The challenge of diagnosis and treatment of neurosyphilis in China: results from a nationwide survey.

Background The uncertainty of how neurosyphilis is diagnosed and treated in clinical settings led us to investigate whether this serious manifestation of syphilis infection is properly managed in China. METHODS: This national cross-sectional study of the diagnosis and treatment of neurosyphilis included 1392 clinicians at 398 hospitals located in 116 cities in China. RESULTS: Of 398 hospitals, 244 (61.3%) failed to perform diagnostic laboratory tests and 181 (45.5%) failed to provide recommended treatment for neurosyphilis. Of 1392 clinicians, 536 (38.5%) had previously diagnosed patients with neurosyphilis, but 419 (78.2%) of the latter provided diagnoses that did not meet the criteria set by national guidelines. Of the 485 clinicians who had previously treated patients with neurosyphilis, 280 (57.7%) failed to follow national guidelines for treatment. Analysis indicated that clinicians working in North China (adjusted odds ratio (aOR), 4.24; 95% confidence interval (CI), 1.65-10.88), tertiary hospitals (aOR, 3.23; 95% CI, 1.63-6.41), and hospitals specialising in sexually transmitted infections (aOR, 2.49; 95% CI, 1.24-4.99) were more likely to follow national guidelines for neurosyphilis treatment. CONCLUSION: Lack of knowledge in disease management poses a great obstacle to prevent the serious consequences of neurosyphilis in Chinese patients. More effective measures are urgently needed to improve this suboptimal situation.

Cognitive impairment in syphilis: Does treatment based on cerebrospinal fluid analysis improve outcome?

BACKGROUND: Individuals with previous syphilis may experience cognitive impairment. The goal of this study was to determine if those at high risk for laboratory-defined neurosyphilis are cognitively impaired, and whether treatment based on cerebrospinal fluid (CSF) findings results in better outcomes. METHODS: Participants had a new syphilis diagnosis, serum RPR titer ≥ 1:32 or peripheral blood CD4+ T cells ≤ 350/ul (in persons living with HIV) and did not endorse neurological symptoms. They underwent computerized cognitive assessment with the CogState. Thirty-two were randomized to either undergo lumbar puncture (LP) or to not undergo LP and 14 underwent LP; 64 were not randomized and 48 opted to undergo LP. RESULTS: Demographics, cognitive complaints and cognitive impairment did not differ between randomized and nonrandomized participants. Two-thirds were cognitively impaired, and impairment was not more common in those with cognitive complaints. The adjusted odds of increased severity of impairment were 3.8 times greater in those with CSF pleocytosis compared to those without. Time to cognitive normalization, improvement or decline did not differ between those who did not undergo LP and those who underwent LP and whose treatment was based on CSF analysis. Taking into account pre-treatment cognitive impairment, the risk of cognitive decline was lower in those with CSF pleocytosis treated for neurosyphilis compared to those without CSF pleocytosis not treated for neurosyphilis, (HR 0.24 (95% CI 0.07-0.88], p = 0.03). CONCLUSION: In individuals at high risk for laboratory-defined neurosyphilis, cognitive complaints are not a good indicator of cognitive impairment. Severity of cognitive impairment was greater in those with CSF pleocytosis. Identification and treatment of those with neurosyphilis may mitigate subsequent cognitive decline.

Neurosyphilis revealed by compressive cervical spine syphilitic gumma: a case report.

INTRODUCTION: Neurosyphilis is a sexually transmitted disease secondary to the invasion of the central nervous system by the Treponema pallidum. The spinal syphilitic gumma is rare. CASE PRESENTATION: We report a case of extradural cervical spinal syphilitic gumma revealed by spinal cord compression in a 58-year-old male. The epidural lesion was removed via a posterior approach. Histological examination revealed syphilis. Syphilis serologies were positive. Brain MRI showed an associated cerebro-meningeal syphilitic gumma. Antibiotic regime based on aqueous penicillin G was introduced for 14 days. DISCUSSION: Currently, there is an increase in the frequency of syphilis and changes in its clinical manifestations. Neurosyphilis can take atypical forms. Spinal syphilitic gumma is a rare manifestation and its association with cerebral involvement is exceptional. Diagnosis is based on serologies in the blood and cerebrospinal fluid. The place of imagery, especially magnetic resonance imaging, is essential. Neurosyphilis should be discussed as a possible differential diagnosis in evaluation of spinal and cerebral lesions.

Malaria therapy in Spain: 100 years after its introduction as a treatment for the general paralysis of the insane.

This article addresses the implementation of malaria fever therapy in Spain. Neuropsychiatrist Rodríguez-Lafora first used it in 1924, but Vallejo-Nágera was the main advocate for the technique. He had learned the method from Wagner von Jauregg himself, and he worked in the Military Psychiatric Clinic and the San José Mental Hospital, both in Ciempozuelos (Madrid). Vallejo-Nágera worked with the parasitologist Zozaya, who had travelled to England with a Rockefeller Foundation grant in order to learn from British malariologist, Sydney Price James. This article details the results of the uneven implementation of this treatment in Spanish psychiatric institutions. Although syphilologists and internists used fever therapy for the treatment of general paralysis of the insane, they were much less enthusiastic than psychiatrists.

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.

Ocular and neurosyphilis: epidemiology and approach to management.

PURPOSE OF REVIEW: In the context of a resurgence of syphilis worldwide, it can be anticipated that a rise in cases of ocular, otic, and neurosyphilis will also be seen. This article reviews the current epidemiology, manifestations, and approach to management and treatment. RECENT FINDINGS: Although studies continue investigating alternate approaches and new diagnostic tests for ocular and neurosyphilis, few data exist to change current diagnostic algorithms and approaches to diagnosis, management, or follow up. SUMMARY: The diagnosis of neurologic and eye/ear involvement with syphilis may be delayed because of a lack of specificity of findings, low suspicion for syphilis, fluctuation in symptoms, and/or similarities in presentation to other diseases. A high index of suspicion for syphilis and re-education about the protean manifestations of syphilis by all clinicians is required provide timely diagnosis and management of ocular, otic, and neurosyphilis.

Medullary involvement in neurosyphilis: a report of 12 cases and a review of the literature.

Study design: Retrospective case series. Objectives: To describe the epidemiological, clinical, MRI and therapeutic features and the outcomes of patients with syphilitic myelitis in a third-level hospital in Marrakesh in southern Morocco. Setting: The Neurology Department, University Hospital Mohamed VI Marrakesh, Morocco. Methods: Twelve charts of persons with syphilitic myelitis over a period of 17 years were reviewed to determine demographics, presenting symptoms, clinical and radiological findings, biological features, treatment received and outcomes. Results: There were 120 reports of neurosyphilis. Twelve patients (10%) had syphilitic myelitis. Eleven patients (92%) were male with mean age of 44 at presentation. Tabes dorsalis was the most common clinical form. Cerebrospinal fluid analysis showed lymphocytic meningitis in nine patients (75%). Spine MRI was abnormal in four patients (33%). All patients were treated with 30 million units of aqueous penicillin G IV per day for 10 days, every 3 months. In follow-up, two patients (17%) with clinical syphilitic meningomyelitis improved significantly, eight patients (66%) with tabes dorsalis and subacute transverse myelitis showed partial improvement but clinical status was stationary for two patients (17%) with Erb paraplegia. Conclusions: All patients with myelopathy should undergo syphilitic serology because of nonspecific manifestations and curability of this disease.

Concurrent aquaporin-4-positive NMOSD and neurosyphilis: A case report.

Neuromyelitis optica spectrum disorder (NMOSD) is a common neuroinflammatory demyelinating disease associated with aquaporin-4 (AQP4) antibody in the central nervous system. Neurosyphilis is a neurological disease caused by Treponema pallidum infection. NMOSD commonly occurs concurrently with autoimmune diseases. However, they have rarely been associated with infectious diseases. In this report we describe a rare case of concurrent AQP4-positive NMOSD and neurosyphilis. A 60-year-old man was admitted to our hospital with a complaint of progressive weakness in his legs for one month. T2-weighted magnetic resonance images of the spinal cord showed longitudinal extensive lesions at C7-T7. The rapid plasma reagin test and T. pallidum particle agglutination assay performed using patient serum and cerebrospinal fluid (CSF) were positive. Additionally, the AQP4-immunoglobulin (Ig) G was detected in the serum and CSF. The patient's symptom gradually improved after penicillin and methylprednisolone treatment. This case report highlights the possibility of the presence of an infectious disease in patients with NMOSD.

Neurosífilis e infección por el virus de inmunodeficiencia humana. Una puesta al día / Neurosyphilis and infection by the virus human immunodeficiency. Update

Medical literature shows that the co-infection of syphilis and human immunodeficiency virus (HIV) is increasing dramatically worldwide. HIV infection and syphilis have a synergistic relationship. Syphilis increases the risk of HIV transmission and acquisition, while HIV affects the presentation, diagnosis, progression and response to syphilis treatment. The diagnosis of syphilis is made with a non-treponemal reactive test (VDRL or RPR) confirmed with a treponemal test (FTA-ABS or MHA-TP). The opportune diagnosis of neurosyphilis is essential, particularly in the asymptomatic stages, given the high risk of serious sequels and lethality. All patients co-infected with HIV and syphilis with neurological symptoms must be studied with PL and other complementary tests. There is controversy about when to perform a lumbar puncture in co-infected patients who do not have neurological symptoms. However, there is consensus that a CD4 count lower than 350/µl or RPR title greater than 1/32 has indication for the study of cerebrospinal fluid. Therapy with penicillin G in high doses is the treatment of choice, in addition to clinical and serological follow-up that must be done to these patients. (AU)

[Variantsand types of clinical course of different forms of early neurosyphilis in patients with HIV infection]. / Varianty i tipy techeniia rannego neirosifilisa u patsientov, infitsirovannykh virusom immunodefitsita.

AIM: To study and compare the frequency and types of clinical course of different forms of early neurosyphilis (NS) in patients with HIV infection. MATERIAL AND METHODS: The results of clinical, laboratory and neuropsychological examinations of two groups of patients: with early NS in combination with HIV infection (n=62) and with early NS without HIV (n=62) were analyzed. RESULTS AND CONCLUSION: The variants (regressive, stationary, slowly progressive, rapidly progressive) and types (favorable, unfavorable) of clinical course of different forms of early NS were identified in these groups. In the group of HIV-positive patients, an unfavorable course of early NS was observed in 75.8% of patients, with stationary and slowly progressive course being most frequent. Patients with early NS without HIV infection had a favorable course of the disease in 95.2% of cases.

[Late neurosyphilis in a psychiatric hospital]. / Pozdnii neirosifilis v psikhiatricheskom statsionare.

AIM: The problem of detection and diagnosis of late forms of neurosyphilis remains relevant and to a large extent concerns the field of psychiatry. The autors study of professional activity of psychiatric hospital in this field with use of clinical and statistical data. MATERIAL AND METHODS: The article presents modern statistical data on the detection of these forms of syphilis in psychiatric hospitals of the Moscow region in comparison with the indicators of 2008-2010. RESULTS AND CONCLUSION: There were 2 clinical cases of late neurosyphilis identified and received specific therapy in a psychiatric hospital in 2016. It is concluded that there is a need for a cerebrospinal fluid analysis of all seropositive patients in psychiatric hospitals, including those who received treatment for various forms of syphilis.

Neuroborreliosis and Neurosyphilis.

PURPOSE OF REVIEW: This article presents an overview of the current diagnosis and management of two spirochetal infections of the nervous system, neuroborreliosis (Lyme disease) and neurosyphilis, focusing on similarities and differences. Although neuroborreliosis was first identified almost a century ago, much confusion remains about how to accurately diagnose this quite treatable nervous system infection. Well-established diagnostic tools and therapeutic regimens exist for neurosyphilis, which has been well-known for centuries. RECENT FINDINGS: Serologic testing targeting the C6 antigen may simplify diagnostic testing in neuroborreliosis while improving accuracy. Historically, screening for syphilis has used a reaginic test followed by a treponeme-specific assay; alternative approaches, including use of well-defined recombinant antigens, may improve sensitivity without sacrificing specificity. In neuroborreliosis, measurement of the chemokine CXCL13 in CSF may provide a useful marker of disease activity in the central nervous system. SUMMARY: Lyme disease causes meningitis, cranial neuritis, radiculitis, and mononeuropathy multiplex. Cognitive symptoms, occurring either during (encephalopathy) or after infection (posttreatment Lyme disease syndrome) are rarely, if ever, due to central nervous system infection. Posttreatment Lyme disease syndrome is not antibiotic responsive. Syphilis causes meningitis, cranial neuritis, chronic meningovascular syphilis, tabes dorsalis, and parenchymal neurosyphilis. The organism remains highly sensitive to penicillin, but residua of chronic infection may be irreversible.

Other central nervous system infections: cytomegalovirus, Mycobacterium tuberculosis, and Treponema pallidum.

Human immunodeficiency virus (HIV)-infected individuals are particularly susceptible to several central nervous system infections: human cytomegalovirus, which may cause encephalitis, ventriculitis, polyradiculitis, or polyradiculomyelitis; Mycobacterium tuberculosis, which can cause meningitis or space-occupying lesions; and Treponema pallidum subspecies pallidum (T. pallidum), which affects the meninges, cerebrospinal fluid, cranial nerves, and vasculature in early neurosyphilis, and additionally the brain and spinal cord parenchyma in late neurosyphilis. Central nervous system cytomegalovirus infection is seen in HIV-infected individuals with very advanced immunosuppression. Its prognosis is poor and optimal therapy has not been determined. Tuberculous meningitis has a high mortality in those also infected with HIV, especially in the developing world, and better therapies are urgently needed. As the rates of syphilis increase in the developed world, neurosyphilis and in particular ocular syphilis are increasingly reported. The likelihood of all three of these central nervous system infections is decreased in individuals who receive potent antiretroviral therapy.

The performance of rapid plasma reagin (RPR) titer in HIV-negative general paresis after neurosyphilis therapy.

BACKGROUND: Repeated nontreponemal serologic test for syphilis titers is recommended to evaluate treatment response. However, it is unknown whether serum rapid plasma reagin (RPR) titer can serve as a surrogate for determining the efficacy of treatment in general paresis (GP) remains unknown. METHODS: We retrospectively reviewed data from 105 GP patients, who were divided into two groups (62 CSF RPR+ patients and 43 CSF RPR- patients) according to reactive RPR test status in CSF. Clinical assessment included the Mini-Mental State Examination (MMSE) scores, CSF examinations (WBC count, protein concentration and RPR titer), and serum tests (RPR titer and TPPA). Among the 105 GP patients, 13 CSF RPR+ patients and 6 CSF RPR- patients had a 12 months follow-up of CSF, serum measures and MMSE. RESULTS: The median serum RPR titer was significantly higher in CSF RPR+ patients than that in CSF RPR- GP patients, 1:8 [IQR 1:4-1:32] vs. 1:4 [IQR 1:4-1:8] (P < 0.001). The number of CSF RPR+ patients with serum RPR titer≥1:32 was significantly higher when compared with CSF RPR- patients (P = 0.001). For CSF RPR+ patients, the MMSE scores improved or remained constantly after penicillin treatment. For CSF RPR+ patients, the CSF RPR titer declined four-fold in 85% (11/13) of the patients, whereas the serum RPR titer declined four-fold in only 46% (6/13) of the patients, the odds ratio is 6.4 (95% confidence interval 1.0-41.2). CONCLUSIONS: A four-fold decline in CSF RPR titer is a good predictor for treatment efficacy in CSF RPR+ GP patients within 12 months after the completion of therapy.

Neurosyphilis in patients with HIV.

Syphilis is a resurgent sexually transmitted infection in the UK that is disproportionately diagnosed in patients living with HIV, particularly in men who have sex with men. Syphilis appears to present differently in patients with HIV, particularly in those with severe immunosuppression. Progression to neurosyphilis is more common in HIV coinfection and can be asymptomatic, often for several years. The presentations of neurosyphilis vary but can include meningitis, meningovascular disease, general paresis and tabes dorsalis. There is debate about the circumstances in which to perform a lumbar puncture, and the current gold standard diagnostics have inadequate sensitivity. We recommend a pragmatic approach to lumbar punctures, interpreting investigations and deciding when to consider treatment with a neuropenetrative antibiotic regimen.

Management of neurosyphilis: time for a new approach?

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.

How Well Do Neurologic Symptoms Identify Individuals With Neurosyphilis?

Background: Current guidelines recommend lumbar puncture (LP) in patients with syphilis who have neurologic symptoms. Methods: A total of 81 human immunodeficiency virus (HIV)-uninfected individuals and 385 HIV-infected individuals enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis underwent LP and a structured symptom history, including assessment of headache; stiff neck; photophobia; ocular inflammation; vision, hearing, or sensory loss; or gait incoordination. Neurosyphilis was defined as a reactive CSF-Venereal Disease Research Laboratory (VDRL) test. Association between categorical variables was assessed using χ2, Fisher exact test, or logistic regression. Association between continuous and categorical variables was assessed using Mann-Whitney U test. Results: CSF-VDRL was reactive in 20 (24.7%) HIV-uninfected and 68 (17.7%) HIV-infected (P = .14) individuals. No symptom was more common in HIV-uninfected individuals with neurosyphilis. Among the HIV-infected, the odds of a reactive CSF-VDRL were higher in those with mild or greater severity photophobia (2.0 [95% confidence interval [CI], 1.1-3.8]; P = .03), vision loss (2.3 [1.3-4.1]; P = .003), or gait incoordination (2.4 [1.3-4.4]; P = .006); or moderate or greater severity hearing loss (3.1 [1.3-7.5]; P = .01). Diagnostic specificity of these 4 symptoms for neurosyphilis was high when limited to moderate or greater severity (91.6%-100%); however, the diagnostic sensitivity was low (1.5%-38.1%). Conclusions: Among HIV-infected patients with syphilis, 4 specific neurologic symptoms are more common in those with a reactive CSF-VDRL. Lack of symptoms does not guarantee that the CSF-VDRL is nonreactive, regardless of HIV status.

Diversity in clinical manifestations and imaging features of neurosyphilis: obstacles to the diagnosis and treatment (report of three cases).

OBJECTIVE: To explore the clinical manifestations and imaging features of neurosyphilis and to discuss the obstacles in the diagnosis and treatment of neurosyphilis. METHODS: We present this case study involving three cases of definite neurosyphilis, focusing on their clinical data. RESULTS: Case 1 is a patient with numb and weak left lower limb. Case 2 showed slow reaction and dementia behaviors including worse memory and the decrease of calculation and orientation ability in this patient. Case 3 is a peripheral incomplete left oculomotor nerve palsy patient. Magnetic resonance imaging findings of three patients are different. And single photon emission computed tomography showed the regional cerebral blood flow was all hypoperfused. There were some difficulties in diagnosing and treating the patients in these three cases. CONCLUSION: The clinical manifestations and imaging findings of neurosyphilis are diverse. Clinicians should pay attention to neurosyphilis. After clear diagnosis, patients would receive norm treatment in time.

[Neurosyphilis: an Age-old Problem that is Still Relevant Today]. / Neurosífilis: un problema antiguo que no pierde actualidad.

Neurosyphilis is the clinical manifestation of syphilis that can arise during either the early or late stages of infection. Even though dedicated treatment for all clinical forms of syphilis has been available for many years, the advanced stages of the disease are still prevalent, with irreversible sequelae. This article reviews the current evidence, diagnostic methods and specific treatment for tertiary syphilis.