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Syphilis is a sexually transmitted disease which incidence increased over the last 10 years in Switzerland. The clinical and neurocognitive manifestations observed in case of symptomatic neurosyphilis can be very heterogeneous and can mimic neurocognitive disorders of other origins. This article discusses the diagnostic and management pitfalls in an older patient whose diagnosis of neurosyphilis was initially suspected during a home visit., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Aim: Neurosyphilis patients exhibited significant expression of long noncoding RNA (lncRNA) in peripheral blood T lymphocytes. In this study, we further clarified the role of lncRNA- ENST00000421645 in the pathogenic mechanism of neurosyphilis. Methods: lncRNA- ENST00000421645 was transfected into Jurkat-E6-1 cells, namely lentivirus (Lv)-1645 cells. RNA pull-down assay, flow cytometry, RT-qPCR, ELISA (Neobioscience Technology Co Ltd, Shenzhen, China) and RNA immunoprecipitation chip assay were used to analyze the function of lncRNA- ENST00000421645 . Results: The expression of IFN-γ in Lv-1645 cells was significantly increased compared to that in Jurkat-E6-1 cells stimulated by phorbol-12-myristate-13-acetate (PMA). Then, it was suggested that lncRNA- ENST00000421645 interacts with PCM1 protein. Silencing PCM1 significantly increased the level of IFN-γ in Lv-1645 cells stimulated by PMA. Conclusion: This study revealed that lncRNA- ENST00000421645 mediates the production of IFN-γ by sponging PCM1 protein after PMA stimulation.

Neuroborreliosis (NB) and neurosyphilis (NS) are abnormal conditions caused by spirochetal bacteria which affect the nervous system. Diagnosis of neuroborreliosis and neurosyphilis is determined by clinical examination of visible symptoms, serum and cerebrospinal fluid (CSF) analysis, and serological detection of antibodies against Borrelia burgdorferi sensu lato and Treponema pallidum, respectively. Establishing a diagnosis may sometimes pose a number of diagnostic difficulties. A potential role of chemokine ligand 13 (CXCL13) as an accurate diagnostic biomarker of intrathecal inflammation has been suggested. In this review, we focused on changes in serum and cerebrospinal fluid concentration of chemokine ligand 13 in selected spirochetal neurological diseases neuroborreliosis and neurosyphilis reported in the available literature. We performed an extensive search of the literature relevant to our investigation via the MEDLINE/PubMed database. It has been proven that CXCL13 determination can provide rapid information regarding central nervous system inflammation in patients with selected spirochetosis. We described that neuroborreliosis and neurosyphilis are associated with an elevated CXCL13 concentration, mainly in the cerebrospinal fluid. Moreover, literature data suggest that CXCL13 determination is the most interesting additional marker for diagnosis and monitoring of neuroborreliosis and neurosyphilis thanks to its high sensitivity. Based on these published findings, we suggest that CXCL13 has high diagnostic utility and may be applied in laboratory diagnostics as a potential diagnostic marker in human spirochetal neurologic diseases.

Introduction: Syphilis is a systemic human disease which is caused by infection with the spirochete Treponema pallidum. It is spread worldwide, and there has recently been an increase in its incidence. Neurosyphilis (NS) can have a variety of presentations; meningovascular NS is a specific affection of the Treponema which occurs in an early stage after the primary infection, causing an inflammatory arteriopathy which may result in an ischemic stroke. As a rare manifestation of syphilis, there are few prevalence and epidemiological studies, and data are almost non-existent. The objective of this study is to analyse the prevalence of meningovascular NS in a stroke unit in a tertiary hospital., Methods: A descriptive retrospective study was carried out over a period of 44 months in a stroke unit. All patients admitted had neurological symptoms compatible with a vascular event, and routine blood tests including infectious screening were performed. Those with positive test results for syphilis were identified and proceeded to lumbar puncture to CSF cytochemical analysis and VDRL. NS was categorized as confirmed or probable (using CDC criteria)., Results: A total of 525 patients were admitted, and 62.53% were submitted to a routine screening for syphilis. A total of 309 patients (95.67%) revealed a negative screening; 12 patients (3.72%) had a positive syphilis serology. Among the 12 patients with positive screening, a single case of NS (0.31%) was identified., Conclusion: We observed a low prevalence of NS (0.31%), but this result was surprisingly higher than what was expected in an elderly population.

Frequency of Treponema pallidum invasion into cerebrospinal fluid (CSF) has not been clear at this present. Since it is impossible to culture T. pallidum in vitro at this present, we need molecular based-approach to detect it in CSF. Additionally, neurosyphilis is usually a late sequela, however it might result in asymptomatic neurosyphilis even at primary or secondary syphilis. This study was to reveal the frequency of T. pallidum invasion into CSF especially at primary or secondary syphilis with polymerase chain reaction (PCR) test. All patients were visited the Aichi Medical University Hospital or Izumi ladies' clinic between 2016 and 2017. Clinical CSF samples were collected from patients with early and late stages of syphilis. The PCR was done using primers targeting the tpN47gene. CSF samples were collected from 9 patients (4 patients with primary syphilis, 3 with secondary syphilis, and 1 early latent syphilis and 1 with late latent syphilis). PCR showed positive reaction in 2 of 7 (28.6%) primary and secondary syphilis patients, in 1 of 1 (100%) early latent syphilis patients, and in 1 of 1 (100%) late latent syphilis patients. Despite its lack of sensitivity for use alone as a diagnostic test, this PCR test should be preferred for the diagnosis of neurosyphilis. Because, T. pallidum was detected in the 28.6% CSF of patients at primary and secondary syphilis, which indicated that they invade the central nervous system from the early stages of infection. However, studies in a larger population are required to confirm these preliminary results., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: After a decade of constant decline, the number of syphilis cases has been steadily increasing since the 2000s, particularly in HIV infected patients. Neurosyphilis is a rare manifestation of this sexually transmitted disease for which we performed a retrospective study and analyzed clinical manifestations., Patients and Methods: We reviewed retrospectively all the neurosyphilis cases admitted to Strasbourg University Hospital between 2004 and 2014. We included and analyzed 13 patients admitted during this period who met the diagnostic criteria for neurosyphilis., Results: Nine of 13 patients had isolated visual manifestations; three (23.1%) experienced posterior uveitis, two (15.4%), panuveitis, and 4 (30.8%) had papillitis. Out of five patients (38.5%) who were HIV positive, three (60%) had a CD4 cell count above 400/mm 3 at the time of diagnosis of neurosyphilis. All patients received parenteral penicillin G or cephalosporin, and 5/13 (38.5%) received systemic corticotherapy., Conclusion: Ophthalmologists appear as key players in the identification, management and follow-up of neurosyphilis, since ocular findings are key diagnostic features in these patients., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Known predictors of neurosyphilis were mainly drawn from human immunodeficiency virus (HIV)-infected syphilis patients, which may not be applicable to HIV-negative populations as they have different characteristics, particularly those with neurological symptoms. This study aimed to identify novel predictors of HIV-negative symptomatic neurosyphilis (S-NS)., Methods: From June 2005 to June 2015, 370 HIV-negative syphilis patients with neurological symptoms were recruited, consisting of 191 S-NS patients (including 123 confirmed neurosyphilis and 68 probable neurosyphilis patients) and 179 syphilis/non-neurosyphilis (N-NS) patients. Clinical and laboratory characteristics of S-NS were compared with N-NS to identify factors predictive of S-NS. Serum rapid plasma reagin (RPR), Treponema pallidum particle agglutination (TPPA), and their parallel testing format for screening S-NS were evaluated., Results: The likelihood of S-NS was positively associated with the serum RPR and TPPA titers. The serum TPPA titers performed better than the serum RPR titers in screening S-NS. The optimal cut-off points to recognize S-NS were serum RPR titer ≥1:4 and serum TPPA titer ≥1:2560 respectively. A parallel testing format of a serum RPR titer ≥1:2 and serum TPPA titer ≥1:1280 screened out 95.8% of S-NS and all confirmed cases of neurosyphilis. S-NS was independently associated with male sex, serum RPR titer ≥1:4, serum TPPA titer ≥1:2560, and elevated serum creatine kinase. Concurrence of these factors increased the likelihood of S-NS., Conclusions: Quantitation of serum TPPA is worthwhile and performs better than serum RPR in screening S-NS. Serum RPR, serum TPPA, male sex, and serum creatine kinase can predict S-NS. Moreover, patients with both a serum RPR titer <1:2 and a serum TPPA titer <1:1280 have a low probability of S-NS, suggesting that it is reasonable to reduce lumbar punctures in such individuals.

Background: The nervous system is among the most frequent and serious targets of human immunodeficiency virus (HIV) infection. The infection usually occurs in patients with profound immunosuppression. In 10 - 20% of the patients, the presence of a neurological disease is the first manifestation of symptomatic HIV infection., Aims and Objective: Despite the wide prevalence of neurological manifestations in HIV, there is no study examining the clinical manifestations of this disease in the resource- limited communities from north-eastern parts of India. To characterize the neurological involvement in patients with HIV infection at a tertiary care institute in northeast India, we studied various neurological presentations of HIV., Setting and Design: This was a retrospective observational study done at a tertiary care institute in northeast India over a period of 6 years from August 2008 to September 2014., Material and Methods: A total of 91 HIV seropositive patients of both genders, aged >18 years, showing clinical evidence of central nervous system (CNS) involvement, and admitted in a tertiary care institute were included. Their clinical manifestations, laboratory investigations, and imaging were studied., Result: Tuberculous meningitis was the most common presentation as secondary CNS illness (43.9%), followed by cryptococcal meningitis (14.2%) and cerebrovascular accidents (5.49%). Furthermore, 6.59% had neurosyphilis, 6.59% had acquired immune deficiency syndrome (AIDS) - associated dementia, and peripheral neuropathy occurred in 16.4% of the patients. Headache was the most common neurological symptom seen in 25% of the patients. Seizures were noted in 25% of the pateints. CD4 was significantly low in most of the patients with progressive multifocal leukoencephalopathy, HIV associated encephalopathy (HAD) and cryptococcal meningitis compared with other neurological manifestations. CD4 counts in tuberculous meningitis and HAD were 110.3/μl and 95/μl, respectively., Conclusion: CNS tuberculosis was the most common secondary infection seen in HIV patients followed by cryptococcal meningitis. A high index of clinical suspicion of neurological involvement in HIV patients helps in the early diagnosis and early institution of specific treatment, which in turn decreases the morbidity and mortality considerably.

Purpose of Review: This article reviews the etiology, clinical manifestations, diagnosis, and treatment of neurosyphilis, with a focus on issues of particular relevance to neurologists., Recent Findings: The number of cases of infectious syphilis in the United States has steadily increased since 2000. The highest rates are among men who have sex with men, and approximately half of these individuals are infected with human immunodeficiency virus (HIV). Neurosyphilis is a serious complication of syphilis that can develop at any time in the course of syphilis. Two neuroimaging patterns should alert the neurologist to a diagnosis of neurosyphilis: cerebral gummas, which are dural-based lesions that can mimic meningiomas, and medial temporal lobe abnormalities that can mimic herpes encephalitis. Penicillin G is the recommended treatment for neurosyphilis, but ceftriaxone may be an acceptable alternative., Summary: The diagnosis of neurosyphilis can be challenging. A sound understanding of the clinical manifestations and the strengths and limitations of diagnostic tests are essential tools for the neurologist.

Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine. Increased production of IL-10 has been found in late syphilis, presumably creating favorable conditions for bacteria persistence. Single-nucleotide polymorphisms (SNPs) within the promoter of IL-10 gene have been found to influence IL-10 production. We investigated whether SNPs in the IL-10 gene promoter are associated with cerebrospinal fluid (CSF) levels of IL-10 and neurosyphilis. Polymorphisms in the gene for IL-10 (G→A mutation at the position -1084 and C→A mutation at the position -592) were sought in 35 patients with syphilis and 24 healthy volunteers. CSF examination (i.e. routine laboratory tests and IL-10 levels) was performed in all syphilis patients. Neurosyphilis was defined as reactive CSF VDRL test or CSF white blood cells⩾5/μL and CSF protein concentration⩾45mg/dL. Overall, 31% of patients with syphilis had neurosyphilis. CSF IL-10 levels were significantly higher in patients with neurosyphilis when compared to those with syphilis but not neurosyphilis. -1082 GG and -592 CC genotypes were significantly associated with higher CSF IL-10 levels. Moreover, these genotypes were found to be more frequent in individuals with neurosyphilis in comparison to those without neurosyphilis. Anti-inflammatory immune response seems to be important in pathogenesis of neurosyphilis. Our data suggest that host-related factors, such as SNPs of immune regulatory genes may influence the susceptibility to neurosyphilis., (Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

This article examines the diagnosis of general paralysis of the insane (GPI) at the Auckland Mental Hospital, New Zealand, between 1868 and 1899, and changes in the identified causes of this condition. It argues that despite long-standing evidence citing the role of syphilis, asylum doctors working in New Zealand were as reluctant as their English and Scottish colleagues to blame syphilis alone for GPI. It also argues that although syphilis became a more popular cause in the aetiology of GPI by the end of the nineteenth century, medical and non-medical sources continued to cite other causes for GPI., (© The Author(s) 2014.)

A 60-year-old man presented with progressive dementia and generalized convulsions. An initial MRI revealed a widespread high-intensity area with a mass effect in the right frontal and temporal lobes on T2-weighted images. Findings on digital subtraction angiography were normal. Serum and CSF tests showed high titers of antibodies to Treponema pallidum, which helped to distinguish neurosyphilis from glioma. He was initially treated with penicillin injection; however, it caused liver dysfunction and penicillin was switched to erythromycin. Even after antibiotic therapy for 2 months, his dementia did not improve. He underwent brain MRI four times during the treatment course, and they showed steady progression of brain atrophy in the right hemisphere. Taking these findings together, we diagnosed Lissauer form of general paresis. To the best of our knowledge, this is the first case of Lissauer form of paretic neurosyphilis, in which the progression of brain atrophy was clearly demonstrated on MRI.

Neurosyphilis is defined as infection of central nervous system by Treponema pallidum subspecies pallidum. Neurosyphilis can develop at any stage after initial infec-tion and is reflected in laboratory results. The pathogenesis of neurosyphilis is similar to that of classical form of syphilis. Individuals with persistent abnormalities in the cerebrospinal fluid are at risk of the development of clinical manifestations. Proper understanding of particular forms of neurosyphilis for differential diagnosis is important to determine potential risk of the development of progressive disease in neurology.

Background and Objective: To study the epidemiology, diagnosis, treatment strategies and perinatal outcomes of gestational syphilis., Patients and Method: We performed a retrospective study of 94 pregnant women with syphilis whose gestation and delivery were monitored in a Department of Obstetrics from 2002 to 2010 among a total of 85,806 births of women without syphilis in the same period., Results: The prevalence of gestational syphilis was 0.11%. Most of the women were foreign and the most prevalent type was late latent syphilis. Only 57 patients underwent right treatment despite adequate prescription. Maternal complications were confirmed in 31 pregnant women and 16 cases had fetal complications. We diagnosed 4 cases of neonatal syphilis, 3 of them with syphilitic meningitis, whose mothers had not completed the treatment correctly., Conclusions: The implementation of a mandatory syphilis serology in the pregnancy has enabled us to diagnose many cases of late latent syphilis. The successful completion of treatment must be ensured to prevent vertical transmission., (Copyright © 2012 Elsevier España, S.L. All rights reserved.)

Importance: The Jarisch-Herxheimer reaction (JHR) is a well-recognized transient worsening of signs and symptoms occurring soon after the first dose of an appropriate antibiotic for several spirochetal infections. The pathogenesis of this reaction is poorly understood. In this case study of cerebrospinal fluid (CSF) cytokines, we aimed to improve understanding of the pathogenesis of JHR in patients with neurosyphilis who develop transient neurologic signs., Observations: Four hours after receiving penicillin for general paresis, a 55-year-old man developed a severe JHR characterized by fever, tachycardia, hypertension, obtundation, seizures, and a neutrophilia lasting 18 hours. Cerebrospinal fluid obtained at the peak of the JHR demonstrated a switch from a mild lymphophilia to a moderate neutrophilia. He had markedly elevated CSF interleukin (IL) 8 and likely elevated IL-1β, IL-10, and IL-15 levels, which returned to normal in follow-up CSF examination results., Conclusions and Relevance: To our knowledge, this is the first report of elevated CSF cytokines in a patient with a JHR, which possibly contributed to the neurologic signs of JHR. Further studies on the innate inflammatory response during episodes of acute infection and inflammation are needed to develop targeted therapies to modulate this system, which could, in turn, improve future outcomes and modify the JHR.

This article is an update and literature review of the clinical and neuroimaging findings of the commonly known rickettsial, spirochetal, and eukaryotic parasitic infections. Being familiar with clinical presentation and imaging findings of these infections is crucial for early diagnosis and treatment especially in patients who live in or have a travel history to endemic regions or are immunocompromised., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: We report the magnetic resonance imaging (MRI) findings in a case of neurosyphilis revealed by the involvement of two cranial nerves., Case Report: A 41-year-old man developed a right cochleovestibular and left trigeminal neuropathy, associated with high serum titers of VDRL and TPHA, high titers of TPHA in the cerebrospinal fluid (CSF) and several CSF oligoclonal IgG bands. On MRI, hypertrophy and gadolinium contrast enhancement of these cranial nerves were associated with several supratentorial cortical nodules surrounded by marked cerebral edema, corresponding to syphilitic gummas. One of these cortical nodules was biopsied. Microscopic examination showed lesions of meningoencephalitis with necrosis and granulomatous vasculitis. After penicillin therapy, the serum VDRL titers and the MRI abnormalities disappeared, a partial clinical recovery was observed and a significant reduction of the serum TPHA titers was found., Discussion: Such MRI abnormalities are not specific and can be observed in various tumoral, auto-immune and infectious diseases. They can also mimic neurofibromatosis type II. Cranial nerve involvements in neurosyphilis can result from nerve inflammation in basal meningitis, nerve ischemia in meningovasculitis or from compression by an adjacent gumma. In our case, the cranial neuropathy was related to a mixed meningovascular and parenchymatous form of neurosyphilis.

In spite of the relative control of the disease in the late 20th century, syphilis, like other sexually transmitted diseases, has undergone a strong resurgence in recent years in the large urban centers of Europe and the US. Many patients with syphilis are also HIV+. The association between the two diseases may modify the clinical evolution of syphilis and increase the incidence of neurological disorders. We discuss the cases of three patients diagnosed with both diseases last year, with neurological presentation of syphilis occurring early and ophthalmic or cochlear vestibular involvement. This recent outbreak of syphilis seems to lead to an increase in the number of atypical cases presenting in our daily practice, where we must be prepared for early diagnosis and treatment.

Central nervous system complications are common in HIV-1 infected patients and occur either as a result of concomitant immunosuppression (opportunistic infections, lymphoma and tumors), as a primary manifestation of HIV infection, or as an adverse effect of therapy (immune restoration and toxicity). These complications contribute largely to patient morbidity and mortality. In the era of highly active antiretroviral therapy (HAART) these disease states have changed in presentation, outcome and incidence. We review in detail the epidemiology, pathogenesis, clinical features, diagnosis, and management of these disorders.

Treponema pallidum, the bacterium that causes syphilis, invades the central nervous system early in the course of disease but causes persistent infection in only a subset of infected persons. Individuals with persistent infection or asymptomatic meningitis are at risk for developing symptomatic neurosyphilis if they are not treated with a drug regimen that achieves sufficient drug levels in cerebrospinal fluid to kill the organism. In this article, recent studies that address the risk, diagnosis, and management of neurosyphilis are discussed within the context of a brief review. Particular attention is given to current controversies. In the developed world, these issues are particularly relevant to persons who are infected with HIV.

Objective: To define clinical and laboratory features that identify patients with neurosyphilis., Methods: Subjects (n=326) with syphilis but no previous neurosyphilis who met 1993 Centers for Disease Control and Prevention criteria for lumbar puncture underwent standardized history, neurological examination, venipuncture, and lumbar puncture. Neurosyphilis was defined as a cerebrospinal fluid (CSF) white blood cell count >20 cells/ microL or reactive CSF Venereal Disease Research Laboratory (VDRL) test result., Results: Sixty-five subjects (20.1%) had neurosyphilis. Early syphilis increased the odds of neurosyphilis in univariate but not multivariate analyses. In multivariate analyses, serum rapid plasma reagin (RPR) titer > or =1 : 32 increased the odds of neurosyphilis 10.85-fold in human immunodeficiency virus (HIV)-uninfected subjects and 5.98-fold in HIV-infected subjects. A peripheral blood CD4+ T cell count < or =350 cells/ microL conferred 3.10-fold increased odds of neurosyphilis in HIV-infected subjects. Similar results were obtained when neurosyphilis was more stringently defined as a reactive CSF VDRL test result., Conclusion: Serum RPR titer helps predict the likelihood of neurosyphilis. HIV-induced immune impairment may increase the risk of neurosyphilis.

Background: Neurosyphilis (NS) is nowadays a less frequent disease. Its incidence and clinical spectrum have changed over time., Objective: To estimate the incidence of NS and describe the clinical spectrum of NS in immunocompetent patients in the last decade., Methods: Demographic and clinical features, cerebrospinal fluid (CSF) changes, neuroimaging findings and outcome were retrospectively analyzed., Results: Forty-three patients met NS criteria. The yearly incidence was 0.2- 2.1 cases per 100,000 inhabitants. The mean age was 48.1 years, males being more frequently involved. The most frequent clinical patterns were meningovascular (30.2%), meningeal (25.6%) and general paresis (25.6%). Compared to prepenicillin series, we observed a decrease in late forms, mainly tabes dorsalis. CSF titers studied by the Venereal Disease Research Laboratory were higher in early NS. Neuroimaging findings were nonspecific. Outcome was better for early forms., Conclusions: Compared to the preantibiotic era, a lower frequency of late NS was observed, similar to that reported in other modern series which include patients with HIV infection. Therefore, this trend seems to be due to the impact of antibiotics rather than to HIV infection., (Copyright 2004 S. Karger AG, Basel)

Forty patients (34 males and 6 females) with neurological complaints/manifestations and with a past history of multiple sexual partners attending the Government Rajaji Hospital, Madurai, India between April 1992 and October 1992 were investigated for neurosyphilis. Metabolic disorders, hypertension, ischaemic heart disease, arrhythmias and trauma were excluded. Seven males (17.5%) were found to have neurosyphilis. The youngest was 26 years old and the oldest was 47. All were married and of low socioeconomic background. Meningovascular syphilis was the predominant presentation (6:1). Associated cardiovascular involvement was noticed in one of the cases. There was no associated HIV infection in these cases. The incidence is higher than previous reports from this centre.

To identify the characteristic features of lues in patients infected with HIV, 402 HIV-positive patients were examined for serological and clinical signs of lues. 141 patients (133 male, 8 female, mean age 36 [18-69] years) had a positive lues serology. Treatment for lues was required in 20 of the 141 cases (14%). In ten patients (one case of lues I, nine cases of lues II) dermatological signs were predominant, macular exanthemas (n = 4) and palmo-plantar syphilides (n = 3) being most frequent. Three patients had seropositive latent lues. Eight patients presented with signs of an active neurolues (lues II: n = 1; lues III: n = 6; lues IV: n = 1). In three of the eight cases the serum FTA-ABS-IgM findings were negative. In these three patients the need for a specific treatment was realized only on the basis of cerebrospinal fluid (CSF) examination in conjunction with the clinical findings and the anamnesis. This result makes it very clear that indication for CSF puncture should be more liberal in some HIV infected patients. The markedly high proportion of cases of neurolues (40% of the luetic patients requiring treatment) is possibly due to reactivation of old lues infections.

Early neurosyphilis, characterized by meningitis, cranial nerve abnormalities, and cerebrospinal accidents, was first described in patients with syphilis who received inadequate courses of arsphenamine. Although more effective, penicillin at conventional doses does not yield treponemacidal levels in the central nervous system and probably does not eradicate the infecting organisms, suggesting that it works synergistically with the host's immune response in preventing neurosyphilis. Neurosyphilis after penicillin therapy was almost unheard of in the United States until it began to appear in human immunodeficiency virus (HIV)-infected patients. Numerous cases of syphilitic meningitis, cranial nerve abnormalities, and strokes have been reported in the past decade; about one-half of reported patients had received penicillin therapy, often within the previous 6 months. Thus, more intensive diagnostic evaluation, perhaps including routine cerebrospinal fluid analysis, more intensive therapy, for example with at least three doses of benzathine penicillin, and far more rigorous follow-up are indicated in HIV-infected subjects with syphilis. Since the efficacy of conventional therapy is now uncertain, novel approaches to treatment deserve systematic evaluation.

Although up to 40% of patients with early syphilis have evidence of central nervous system (CNS) invasion by Treponema pallidum, the pathogenesis of CNS syphilis is not understood. A rabbit model that mimics early CNS involvement in humans was developed and characterized. Mild cerebrospinal fluid pleocytosis was evident 2 weeks after intracisternal inoculation of T. pallidum and peaked at 9 weeks. The VDRL test in cerebrospinal fluid was reactive in 24% of animals, most commonly at 9 weeks after infection. T. pallidum could be isolated from the CNS of animals infected for 4, 6, or 9 weeks but not from animals infected for 12 or 20 weeks. Clinically, 6% of animals developed uveitis, similar to the frequency in patients with secondary syphilis. Thus, this model of meningeal and ocular syphilis seems to be analogous to the early CNS infection in humans and can be used for studies of pathogenesis and treatment.

Ocular syphilis is rare in human immunodeficiency virus infected individuals. We think that syphilis should be considered in evaluating such patients presenting with uveitis. Most often, ocular syphilis includes retinitis associated with anterior or posterior uveitis, sometimes with optic neuritis. Concurrent neurosyphilis is frequent and may be more aggressive; it may progress more rapidly and cause more atypical signs than in patients without human immunodeficiency virus infection. This suggests the need for lumbar puncture in the evaluation of coinfected patients. The standard serological tests for syphilis (in blood and cerebrospinal fluid) may be nonreactive in human immunodeficiency virus seropositive patients. It may be because of the alteration of immunologic response of such patients. All coinfected patients with human immunodeficiency virus and syphilis should be treated with high-dose intravenous penicillin G sodium as recommended for neurosyphilis. We describe two human immunodeficiency virus infected patients with ocular syphilis and neurosyphilis.

A literature survey is presented concerning the clinical pattern of early syphilis in subjects infected with HIV. The course of syphilis infection in HIV-positive subjects differs often from the usual one, the clinical picture may be that of the so called malignant syphilis with early development of syphilitic lesions in the central nervous system and involvement of the visual system; Serological reactions differ also, they may give negative results or may appear with delay, sometimes high titres of these reactions are found.

Two case histories, each spanning more than 20 years, demonstrate the complexity and persistence of modern neurosyphilis. Both patients present uncommon manifestations of neurosyphilis that may be easily overlooked today: superior orbital fissure syndrome, posterior fossa gumma, and bilateral deafness. Computed tomographic scans were performed in both patients but were diagnostically nonspecific, and syphilis serology testing in both serum and cerebrospinal fluid was repeatedly misleading. Numerous mistaken diagnoses were put forward until tissue was finally available for histologic examination. Perhaps the most disturbing aspects of these two cases are the persistent failure of specific treponemal serologic testing to indicate the diagnosis, and the inability of repeated "adequate" and/or supramaximal doses of penicillin to prevent continued neurologic deterioration. We believe that chronic neurosyphilis may demand a reevaluation of current diagnostic and therapeutic practice.

Meningovascular syphilis developed in a patient two years after the treatment of primary syphilis with a single intramuscular injection of 2.4 million units of penicillin G benzathine as recommended by the Centers for Disease Control. Although it could not be established with certainty whether this infection represented a reinfection or a treatment failure, the case emphasizes the necessity for serologic follow-up examination in all patients treated for primary syphilis.

Given the high rate of infection by HIV in the APAD in our country, the description of localized infectious problems in the CNS secondary to drug-addiction should always take into account opportunistic infections or tumours occurring there. The initial clinical evaluation should highlight or rule out the presence of clinical indications (specially polyadenia and oral candidiasis) which suggest a clinical condition of immunodepression. Septic embolization due to bacteremia and fungemia is common among drug-addicts, sometimes causing, although not very often in comparison with other sites, various infectious complications in the CNS (meningitis, cerebral abscess, subdural empyema or epidural abscess), "Staphylococcus aureus" being the micro-organism most frequently involved. From 1977 to 1986 the work-group for the study of infections among drug-addicts has listed 6,481 infections. Disseminated candidiasis (582 cases) and infectious endocarditis (506 cases) were the most frequent types of primary infection. Only 33 cases of infection of the CNS were observed, meningitis being the most frequent (57%). The usual empirical antibiotic treatment for meningitis is cefotaxime or cefotriaxona plus cloxacillin, and for cerebral abscess we substitute metronidazole for isoxazolic penicillin. Given the sexual habits frequently associated with APAD, neurosyphilis is suspect, since immunodepression secondary to infection by HIV causes changes in its natural behaviour. Tetanus is the most serious and uncommon infectious complication connected with drug-addiction. In our society, up to 1986 only 5 cases had been described. As for paludism, the cases detected in this country have belonged to two small outbreaks: one with four cases in Madrid with "Plasmodium vivax" and the other with three cases in Tortosa (Tarragona) with "P. falciparum".

Neurosyphilis remains a source of perplexity for today's physicians. Controversies exist over the interpretation of serologic tests, cerebrospinal fluid (CSF) abnormalities, diagnostic criteria, and treatment regimens. Its occurrence with human immunodeficiency virus (HIV) infection has raised fears of its recrudescence. A critical analysis of the evidence behind these viewpoints leads to several conclusions: the CSF VDRL is the most appropriate diagnostic test; pleocytosis is the only reliable CSF measure of disease activity; commonly accepted diagnostic criteria do not exclude nonsyphilitic disease; and treatment requires the prolonged use of parenteral penicillin, but no superior regimen has been found. Most data do not currently support the view that concurrent HIV infection produces accelerated or resistant neurosyphilis.