Neurosyphilis Research Articles

Neurosyphilis, A True Chameleon of Neurology.

Background:Neurosyphilis (NS) is a rarely encountered scenario today. Manifestations are heterogeneous, and their characteristics have changed in the antibiotic era. A differential diagnosis of NS is not commonly thought of even with relevant clinical-radiological features, as it mimics many common neurological syndromes.Objectives:To study the manifestations of NS in the present era and the process of diagnosis.Method:The data of ten patients with NS was collected and analyzed. Their background data, clinical features, investigations, the process of reaching the diagnosis, management and outcomes were recorded.Observations and Results:The manifestations of NS in our cohort included six patients with cognitive decline/encephalopathy and one each with meningitis with cranial nerve palsies, cerebellar ataxia, myelitis and asymptomatic NS. The presence of Argyll Robertson pupil helped to clinch diagnosis in one patient. Treponemal tests were ordered in two patients only after alternative etiologies were looked at, to begin with, whereas in six patients treponemal test was requested as a part of standard workup for dementia/ataxia.Conclusions:NS dementia and behavior changes are mistaken for degenerative, vascular, nutritional causes, autoimmune encephalitis or prion disease. Meningitis has similarities with infective (tubercular), granulomatous (sarcoidosis, Wegener's), collagen vascular disease and neoplastic meningitis, and myelitis simulates demyelination or nutritional myelopathy (B12 deficiency). Rarely, NS can also present with cerebellar ataxia. Contemplate NS as one of the rare causes for such syndromes, and its early treatment produces good outcomes.

Development and External Validation of a Nomogram for Neurosyphilis Diagnosis Among Non-Hiv Patients: A Cross-Sectional Study

Background: The diagnosis of neurosyphilis (NS) is challenging due to the requirement of a lumbar puncture and cerebrospinal fluid (CSF) tests. Methods: This cross-sectional study constructed diagnostic models for diagnosing NS with data gathered from the Western China Hospital of Sichuan University between September 2015 and April 2021 and Shangjin hospital between September 2019 and April 2021, which formed the development and validation cohorts, respectively. A logistic analysis was performed to predict reactive neurosyphilis diagnosis and was presented as a nomogram. Clinical usefulness of the diagnostic models was assessed using a receiver operating characteristic (ROC) curve analysis, and Harrell C index was used for discrimination and calibration plots for accuracy, adopting bootstrap resampling 500 times. Findings: Overall, 149 and 67 patients were included in development and validation cohorts, respectively. Of those, 131 were diagnosed as having reactive NS with positive results in CSF treponemal and non-treponemal tests. In the development cohort, male sex, psychiatric symptoms, and serum toluidine red unheated serum test were selected as diagnostic indicators. The model reached 80% specificity, 79% sensitivity , and 0·85 area under the curves (AUC) (95% CI, 0·76-0·91). In the validation cohorts, the Harrell C index for the diagnostic possibility of reactive NS was 0·71. Interpretation: Both the nomograms were convenient, could discriminate and calibrate well when applied to the validation cohorts, and aid in NS diagnosis. Funding: The National Key Research and Development Program of China (Nos. 2018YFC1311400, 2018YFC1311401) and Clinical Research Incubation Project of West China Hospital of Sichuan University (Grant 2018HXFH022). Declaration of Interest: The authors declare that they have no conflict of interests. Ethical Approval: The ethics committee on biomedical research, West China Hospital of Sichuan University approved the study and waived informed consent from all subjects. The committee’s reference number was 1163 in 2020 approval.

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.

Frequency of Screening and Prevalence of Neurosyphilis in Stroke Population

Background and Aims: Syphilis and stroke are high prevalent diseases in south Brazil and estimates of concomitance and possible role of syphilis in acute stroke are lacking. Our aims are to estimate the prevalence of syphilis and neurosyphilis (NS) in a cohort of tertiary stroke center. Methods: We reviewed all hospital records of stroke/transitory ischemic attack (TIA) using International Classification of Diseases, 10th revision, at discharge, frequency of syphilis screen, serology positivity, cerebrospinal fluid (CSF) analysis, and prevalence of NS in this stroke population applying CDC criteria. Results: Between 2015 and 2016, there were 1,436 discharges for cerebrovascular events and in 78% (1,119) of these cases, some syphilis screening was performed. We have found a frequency of positive serology for syphilis of 13% (143/1,119), and higher stroke severity was the main determinant for non-screening. Applying standard NS criteria, 4.7% (53/1,119) cases with CSF analysis had NS diagnosis: 8 based on CSF-Venereal Disease Research Laboratory (VDRL) positive and 45 based on abnormal CSF white cells or protein, but CSF VDRL negative. NS VDRL positive cases were younger, had higher serum VDRL title, had more frequent HIV infection, and received NS treatment more often. Demographic and clinical characteristics were not different between NS VDRL negative and non-NS cases. Conclusion: Positive syphilis serology is frequent in patients with acute stroke/TIA in our region. Acute post-stroke CSF abnormalities make the diagnosis of NS difficult in the context of CSF VDRL negative.

Chemokine Ligand 13 (CXCL13) in Neuroborreliosis and Neurosyphilis as Selected Spirochetal Neurological Diseases: A Review of Its Diagnostic Significance.

Neuroborreliosis (NB) and neurosyphilis (NS) are abnormal conditions caused by spirochetal bacteria which affect the nervous system. Diagnosis of neuroborreliosis and neurosyphilis is determined by clinical examination of visible symptoms, serum and cerebrospinal fluid (CSF) analysis, and serological detection of antibodies against Borrelia burgdorferi sensu lato and Treponema pallidum, respectively. Establishing a diagnosis may sometimes pose a number of diagnostic difficulties. A potential role of chemokine ligand 13 (CXCL13) as an accurate diagnostic biomarker of intrathecal inflammation has been suggested. In this review, we focused on changes in serum and cerebrospinal fluid concentration of chemokine ligand 13 in selected spirochetal neurological diseases neuroborreliosis and neurosyphilis reported in the available literature. We performed an extensive search of the literature relevant to our investigation via the MEDLINE/PubMed database. It has been proven that CXCL13 determination can provide rapid information regarding central nervous system inflammation in patients with selected spirochetosis. We described that neuroborreliosis and neurosyphilis are associated with an elevated CXCL13 concentration, mainly in the cerebrospinal fluid. Moreover, literature data suggest that CXCL13 determination is the most interesting additional marker for diagnosis and monitoring of neuroborreliosis and neurosyphilis thanks to its high sensitivity. Based on these published findings, we suggest that CXCL13 has high diagnostic utility and may be applied in laboratory diagnostics as a potential diagnostic marker in human spirochetal neurologic diseases.

Infections causing stroke or stroke-like syndromes.

Stroke has relevant morbidity and mortality despite appropriate treatments and early diagnosis. Beside common risk factors such as diabetes and atrial fibrillation, infections can be involved in stroke pathogenesis, probably causing a systemic release of cytokines and other inflammatory mediators, triggering a latent pro-thrombotic state or damaging the vascular endothelium. In other cases, infections can occur as stroke-like syndromes, requiring a high grade of suspicion to avoid a delay in establishing a correct diagnosis. Treatment of stroke or stroke-like syndromes of infectious origin can be difficult. When a previous infective event triggers stroke, Alteplase administration can be associated with a higher incidence of bleeding and the extension of the ischaemic area can be major than expected. On the other hand, when stroke is part of some infectious diseases' presentation as in endocarditis, bacterial or tuberculous meningitis and meningo-vascular syphilis, a correct diagnosis can be difficult. The management of these stroke-like syndromes is not standardised because common treatments proven to be effective for patients with stroke of vascular origin can worsen the prognosis, as it can be demonstrated after to be incorrect Alteplase administration to patients with endocarditis with septic embolism to the brain is associated with an increase of the risk of haemorrhage. Stroke or stroke-like syndrome of infectious origin can be observed in an important proportion of case presenting with sensory-motor deficit of unknown origin; their accurate diagnosis has a considerable impact in terms of treatment choices and outcome.

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.

Gene Expression Profiling in Human Brain Microvascular Endothelial Cells in Response to Treponema pallidum Subspecies pallidum.

Neurosyphilis (NS) is a neurological disorder caused by Treponema pallidum subspecies pallidum (T. pallidum), but how T. pallidum attach to and cross the blood-brain barrier (BBB) and how BBB response to this bacteria remain unclear. To explore how the human brain microvascular endothelial cells (HBMECs) response to T. pallidum, the Agilent SurePrint G3 Human Gene Expression 8×60K microarray was used. The results revealed that 249 genes were differentially expressed in HBMECs infected with T. pallidum. In particular, genes encoding proteins involved in bacterial adhesion, endothelial cell activation and immune response were regulated by T. pallidum. Furthermore, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to determine the biological functions of differentially expressed genes. In summary, T. pallidum changes the gene expression profile in HBMECs, and differentially expressed genes are associated with widespread biological and pathophysiological functions. Above all, this is the first paper reporting the effects of T. pallidum on HBMECs. These data develop a new platform for further molecular experiments on the pathogenesis of NS.

Levodopa-Responsive Chorea: A Review.

Background:Chorea is one of the disabling movement disorders, and the number of drugs which can treat this disorder effectively is limited. Tetrabenazine and deutetrabenazine are the two drugs approved by the US-FDA for the treatment of chorea associated with HD. Levodopa can improve chorea in some disorders, and this review aims to provide information on the use of levodopa in chorea.Methods:A literature search was performed in February 2019 using the following terms “levodopa chorea,” “levodopa TITF-1,” levodopa brain-lung-thyroid syndrome,” and “levodopa Huntington's Disease.” The information regarding the etiology, outcome, and dose of levodopa was collected.Results:We found a total of 18 cases in the literature where the benefit was reported with levodopa. Majority of the cases were brain-thyroid-lung (BTL) syndrome (50%). Another 5 cases were HD (Huntington's Disease), one with PCH type 2 (Pontocerebellar hypoplasia type 2), one with meningovascular syphilis, and two patients with Sydenham chorea. The patients with BTL syndrome responded to a very low dose of levodopa.Discussion:This review suggests that levodopa has the potential to improve chorea in BTL syndrome while its use in chorea due to other disorders requires further study. BTL syndrome due to NKX2-1 mutation responded to levodopa while we did not find any case of chorea due to ADCY-5 mutation responding to levodopa.

The many faces of neurosyphilis: Experience in a Colombian Hospital

Neurosyphilis, a systemic disease secondary to an infection by Treponema pallidum that affects the central nervous system at any stage of the disease, remains a diagnostic challenge for the neurologist due to its wide variety of clinical presentation, which led to the name of “the great mimicker”. Despite being in the post-penicillin era, in Colombia it persists being endemic, although its exact prevalence regarding neurological manifestations is still unknown. We present a series of 10 cases of patients hospitalized between 2017 and 2019 at the San José Hospital in Bogotá, Colombia, admitted with different neurological manifestations in whom the diagnosis of neurosyphilis is confirmed. Of the clinical presentations described in the literature were: 1 patient with asymptomatic neurosyphilis, 2 patients with syphilitic meningitis (1 with vertex involvement and 1 with basilar involvement), 5 with meningovascular syphilis and finally 2 with a general paresis type. Of the 10 patients, the 50% course with human immunodeficiency virus and presented a favorable clinical evolution after the treatment with crystalline penicillin for 14 days. We can observe that neurosifilis is still a health problem in developing countries and given its extensive neurological manifestations associated with presentation in immunocompromised and immunocompetent patients, it remains a diagnostic challenge and should be considered as a differential diagnosis in daily clinical practice.

High HbA1c level is correlated with blood-brain barrier disruption in syphilis patients.

Diabetes mellitus (DM) and neurosyphilis (NS) may both damage the blood-brain barrier (BBB). It seems that non-neurosyphilis (non-NS) patients with high HbA1c levels are likely to develop into NS. However, the correlation of HbA1c level with BBB disruption in syphilis (non-NS) patients is unclear. In this study, we used dynamic contrast-enhanced (DCE) MRI to quantify regional BBB permeability in syphilis (non-NS) patients and detected several molecular biomarkers of cerebrospinal fluid (CSF). We found that BBB permeability values in the hippocampus, white matter, and cortex inferior temporal gyrus were correlated with albumin quotient (Qalb), CSF concentrations of interleukin IL-6 and IL-10. Moreover, BBB breakdown in white matter was correlated with CSF concentrations of sICAM-1 and sVCAM-1. In conclusion, our data suggest that BBB integrity may be liable to be disrupted in syphilis (non-NS) patients, patients with high HbA1c levels, as well as syphilis (non-NS) patients with high HbA1c levels, and it is particularly important to control blood glucose in these patients.

Neurosyphilis in the modern era: Literature review and case series

The term of neurosyphilis (NS) refers to infection of central nervous system by Treponema pallidum. Classically, it has been divided into early (meningitis, meningovascular) and late forms (general paresis and tabes dorsalis). The availability of penicillin and high sensitivity of Treponema pallidum to this antibiotic has led to a widely held perception about rarity of syphilitic forms with central nervous system involvement. However, patient can exhibit atypical clinical presentation. Recently different clinical cases with autoimmune encephalitis-mimicking presentation or atypical movement disorders were described.In this article we presented clinical case series with different clinical and MRI presentation and discuss diagnostic and treatment challenges. During our screening period at neurological department we revealed 6 NS cases. Three of them have an atypical presentation. The first patient was misdiagnosed as acute disseminated encephalomyelitis, the second patient had hippocampal sclerosis and epileptic seizures. Another patient had cognitive decline and autoimmune encephalitis-like MRI lesions.We put an emphasis on widening of indication for lumbar puncture and NS tests in patients with syphilitic anamnesis and neurological manifestations.

Clinical case of meningovascular syphilis in combination with HIV infection

Purpose: to study the features of clinical course, diagnosis and treatment of meningovacular syphilis associated with HIV infection. Materials and methods. Clinical case of meningovascular syphilis in the context of HIV infection in a 55-year-old man, methods of diagnosis and treatment. Results. The article deals with a special case of meningovascular syphilis associated with HIV in the man of 55 years, as well as the features of the clinical course and treatment of this pathology are discussed based on the analysis of the professional literature data. The data of anamnesis, objective, laboratory and instrumental examination, results of patient's treatment are presented. It is noted that a stroke may be the first manifestation of neurosyphilis and HIV infection. Changes in the cerebrospinal fluid were accompanied by a slight increase in lymphocytes. Specific immunological examination of blood and liquor was the key to the diagnosis. Treatment with ceftriaxone has resulted in improvement of the patient's health condition and a regression of motor neurologic deficit. Conclusions. Patients with HIV infection are vulnerable to cerebrovascular diseases due to various etiological factors. Meningovascular form of neurosyphilis may be the initial manifestation of syphilis in both HIV-positive and HIV-negative individuals. Due to the increased incidence of syphilis, as well as co-infection with HIV, it is recommended to examine young patients with a stroke of unknown etiology with a presence of undetermined neurological symptoms and changes in the cerebrospinal fluid for HIV and syphilis. Clinical manifestations of neurovascular syphilis tend to be regressed in the course of specific antibiotic therapy.

Exosomal microRNA profiles from serum and cerebrospinal fluid in neurosyphilis

ObjectiveChanges in microRNAs (miRNAs) in the cerebrospinal fluid (CSF) are associated with different neurological diseases. Since alternations of miRNAs in neurosyphilis are insufficiently investigated, we analysed miRNAs in the CSF...

2273. Neurosyphilis in Pacients With HIV Infection: Clinical Presentation of 94 Cases

BackgroundSyphilis remains highly prevalent, particularly in men with HIV infection (HIV+), in whom atypical manifestations and neurosyphilis (NS) are frequent. NS may be asymptomatic and IM benzathine penicillin treatment is ineffective. Although ideal-but not practical-all cases of syphilis in HIV+ patients (patients) should have CSF study to rule out NS. The objective of this study was to quantify and characterize NS cases in HIV+ patients with syphilis.MethodsRetrospective study from 01-02-2013 to 04-30-2018 at Fundación Arriarán in Santiago, Chile of 618 coinfected patients with CSF study due to neurological, visual or auditory symptoms, or serum VDRL ≥ 1:32. Any positive VDRL titer in CSF was considered demonstrated NS (dNS) and isolated pleocytosis ≥ 20 cells/μL considered probable NS (pNS). Status of HIV infection, syphilis, CSF analysis, NS treatment, and follow-up were characterized.ResultsNS was diagnosed in 94/618 patients (15.2%) with CSF study, (3 women), 80.8% were dNS and 19.2% pNS. Median age was 32 years (range 20–67); median CD4 cell count was 317 cells/μL (IQR of 188–473). In 41.5% NS was diagnosed at entry into care; syphilis was classified as primary in 2.1%, secondary in 22.3%, early–latent in 29.8% and late latent in 45.8%. Most cases of NS (84%) were neurologically asymptomatics (88.8% in pNS). Median CSF leukocytes in dNS was 5 cells/μL (range 0–338), and in pNS 31 cells/μL (range 16–90). Treatment was with IV ceftriaxone in 57/94 (60.6%), and in 39.4% with IV sodium penicillin. Follow-up data with serum VDRL at 3, 6 and 12 months were obtained in 44/94 (41.4%), 37.6% and 24.4% of patients respectively, who presented a decrease of 2-fold serum VDRL in 35/44 (79.5%), 82.5% and 92.3% with data, according to baseline, respectively.ConclusionNS is an important complication of syphilis in HIV+ patients; and it should be suspected and actively investigated throughout their care given the high rate of asymptomatic status, even in NSd. Positivity of VDRL in CSF is associated with more symptoms. Ceftriaxone is an alternative therapy, but that requires larger and longer prospective studies for confirmation. The decrease of 2-fold serum VDRL in 6 months may predict treatment success. The role of CSF study post treatment to evaluate this outcome and the criteria for cure have not been well established.Disclosures All authors: No reported disclosures.

Predictors of unfavorable outcome in neurosyphilis: Multicenter ID-IRI Study.

Neurosyphilis (NS) has different clinical manifestations and can appear during any stage of syphilis. We aimed to identify the factors affecting poor outcome in NS patients. Patients with positive cerebrospinal fluid Venereal Disease Research Laboratory test, and positive serological serum treponemal or nontreponemal tests were classified as definite NS. The data of 141 patients with definite NS were submitted from 22 referral centers. Asymptomatic NS, syphilitic meningitis, meningovascular syphilis, tabes dorsalis, general paresis, and taboparesis were detected in 22 (15.6%), 67 (47.5%), 13 (9.2%), 10 (7%), 13 (9.2%), and 16 patients (11.3%), respectively. The number of HIV-positive patients was 43 (30.4%). The most common symptoms were headache (n= 55, 39%), fatigue (n= 52, 36.8%), and altered consciousness (50, 35.4%). Tabetic symptoms were detected in 28 (19.8%), paretic symptoms in 32 (22.6%), and vascular symptoms in 39 patients (27.6%). Eye involvement was detected in 19 of 80 patients (23.7%) who underwent eye examination and ear involvement was detected in eight of 25 patients (32%) who underwent ear examination. Crystallized penicillin was used in 109 (77.3%), procaine penicillin in seven (4.9%), ceftriaxone in 31 (21.9%), and doxycycline in five patients (3.5%). According to multivariate regression analysis, while headache was a protective factor in NS patients, double vision was significantly associated to poor outcome. We concluded that double vision indicated unfavorable outcome among NS patients. A high clinical suspicion is needed for the diagnosis NS. As determined in our study, the presence of headache in syphilitic patients can help in early diagnosis of central nervous system disease.

Neurosyphilis prevalence at a Portuguese stroke unit care.

Syphilis is a systemic human disease which is caused by infection with the spirochete Treponema pallidum. It is spread worldwide, and there has recently been an increase in its incidence. Neurosyphilis (NS) can have a variety of presentations; meningovascular NS is a specific affection of the Treponema which occurs in an early stage after the primary infection, causing an inflammatory arteriopathy which may result in an ischemic stroke. As a rare manifestation of syphilis, there are few prevalence and epidemiological studies, and data are almost non-existent. The objective of this study is to analyse the prevalence of meningovascular NS in a stroke unit in a tertiary hospital. A descriptive retrospective study was carried out over a period of 44 months in a stroke unit. All patients admitted had neurological symptoms compatible with a vascular event, and routine blood tests including infectious screening were performed. Those with positive test results for syphilis were identified and proceeded to lumbar puncture to CSF cytochemical analysis and VDRL. NS was categorized as confirmed or probable (using CDC criteria). A total of 525 patients were admitted, and 62.53% were submitted to a routine screening for syphilis. A total of 309 patients (95.67%) revealed a negative screening; 12 patients (3.72%) had a positive syphilis serology. Among the 12 patients with positive screening, a single case of NS (0.31%) was identified. We observed a low prevalence of NS (0.31%), but this result was surprisingly higher than what was expected in an elderly population.