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The profile of neurosyphilis in Denmark A clinical and serological study of all patients in Denmark with neurosyphilis disclosed in the years 1971-1979 incl. by Wassermann reaction (CWRM) in the cerebrospinal fluid.

55 cases of neurosyphilis, probably all that has been disclosed in Denmark in the nine year period 1971 to 1979 are submitted. 55 case histories and 10 tables illustrate the variegated clinical features and the differential diagnoses, the serological data, and CSF findings, the treatment and its results. As the symptomatology of the series fits well into the classification of neurosyphilis of the past our cases are classified accordingly in five clinical groups with seven subgroups. Penicillin treatment was applied to all the patients in current dosages and proved beneficial in most patients with regard to clinical symptoms and to laboratory parameters. The outcome here registered seem, however, to be related more to the character of the disease than to the types or amounts of penicillin. Eleven of the patients had a history of previous positive serology and two of them had been treated with penicillin for early syphilis but their neurosyphilis was evidently due to an untreated reinfection. Ten of the patients had aortitis.

Adolescent↗

Neurosyphilis in HIV-infected patients.

To determine the prevalence and the clinical and serological findings of neurosyphilis in HIV-infected patients, Treponema pallidum hemagglutination (TPHA) tests, CD4+ lymphocyte counts and determination of rapid plasma reagin (RPR) titers were performed in 972 HIV-infected patients over a period of 3.5 years. Patients were scored according to the Centers for Disease Control's classification for HIV infection. Reactive serum syphilis tests and positive cerebrospinal fluid (CSF)-Venereal Disease Research Laboratory (VDRL) tests, with or without clinical symptoms, were used as the criteria for diagnosis of neurosyphilis. The TPHA test was positive in 31 patients, representing 3.1% of all HIV-infected patients included in the study. Of these, 13 were intravenous drug addicts, 14 were homosexuals and 4 were heterosexuals. Diagnosis of syphilis was concurrent with HIV infection in 19 patients, prior to HIV infection in 6 patients and after HIV infection in 6 patients. CSF examinations were performed in 28 of the 31 (90.3%) patients with serologically evident syphilis. Four patients had positive CSF-VDRL tests with pleocytosis (23.5% of untreated syphilis patients in whom CSF was examined), three of whom reported mild headache, which was considered a doubtful manifestation of neurosyphilis. Patients with syphilis diagnosed and treated prior to diagnosis of HIV infection did not have evidence of neurosyphilis. Seven patients had pleocytosis with a negative CSF-VDRL test, without any clinical manifestations of neurosyphilis. There was no significant difference in the mean CD4+ lymphocyte count between patients with and without neurosyphilis (p = 0.5). RPR titers in neurosyphilis patients were greater than those in patients previously treated for syphilis and in those with pleocytosis only (p = 0.046 and 0.036, respectively). All neurosyphilis patients had an RPR titer > 1:8. After therapy, neurosyphilis patients had negative CSF-VDRL tests with a lower level of pleocytosis. The prevalence of neurosyphilis was 0.4% in HIV-infected patients and 23.5% in HIV-infected patients with untreated syphilis. This high prevalence of neurosyphilis warrants CSF examination in HIV-infected patients with syphilis, regardless of the stage of syphilis.

Adult↗

Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus.

OBJECTIVE: To evaluate the effect of ceftriaxone in treating latent syphilis or asymptomatic neurosyphilis in patients infected with the human immunodeficiency virus (HIV). DESIGN: Follow-up study of patients treated at two HIV-based clinics during 16 months from 1989 to 1991. PATIENTS: Patients were those in whom a clinical diagnosis of latent syphilis or asymptomatic neurosyphilis was made, who received all recommended doses of antimicrobial therapy, and who returned for follow-up visits for 6 or more months. RESULTS: Forty-three patients were treated with ceftriaxone, 1 to 2 g daily for 10 to 14 days. Thirteen underwent lumbar puncture before treatment; 7 (58%) had documented neurosyphilis (pleocytosis in 5, elevated protein levels in 6, VDRL reactive in cerebrospinal fluid [CSF] in 7), and 6 had documented latent syphilis (entirely normal CSF). The remaining 30 were said to have presumed latent syphilis. There was no relation between the diagnosis and the selected dosage of ceftriaxone. Response rates were similar in those who had documented neurosyphilis and documented or presumed latent syphilis. Overall, 28 patients (65%) responded to therapy, 5 (12%) were serofast, 9 (21%) had a serologic relapse, and 1 (2%) who experienced progression to symptomatic neurosyphilis was a therapeutic failure. Thirteen patients received benzathine penicillin for presumed latent syphilis; results were similar to those observed after ceftriaxone therapy, with 8 (62%) responders, 1 (8%) serofast, 2 (15%) relapses, and 2 (15%) failures. CD4 cell counts in responders were not different from those who failed to respond. CONCLUSIONS: Even in the absence of neurologic symptoms, half of the HIV-infected persons who have serologic evidence of syphilis may have neurosyphilis. Although ceftriaxone achieves high serum and CSF levels, 10 to 14 days of treatment with this drug were associated with a 23% failure rate in HIV-infected patients who had latent syphilis or asymptomatic neurosyphilis. Three doses of benzathine penicillin did not have a significantly higher relapse rate and may provide appropriate therapy, at least for documented latent syphilis in persons co-infected with HIV. Studies comparing ceftriaxone with 10 to 14 doses of procaine penicillin are needed to determine the most cost-effective treatment for asymptomatic neurosyphilis or presumed latent syphilis in this group of patients.

Adult↗

Neurosyphilis during the AIDS epidemic, San Francisco, 1985-1992.

To investigate the epidemiology and clinical spectrum of neurosyphilis in a population with high rates of coexisting syphilis and human immunodeficiency virus (HIV) infection, a retrospective analysis of cases in all San Francisco hospitals from 1985 to 1992 was conducted. Neurosyphilis was defined by a newly reactive cerebrospinal fluid VDRL; 117 patients with neurosyphilis were identified. The median age was 39 years, 91% were male, 74 (63%) were white, and 75 (64%) were HIV-infected. Thirty-eight (33%) presented with an early symptomatic neurosyphilis syndrome. Six (5%) had late neurosyphilis. Thirty-eight (32%) patients were asymptomatic, and 35 (30%) had findings attributable to coexisting neurologic diseases. Patients demonstrated high serum nontreponemal (VDRL) titers (median, 1:128) at neurosyphilis presentation. In contrast to the findings from the preantibiotic era, neurosyphilis was identified in young patients most often with HIV coinfection, and early symptomatic syndromes were identified more frequently than late neurosyphilis syndromes.

AIDS-Related Opportunistic Infections↗

Evaluation of neurosyphilis in human immunodeficiency virus-infected individuals.

The diagnosis of neurosyphilis in patients infected with the human immunodeficiency virus (HIV) remains problematic. We examined the use of the Treponema pallidum hemagglutination (TPHA) index and quantitative tests of CSF by means of microhemagglutination-T. pallidum for diagnosis of neurosyphilis in 58 HIV-infected persons with latent syphilis who had not recently received therapy for syphilis. Five patients (9%) had reactive CSF VDRL tests and thus had proven neurosyphilis. For 13 patients (22%), CSF findings were normal and revealed no evidence of neurosyphilis. For 40 patients (69%), abnormal CSF findings were characteristic of neurosyphilis, but their CSF VDRL tests were nonreactive. Twenty-five of the 40 patients with possible neurosyphilis had pleocytosis and elevated CSF levels of protein and/or IgG. Five (12.5%) of these 40 patients had positive TPHA indices that indicated intrathecal antitreponemal antibody production, a finding that provided greater support for the diagnosis of active neurosyphilis. With use of the TPHA index, patients with CSF abnormalities can be better classified in regard to their need for therapy for neurosyphilis.

Adult↗

Neurosyphilis is unlikely in patients with late latent syphilis and a negative blood VDRL-test.

Patients with latent syphilis or syphilis of unknown duration should be evaluated for tertiary disease and neurosyphilis. The aim of this retrospective study was to determine relevant serological parameters for the identification of those individuals with syphilis who are most likely to have neurosyphilis and who therefore require lumbar puncture. After excluding repeated estimates and patients whose blood syphilis serology had either been negative or not been determined within 3 months of lumbar puncture, 265 out of 710 cerebrospinal fluids from 1988 to 2004 were analysed. In each of those patients the earliest available pairs of serum and cerebrospinal fluid samples were evaluated. The diagnosis of neurosyphilis was based on criteria according to established guidelines. Forty-three of 265 patients (16.2%; 5 women, 38 men; mean age 47+/-16 years) had neurosyphilis. Seven of 72 (9.7%) of those testing HIV-positive, fulfilled the criteria of neurosyphilis. Not a single patient with neurosyphilis tested Venereal Disease Research Laboratory test (VDRL)-negative in peripheral blood, an effect which was highly significant (p < 0.01, chi2-test). The median blood-VDRL titre was significantly higher in patients with neurosyphilis than in those without (1:32 vs. 1:0; p < 0.01, t-test, two-sided). Hence, neurosyphilis is very unlikely in patients with a negative blood-VDRL. Therefore, lumbar puncture is not recommended in these patients.

Adult↗

Neurosyphilis in a tertiary care hospital in north India.

BACKGROUND AND OBJECTIVES: The clinical diagnosis of neurosyphilis is very rarely encountered today in the developed world although syphilis remains a significant health problem in few areas of the industrialized countries and in most of the third world nations. This apparent decline may be due to increase in number of asymptomatic neurosyphilis and cases presenting as subtle, illdefined syndromes rather than classic presentation of tabes dorsalis and general paresis in the post penicillin era. This retrospective study was carried out to report the neurosyphilis cases diagnosed at a tertiary care hospital in North India, and to analyse the laboratory and clinical parameters of these cases. METHODS: Suspected cases of neurosyphilis presenting at Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh over a period of 13 yr (January 1990 to December 2002) were identified. Diagnosis of neurosyphilis was based on clinical presentation, prior history of syphilis, routine CSF biochemistry (protein and leukocytes) and serological evidence [serum and CSF venereal disease research laboratory (VDRL) and Treponema pallidum particle agglutination (TPPA) tests]. RESULTS: A total of 25 cases of neurosyphilis were identified, 18 (72%) with reactive CSF-VDRL, 22 (88%) with elevated CSF protein and 24 (96%) with CSF mononuclear leukocytosis. Serum VDRL was reactive in all 25 cases. Three patients were asymptomatic (2 primary syphilis; 1 early latent stage), 8 had secondary and 14 had tertiary syphilis. Two of the neurosyphilis cases were also seropositive for HIV. Radiology was abnormal in 7 (28%) patients. INTERPRETATION AND CONCLUSION: Neurosyphilis still remains a problem in a country like India and a high index of suspicion and clinical expertise are required for appropriate diagnosis and proper management especially in the era of AIDS pandemic.

Cerebrospinal Fluid↗

Neurosyphilis. A comparative study of the effects of infection with human immunodeficiency virus.

BACKGROUND: The course of neurosyphilis has been reported to be altered by human immunodeficiency virus (HIV) infection. Prior reports of neurosyphilis occurring in association with HIV infection have been largely anecdotal and have failed to compare neurosyphilis in patients with HIV infection with an uninfected control group. This study was performed to determine if the clinical presentation encountered is different in the presence of HIV infection. DESIGN: A retrospective, hospital-based, case series study based on chart review encompassing a 64-month period. SETTING: The study was performed in a large, university-affiliated, public health trust hospital in south Florida. PATIENTS: Forty-six hospitalized patients with neurosyphilis were identified; 13 patients fulfilled Centers for Disease Control and Prevention (Atlanta, Ga) criteria for acquired immunodeficiency syndrome (AIDS), 11 were HIV seropositive only, and 22 were HIV uninfected. Neurosyphilis was determined by a reactive cerebrospinal fluid VDRL slide test. RESULTS: The HIV-infected patients (both AIDS and HIV-seropositive groups) were younger and more frequently had features of secondary syphilis, such as rash, fever, adenopathy, headache, or meningismus. Significant differences were observed in cerebrospinal fluid measurements when the HIV-infected group was compared with the HIV-uninfected group, including a higher mean white blood cell count in patients with AIDS and a higher mean protein level and a lower mean glucose level in the HIV-infected group. Syphilitic meningitis was more common in HIV-seropositive patients, although the HIV-uninfected patients presented with a greater variety of types of neurosyphilis. Ophthalmic syphilis was observed more frequently in the HIV-infected group. CONCLUSIONS: Significant differences exist between neurosyphilis occurring in the presence and absence of HIV infection.

Adult↗

Clinical significance of cerebrospinal fluid tests for neurosyphilis.

From 1978 to 1987, 1,665 cerebrospinal fluid (CSF) fluorescent treponemal antibody absorption (CSF-FTA-ABS) tests were performed as the screening procedure for neurosyphilis. The CSF samples from 48 patients were reactive, and the medical history and results of the CSF-Venereal Disease Research Laboratory test (CSF-VDRL) for syphilis for 38 of these patients were reviewed. Likely active neurosyphilis was diagnosed if the patient had a reactive CSF-FTA-ABS test, recent onset of neurological signs consistent with neurosyphilis, abnormal CSF, and no other recognized cause for the neurological illness. Fifteen patients were so classified. Four had a reactive CSF-VDRL test. The specificity of the CSF-VDRL in diagnosing likely active neurosyphilis was 100%, but the sensitivity was only 27%. The insensitivity of the CSF-VDRL test limits its usefulness as a screening test for neurosyphilis. The CSF-FTA-ABS test appears more sensitive for screening but is less specific than the CSF-VDRL test in distinguishing currently active neurosyphilis from past syphilis. These findings imply that clinical judgment is still essential in establishing the diagnosis of active neurosyphilis.

Adolescent↗

Intrathecal IgA synthesis in neurosyphilis.

Neurosyphilis can develop during any stage of syphilis. It has recently been reported that cerebrospinal fluid (CSF) data from patients with parenchymal or meningovascular neurosyphilis all show the absence of IgA synthesis and occasionally a concomitant IgM synthesis. In this context, it has been stated that intrathecal IgA synthesis contradicts the diagnosis of neurosyphilis. In our CSF analysis of four patients with definite neurosyphilis we observed an intrathecal synthesis of IgA, IgG and IgM in two patients. Our data are consistent with data of other studies suggesting that about 50% of patients with neurosyphilis show intrathecal synthesis of IgA. Therefore, intrathecal synthesis of IgA does not necessarily contradict the diagnosis of neurosyphilis. We hypothesize that intrathecal synthesis of IgA does not necessarily serve as a discriminating feature between neurosyphilis and other inflammatory central nervous system (CNS) disorders and that other laboratory parameters and the clinical picture have to be taken into account as well.

Adult↗

Posterior segment manifestations of active ocular syphilis, their response to a neurosyphilis regimen of penicillin therapy, and the influence of human immunodeficiency virus status on response.

OBJECTIVE: To determine the relative frequencies of signs in posterior segment ocular syphilis, the response to a neurosyphilis regimen of penicillin, and differences in findings between human immunodeficiency virus (HIV)-coinfected and -noncoinfected patients in a community setting. DESIGN: Retrospective, noncomparative, consecutive case series. PARTICIPANTS: Fourteen consecutive patients with posterior segment ocular syphilis over a 14-year period within or during the acquired immune deficiency syndrome era. INTERVENTION: Neurosyphilis intravenous penicillin regimen. MAIN OUTCOME MEASURES: Initial and final visual acuity; treponemal and nontreponemal serologic analyses; cerebrospinal fluid cell count, protein, and Venereal Disease Research Laboratory analyses; posterior segment signs; and relapses and recurrences. RESULTS: Blacks and males were predominantly affected. Five (36%) of patients were HIV coinfected, and ocular syphilis led to the HIV infection diagnosis in three. Four (29%) patients had received previous antibiotic therapy for primary or secondary syphilis, raising the suspicion of relapse. Two patients had negative nontreponemal serologic results. All patients responded rapidly to neurosyphilis therapy. One patient subsequently relapsed after neurosyphilis therapy, and a second was reinfected with recurrence of ocular involvement. One previously undescribed retinal manifestation was discovered: a sectorial retinochoroiditis with delayed retinal circulation in the involved area. CONCLUSIONS: Ocular syphilis is a form of neurosyphilis and requires neurosyphilis therapy regardless of when it develops after primary infection. Conventional syphilis staging is of little use in understanding ocular syphilis. A high suspicion for this diagnosis is appropriate, especially in poorer black males with posterior segment inflammatory disease. Human immunodeficiency virus coinfection with ocular syphilis is common, but does not affect response to a neurosyphilis regimen of penicillin in the short term. Awareness of the multiple presentations of posterior segment ocular syphilis will aid ophthalmologists in averting misdiagnosis or delayed diagnosis.

Acquired Immunodeficiency Syndrome↗

Finding neurosyphilis without the Venereal Disease Research Laboratory test.

BACKGROUND: The cerebrospinal fluid (CSF)-Venereal Disease Research Laboratory (VDRL) test is only 27% sensitive for diagnosing neurosyphilis. Discriminant analysis, used on 124 patients, shows that other commonly used laboratory tests can, in combination, identify 87% of patients with neurosyphilis with 94% specificity. STUDY DESIGN: The insensitivity of the CSF-VDRL (27% in persons with neurosyphilis) and the foreseen greater need to identify and treat neurosyphilis in the era of human immunodeficiency virus caused us to analyze the serum and cerebrospinal fluid results of 73 patients with syphilis and of 51 patients with clinically diagnosed neurosyphilis. Discriminant analysis was applied to different sets of laboratory tests to find the combination of test results best able to predict retrospectively the clinical diagnosis of syphilis or neurosyphilis, without reference to the CSF-VDRL. RESULTS: The predicting function averages 94% specificity and 87% sensitivity. Test result variables considered together are: CSF-FTA-ABS, serum FTA-ABS, CSF-TPHA, serum TPHA, and CSF cells. CONCLUSIONS: The authors conclude that clinicians or laboratories can, independently of the CSF-VDRL, compute a score showing whether the results of a set of commonly used tests suggest neurosyphilis in a patient.

Cardiolipins↗

Diagnosis of neurosyphilis: a critical assessment of current methods.

Clinical features of 74 patients with neurosyphilis and 38 syphilitic patients with nonsyphilitic neurologic disorders were correlated with results of their serum and cerebrospinal fluid (CSF) VDRL and FTA tests, and with the WBC count and total protein level in the CSF. The most common clinical features in those having neurosyphilis were reflex changes (53.9%), peripheral neuropathy (44.5%), ataxia (38%), and cranial nerve palsies (24.3%). In 27% of the patients with neurosyphilis the CSF was VDRL-reactive, while in 77% the CSF was FTA-reactive. The frequency of elevated WBC counts in various serologic categories ranged from 23% to 46%, and the frequency of elevated protein levels ranged from 23% to 27%; neither the mean WBC count nor the protein level differed significantly among the different serologic categories (P less than .05). Only two of the 74 patients with neurosyphilis had elevation of both the WBC and protein level. None of the syphilitic patients without neurosyphilis had an elevated WBC or protein level, though the CSF was FTA-reactive in all 38. Among the neurosyphilis patients whose CSF was VDRL-nonreactive but FTA-reactive, 21% had an elevated protein level and 26% had an elevated WBC count. These results support the view that patients having neurosyphilis will not necessarily have either VDRL-reactive CSF or the other expected CSF abnormalities.

Humans↗