Cerebrospinal Fluid Venereal Disease Research Laboratory Research Articles

Posterior Segment Manifestations of Syphilis and Correlation With Serologic Markers of Infection.

Retrospective analysis correlating serologic titers of ocular syphilis with posterior segment manifestations. This study consisted of 40 patients (80 eyes imaged, 68 affected) with positive rapid plasma reagin (RPR) and Treponema Pallidum immunoglobulin G. We collected demographic and presentation data including HIV status, absolute CD4 count, RPR, cerebrospinal fluid-venereal disease research laboratory (CSF-VDRL) test, and retinal zone. We categorized imaging into syphilitic outer retinopathy (SOR), acute syphilitic posterior placoid chorioretinopathy, retinitis/chorioretinitis (RC), and papillitis. Multivariate analysis correlated HIV status, RPR, and VDRL titers with posterior segment findings and zone. Mean age of 42.8 ± 10.7 years, with 70% male patients. Presenting visual acuity (logMAR) 0.66 ± 0.74 did not correlate with RPR, nor was it associated with papillitis, RC, or acute syphilitic posterior placoid chorioretinopathy. Higher RPR (≥ 1:128) positively associated with SOR (P = 0.031) and zone 1 (odds ratio [OR], 1.62; P = 0.02), but negatively associated with zone 2 (OR 0.35; P = 0.005). HIV positivity increased RC odds (OR, 4.45; P = 0.047). Higher RPR correlated with SOR and zone 1, whereas HIV positivity correlated with RC. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Neurological manifestations of syphilis-HIV coinfection in South Africa

ObjectiveSyphilis and HIV coinfection is highly prevalent in South Africa, and both can cause neurological complications. We describe the clinical presentation and outcome of neurosyphilis in patients with and without HIV coinfection diagnosed at a tertiary facility, Groote Schuur Hospital (GSH), in South Africa. MethodsWe retrospectively analyzed folders of adults with positive cerebrospinal fluid (CSF) fluorescent treponemal antibody absorption test in 2018 and 2019, with follow-up data collected until 2022. ResultsHIV-coinfection was identified in 35% of the 69 included patients. Patients with HIV-coinfection were more likely to be female (58% vs 25% female, p < 0.01), and present earlier (median age = 31 years vs. 40 years, p < 0.001). Neuropsychiatric manifestations (confusion, dementia, psychosis), and strokes were the commonest clinical presentations in both groups. Those with HIV-coinfection were significantly less likely to be diagnosed with neurosyphilis by the treating clinician (71% vs. 91%, p < 0.05), as were those with a negative CSF Venereal Disease Research Laboratory (74% vs. 94%, p < 0.05). Accurate diagnosis of neurosyphilis was associated with an increased 12-month survival (alive: N = 36 [63%]) relative to those who did not receive an accurate diagnosis (alive: N = 2 [17%], p < 0.05). Those who were optimally treated with antibiotics had significantly higher 12-month survival (alive: N = 33, 63%) compared to those with suboptimal treatment (alive: N = 5, 29%), p < 0.01. ConclusionNeurosyphilis presented similarly in those with and without HIV-coinfection. Accurate identification and optimal antibiotic treatment of neurosyphilis, particularly in CSF VDRL negative patients and those with HIV-coinfection, is necessary to improve patient survival.

Diagnosis of neurosyphilis in HIV-negative patients with syphilis: development, validation, and clinical utility of a suite of machine learning models

The ability to accurately identify the absolute risk of neurosyphilis diagnosis for patients with syphilis would allow preventative and therapeutic interventions to be delivered to patients at high-risk, sparing patients at low-risk from unnecessary care. We aimed to develop, validate, and evaluate the clinical utility of simplified clinical diagnostic models for neurosyphilis diagnosis in HIV-negative patients with syphilis. We searched PubMed, China National Knowledge Infrastructure and UpToDate for publications about neurosyphilis diagnostic guidelines in English or Chinese from database inception until March 15, 2023. We developed and validated machine learning models with a uniform set of predictors based on six authoritative diagnostic guidelines across four continents to predict neurosyphilis using routinely collected data from real-world clinical practice in China and the United States (through the Dermatology Hospital of Southern Medical University in Guangzhou [659 recruited between August 2012 and March 2022, treated as Development cohort], the Beijing Youan Hospital of Capital Medical University in Beijng [480 recruited between December 2013 and April 2021, treated as External cohort 1], the Zhongshan Hospital of Xiamen University in Xiamen [493 recruited between November 2005 and November 2021, treated as External cohort 2] from China, and University of Washington School of Medicine in Seattle [16 recruited between September 2002 and April 2014, treated as External cohort 3] from United States). We included all these patients with syphilis into our analysis, and no patients were further excluded. We trained eXtreme gradient boosting (XGBoost) models to predict the diagnostic outcome of neurosyphilis according to each diagnostic guideline in two scenarios, respectively. Model performance was measured through both internal and external validation in terms of discrimination and calibration, and clinical utility was evaluated using decision curve analysis. The final simplified clinical diagnostic models included neurological symptoms, cerebrospinal fluid (CSF) protein, CSF white blood cell, and CSF venereal disease research laboratory test/rapid plasma reagin. The models showed good calibration with rescaled Brier score of 0.99 (95% CI 0.98-1.00) and excellent discrimination (the minimum value of area under the receiver operating characteristic curve, 0.84; 95% CI 0.81-0.88) when externally validated. Decision curve analysis demonstrated that the models were useful across a range of neurosyphilis probability thresholds between 0.33 and 0.66 compared to the alternatives of managing all patients with syphilis as if they do or do not have neurosyphilis. The simplified clinical diagnostic models comprised of readily available data show good performance, are generalisable across clinical settings, and have clinical utility over a broad range of probability thresholds. The models with a uniform set of predictors can simplify the sophisticated clinical diagnosis of neurosyphilis, and guide decisions on delivery of neurosyphilis health-care, ultimately, support accurate diagnosis and necessary treatment. The Natural Science Foundation of China General Program, Health Appropriate Technology Promotion Project of Guangdong Medical Research Foundation, Department of Science and technology of Guangdong Province Xinjiang Rural Science and Technology（Special Commissioner）Project, Southern Medical University Clinical Research Nursery Garden Project, Beijing Municipal Administration of Hospitals Incubating Program.

Neurosyphilis Presenting as Limbic Encephalitis: a Case Report (P10-10.007)

<h3>Objective:</h3> To present an interesting case of neurosyphilis mimicking limbic encephalitis. <h3>Background:</h3> Neurosyphilis can occur at any stage of infection and it classically presents as meningitis, cranial neuropathies, vasculitis, tabes dorsalis, or neuropsychiatric manifestations, however rarely temporal lobe abnormalities resembling limbic encephalitis have been reported. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> 51-year-old male with no past medical history presents initially with 3 weeks of altered mental status, confusion and memory loss. Prior to admission to the hospital, he presented with a generalized tonic-clonic seizure. His MRI showed T2 hyperintensities in the left hippocampus, amygdala, and mesial temporal lobe with associated diffusion restriction. Cerebrospinal fluid (CSF) studies showed 58 white blood cells/mm3 (73% lymphocytes), a protein concentration of 165 mg/dL and a glucose concentration of 35 mg/dL. HIV serology, serum cryptococcal Antigen, HSV and VZV PCR on CSF and neuronal autoantibodies on serum were negative. EEG showed left lateralized periodic discharges. The patient was initially treated with empiric anti-infective therapy including acyclovir, ceftriaxone, and ampicillin. Subsequently, serum syphilis screen was positive with reflex Rapid Plasma Reagin (RPR) titer at 1:64. CSF Venereal Disease Research Laboratory (VDRL) was positive at 1:64. In light of these results, the patient was transitioned to intravenous aqueous penicillin G 24 million units daily through continuous infusion. His mental status markedly improved after a few days of treatment. Repeat EEG showed only mild encephalopathy. He was discharged on levetiracetam and high dose IV penicillin G to complete a 14-day course. <h3>Conclusions:</h3> Syphilis is commonly known as a great imitator; it is a treatable condition so it should not be missed. We need to be more cognizant of this diagnosis when evaluating patients with temporal lobe involvement on MRI, lymphocytic pleocytosis and hypoglycorrhachia. Although HSV and autoimmune diseases are the most common causes of limbic encephalitis, as presented in our case, syphilis testing should be considered. <b>Disclosure:</b> Dr. Hu has nothing to disclose. Dr. El Helou has nothing to disclose. Nayrobi Pena Cotui has nothing to disclose. Dr. Balobaid has nothing to disclose. Dr. Montalvo Perero has nothing to disclose.

Unusual Presentation of PLA2G6-Related Neurodegeneration with Retinal Vasculitis.

Unusual Presentation of PLA2G6-Related Neurodegeneration with Retinal Vasculitis.

Increased CCL24 and CXCL7 levels in the cerebrospinal fluid of patients with neurosyphilis.

BackgroundMonocytes are recruited into the cerebrospinal fluid (CSF) of patients with neurosyphilis, suggesting abnormal chemokine expression. We aimed to investigate the aberrant expression of chemokines in the CSF of these patients.MethodsCSF and serum samples were collected from patients with neurosyphilis between July 2017 and June 2019 in the Dermatology Department, Second Affiliated Hospital of Zhejiang University. Differences in the expression of 38 chemokines between patients with and without neurosyphilis were detected using RayBio® Human Chemokine Antibody Array C1. CCL24 and CXCL7 levels in the patients’ CSF and serum were further measured using RayBio® CCL24 and CXCL7 ELISA kits.ResultsNinety‐three CSF and serum samples of patients with syphilis were collected. Antibody array analysis showed that the CSF levels of CCL24 (P = .0185), CXCL7 (P < .0001), CXCL13 (P < .0001), CXCL10 (P < .0001), and CXCL8 (P < .0001) were significantly higher in patients with than without neurosyphilis. ELISA confirmed significantly higher CCL24 and CXCL7 levels in the CSF of patients with than without neurosyphilis (CCL24: 6.082 ± 1.137 pg/mL vs 1.773 ± 0.4565 pg/mL, P = .0037; CXCL7: 664.3 ± 73.19 pg/mL vs 431.1 ± 90.54 pg/mL, P = .0118). Increased CCL24 and CXCL7 expression was seen throughout all neurosyphilis stages, had moderate diagnostic efficiency for neurosyphilis, and correlated poorly with CSF cell count and Venereal Disease Research Laboratory titer. CSF CCL24 levels also correlated poorly with CSF protein concentration.ConclusionAbnormally high CSF chemokines levels may play a role in the pathogenesis of neurosyphilis.

Cerebrospinal fluid TPPA titres in the diagnosis of neurosyphilis

Treponema pallidum can be detected in the cerebrospinal fluid (CSF) in up to 30% of early syphilis infection.1 The BASHH guidelines2 recommend a diagnosis of neurosyphilis is based on symptomatology...

Ocular syphilis in an immunocompetent man.

A healthy 47-year-old immunocompetent man from Northern Canada presented for ophthalmologic assessment after experiencing one month of right-sided photopsias, floaters, and a right lower nasal quadrant visual field defect. Optic disc swelling, vitritis, chorioretinitis, peripheral retinal infiltrates and hemorrhages were noted in the right eye. A broad right inferior arcuate and nasal visual field defect were also present. Fluorescein angiography of the right retina showed dilated disc vessels and staining of the optic disc.Treponemal antibody testing, using chemiluminescent microparticle immunoassay, was highly positive; this was followed by a Venereal Disease Research Laboratory (VDRL) test with a titre of 1:32 and confirmed by Treponema pallidum particle agglutination (TP-PA) test. Testing did not demonstrate any co-infections.Cerebrospinal fluid (CSF) analysis revealed strong reactivity (4+) to the Treponemal antibody by immunofluorescence antibody absorbed (FTA-ABS) test and non-reactivity by CSF VDRL test. Syphilis PCR of CSF was negative. A diagnosis of neurosyphilis was made. He was treated with ceftriaxone 2 grams IV q24h for 14 days. The vitritis gradually improved.Familiarity with syphilis diagnostics is becoming increasingly important, especially given its recent resurgence amongst several at risk groups. This patient’s case highlights that non-reactive CSF VDRL is not a reliable test in the context of positive serum results and a compatible clinical picture. CSF Treponemal tests such as TP-PA and FTA-ABS offer higher sensitivity than non-treponemal tests such as VDRL in the context of CNS involvement and ocular syphilis.

325. Neurosyphilis Management in the Post-Procaine Penicillin Era

BackgroundNeurosyphilis (NS) is an infection of the central nervous system caused by Treponema pallidum. Intramuscular (IM) penicillin (PCN) G procaine is a treatment option for those who cannot receive or decline intravenous (IV) therapy. Since August 24, 2016, it has been unavailable from the manufacturer, necessitating the use of IV PCN for NS. Our institutions organized a multidisciplinary, coordinated care system to expedite outpatient treatment of NS upon diagnosis. We report successful management of NS at an urban safety-net hospital in the post-procaine PCN era.MethodsWe identified patients with suspected NS from the King County Public Health STD and Harborview Infectious Disease clinics from October 2016 to February 2018. Demographics, clinical symptoms, diagnostics, treatment, and outcomes were collected by chart review. Successful NS treatment was defined as resolution of cerebrospinal fluid (CSF) pleocytosis or elevated protein, improvement in neurologic symptoms or appropriate decrease in serum rapid plasma reagin (RPR) or CSF Venereal Disease Research Laboratory (VDRL) titers.Table 1: Demographic and Socioeconomic CharacteristicsTotal = 43 n (%)GenderMale39 (91)RaceWhite29 (67)Black3 (7)Asian3 (7)Homeless5 (12)Insurance statusaPrivate15Medicaid20Medicare8Charity care11Substance use disorder15 (35)HIV Positive22 (51)Viral load suppressed (< 200 copies/mL)13 (59) aRepresents more than one payer per patient.ResultsWe identified 43 cases of suspected NS. The most common symptoms were blurred vision, headache, and tinnitus. All had a lumbar puncture (LP). Median days from LP to treatment initiation was 6—many starting on day of diagnosis. Fourteen patients (33%) required admission for treatment. Two patients declined therapy. IV PCN G was used in 93% of cases; one received IM ceftriaxone. Treatment was successful in 32 of 41 (78%) cases, with 23 of these (72%) managed as outpatients. Three cases were treatment failures for incomplete therapy adherence or equivocal response and uncertain diagnosis.ConclusionWithout available IM procaine PCN, neurosyphilis is challenging to manage in vulnerable populations or those wishing to avoid inpatient admission. Employing a multidisciplinary, coordinated care approach can lead to successful treatment of NS using IV PCN in the outpatient setting.Disclosures All authors: No reported disclosures.

Clinical manifestations and cerebrospinal fluid status in ocular syphilis in HIV-Negative patients.

BackgroundSyphilis with ocular involvement has reemerged as a critical health problem. The aim of the present study was to explore the clinical manifestations and cerebrospinal fluid (CSF) status in ocular syphilis in human immunodeficiency virus (HIV)-negative patients.MethodsThe clinical records of patients with ocular syphilis presenting to the Shanghai Xuhui Central Hospital in the period from January 2011 to December 2012 were retrospectively reviewed.ResultsThe median age of 25 HIV-negative patients with ocular syphilis was 53 years, 18 patients (72.0 %) were males and 7 (28.0 %) were females. None of them self-identified themselves as men who had sex with men (MSM). The ocular lesions included: uveitis (13 cases), optic neuropathy (6 cases), retinal vasculitis (5 cases), retinal detachment (3 cases), and neuroretinitis (4 cases). Serum toluidine red unheated serum test (TRUST) titer ranged from 1 to 512, with a median of 64. Overall, 18 (72.0 %) of the 25 patients had abnormal CSF results, 15 (60.0 %) CSF samples had elevated white blood cell counts, 13 (52.0 %) had elevated protein levels, and 9 (36.0 %) had reactive CSF Venereal Disease Research Laboratory (VDRL) test, respectively. Mann–Whitney U tests showed higher serum TRUST titer (>32) correlated with the abnormal CSF results.ConclusionsThe demographic characteristics of patients with ocular syphilis in this study were different from previous reports. The study showed a high CSF abnormal rate in HIV-negative patients. The recommendation for CSF examination from all patients with ocular syphilis, including HIV-negative cases, is strongly supported by the present data.

Clinical and laboratory characteristics of ocular syphilis: a new face in the era of HIV co-infection.

BackgroundOcular syphilis is reemerging as an important cause of uveitis in the new era of common co-infection with HIV. This study will reveal the clinical and laboratory characteristics in the group of individuals co-infected with ocular syphilis and HIV compared with HIV-negative individuals. In this retrospective observational case series, medical records of patients diagnosed with ocular syphilis with serologic support from 2008 to 2014 were reviewed. Ocular and systemic manifestation and laboratory profiles were reviewed.ResultsTwenty-nine eyes of 16 consecutive patients (10 HIV-positive and 6 HIV-negative) were included. All patients were males, and mean age of onset for ocular syphilis was 43 (mean 42.65 ± 13.13). In both HIV-positive and HIV-negative groups, ocular manifestations of syphilis were variable including anterior uveitis (4 eyes), posterior uveitis (8 eyes), panuveitis (13 eyes), and isolated papillitis (4 eyes). In HIV-positive patients, panuveitis was the most common feature (12/18 eyes, 67 %) and serum rapid plasma reagin (RPR) titers were significantly higher (range 1:64–1:16,348; mean 1:768; p = 0.018) than in HIV-negative patients. Upon the diagnosis of ocular syphilis in HIV-positive patients, HIV-1 viral load was high (median 206,887 copies/ml) and CD4 cell count ranged from 127 to 535 cells/ml (mean 237 ± 142; median 137). Regardless of HIV status, cerebrospinal fluid (CSF) exam was frequently abnormal: positive CSF fluorescent treponemal antibody absorption (FTA-ABS) or Venereal Disease Research Laboratory (VDRL) test results in seven patients or either elevated CSF WBC count or elevated CSF protein in six patients.ConclusionsOur results reveal that the patients with ocular syphilis with high serum RPR titers may have concomitant HIV infection requiring further testing for HIV status and ocular syphilis is likely associated with the central nervous system involvement and therefore needs to be managed according to the treatment recommendations for neurosyphilis.

False-Positive Venereal Disease Research Laboratory Tests in the Cerebrospinal Fluid With Meningeal Carcinomatosis

There are many causes of false-positive Venereal Disease Research Laboratory (VDRL) tests in serum, for example, systemic lupus erythematosus, pregnancy, liver disease, intravenous drug abuse. Such patients have a negative serum fluorescent treponemal antibody absorption test. False-positive VDRLs in the cerebrospinal fluid (CSF) are extremely rare. We present a case of suspected neurosyphilis in a patient with a negative serum VDRL and fluorescent treponemal antibody absorption test but with a positive CSF VDRL. This is only the third reported case of a false-positive CSF VDRL, which, in this case, was caused by meningeal carcinomatosis.

Point-of-care treponemal tests for neurosyphilis diagnosis.

The laboratory diagnosis of neurosyphilis rests upon identifying cerebrospinal fluid (CSF) abnormalities, including CSF-Venereal Disease Research Laboratory (VDRL) reactivity. The CSF-VDRL may not be available in the parts of the world where neurosyphilis is most common. Treponemal immunochromatographic strip tests (ICSTs) have been developed as point-of-care tests on blood for syphilis diagnosis in resource-limited settings. We optimized 3 commercial ICSTs for performance on CSF and tested CSF samples from 217 patients with syphilis. The Syphicheck-WB test (Qualpro Diagnostics, Goa, India; "Syphicheck") was chosen for further study based on agreement with CSF-VDRL test results. We determined CSF-Syphicheck titers for 152 samples. We modified the CSF-Syphicheck for point-of-care testing in a US sexually transmitted diseases clinic and compared results on 102 paired centrifuged and uncentrifuged CSF samples obtained in the laboratory to the results obtained at point of care; results of samples diluted 1:4 were compared in a subset. The diagnostic sensitivity of a reactive CSF-Syphicheck (62%-64%) and the diagnostic specificity of a CSF-Syphicheck titer at or above 1:4 (79%-81%) were equivalent to the CSF-VDRL (54%-69% sensitivity, 73%-75% specificity) for laboratory and clinical neurosyphilis diagnoses. The CSF-Syphicheck normalized after neurosyphilis therapy similarly to the CSF-VDRL. The modified CSF-Syphicheck performed well at the point of care, albeit with better performance on cell-free compared with uncentrifuged CSF. Cerebrospinal fluid treponemal ICSTs hold promise for point-of-care neurosyphilis diagnosis in regions where the CSF-VDRL is not available. Further study should address the performance of CSF ICSTs in resource-limited settings.

Increased interleukin-17 in peripheral blood and cerebrospinal fluid of neurosyphilis patients.

Background Treponema pallidum infection evokes vigorous immune responses, resulting in tissue damage. Several studies have demonstrated that IL-17 may be involved in the pathogenesis of syphilis. However, the role of Th17 response in neurosyphilis remains unclear.Methodology/Principal FindingsIn this study, Th17 in peripheral blood from 103 neurosyphilis patients, 69 syphilis patients without neurological involvement, and 70 healthy donors were analyzed by flow cytometry. The level of IL-17 in cerebrospinal fluid (CSF) was quantified by ELISA. One-year follow up for 44 neurosyphilis patients was further monitored to investigate the role of Th17/IL-17 in neurosyphilis. We found that the frequency of Th17 cells was significantly increased in peripheral blood of patients with neurosyphilis, in comparison to healthy donors. IL-17 in CSF were detected from 55.3% neurosyphilis patients (in average of 2.29 (0–59.83) pg/ml), especially in those with symptomatic neurosyphilis (61.9%). CSF IL-17 was predominantly derived from Th17 cells in neurosyphilis patients. Levels of IL-17 in CSF of neurosyphilis patients were positively associated with total CSF protein levels and CSF VDRL (Venereal Disease Research Laboratory) titers. Notably, neurosyphilis patients with undetectable CSF IL-17 were more likely to confer to CSF VDRL negative after treatment.ConclusionsThese findings indicate that Th17 response may be involved in central nervous system damage and associated with clinical symptoms in neurosyphilis patients. Th17/IL-17 may be used as an alternative surrogate marker for assessing the efficacy of clinical treatment of neurosyphilis patients.

Expression of CXCL2 in the Serum and Cerebrospinal Fluid of Patients with HIV and Syphilis or Neurosyphilis

The potential mechanisms for blood-brain barrier damage and the diagnosis of neurosyphilis in HIV patients co-infected with syphilis (HIV-S) are unclear. The aim of the study was to determine the expression of CXCL2 in the serum and cerebrospinal fluid (CSF) of HIV-S patients. A total of 34 HIV patients and 7 controls were enrolled in a HIV clinical cohort for diagnosis of neurosyphilis in Taiwan. Serum and CSF concentrations of CXCL2 were determined by ELISA. Neurosyphilis was defined as a CSF white blood cell count of ≧20 cells/μl or a reactive CSF Venereal Disease Research Laboratory (VDRL). Demographics and medical histories were collected. All the patients with HIV-S were males. Most (80%) had sex with men (MSM) and serum rapid plasma reagin (RPR) titers of ≧1:32. The medium age was 37 (range 21-68) years. The medium CD4 T cell counts at the time of the diagnosis of syphilis were 299 (range 92-434) cells/μl. Eight patients (24%) had neurosyphilis based on a reactive CSF VDRL test (n = 5) or increased CSF white blood cell counts of ≧20 cells/μl (n = 3). The concentrations of CSF CXCL2 were significantly higher in patients with HIV and neurosyphilis as compared to HIV with syphilis, HIV, and controls (p = 0.012). There were no significant differences in serum concentrations between the four groups. There was a correlation between CSF CXCL2 concentrations with neurosyphilis (p = 0.017), CSF white blood cell count (p = 0.001), and CSF protein levels (p = 0.005). The CSF level of CXCL2 can be used to distinguish those with or without neurosyphilis in HIV infected patients.

Elevated Cerebrospinal Fluid Interleukin-17A and Interferon-γ Levels in Early Asymptomatic Neurosyphilis

The mechanisms underlying the process of Treponema pallidum clearance from the central nervous system have not yet been established. Considering that neurosyphilis is associated with mild cerebrospinal fluid (CSF) pleocytosis with a lymphocytic predominance, it has been suggested that cells involved in the adaptive immune response may play a role in this process. In the current study, we assessed the cytokine production profile of T-helper cells in the serum and CSF of patients with early syphilis, with and without CSF abnormalities. Cerebrospinal fluid and blood samples were collected from 33 patients with secondary and early latent syphilis. Five patients (15%) had a reactive CSF Venereal Disease Research Laboratory test without any accompanying neurological symptoms. According to the Centers of Disease Control and Prevention classification, they were diagnosed with asymptomatic neurosyphilis. Serum and CSF levels of interferon-γ (IFN-γ; Th1-type cytokine), interleukin-4 (IL-4; Th2-type cytokine), and interleukin-17A (IL-17A; Th17-type cytokine) were determined by enzyme-linked immunosorbent assay. Patients with asymptomatic neurosyphilis had significantly higher levels of IL-17A (8-fold) and IFN-γ (7.8-fold) in the CSF compared with patients in the no-neurosyphilis group. Six individuals had CSF pleocytosis but a negative CSF Venereal Disease Research Laboratory test result (presumptive neurosyphilis group). In this group, CSF IFN-γ and CSF IL-17A levels were also significantly elevated when compared with no-neurosyphilis group. There was no correlation between serum and CSF concentrations of IL-17A. However, CSF pleocytosis correlated positively with both CSF IL-17A (r = 0.4, P = 0.01) and IFN-γ (r = 0.42, P = 0.01). Increased CSF levels of IFN-γ and IL-17A in syphilitic patients with CSF abnormalities suggest that cells of adaptive immunity (probably T-helper cells producing IFN-γ and IL-17) may contribute to the inflammatory response associated with neurosyphilis. In addition, the lack of correlation between serum and CSF IL-17A levels suggests intrathecal production of this cytokine. Further studies are needed to establish the exact nature of the immune response accompanying neurosyphilis and its clinical significance.

Unilateral mydriasis as the primary sign of neurosyphilis

Syphilis can mimic most ocular disorders, and there is no characteristic to distinguish ocular syphilis from other eye diseases. We report a rare case of a 41-year-old man who presented with an Adie's-like pupil as the only feature of neurosyphilis. The patient met the criteria for the diagnosis of neurosyphilis by the finding of positive cerebrospinal fluid-Venereal Disease Research Laboratory (CSF-VDRL) and CSF-Treponema pallidum particle agglutination tests. The patient was then treated with 2 g intravenous ceftriaxone per day for 15 days because of penicillin allergy. Nine months after anti-syphilitic treatment alone, the diameter of the patient's left pupil reduced from 10 to 5 mm. The CSF-VDRL test was negative. It is highly recommended that any patients with ocular disease that does not respond to the routine treatment should undergo syphilis evaluation to avoid misdiagnosis.

Prevalence of positive syphilis serology and meningovascular neurosyphilis in patients admitted with stroke and TIA from a culturally diverse population (2005–09)

The study aims were to determine the prevalence of positive syphilis serology and meningovascular neurosyphilis (NS) in patients admitted with transient ischaemic attack (TIA) and stroke to a tertiary hospital serving a culturally diverse community. A retrospective cohort analysis was conducted using routinely collected administrative data and medical records to identify patients admitted with TIA, stroke and other conditions, with positive syphilis serology, between 2005 and 2009. Direct medical record review confirmed diagnoses of meningovascular NS. Syphilis serology was requested in 27% (893/3270) of all patients with TIA and stroke (2005–09) of whom 4% (38/893) were positive. Thirty-seven patients with positive serology had clinical characteristics consistent with meningovascular NS. Their mean age was 72±13years; 65% were male and 68% had a recorded place of birth in South-East Asia or the Pacific Islands. One of 12 patients with suspected meningovascular NS with cerebrospinal fluid (CSF) analysis had a positive CSF Venereal Disease Research Laboratory (VDRL) test. Three patients (8%) met diagnostic criteria for “definite or probable” meningovascular NS. All three patients with a “definite or probable” meningovascular NS and 15 (44%) of the remainder who had positive serology without confirmation of NS were treated with intravenous or intramuscular penicillin. Lumbar puncture (LP) and penicillin were underutilised in patients with TIA and stroke with positive serology. In conclusion, syphilis testing should be considered part of the diagnostic work-up of TIA and stroke, particularly in ethnically diverse populations. In patients with TIA and stroke with positive syphilis serology, it would seem appropriate to further pursue diagnosis and treatment and in patients unable to undergo LP, empiric treatment for NS should be considered.

A Case of Neurosyphilis Presenting as a Stroke in a Patient with Human Immunodeficiency Virus Infection

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Antiretroviral Therapy–associated Coccidioidal Meningitis

Antiretroviral Therapy–associated Coccidioidal Meningitis