LncRNA-ENST00000421645 promotes T cells to secrete IFN-γ by sponging PCM1 in neurosyphilis.

Aim: Neurosyphilis patients exhibited significant expression of long noncoding RNA (lncRNA) in peripheral blood T lymphocytes. In this study, we further clarified the role of lncRNA-ENST00000421645 in the pathogenic mechanism of neurosyphilis. Methods: lncRNA-ENST00000421645 was transfected into Jurkat-E6-1 cells, namely lentivirus (Lv)-1645 cells. RNA pull-down assay, flow cytometry, RT-qPCR, ELISA (Neobioscience Technology Co Ltd, Shenzhen, China) and RNA immunoprecipitation chip assay were used to analyze the function of lncRNA-ENST00000421645. Results: The expression of IFN-γ in Lv-1645 cells was significantly increased compared to that in Jurkat-E6-1 cells stimulated by phorbol-12-myristate-13-acetate (PMA). Then, it was suggested that lncRNA-ENST00000421645 interacts with PCM1 protein. Silencing PCM1 significantly increased the level of IFN-γ in Lv-1645 cells stimulated by PMA. Conclusion: This study revealed that lncRNA-ENST00000421645 mediates the production of IFN-γ by sponging PCM1 protein after PMA stimulation.

Lay abstract The mechanisms underlying Treponema pallidum (a type of bacterium that causes syphilis) invasion into the CNS have not yet been established. In this study, we further clarified the role of long noncoding RNA (lncRNA) in the pathogenic process causing nerve damage. The results suggested that lncRNA-ENST00000421645 interacts with an important protein named PCM1. Suppressing the expression of PCM1 significantly increased the level of IFN-γ cytokines (substances secreted by immune cells that effect other cells) with an increased level of lncRNA-ENST00000421645 when immune cells were stimulated by phorbol-12-myristate-13-acetate a specific activator of the PKC signaling enzyme involved in gene transcription pathways. This study revealed that lncRNA-ENST00000421645 mediates the production of IFN-γ by interacting with PCM1 protein.

Multi-syphilitic gummas in pituitary and cerebellopontine angle in a patient.

PURPOSE: Multi-syphilitic gummas in pituitary and cerebellopontine angle (CPA) are extremely rare and easily misdiagnosed especially in patients with antibiotic abuse. We write this paper for clinicians to better understanding of cerebral gumma. METHODS: We report a patient with syphilitic gummas in pituitary and left CPA. The definite diagnosis is made by histopathology after surgery. RESULTS: A 49-years-old woman suffered from headaches with tinnitus and hypoacusis in left ear. She was diagnosed with syphilis but untreated. There were no chancre and rashes in the course of disease. Syphilis serological tests were positive. Brain MRI found two masses located in the left CPA and hypophysial fossa. The two masses were removed successively. We found a large number of Treponemapallidum in paraffin-embedded specimens by immunohistochemical staining. CONCLUSIONS: Syphilitic gummas in pituitary and CPA are similar to benign or malignant brain tumors, easily leading to misdiagnosis. Gumma should be considered in differential diagnosis when a patient has unexplained nervous system symptoms or signs and imaging findings suggest intracranial mass in syphilis seropositive patients.

Diagnosis of Syphilitic Bilateral Papillitis Mimicking Papilloedema.

Syphilis produces myriad nonspecific signs and symptoms. For example, optic disk swelling might be seen in patients with syphilis as a result of cranial hypertension (papilloedema), inflammatory optic neuritis with papillitis, or optic perineuritis. We report a case involving differential diagnosis of syphilitic bilateral papillitis mimicking papilloedema.

Clinical and Laboratory Characteristics of Symptomatic and Asymptomatic Neurosyphilis in HIV-Negative Patients: A Retrospective Study of 264 Cases.

A retrospective study was performed to compare the differences in clinical and laboratory features of asymptomatic neurosyphilis (ANS) and symptomatic neurosyphilis (SNS). A total of 264 HIV-negative inpatients with neurosyphilis were enrolled from Beijing Ditan Hospital and Beijing Tiantan Hospital between January 2014 and May 2018, including 110 SNS and 154 ANS. The SNS group had more patients in males, older median age and without antisyphilis treatment than ANS group (P<0.001, P<0.001, and P<0.001, respectively). The laboratory findings showed that the SNS group had higher pretreatment serum rapid plasma regain (RPR) titer, current serum RPR titer, cerebrospinal fluid (CSF) white blood cell (WBC) counts, CSF protein concentrations, and higher positive CSF RPR rate than those in the ANS group (P=0.011, P<0.001, P<0.001, P<0.001, and P<0.001, respectively). The multivariate logistic regression analysis revealed that male (OR=2.833, P=0.009), age≥45 years (OR=3.611, P=0.001), without antisyphilis treatment (OR=0.247, P<0.001), higher current serum RPR titer (OR=1.373, P=0.022), positive CSF RPR (OR=4.616, P<0.001), and higher CSF protein concentration (OR=1.017, P=0.026) were independent risk predictors for SNS. Therefore, clinical and laboratory features between SNS and ANS are quietly different. Male gender, age≥45 years, and lack of antisyphilis treatment are risk factors for SNS. The elevated level of serum RPR titer, CSF protein concentration, and CSF RPR titer may indicate the development of neurosyphilis and the aggravation of neurological symptoms.

Lesson of the month 1: Neurosyphilis mimicking viral encephalitis and ischaemic stroke.

With the incidence of syphilis more than doubling over the last decade, knowledge of its manifestations is of increasing importance. Yet, today's clinicians are less experienced in the recognition of syphilis than the physicians of Osler's day.In this case, a 56-year-old man presented with acute confusion and a history suggestive of encephalitis. Neuroimaging revealed cystic infarcts. He was subsequently tested for HIV and syphilis and found to be positive for both. HIV co-infection had accelerated the rate of neurosyphilis progression. After timely diagnosis and treatment of both conditions, cognitive testing returned to baseline.This case highlights that neuroimaging can often show non-specific infarcts and haemorrhages instead of characteristic syphilitic gummae. This variability adds to the challenge of diagnosis. Thus syphilis serology screening should be sent in those presenting with acute confusion and neuroimaging abnormalities. In cases of cryptogenic stroke, syphilis serology should be added to the screening tests.

[Interleukins - 23, -12p40 as markers of neural tissue damage in neurosyphilis.]

To study the features of cytokines in patients with various forms of neurosyphilis. The complex laboratory examination of patients with neurosyphilis and syphilis without specific lesion of the nervous system was observed in the venereological department of the OSH "Clinical Dermatological and Venereological Dispensary" in Omsk in order to determine the concentration of interleukins - 23, 12p40 in CSF and assess their relationship with the course of syphilitic infection. The presence of regularities and features in the deviation of the immune status in the examined disease was established. Analysis of immunological changes in patients' cerebrospinal fluid showed that in patients with neurosyphilis, regardless of the presence or absence of clinical symptoms, the levels of IL-23 and IL-12p40 in CSF significantly exceed those in patients without specific lesion of the nervous system.

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

OBJECTIVES: The 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. METHODS: In 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. RESULTS: The 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. CONCLUSIONS: High 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.

Risk of neurosyphilis in HIV-infected persons with syphilis lacking signs or symptoms of central nervous system infection.

OBJECTIVES: People living with HIV (PLWH) are at increased risk of asymptomatic neurosyphilis; thus, it has been common practice to perform a lumbar puncture (LP) in all PLWH presenting with syphilis regardless of stage, signs or symptoms. However, this practice varies widely among clinicians. Our objective was to elucidate the number of LPs required to diagnose a single case of asymptomatic neurosyphilis. METHODS: We performed an electronic health record (EHR) review of PLWH who were diagnosed with syphilis of any stage over a 10-year period. EHRs were reviewed to determine the number of subjects who had an LP performed, what proportion had neurological signs or symptoms, and whether a diagnosis of neurosyphilis was made at presentation or follow-up. RESULTS: In 261 separate episodes of syphilis in 230 subjects, we found the major risk factors for asymptomatic neurosyphilis to be low CD4 T-cell count (P = 0.0007), high rapid plasma reagin (RPR) titre (P = 0.019) and lack of HIV virological suppression (P = 0.003). The majority of our subjects (78%) with neurosyphilis presented with central nervous system (CNS) symptoms. We estimate, if standard practice is to perform LP in all patients, that the number needed to test (NNTT) = 38. CONCLUSIONS: This large number of potentially unnecessary LPs, along with heterogeneity of presentation, and the never-nil risk of asymptomatic neurosyphilis should be incorporated into clinical decision-making. The majority of PLWH presenting with a serological diagnosis of syphilis, but no neurological signs or symptoms, do not necessarily require an LP for an evaluation of asymptomatic neurosyphilis.

Neurosyphilis: mighty imitator forays with benign presentation and unique neuroimaging findings.

Background Common causes of temporal lobe hyper intensities are central nervous system infections like herpes simplex encephalitis, Lyme disease, limbic encephalitis and vascular pathology like Cerebral Autosomal Dominant Arteriopathy with Subcortical infarcts and Leukoencephalopathy. METHODS: Personal assessment, laboratory data analysis and neuroimaging for the patient who was admitted to a central Pennsylvania tertiary care referral centre were conducted. RESULTS: A 52-year-old male presented with a 1-year history of diffuse dysesthesia in upper and lower extremities with associated intermittent headaches and neck stiffness. Evaluation with lumbar puncture revealed increased nucleated cells (50ul) with lymphocytic predominance (96%) and an elevated protein level of 109mg/dl. Magnetic resonance imaging (MRI) of the brain showed T2/FLAIR hyper intensity in bilateral subcortical temporal white matter, left-greater-than-right and associated volume loss in cerebral parenchyma. Additional abnormal work up included reactive serum reactive plasma regain and Treponema pallidum antibody particle agglutination. Diagnosis of neurosyphilis was made and the patient was treated with intramuscular (IM) penicillin for 3 weeks. At the time of discharge, his headache and neck stiffness resolved and dysesthesias were decreased in intensity. CONCLUSIONS: The diagnosis of neurosyphilis is intricate, and no reference standard exists. Neuroimaging findings of neurosyphilis commonly are cerebral infarctions, leptomeningeal enhancement or non-specific white matter lesions. Less common features on fluid-attenuated inversion recovery (FLAIR) sequences are cortical atrophy and mesial temporal parenchymal signal changes. It is prudent to keep neurosyphilis in differential of mesial temporal lobe white matter changes, as early diagnosis and treatment results in better prognosis.

Cerebral Syphilitic Gumma Misdiagnosed as a Malignant Brain Tumor.

Syphilitic gumma involvement of the central nervous system is extremely rare and frequently misdiagnosed. The authors report a patient of a cerebral syphilitic gumma resembling a malignant brain tumor in a 62-year-old male. He was first suspected of a malignant brain tumor, but the pathological diagnosis was cerebral syphilitic gumma. This patient with unusual findings illustrates the clinical manifestations, imaging, and therapeutic aspects of cerebral syphilitic gumma.

Multifocal neuropathic arthropathy in patient with undiagnosed neurosyphilis: A case report.

Although the prevalence of syphilis has decreased significantly, syphilis is still a common cause of neuropathic arthropathy. Tabetic arthropathy means progressive painless joint destruction that is related to neurosensory deficits caused by syphilis. In general, lower limb joints are involved and gradual swelling and instability of the involved joints are observed. Diagnosis of tabetic arthropathy is difficult as its clinical presentation is not specific and differential diagnosis is wide ranging. Hence, diagnosis of tabetic arthropathy requires clinical suspicion and an appropriate serological test. Laboratory tests for the diagnosis of syphilis include nontreponemal tests and treponemal tests. Conventionally, a nontreponemal test such as the Venereal Disease Research Laboratory test or the Rapid Plasma Reagin test is performed first as a screening test for syphilis, followed by a treponemal test to confirm the positive response found in the screening test. However, the sensitivity and specificity of the serum nontreponemal and treponemal tests for the diagnosis of syphilis are different based on the test type and the syphilis stages. We herein report a case of multifocal neuropathic arthropathy found in a patient whose syphilis was not diagnosed due to a nonreactive screening test result.

Occipital lobe gumma: a case report and review of the literature.

Syphilis has plagued humanity for thousands of years. Despite the measures of precaution against its transmission and the advancement of modern pharmacology, late-stage phenomena like intracerebral gumma are not uncommon even today. We present a complex case, which has misled the physicians twice. Additionally, we performed a review of the contemporary literature about the common location, clinical findings and up-to-date treatment of intracerebral gummas.

[Neurosyphilis in the 21st century: a descriptive study in a tertiary hospital in Madrid]. / Neurosifilis en el siglo XXI: estudio descriptivo en un hospital terciario de Madrid.

INTRODUCTION: Neurosyphilis can occur at any time following infection by Treponema pallidum and its incidence has increased over recent years. The epidemiological and clinical pattern has undergone a substantial change in the post-antibiotic era. AIMS: To describe and analyse the population of patients diagnosed with neurosyphilis at a tertiary hospital in Madrid from January to May 2015. PATIENTS AND METHODS: A retrospective analysis of the following data was performed: demographic, clinical, complementary tests -serology, cerebrospinal fluid (CSF), neuroimaging- and progression of 28 patients diagnosed between 2008 and 2015. RESULTS: Most of the patients were males (89.3%), Spanish (60.7%), with a mean age of 53 ± 16.4 years. The most frequent forms were asymptomatic (39.3%), followed by ocular syphilis (21%), non-classical forms (14.3%), cognitive deterioration and neuropsychiatric alterations (11%). Fifty per cent presented a concomitant infection by human immunodeficiency virus, most of them asymptomatic, with a significant correlation between CD4+ T-cells and asymptomatic neurosyphilis. Only 50% presented VDRL+ in CSF, the diagnosis being based on the clinical features, serology and alterations in CSF (cytobiochemical or serological). Neuroimages were unspecific in most cases. The early and ocular forms were associated to a better clinical course. CONCLUSIONS: With respect to the pre-antibiotic era, an important decrease can be observed in the late-onset forms, as well as the appearance of non-classical forms that can mimic other conditions such as viral encephalitis. Diagnosis is complex and based on the clinical features, the serology and study of CSF, often with a complex interpretation, and thus clinical suspicion plays a fundamental role in the diagnosis.

TITLE: Neurosifilis en el siglo XXI: estudio descriptivo en un hospital terciario de Madrid.Introduccion. La neurosifilis puede ocurrir en cualquier momento tras la infeccion por Treponema pallidum y su incidencia esta aumentando en los ultimos años. El patron epidemiologico y clinico ha experimentado un cambio sustancial en la era postantibiotica. Objetivo. Describir y analizar la poblacion de pacientes con diagnostico de neurosifilis de un hospital terciario de Madrid desde enero de 2008 a mayo 2015. Pacientes y metodos. Se analizaron retrospectivamente datos demograficos, clinicos, pruebas complementarias ­serologia, liquido cefalorraquideo (LCR), neuroimagen­ y evolucion de 28 pacientes diagnosticados entre 2008 y 2015. Resultados. La mayoria fueron varones (89,3%), españoles (60,7%), con una edad media de 53 ± 16,4 años. Lo mas frecuente fueron las formas asintomaticas (39,3%), seguidas de sifilis ocular (21%), formas no clasicas (14,3%), deterioro cognitivo y alteraciones neuropsiquiatricas (11%). El 50% presentaba infeccion concomitante por virus de la inmunodeficiencia humana, la mayoria asintomaticos, con una correlacion significativa entre linfocitos T CD4+ y neurosifilis asintomatica. Unicamente el 50% presento VDRL+ en el LCR, basandose el diagnostico en la clinica, la serologia y las alteraciones en el LCR (citobioquimicas o serologicas). La neuroimagen fue inespecifica en la mayoria de los casos. Las formas tempranas y las formas oculares se asociaron a una mejor evolucion clinica. Conclusiones. Respecto a la era preantibiotica, se observa un descenso muy importante en las formas tardias, asi como la aparicion de formas no clasicas que pueden simular otras entidades, como encefalitis viricas. El diagnostico es complejo y se basa en la clinica, la serologia y el estudio del LCR, a menudo con una interpretacion compleja, por lo que la sospecha clinica es fundamental en el diagnostico.