Diagnosis Of Neurosyphilis Research Articles

Clinical and Laboratory Characteristics, Diagnosis, and Treatment of Patients with Neurosyphilis in Emergency Department: A Retrospective Study of 12 Patients.

Syphilis, caused by Treponema pallidum, presents a diagnostic challenge due to its diverse clinical manifestations. Neurosyphilis has seen a resurgence in recent years, particularly among men who have sex with men and those living with HIV. Diagnosis of neurosyphilis in emergency settings is challenging due to its varied neurological presentations. This study aims to serve as a reference for dermatologists and neurologists in diagnosing and treating neurosyphilis. This retrospective study analyzed patients who presented with neuropsychiatric symptoms and were ultimately diagnosed with neurosyphilis. These patients were collected from the emergency department in Peking Union Medical College Hospital between January 2018 and November 2023. The medical history, clinical symptoms, laboratory examinations, cranial MRI characteristics, and treatment regimens of these patients were investigated. Among the included 12 neurosyphilis patients, memory deterioration was observed in 8 out of the 12 neurosyphilis patients. Diagnosis often resulted in delays, with misdiagnoses mainly including Alzheimer's disease, stroke, and epilepsy. Neuroimaging revealed various abnormalities, predominantly affecting ventricular and temporal regions. Treatment with penicillin-based regimens varied in compliance, with only a minority of patients adhering to guidelines. Treatment outcomes were inconsistent, with some patients experiencing irreversible neurological damage and fluctuating serum rapid plasma reagin (RPR) titers. Diagnosis of neurosyphilis in the emergency department remains challenging, necessitating awareness of its varied neurological presentations. Enhanced diagnostic strategies are imperative to accelerate treatment initiation and improve outcomes for affected individuals.

Syphilis Should not be Overlooked in any Individual, Irrespective of their Condition.

Syphilis remains a significant challenge in public health, largely because of its diverse clinical manifestations, often resulting in underdiagnosis especially among patients with neurogenic disability. We present a case of neurosyphilis in a 63-year-old patient with a spinal cord injury. Despite syphilis being a well-established sexually transmitted infection, the exacerbation of neurological and dermatological symptoms during physical examination prompted an investigation into alternative causes beyond the patient's pre-existing paraparesis, ultimately resulting in the diagnosis of neurosyphilis. This case highlights the importance of considering syphilis as a potential diagnosis in individuals regardless of their medical history. The incidence of syphilis cases is on the rise, presenting an ongoing challenge.Faced with atypical neurological symptomatology, it is necessary to know how to investigate and discuss tertiary syphilis.In the event of neurological worsening in a neuro-injured patient, it is necessary to know how to discuss a curable diagnosis.

Neurosyphilis patients presenting with ocular motor cranial nerve palsy in the modern antibiotic era: Case series from two centers and review of the literature

BackgroundSyphilis can mimic the clinical features of many neurological disorders and cause ocular motor cranial nerve palsy (OMCNP). This study aims to characterize the clinical features of neurosyphilis patients presenting with OMCNP. Methods In a retrospective study and literature review, demographic data, clinical presentations, laboratory findings, radiological findings, treatment approaches, and outcomes were recorded and analyzed. ResultsOverall, 0.74 % and 1.64 % of patients presenting to two institutes exhibited syphilitic OMCNP, respectively. A total of 32 patients (23 from the literature) were recruited, with a median age of 46 years and a predominance of males (81.3 %). Meningovascular neurosyphilis was diagnosed in 29 patients (90.6 %), and tabes dorsalis was found in 3 patients (9.4 %). Unilateral OMCNP was present in 24 patients (65.5 %). Unilateral sixth nerve palsy was observed in 10 patients (34.5 %), followed by unilateral third nerve palsy in 9 patients (31.0 %), and unilateral multiple OMCNP in 5 patients (17.2 %). A total of 12 patients (41.4 %) presented with isolated OMCNP, and 4 of these individuals developed other neurological deficits during the disease. Pupillary involvement was found in all patients who presented unilateral third nerve palsies. After treatment, 17 patients (58.6 %) achieved complete recovery of ocular motility; 6 patients (20.7 %) achieved partial recovery; 5 patients (17.2 %) remained stable; and 1 patient (3.5 %) became progressive. ConclusionsPatients presenting with OMCNP alone or combined with other cranial nerve deficits should be screened for neurosyphilis, and the standard treatment regimen should be initiated if a diagnosis of neurosyphilis is established.

Novel and characteristic radiological features of neurosyphilis: a case series

BackgroundTreponema pallidum can invade the central nervous system (CNS) early in its infection, causing neurosyphilis. Neurosyphilis typically presents with meningovasculitis in the acute or subacute phase, while tabes dorsalis and dementia paralytica are classical conditions in the later stages. However, syphilis is often misdiagnosed as other conditions such as tumors or autoimmune diseases including vasculitis and encephalitis, which is why the condition is known as “The Great Mimicker.” The increasing incidence of syphilis in recent years emphasizes the importance of early diagnosis and treatment; however, its multiple clinical manifestations impose diagnostic challenges for clinicians because it resembles other diseases. In this case series, we present the impressive manifestations of neurosyphilis through three unique radiological presentations.Case presentationCase 1 details optic nerve involvement in an HIV-positive male, where MRI and fundoscopic findings confirmed syphilitic optic neuritis. Case 2 describes a patient in her pregnancy initially suspected of acoustic neuroma on MRI, later diagnosed with syphilitic gumma affecting the inner ear canal. Case 3 is a young male with clinical features mimicking temporal arteritis, ultimately identified as skull osteomyelitis secondarily causing inflammation of the musculus temporalis and meningitis.ConclusionsThese cases underscore the necessity of considering syphilis in differential diagnoses, given the diversity of its clinical presentations. Radiology plays an important role in avoiding unnecessary interventions. The increasing prevalence of recurrent syphilis imposes diagnostic challenges, emphasizing the importance of the early diagnosis and treatment of neurosyphilis by clinicians.

Refining a non-invasive prediction model for neurosyphilis diagnosis by using immunoassay to detect serum anti-TP0435 (TP17) and TP0574 (TP47) IgG antibodies: two-centre cross-sectional retrospective study in China

ObjectivesInvasive lumbar puncture is the conventional method for diagnosing neurosyphilis (NS). We investigated a non-invasive alternative method to detect serum Treponema pallidum-specific antibodies against highly immunogenic antigens TP0171 (TP15), TP0435 (TP17), and TP0574 (TP47) by using luciferase immunosorbent assay. MethodsA total of 816 HIV-negative patients suspected of NS from the Beijing and Guangzhou cohorts were retrospectively selected and tested for serum anti-TP15, TP17, and TP47 IgG antibodies. Two diagnostic prediction models were developed using stepwise logistic regression in the Beijing cohort, and evaluated in the Guangzhou cohort for external validation. ResultsSerum antibodies against TP15, TP17, and TP47 showed moderate capability for NS diagnosis in the Beijing cohort and the corresponding area under the receiver operating characteristic curves (AUCs) were 0.722 [95% confidence interval (CI): 0.680–0.762)], 0.780 (95% CI: 0.741–0.817), and 0.774 (95% CI: 0.734–0.811), respectively. An expanded NS prediction model integrated with anti-TP17 and anti-TP47 antibodies showed better performance than the base NS diagnostic model without anti-TP17 and anti-TP47 antibodies with the AUC of 0.874 (95% CI: 0.841–0.906) vs. 0.845 (95% CI: 0.809–0.881) (p = 0.007) in the development cohort, and 0.934 (95% CI: 0.909–0.960) vs. 0.877 (95% CI: 0.840–0.914) (p < 0.001) in validation cohort, respectively. Decision curve analysis revealed that the net benefit of the expanded model exceeded that of the base model when the threshold probability was between 0.10 and 0.95 in both the development and external validation cohorts. DiscussionSerum antibodies against TP17 and TP47 exhibited promising diagnostic capability for NS and significantly enhanced the predictive accuracy of model for NS diagnosis. Our study highlights the potential of serum treponemal antibody detection as a non-invasive method for NS diagnosis to substitute invasive lumbar puncture in NS diagnosis.

Clinical spectrum of late symptomatic neurosyphilis in China: an 11-year retrospective study

ObjectivesThis study aimed to describe the clinical features of neurosyphilis in Chinese patients in an attempt to find clinical features that are helpful for the early identification of neurosyphilis.MethodsThis retrospective...

Cerebrospinal fluid CXCL13 concentration for diagnosis of neurosyphilis: a systematic review and meta-analysis

ObjectiveTo systematically assess the diagnostic accuracy of CXCL13 testing of cerebrospinal fluid (CSF) for neurosyphilis diagnosing.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase, Cochrane Library and Web of Science databases from their...

Detection of intrathecal antibodies for diagnosis of neurosyphilis

Detection of intrathecal antibodies for diagnosis of neurosyphilis

Efficiency of Immunoblot While Determination of Antibodies to Treponema Pallidum in Cerebrospinal Fluid

BACKGROUND: A decrease in the incidence of syphilis has been observed in the world and in Ukraine in recent years. At the same time, an increase in cases of neurosyphilis is recorded. Diagnosis of neurosyphilis is quite difficult and based on the correct interpretation of the complex of various diagnostic tests. OBJECTIVES: The paper is aimed to determine diagnostic potential of treponemal tests (TTs) and evaluate effectiveness of Treponema pallidum immunoblot (TPI) while research on cerebrospinal fluid (CSF) in differential diagnosis of neurosyphilis. MATERIALS AND METHODS: The research object was CSF of patients with late forms of syphilis. The regulated serological and immunological methods in accordance with current guidelines and orders of the Ministry of Healthcare of Ukraine were used for laboratory diagnosis of neurosyphilis: Enzyme immunoassays (EIA), fluorescent treponemal antibody (FTA), T. pallidum hemagglutination assay (TPHA), and TPI. RESULTS: Effectiveness of TTs in the diagnosis of neurosyphilis while research on 23 samples of CSF was carried out by the following methods: EIA (Immunoglobulin [Ig]M + IgG), FTA, andTPHA. The above-mentioned TTs used in serological diagnosis of CSF do not always meet the problem of confirming neurosyphilis diagnosis. According to these investigations, both positive and false positive results were obtained. In order to verify the diagnosis, a study on positive and false positive samples of CSF by TPI method was carried out. Positive results were obtained in 13 samples with the established duration of the disease. CONCLUSIONS: TPI is an optimal treponemal immunological method of examination of CSF to diagnose neurosyphilis with a high degree of reliability. The use of TPI while research on CSF makes it possible to verify the diagnosis of neurosyphilis by differentiated detection of antibodies to the most immunogenic antigens of T. pallidum eliminating the subjective factor of the reaction and simplifies diagnostic procedure.

Neutrophil CD64 index as a potential blood biomarker for the diagnosis of neurosyphilis in secondary and tertiary syphilis: A retrospective study

ObjectiveTo examine the correlation of neutrophil CD64 (nCD64) index with neurosyphilis (NS) across different stages of syphilis. MethodsA total of 1243 syphilis patients at different stages (344 of primary, 385 of secondary, and 514 of tertiary) included in this study were divided into NS and non-NS (NNS). Correlations of nCD64 index with currently used syphilis biomarkers were explored using Spearman correlation test. Relationships between nCD64 index and NS at different stages were investigated by stratified analysis and restricted cubic spline model. The diagnostic performance of nCD64 index for NS was assessed by receiver operating characteristic (ROC) curve. ResultsSignificant statistical correlations of nCD64 index with cerebrospinal fluid (CSF) NS indicators were found in secondary and tertiary syphilis. Increased nCD64 index was associated with increased risk of NS in secondary and tertiary syphilis. ROC analysis values further confirmed the diagnostic potential of nCD64 index for NS. Marked decrease of nCD64 index was observed in NS patients after effective antisyphilitic treatments. ConclusionsThe nCD64 index may help to the diagnosis of NS in secondary and tertiary syphilis.

Late-onset mania as a manifestation of neurosyphilis: A Case Report

IntroductionThe evaluation of manic behavior with later onset is crucial, as various organic factors such as medications, infections, metabolic disturbances, tumors, and epilepsy can serve as potential etiological causes. While not universally observed, most studies indicate a connection between late-onset mania and neurological disorders like neurosyphilis.ObjectivesOur study aims to investigate the relationship between late-onset mania and neurosyphilis.MethodsIn this paper, we present a case of neurosyphilis presenting exclusively with symptoms of mania.ResultsA 72-year-old Tunisian woman with no prior medical or psychiatric history was referred to the psychiatric emergency room due to alterations in her mental state and behavior over the past ten days. During the psychiatric assessment, she displayed increased motor activity, fluctuating emotions, and rapid flow of ideas. The general physical examination yielded no notable findings. The serum Venereal Disease Research Laboratory (VDRL) test returned a strongly positive result (+++), and the TPHA examination confirmed a positive result at a titer of 1/60. In the serologic analysis of cerebrospinal fluid, VDRL was also positive, thereby confirming the diagnosis of neurosyphilis (NS). The diagnosis of mania secondary to a medical condition was established. The patient was treated with ceftriaxone and antimanic medications, resulting in a significant improvement in her psychiatric symptoms within a few days.ConclusionsThis case underscores the importance of conducting serologic testing for syphilis in patients who present with manic symptoms, experience a late-onset mental disorder, and have no prior history or family history of affective disorders.Disclosure of InterestNone Declared

Cerebrospinal Fluid Biomarkers of Symptomatic Neurosyphilis in People With HIV Compared with Uninfected Individuals.

We evaluated the diagnostic clinical performance characteristics (DCPC) of cerebrospinal fluid (CSF) total protein (TP), white blood cell count (WBC), and lactate (LA) with different cutoff points as adjunct biomarkers of confirmed or presumptive symptomatic neurosyphilis (NS) and the impact of HIV infection. From 5,640 participants who underwent lumbar punctures, 236 participants were included, and classified as either people with HIV (PWH) or people without HIV (PWoH) according to the CDC criteria for confirmed NS (n = 42), presumptive NS (n = 74), systemic syphilis (SS) (n = 38), serological diagnosis of syphilis (n = 18), PWH without SS and NS (n = 10), and negative control (n = 72). In PWoH, for presumptive NS, the combination of CSF TP > 45mg/dL and/or WBC > 5.0 cells/mm3 is valuable for screening, whereas in PWH, it is not recommended for either screening or case-finding NS, however the DCPC were better in the suppressed group. In PWoH, the value of CSF TP > 45mg/dL is adequate for both screening and confirmation of presumptive NS, subject to prevalence. For WBC count > 20 cell/mm3, the positive predictive value (PPV) of the test is almost perfect, suggesting a confirmatory test. In PWH, CSF TP is an inadequate marker of NS. The WBC count, with cutoffs of > 10 or > 20 cells/mm3, was moderately applicable for screening.As conclusions: CSF WBC count and TP showed distinct DCPC in confirmed or presumptive NS, better in the former. These biomarkers could be included for presumptive NS diagnosis. DCPC of these biomarkers for the diagnosis of NS is greatly affected by HIV co-infection.

Neutrophil-Associated Proteins as Novel Biomarkers Elevated in Cerebrospinal Fluid of Patients With Neurosyphilis.

The immunopathological mechanisms underlying neurosyphilis remain incompletely elucidated, and the diagnosis of neurosyphilis presents challenges. We used an antibody microarray to detect 640 proteins in cerebrospinal fluid (CSF) samples collected from 6 patients with non-neurosyphilis and 10 with neurosyphilis. The levels of CSF CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9 in 46 patients with non-neurosyphilis, 51 with untreated neurosyphilis, and 31 posttreatment for neurosyphilis were quantified using enzyme-linked immunosorbent assay. The associations between the levels of these proteins and clinical parameters in neurosyphilis were evaluated using Spearman analysis, and the diagnostic performance of these proteins in neurosyphilis was assessed using receiver operating characteristic curve. A total of 102 differentially expressed proteins between neurosyphilis and non-neurosyphilis were identified. The levels of significantly elevated neutrophil-associated proteins (CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9) in neurosyphilis positively correlated with white blood cell counts, rapid plasma regain (RPR) titer, and protein concentration in CSF. The combination of CSF CXCL8, MMP9, and LCN2 yielded an area under the curve of 0.92 for diagnosing neurosyphilis, surpassing that of CSF RPR. CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9 could be associated with central nervous system damage of neurosyphilis. The combination of CSF CXCL8, MMP9, and LCN2 is a promising biomarker for diagnosing neurosyphilis.

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.

Neurosyphilis: insights into its pathogenesis, susceptibility, diagnosis, treatment, and prevention.

Invasion of the central nervous system by Treponema pallidum can occur at any stage of syphilis. In the event that T. pallidum is not cleared promptly, certain individuals may experience progression to neurosyphilis, which manifests as cognitive and behavioral abnormalities, limb paralysis, and potentially fatal outcomes. Early identification or prevention of neurosyphilis is therefore crucial. The aim of this paper is to conduct a critical and narrative review of the latest information focusing exclusively to the pathogenesis and clinical management of neurosyphilis. To compile this review, we have conducted electronic literature searches from the PubMed database relating to neurosyphilis. Priority was given to studies published from the past 10 years (from 2013 to 2023) and other studies if they were of significant importance (from 1985 to 2012), including whole genome sequencing results, cell structure of T. pallidum, history of genotyping, and other related topics. These studies are classic or reflect a developmental process. Neurosyphilis has garnered global attention, yet susceptibility to and the pathogenesis of this condition remain under investigation. Cerebrospinal fluid examination plays an important role in the diagnosis of neurosyphilis, but lacks the gold standard. Intravenous aqueous crystalline penicillin G continues to be the recommended therapeutic approach for neurosyphilis. Considering its sustained prominence, it is imperative to develop novel public health tactics in order to manage the resurgence of neurosyphilis. This review gives an updated narrative description of neurosyphilis with special emphasis on its pathogenesis, susceptibility, diagnosis, treatment, and prevention.

Acute Ischaemic Stroke in the Context of Neurosyphilis: How Does Antibiotic Therapy Help, and When Should It Be Given?

Neurosyphilis (NS) refers to a central nervous system infection caused by Treponema pallidum. In recent years, there has been an increasing incidence of syphilis; however, NS is uncommon compared to the era before the discovery of penicillin. Manifestations are usually non-specific, ranging from asymptomatic cases to syphilitic meningitis, meningovascular syphilis, general paresis and tabes dorsalis. Meningovascular syphilis can cause an inflammatory arteritis of cerebral arteries, leading to vascular occlusion and cerebral infarction. We report a case of an ischaemic stroke in a patient with several vascular risk factors, presenting with right hemiparesis, hemihypesthesia and dysarthria. Initial computed tomography with angiography of the head and neck was normal; however, magnetic resonance imaging of the brain revealed a thalamic and internal capsule infarct. Serum T. pallidum antibodies were positive, as well as a rapid plasma reagin test. Cerebrospinal fluid analysis confirmed the diagnosis of neurosyphilis, and the patient was treated with ceftriaxone for 14 days due to a penicillin allergy. Although there is a high prevalence of stroke in patients with NS, this condition is typically underdiagnosed. Untreated NS carries a higher risk of stroke recurrence compared to other risk factors. Therefore, early diagnosis and treatment are essential. This case highlights the importance of considering NS in stroke victims, even in older patients with several additional vascular risk factors, to prevent recurrence and other complications. Neurosyphilis (NS) can occur at any stage of syphilis infection, and it can be asymptomatic or symptomatic, presenting as syphilitic meningitis, meningovascular syphilis, general paresis or tabes dorsalis.Ischaemic strokes are a frequent complication of NS, occurring in 14% of the cases. However, only 19% of the cases are correctly diagnosed.NS should be considered as a potential cause of stroke, even in older patients with several other vascular risk factors. This is essential to prevent future strokes, as well as dementia and other complications.

Enhancing clinical awareness: retrospective analysis of neurosyphilis cases and diagnostic predictors for early recognition and treatment.

This is a retrospective analysis of clinical data from individuals diagnosed with neurosyphilis, aiming to enhance healthcare professionals' understanding of the disease and expedite early diagnosis and intervention. A retrospective analysis was conducted on the clinical records of 50 patients who received a diagnosis of symptomatic neurosyphilis and were admitted to the Neurology Department during the period spanning January 2012 to December 2022. Clinical manifestations encompassed diverse phenotypes, with syphilitic meningitis accounting for 16% of cases, characterized by symptoms such as headache, blepharoptosis, paralysis, blurred vision, and tinnitus. Meningovascular syphilis presented in 36% of cases, exhibiting episodic loss of consciousness, limb numbness, and limb convulsion. Paralytic dementia manifested in 36% of cases, featuring symptoms such as memory loss, sluggish response, and slow movement. Tabes dorsalis was observed in 12% of cases, presenting with weakness, numbness, and staggering. Routine cerebrospinal fluid (CSF) analysis indicated abnormal white blood cell counts in 60% of patients, while biochemical testing revealed abnormal protein content in 52% of patients. Notably, statistically significant differences were observed between patients with interstitial and parenchymatous neurosyphilis (Z = 2.023, P = 0.044) in terms of CSF protein content. Electroencephalogram (EEG) results were abnormal in six patients, and imaging studies unveiled diverse findings in 46 patients. The study highlights the importance of neurological and/or ocular symptoms in diagnosing symptomatic neurosyphilis. Individuals with hypomnesia should be closely monitored for potential neurosyphilis. Integrating clinical manifestations, laboratory tests, EEG, and imaging can reduce misdiagnosis. This comprehensive approach shows promise in improving early identification and management of neurosyphilis.

A Case of Neurosyphilis Presenting with Isolated Abducens Nerve Palsy.

We herein report a case of neurosyphilis that presented with isolated bilateral abducens nerve palsy. A 39-year-old man was referred to our department with diplopia. He had a history of homosexual relationships and showed only bilateral abducens nerve palsy upon a neurological examination. Positive syphilis tests in the serum and cerebrospinal fluid and a contrasting effect on the abducens nerve on magnetic resonance imaging (MRI) confirmed the diagnosis of active neurosyphilis. When a patient manifests isolated abducens nerve palsy, neurosyphilis can be a differential diagnosis, although rare, and contrast-enhanced MRI may help diagnose the disease.

Laboratory diagnosis of neurosyphilis: optimization ways. Part II. Current approaches and biomarkers

Laboratory diagnosis of neurosyphilis: optimization ways. Part II. Current approaches and biomarkers

Cerebrospinal fluid CXCL13 concentration for diagnosis and monitoring of neurosyphilis in people with HIV.

The study aimed to assess and compare cerebrospinal fluid (CSF)-CXCL13 levels in People with HIV (PWH) with suspected neurosyphilis (NS), those with syphilis but without NS, and patients without treponema infection. Additionally, it aimed to evaluate changes in CSF-CXCL13 concentrations before and after antibiotic treatment. This was a prospective cohort study involving 93 PWH suspected of NS. All participants underwent lumbar puncture, with CSF-CXCL13 levels measured at baseline and during follow-up in patients diagnosed with NS. CSF-CXCL13 levels were quantified using ELISA. The Mann-Whitney U test was used to analyze differences between groups, while the Wilcoxon test assessed within subject changes. ROC curve analysis determined the diagnostic efficacy of CSF-CXCL13 for NS. Significantly higher CSF-CXCL13 levels were observed in patients with NS compared to those with syphilis without NS and non-syphilis patients. Posttreatment, a decline in CSF-CXCL13 levels was noted in all NS cases. A CSF-CXCL13 threshold exceeding 60.0 pg/ml, in conjunction with reactive CSF-FTA-ABS, yielded a sensitivity of 88.9% and a specificity of 97.6% for NS diagnosis. CSF-CXCL13 emerges as a valuable adjunctive biomarker for detecting NS in PWH, especially in cases with nonreactive CSF-VDRL. Monitoring CSF-CXCL13 levels also appears effective in evaluating therapeutic response in PWH undergoing NS treatment.