspecificity qf the CSF FTA-ABS test raises concern about its value in diagnosing neurosyphilis. Davis and Schmitt suggest that other CSF measures (e.g., elevated IgG index and oligoclonal bands) can help to distinguish the “truly positive” CSF FTA-ABS from falsely positive tests, but many of the CSF abnormalities commonly found in neurosyphilis, such as increased protein, increased immunoglobulins, and oligoclonal bands are also found in asymptomatic HIV infection {67. The sensitivity of the CSF ETA-ABS test has also been questioned by a number of investigators. Duncan and coworkers {37 reported that 19 (50%) of 38 patients with clinical neurosyphilis had a negative CSF ETA-ABS test. Similarly, Wilkinson { 7) noted false-negative results for CSF ETA-ABS tests in 16 (33%) of 49 patients with neurosyphilis, and Mahoney and associates 181 reported false-negative results in 5 (25%) of 20 with the disease. Importantly, false-negative results of serological studies for syphilis have been reported in the setting of HIV infection [9, 10). In one recent study, 43% of patients with AIDSrelated complex had “seroreversion” of their treponemal tests (i.e., serum FTA-ABS andor MHA-TP) {lo}. HOWever, the sensitivity of the CSF ETA-ABS test in the HIVinfected patient with neurosyphilis awaits further investigation.
Editor’s Note Please see the editorial by D r Davis on this topic on page 2 11 of this issue. A.K.A. Supported by National Institute of Neurological Disorders and Stroke grant Pol-NS-25569-01.
References 1. Davis LE, Schmitt JW. Clinical significance of cerebrospinal fluid tests for neurosyphilis. Ann Neurol 1989;25:50-55 2. Escobar MR, Dalton HP, Allison MJ. Fluorescent antibody test for syphilis using cerebrospinal fluid: clinical correlation in 150 cases. Am J Clin Pathol 1970;53:886-890 3. Duncan WP, Jenkins TW, Parham CE. Fluorescent treponemal antibody cerebrospinal fluid (ETA-ABS) tests. Br J Vener Dis 1972;48:97-101 4. Jaffe HW, Larsen SA, Peters M, et al. Tests for treponemal antibody in CSF. Arch Intern Med 1978;138:252-255 5. Harris A, Bossak HM, Deacon WE, Bunch W. Comparison of the fluorescent treponemal antibody test with other tests for syphilis on cerebrospinal fluids. Br J Vener Dis 1960;36:178180 6. Marshall DW, Brey RL,Cahill WT, et al. Spectrum of cerebrospinal fluid findings in various states of human immunodeficiency virus infection. Arch Neurol 1988;45:954-958 7. Wilkinson AE. Fluorescent treponemal antibody tests on cerebrospinal fluid. Br J Vener Dis 1973;49:346-349 8. Mahoney JDH, Harris JRW, Sydney-McCannJ, et al. Evaluation of the CSF ETA-ABS test in latent and tertiary treated syphilis. Acta Derm Venereol (Stockh) 1972;52:71-74 9. Hicks CB, Benson PM, Lupton GP, Tramont EC. Seronegative secondary syphilis in a patient infected with the human immunodeficiency virus (HIV) with Kaposi sarcoma. A diagnostic dilemma. Ann Intern Med 1987;107:492-495 10. Haas JS, Bolan G, Larsen S, et al. “Seroreversion” of treponemal tests during HIV infection. Fifth International Conference on AIDS, Montreal, June, 1989: 360 (Abstract)
Obercular Sign: S&nlficance Beyond Cerebral Dysgenesis Naomi Amir, MD, Orly El-Peleg, MD, and Varda Gross. M D Tatum and co-workers [l) reported 4 children in whom magnetic resonance imaging disclosed bilaterally enlarged sylvian fissures. They concluded that the pathogenesis is a
Copyright 0 1990 by the American Neurological Association 213
