Neurosyphilis In Patients Research Articles

Neurodegenerative proteinopathies associated with neuroinfections.

Infectious agents, including viruses and bacteria, are proposed to be involved in the pathogenesis of Alzheimer’s disease (AD). According to this hypothesis, these agents have capacity to evade the host immune system leading to chronic infection, inflammation, and subsequent deposition of Aβ and phosphorylated-tau in the brain. Co-existing proteinopathies and age-related pathologies are common in AD and the brains of elderly individuals, but whether these are also related to neuroinfections remain to be established. This study determined the prevalence and distribution of neurodegenerative proteinopathies in patients with infection-induced acute or chronic inflammation associated with herpes simplex virus (HSV) encephalitis (n = 13) and neurosyphilis (n = 23). The mean age at death in HSV patients was 53 ± 12 years (range 24–65 years) and survival was 9 days–6 years following initial infection. The mean age at death and survival in neurosyphilis patients was 60 ± 15 years (range 36–86 years) and 1–5 years, respectively. Neuronal tau-immunoreactivity and neurites were observed in 8 HSV patients and 19 neurosyphilis patients, and in approximately half of these, this was found in regions associated with inflammation and expanding beyond regions expected from the Braak stage of neurofibrillary degeneration. Five neurosyphilis patients had cortical ageing-related tau astrogliopathy. Aβ-plaques were found in 4 HSV patients and 11 neurosyphilis patients. Lewy bodies were observed in one HSV patient and two neurosyphilis patients. TDP-43 pathology was absent. These observations provide insights into deposition of neurodegenerative proteins in neuroinfections, which might have implications for COVID-19 patients with chronic and/or post-infectious neurological symptoms and encephalitis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00702-021-02371-7.

The associations of increased cerebral small vessel disease with cognitive impairment in neurosyphilis presenting with ischemic stroke.

Background and PurposeIschemic stroke is a common clinical feature of neurosyphilis, but its accompanying cognitive decline is often overlooked. The mechanisms of cognitive impairment in neurosyphilis presenting with ischemic stroke are not fully understood. Cerebral small vessel disease (CSVD) was recently shown to predict post‐stroke cognitive decline. Therefore, this study aims to validate the correlation between CSVD and cognitive impairment in neurosyphilis presenting with ischemic stroke.MethodsWe enrolled 179 neurosyphilis patients diagnosed as acute ischemic stroke and performed a 12‐month cognitive assessment follow‐up. CSVD burden was evaluated by neuroimaging markers, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), and perivascular spaces (PVS). We performed multivariate logistic regression analysis to determine the association between cognitive decline and total CSVD burden score in neurosyphilis patients.ResultsThe neurosyphilis participants had a significantly higher total CSVD score and lower cognitive function score compared with the syphilis‐uninfected patients. Acute cognitive impairment was associated with total CSVD score, extensive microbleeds, and Grade 3 WMHs. After 12‐month follow‐up, the poor prognosis of post‐stroke cognitive impairment was associated with a higher burden of CSVD and extensive microbleeds.ConclusionsCerebral small vessel disease loads in neurosyphilis patients presenting with ischemic stroke are independently associated with acute cognitive impairment and have a prospective value for post‐stroke cognitive outcomes.

Combination of the neutrophil to lymphocyte ratio and serum toluidine red unheated serum test titer as a predictor of neurosyphilis in HIV-negative patients.

The present study explored the associations of the neutrophil to lymphocyte ratio (NLR) and the serum toluidine red unheated serum test (TRUST) titer with neurosyphilis (NS). The present retrospective study examined 87 NS patients and 80 Non-NS patients from an HIV-negative cohort and 1:1 age- and gender-matched healthy controls. The results demonstrated that the NLR was increased in both NS and Non-NS groups compared with that in the healthy controls (P<0.001 and P=0.01, respectively). The NLR and serum TRUST titer in the NS group were significantly higher than those in the Non-NS group (P=0.004 and P<0.001, respectively). The NLR was positively correlated with the serum TRUST titer (r=0.298, P<0.001). Age, elevated NLR and serum TRUST titer were distinctly associated with NS by binomial logistic regression analysis [odds ratio (OR)=1.10, P<0.001; OR=1.36, P=0.028; OR=3.07, P<0.001; respectively]. The cut-off values for the NLR and serum TRUST titer were 1.97 and 1:8, respectively. A significantly higher sensitivity of 90.8% was obtained for screening out NS with a combination of the NLR and serum TRUST titer compared with each test alone. Age, elevated NLR and serum TRUST titer were associated with NS. The combination of NLR and serum TRUST titer is a potential predictor for NS, and the reduced NLR and serum TRUST titer at the 6-month follow up suggested that the NLR and serum TRUST titer were biomarkers for monitoring the disease course.

An unusual presentation of neurosyphilis with complicated pulmonary involvement in a patient without HIV infection

Background: Neurosyphilis could develop at any time in the course of syphilis; with an annual incidence of 0.7 per 100,000 men. Homosexual and HIV were risk factors. Here we report an unusual case of neurosyphilis in non-HIV patient with complicated pulmonary involvement. Case description: A fifty-six-year-old promiscuity, heterosexual man, active smoker presented with a three-month history of pruritic maculopapular rashes on his body associated with low-grade fever, and a two-week history of productive cough with dyspnea. On physical examination, he was tachypnea, with crackles on the base of the right lung. There was plaque hyperpigmentation on his malar area and multiple maculopapular, erythematous lesions on his trunk, extremities including palms of the hands, and scrotal area. No ulcer was found on his penis. Laboratory results revealed leukocytosis (19.9 × 103/μl), non-reactive HIV test, with high titer of serum VDRL (1/8) and TPHA (1/1280). Chest X-ray showed infiltrate on right perihilar area. Patient was diagnosed as pneumonia with secondary syphilis. The patient was treated with a single dose of benzathine penicillin G 2.4 million units intramuscular and azithromycin 500 mg tablet OD. During observation, he had altered mental status, generalized tonic seizure, high-grade fever with respiratory distress. He had Argyll Robertson pupil, left central facial and hypoglossal nerve paralysis, and positive meningeal signs, with normal brain CT scan result, non-reactive CSF-VDRL and TPHA, with high leucocyte (17 cells/μl) and protein (54 mg/dl). He was diagnosed neurosyphilis with hospital-acquired pneumonia and treated with ceftriaxone and vancomycin, 2 g OD and 750 mg OD intravenous, respectively. The patient showed no significant improvement and unfortunately, he progressed to death caused by multiple organ dysfunctions due to septic shock. Discussion: There is no single, highly sensitive and specific diagnostic test exists for neurosyphilis. The diagnosis of neurosyphilis is based on clinical findings and the results of serologic tests and CSF examination. The CSF-VDRL has sensitivity 30–70%, non-reactive test does not exclude neurosyphilis. Neurosyphilis in a patient without HIV infection could be diagnosed by a high WBC or protein in CSF with symptoms or signs of neurosyphilis even with non-reactive CSF-VDRL. Conclusion: Neurosyphilis could be considered even with a non-reactive CSF-VDRL result in non-HIV patient.

Circulating MicroRNAs as Potential Biomarkers in the Diagnosis of Neurosyphilis: A Case Control Study

Abstract Objective: Laboratory diagnosis of neurosyphilis (NS) remains a great challenge. This study was the aimed to identify miRNA candidates as biomarkers to distinguish between NS, non-neurosyphilis, and healthy controls (HCs). Methods: We analyzed miRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from six patients with NS, eight patients with secondary syphilis (SS), and five HCs using microarray technology. The differentially expressed miRNAs were validated in 33 NS samples, 31 SS samples, and 30 HC samples using TaqMan miRNA real-time qPCR (qRT-PCR). Results: Thirty-nine miRNAs were differentially expressed in SS and NS patients compared with HCs. Thirteen miRNAs were randomly selected to validate their expression levels in the same samples used in microarray assay by qRT-PCR. All miRNAs were upregulated in SS and NS samples compared with HC. qRT-PCR analysis of the expression of the 13 miRNAs in a second cohort (76 samples) showed that the average expression levels of nine miRNAs were higher in SS than in NS (SS: 0.185, NS: 0.136, P=3.8E-10), while the expressions of the other four miRNAs were lower in SS than in NS (SS: 0.000757, NS: 0.000873, P=0.022). ROC curve analysis of the 13 miRNAs showed the area under the curve value to be 1.00 for distinguishing SS patients from HCs, 1.00 for distinguishing NS patients from HCs, 1.00 for distinguishing SS and NS patients from HCs, and 0.968 for distinguishing NS from SS patients. Conclusion: The present study is the first one that identified differentially expressed miRNAs in PBMCs from patients with NS. Our results suggest that the 13 candidate miRNAs in PBMCs may be novel noninvasive biomarkers for NS diagnosis.

Neurosyphilis: Still prevalent and overlooked in an at risk population

Neurosyphilis (NS) presents with a variety of clinical syndromes that can be attributed to other aetiologies due to difficulties in its diagnosis. We reviewed all cases of NS from the "Top End" of the Australian Northern Territory over a ten-year period to assess incidence, clinical and laboratory manifestations. Patient data (2007-2016) were extracted from hospital records, centralised laboratory data and Northern Territory Centre for Disease Control records. Clinical records of patients with clinically suspected NS were reviewed. A diagnosis of NS was made based on the 2014 US CDC criteria. Results were also recategorized based on the 2018 US CDC criteria. The population of the "Top End" is 185,570, of whom 26.2% are Indigenous. A positive TPPA was recorded in 3126 individuals. A total of 75 (2.4%) of TPPA positive patients had a lumbar puncture (LP), of whom 25 (35%) were diagnosed with NS (9 definite, 16 probable). Dementia was the most common manifestation (58.3%), followed by epilepsy (16.7%), psychosis (12.5%), tabes dorsalis (12.5%) and meningovascular syphilis (8.3%). 63% of probable NS cases were not treated appropriately due to a negative CSF VDRL. Despite increased specificity of the 2018 US CDC criteria, 70% of patient in the probable NS group were not treated appropriately. The overall annual incidence [95%CI] of NS was 2.47[1.28-4.31] per 100 000py in the Indigenous population and 0.95[0.50-1.62] in the non-Indigenous population (rate ratio = 2.60 [1.19-5.70];p = 0.017). Neurosyphilis is frequently reported in the NT, particularly in Indigenous populations. Disturbingly, 60% of probable neurosyphilis patients based on the 2014 criteria, and 70% based on the 2018 criteria with were not treated appropriately. It is critical that clinicians should be aware of the diagnosis of NS and treat patients appropriately.

Cerebrospinal Fluid Cytokines in Patients with Neurosyphilis: The Significance of Interleukin-10 for the Disease.

The aim of this study was to examine the cerebrospinal fluid (CSF) concentrations of proinflammatory and anti-inflammatory cytokines in neurosyphilis (NS), analyze the differences between asymptomatic NS (ANS) and symptomatic NS (SNS), and explore the diagnostic value of these cytokines. We enrolled 45 patients with a diagnosis of NS, including 18 patients with ANS and 27 patients with SNS, whose cerebrospinal fluid (CSF) samples were collected before penicillin therapy. Twelve patients with syphilis but non-NS (NNS) were also included. We measured the CSF levels of interleukin- (IL-) 1β, IL-4, IL-6, IL-10, IL-17A, IL-21, and tumor necrosis factor- (TNF-) α; the CSF levels of the microglial activation marker soluble triggering receptor expressed on myeloid cells 2 (sTREM2); and the CSF levels of the neuronal injury marker neurofilament light proteins (NFL) using the human cytokine multiplex assay or ELISA. Of the measured cytokines in the CSF, only IL-10 levels were significantly increased in NS patients compared to NNS patients (p < 0.001). In a subgroup analysis, the CSF levels of IL-10 were significantly elevated in SNS patients compared to ANS and NNS patients (p = 0.024 and p < 0.001, respectively). The CSF IL-10 levels had a significant correlation with the markers of microglial activation and neuronal injury, and they also correlated with CSF rapid plasma reagin (RPR) titer, CSF white blood cell (WBC) count, and CSF protein concentration. The areas under the ROC curve (AUC) of CSF IL-10 in the diagnosis of NS and ANS were 0.920 and 0.891, respectively. The corresponding sensitivities/specificities were 86.7%/91.7% and 83.3%/91.7%, respectively. Therefore, the excessive production of IL-10 might facilitate bacterial persistent infection, play an important role in the pathogenesis of NS, and associate with the progression of the disease. CSF IL-10 concentration had a useful value in the diagnosis of NS, especially in ANS.

BACE1 and Other Alzheimer's-Related Biomarkers in Cerebrospinal Fluid and Plasma Distinguish Alzheimer's Disease Patients from Cognitively-Impaired Neurosyphilis Patients.

Patients with spirochetal infection, which causes neurosyphilis (NS) and at a later stage general paresis of the insane (GPI), present with brain pathology features of Alzheimer's disease (AD). However, the relationships among these illnesses regarding biomarker levels are still unclear. To explore biomarker levels in NS and GPI compared with those in AD and the relationship between biomarker levels and cognitive function in NS and GPI. Levels of neurogranin (NGRN) and β-amyloid precursor protein cleaving enzyme (BACE1) in cerebrospinal fluid (CSF)/plasma, together with amyloid-β 1-40 (Aβ40), Aβ42, and total tau in the CSF of 23 AD patients, 55 GPI patients, and 13 NS patients were measured. Patients were classified into none-to-mild, moderate, and severe stages of cognitive impairment. Levels of CSF NGRN, BACE1, and tau as well as plasma BACE1 levels were significantly different among groups. In the none-to-mild stage, plasma BACE1 levels correlated with the protein levels in CSF and were significantly increased in AD patients versus GPI patients. The CSF tau levels in AD patients were significantly increased versus GPI patients in the moderate and severe stages. Pooling data from GPI and NS patients, both CSF tau and plasma NGRN levels correlated with cognitive scale scores. GPI and NS patients might have different biomarker level patterns compared to AD patients. While plasma BACE1 could be a promising early biomarker for distinguishing AD from GPI, CSF tau and plasma NGRN levels might be valuable in indications of cognitive function in pooled NS populations.

Elevation of Cerebrospinal Fluid Light and Heavy Neurofilament Levels in Symptomatic Neurosyphilis.

Although clinical manifestations of symptomatic and asymptomatic neurosyphilis are different, few laboratory tests could reflect the difference. A total of 92 non-HIV-infected patients with syphilis were enrolled in this study, including 23 with symptomatic neurosyphilis, 51 with asymptomatic neurosyphilis, and 18 with latent syphilis, which were excluded neurosyphilis because they were found to have no symptom and normal cerebrospinal fluid (CSF) tests and served as the control group. The concentrations of neurofilament light subunit (NF-L) and phosphorylated neurofilament heavy subunit (pNF-H) in the CSF were measured and compared among these groups, as well as before and after treatment in the symptomatic and asymptomatic groups. The median concentrations of NF-L in the symptomatic neurosyphilis, asymptomatic neurosyphilis, and control groups were 5806, 218, and 266 pg/mL, respectively (P < 0.001), and the median concentrations of pNF-H were 986, 43, and 49 pg/mL, respectively (P < 0.001). A subgroup of 15 symptomatic neurosyphilis and 10 asymptomatic neurosyphilis patients were followed up and underwent CSF examination 6 months after the antineurosyphilis treatment. The median concentration of NF-L in the symptomatic neurosyphilis group decreased from baseline 6420 to 2914 pg/mL after the treatment (P = 0.03), and the median concentration of pNF-H in the symptomatic neurosyphilis group decreased from baseline 1399 to 246 pg/mL after the treatment (P = 0.03). Neurofilament light subunit and pNF-H were significantly elevated in the symptomatic neurosyphilis patients, not in asymptomatic neurosyphilis, which was an implication of the different pathogeneses in neurosyphilis.

Neuroimaging Features, Follow-Up Analyses, and Comparisons Between Asymptomatic and Symptomatic Neurosyphilis.

IntroductionMany studies have explored the imaging characteristics of patients with neurosyphilis, but no systematic study has been made on the neuroimaging changes after anti-syphilitic treatment. The purpose of this study was to examine neuroimaging differences before and after treatment, comparing patients with asymptomatic and symptomatic neurosyphilis.MethodsA total of 102 patients with neurosyphilis, including 60 cases of symptomatic neurosyphilis and 42 cases of asymptomatic neurosyphilis, were identified between December 2012 and June 2019. Their demographics, medical histories, serological tests of peripheral blood and cerebrospinal fluid, and especially neuroimaging features before and after anti-syphilitic treatment were collected and analyzed.ResultsThe patients presented with variable clinical and neuroimaging features, including cerebral infarction or hemorrhage, atrophy, demyelination, arteritis, encephalitis, and hippocampal sclerosis. A total of 29 neuroradiological re-examinations were performed in 19 patients treated with anti-syphilitic medicine. The results indicated that some patients still presented neuroradiological progression after treatment, including 42.1% showing infarction lesions, 47.4% mild to severe brain atrophy, and 15.8% white matter demyelination.ConclusionThe clinical and neuroimaging features of neurosyphilis patients are diverse, and their follow-up neuroimaging continued to show progression even with standardized treatment.Electronic supplementary materialThe online version of this article (10.1007/s13555-020-00361-3) contains supplementary material, which is available to authorized users.

Increased CSF Soluble TREM2 Concentration in Patients With Neurosyphilis.

Objective: To explore cerebrospinal fluid (CSF) levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and neurofilament light proteins (NFL) in patients with neurosyphilis (NS).Methods: We enrolled 71 NS patients (41 early-NS and 30 late-NS patients) and 20 syphilis but non-NS patients whose CSF samples were collected. The CSF levels of the microglial activation biomarker sTREM2 and neuronal injury biomarker NFL were measured using ELISA.Results: CSF sTREM2 levels were significantly higher in NS patients compared to those in syphilis/non-NS patients (p < 0.001). In a subgroup analysis, the CSF sTREM2 levels elevated significantly in late-NS patients than those in early-NS patients (p < 0.001). The CSF sTREM2 levels in early-NS group were also significantly higher than those in syphilis/non-NS group (p = 0.024). Like CSF sTREM2, similar differences between groups were also found in CSF NFL. There was a moderate correlation between CSF sTREM2 and CSF NFL (r = 0.406, p < 0.001) in NS group.Conclusions: CSF sTREM2 levels elevated in NS and peaked at the late stage, suggesting that CSF sTREM2 may be a useful marker to quantify microglia activation in NS and may play a role in the progression of NS. The positive correlation between CSF sTREM2 and CSF NFL indicates a linkage between microglial activation and neuronal injury in NS.

Immunological markers of defeat of nervous tissue as an element of predictive model of damage of nervous system at syphilis.

To develop predictive model of damage of nervous system on the basis of definition of concentration of interleukins-23, 12p40 and also a glial fibrillar acid protein (GFAP) in liquor of patients with various forms of syphilis. Comprehensive laboratory examination of patients with neurosyphilis and syphilis without specific damage of nervous system who were observed in venereologic office of BOUZAS of OO «Clinical Dermatovenerologic Clinic» of Omsk is conducted. To all patients were carried out: a serological blood analysis, serological and clinical trial of liquor, and also immunological research of liquor (interleukins - 23, 12p40, and also GFAP). On the basis of the research IL-23, SILT-12p40, GFAP, the level of protein and a pleocytosis in liquor the predictive model of development of neurosyphilis in patients with syphilis without specific damage of nervous system is offered. The analysis of immunological changes in liquor of patients showed that the research of a number of cytokines and markers of damage of nervous tissue to liquor as the most specific and reliable, especially in the absence of clinical symptomatology from central nervous system can be an integral part of diagnostics of neurosyphilis also.

Metabolic Disorders in Patients with Central Nervous System Infections: Associations with Neurosyphilis

Introduction: Recently, neurosyphilis was found to be associated with diabetes mellitus (DM). Whether the association was specific to neurosyphilis among central nervous system (CNS) infections, and whether neurosyphilis is associated with other prevalent metabolic disorders deserves further study. Methods: An in-depth cross-sectional study was conducted with 74 neurosyphilis patients and 74 sex- and age-matched patients with other CNS infections. DM-, hypertension-, and dyslipidemia-related factors were compared between patients with neurosyphilis and those with other CNS infections. Results: The prevalence rates of hypertension and hyperlipidemia in neurosyphilis patients were 45.9 and 21.4%, respectively, which were higher than those in patients with other CNS infections (45.9 vs. 28.4%, p = 0.027; 21.4 vs. 8.3%, p = 0.028). In addition, neurosyphilis patients had significantly higher systolic blood pressure (BP; median 139 mm Hg; interquartile range [IQR] 121–151 mm Hg), ­diastolic BP (median 83 mm Hg; IQR 76–89 mm Hg), total cholesterol (median 4.86 mmol/L; IQR 3.80–5.51 mmol/L), low-density lipoprotein (median 3.39 mmol/L; IQR 2.52–3.95 mmol/L), and apolipoprotein A1 (apoA1; median 1.31 g/L; IQR 1.06–1.52 g/L) levels and lower apoB/A1 ratios (median 0.67; IQR 0.49–0.99) than patients with other CNS infections (p< 0.05). There were no differences in the DM-related factors between patients with neurosyphilis and those with other CNS infections (p> 0.05). Conclusion: Potential association between neurosyphilis and metabolic disorders was found among CNS infections. The results could have important implications for clinical practice, alerting more clinicians to this issue.

Novel Biochemical Insights in the Cerebrospinal Fluid of Patients with Neurosyphilis Based on a Metabonomics Study.

Neurosyphilis is a chronic central nervous system infectious disease caused by Treponema pallidum. Our aim was to study the metabolic profiling in the cerebrospinal fluid of neurosyphilis patients and identify specific potential biomarkers. Fifteen cerebrospinal fluid samples from neurosyphilis patients and 14 non-neurosyphilis samples were analyzed by liquid chromatography-mass spectrometer (LC-MS). The LC-MS data were preprocessed by supervised pattern recognition to obtain diagnostic models. Both orthogonal projections to a latent structures discriminant analysis (OPLS-DA) and a t test were used to obtain specific metabolites for neurosyphilis. LC-MS data showed that the metabolites in cerebrospinal fluid (CSF) from neurosyphilis are different from the non-neurosyphilis group. The OPLS-DA model parameters R2Y and Q2Y are both more than 0.7 and indicated a satisfactory diagnostic performance. Bilirubin, L-histidine, prostaglandin E2, alpha-kamlolenic acid, and butyryl-L-carnitine and palmitoyl-L-carnitine were identified as novel potential biomarkers for neurosyphilis. The metabolic study of CSF may provide a new way to explore the pathogenesis of neurosyphilis.

Changes of T lymphocyte subsets in patients with HIV-negative symptomatic neurosyphilis

ObjectivesThe host immune response could be an imperative factor in the pathogenesis of neurosyphilis, but the role of T lymphocyte subsets remains unclear. In the present study, we assessed the CD4+ T and CD8+ T cell subsets in the peripheral blood of patients with HIV-negative symptomatic neurosyphilis and then explored the clinical application value of neurosyphilis. MethodsIn total, 24 patients with HIV-negative symptomatic neurosyphilis and 22 patients with syphilis/non-neurosyphilis were included in this study and cerebrospinal fluid (CSF) and blood samples were obtained. Th1, Th2, Th17, Th9, CD8+IFN-γ+, CD8+IL-4+, CD8+IL-9+, and CD8+IL-17 + cells were identified by flow cytometry. ResultsThe levels of CD8+IFN-γ+ were significantly increased in the peripheral blood of neurosyphilis patients compared to that in syphilis/non-neurosyphilis patients, but it was opposite to Th2, Th9, CD8+IL-4+, CD8+IL-9+, and CD8+IL-17 + cells. Dendritic cells (DCs) of neurosyphilis matured by T. pallidum induced the development of a combination of IFN-γ-producing Th1 cells. The number of CD8+IL-17 + cells was significantly correlated with the CSF RPR and CSF TPPA levels. ROC curve analysis revealed that the number of CD8+IFN-γ+ cells could be a potential biomarker for neurosyphilis from non-neurosyphilis/syphilis. ConclusionsHigh expression of CD8+IFN-γ+ cells and low expression of CD8+IL-17 + cells in patients with symptomatic neurosyphilis, which explains the pathogenesis of symptomatic neurosyphilis, meanwhile CD8+IFN-γ+ cells may be a better indicator in classifying symptomatic neurosyphilis from non-neurosyphilis/syphilis among patients without HIV infection.

Analysis of EEG Lemple–Ziv complexity and correlative aspects before and after treatment of anti-syphilis therapy for neurosyphilis

ABSTRACTObjective To investigate the diagnostic value of electroencephalogram (EEG) complexity in patients with neurosyphilis by comparing the changes of electroencephalogram Lempel-Ziv complexity (EEG-LZC) before and after anti-syphilis treatment.Methods The EEG complexity of neurosyphilis patients diagnosed in our hospital from July in 2015 to June in 2017 was analyzed and compared with other diagnostic results such as serology examination and cerebrospinal fluid examination.Results A total of 27 patients were diagnosed, including 19 males and 8 females, of which 6 were mesenchymal(cerebrospinal membrane and meningeal vascular), 16 were parenchymal(paralytic dementia, spinal cord tuberculosis and optic neuropathy), and 5 were asymptomatic. After intensive anti-syphilis therapy, the LZC increased significantly in all patients while the trend and degree of change were consistent with other diagnostic results.Conclusion The LZC can be used as one of the diagnostic indexes meanwhile the trend and degree of its change can be used as the reference index of curative effect to neurosyphilis.

Metabolite Profiles of the Cerebrospinal Fluid in Neurosyphilis Patients Determined by Untargeted Metabolomics Analysis.

The mechanism underlying the stealth property of neurosyphilis is still unclear. Global metabolomics analysis can provide substantial information on energy metabolism, physiology and possible diagnostic biomarkers and intervention strategies for pathogens. To gain better understanding of the metabolic mechanism of neurosyphilis, we conducted an untargeted metabolomics analysis of cerebrospinal fluid (CSF) from 18 neurosyphilis patients and an identical number of syphilis/non-neurosyphilis patients and syphilis-free patients using the Agilent, 1290 Infinity LC system. The raw data were normalized and subjected to subsequent statistical analysis by MetaboAnalyst 4.0. Metabolites with a variable importance in projection (VIP) greater than one were validated by Student’s T-test. A total of 1,808 molecular features were extracted from each sample using XCMS software, and the peak intensity of each feature was obtained. Partial-least squares discrimination analysis provided satisfactory separation by comparing neurosyphilis, syphilis/non-neurosyphilis and syphilis-free patients. A similar trend was obtained in the hierarchical clustering analysis. Furthermore, several metabolites were identified as significantly different by Student’s T-test, including L-gulono-gamma-lactone, D-mannose, N-acetyl-L-tyrosine, hypoxanthine, and S-methyl-5′-thioadenosine. Notably, 87.369-fold and 7.492-fold changes of N-acetyl-L-tyrosine were observed in neurosyphilis patients compared with syphilis/non-neurosyphilis patients and syphilis-free patients. These differential metabolites are involved in overlapping pathways, including fructose and mannose metabolism, lysosomes, ABC transporters, and galactose metabolism. Several significantly expressed metabolites were identified in CSF from neurosyphilis patients, including L-gulono-gamma-lactone, D-mannose, N-acetyl-L-tyrosine, and hypoxanthine. These differential metabolites could potentially improve neurosyphilis diagnostics in the future. The role of these differential metabolites in the development of neurosyphilis deserves further exploration.

Neurosyphilis in patients with HIV infection: difficulties in diagnostics

Neurosyphilis in patients with HIV infection: difficulties in diagnostics

A Case of Rapid Progressive Neurosyphilis in Patient with Ankylosing Spondylitis Who Is Treating Anti-interleukin 17A Monoclonal Antibody, Secukinumab

Anti-interleukin 17A agent, secukinumab is remarkably effective for treating patients with ankylosing spondylitis. However, the main safety concern of secukinumab is an increased risk of infection. Generally, neurosyphilis occurs a few years after the pri-mary syphilitic infection. Rare cases of progressing to neurosyphilis with a much lower latency were reported. We report a case of rapid progressive neurosyphilis involving hearing loss in both ears in a patient with ankylosing spondylitis who was treated with secukinumab. (J Rheum Dis 2019;26:278-281)

Clinical and socio-demographic profile of neurosyphilis: a retrospective study in a reference centre in Colombia

Neurosyphilis is the Treponema pallidum infection of the central nervous system and can occur at any time after the initial infection. In the 21st century, the incidence of neurosyphilis has increased in the post-antibiotic era. The highest rates of neurosyphilis are from low-income countries and the published studies are limited. To determine the clinical and sociodemographic characteristics of neurosyphilis patients in a tertiary care center in Pereira, Colombia. Retrospective study of diagnosed neurosyphilis patients in a tertiary care center in Pereira, Colombia, between 2012 to 2017. The diagnosis was established based on serologic treponemal tests, VDRL in CSF, and CSF analysis. Sociodemographic, clinical, and laboratory parameters variables were obtained. Sixteen patients were included, 11 with definitive neurosyphilis and 5 with probable neurosyphilis. The median age was 59.50 ± 13.78 years. Men accounted for 75% (n = 12) of the patients. Four patients were (25%) HIV-infected. All the patients had positive peripheral FTA-ABS and 11 had reactive VDRL in CSF. The most frequent form was late neurosyphilis (62.5%), being general paralysis the most common. The most frequently clinical manifestations were neuropsychiatric alterations (46.9%), predominantly disorientation, behavioral changes, and cognitive impairment, followed by motor changes (36.7%). Late neurosyphilis was the most prevalent form, predominantly neuropsychiatric alterations. Only a quarter of patients presented HIV coinfection.