Clinical and laboratory characteristics of asymptomatic and symptomatic neurosyphilis in HIV-infected patients: A retrospective study in China.

There are high rates of human immunodeficiency virus (HIV) and Treponema pallidum coinfection, HIV can increase the incidence and disability rate of neurosyphilis. However, there is a lack of data about the risk factors associated with the development of symptomatic neurosyphilis (SNS). We retrospectively reviewed the medical records of inpatients with concurrent syphilis and HIV infection who underwent a lumbar puncture and completed cerebrospinal fluid (CSF) examination. Sixty inpatients were consecutively enrolled from Beijing Ditan Hospital between January 2015 and March 2023. The clinical and laboratory features were evaluated between the SNS and asymptomatic neurosyphilis (ANS) groups. All patients were male, 25% (15/60) patients were diagnosed with ANS, and 75% (45/60) patients were diagnosed with SNS. Meningovascular neurosyphilis was the most prevalent clinical form in this study. Age, CD4 cell count, highly active antiretroviral therapy use, and serum HIV viral load showed no statistically significant differences between the 2 groups. The SNS group lacked early detection of syphilis (P < .001) and did not get previous adequate therapy for syphilis (P < .001) than the ANS group, as well as a higher initial serum toluidine red unheated serum test (TRUST) titer, current serum TRUST titer, CSF white blood cell count (WBC), protein concentration, and CSF TRUST titer (P = .014, P = .042, P = .01, P = .007, and P = .007, respectively). In multivariable logistic regression, high CSF WBC count (odds ratio = 1.08; P = .032) and previous treatment of syphilis (odds ratio = 0.01; P = .049) related to the SNS. Lack of antisyphilis treatment in the early stage of syphilis and a higher CSF WBC count are related risk factors for SNS in HIV-infected patients. Meningovascular neurosyphilis should get more attention in young patients with cryptogenic stroke.

Coinfection of cerebral toxoplasmosis and neurosyphilis as the first manifestation of AIDS.

A male in his 30s with a medical history of newly diagnosed HIV with a CD4 count of 292 cells/mm3 presented with a bilateral frontal headache and left upper and lower extremity weakness and paraesthesias. A few months prior, the patient experienced a desquamating rash on his scalp and a pruritic, papular genital rash, which both self-resolved. CT head without contrast revealed extensive vasogenic oedema involving the right basal ganglia, thalamus, temporal and occipital lobes. MRI of the brain with and without contrast revealed two enhancing masses in the right lentiform nucleus and right temporal-occipital junction with associated vasogenic oedema. Cerebrospinal fluid (CSF) studies confirmed cerebral toxoplasmosis with positive CSF Toxoplasma gondii PCR and neurosyphilis with positive serum rapid plasma reagin and CSF venereal disease research laboratory test. He was treated with trimethoprim/sulfamethoxazole and intravenous penicillin G with the resolution of his symptoms.

Syphilis presenting as optic neuritis and subdural haematoma with complicating neuro Jarisch-Herxheimer reaction.

A man in his 50s presented with a 3-week history of painless blurry vision. The ocular examination showed decreased visual acuity and 3+ bilateral papilloedema. A CT of the brain without contrast revealed a 5 mm left subdural haematoma. Anti-treponemal IgG antibodies were positive, and a reflex rapid plasma regain (RPR) was >1:64. HIV serology was negative. Ophthalmology and infectious diseases agreed that the presentation was consistent with ocular syphilis. Cerebrospinal fluid (CSF) examination revealed an elevated CSF protein of 52 mg/dL and CSF Venereal Disease Research Laboratory (VDRL) of 1:1. Penicillin was started. The patient developed a Jarisch-Herxheimer reaction soon after. He had a fever, rash and worsening headaches due to the enlargement of subdural haematoma for which he underwent a burr hole drainage. Vision improved after completing penicillin therapy but did not recover fully. The CSF VDRL became non-reactive and serum RPR titre decreased to 1:8 3 months later.

Analysis of brain activity for speech stimuli and child development of an infant with neurosyphilis: case report. / Análise da atividade cerebral para estímulos de fala e desenvolvimento infantil de um lactente com neurossífilis: relato de caso.

Neurosyphilis is an infection of the central nervous system caused by Treponema pallidum and may be symptomatic or asymptomatic in children with congenital syphilis. This study aims to describe the cortical activation pattern of a four-month-old infant with neurosyphilis using functional near-infrared spectroscopy (fNIRS). Born at term weighing 3,475 kg, she presented a Venereal Disease Research Laboratory (VDRL) test of 1:32 and changes in the cerebrospinal fluid test. She underwent treatment with crystalline penicillin for 10 days before discharge from the hospital. In the audiological evaluation, she presented normal tympanometry, otoacoustic emissions evoked by transient stimulus, brainstem auditory evoked potential with click stimulus at 80 and 30 dB nHL bilaterally. The Bayley III Scale was applied to assess language, cognition and motor development, showing delays in expressive language and broad motor skills. In the fNIRS acquisition, data were collected through 20 channels divided between the cerebral hemispheres. The /ba/ and /da/ stimuli were presented at 40 dB HL with the Psychopy software through a headphone. Data analysis used the MNE and MNE-NIRS toolboxes in the Spyder environment. The average by channel, ROI, and condition was exported for analysis. A similar theta coefficient was observed between the conditions and channels evaluated in both cerebral hemispheres, with a greater amplitude of oxyhemoglobin (HbO) being observed in the anterior position when compared to the posterior region of the temporal lobe. Therefore, this case report highlights the need to monitor the child development of babies with neurosyphilis.

A neurossífilis é uma infecção do sistema nervoso central causada pelo Treponema pallidum, podendo ser sintomática ou assintomática nas crianças com sífilis congênita. Este estudo visa descrever o padrão de ativação cortical de uma lactente de quatro meses com neurossífilis utilizando o funcional near-infrared spectroscopy (fNIRS). Nascida a termo com 3.475 Kg, apresentou teste Venereal Disease Research Laboratory (VDRL) de 1:32 e alteração no exame de líquor cefalorraquidiano. Realizou tratamento com penicilina cristalina por 10 dias antes da alta hospitalar. Na avaliação audiológica apresentou normalidade na timpanometria, emissões otoacústicas evocadas por estímulo transiente, potencial evocado auditivo de tronco encefálico com estímulo clique a 80 e 30 dB nNA bilateralmente. Foi aplicada a Escala Bayley III para a avaliação do desenvolvimento de linguagem, cognição e motor, apresentando atrasos na linguagem expressiva e no motor amplo. Na aquisição do fNIRS os dados foram coletados por 20 canais divididos entre os hemisférios cerebrais. Os estímulos /ba/ e /da/ foram apresentados a 40 dB NA com o auxílio do programa Psychopy por um fone de ouvido. A análise dos dados utilizou as toolboxes MNE e MNE-NIRS no ambiente Spyder. A média por canal, ROI e condição foi exportada para análise. Observou-se um coeficiente theta similar entre as condições e canais avaliados de ambos os hemisférios cerebrais, sendo observado maior amplitude da oxihemoglobina (HbO) na posição anterior quando comparados a região posterior do lobo temporal. Desta forma, este relato de caso evidencia a necessidade de monitoramento do desenvolvimento infantil de lactentes com neurossífilis.

Unusual demyelinating disease in a patient with HIV infection.

Demyelinating central nervous system (CNS) disorders are a diverse group of conditions characterised by damage to the myelin sheath. These include not only primary autoimmune disorders such as multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD), but secondary demyelinating conditions caused by infection and neoplasm, where immunosuppressive therapy may worsen the condition or delay definitive treatment. We describe a young man with an unusual presentation of CNS demyelinating disease associated with HIV infection and positive syphilis serology. MRI brain and spine showed a demyelinating tumefactive lesion accompanied by longitudinal extensive transverse myelitis, and we initially suspected NMOSD. However anti-aquaporin 4 antibodies were negative, going against a diagnosis of NMOSD and he then tested positive for HIV which led us to consider TB myelitis, neurosyphilis and HIV vacuolar myelopathy. He was commenced on highly active retroviral therapy and treated with steroids and immunosuppression. He did not respond to treatment as expected so a brain biopsy was required to narrow the differential. Brain biopsy initially raised the possibility of progressive multifocal leukoencephalopathy which is associated with infection with the John Cunningham (JC) virus. Ultimately JC Virus PCR on the biopsy was negative, the final report suggesting nonspecific active chronic inflammation. We detail his clinical course and the diagnostic challenges along the way.

Ischaemic apoplexy caused by syphilis.

Syphilis is a sexually transmitted disease caused by the spirochaete Treponema pallidum. Patients with untreated syphilis can develop meningovascular syphilis at any stage of the disease. This is a case report of a 44-year-old man displaying two instances of acute vertigo and lateralized paraesthesia. MRI showed infarctions in the left thalamus and capsula interna. Subsequent investigations including cerebral spinal fluid analysis revealed a diagnosis of neurosyphilis. The patient was treated intravenously with benzylpenicillin and ceftriaxone with complete clinical remission.

Novel and characteristic radiological features of neurosyphilis: a case series.

BACKGROUND: Treponema 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 PRESENTATION: Case 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. CONCLUSIONS: These 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.

Syphilis.

This is a case report of 51-year-old male patient with various symptoms including skin rashes, sensory disturbances, and non-cicatricial hair loss. Despite previous tests, the cause remained elusive until a dermatological examination revealed signs of syphilis. The patient's history, including his sexual relationships, became key in confirming the diagnosis, leading to treatment for neurosyphilis. With a rising incidence of syphilis in Denmark, this case highlights the importance of considering syphilis as a potential diagnosis across medical specialities because of the diverse and challenging clinical manifestations.

Characteristic Profiling of Soluble Factors in the Cerebrospinal Fluid of Patients With Neurosyphilis.

BACKGROUND: Soluble inflammatory factors in the cerebrospinal fluid (CSF) of patients with neurosyphilis have been investigated with low-throughput technology. This study aimed to illustrate the characteristics of soluble factor profiles in CSF of patients with neurosyphilis. METHODS: We measured the concentrations of 45 cytokines, chemokines, and growth factors in CSF from 112 untreated syphilis cases, including latent syphilis (LS), asymptomatic neurosyphilis (ANS), meningeal neurosyphilis (MNS), meningovascular neurosyphilis (MVNS), paralytic dementia (PD), and ocular syphilis (OS). RESULTS: Thirty-three differentially expressed soluble factors (DeSFs) were categorized into 3 clusters. DeSF scores of clusters 1 and 2 (DeSFS1 and DeSFS2) were positively correlated with elevated neopterin and neurofilament light subunit (NF-L) concentration, respectively. DeSF scores of cluster 3 were positively correlated with white blood cells, protein, NF-L, and neopterin. Patients with LS, ANS, and OS exhibited an overall lower abundance of DeSFs. Patients with PD exhibited significantly increased levels of clusters 1 and 3, and the highest total DeSF score, whereas patients with MNS and MVNS showed enhanced levels of cluster 2. Receiver operating characteristic analysis revealed that DeSFS1 effectively discriminated PD, and DeSFS2 discriminated MNS/MVNS with high accuracy. CONCLUSIONS: Patients with neurosyphilis at different stages have distinctive patterns of soluble factors in CSF, which are correlated with immune status and neuronal damage.

Early neurosyphilis with serofast state.

We report a rare case of confirmed early neurosyphilis with serofast state in HIV-negative patient, with uncontrolled type 2 diabetes mellitus. Syphilitic meningitis was diagnosed initially on serology and cerebrospinal fluid (CSF) analysis. The patient had persistently raised non-treponemal titres on serum with negative CSF venereal disease research laboratory result, following treatment during 3 years of follow-up.

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.

OBJECTIVES: Invasive 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. METHODS: A 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. RESULTS: Serum 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. DISCUSSION: Serum 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.

Ocular vs neurosyphilis. are they the same? A guide to investigation and management.

This article reviews key concepts in the epidemiology, clinical features, diagnosis and management of ocular syphilis. It is not a systematic review or meta-analysis, but highlights the critical clinical features and investigations in patients with ocular syphilis. It reviews the overlap and interplay between ocular and neuro syphilis and provides practical guidance to diagnose and manage patients with ocular syphilis.

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

OBJECTIVE: To systematically assess the diagnostic accuracy of CXCL13 testing of cerebrospinal fluid (CSF) for neurosyphilis diagnosing. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Cochrane Library and Web of Science databases from their inception until 1 May 2023. ELIGIBILITY CRITERIA: 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. DATA EXTRACTION AND SYNTHESIS: 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. PROSPERO REGISTRATION NUMBER: CRD42023414212.

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 > 45 mg/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 > 45 mg/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.

BACKGROUND: The immunopathological mechanisms underlying neurosyphilis remain incompletely elucidated, and the diagnosis of neurosyphilis presents challenges. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.