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PubMed2004

Neurosyphilis in the modern era.

OBJECTIVE: To review the nature of the presentation of neurosyphilis, the value of diagnostic tests, and the classification of the disease. METHODS: A retrospective review was carried out of the records of patients who had been identified as possible cases of neurosyphilis by a positive FTA-abs test in the CSF. The review extended over 10 years at a single hospital which served a population of mixed ancestry in a defined catchment area in the Western Cape province of South Africa. Patients were placed in predefined diagnostic categories, and clinical, radiological, and laboratory features were assessed. RESULTS: 161 patients met diagnostic criteria for neurosyphilis: 82 presented with combinations of delirium and dementia and other neuropsychiatric conditions, and the remainder had typical presentations such as stroke (24), spinal cord disease (15), and seizures (14). The average age of presentation ranged from 35.9 to 42.6 years in the different categories of neurosyphilis. Of those followed up, 77% had residual deficits from their initial illness. Cerebrospinal fluid (CSF) VDRL was positive in 73% of cases. CONCLUSIONS: The diagnosis of neurosyphilis can be made with reasonable certainty if there is an appropriate neuropsychiatric syndrome associated with a positive CSF VDRL. If the 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. Tabes dorsalis has become uncommon, but this is likely to be the only manifestation of neurosyphilis that has been altered during the antibiotic era.

Adolescent↗
PubMed1986

Inappropriate use of the cerebrospinal fluid Venereal Disease Research Laboratory (VDRL) test to exclude neurosyphilis.

Only 3 of 2536 cerebrospinal fluid (CSF) VDRL tests ordered at the Johns Hopkins Hospital in 1980 were positive. Of patients on whom the test was ordered, 226 had a positive or borderline serum fluorescent treponemal antibody absorption test. Records from 156 (69%) of these patients, including all 3 with positive CSF-VDRL tests, were reviewed and showed that the diagnosis of neurosyphilis had been considered only in 44 (28%). One third of records lacked notations of historical and physical findings characteristic of neurosyphilis. Forty seropositive patients who had lumbar puncture to rule out asymptomatic neurosyphilis had negative CSF-VDRL tests; none had neurosyphilis diagnosed. Use of the CSF-VDRL test seemed to represent predominantly "box-checking" on the requisition to rule out neurosyphilis. Yet the test performs better when "ruling in" rather than ruling out neurosyphilis. The Centers for Disease Control should reevaluate its recommendation to rule out neurosyphilis in asymptomatic patients with untreated syphilis of greater than 1 year's duration, given the costs, risks, and dubious benefits.

Antibodies, Bacterial↗
PubMed2006

Treatment of neurosyphilis.

In 2001, the incidence of primary and secondary syphilis increased in the United States for the first time in a decade. Increasing rates of early syphilis among men who have sex with men have been reported in many American cities, with similar outbreaks noted in Canada and Europe. In San Francisco, the increase has been particularly sharp and accompanied by an increase in the incidence of neurosyphilis. Early neurosyphilis develops within weeks to years of primary infection and primarily involves the meninges. Syndromes include syphilitic meningitis (often accompanied by cranial neuropathies), meningovascular syphilis (with associated ischemic stroke), or asymptomatic neurosyphilis. Late neurosyphilis occurs years to decades after exposure as cerebral or spinal gummatous disease or the classic parenchymal forms affecting the brain (general paresis or syphilitic encephalitis) or spinal cord and nerve roots (tabes dorsalis). 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 suboptimal sensitivity and specificity of these tests complicate diagnosis, particularly among patients coinfected with HIV. CSF examination should be performed to evaluate for neurosyphilis in all patients with positive serum syphilis serology and neurologic, ophthalmic, or tertiary disease, or in those who have failed therapy, and in HIV-infected patients with late latent syphilis or syphilis of unknown duration. Intravenous penicillin G is the recommended treatment for all forms of neurosyphilis and for syphilitic eye disease. An outpatient alternative, if adherence can be assured, is intramuscular benzathine penicillin with oral probenecid. Newer drugs that penetrate CSF, such as ceftriaxone or azithromycin, have not yet been adequately tested for neurosyphilis. Syphilis facilitates transmission of HIV (and vice versa), and thus all patients diagnosed with syphilis should be offered HIV testing.

Journal Article↗
PubMed2006

Evaluation of the Treponema pallidum particle agglutination technique (TP.PA) in the diagnosis of neurosyphilis.

The Treponema pallidum particle agglutination technique (TP.PA) was evaluated, in comparison with the Venereal Disease Research Laboratory (VDRL) test, microhemagglutination assay for Treponema pallidum antibodies (MHA-TP), and fluorescent treponemal antibody-ABS (FTA-Abs) test for the diagnosis of neurosyphilis. We have studied 198 cerebrospinal fluid (CSF) samples from patients with syphilis, including neurosyphilis, treated syphilis, and with other neurological manifestations than neurosyphilis. All tests were nonreactive in these last group of patients. In the neurosyphilis patients, sensitivity of the TP.PA was 100%. The performance of this test in CSF from patients with primary syphilis was as good as that of the other tests. In secondary and latent syphilis, the TP.PA results (27 reactive samples/73) were similar to those of the MHA-TP (25 reactive samples/73). In the individuals treated for syphilis, the TP.PA, FTA-Abs, and MHA-TP tests were found to be reactive in eight, six, and eight samples, respectively. In conclusion, it seems that the TP.PA can be used in CSF to diagnose neurosyphilis, although as for other serological tests, interpretation of results should be done in conjunction with other neurosyphilis parameters.

Agglutination Tests↗
PubMed1994

The response of symptomatic neurosyphilis to high-dose intravenous penicillin G in patients with human immunodeficiency virus infection.

BACKGROUND: Infection with the human immunodeficiency virus (HIV) may affect both the natural course of syphilis and the response to treatment. We examined the response to treatment with high-dose penicillin G in HIV-infected patients with symptomatic neurosyphilis. METHODS: Neurosyphilis was defined by reactivity in serum treponemal tests for syphilis, neurologic manifestations consistent with neurosyphilis, and a positive Venereal Disease Research Laboratory (VDRL) test on cerebrospinal fluid. We identified 11 HIV-infected patients with symptomatic neurosyphilis; 5 had been treated previously for early syphilis with penicillin G benzathine. Patients were treated with 18 million to 24 million units of penicillin G per day administered intravenously for 10 days. Cerebrospinal fluid was examined approximately 6 and 24 weeks after treatment, when the polymerase chain reaction and rabbit inoculation were used to detect Treponema pallidum. RESULTS: In four of the seven patients studied 24 weeks after treatment, the serum titers on rapid plasma reagin (RPR) testing decreased by at least two doubling dilutions, and four patients had reductions in the cerebrospinal fluid titers on VDRL testing or reverted to nonreactive results. In two patients there was no normalization or improvement in serum titers on RPR testing or cerebrospinal fluid titers on VDRL testing, cell counts, or protein concentrations. One patient relapsed with meningovascular syphilis six months after therapy. T. pallidum was detected by the polymerase chain reaction in cerebrospinal fluid from 3 of 10 patients before treatment, but in none of the 10 post-treatment specimens. CONCLUSIONS: In patients with early syphilis who are also infected with HIV, therapy with penicillin G benzathine may fail, and neurosyphilis may develop. The regimen of high-dose penicillin recommended for neurosyphilis is not consistently effective in patients infected with HIV.

Adult↗
PubMed1997

Diagnosis of neurosyphilis: appraisal of clinical caseload.

OBJECTIVES: To review the management of a cohort of patients with positive treponemal serology and psychiatric and/or neurological disorders. METHODS: A retrospective case note review of 172 patients with positive treponemal serology attending the Patrick Clement's Clinic, Central Middlesex Hospital between December 1990 and November 1995 was performed. RESULTS: 101 men and 71 women were new attenders diagnosed with positive treponemal serology. A neurological problem was identified in 27 patients (12 women and 15 men) with psychiatric and/or neurological disorders, of whom 20 (six women and 14 men) underwent investigation of the cerebrospinal fluid (CSF). With the medical history and results of CSF-RPR and FTA tests, white cell count (WCC), and total protein level in the CSF, 10 patients (eight men and two women) were diagnosed with likely neurosyphilis and 17 with neurological disorders not thought to be caused by syphilis. The clinical features in those having neurosyphilis were sensorineural hearing loss (n = 5) and tabes dorsalis (n = 5). In the seven patients diagnosed with neurosyphilis who underwent CSF examination one patient had a reactive CSF-FTA, elevated protein, and elevated WCC; one patient had a reactive CSF-FTA and RPR with elevated protein; the total protein only was elevated in three cases and the WCC elevated in one case. Nine of the 10 patients with neurosyphilis received adequate neurosyphilitic treatment; one patient was lost to follow up. CONCLUSIONS: The management of patients with positive treponemal serology and psychiatric and/or neurological disorders was consistent. Patients with suspected neurosyphilis or patients with neurological signs compatible with neurosyphilis (who did not undergo CSF examination) were treated with adequate neurosyphilitic therapy.

Adult↗
PubMed2004

Alternative cerebrospinal fluid tests to diagnose neurosyphilis in HIV-infected individuals.

OBJECTIVE: To identify alternatives to the CSF-Venereal Disease Research Laboratory (VDRL) test for the diagnosis of neurosyphilis in HIV-infected individuals. METHODS: CSF fluorescent treponemal antibody (FTA) reactivity and % CSF lymphocytes that were B cells in fresh and frozen samples were determined for 47 HIV-infected cases with syphilis and 26 HIV-infected controls. As for serum, CSF fluorescent treponemal antibody reactivity > or =2+ was considered positive. Based on the results in controls and cases with normal CSF measures, cut-offs for elevated CSF B cells were proposed to be > or =9% in fresh and > or =20% in frozen samples. Neurosyphilis was defined as a reactive CSF-VDRL. RESULTS: CSF-FTA-ABS (absorbed) and CSF-FTA (unabsorbed and undiluted) were 100% sensitive for the diagnosis of neurosyphilis. Elevated % CSF B cells in fresh and cryopreserved samples was specific (100%) but not sensitive (40 and 43%) in post hoc analyses. The results of CSF-FTA and assessment of % CSF B cells together allowed 16% of cases with pleocytosis but nonreactive CSF-VDRL to be diagnosed with neurosyphilis and 26% to be diagnosed as not having neurosyphilis. CONCLUSION: When the CSF-VDRL is nonreactive, CSF-FTA and % CSF B cells may help exclude or establish the diagnosis of neurosyphilis.

Absorption↗
PubMed1992

Neurosyphilis in HIV carriers: MR findings in six patients.

Neurosyphilis, a sexually transmitted disease that can cause neurologic damage, has become increasingly prevalent in the AIDS era. HIV carriers can contract neurosyphilis without the presence of other concurrent opportunistic infections. Because MR findings of neurosyphilis are seldom reported, we retrospectively reviewed and evaluated contrast-enhanced MR images of six young (average age, 33 years) HIV-positive men with high serum and CSF VDRL titers indicative of neurosyphilis. All six patients tested negative for concurrent opportunistic infections. Five patients had acute or subacute strokelike symptoms involving the basal ganglia or middle cerebral arteries; one had a parietal convexity mass mimicking meningioma with headache and ataxia. Contrast-enhanced MR images showed patchy enhancement involving the basal ganglia and middle cerebral artery territories in the first five patients and the convexity mass in the sixth patient. On the basis of brain biopsy, a convexity mass was diagnosed in the patient with syphilitic gumma. The imaging findings of the remaining five patients represented ischemic infarct caused by meningovascular syphilis. After penicillin treatment, serum and CSF VDRL titers decreased, and neurologic signs and symptoms improved in all six patients. A follow-up MR study in the patient with the gumma showed that the lesion resolved almost completely. In young HIV patients with stroke symptoms or a convexity mass, neurosyphilis should be considered. Contrast-enhanced MR can reveal the extent of involvement by neurosyphilis and should be used to facilitate diagnosis and proper treatment.

Adult↗
PubMedDate not supplied

[Diagnosis and biological monitoring of 6 neurosyphilis cases: value of cerebrospinal fluid analysis].

Our objective is to assess the relevance of the different laboratory findings in cerebrospinal fluid (CSF) and serum for the diagnosis and survey of active neurosyphilis. A retrospective study of six hospitalized neurosyphilitic patients at Neurological Hospital of Lyon from 1987 to 2002 was carried out. Six males were found, aged from 29 to 72 years. Neurosyphilis can be group in two categories: early (meningeal and meningovascular neurosyphilis) and late (progressive general paralysis and tabes dorsalis). All were tertiary stage and HIV negative. We performed in CSF, white and red cell count, cytology, total protein, glucose levels, in CSF and serum, albumin, total IgG, IgA, IgM for calculation of albumin quotient and IgG, IgA and IgM index. Serological tests for syphilis in CSF and serum are VDRL and TPHA. To increase the reliability of treponema antibody tests, the ratio of serum-to-CSF content of albumin is used to assess intrathecal production of treponema antibodies, especially the treponema pallidum hemagglutination assay (TPHA index). The CSF changes in neurosyphilis included elevated cell count with lymphocytic-plasmocytic cell reaction, increased protein content, strongly positive IgG index, numerous positive IgG oligoclonal bands, positive blood and CSF serology. Serological tests are difficult to interpret. Examination of CSF played a major role in the diagnosis and treatment of all forms of neurosyphilis. The CSF abnormalities improved with clinical improvement, especially in meningeal and vascular neurosyphilis, but the response in paresis and tabes was slower or nonexistent. Pleocytosis and protein are indicators of inflammatory activity in the central nervous system and are used as a clinical guide in the diagnostic, for treatment and re-treatment.

Adult↗
PubMedDate not supplied

[Neurosyphilis presenting the left total ophthalmoplegia: a case report].

We report a 73-year-old woman with meningitis-type neurosyphilis presenting the main symptom of the left total ophthalmoplegia. Three months after the appearance of the deviation of the eyeball to the inside and ptosis of the left eyelid, the left eyelid was completely closed. On admission, about four months after the appearance of neurosyphilis, she showed paralysis of the left oculomotor nerve, trochlearis nerve and abducens nerve, and the right mydriasis and absent light reflex. She was diagnosed as meningovascular neurosyphilis because syphilitic antibodies reactions in both serum and cerebrospinal fluid were highly positive. We treated her with intravenous infusion drop of penicillin G (eighteen-million units/day) for ten days, and those symptoms mentioned above other than light reflex were completely recovered. Bilateral internal carotid arteries situated close each other at the supraclinoid portion. The internal carotid arteries were not enhanced on Gd-MRI and the stenosis of the arteries were not detected on MRA. However, we suppose that the inflammation of meninges at that portion spreads to the bilateral internal carotid arteries, and that the III, IV and VI nerves close to the left internal carotid artery were damaged. There have been no reports of meningovascular neurosyphilis with the manifestation of unilateral ophthalmoplegia. In the patients of meningovascular neurosyphilis, however, various cranial nerve palsies can be appeared. Therefore we suggest that neurosyphilis should always be taken into consideration as differential diagnosis of cranial nerve palsies.

Aged↗
PubMed1989

Neurosyphilis in acquired immunodeficiency syndrome.

In a retrospective study encompassing 42 months (January 1984 through July 1987), 12 patients were identified as having both neurosyphilis and acquired immunodeficiency syndrome. These patients constituted 44% of the entire group meeting rigorous diagnostic criteria for neurosyphilis and 1.5% of all patients hospitalized with acquired immunodeficiency syndrome. The typical patient with acquired immunodeficiency syndrome and neurosyphilis was young (mean age, 37 years) and male (83%). All had serological evidence of syphilis in both blood and cerebrospinal fluid. Syphilitic eye disease was surprisingly common in this group, occurring in 5 (42%). Four patients (33%) had been previously treated for syphilis. In 2, treatment for latent syphilis had been completed 3 and 5 months, respectively, before neurosyphilis was documented. Neurosyphilis is not uncommon in patients with acquired immunodeficiency syndrome in our population. In light of its diverse manifestations, syphilis should be considered in the differential diagnosis of any human immunodeficiency virus type 1-infected individual presenting with neurological, psychiatric, or ophthalmological disease.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Somatosensory evoked potential in neurosyphilis.

Since the development of effective antibiotic therapy, the occurrence of neurosyphilis has become less frequent. The number of syphilitic patients is gradually increasing as a complication in acquired immunodeficiency syndrome, but the diagnosis of neurosyphilis sometimes is difficult. We describe six patients with neurosyphilis and an analysis of their tibial nerve somatosensory evoked potentials. Four of them, including two with no tabes dorsalis symptoms, had delayed P15-N21 or the absence of N21. These abnormalities were ameliorated by treatment for syphilis. Analysis of tibial nerve SEPs provides a useful tool for the diagnosis of neurosyphilis and the evaluation of the extent to which neurosyphilis has progressed.

Adult↗
PubMed1988

Central nervous system involvement in early and late syphilis: the problem of asymptomatic neurosyphilis.

Patients with syphilitic infections are at risk of development of symptomatic neurosyphilis. Adequate treatment with 2.4-7.2 x 10(6) units benzyl penicillin-G intramuscularly within 1 year after infection will rule out this risk. However, more than 1 year after infection this treatment is not fully reliable. In asymptomatic CNS involvement (asymptomatic neurosyphilis) only intravenous penicillin treatment is considered to be adequate in the prevention of neurosyphilis. In this study we redefined criteria for this condition by comparing serum and cerebrospinal fluid (CSF) samples of symptomatic neurosyphilitic patients with those of latent syphilitic patients without CNS involvement. Diagnostic criteria of the World Health Organization and of Centers of Disease Control for asymptomatic neurosyphilis (positive CSF Venereal Disease Research Laboratory (VDRL) test, combined with raised CSF cell count and/or protein content) were studied and compared with some newer parameters such as signs of intrathecal treponemal antibody production (Treponema pallidum haemagglutination assay and intrathecal Treponema pallidum assay index), immunoglobulin G (IgG) and M (IgM) index. The results of this study in 203 syphilitic patients revealed that either a positive CSF-VDRL or combination of a raised IgG and/or IgM index with an elevated CSF cell count both are useful criteria for "ruling-in" asymptomatic neurosyphilis.

Humans↗
PubMed1997

Psychiatric manifestations and magnetic resonance imaging in HIV-negative neurosyphilis.

Neurosyphilis can mimic virtually any psychiatric disorder. Since there are no studies measuring the relationship between its psychiatric manifestations and neuroradiological findings, we performed magnetic resonance imaging (MRI) on 20 newly diagnosed patients with neurosyphilis and 20 healthy volunteers. MRI abnormalities occurred in 13 neurosyphilis patients. These included foci of increased signal intensity of T2-weighted images, and generalized cerebral atrophy. Two control subjects showed minor focal changes. In the neurosyphilis patients, frontal lesions showed statistically significant associations with the overall degree of psychiatric morbidity as measured by the brief psychiatric rating scale (p < 0.05). Temporo-parietal lesions showed a near significant association with cognitive impairment as measured by the Mini mental-state examination (p = 0.06). Atrophy measures correlated significantly with cognitive impairment. The results suggest that the site of brain lesions may be important in determining the nature of the psychiatric symptoms in neurosyphilis.

Adult↗
PubMed1996

Comparison of intrathecal synthesis of Treponema pallidum-specific IgG antibodies and polymerase chain reaction for the diagnosis of neurosyphilis.

An indirect Treponema pallidum-IgG enzyme-linked immunosorbent assay (Tp-IgG-ELISA) was used for the estimation of intrathecal synthesis of specific IgG antibodies in patients with syphilis. Detection of T. pallidum DNA in cerebrospinal fluid (CSF) samples of syphilitic patients was performed by amplification of treponemal DNA, using the polymerase chain reaction (PCR). Both methods were compared as to their suitability for diagnosis of neurosyphilis in 37 patients with syphilis. Intrathecal synthesis of T. pallidum-specific IgG and PCR was negative in 16 patients with treated syphilis or untreated secondary syphilis. In contrast, an intrathecal IgG antibody production was found in all 21 patients with treated or untreated neurosyphilis. PCR was only positive in CSF samples from six out of ten patients with untreated neurosyphilis. The findings suggest that the intrathecal production of T. pallidum-specific IgG antibodies is an important indicator for the diagnosis of neurosyphilis. In addition, a positive result by PCR performed in CSF establishes a diagnosis of active neurosyphilis.

Antibodies, Bacterial↗
PubMed2006

Status epilepticus as an initial manifestation of neurosyphilis: a case report.

Seizures and focal neurologic deficits may be the complications of neurosyphilis, but status epilepticus as a presenting picture of neurosyphilis is rare. We describe a 41-year-old man with an acute onset of expressive dysphasia, followed by persistent seizure state and severe complications of systemic medical problems. An extensive laboratory evaluation confirmed the diagnosis of neurosyphilis and diabetes mellitus. Brain magnetic resonance imaging showed edematous change in the left cingulate gyrus, left temporal lobe, and peri-Rolandic area, which suggested an inflammatory process. Due to varied clinical manifestations of neurosyphilis, we underscore the importance of considering neurosyphilis among the possible causes of status epilepticus and any central nervous system diseases.

Adult↗
PubMed1987

Alteration in the natural history of neurosyphilis by concurrent infection with the human immunodeficiency virus.

Within the past 18 months, we have seen four cases of neurosyphilis at our institution (two of meningovascular syphilis, one of acute syphilitic meningitis, and one of asymptomatic neurosyphilis) in young homosexual men with serologic evidence of exposure to human immunodeficiency virus (HIV). Two of the four patients had neurosyphilis despite previous adequate therapy for early syphilis with benzathine penicillin. Meningovascular syphilis developed in one patient within four months after a primary infection, in a manner consistent with an accelerated course of syphilitic infection. These findings suggest the possibility that HIV infection may alter the natural course of syphilis because of the profound defects in cell-mediated immunity it causes. The possible potentiating effects of HIV on Treponema pallidum infection suggest the need for lumbar puncture in the evaluation of HIV-seropositive patients with syphilis, as well as modifications of the currently recommended treatment regimens for primary, secondary, and latent syphilis and neurosyphilis in this patient population. Neurosyphilis should probably be added to the growing list of infectious complications of the acquired immunodeficiency syndrome (AIDS) and may be the first such complication to appear.

Acquired Immunodeficiency Syndrome↗
PubMed2007

Cerebrospinal fluid tau protein is increased in neurosyphilis: a discrimination from syphilis without nervous system involvement?

OBJECTIVE: The objective of this study was to investigate the levels of tau protein in neurosyphilis. STUDY DESIGN: Total tau protein in the cerebrospinal fluid of 12 patients with neurosyphilis, 17 with syphilis without nervous system involvement, 14 controls, and 14 patients with Alzheimer disease of comparable age were analyzed. Double-sandwich enzyme-linked immunosorbent assay was used for measurements. RESULTS: Increased levels of cerebrospinal fluid total tau were observed in neurosyphilis (median [25th-75th percentile]: 349 pg/mL [312-429]) and in Alzheimer disease (543 [441-1017]) as compared with the controls (189 [106-220]) and syphilis without nervous system involvement (190 [160-223]). Using a cutoff level of 300 pg/mL, increased tau discriminated cases of neurosyphilis from syphilis without nervous system involvement with a sensitivity and specificity of 83% and 94%, respectively. CONCLUSIONS: These results indicate that increased total tau may be useful in the discrimination of neurosyphilis from syphilis without nervous system involvement.

Adult↗