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Symptomatic neurosyphilis.

We observed 24 patients with symptomatic neurosyphilis. Of these 24 patients, nine had clinical manifestations of general paresis, seven tabetic neurosyphilis, five meningovascular neurosyphilis, one taboparetic, one tabomeningovascular, and one spinal neurosyphilis. Confusion, disorientation, lancinating pain, impaired memory, and bizarre behavior were the most prevalent symptoms. Sensitivity of the CSF FTA-ABS test was higher (96%) than that of the CSF VDRL test (79%). CSF cell count and total protein determination may be inadequate for assessing activity of neurosyphilis.

Adult↗

Diagnosis of neurosyphilis by examination of the cerebrospinal fluid.

Thirty-six patients with reactive results in the cerebrospinal fluid to the Treponema pallidum haemagglutination assay (CSF-TPHA) were investigated by further serological tests for confirmation of active neurosyphilis. The results of the TPHA and fluorescent treponemal antibody tests were reactive in all CSF samples from patients with acute untreated neurosyphilis and from most patients with late latent syphilis but no signs of involvement of the central nervous system. The demonstration of 19S-IgM antibodies against Treponema pallidum in the CSF was a better indication of activity of the disease than the Venereal Disease Research Laboratory test. Ten of 11 patients with untreated acute neurosyphilis had reactive results in the solid-phase haemadsorption test for CSF-IgM (CSF-IgM-SPHA test). The TPHA index, which relates the CSF-TPHA titre to the albumin quotient and thus excludes errors from disturbed function of the blood-brain barrier, was above 100 in all but one of the patients with acute neurosyphilis but below 100 after treatment. Patients with late latent syphilis and without CNS signs had TPHA indices below 5. Thus a nonreactive CSF-TPHA test result excludes neurosyphilis but reactive CSF-IgM-SPHA results and TPHA indices above 100 strongly indicative active disease.

Adult↗

Neurosyphilis: a changing diagnostic problem?

In the recent literature about neurosyphilis, several publications have mentioned more atypical presentations of neurosyphilis. Inadequate penicillin therapy and improved serological methods are supposed to be responsible for these findings. In contrast with this proposition the present retrospective study of two groups of neurosyphilitic patients (518 patients during the period 1930-1940 and 121 during 1970-1984) reveals no marked differences in clinical data of these groups. Besides the fall in incidence of syphilis and neurosyphilis and the shift in the male/female ratio, conforming to modern literature, there is an increase in the cases of asymptomatic neurosyphilis, due to development of the immunological techniques to detect the diagnosis 'neurosyphilis' earlier.

Adult↗

Significance of laboratory findings for the diagnosis of neurosyphilis.

Our objective is to assess the specificity and sensitivity, and thus elaborate the relevance, of different laboratory findings for the diagnosis of neurosyphilis. One hundred and fourteen HIV-negative pairs of serum and cerebrospinal fluid (CSF) samples were examined by the Venereal Disease Research Laboratory (VDRL) test, a fluorescent treponemal antibody-absorption (FTA-ABS) test, microhaemagglutination assay with Treponema pallidum antigen (MHA-TP) test (serum) and Treponema pallidum haemagglutination assay (TPHA) test (CSF); further, albumin, total protein, and total IgG were determined and, in the CSF, cell count was performed. The donors were 60 patients with active neurosyphilis and 54 healthy persons with a former history of syphilis and with persisting positive results in the T. pallidum haemagglutination tests (serum: MHA-TP, CSF: TPHA), who supplied specimens for control. Albumin quotient, IgG index, TPHA index, modified TPHA index, Intrathecally produced T. pallidum Antigen (ITpA) index, its 2 modifications and, in 12 samples, the adenovirus group antibody (AVGA)/TPHA index were ascertained. The specificity and sensitivity of the TPHA index were 100% and 98.3%, of the modified TPHA index 50.0% and 96.7%, of the ITpA index 42.6% and 90.0%, of the modified ITpA indices 51.8% and 68.3% (first modification) and 53.7% and 63.3% (second modification). The AVGA/TPHA index yielded a specificity of 91.7% (11/12). The CSF VDRL test was positive in 55/60 (91.7%) of samples from patients with neurosyphilis and in none of the controls (0/54). A CSF-TPHA titre greater than 1:320 was observed in 59/60 (98.3%) of the neurosyphilis specimens and in none of the controls (0/54). A TPHA index above an outcome of 70, a positive CSF-TPHA test at a titre greater than 1:320 and, with lower sensitivity, the criteria of the Centers for Disease Control (CDC) guidelines yield the most reliable results for laboratory support to a diagnosis of neurosyphilis. The modified TPHA index, the ITpA index, and its 2 modifications produce results of minor sensitivity and poor specificity. Observations on the AVGA/THPA index are too limited yet for judgement. The diagnostic significance of a CSF-TPHA titre above 320 needs further confirmation on a greater number of observations made by different laboratories.

Adult↗

Neurosyphilis in a young adult: very early tertiary syphilis?

A rare episode of early neurosyphilis occurred in a 34-year-old, otherwise healthy, woman. Based on an isolated positive Borrelia burgdorferi serology (later interpreted as a cross-reaction), early ceftriaxone was initiated, in the suspect of Lyme borreliosis. Even after the diagnosis was corrected into that of a neurosyphilis, ceftriaxone administration was continued, until it achieved complete clinical and microbiological success after 24 days of treatment in a day-hospital setting, and three-weekly penicillin administrations. When considering the differential diagnosis, a luetic aetiology should not be underestimated when facing young patients with signs-symptoms of a meningoencephalitis. Our case report was characterized by an extremely low patient's age, compared with the occurrence of tertiary neurosyphilis, more than three years after the last sexual contacts. The diagnosis was confirmed by highly positive treponemal and non-treponemal serum and cerebrospinal fluid serology, and several suggestive clinical manifestations: seizures, altered mentation, cognitive impairment, lip drop, and anisochoria. These concomitant findings, together with a neuroradiological report indicating a diffuse meningoencephalitis, allowed us to confirm the diagnosis of neurosyphilis, together with a demonstrated cross-reaction of B. burgdorferi serology. Although ceftriaxone benefits from its once-daily administration (and can be easily delivered on outpatient basis), it is not the firstline treatment of neurosyphilis. However, our experience demonstrated a favourable and rapid response to ceftriaxone, in the absence of toxicity and disease sequelae.

Adult↗

[Clinical characteristics and therapy of neurosyphilis in patients who are negative for human immunodeficiency virus].

INTRODUCTION: Neurosyphilis is still a significant medical problem in developing countries and its occurrence in HIV infection is the reason for a growing number of new cases in developed countries [1-4]. Personality changes are the commonest symptom of late neurosyphilis [5]. Neurologic deficits are usually due to syphilitic vasculitis with lacunar infarctions [6]. The laboratory confirmation of neurosyphilis must depend on a cluster of tests (Venereal Disease Research Laboratories--VDRL; Fluorescent Treponemal Antibody-Absorption--FTA-ABS; Treponema Pallidum Immobilization--TPI or Nelson-Mayer). The diagnosis of active neurosyphilis also requires an inflammatory cerebrospinal fluid (CSF) test [4]. METHODS: A retrospective study of hospitalized neurosyphilitic patients at the Institute of Neurology, Belgrade, Serbia, was carried out. Between 1990 and 1996 seven cases were found: five males and two females, aged from 22 to 66 years, mean 56 years. All were in tertiary stage and HIV negative. None of them reported previous veneral disease and only one reported meningitis. In all patients neurological examination, VDRL and TPI in blood and CSF, CT or MRI of the brain, Mini Mental State (MMS) test [11] and psychiatric evaluation were performed. To patients with active disease 24 million units of crystalline penicillin were administered, in divided daily doses in continuous intravenous infusions for three weeks. RESULTS: Symptoms. Five patients (71%) had gait disturbances, four (57%) headache, three (43%) hearing loss, speech complaints, forgetfulness, mood changes, and two (29%) seizures and stroke-like episodes. Malaise, diplopia, visual loss, vertigo, loss of sphincter control and paresthesia were noticed in one patient (14%). Neurologic findings. Five patients (71%) had pupillary changes. In four (57%) of them we found hemiparesis, gait disturbances and signs of cerebellar involvement, in three (43%) hearing loss, dysarthria, paraparesis, hypesthesia for light touch, mood disorders (depression in two, hypomania in one), mild cognitive decline and tremor of the tongue and hands. Lesion of the second and the sixth cranial nerve, position sense and positive release signs were recorded in one patient (14%). Gonarthrotic changes were observed in two (29%) patients. Cerebrospinal fluid. Elevated cell count and high protein level were detected in four (57%) patients. Three had also positive oligoclonal bands. Serological tests. In six patients (86%) serological tests for syphilis were positive (VDRL and/or Nelson-Mayer Test) in serum and in three (43%) in CSF. Results in one patient were negative both regarding serum and CSF, as he was treated for secondary syphilis in his twenties (now 65 years old) presumably as a "burnt out" case with neurologic sequelae. Neuroimaging. CT and MRI of the brain showed cortical and subcortical reduction in the brain parenchyma in four (57%) and multiischaemic changes in two (29%) patients. Therapy. Crystalline penicillin was administered to five patients with no side effects. Improvement of mood and cognitive status were noted in three patients, improvement of neurologic status in two subjects and arrest of progression in two patients. DISCUSSION: None of our patients reported previous venereal disease. They complained of impaired gait, headache, hearing loss, speech difficulties, forgetfulness, and mood changes. Pupillary changes, hemiparesis, gait disturbances and cerebellar signs, hearing loss, dysarthria, paraparesis, hypesthesia, mood disorders, mild cognitive decline and tremor of the tongue and hands were found during the examination. Pupillary signs are the most important symptoms because they can point to neurosyphilis. A two-step approach is recommended for establishing the diagnosis of syphilis with simple nontreponemal tests for screening purpose, and specific treponemal tests for its confirmation [21]. In our patients all but one were positive for syphilis in serum-tests and/or CSF. (ABS

Adult↗

Pitfalls in cerebrospinal fluid test for the diagnosis of neurosyphilis.

OBJECTIVE: To determine the usefulness of cerebrospinal fluid tests in the diagnosis of neurosyphilis. METHODS: Two hundred and seven cerebrospinal fluid-Venereal Disease Research Laboratories tests were performed at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia between 1992 and 1997. The records of 14 cases with progressive neurological disease and reactive serum fluorescent treponemal absorbent antibodies or treponemal pallidum hemagglutination test were reviewed for clinical presentation, cerebrospinal fluid analysis and Venereal Disease Research Laboratories, neuro-imaging abnormalities and compatibility with the diagnosis of neurosyphilis. The diagnosis of neurosyphilis was made if the patient had reactive serum fluorescent treponemal absorbent antibodies or treponemal pallidum hemagglutination, history of progressive neurological disease and increased cerebrospinal fluid cells or protein. RESULTS: None of the 207 cerebrospinal fluid-Venereal Disease Research Laboratories tests were reactive. The diagnosis of neurosyphilis was made in 10 out of 14 cases with progressive neurological disease and reactive serum rapid plasma reagin, fluorescent treponemal absorbent antibodies and treponemal pallidum hemagglutination. CONCLUSION: We conclude that if reactive cerebrospinal fluid-Venereal Disease Research Laboratories is required to confirm or diagnose neurosyphilis, most cases will be overlooked.

Cerebrospinal Fluid Proteins↗

[Diagnosis and forensic-psychiatric expert opinion in neurosyphilis].

Having examined 77 patients with neurosyphilis the authors diagnosed early neurosyphilis (chronic cerebrospinal syphilitic meningitis and cerebrospinal syphilis) in 22 patients and late neurosyphilis (tabes dorsalis) in 55 patients. Early neurosyphilis was characterized by affective volitional, asthenic, and hypochondriac disorders, whereas late neurosyphilis was manifested in neurosis-like disturbances, partial and total dementia and hallucinational paranoid syndrome. The main principles of forensic psychiatric medical examination of this group of patients are outlined.

Adult↗

Modern neurosyphilis: a partially treated chronic meningitis.

Approximately 5,000 new cases of neurosyphilis may occur in the United States each year. General paresis and tabes dorsalis, however, have become relatively rare since the introduction of penicillin. Seizures, neuro-ophthalmologic symptoms, stroke and acute meningoencephalitis are currently the most common manifestations of neurosyphilis. In more than a third of patients with neurosyphilis, nontreponemal tests for syphilis (such as VDRL) are negative and should not be used to exclude the diagnosis. Specific treponemal tests are more sensitive and more specific. Examination of the cerebrospinal fluid may show no abnormalities in neurosyphilis and is not an infallible guide to the activity of the infection. Penicillin is the only proven antibiotic treatment of neurosyphilis. However, low-dose regimens do not produce spirocheticidal concentrations in the brain, and high-dose penicillin therapy is recommended to insure eradication of the spirochetes. Doxycycline, a tetracycline derivation that achieves relatively high concentration in the brain, may also be effective.

Adolescent↗

Oligosymptomatic neurosyphilis with false negative CSF-VDRL in HIV-infected individuals?

The true prevalence of neurosyphilis in HIV-infection is unknown, since a sufficiently sensitive and specific test is lacking. In a prospective study we found reactive serum TPHA and FTA-ABS IgG tests in 95 (31%) of 307 HIV-infected patients. Three of 11 patients with latent syphilis revealed reactive CSF-VDRL tests, six others only demonstrated CSF abnormalities. Resolution of CSF abnormalities during a six month follow up after high dose antibiotic therapy led to the diagnosis of oligosymptomatic or asymptomatic neurosyphilis in all nine patients. Thus, the specificity of the CSF-VDRL was 100%, but the sensitivity was only 33%. The overall prevalence of neurosyphilis was 2.9%, increasing to 9.5% in patients with a reactive serum TPHA. Our study emphasizes the importance of antibiotic therapy for presumptive neurosyphilis in HIV-infected patients with latent syphilis and CSF abnormalities but nonreactive CSF-VDRL tests, even if they are neurologically asymptomatic or present with complaints inconclusive of neurosyphilis.

Adult↗

Neurosyphilis: A Current Review.

Neurosyphilis continues to be a difficult diagnosis for clinicians. The decision to perform a lumbar puncture, interpretation of cerebrospinal fluid findings, clear diagnostic guidelines, establishment of definitive therapy (including alternatives to penicillins), and approach to the follow-up of patients with neurosyphilis are all areas that pose ongoing challenges to clinicians. Coinfection with HIV has also further complicated the already challenging arena of neurosyphilis presentation, diagnosis, and management. Clinicians must recognize the recent changes in the epidemiology of syphilis and know when to initiate appropriate screening. This article highlights the limitations and controversies related to neurosyphilis diagnosis and treatment, and current recommendations on management of patients with neurosyphilis, including those coinfected with HIV.

Journal Article↗

Prevalence of neurosyphilis in human immunodeficiency virus-infected patients with latent syphilis.

PURPOSE: A prospective study was done to determine the prevalence of confirmed neurosyphilis (cerebrospinal fluid [CSF] Venereal Disease Research Laboratory [VDRL]-reactive) in human immunodeficiency virus (HIV)-infected patients with latent syphilis (reactive serum rapid plasma reagin [RPR] and microhemagglutination-Treponema pallidum [MHA-TP]). PATIENTS AND METHODS: All HIV-infected patients seen for their first visit at the Los Angeles County/University of Southern California Medical Center AIDS Clinic from June through December 1990 were screened for latent syphilis. Those with reactive serum RPRs and MHA-TPs who had not received recent (within 6 months) therapy for syphilis were offered diagnostic CSF sampling. RESULTS: A total of 312 patients were screened, of whom 71 (22.8%) had reactive serum RPRs and MHA-TPs. Thirty-three of these patients (47%) had diagnostic CSF sampling (26 refused lumbar puncture or were lost to follow-up; 12 had had recent therapy for syphilis and thus did not have CSF sampling). Among the 33 patients who had CSF sampling, 20 (60.6%) had normal CSF profiles (white blood cell count less than 8/mm3; protein less than 0.60 g/L; glucose greater than 2.8 mmol/L) and nonreactive CSF VDRLs. Ten of the 33 patients (30.3%) had abnormal CSF profiles and nonreactive CSF VDRLs, and three of 33 (9.1%) had reactive CSF VDRLs. CONCLUSIONS: Asymptomatic neurosyphilis was found in 9.1% of our patient population undergoing CSF sampling, giving a 1.0% prevalence of CSF VDRL-reactive neurosyphilis in the population we screened. The abnormal CSF findings may have been due to either nonreactive CSF VDRL neurosyphilis, central nervous system infection with HIV, or infection with some unrecognized agent.

Adult↗

A case of neurosyphilis showing a marked improvement of clinical symptoms and cerebral blood flow on single photon emission computed tomography with quantitative penicillin treatment.

A 31-year-old woman manifested significant emotional symptoms and personality change due to neurosyphilis; her clinical symptoms were improved with quantitative penicillin treatment. On admission, magnetic resonance imaging (MRI) showed no abnormal findings, while N-isopropyl-p-[123I] iodoamphetamine single photon emission computed tomography (123I-IMP SPECT) initially showed a remarkable increase in cerebral blood flow (CBF) in the cerebral cortex. This increase disappeared after improvement of the patient's clinical symptoms with treatment. It appears that the increase in CBF might have reflected an active inflammatory state of neurosyphilis and that its disappearance might therefore represent successful treatment with penicillin for neurosyphilis. Our case study suggests that single photon emission computed tomography (SPECT) is a useful method for evaluating an inflammatory state and for assessing the effect of therapy on neurosyphilis.

Adult↗

Congenital neurosyphilis: a re-appraisal.

An investigation was undertaken to determine the presence and incidence of neurosyphilis in cases of congenital syphilis. Twenty infants, diagnosed as having congenital syphilis on the basis of a positive serum fluorescent-treponemal-antibody-absorbed immunoglobulin M (FTA-IgM) test, were studied. Eleven had clinical disease, while 3 had non-specific illnesses, but x-rays very suggestive of syphilis. Six were asymptomatic newborns, born of mothers known to have positive VDRL tests. There was no clinical evidence of neurosyphilis. The cerebrospinal fluid (CSF) was definitely abnormal in 2 babies, most likely abnormal in a third, and very doubtfully positive in 2 premature babies. The incidence of neurosyphilis in this series is much lower than that reported in the past. The problems of diagnosing neurosyphilis, and reasons for the low incidence here are discussed.

Diagnosis, Differential↗

A pilot study evaluating ceftriaxone and penicillin G as treatment agents for neurosyphilis in human immunodeficiency virus-infected individuals.

To compare intravenous (iv) ceftriaxone and penicillin G as therapy for neurosyphilis, blood and CSF were collected before and 14-26 weeks after therapy from 30 subjects infected with human immunodeficiency virus (HIV)-1 who had (1) rapid plasma reagin (RPR) test titers >/=1&rcolon;16, (2) reactive serum treponemal tests, and (3) either reactive CSF-Venereal Disease Research Laboratory (VDRL) tests or CSF abnormalities: (a) CSF WBC values >/=20/microL or (b) CSF protein values >/=50 mg/dL. At baseline, more ceftriaxone recipients had skin symptoms and signs (6 [43%] of 14 vs. 1 [6%] of 16; P=.03), and more penicillin recipients had a history of neurosyphilis (7 [44%] of 16 vs. 1 [7%] of 14; P=.04). There was no difference in the proportion of subjects in each group whose CSF measures improved. Significantly more ceftriaxone recipients had a decline in serum RPR titers (8 [80%] of 10 vs. 2 [13%] of 15; P=. 003), even after controlling for baseline RPR titer, skin symptoms and signs, or prior neurosyphilis were controlled for. Differences in the 2 groups limit comparisons between them. However, iv ceftriaxone may be an alternative to penicillin for treatment of HIV-infected patients with neurosyphilis and concomitant early syphilis.

Adult↗

Diagnosis of neurosyphilis in patients infected with human immunodeficiency virus type 1.

Establishing the diagnosis of neurosyphilis may be particularly difficult in human immunodeficiency virus type 1 (HIV)-infected persons. Polymerase chain reaction (PCR) was used to detect Treponema pallidum DNA in cerebrospinal fluid (CSF) from 81 HIV-infected patients. On the basis of reactive serum and CSF-VDRL tests, 2 patients were diagnosed as having neurosyphilis. T. pallidum DNA was not consistently detected in any sample, even when the CSF-VDRL was reactive. CSF pleocytosis, elevated protein, or depressed glucose concentration was not significantly associated with a history of exposure to or infection with T. pallidum. On the basis of results of routine CSF measurements and T. pallidum PCR results, no evidence was found for undiagnosed neurosyphilis in HIV-infected patients. T. pallidum DNA PCR on CSF did not provide more information than conventional CSF analysis. Further study is needed to determine the utility of this test in the diagnosis and treatment of neurosyphilis.

DNA, Bacterial↗

Detection by polymerase chain reaction of Treponema pallidum DNA in cerebrospinal fluid from neurosyphilis patients before and after antibiotic treatment.

A polymerase chain reaction with nested primer pairs based on the DNA sequence of the 39-kDa bmp gene of Treponema pallidum subsp. pallidum is described. The method allowed the detection of purified T. pallidum DNA equivalent to the amount of DNA in a single bacterium and was specific for T. pallidum subspecies. After concentration of DNA, using diatomaceous earth, it was possible to detect about 100 treponemes in 1 ml of cerebrospinal fluid. Cerebrospinal fluid samples from a total of 29 symptomatic and asymptomatic patients with neurosyphilis were tested for the presence of treponemal DNA before and at various intervals after intravenous treatment with penicillin. Prior to the penicillin treatment, we detected T. pallidum DNA in 5 of 7 patients with acute symptomatic neurosyphilis, in none of the 4 patients with chronic symptomatic neurosyphilis tested before treatment, and in 2 of 16 patients with asymptomatic neurosyphilis. Unexpectedly, T. pallidum DNA was also often detected in cerebrospinal fluid long after intervenous treatment with penicillin, sometimes up to 3 years after therapy.

Base Sequence↗

A patient with neurosyphilis presenting as chorea.

Despite the marked decline in frequency of neurosyphilis over the past three decades in the United Kingdom, new cases continue to appear both sporadically and as a complication of HIV infection. There is clinical evidence that neurosyphilis is becoming less typical. We describe a case of neurosyphilis presenting predominantly with choreoathetosis and associated hemiparesis in an otherwise healthy, immunocompetent patient. Only six cases of neurosyphilis presenting with features of basal ganglia damage have been reported in the recent literature, five of whom had HIV infection.

Athetosis↗