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.

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.

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.

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.

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.

Selective attention function impairment in HIV-negative patients with early forms of neurosyphilis.

BACKGROUND: The attentional network test (ANT) is widely used to evaluate the performance of three attentional networks: alerting, orienting and executive attention networks. This study aimed to investigate the characteristics of attention functions in HIV-negative patients with early forms of neurosyphilis (NS) and their correlation with abnormalities in brain magnetic resonance imaging (MRI). METHODS: Thirty patients with early forms of NS, 31 patients with syphilis but without NS (Non-NS) and 35 healthy controls were recruited from an HIV-negative cohort between September 2020 and November 2022. The participants were evaluated with the ANT and the Mini-Mental State Examination (MMSE). Brain MRI was performed in NS and Non-NS patients. RESULTS: No significant differences were observed in the MMSE scores among the three groups. However, patients with early forms of NS showed poorer performance in orienting and alerting functions than Non-NS group (F = 6.952, P = 0.011 and F = 8.794, P = 0.004, respectively); No significant difference was observed in executive function between the two groups (F = 0.001, P = 0.980). Multivariate analysis of variance using the Bonferroni post hoc test indicated that patients with NS exhibited less efficient orienting function (P = 0.023), and alerting function (P = 0.003) but not executive function (P = 0.99), compared to Non-NS patients. Additionally, a significant difference was found in orienting function between patients with NS and healthy controls (P < 0.001) compared to healthy controls. MRI scans revealed that the NS group had a higher prevalence of abnormalities in the frontal lobes and/or the temporoparietal junction compared to the Non-NS group (24/25 vs. 13/19, P = 0.032). CONCLUSIONS: The orienting and alerting functions but not executive function were significantly less efficient in early forms of NS group than in the Non-NS group (P < 0.01). This indicates deficits in selective attention in patients with early forms of NS. Brain MRI scans revealed abnormalities in the frontal and/or parietal lobes, as well as the temporoparietal junction, suggesting potential neuropathological correlates of these attentional deficits.

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.

Immune Dysfunction in Schizophrenia Spectrum Disorders.

Evidence from epidemiological, clinical, and biological research resulted in the immune hypothesis: the hypothesis that immune system dysfunction is involved in the pathophysiology of schizophrenia spectrum disorders (SSD). The promising implication of this hypothesis is the potential to use existing immunomodulatory treatment for innovative interventions for SSD. Here, we provide a selective historical review of important discoveries that have shaped our understanding of immune dysfunction in SSD. We first explain the basic principles of immune dysfunction, after which we travel more than a century back in time. Starting our journey with neurosyphilis-associated psychosis in the nineteenth century, we continue by evaluating the role of infections and autoimmunity in SSD and findings from assessment of immune function using new techniques, such as cytokine levels, microglia density, neuroimaging, and gene expression. Drawing from these findings, we discuss anti-inflammatory interventions for SSD, and we conclude with a look into the future.

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.

Clinical characteristics and outcomes of people living with HIV and ocular syphilis during the COVID-19 health emergency.

BACKGROUND: The global shift in healthcare during the COVID-19 pandemic led to challenges in the care of people living with HIV. METHODS: We conducted a retrospective study that aimed to delineate sociodemographic, clinical characteristics and outcomes, of people living with HIV diagnosed with ocular syphilis. RESULTS: Fifty-three people living with HIV were identified with ocular syphilis. Thirty-eight (71.6%) presented ocular symptoms. Twenty-three (43.3%) underwent lumbar puncture, 5 (9.4%) were positive for neurosyphilis. Forty-seven (88.6%) received treatment, 32 (68%) received standard treatment with aqueous crystalline penicillin G, and 15 (31.9%) were treated with alternative regimens due to the impossibility of hospitalization. Six (11.3%) individuals were lost to follow-up and/or did not receive treatment. Eighteen (56.2%) out of 32 individuals in the aqueous crystalline penicillin G group experienced serological response, 5 (15.6%) experienced treatment failure, and 9 (28.1%) were lost to follow-up. In the alternative therapy group, 12 out of 15 individuals (80%) experienced serological response. One (6.7%) experienced treatment failure, and 2 (13.3%) were lost to follow-up. CONCLUSIONS: During the COVID-19 health emergency in Mexico, alternative treatments for ocular syphilis demonstrated favorable clinical outcomes amid challenges in accessing hospitalization.

The Etiology of Rapidly Progressive Dementia: A 3-Year Retrospective Study in a Tertiary Hospital in China.

Background: Rapidly progressive dementia (RPD), characterized by a rapid cognitive decline leading to dementia, comprises a diverse range of disorders. Despite advancements in diagnosis and treatment, research on RPD primarily focuses on Western populations. Objective: This study aims to explore the etiology and demographics of RPD in Chinese patients. Methods: We retrospectively analyzed 323 RPD inpatients at Huashan Hospital from May 2019 to March 2023. Data on sociodemographic factors, epidemiology, clinical presentation, and etiology were collected and analyzed. Results: The median onset age of RPD patients was 60.7 years. Two-thirds received a diagnosis within 6 months of symptom onset. Memory impairment was the most common initial symptom, followed by behavioral changes. Neurodegenerative diseases accounted for 47.4% of cases, with central nervous system inflammatory diseases at 30.96%. Autoimmune encephalitis was the leading cause (16.7%), followed by Alzheimer's disease (16.1%), neurosyphilis (11.8%), and Creutzfeldt-Jakob disease (9.0%). Alzheimer's disease, Creutzfeldt-Jakob disease, and frontotemporal dementia were the primary neurodegenerative causes, while autoimmune encephalitis, neurosyphilis, and vascular cognitive impairment were the main non-neurodegenerative causes. Conclusions: The etiology of RPD in Chinese patients is complex, with neurodegenerative and non-neurodegenerative diseases equally prevalent. Recognizing treatable conditions like autoimmune encephalitis and neurosyphilis requires careful consideration and differentiation.

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.

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.

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.

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.