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Bruce H Price - One of the best experts on this subject based on the ideXlab platform.
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Neurosyphilis in psychiatric practice a case based discussion of clinical evaluation and diagnosis
General Hospital Psychiatry, 2015Co-Authors: Jennifer R Gatchel, Benalfew Legesse, Safwan Tayeb, Evan D Murray, Bruce H PriceAbstract:Abstract Objective Neurosyphilis can present with a wide range of neuropsychiatric symptoms. Hence, psychiatrists need to be familiar with tests for syphilis screening and how to interpret syphilis serologic tests. Methods We present four cases of patients with positive syphilis tests encountered in a psychiatric hospital. Results Two cases were treated for Neurosyphilis, while the other two cases did not have active syphilis infection despite positive results. Conclusion We thus highlight the challenges encountered by psychiatrists in screening for and diagnosing cases of Neurosyphilis.
Adam Jenney - One of the best experts on this subject based on the ideXlab platform.
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Neurosyphilis: Concordance between cerebrospinal fluid analysis and subsequent antibiotic strategy for patients undergoing evaluation of a diagnosis of Neurosyphilis.
International Journal of Infectious Diseases, 2019Co-Authors: Olivia C. Smibert, Denis Spelman, S. Abbinga, Adam JenneyAbstract:Abstract Introduction The confirmation or analysis and exclusion of a diagnosis of Neurosyphilis has long presented a challenge for infectious diseases clinicians. The authors reviewed the concordance between cerebrospinal fluid (CSF) analysis and the subsequent antibiotic strategy for patients undergoing evaluation of a diagnosis of Neurosyphilis. Methods All patients with positive serum syphilis serology referred for CSF analysis between January 2009 and May 2016 were included. Indications for CSF analysis were determined by review of the hospital electronic medical records. CSF parameters were determined from the hospital pathology database. Cases were defined as either ‘confirmed’, ‘supportive’ of, or ‘not supportive’ of a diagnosis of Neurosyphilis based on existing definitions. Subsequent therapy was defined as for Neurosyphilis, late latent primary syphilis or no therapy based on existing guidelines. Results Of 131 patients reviewed, 95.4% were male and HIV co-infected (74%). A confirmed diagnosis of Neurosyphilis was met by fourteen patients (10.7%). All but two of these were treated with a Neurosyphilis-directed regimen. Of the 58 patients treated with Neurosyphilis antibiotics, 17.2% had no CSF findings suggestive of the diagnosis. Seventy-three patients were not treated for Neurosyphilis; however 35 of these met the CSF criteria for a diagnosis supportive of Neurosyphilis. Conclusions The results of routine CSF analysis in patients with a possible diagnosis of Neurosyphilis are inconsistently applied in the clinical setting, calling into question the value of routine CSF. Empirical Neurosyphilis treatment should be considered up front in patients with high pre-test probability of the diagnosis.
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Neurosyphilis: Concordance between cerebrospinal fluid analysis and subsequent antibiotic strategy for patients undergoing evaluation of a diagnosis of Neurosyphilis
Elsevier, 2019Co-Authors: O.c. Smibert, Denis Spelman, S. Abbinga, Adam JenneyAbstract:Introduction: The confirmation or analysis and exclusion of a diagnosis of Neurosyphilis has long presented a challenge for infectious diseases clinicians. The authors reviewed the concordance between cerebrospinal fluid (CSF) analysis and the subsequent antibiotic strategy for patients undergoing evaluation of a diagnosis of Neurosyphilis. Methods: All patients with positive serum syphilis serology referred for CSF analysis between January 2009 and May 2016 were included. Indications for CSF analysis were determined by review of the hospital electronic medical records. CSF parameters were determined from the hospital pathology database. Cases were defined as either ‘confirmed’, ‘supportive’ of, or ‘not supportive’ of a diagnosis of Neurosyphilis based on existing definitions. Subsequent therapy was defined as for Neurosyphilis, late latent primary syphilis or no therapy based on existing guidelines. Results: Of 131 patients reviewed, 95.4% were male and HIV co-infected (74%). A confirmed diagnosis of Neurosyphilis was met by fourteen patients (10.7%). All but two of these were treated with a Neurosyphilis-directed regimen. Of the 58 patients treated with Neurosyphilis antibiotics, 17.2% had no CSF findings suggestive of the diagnosis. Seventy-three patients were not treated for Neurosyphilis; however 35 of these met the CSF criteria for a diagnosis supportive of Neurosyphilis. Conclusions: The results of routine CSF analysis in patients with a possible diagnosis of Neurosyphilis are inconsistently applied in the clinical setting, calling into question the value of routine CSF. Empirical Neurosyphilis treatment should be considered up front in patients with high pre-test probability of the diagnosis. Keywords: Neurosyphilis, Rapid plasma reagin, Fluorescent treponemal antibody, Lumbar puncture, Cerebrospinal flui
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Management of Neurosyphilis: time for a new approach?
Internal Medicine Journal, 2018Co-Authors: Olivia C. Smibert, Adam Jenney, Denis SpelmanAbstract:: Given the long term sequelae of untreated Neurosyphilis and insensitive tests to detect treponemes in the cerebrospinal fluid, questions regarding the utility of a lumbar puncture and cerebrospinal fluid analysis either to confirm or exclude Neurosyphilis are raised.
Christina M Marra - One of the best experts on this subject based on the ideXlab platform.
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Update on Neurosyphilis
Current Infectious Disease Reports, 2009Co-Authors: Christina M MarraAbstract:Neurosyphilis literally means syphilitic infection of the central nervous system, but it is often referred to incorrectly as “tertiary syphilis.” Neurosyphilis can occur at any time in the course of syphilis, even in the earliest, primary, stage. Early forms of Neurosyphilis primarily affect the meninges, cerebrospinal fluid, and cerebral or spinal cord vasculature. Late forms of Neurosyphilis primarily affect the brain and spinal cord parenchyma. Uveitis and hearing loss related to syphilis are most common in early syphilis and may be accompanied by early Neurosyphilis. The treatment for syphilis-related eye disease and hearing loss is the same as the treatment for Neurosyphilis. Neurosyphilis is more commonly seen in patients infected with HIV, and much of the recent literature pertains to this risk group. This article provides a critical review of recent literature on the diagnosis, clinical findings, risk factors, and management of Neurosyphilis.
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normalization of serum rapid plasma reagin titer predicts normalization of cerebrospinal fluid and clinical abnormalities after treatment of Neurosyphilis
Clinical Infectious Diseases, 2008Co-Authors: Christina M Marra, Clare L Maxwell, Lauren C Tantalo, Sharon K Sahi, Sheila A LukehartAbstract:Syphilis is caused by infection due to Treponema pallidum subspecies pallidum, a spirochete that cannot be visualized by light microscopy and cannot be cultured. Depending on the stage of infection, the diagnosis of syphilis is established by documentation of reactive serum nontreponemal tests (rapid plasma reagin [RPR] test or venereal disease research laboratory [VDRL] test) and treponemal tests (T. pallidum particle agglutination assay [TPPA] or fluorescent treponemal anti-body-absorption [FTA-ABS] test), with or without characteristic symptoms or signs of syphilis. Because T. pallidum cannot be cultured, diagnosis of Neurosyphilis relies on the following indirect measures: elevated CSF WBC count or protein concentration or reactivity of the CSF VDRL test. A reactive CSF VDRL test is considered to be diagnostic of Neurosyphilis, but depending on the criteria used to define Neurosyphilis, this test may be nonreactive in patients with Neurosyphilis [1–3]. Standard benzathine penicillin G therapy is not recommended for persons with Neurosyphilis, because it yields penicillin concentrations in the CSF that are too low to kill T. pallidum. Instead, treatment specifically for Neurosyphilis, with intravenous (IV) aqueous crystalline penicillin G or with intramuscular (IM) aqueous procaine penicillin G (APPG) plus probenecid, is recommended [4]. Alternative regimens of doxycycline or ceftriaxone are also sometimes used, but there are few data on the efficacy of these regimens [5–8]. For patients who are neurologically asymptomatic, assessment of the efficacy of Neurosyphilis treatment relies solely on normalization of CSF measures. For those with symptoms or signs, resolution of clinical abnormalities is also considered when determining the efficacy of treatment. Current guidelines recommend that lumbar puncture be serially repeated after Neurosyphilis therapy until all CSF measures have normalized [4]. However, patients who have received treatment of Neurosyphilis may be reluctant to undergo repeated lumbar punctures to assess the effectiveness of therapy. The goal of this study was to determine whether a decrease in serum RPR titer could serve as a surrogate for normalization of CSF and clinical abnormalities after treatment of asymptomatic or symptomatic Neurosyphilis.
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alternative cerebrospinal fluid tests to diagnose Neurosyphilis in hiv infected individuals
American Journal of Ophthalmology, 2004Co-Authors: Christina M Marra, Clare L Maxwell, Lauren C Tantalo, K Dougherty, B WoodAbstract:Neurosyphilis is commonly present in patients with ocular syphilis who are also infected by HIV. The diagnosis of Neurosyphilis may be difficult as up to 70% of HIV-positive patients with Neurosyphilis have a negative cerebrospinal fluid (CSF)-Venereal Disease Research Laboratory (VDRL) test. The aim of this study was to identify alternatives to the CSF-VDRL test for the diagnosis of Neurosyphilis in HIV-infected individuals. CSF fluorescent treponemal antibody (FTA) reactivity and % CSF lymphocytes that were B cells in fresh and frozen samples were determined for 47 HIV-infected cases with syphilis and 26 HIV-infected controls. As for serum, CSF fluorescent treponemal antibody reactivity ≥2+ was considered positive. Based on the results in controls and cases with normal CSF measures, cut-offs for elevated CSF B cells were proposed to be ≥9% in fresh and ≥20% in frozen samples. Neurosyphilis was defined as a reactive CSF-VDRL. The authors found that CSF-FTA-ABS (absorbed) and CSF-FTA (unabsorbed and undiluted) were 100% sensitive for the diagnosis of Neurosyphilis. Elevated % CSF B cells in fresh and cryopreserved samples was specific (100%) but not sensitive (40 and 43%) in post hoc analyses. The results of CSF-FTA and assessment of % CSF B cells together allowed 16% of cases with pleocytosis but nonreactive CSF-VDRL to be diagnosed with Neurosyphilis and 26% to be diagnosed as not having Neurosyphilis. The authors conclude that when the CSF-VDRL is nonreactive, CSF-FTA and % CSF B cells may help exclude or establish the diagnosis of Neurosyphilis.—Valerie Biousse
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alternative cerebrospinal fluid tests to diagnose Neurosyphilis in hiv infected individuals
Neurology, 2004Co-Authors: Christina M Marra, Clare L Maxwell, Lauren C Tantalo, K Dougherty, B WoodAbstract:Objective: To identify alternatives to the CSF-Venereal Disease Research Laboratory (VDRL) test for the diagnosis of Neurosyphilis in HIV-infected individuals. Methods: CSF fluorescent treponemal antibody (FTA) reactivity and % CSF lymphocytes that were B cells in fresh and frozen samples were determined for 47 HIV-infected cases with syphilis and 26 HIV-infected controls. As for serum, CSF fluorescent treponemal antibody reactivity ≥2+ was considered positive. Based on the results in controls and cases with normal CSF measures, cut-offs for elevated CSF B cells were proposed to be ≥9% in fresh and ≥20% in frozen samples. Neurosyphilis was defined as a reactive CSF-VDRL. Results: CSF-FTA-ABS (absorbed) and CSF-FTA (unabsorbed and undiluted) were 100% sensitive for the diagnosis of Neurosyphilis. Elevated % CSF B cells in fresh and cryopreserved samples was specific (100%) but not sensitive (40 and 43%) in post hoc analyses. The results of CSF-FTA and assessment of % CSF B cells together allowed 16% of cases with pleocytosis but nonreactive CSF-VDRL to be diagnosed with Neurosyphilis and 26% to be diagnosed as not having Neurosyphilis. Conclusion: When the CSF-VDRL is nonreactive, CSF-FTA and % CSF B cells may help exclude or establish the diagnosis of Neurosyphilis.
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cerebrospinal fluid abnormalities in patients with syphilis association with clinical and laboratory features
The Journal of Infectious Diseases, 2004Co-Authors: Christina M Marra, Clare L Maxwell, Stacy L Smith, Sheila A Lukehart, Anne Marie Rompalo, Molly Eaton, Bradley P Stoner, Michael Augenbraun, David E Barker, James J CorbettAbstract:Objective. To define clinical and laboratory features that identify patients with Neurosyphilis. Methods. Subjects (n = 326) with syphilis but no previous Neurosyphilis who met 1993 Centers for Disease Control and Prevention criteria for lumbar puncture underwent standardized history, neurological examination, venipuncture, and lumbar puncture. Neurosyphilis was defined as a cerebrospinal fluid (CSF) white blood cell count >20 cells/μL or reactive CSF Venereal Disease Research Laboratory (VDRL) test result. Results. Sixty-five subjects (20.1%) had Neurosyphilis. Early syphilis increased the odds of Neurosyphilis in univariate but not multivariate analyses. In multivariate analyses, serum rapid plasma reagin (RPR) titer ≥1:32 increased the odds of Neurosyphilis 10.85-fold in human immunodeficiency virus (HIV)-uninfected subjects and 5.98-fold in HIV-infected subjects. A peripheral blood CD4 + T cell count ≤350 cells/μL conferred 3.10-fold increased odds of Neurosyphilis in HIV-infected subjects. Similar results were obtained when Neurosyphilis was more stringently defined as a reactive CSF VDRL test result. Conclusion. Serum RPR titer helps predict the likelihood of Neurosyphilis. HIV-induced immune impairment may increase the risk of Neurosyphilis.
David Mabey - One of the best experts on this subject based on the ideXlab platform.
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diagnostic performance of pcr assays for the diagnosis of Neurosyphilis a systematic review
Sexually Transmitted Infections, 2018Co-Authors: Michael Marks, David Lawrence, Christian Kositz, David MabeyAbstract:Introduction Syphilis continues to be a major public health problem and the recent resurgence in syphilis in high-income settings has seen an accompanying increase in cases of Neurosyphilis. While the introduction of PCR has had a significant impact on the diagnosis of early syphilis, cerebrospinal fluid (CSF) serological assays remain the most commonly used tests to diagnosis Neurosyphilis. We reviewed data on the performance of CSF-PCR for the diagnosis of Neurosyphilis. Methods We searched Pubmed, Medline, EMBASE and the grey literature for references on PCR in Neurosyphilis. We calculated the sensitivity and specificity of PCR compared with reference testing for the diagnosis of Neurosyphilis. Results We identified 66 articles of which seven met the study inclusion criteria. The sensitivity of PCR for definite Neurosyphilis varied between 40% and 70% and specificity between 60% and 100% across the studies. The most commonly used PCR assay targeted Tp47 which had an overall sensitivity of 68% and a specificity of 91.9%. Discussion The sensitivity of PCR was low compared with CSF-serological assays but the challenges of evaluating a diagnostic test in the absence of a clear gold standard make definitive interpretation challenging. Most studies were small and not adequately powered highlighting the need for multicentre, multicountry trials to provide adequate statistical power in evaluations of new tests the diagnosis of Neurosyphilis.
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Neurosyphilis in Africa: A systematic review.
PLOS Neglected Tropical Diseases, 2017Co-Authors: Michael Marks, Joseph N. Jarvis, William Howlett, David MabeyAbstract:Introduction Neurological involvement is one of the most important clinical manifestations of syphilis and neurological disease occurs in both early and late syphilis. The impact of HIV co-infection on clinical Neurosyphilis remains unclear. The highest prevalence of both syphilis and HIV is in Africa. Therefore it might be expected that Neurosyphilis would be an important and not uncommon manifestation of syphilis in Africa and frequently occur in association with HIV co-infection; yet few data are available on Neurosyphilis in Africa. The aim of this study is to review data on Neurosyphilis in Africa since the onset of the HIV epidemic. Methods We searched the literature for references on Neurosyphilis in Africa for studies published between the 1st of January 1990 and 15th February 2017. We included case reports, case series, and retrospective and prospective cohort and case-control studies. We did not limit inclusion based on the diagnostic criteria used for Neurosyphilis. For retrospective and prospective cohorts, we calculated the proportion of study participants who were diagnosed with Neurosyphilis according to the individual study criteria. Depending on the study, we assessed the proportion of patients with syphilis found to have Neurosyphilis, and the proportion of patients with neurological syndromes who had Neurosyphilis. Due to heterogeneity of data no formal pooling of the data or meta-analysis was undertaken. Results Amongst patients presenting with a neurological syndrome, three studies of patients with meningitis were identified; Neurosyphilis was consistently reported to cause approximately 3% of all cases. Three studies on stroke reported mixed findings but were limited due to the small number of patients undergoing CSF examination, whilst Neurosyphilis continued to be reported as a common cause of dementia in studies from North Africa. Ten studies reported on cases of Neurosyphilis amongst patients known to have syphilis. Studies from both North and Southern Africa continue to report cases of late stage syphilis, including tabes dorsalis and Neurosyphilis, in association with ocular disease. Discussion This is the first systematic review of the literature on Neurosyphilis in Africa since the beginning of the HIV epidemic. Neurosyphilis continues to be reported as a manifestation of both early and late syphilis, but the methodological quality of the majority of the included studies was poor. Future well-designed prospective studies are needed to better delineate the incidence and clinical spectrum of Neurosyphilis in Africa and to better define interactions with HIV in this setting.
Sheila A Lukehart - One of the best experts on this subject based on the ideXlab platform.
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normalization of serum rapid plasma reagin titer predicts normalization of cerebrospinal fluid and clinical abnormalities after treatment of Neurosyphilis
Clinical Infectious Diseases, 2008Co-Authors: Christina M Marra, Clare L Maxwell, Lauren C Tantalo, Sharon K Sahi, Sheila A LukehartAbstract:Syphilis is caused by infection due to Treponema pallidum subspecies pallidum, a spirochete that cannot be visualized by light microscopy and cannot be cultured. Depending on the stage of infection, the diagnosis of syphilis is established by documentation of reactive serum nontreponemal tests (rapid plasma reagin [RPR] test or venereal disease research laboratory [VDRL] test) and treponemal tests (T. pallidum particle agglutination assay [TPPA] or fluorescent treponemal anti-body-absorption [FTA-ABS] test), with or without characteristic symptoms or signs of syphilis. Because T. pallidum cannot be cultured, diagnosis of Neurosyphilis relies on the following indirect measures: elevated CSF WBC count or protein concentration or reactivity of the CSF VDRL test. A reactive CSF VDRL test is considered to be diagnostic of Neurosyphilis, but depending on the criteria used to define Neurosyphilis, this test may be nonreactive in patients with Neurosyphilis [1–3]. Standard benzathine penicillin G therapy is not recommended for persons with Neurosyphilis, because it yields penicillin concentrations in the CSF that are too low to kill T. pallidum. Instead, treatment specifically for Neurosyphilis, with intravenous (IV) aqueous crystalline penicillin G or with intramuscular (IM) aqueous procaine penicillin G (APPG) plus probenecid, is recommended [4]. Alternative regimens of doxycycline or ceftriaxone are also sometimes used, but there are few data on the efficacy of these regimens [5–8]. For patients who are neurologically asymptomatic, assessment of the efficacy of Neurosyphilis treatment relies solely on normalization of CSF measures. For those with symptoms or signs, resolution of clinical abnormalities is also considered when determining the efficacy of treatment. Current guidelines recommend that lumbar puncture be serially repeated after Neurosyphilis therapy until all CSF measures have normalized [4]. However, patients who have received treatment of Neurosyphilis may be reluctant to undergo repeated lumbar punctures to assess the effectiveness of therapy. The goal of this study was to determine whether a decrease in serum RPR titer could serve as a surrogate for normalization of CSF and clinical abnormalities after treatment of asymptomatic or symptomatic Neurosyphilis.
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cerebrospinal fluid abnormalities in patients with syphilis association with clinical and laboratory features
The Journal of Infectious Diseases, 2004Co-Authors: Christina M Marra, Clare L Maxwell, Stacy L Smith, Sheila A Lukehart, Anne Marie Rompalo, Molly Eaton, Bradley P Stoner, Michael Augenbraun, David E Barker, James J CorbettAbstract:Objective. To define clinical and laboratory features that identify patients with Neurosyphilis. Methods. Subjects (n = 326) with syphilis but no previous Neurosyphilis who met 1993 Centers for Disease Control and Prevention criteria for lumbar puncture underwent standardized history, neurological examination, venipuncture, and lumbar puncture. Neurosyphilis was defined as a cerebrospinal fluid (CSF) white blood cell count >20 cells/μL or reactive CSF Venereal Disease Research Laboratory (VDRL) test result. Results. Sixty-five subjects (20.1%) had Neurosyphilis. Early syphilis increased the odds of Neurosyphilis in univariate but not multivariate analyses. In multivariate analyses, serum rapid plasma reagin (RPR) titer ≥1:32 increased the odds of Neurosyphilis 10.85-fold in human immunodeficiency virus (HIV)-uninfected subjects and 5.98-fold in HIV-infected subjects. A peripheral blood CD4 + T cell count ≤350 cells/μL conferred 3.10-fold increased odds of Neurosyphilis in HIV-infected subjects. Similar results were obtained when Neurosyphilis was more stringently defined as a reactive CSF VDRL test result. Conclusion. Serum RPR titer helps predict the likelihood of Neurosyphilis. HIV-induced immune impairment may increase the risk of Neurosyphilis.
