OBJECTIVE: To systematically assess the diagnostic accuracy of CXCL13 testing of cerebrospinal fluid (CSF) for neurosyphilis diagnosing.
METHODS: Systematic review and meta-analysis.
METHODS: PubMed, Embase, Cochrane Library and Web of Science databases from their inception until 1 May 2023.
METHODS: Both cross-sectional and case-control diagnostic test studies evaluating the diagnostic value of CSF CXCL13 in diagnosing neurosyphilis were included, with no language restrictions.
METHODS: Two researchers extracted data independently from all finally included articles. The updated Quality Assessment of Diagnostic Accuracy Studies tool was used to assess the quality of the included studies. Quantitative synthesis was done using a bivariate random-effects model.
RESULTS: This meta-analysis included seven eligible studies involving a total of 1152 patients with syphilis and 430 patients with neurosyphilis. The pooled sensitivity, specificity and summary area under the curve (AUC) of CSF CXCL13 testing for the diagnosis of neurosyphilis were 0.76 (95% CI 0.64 to 0.85; I2=82%), 0.83 (95% CI 0.80 to 0.85; I2=32.29%) and 0.84 (95% CI 0.81 to 0.87), respectively. Sensitivity analysis confirmed the stability of the combined results. Meta-regression analysis revealed that the heterogeneity of pooled sensitivity was related to different study regions; subgroup analysis indicated that the diagnostic value of CSF CXCL13 testing reported in studies from China was superior to that reported in non-Chinese studies (pooled sensitivity, specificity and summary AUC values were 0.84 (I2=0) vs 0.64 (I2=79.53%), 0.83 (I2=42.03%) vs 0.83 (I2=32.87%) and 0.87 vs 0.83, respectively). The diagnostic value reported in studies with a sample size ≥200, unclassified neurosyphilis and HIV-negative subgroups was superior to the total combined value.
CONCLUSIONS: This meta-analysis has demonstrated a reasonable level of accuracy for diagnosis of neurosyphilis with CSF CXCL13 testing. Further multicentre, prospective diagnostic studies, especially in asymptomatic neurosyphilis and HIV-infected patients, are needed to provide more evidence for evaluation before clinical application.
UNASSIGNED: CRD42023414212.

暂无摘要。

With syphilis resurgence, physicians should be more vigilant to infection-induced cerebral vasculitis in high-risk patients presenting with neurological symptoms. In this case, neurosyphilis should not be missed. Thorough serologic screening and lumbar puncture are crucial for diagnosis, and further research is needed for safe and effective treatments in these populations.

Neurosyphilis is an infection of the central nervous system caused by the spirochete, Treponema pallidum. New syphilis infections have been increasing around the world each year. This disease was much of a concern in the pre-penicillin era, where when left untreated many cases progressed to tertiary syphilis which can commonly manifest as neurosyphilis. Of particular interest, neurosyphilis has been linked to masquerading itself as various psychiatric conditions. This narrative review focuses on exploring psychiatric manifestations of neurosyphilis as well as the importance of screening in psychiatric settings and clinicians maintaining high clinical suspicion of the disease. A systematic search was conducted for published articles from 2003 to 2023 using PubMed, EMBASE, and Google Scholar. A total of 66 articles met the criteria and were used for detailed analysis, where psychiatric manifestations and clinical progression of patients were discussed in detail. Psychiatric manifestations that were explored include dementia, delirium, depression, mania, personality changes, and psychosis. One of the most common manifestations of neurosyphilis appears to be severe neurocognitive impairment. There are also rare psychiatric conditions neurosyphilis mimics that have been described in literature such as Capgras syndrome and Geschwind syndrome. A narrative review of the literature revealed a low level of clinical awareness of neurosyphilis as a possible etiology of various psychiatric disorders. This resulted in delayed or inaccurate diagnosis and consequently delayed initiation of adequate treatment. Considering that many psychiatric manifestations of neurosyphilis are reversible with proper treatment, it is imperative to implement routine screening for syphilis among psychiatric patients.

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.

We review key concepts in the diagnosis, treatment, and follow-up of individuals with neurosyphilis. We describe the epidemiology of syphilis in the United States, highlight populations that are markedly affected by this infection, and attempt to estimate the burden of neurosyphilis. We describe the cardinal clinical features of early and late (tertiary) neurosyphilis and characterize the clinical significance of asymptomatic neurosyphilis in the antibiotic era. We review the indications for cerebrospinal fluid (CSF) examination and the performance characteristics of different CSF assays including treponemal and lipoidal antibodies, white cell count, and protein concentration. Future biomarkers and the role of imaging are briefly considered. We review preferred and alternative treatments for neurosyphilis and evidence for their use, including evidence for the use of enhanced intramuscular benzathine penicillin G to supplement intravenous penicillin.

The gold standard for diagnosing neurosyphilis (NS) is currently unavailable; various laboratory parameters in cerebrospinal fluid (CSF) and blood can assist in the diagnosis.
PubMed, Embase, and the Cochrane Library were searched. Studies utilizing laboratory tests to assist in the diagnosis of NS were included. The pooled indicators for diagnostic performance and their respective 95% confidence intervals (CIs) were calculated. We used the superiority index to test the superiority of a diagnostic test.
Eleven citations were included in the study. Albumin quotient, CSF-TPHA, CSF-EIA, CSF-LDH, CSF-WBC, CSF-CXCL13, FTA-ABS, CSF-PCR, RPR, CSF-TPPA, TRUST, and CSF-venereal diseases research laboratory (VDRL) were assessed in the studies included. The pooled estimates of sensitivity, specificity, AUC of SROC and their respective 95% CIs for CSF-TPPA and CSF-VDRL were 0.97 (0.17, 1.00), 0.84 (0.62, 0.95), 0.93 (0.91, 0.95) and 0.74 (0.59, 0.85), 0.99 (0.93, 1.00), 0.94 (0.91, 0.96), respectively. CSF-TPHA demonstrated the highest relative sensitivity. CSF-VDRL manifested the highest specificity. CSF-TPHA, TRUST, CSF-VDRL, CSF-EIA, and RPR ranked in the top five laboratory tests with superiority index.
CSF-TPHA, TRUST, CSF-VDRL, CSF-EIA, and RPR indicate acceptable performance in detecting NS compared to other modalities. Comprehensive diagnostic strategies still play a significant role in the diagnosis of NS.

Neurosyphilis with mesiotemporal lobe lesions remains a difficult entity to diagnose, especially when it mimics herpes simplex encephalitis (HSE). Here, we report what appeared to be the first case of mesiotemporal imaging of neurosyphilis presenting as a \"knife-cut\" sign and mimicking HSE pathological hallmarks on imaging. The magnetic resonance imaging (MRI) changes in neurosyphilis and HSE were indistinguishable in the initial diagnosis because of the common involvement of the mesiotemporal lobe. Neurosyphilis was diagnostically confirmed by positive readings in the treponema pallidum hemagglutination assay (TPHA), rapid plasma reagin (RPR) and cerebrospinal fluid-polymerase chain reaction (CSF-PCR) tests for Treponema pallidum infection. Neurosyphilis and HSE had similar clinical features and signs on MRI, except the knife-cut sign which is a common diagnosis in HSE. Therefore, neurosyphilis with mesiotemporal changes and knife-cut signs on MRI should be evaluated in the differential diagnosis in all patients, as similar changes may also occur in HSE patients. The literature review of published articles between 1997 and 2020 was conducted to further validate our clinical observations and discuss diagnostic and treatment options for neurosyphilis with mesiotemporal lobe lesions.

Routinely available laboratory tests for Treponema pallidum remain suboptimal for diagnostic, prognostic, predictive, and monitoring purposes. Biomarkers with enhanced performance characteristics can improve diagnostic confidence and facilitate management. We conducted a systematic review to examine the utility of biomarkers in the diagnosis and management of syphilis.
We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses to identify articles for inclusion and independently reviewed them for eligibility and study quality using a 3-stage procedure. The search, conducted by a senior library informationist, used PubMed, Embase, Cochrane Library, and Scopus and included any study published before May 2022.
Of the 111 studies identified, 31 (27.9%) were included in our review. Most studies were cross-sectional or prospective. The data were strikingly heterogeneous examining a variety of biomarkers across different syphilis stages, using different methodologies and definitions of treatment success. Available publications chiefly focused on diagnosing various syphilis stages, neurosyphilis and congenital syphilis, serological cure, the serofast state, and reinfection.
Despite increasing attempts to identify novel biomarkers, we found limited evidence to support the use of any biomarker in clinical decision making at this time; the syphilis biomarker literature is heterogenous and lacks measurement of clinically meaningful end points. We recommend the formation of a working group to set priorities for syphilis biomarker research and to guide future study of clinically meaningful biomarkers.

Chronic meningitis (CM) is characterized by neurological symptoms associated with the evidence of cerebrospinal fluid pleocytosis lasting > 4 weeks. Studies on the management of CM in Brazil are scarce.
To critically review the literature on CM and propose a rational approach in the Brazilian scenario.
Narrative literature review discussing the epidemiology, clinical evaluation, basic and advanced diagnostic testing, and empirical and targeted therapy for the most relevant causes of CM. The present review was contextualized with the local experience of the authors. In addition, we propose an algorithm for the management of CM in Brazil.
In Brazil, tuberculosis and cryptococcosis are endemic and should always be considered in CM patients. In addition to these diseases, neurosyphilis and other endemic conditions should be included in the differential diagnosis, including neurocysticercosis, Baggio-Yoshinari syndrome, and endemic mycosis. After infectious etiologies, meningeal carcinomatosis and autoimmune diseases should be considered. Unbiased and targeted methods should be used based on availability and clinical and epidemiological data.
We propose a rational approach to CM in Brazil, considering the epidemiological scenario, systematizing the etiological investigation, and evaluating the timely use of empirical therapies.
BACKGROUND:  A meningite crônica (MC) é caracterizada por sintomas neurológicos associados à evidência de pleiocitose do líquido cefalorraquidiano por > 4 semanas. Os estudos sobre o manejo da MC no Brasil são escassos.
OBJECTIVE:  Rever criticamente a literatura sobre MC e propor uma abordagem racional no cenário brasileiro. MéTODOS:  Revisão da literatura narrativa discutindo a epidemiologia, avaliação clínica, testes diagnósticos básicos e avançados, além da terapia empírica e direcionada para as causas mais relevantes do MC. A presente revisão foi contextualizada com a experiência local dos autores. Além disso, propomos um algoritmo para o manejo da MC no Brasil.
RESULTS:  No Brasil, a tuberculose e a criptococose são endêmicas e devem ser sempre consideradas em pacientes com MC. Além destas doenças, a neurossífilis e outras condições endêmicas devem ser incluídas no diagnóstico diferencial, incluindo: neurocisticercose, síndrome de Baggio-Yoshinari e micoses endêmicas. Após etiologias infecciosas, devem ser consideradas a carcinomatose meningeal e doenças autoimunes sistêmicas. Métodos diagnósticos devem ser utilizados com base na disponibilidade, nos dados clínicos e nos dados epidemiológicos. CONCLUSãO:  Propomos uma abordagem racional para a MC no Brasil, considerando o cenário epidemiológico, sistematizando a investigação etiológica e avaliando o uso oportuno de terapias empíricas.