Neurosyphilis is characterized by a compartmentalized and robust neuroimmune response but not by neuronal injury.

BACKGROUND: Neurosyphilis is increasing in prevalence but its pathophysiology remains incompletely understood. This study assessed for CNS-specific immune responses during neurosyphilis compared to syphilis without neurosyphilis and compared these immune profiles to those observed in other neuroinflammatory diseases. METHODS: Participants with syphilis were categorized as having neurosyphilis if their cerebrospinal fluid (CSF)-venereal disease research laboratory (VDRL) test was reactive and as having syphilis without neurosyphilis if they had a non-reactive CSF-VDRL test and a white blood cell count <5/µL. Neurosyphilis and syphilis without neurosyphilis participants were matched by rapid plasma reagin titer and HIV status. CSF and plasma were assayed for markers of neuronal injury and glial and immune cell activation. Bulk RNA sequencing was performed on CSF cells, with results stratified by the presence of neurological symptoms. FINDINGS: CSF neopterin and five CSF chemokines had levels significantly higher in individuals with neurosyphilis compared to those with syphilis without neurosyphilis, but no markers of neuronal injury or astrocyte activation were significantly elevated. The CSF transcriptome in neurosyphilis was characterized by genes involved in microglial activation and lipid metabolism and did not differ in asymptomatic versus symptomatic neurosyphilis cases. CONCLUSIONS: The CNS immune response observed in neurosyphilis was comparable to other neuroinflammatory diseases and was present in individuals with neurosyphilis regardless of neurological symptoms, yet there was minimal evidence for neuronal or astrocyte injury. These findings support the need for larger studies of the CSF inflammatory response in asymptomatic neurosyphilis. FUNDING: This work was funded by the National Institutes of Health, grants K23MH118999 (S.F.F.) and R01NS082120 (C.M.M.).

Large-Scale Proteome Profiling Identifies Biomarkers Associated with Suspected Neurosyphilis Diagnosis.

Neurosyphilis (NS) is a central nervous system (CNS) infection caused by Treponema pallidum (T. pallidum). NS can occur at any stage of syphilis and manifests as a broad spectrum of clinical symptoms. Often referred to as "the great imitator," NS can be easily overlooked or misdiagnosed due to the absence of standard diagnostic tests, potentially leading to severe and irreversible organ dysfunction. In this study, proteomic and machine learning model techniques are used to characterize 223 cerebrospinal fluid (CSF) samples to identify diagnostic markers of NS and provide insights into the underlying mechanisms of the associated inflammatory responses. Three biomarkers (SEMA7A, SERPINA3, and ITIH4) are validated as contributors to NS diagnosis through multicenter verification of an additional 115 CSF samples. We anticipate that the identified biomarkers will become effective tools for assisting in diagnosis of NS. Our insights into NS pathogenesis in brain tissue may inform therapeutic strategies and drug discoveries for NS patients.

Multicentric evaluation of a specific intrathecal anti-Treponema pallidum IgG index as a diagnostic biomarker of neurosyphilis: results from a retro-prospective case-control study.

BACKGROUND AND OBJECTIVES: The diagnosis of neurosyphilis (NS) lacks a true 'gold standard', making the diagnosis challenging while consequences of a misdiagnosis are potentially severe. The aim of this study was to evaluate the diagnostic performance of measuring an antibody index (AI) for the intrathecal synthesis of specific anti-Treponema pallidum (T. pallidum) IgG for the diagnosis of NS. METHODS: Specific anti-T. pallidum IgG were measured simultaneously in paired cerebrospinal fluid (CSF)-serum samples collected retrospectively and prospectively between 2007 and 2022, from patients suspected of NS, in Switzerland. An AI was calculated to account for blood-brain barrier integrity. Area under the receiver operating characteristic curve, sensitivity/specificity and positive/negative predictive values of AI test were estimated. Two NS definitions were used: NS1 included patients with NS suspicion presenting with neurological symptoms and/or acute neurosensory signs, and positive T. Pallidum Hemagglutinations Assay (TPHA)/T. pallidum particle agglutination assay (TPPA) serology and CSF-TPHA/TPPA ≥320, and either CSF-leucocytes >5 cells/mm3 and/or CSF-protein >0.45 g/L and/or a reactive CSF-venereal disease research laboratory (VDRL)/rapid plasma reagin (RPR) test. NS2 included patients with suspected NS presenting with acute ocular and/or otologic symptoms, and positive TPHA/TPPA serology, and a favourable response to NS treatment. Controls were patients diagnosed with any other central nervous system (CNS) pathologies and with positive TPHA/TPPA serology. RESULTS: The study included 71 NS (43 NS1 and 28 NS2) and 110 controls. With a threshold of ≥1.7, sensitivity and specificity of the specific AI test were 90.7% (CI 77.7 to 97.4) and 100% (CI 96.7 to 100.0), respectively, for NS1 and 14.3% (CI 4 to 32.7) and 100% (CI 96.7 to 100.0) for NS2. In patients suspected of NS with a CNS involvement (NS1 group), NS could be confirmed by the positivity of this specific AI. CONCLUSIONS: Measurement of an intrathecal synthesis index of specific anti-T. pallidum IgG in patients with CSF inflammatory signs appears to be a valuable diagnostic test. However, in otic or ocular syphilis, presenting few CSF abnormalities, AI is not sufficient alone to confirm NS diagnosis. TRIAL REGISTRATION: Swiss Association of Research Ethics Committees number 2019-00232.

Diagnostic value of cerebrospinal fluid chemokine c-x-c motif ligand 13 for neurosyphilis: A systematic review and meta-analysis.

The diagnostic value of cerebrospinal fluid chemokine c-x-c motif ligand 13 (CSF CXCL13) for neurosyphilis was assessed by meta-analysis in this study. PubMed, Web of Science and Embase databases were searched to identify relevant articles by using MeSH and free terms of CXCL13 and neurosyphilis. A total of 720 syphilis and 338 neurosyphilis individuals in 6 articles were involved in this meta-analysis. The pooled sensitivity and specificity were 0.82 (95% confidence intervals (CI), 0.77-0.87) and 0.84 (95% CI, 0.79-0.87). The pooled positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under receiver operating characteristic curve were 5.10 (95% CI, 3.90-6.60), 0.21 (95% CI, 0.16-0.28), 24.00 (95% CI, 14.00-39.00) and 0.88 (95% CI, 0.84-0.90), respectively. In subgroup analysis, human immunodeficiency virus infection and diagnostic criteria for neurosyphilis were identified to be associated with heterogeneity. Based on limited evidence, CSF CXCL13 can be helpful in diagnosing neurosyphilis.

Neurosyphilis Mimicking Connective Tissue Disease.

A male in his 60s developed a pruritic, maculopapular rash on his torso and arms, sparing his palms and soles. He tested positive for ANA and an initial skin biopsy identified "bullous lupus," supporting the diagnosis of a connective tissue disease. Additional symptoms included headaches, facial nerve palsy and hearing loss, which partially responded to oral corticosteroids. He subsequently developed a steroid-dependent left eye scotoma, neuroretinitis and optic nerve papillitis. Mycophenolate mofetil was added but an attempted oral steroid taper led to a worsening rash, progressive retinitis and papillitis. Neurosyphilis was confirmed by serum positive rapid plasma reagin test, reactive treponema pallidum antibodies, positive cerebrospinal fluid venereal disease research laboratory and positive spirochete immunostain of skin biopsy of lesional (rash) tissue. Treatment with intravenous ceftriaxone resolved his rash and visual symptoms. It is important to consider syphilis as a mimicker of connective tissue diseases.

Identification of potential biomarkers for diagnosis of syphilis from the cerebrospinal fluid based on untargeted metabolomic analysis.

The infection rate of syphilis continues to rise globally, and the difficulty in diagnosis of neurosyphilis promptly needs to be resolved. More specific and sensitive diagnostic markers for latent syphilis and neurosyphilis should be found. Here the metabolic profiles of 88 cerebrospinal fluid samples from syphilis patients and controls were analyzed by LC/MS-based untargeted metabolomics. In total, 272 metabolites based on 3937 features obtained in ESI- mode and 252 metabolites based on 3799 features in ESI+ mode were identified. The experimental process was evaluated by principal component analysis, partial least squares discriminant analysis, and hierarchical cluster analysis. A clear separation between latent syphilis and neurosyphilis was found. Levels of lipid and linoleic acid metabolites, such as 9-oxo-octadecadienoic acid and 9,10,13-trihydroxyoctadecenoic acid, were increased in syphilis patients. In patients with neurosyphilis, significant changes in levels of 5-hydroxy-L-tryptophan (5-HTP) and acetyl-N-formyl-5-methoxykynurenamine (AFMK) in the tryptophan-kynurenine pathway were also detected. Only one metabolite, theophylline, differed significantly between symptomatic and asymptomatic neurosyphilis patients. Additionally, KEGG analysis revealed significant enrichment of tryptophan metabolism pathways, indicating a high correlation between tryptophan metabolism and syphilis symptoms. Levels of linoleic acid metabolites, 5-HTP, AFMK and theophylline were significantly altered in different patients. The role of these differential metabolites in the development of syphilis is worthy of further exploration. Our results may promote the development of biomarkers for diagnosis of latent syphilis from neurosyphilis, and for that of asymptomatic neurosyphilis from symptomatic neurosyphilis in the future.

Performance of the nontreponemal tests and treponemal tests on cerebrospinal fluid for the diagnosis of neurosyphilis: A meta-analysis.

Background: Nontreponemal and treponemal tests for analyzing cerebrospinal fluid to confirm the existence of neurosyphilis have been widely used, so we aim to evaluate and compare their performance on the cerebrospinal fluid in the diagnosis of neurosyphilis. Methods: We conducted a systematic literature search on five databases and utilized a bivariate random-effects model to perform the quantitative synthesis. Results: Nontreponemal tests demonstrated a pooled sensitivity of 0.77 (95% CI: 0.68-0.83), a pooled specificity of 0.99 (95% CI: 0.97-1.00), and a summary AUC of 0.97 (95% CI: 0.95-0.98). The pooled sensitivity, pooled specificity, and summary AUC of treponemal tests were 0.95 (95% CI: 0.90-0.98), 0.85 (95% CI: 0.67-0.94), and 0.97 (95% CI: 0.95-0.98), respectively. The pooled specificity of all nontreponemal tests varied minimally (ranging from 0.97 to 0.99), with TRUST (0.83) having a higher pooled sensitivity than VDRL (0.77) and RPR (0.73). Among all treponemal tests, EIA has outstanding diagnostic performance with a pooled sensitivity of 0.99 and a pooled specificity of 0.98. Conclusion: Nontreponemal tests exhibited a higher pooled specificity, and treponemal tests exhibited a higher pooled sensitivity in diagnosing neurosyphilis on cerebrospinal fluid. TRUST may be a satisfactory substitute for VDRL. EIA is a prospective diagnostic tool that deserves further study in the future. Our study may be useful to clinical laboratories in selecting appropriate serological tests on the cerebrospinal fluid for the diagnosis of neurosyphilis.

Imaging features of neurosyphilis.

Syphilis is an infectious disease caused by the spirochete Treponema pallidum, subspecies pallidum. Although its incidence has declined after the widespread availability of penicillin, it has recently re-emerged, especially in men who have sex with men and in people living with human immunodeficiency virus (HIV). The neurological manifestations of syphilis, generally known as neurosyphilis, may appear at any time during the infection, including the initial years after the primary infection. Neurosyphilis can be asymptomatic, only with cerebrospinal fluid abnormalities, or symptomatic, characterized by several different clinical syndromes, such as meningitis, gumma, meningovascular, brain parenchyma involvement, meningomyelitis, tabes dorsalis, and peripheral nervous system involvement. However, these syndromes may simulate several other diseases, making the diagnosis often a challenge. In addition, syphilis can also be vertically transmitted from mother to child during pregnancy, leading to neurological manifestations. Neuroimaging is essential to demonstrate abnormal brain or spinal cord findings in patients with neurosyphilis, aiding in the diagnosis, treatment, and follow-up of these patients. This article aims to review the imaging features of neurosyphilis, including the early and late stages of the infection.

Comparison of molecular and serological assays on cerebrospinal fluid for the diagnosis of neurosyphilis.

BACKGROUND: Many assays are available on cerebrospinal fluid (CSF) for the diagnosis of neurosyphilis (NS) but there is no 'gold standard'. OBJECTIVES: The aim of this study was to evaluate different molecular and serological assays used in NS. METHODS: We evaluated two PCR assays and three serological techniques in parallel on CSF samples collected between 2019 and 2020 from patients suspected of NS. RESULTS: The study included 143 patients comprising 30 early NS, 7 late NS and 106 patients without a diagnosis of NS. All patients with NS were symptomatic and had either neurological (67.6%) or ophthalmological signs (54.1%). The qPCR and nPCR assays had overall sensitivities (Se) of 41% and 27%, respectively; with each an overall specificity (Sp) of 100%. VDRL had a Se of 51% and a Sp of 92%. Immunoblot had a Se of 62% and a Sp of 85%. Finally, treponemal tests (TT) had a Se of 96% and a Sp of 69%. CONCLUSIONS: Our study confirms the excellent specificity of molecular techniques allowing to avoid overdiagnosis of NS, and thus, unjustified intensive antibiotic therapy protocols. CSF TT, although not very specific, has an excellent Se confirming that there is almost never NS with negative CSF TT. VDRL and immunoblot tests have better overall diagnostic performance. However, none of these techniques has sufficient diagnostic performance to represent a 'gold standard'. Thus, the diagnosis of NS relies on a combination of clinical and biological parameters with the association of PCR with serology, associating VDRL and immunoblot, in CSF.

Investigation of the role of interleukin 27 in the immune regulation of Treg and Th17 cells in neurosyphilis patients.

INTRODUCTION: Neurosyphilis (NS) is known as a sexually transmitted disease that is very difficult to diagnose and its diagnosis is delayed. Some studies have suggested that the level of interleukin (IL)-27 decreases in syphilis patients and the level of IL-17 increases in these patients, and these immunological changes can be a therapeutic target for these patients. The present study aims to evaluate IL-27's role in the immune regulation of Treg and Th17 cells in NS patients. MATERIAL AND METHODS: 400 documented diagnosed syphilis patients were enrolled to the study and divided into two groups of neurosyphilis (NS) and non-neurosyphilis (S). Also 40 healthy volunteers were enrolled as a healthy control group (C). Peripheral blood mononuclear cells (PBMCs) from peripheral blood and cerebrospinal fluid (CSF) by lumbar puncture were collected as samples. mRNA expression and level of IL-27, IL-17, Th17, IL-17-producing CD4 + T cells and also protein concentration and VDRL of CSF were investigated. To obtain proposed results, flow cytometry, RT-PCR and ELISA were used. RESULTS: The mRNA expression of IL-27 in PBMCs declined significantly in NS patients compared to healthy controls ( p = 0.002) and S patients ( p = 0.005) and decreased significantly in CSF of NS patients in comparison to healthy controls ( p = 0.002) and S patients ( p = 0.003). The frequency of IL-17-producing CD4 + T cells increased significantly in PBMCs of NS patients in comparison to healthy controls ( p = 0.004) and S patients ( p = 0.004). This frequency also increased significantly in CSF of NS patients compared to C ( p = 0.007) and S patients ( p = 0.003). Adding rIL-27 significantly prevented the frequency of IL-17-producing CD4 + T cells from naïve CD4 + T cells under Th17 polarizing conditions from NS patients ( p = 0.043), C ( p = 0.043), and S patients ( p = 0.002) in PBMCs, and also 0.03, 0.02 and 0.03 respectively for NS, S and C of CSF. The results revealed a significant negative relationship between CSF protein and VDRL concentrations and CSF IL-27 levels. CONCLUSIONS: This study confirms previous efforts on the critical role of IL-17 in NS. Also, it supports other results on the inhibitory effects of IL-27 on the therapeutic potential of IL-27 in NS and the inflammation process.

When modern diagnostics is challenged by a historical disease: A case report.

RATIONALE: Syphilis is a bacterial, systemic infectious disease caused by Treponema pallidum spirochetes, which spread rapidly through the body affecting various organs. The term neurosyphilis (NS) refers to a CNS infection that can occur at any stage of the disease. The lack of a gold standard for the diagnosis of NS greatly hinders diagnosis, which must be based mainly on clinical assessment. PATIENT CONCERNS: A 58-year-old man reported dizziness and headache for a week and right-sided hearing impairment, with suspected transient cerebral ischemic attack. A month later he experience transient speech disturbance and suspected cerebral ischemic stroke. DIAGNOSIS: MRI showed fresh ischemic lesions with a diameter up to 10 mm in the deep brain structures on the left side and foci of subacute ischemia also in the deep structures and the brain stem. Cerebrospinal fluid examination showed positive Pandy's reaction, doubtful Noone-Apelt reaction, increased protein level and decreased glucose level. The reactive result of the USR test performed (VDRL) finally allowed the diagnosis of symptomatic CNS syphilis. INTERVENTIONS: Empiric treatment for bacterial meningitis was administered. The patient was transferred to the Department of Infectious Diseases for further treatment. OUTCOMES: The diagnosis has been confirmed at the Department of Infectious Diseases after repeating CSF analysis including VDRL and FTA-ABS. LESSON: Symptoms of NS are nonspecific, hence the diagnostic process is not straightforward. Despite the availability of modern diagnostic techniques, establishing a final diagnosis was challenging, but the patient ultimately received appropriate treatment. It is important to remember that syphilis is not only a disease known from history lessons but is still present in modern times and its incidence is increasing.

Clinical and laboratory features in patients with positive syphilis serology presenting with acute ischemic stroke or transient ischemic attack: a prospective cohort study.

BACKGROUND: Neurosyphilis (NS) can lead to acute ischemic stroke (AIS) or transient ischemic attack (TIA). We compared the clinical characteristics and laboratory features among AIS and TIA patients who were syphilis-seronegative (control group) or had latent syphilis (LS) or NS to evaluate their stroke outcome. METHODS: This prospective cohort study was conducted on patients who had recently suffered AIS or TIA. After serological syphilis screening, clinical and laboratory data were collected, and brain imaging and spinal tap (serologically syphilis-positive patients only) were performed. Stroke outcome was re-evaluated approximately three months later. RESULTS: The 344 enrolled patients were divided into three groups: control group (83.7%), LS (13.1%), and NS (3.2%). A multivariate analysis revealed: 1) age of ≥ 70 years, generalized brain atrophy via imaging, and alopecia (adjusted odds ratio [AOR] = 2.635, 2.415, and 13.264, respectively) were significantly associated with LS vs controls; 2) age of ≥ 70 years (AOR = 14.633) was significantly associated with NS vs controls; and 3) the proportion of patients with dysarthria was significantly lower (AOR = 0.154) in the NS group than in the LS group. Regarding the NS patient cerebrospinal fluid (CSF) profile, only 2/11 cases had positive CSF-Venereal Disease Research Laboratory (VDRL) test results; the other nine cases were diagnosed from elevated white blood cell counts or protein levels combined with positive CSF fluorescent treponemal antibody absorption (FTA-ABS) test results. Regarding disability, the initial modified Rankin scale (mRS) score was lower in the control group than in the NS group (p = 0.022). At 3 months post-stroke, the mRS score had significantly decreased in the control (p < 0.001) and LS (p = 0.001) groups. Regarding activities of daily living, the 3-month Barthel Index (BI) score was significantly higher in control patients than in LS (p = 0.030) or NS (p = 0.002) patients. Additionally, the 3-month BI score was significantly increased in the control (p < 0.001) and LS (p = 0.001) groups. CONCLUSIONS: Because syphilis was detected in many AIS and TIA patients, especially those aged ≥ 70 years, routine serological syphilis screening may be warranted in this population. Patients with syphilitic infection had worse stroke outcomes compared with NS patients.

Neurosyphilis with a rare magnetic resonance imaging pattern confirmed by metagenomic next-generation sequencing: a case report.

BACKGROUND: Neurosyphilis refers to infection of the central nervous system by Treponema pallidum. The clinical presentation is variable and nonspecific. Neuroimaging findings are complex and that the diagnosis is based on clinical presentation, cerebrospinal fluid (CSF) parameters, and serologic and CSF evidence of syphilis. To date, there is no case report describing Treponema pallidum detected by metagenomic next-generation sequencing (mNGS) in CSF. CASE PRESENTATION: In this report, we describe a case of neurosyphilis in a HIV-negative, 29-year-old man, who was admitted to our hospital with an epileptic seizure and progressive cognitive impairment. Brain magnetic resonance imaging (MRI) revealed fluid-attenuated inversion recovery (FLAIR) high signal intensities in bilateral medial and anterior temporal lobes, insula, right pulvinar of the thalami, precuneus, frontal and temporo-occipital lobes. Laboratory examination showed positive results by means of nontreponemal or specific treponemal test in serum and CSF. mNGS of the CSF was also performed to identify Treponema pallidum for the first time. CONCLUSIONS: This case underscores the importance of considering neurosyphilis as a potential cause of mesiotemporal abnormality. In addition, the rapid improvement and wide usability of mNGS technology will bring new breakthroughs in the clinical diagnosis of neurosyphilis.

Platelet Indices Are the Promising Biomarkers in Monitoring Disease Activities in Patients with Syphilis.

OBJECTIVES: To uncover the role of the platelet indices in patients with syphilis. METHODS: A total of 2061 patients with syphilis and 528 healthy controls were enrolled in this retrospective cohort study. The data of platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and indicators of syphilis activities were collected. The correlations between the platelet indices and disease activities were analyzed. RESULTS: A total of 425 (20.6%) of the 2061 patients were of primary and secondary syphilis, 433 (21.0%) latent, 463 (22.5%) serofast, 350 (17.0%) asymptomatic neurosyphilis, and 390 (18.9%) symptomatic neurosyphilis. Compared with the healthy controls, PLT was significantly increased in the primary and secondary syphilis group; whereas, MPV and PDW were significantly decreased in all stages of syphilis. These changes of platelet indices were reversed after anti-treponemal therapy. Further correlation analysis showed that PLT was positively associated with the syphilis activity indicators [rapid plasma reagin (RPR) titer, cerebrospinal fluid white blood cell (CSF-WBC), CSF-protein, and CSF-VDRL (venereal disease research laboratory)] and inflammatory markers [WBC, C-reaction protein (CRP), and erythrocyte sedimentation rate (ESR)]. Conversely, PDW was negatively correlated with all of these parameters. MPV had an inverse relationship with RPR, ESR, and CRP. CONCLUSIONS: Platelet indices are associated with syphilis activities.

Intrathecal Synthesis Index of Specific Anti-Treponema IgG: a New Tool for the Diagnosis of Neurosyphilis.

Neurosyphilis (NS) diagnosis is challenging because clinical signs are diverse and unspecific, and a sensitive and specific laboratory test is lacking. We tested the performance of an antibody index (AI) for intrathecal synthesis of specific anti-Treponema IgG by enzyme-linked immunosorbent assay (ELISA) for NS diagnosis. We conducted a retroprospective monocentric study including adults with neurological symptoms who had serum and cerebral spinal fluid (CSF) samples collected between 2006 and 2021. Two NS definitions were used. NS1 included patients with neurological symptoms, positive Treponema pallidum particle agglutination (TPPA) serology, and CSF-TPPA of ≥320, as well as CSF-leukocytes of >5 cells/mm3 and/or CSF-protein of >0.45 g/L and/or a reactive CSF-VDRL/RPR test. NS2 included patients with acute ocular and/or otologic symptoms, positive TPPA serology, and a response to NS treatment. Controls were patients with central nervous system disorders other than neurosyphilis. Anti-Treponema pallidum IgG were measured simultaneously in serum and CSF, and AI was calculated according to Reiber diagram. We assessed the AI test area under the curve (AUC), sensitivity/specificity, and estimated positive and negative predictive values. In total, 16 NS1 patients, 11 NS2 patients, and 71 controls were included. With an AI of ≥1.7 as a positive test for NS diagnostic, specificity was 98.6% (95% confidence interval [CI 95%] of 92.4 to 100.0) and sensitivity was 81.3% (CI 95% of 54.4 to 96.0) for NS1 and 98.6% (CI 95% 92.4 to 100.0) and 27.3% (CI 95% 6.0 to 61.0), respectively, for NS2. Positive and negative predictive values were >95% for NS1 and >85% for NS2, for prevalence above and below 20%. Measuring an AI for intrathecal synthesis of specific anti-Treponema pallidum IgG is a new promising tool highly specific for NS diagnosis. IMPORTANCE In the context of a lack of a gold standard for the diagnosis of neurosyphilis due to either nonspecific or nonsensitive tests, we present in this article a new promising tool highly specific for NS diagnosis. This new test involves measuring an intrathecal synthesis index of specific anti-Treponema IgG by ELISA.

Previous Syphilis Alters the Course of Subsequent Episodes of Syphilis.

BACKGROUND: The influence of previous syphilis on the course of a subsequent episode is unknown. METHODS: Individuals enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis were allowed to enroll in the study again with subsequent syphilis. For each participant, the index episode was defined as the most recent syphilis episode for which the study entry visit was performed within 30 days of the syphilis diagnosis date. Venipuncture and lumbar puncture (LP) were performed. Total number of syphilis episodes was determined by review of medical and public health records. T. pallidum DNA in blood and rRNA in CSF were detected by polymerase chain reaction (PCR) and reverse transcriptase PCR. Odds ratios (ORs) with 95% confidence intervals (95% CI) were determined by logistic regression. RESULTS: 651 individuals had one (n = 482), two (n = 121) or three or more (n = 48) episodes of syphilis. The proportion of individuals whose index episode was early latent stage was significantly higher in those with ≥3 syphilis episodes; this relationship was reduced to a trend when rate of testing was taken into account. Adjusted odds (aOR) of detection of T. pallidum DNA in blood or rRNA in CSF at the index episode were significantly lower in those with previous syphilis (0.17 [95% CI, 0.09-0.31] and 0.15 [95% CI, 0.07-0.35]). The aOR for neurosyphilis at the index episode was also significantly lower in individuals with previous syphilis (0.54 [95% CI, 0.34-0.87]). CONCLUSIONS: Previous syphilis attenuates the manifestations of subsequent infection with T. pallidum.

Diagnostic tools for neurosyphilis: a systematic review.

PURPOSE: Increasing incidences of syphilis highlight the preoccupation with the occurrence of neurosyphilis. This study aimed to understand the current diagnostic tools and their performance to detect neurosyphilis, including new technologies and the variety of existing methods. METHODS: We searched databases to select articles that reported neurosyphilis diagnostic methods and assessed their accuracy, presenting sensitivity and specificity values. Information was synthesized in tables. The risk of bias was examined using the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy recommendations. RESULTS: Fourteen studies were included. The main finding was a remarkable diversity of tests, which had varied purposes, techniques, and evaluation methodologies. There was no uniform criterion or gold standard to define neurosyphilis. The current basis for its diagnosis is clinical suspicion and cerebrospinal fluid analysis. There are new promising tests such as PCR tests and chemokine measurement assays. CONCLUSIONS: The diagnosis of neurosyphilis is still a challenge, despite the variety of existing and developing tests. We believe that the multiplicity of reference standards adopted as criteria for diagnosis reveals the imprecision of the current definitions of neurosyphilis. An important next step for the scientific community is to create a universally accepted diagnostic definition for this disease.

Cerebrospinal Fluid Analysis.

Cerebrospinal fluid (CSF) analysis is a diagnostic tool for many conditions affecting the central nervous system. Urgent indications for lumbar puncture include suspected central nervous system infection or subarachnoid hemorrhage. CSF analysis is not necessarily diagnostic but can be useful in the evaluation of other neurologic conditions, such as spontaneous intracranial hypotension, idiopathic intracranial hypertension, multiple sclerosis, Guillain-Barré syndrome, and malignancy. Bacterial meningitis has a high mortality rate and characteristic effects on CSF white blood cell counts, CSF protein levels, and the CSF:serum glucose ratio. CSF culture can identify causative organisms and antibiotic sensitivities. Viral meningitis can present similarly to bacterial meningitis but usually has a low mortality rate. Adjunctive tests such as CSF lactate measurement, latex agglutination, and polymerase chain reaction testing can help differentiate between bacterial and viral causes of meningitis. Immunocompromised patients may have meningitis caused by tuberculosis, neurosyphilis, or fungal or parasitic infections. Subarachnoid hemorrhage has a high mortality rate, and rapid diagnosis is key to improve outcomes. Computed tomography of the head is nearly 100% sensitive for subarachnoid hemorrhage in the first six hours after symptom onset, but CSF analysis may be required if there is a delay in presentation or if imaging findings are equivocal. Xanthochromia and an elevated red blood cell count are characteristic CSF findings in patients with subarachnoid hemorrhage. Leptomeningeal carcinomatosis can mimic central nervous system infection. It has a poor prognosis, and large-volume CSF cytology is diagnostic.

Diagnostic role of CXCL13 and CSF serology in patients with neurosyphilis.

BACKGROUND: Considering the unknown prevalence of neurosyphilis in West China, and the confusing diagnosis of neurosyphilis, the role of CSF_CXCL13 and syphilis serology was studied to provide a more accurate reference for the clinical detection and diagnosis of neurosyphilis. METHODS: A retrospective data set I was used to investigate the prevalence of neurosyphilis, as well as the laboratory characteristics of 244 patients. Besides, to explore the diagnostic value of CSF_CXCL13 and syphilis serology for neurosyphilis, another 116 CSF_serum paired samples (data set II) were collected from 44 neurosyphilis and 72 non-neurosyphilis/syphilis patients. RESULTS: About 6.25% (156 out of 2494) syphilis was neurosyphilis. When Treponema pallidum infection occurs, syphilis serology (sero_TRUST ≥1:16 and sero_TPPA titre ≥1:10240) can be good predictors of neurosyphilis, as well as syphilis CSF serology (CSF_TPPA ≥1:320, CSF_TRUST and venereal disease research laboratory). The sensitivity of serology in neurosyphilis can be complemented by CSF_CXCL13, which could be the therapy monitor of neurosyphilis. CONCLUSION: Due to the lack of ideal biomarkers for neurosyphilis, the importance of syphilis serology cannot be ignored, and their combination with CSF_CXCL13 or other biomarkers should be further investigated.

Neurosyphilis cerebrospinal fluid findings in patients with ocular syphilis.

Purpose: To evaluate neurosyphilis cerebrospinal fluid (CSF) findings and initial ophthalmic manifestations in patients with syphilitic uveitis.Methods: We retrospectively reviewed the records of CSF analysis of 14 patients with syphilitic uveitis with treponemal analysis - chemiluminescent immunoassay and TPHA- and non-treponemal analysis - Rapid Plasma Reagin test - RPR.Results: 86% were males and 43% HIV+. Ocular signs of syphilis lead to the diagnosis of syphilis in 78% of patients. Typical syphilitic uveitis presentations included: acute syphilitic posterior placoid chorioretinitis (50% of patients), retinitis (21% of patients) and punctate inner retinitis (7% of patients). 57% of patients had definite neurosyphilis by the CDC criteria, while 71% had CSF abnormalities suggestive of central nervous system involvement.Conclusion: Based on international guidelines, the frequent CSF abnormalities found in syphilitic uveitis patient supports the diagnosis of neurosyphilis in a majority of patients.