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Determining the prevalence of neurosyphilis in a cohort co-infected with HIV.

A retrospective study of 767 HIV positive patients from a large urban public hospital, 238 of whom were co-infected with syphilis, was performed to determine the prevalence of neurosyphilis. A prevalence of 3% of neurosyphilis in the co-infected cohort was demonstrated. The 7 cases of neurosyphilis ascertained were of the early stage variety, with cranial nerve involvement the predominant focal deficit. Of the 5 cases presenting after initial diagnosis and treatment of syphilis, 4 were felt to be inadequately treated. An overall prevalence of 1% (7/767) was determined for the entire HIV(+) cohort. The majority of the cases of syphilis (90%) were characterized as latent syphilis. Based on these findings, the authors recommend routine CSF examination in all patients who are HIV positive and who present with latent syphilis. Treatment regimens should be maximized in an effort to reduce the prevalence of neurosyphilis in such a co-infected cohort.

Acquired Immunodeficiency Syndrome↗

Psychosis or simply a new manifestation of neurosyphilis?

The widespread use of antibiotics in recent years has caused a significant reduction in the incidence of neurosyphilis and changes in its clinical features. We present a case that initially presented as persistent headache and untreatable psychosis. Neurosyphilis was diagnosed during the clinical evaluation. Blood serum analyses for syphilis were positive for rapid plasma reagin titres, the Venereal Disease Research Laboratories test and fluorescent treponemal antibody absorption. A lumbar puncture was performed and cerebrospinal fluid analysis resulted in the diagnosis of neurosyphilis. The patient completed a 2-week course of treatment with aqueous crystalline penicillin G and his symptoms subsequently improved. We suggest that neurosyphilis should always be included in the differential diagnosis of untreatable psychosis.

Adult↗

Generalized periodic EEG activity in two cases of neurosyphilis.

Neurosyphilis is a recognized cause of epileptic seizures and cognitive impairment, but is not usually associated with the finding of generalized periodic activity in the EEG. We report two similar cases characterized by progressive cognitive impairment followed by partial complex seizures, in whom the EEG showed generalized periodic activity. Both cerebrospinal fluid and the response to penicillin therapy confirmed the diagnoses of neurosyphilis in the two cases. The finding of EEG generalized periodic activity in patients with cognitive or behavioral disorders is usually associated with Creutzfeldt-Jakob disease, although there are other conditions, some of them potentially reversible, which may also present this EEG abnormality. Neurosyphilis has tended not to be included among them, and our present findings support the importance of first ruling out neurosyphilis in those patients with cognitive or behavioral disorders associated with generalized periodic epileptiform discharges.

Adult↗

Neurosyphilis presenting as schizophrenialike psychosis.

OBJECTIVE: The authors present a 30-year-old pregnant and previously healthy woman with sudden onset of agitation, delusions, and frontal lobe dementia. Serum and cerebrospinal fluid findings revealed the presence of untreated syphilis. BACKGROUND: Neurosyphilis can present a variety of behavioral symptoms, including mania, depression, and psychosis. METHOD: A neuropsychiatric and neurologic workup was performed before the start of antibiotic treatment. The status of the patient was observed throughout the course of her hospital stay for 7 months. Additionally, a neuropsychological evaluation was administered before treatment, and 2 weeks and 4 months after treatment. RESULTS: After treatment of neurosyphilis, steady improvements were noted in psychotic and cognitive symptoms. By the end of 7 months, and after discontinuation of antipsychotic medication, no psychiatric symptoms were evident. CONCLUSIONS: This case emphasizes the importance of considering neurosyphilis in the differential diagnosis of acute psychosis. Furthermore, this case shows the dramatic improvement in psychiatric symptoms and cognitive dysfunction in response to the treatment of neurosyphilis.

Acute Disease↗

[Neurosyphilis: forms of presentation and clinical management].

INTRODUCTION AND AIMS: Neurosyphilis results from the infection of the central nervous system by Treponema pallidum. It causes diverse clinical pictures which are occasionally similar to other, better known neurological diseases. In this paper our aim is to offer a global clinical vision of this entity by reviewing the different forms it can take and its diagnostic and therapeutic management. DEVELOPMENT: The forms of presentation of neurosyphilis can be grouped in two categories: early (asymptomatic, meningeal and meningovascular neurosyphilis) and late (progressive general paralysis and tabes dorsalis). Other less important forms, such as gummas, ocular forms, syphilitic amyotrophy or hypoacusis, have also been described. Diagnosis is complex and is based on the study of the cerebrospinal fluid. Given the difficulty involved in performing an accurate diagnosis, different criteria have been developed in which T. pallidum serology plays a key role. The most effective treatment is penicillin, although on occasions it may have no effect and we therefore recommend clinical and fluid analysis follow ups. Lastly, we describe the changes in incidence and clinical presentation, and the complications that may arise in diagnosis when HIV carrying patients also suffer from this disease. CONCLUSIONS: Neurosyphilis is a disease that still occurs nowadays and, due to its clinical polymorphism, must be borne in mind as a differential diagnosis in a number of neurological and psychiatric illnesses. This, together with the fact the serological tests are difficult to interpret and its irregular response to the usual treatment, makes it difficult to manage and means that the neurologist must have a thorough knowledge of the disorder.

Anti-Bacterial Agents↗

Neurosyphilis in newly admitted psychiatric patients: three case reports.

BACKGROUND: Neurosyphilis, also known as "general paresis of the insane," at one time accounted for a large portion of admissions to state psychiatric facilities. With the introduction of antibiotics, neurosyphilis is now considered very rare. METHOD: Chart review was performed on patients diagnosed with neurosyphilis who were admitted to a state psychiatric hospital in Raleigh, N.C., during 2002. RESULTS: We identified 3 cases of confirmed neurosyphilis, representing 0.1% of adult admissions, diagnosed in newly admitted psychiatric patients. None of the patients were immunocompromised. Response to antibiotic treatment was poor. CONCLUSIONS: Given the increase in primary and secondary syphilis reported in the 1980s and early 1990s, routine screening of psychiatric patients for the presence of syphilis should be considered.

Comorbidity↗

Screening for syphilis and neurosyphilis in acute psychiatric admissions.

The value of blood screening for syphilis and cerebrospinal fluid (CSF) screening for neurosyphilis in acute psychiatric admissions is assessed. Of 1,296 patients, 248 (19%) had evidence of previous or current syphilis as shown by a positive Treponema pallidum haemagglutination test, and 68 (5.2%) had potentially treatable syphilis as shown by a positive Venereal Disease Research Laboratory (VDRL) titre. CSF examination was performed on 169 patients with a positive blood test. Seventeen (i.e. 1.3% of all patients included in the study) met our criteria for neurosyphilis. The best predictor for neurosyphilis was the presence of a reactive serum VDRL. However, it is recommended that all patients with a positive blood test and symptoms that could possibly be ascribed to neurosyphilis undergo CSF examination.

Adult↗

Neurosyphilis yesterday and today.

Ten years ago it might have been predicted that neurosyphilis would disappear, but this has not happened. It has altered in character so that almost all of the cases seen are meningovascular in type. Even with the acceleration of neurosyphilis that occurs with immunodeficiency it is unlikely that there will be a resurgence of tabes dorsalis, general paralysis of the insane (GPI) or gummatous involvement of the central nervous system. These entities are still reported as single cases in the literature and this is unlikely to change. Diagnostic vigilance is required in respect of meningovascular syphilis which presents in so many different guises, and it seems prudent to advocate that all patients admitted to hospital with a neurological or psychiatric disorder should have syphilis serology checked routinely, though it no longer seems necessary to perform the tests routinely on outpatients. Advances in serological testing have made the diagnosis of syphilis easier to establish, and further advances in the diagnosis of neurosyphilis are likely with the perfection of techniques to culture treponemes in the cerebrospinal fluid (CSF) or the detection of surface antigens in the CSF. Although syphilis remains a treatable disease the impact of AIDS has necessitated modifications to the treatment regime. It is now recommended that patients who are HIV-positive and who have early syphilis should be treated as for neurosyphilis, as the former regime for treating primary syphilis may not be adequate.

Acquired Immunodeficiency Syndrome↗

Neurosyphilis and ocular syphilis in patients with concurrent human immunodeficiency virus infection.

Epidemiologic studies have demonstrated a strong association between human immunodeficiency virus (HIV) and syphilitic infection. Recent reports have suggested that concurrent HIV and luetic infection may lead to an accelerated and more fulminant course of syphilis. Specifically, neurosyphilis is encountered much earlier in such patients. We report two cases in which both neurosyphilis and ocular syphilis were present in HIV sero-positive patients. A review of the literature reveals that 11 of 13 (85%) HIV-infected patients with ophthalmic syphilis also had neurosyphilis. In patients who present with signs of ocular inflammation and pose a diagnostic dilemma, syphilis and possible concurrent HIV infection merit strong consideration. We wish to emphasize that patients should be evaluated for the presence of neurosyphilis if co-infection exists. Ophthalmologists should be aware that neuro-ophthalmic lues may prove to be the presenting feature of infection with HIV.

Adult↗

Neurosyphilis in HIV-positive and HIV-negative patients: neuroimaging findings.

PURPOSE: To evaluate and describe the neuroimaging findings of patients with neurosyphilis. METHODS: The neuroimaging studies of 35 patients with documented neurosyphilis were reviewed. Diagnosis was established in 34 patients with cerebrospinal fluid for a Venereal Disease Research Laboratory test, complemented by autopsy in 1 and brain biopsy in 1. All patients had reactive fluorescent treponemal antibody tests with absorption in their sera. Imaging studies included plain and contrast-enhanced CT of the brain, plain and gadolinium-enhanced MR, MR angiography, and conventional angiography. Imaging findings were also correlated with the relevant pathologic findings at autopsy in three additional patients with neurosyphilis who did not have brain imaging studies. RESULTS: Of the 35 patients with imaging studies, 32 tested human immunodeficiency virus (HIV)-seropositive, and 3 were HIV-seronegative. Eleven (31%) of 35 patients had normal radiographic findings. Cerebral infarctions were seen in 8 (23%) of 35 patients, and nonspecific white matter lesions in 7 (20%) of 35. Cerebral gummas and extraaxial enhancement indicating meningitis were noted in 2 (6%) of 35 patients, respectively. Arteritis was demonstrated in 2 (50%) of 4 patients who underwent either MR angiography or conventional angiography. The 3 subjects who had autopsy but not imaging studies were found to have manifestations of meningovascular syphilis, including syphilitic leptomeningitis and an obliterative endarteritis. CONCLUSION: We conclude that findings of vascular occlusive disease manifested as infarction or arteritis, enhancing cortical lesions with or without adjacent meningeal enhancement, focal or diffuse extraaxial enhancement, and white matter disease, although nonspecific, in the proper clinical setting should prompt appropriate testing for neurosyphilis, a treatable disease, in patients with and without HIV infection.

AIDS Dementia Complex↗

Neurosyphilis.

Central nervous system invasion by Treponema pallidum, the causative agent of syphilis, occurs in many, if not most, patients with syphilis. Laboratory findings from untreated asymptomatic syphilis patients with abnormalities of cerebrospinal fluid are termed asymptomatic neurosyphilis and represent a group that has an increased risk for developing clinical neurosyphilis syndromes. Clinical neurosyphilis syndromes, which occur in a minority of patients, may become apparent at any time in the natural history of untreated disease and often cause serious morbidity for individuals who develop them. Because there is no single sensitive and highly specific test for neurosyphilis diagnosis, clinicians must approach this important syndrome using a combination of clinical and laboratory data and a firm understanding of the disease.

HIV Infections↗

Neurosyphilis in human immunodeficiency virus type 1-seropositive individuals. A prospective study.

The prevalence of neurosyphilis in human immunodeficiency virus type 1 (HIV-1)-seropositive (HIV+) persons was assessed during the course of a study of the neurological complications of HIV-1 infection. One hundred sixty-six asymptomatic HIV+ subjects, 63 neurologically symptomatic HIV+ subjects, and six at-risk HIV-1-seronegative (HIV-) control subjects underwent cerebrospinal fluid (CSF) analysis on entry into this longitudinal study. Three (1.8%) of the asymptomatic HIV+ subjects had both a reactive CSF VDRL test and a reactive CSF fluorescent treponemal antibody-absorption (FTA-ABS) test. Two of these three subjects had a history of appropriately treated early syphilis, and all had a reactive serum rapid plasma reagin test. Of the 63 neurologically symptomatic HIV+ subjects, one patient with dementia had both a reactive CSF VDRL test and a fluorescent treponemal antibody-absorption test. Subjective improvement in cognitive skills followed high-dose, intravenous penicillin therapy. Another subject had a penicillin-responsive myelopathy accompanied by a reactive CSF fluorescent treponemal antibody-absorption test result, but a nonreactive CSF VDRL. Unsuspected neurosyphilis is relatively common in our population of asymptomatic HIV+ subjects and may be responsible for neurological disease in a significant minority of neurologically symptomatic HIV+ persons. Cerebrospinal fluid examination should be performed in all HIV+ persons with a history of syphilis or serological evidence of syphilis, regardless of prior treatment. Additionally, neurosyphilis should be considered in the differential diagnosis of neurological disease in any HIV+ person.

Adult↗

Relationship between neurological features and intrathecal synthesis of IgG antibodies to Treponema pallidum in untreated and treated human neurosyphilis.

In syphilitic patients with or without CNS involvement the correlation of Treponema-specific IgG titre per milligram total IgG in CSF and serum (ITPA index) is a dependable source of information on the synthesis of treponemal IgG antibodies in the CNS. This index also provides a more reliable definition of asymptomatic neurosyphilis. Further, a discrimination between Treponema-specific and Treponema-non-specific IgG synthesis in the CNS is possible. Of 261 patients with clinical symptoms of neurosyphilis, 82% had a local production of treponemal IgG antibodies as shown by an elevated ITPA index. In patients with neurosyphilis and intrathecal synthesis of Treponema-specific IgG antibodies, 94% had oligoclonal IgG in the CSF. Comparison of different CSF protein alteration groups in untreated and treated neurosyphilitic patients showed that early diagnosis (and early treatment) led to improvement of the impairment of the blood-CSF barrier and reduction of the immune reaction in the CNS. However, synthesis of treponemal IgG antibodies in the CNS could persist as a 'scar syndrome' even after adequately cured infection.

Antibody Formation↗

[Neurosyphilis and neuroborreliosis. Retrospective evaluation of 22 cases].

We present laboratory data from 22 patients suspected of having neurosyphilis. In two cases the suspicion could not be confirmed, and in 20 cases neurosyphilis was detected. The sera from 17 patients were also assayed for Borrelia-specific antibodies. Suspicious immunoglobulin G antibody indices were detected in nine cases and a suspicious immunoglobulin M antibody index in one. In six of these, stored CSF/serum pairs were available to specify the antibodies by immunoblotting. This allowed for the identification of one patient apparently infected by both Borrelia spp. and Treponema pallidum. In all cases of newly suspected neurosyphilis, we recommend considering neuroborreliosis at the same time.

Adult↗

Quaternary neurosyphilis in a Haitian man with human immunodeficiency virus infection.

A 22-year-old Haitian man had a 15-month course of progressive meningitis accompanied by multiple cerebral infarcts. Multiple areas of stenosis and occlusion in all branches of the circle of Willis, and hypertrophy of collateral perforating vessels at the base of the brain in a "puff of smoke" appearance typical of moyamoya disease were seen on cerebral angiogram 5 months before the patient died. At autopsy, the patient had meningovascular syphilis and a necrotizing encephalitis with massive treponemal invasion of the brain, the pathology of late-stage degenerative, "quaternary", neurosyphilis. The patient was also infected with human immunodeficiency virus (HIV). Retrovirus-like particles 100 nm in diameter with dense cores were seen by electron microscopy. Nucleic acid obtained from the patient's brain contained sequences homologous to HIV DNA as determined by dot blot hybridization. The moyamoya-like radiologic appearance of neurosyphilis has not been previously described. The autopsy finding of quaternary neurosyphilis in a patient with HIV infection supports the hypothesis that retrovirus may alter the natural history of syphilitic infection.

Acquired Immunodeficiency Syndrome↗

Cognitive change after treatment for neurosyphilis. Correlation with CSF laboratory measures.

The decision to re-treat a patient with neurosyphilis is usually based on the clinical response, cerebrospinal fluid (CSF), cell count, and CSF protein concentration. The value of the CSF Venereal Disease Research Laboratory (VDRL) test on its own as a marker for treatment response in neurosyphilis has not been established. To assess the usefulness of CSF markers for continuing infection, 12 patients with neurosyphilis were reevaluated 1 year after treatment. Change in cognitive functioning, as assessed by the Mini-mental State Examination (MMSE), was correlated with the CSF cell count, protein content, IgG index, and VDRL test titer at follow-up. A significant negative correlation was obtained between 1 year improvement in MMSE score and CSF VDRL titers at both the 6- and the 12-month follow-up examinations, and with the 6-month CSF protein concentration. These findings suggest that the CSF VDRL titer may be an indicator of continued Treponema pallidum activity in patients without obvious clinical deterioration.

Adult↗

Neurosyphilis and status epilepticus: case report and literature review.

We review the literature concerning the initial presentation of neurosyphilis in status epilepticus (SE) and provide an additional case of a 41-year-old male with no past medical history of seizures who presented in status epilepticus with subsequent laboratory confirmation of neurosyphilis. Neurosyphilis should be considered in the differential diagnosis of patients presenting with status epilepticus.

Adult↗

[Neurosyphilis: a rare cause of dementia].

INTRODUCTION: Neurosyphilis had to be evoked in the face of an atypical dementia. CASE RECORD: We describe the case of a 65-year-old man who presented with neurosyphilis suspected to precede behavioral and cognitive problems in the context of risky sexual behavior and was confirmed by serologic tests in the cerebrospinal fluid. DISCUSSION: This case proves the necessity to investigate the possibility of neurosyphilis in subjects with dementia syndrome which does not correspond to classic etiologies.

Aged↗