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BACKGROUND: Penicillin has remained the most effective treatment for syphilis for several decades. Syphilitic retinal manifestations may persist following treatment and cause visual problems. In this case series, we describe three syphilis patients with persistent posterior segment manifestations due to chronic inflammation, incomplete treatment, and reinfection. CASE SERIES: Recommended initial treatment for all patients was 14 days of intravenous penicillin. Oral prednisone was added 48 h after initiation of penicillin therapy. Case 1: A 48-year-old female presented with gradual vision loss for two months. Fundus imaging revealed syphilitic outer retinopathy (SOR), papillitis, and acute syphilitic posterior placoid chorioretinopathy (ASPPC). After treatment, she had persistent cystoid macular edema (CME) and was treated with intravitreal triamcinolone injections and ketorolac drops. CASE 2: A 24-year-old male presented with sudden vision loss for two days. On imaging, he had ASPPC, papillitis, and SOR. IV penicillin treatment was given for 10 days only. He had persistent SOR and was retreated with doxycycline and prednisone. Case 3: A 52-year-old male presented with eye pain and visual loss for one week. There was evidence of ASPPC and papillitis on imaging. One month after treatment, he had persistent papillitis and was restarted on oral prednisone. One year later, he was found to have recurrent ASPPC and was confirmed to be reinfected with syphilis, for which he was retreated. CONCLUSION: When treating persistent syphilitic ocular manifestations, we recommend checking that the penicillin treatment was complete and the RPR titers are declining. If both hold true, then the affected eye should be treated with anti-inflammatory therapy. Other factors that contribute to poor visual prognosis include treatment delay, poor initial visual acuity, macular edema, and HIV coinfection.
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Epigenetic changes within immune cells may contribute to neuroinflammation during bacterial infection, but its role in neurosyphilis pathogenesis and response has not yet been established. We longitudinally analyzed DNA methylation and RNA expression changes in cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMCs) from 11 participants with laboratory-confirmed NS (CSF VDRL positive) and 11 matched controls with syphilis without NS (non-NS). DNA methylation profiles from CSF and PBMCs of participants with NS significantly differed from those of participants with non-NS. Some genes associated with these differentially methylated sites had corresponding RNA expression changes in the CSF (111/1097, 10.1%), which were enriched in B-cell, cytotoxic-compounds, and insulin-response pathways. Despite antibiotic treatment, approximately 80% of CSF methylation changes persisted; suggesting that epigenetic scars accompanying NS may persistently affect immunity following infection. Future studies must examine whether these sequelae are clinically meaningful.
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Syphilis, a sexually transmitted disease caused by Treponema pallidum subsp. pallidum (T. pallidum), can lead to a complication known as neurosyphilis. Neurosyphilis affects multiple components of the nervous system, including the meninges, blood vessels, brain parenchyma, and others, significantly impacting the central nervous system (CNS). Despite the effective control of syphilis spread by antibiotics, recent years have seen a resurgence in incidence among high-risk populations. The blood-brain barrier (BBB) is a critical defense for the CNS, preventing toxins and pathogens, including viruses, from entering and ensuring CNS function. The exact mechanisms of how T. pallidum penetrates the BBB are still not fully understood. Extensive research suggests that T. pallidum can disrupt endothelial cells and intercellular junctions, as well as induce abnormal activation of immune cells and aberrant cytokine expression, potentially facilitating its breach of BBB. Based on current research, we focus on the detrimental effects of cytokines on BBB integrity. We have also summarized the pathways T. pallidum uses to penetrate cellular barriers. Understanding the interaction between T. pallidum and the BBB is essential for revealing neurosyphilis pathogenesis and developing new therapies. DATA AVAILABILITY: Data used to support the findings of this study are included in the article.
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Introduction: Syphilis remains a significant challenge in public health, largely because of its diverse clinical manifestations, often resulting in underdiagnosis especially among patients with neurogenic disability. Case description: We present a case of neurosyphilis in a 63-year-old patient with a spinal cord injury. Despite syphilis being a well-established sexually transmitted infection, the exacerbation of neurological and dermatological symptoms during physical examination prompted an investigation into alternative causes beyond the patient's pre-existing paraparesis, ultimately resulting in the diagnosis of neurosyphilis. Conclusion: This case highlights the importance of considering syphilis as a potential diagnosis in individuals regardless of their medical history. LEARNING POINTS: The incidence of syphilis cases is on the rise, presenting an ongoing challenge.Faced with atypical neurological symptomatology, it is necessary to know how to investigate and discuss tertiary syphilis.In the event of neurological worsening in a neuro-injured patient, it is necessary to know how to discuss a curable diagnosis.
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Syphilis -the "great simulator" for classical venereologists-is re-emerging in Western countries despite adequate treatment; several contributing factors have been identified, including changes in sexual behaviour, which won't be the topic of this article though. In 2021, a total of 6613 new cases of syphilis were reported in Spain, representing an incidence of 13.9×100 000 inhabitants (90.5%, men). Rates have increased progressively since 2000. The clinical presentation of syphilis is heterogeneous. Although chancroid, syphilitic roseola and syphilitic nails are typical lesions, other forms of the disease can be present such as non-ulcerative primary lesions like Follmann balanitis, chancres in the oral cavity, patchy secondary lingual lesions, or enanthema on the palate and uvula, among many others. Regarding diagnosis, molecular assays such as PCR have been replacing dark-field microscopy in ulcerative lesions while automated treponemal tests (EIA, CLIA) are being used in serological tests, along with classical tests (such as RPR and HAART) for confirmation and follow-up purposes. The interpretation of these tests should be assessed in the epidemiological and clinical context of the patient. HIV serology and STI screening should be requested for anyone with syphilis. Follow-up of patients under treatment is important to ensure healing and detect reinfection. Serological response to treatment should be assessed with the same non-treponemal test (RPR/VDRL); 3-, 6-, 12-, and 24-month follow-up is a common practice in people living with HIV (PLHIV). Sexual contacts should be assessed and treated as appropriate. Screening is advised for pregnant women within the first trimester of pregnancy. Pregnant women with an abortion after week 20 should all be tested for syphilis. The treatment of choice for all forms of syphilis, including pregnant women and PLHIV, is penicillin. Macrolides are ill-advised because of potential resistance.
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Sífilis , Humanos , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Sífilis/epidemiologia , Feminino , Masculino , Espanha/epidemiologia , Infecções por HIV/complicações , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/diagnóstico , Antibacterianos/uso terapêutico , Sorodiagnóstico da SífilisRESUMO
BACKGROUND: The attentional network test (ANT) is widely used to evaluate the performance of three attentional networks: alerting, orienting and executive attention networks. This study aimed to investigate the characteristics of attention functions in HIV-negative patients with early forms of neurosyphilis (NS) and their correlation with abnormalities in brain magnetic resonance imaging (MRI). METHODS: Thirty patients with early forms of NS, 31 patients with syphilis but without NS (Non-NS) and 35 healthy controls were recruited from an HIV-negative cohort between September 2020 and November 2022. The participants were evaluated with the ANT and the Mini-Mental State Examination (MMSE). Brain MRI was performed in NS and Non-NS patients. RESULTS: No significant differences were observed in the MMSE scores among the three groups. However, patients with early forms of NS showed poorer performance in orienting and alerting functions than Non-NS group (F = 6.952, P = 0.011 and F = 8.794, P = 0.004, respectively); No significant difference was observed in executive function between the two groups (F = 0.001, P = 0.980). Multivariate analysis of variance using the Bonferroni post hoc test indicated that patients with NS exhibited less efficient orienting function (P = 0.023), and alerting function (P = 0.003) but not executive function (P = 0.99), compared to Non-NS patients. Additionally, a significant difference was found in orienting function between patients with NS and healthy controls (P < 0.001) compared to healthy controls. MRI scans revealed that the NS group had a higher prevalence of abnormalities in the frontal lobes and/or the temporoparietal junction compared to the Non-NS group (24/25 vs. 13/19, P = 0.032). CONCLUSIONS: The orienting and alerting functions but not executive function were significantly less efficient in early forms of NS group than in the Non-NS group (P < 0.01). This indicates deficits in selective attention in patients with early forms of NS. Brain MRI scans revealed abnormalities in the frontal and/or parietal lobes, as well as the temporoparietal junction, suggesting potential neuropathological correlates of these attentional deficits.
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Atenção , Imageamento por Ressonância Magnética , Neurossífilis , Humanos , Masculino , Adulto , Feminino , Neurossífilis/fisiopatologia , Neurossífilis/complicações , Neurossífilis/diagnóstico por imagem , Atenção/fisiologia , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Estudos de Casos e Controles , Função Executiva/fisiologia , Testes Neuropsicológicos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Encéfalo/patologiaRESUMO
We herein report a case of neurosyphilis that presented with isolated bilateral abducens nerve palsy. A 39-year-old man was referred to our department with diplopia. He had a history of homosexual relationships and showed only bilateral abducens nerve palsy upon a neurological examination. Positive syphilis tests in the serum and cerebrospinal fluid and a contrasting effect on the abducens nerve on magnetic resonance imaging (MRI) confirmed the diagnosis of active neurosyphilis. When a patient manifests isolated abducens nerve palsy, neurosyphilis can be a differential diagnosis, although rare, and contrast-enhanced MRI may help diagnose the disease.
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Teaching point: Meningovascular neurosyphilis is a cause of stroke in the young, and the diagnosis could be aided by black-blood MRI sequences.
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BACKGROUND: Treponema pallidum can invade the central nervous system (CNS) early in its infection, causing neurosyphilis. Neurosyphilis typically presents with meningovasculitis in the acute or subacute phase, while tabes dorsalis and dementia paralytica are classical conditions in the later stages. However, syphilis is often misdiagnosed as other conditions such as tumors or autoimmune diseases including vasculitis and encephalitis, which is why the condition is known as "The Great Mimicker." The increasing incidence of syphilis in recent years emphasizes the importance of early diagnosis and treatment; however, its multiple clinical manifestations impose diagnostic challenges for clinicians because it resembles other diseases. In this case series, we present the impressive manifestations of neurosyphilis through three unique radiological presentations. CASE PRESENTATION: Case 1 details optic nerve involvement in an HIV-positive male, where MRI and fundoscopic findings confirmed syphilitic optic neuritis. Case 2 describes a patient in her pregnancy initially suspected of acoustic neuroma on MRI, later diagnosed with syphilitic gumma affecting the inner ear canal. Case 3 is a young male with clinical features mimicking temporal arteritis, ultimately identified as skull osteomyelitis secondarily causing inflammation of the musculus temporalis and meningitis. CONCLUSIONS: These cases underscore the necessity of considering syphilis in differential diagnoses, given the diversity of its clinical presentations. Radiology plays an important role in avoiding unnecessary interventions. The increasing prevalence of recurrent syphilis imposes diagnostic challenges, emphasizing the importance of the early diagnosis and treatment of neurosyphilis by clinicians.
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Neurossífilis , Humanos , Neurossífilis/diagnóstico por imagem , Neurossífilis/diagnóstico , Neurossífilis/tratamento farmacológico , Masculino , Adulto , Feminino , Imageamento por Ressonância Magnética/métodos , Gravidez , Pessoa de Meia-Idade , Neurite Óptica/diagnóstico por imagem , Neurite Óptica/diagnósticoRESUMO
Neurosyphilis is a central nervous system infection caused by Treponema pallidum that imitates various neurological and mental disorders. Therefore, patients with this disease are prone to misdiagnoses. Here, we report a case of neurosyphilis with a psychotic disorder as the main manifestation. A young girl exhibited mental and behavioural abnormalities after a heartbreak, which manifested as alternating low mood, emotional irritability, and a lack of interest in social relations, followed by memory loss. The cerebrospinal fluid protein - Treponema pallidum particle agglutination test was positive, the toluidine red unheated serum test titre was 1:4, the white blood cell count was 5 × 10^6/L, the cerebrospinal fluid protein level was 0.97 g/L, and the brain CT was abnormal. After admission, the possibility of neurosyphilis was considered and the patient received intravenous penicillin G treatment. The patient's clinical symptom ms improved. This case emphasises that doctors should maintain clinical suspicion of Treponema pallidum infection in adolescent patients with mental abnormalities.
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West Nile Virus (WNV) belongs to the Flaviviridae family of viruses. It was first isolated and identified in 1937. Patients typically present with flu-like symptoms or are asymptomatic; however, neuroinvasive West Nile can lead to significant neurological impairment. Herein presented is a catastrophic case of WNV rhombencephalitis in a male patient newly diagnosed with AIDS. This report sheds light on the potential for severe neurological complications in co-infected patients and emphasizes the importance of early recognition.
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Síndrome da Imunodeficiência Adquirida , Febre do Nilo Ocidental , Vírus do Nilo Ocidental , Humanos , Masculino , Febre do Nilo Ocidental/complicações , Febre do Nilo Ocidental/diagnóstico , Vírus do Nilo Ocidental/isolamento & purificação , Síndrome da Imunodeficiência Adquirida/complicações , Imageamento por Ressonância Magnética , Evolução Fatal , Adulto , Rombencéfalo/diagnóstico por imagemRESUMO
BACKGROUND: Soluble inflammatory factors in the cerebrospinal fluid (CSF) of patients with neurosyphilis have been investigated with low-throughput technology. This study aimed to illustrate the characteristics of soluble factor profiles in CSF of patients with neurosyphilis. METHODS: We measured the concentrations of 45 cytokines, chemokines, and growth factors in CSF from 112 untreated syphilis cases, including latent syphilis (LS), asymptomatic neurosyphilis (ANS), meningeal neurosyphilis (MNS), meningovascular neurosyphilis (MVNS), paralytic dementia (PD), and ocular syphilis (OS). RESULTS: Thirty-three differentially expressed soluble factors (DeSFs) were categorized into 3 clusters. DeSF scores of clusters 1 and 2 (DeSFS1 and DeSFS2) were positively correlated with elevated neopterin and neurofilament light subunit (NF-L) concentration, respectively. DeSF scores of cluster 3 were positively correlated with white blood cells, protein, NF-L, and neopterin. Patients with LS, ANS, and OS exhibited an overall lower abundance of DeSFs. Patients with PD exhibited significantly increased levels of clusters 1 and 3, and the highest total DeSF score, whereas patients with MNS and MVNS showed enhanced levels of cluster 2. Receiver operating characteristic analysis revealed that DeSFS1 effectively discriminated PD, and DeSFS2 discriminated MNS/MVNS with high accuracy. CONCLUSIONS: Patients with neurosyphilis at different stages have distinctive patterns of soluble factors in CSF, which are correlated with immune status and neuronal damage.
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Citocinas , Neurossífilis , Humanos , Neurossífilis/líquido cefalorraquidiano , Neurossífilis/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Citocinas/líquido cefalorraquidiano , Neopterina/líquido cefalorraquidiano , Idoso , Biomarcadores/líquido cefalorraquidiano , Peptídeos e Proteínas de Sinalização Intercelular/líquido cefalorraquidiano , Curva ROC , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Quimiocinas/líquido cefalorraquidiano , Adulto JovemRESUMO
Syphilis is a complex, systemic infectious disease caused by Treponema pallidum subspecies pallidum. Secondary syphilitic lesions typically manifest within 3 months following initial exposure to T. pallidum. The predominant cutaneous manifestations of secondary syphilis are macula and papule. Certain individuals with syphilis may present with an atypical rash during the secondary stage owing to immunosuppression and other factors. Herein, we report a rare case of atypical recurrent secondary syphilis around the anus in a 65-year-old woman. Based on cerebrospinal fluid findings and skin biopsy results, the patient was ultimately diagnosed as neurosyphilis and recurrent secondary syphilis. Following intravenous antibiotic therapy, the patient's rash improved significantly. This case underscores the importance for physicians to remain vigilant regarding the possibility of syphilis when encountering cases exhibiting unusual clinical manifestations, as a definitive diagnosis necessitates a comprehensive evaluation.
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Background: Tabes dorsalis is a late manifestation of neurosyphilis, characterized by progressive ataxia, lightning pains, loss of proprioception, and urinary incontinence. The absence of a definitive diagnostic standard and the non-specific clinical manifestations have led to a significant rate of misdiagnoses. Methods: Hospitalized patients with tabes dorsalis at Peking Union Medical College Hospital between January 2010 and December 2023 were reviewed. Results: A total of 13 patients were included, with 10 males and 3 females. The median age was 50 years (range, 34-64). The most frequent initial symptoms were limb numbness (30.8%) and lightning pains (30.8%). Eleven patients (84.6%) received misdiagnoses prior to the final diagnosis. The most frequently observed physical sign was positive Romberg's sign (84.6%). Notably, Argyll Robertson pupil was presented in 7 subjects (53.8%). Serological tests revealed positive rapid plasma regain (RPR) and Treponema pallidum particle agglutination (TPPA) for all patients. All CSF samples were TPPA-reactive. Intramedullary hyperintensity on T2-weighted imaging of spinal MRI was found in 5 patients (38.5%). All patients received anti-syphilitic treatment, with effective treatment recorded in five cases. Conclusion: This study underscores the importance of neurological symptoms and signs in diagnosing tabes dorsalis. Individuals with progressive ataxia and positive Romberg's sign should be closely monitored for potential neurosyphilis. Integrating clinical features, laboratory tests, and neuroimaging could reduce misdiagnosis and expedite the initiation of anti-syphilitic therapy.
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We report a rare case of confirmed early neurosyphilis with serofast state in HIV-negative patient, with uncontrolled type 2 diabetes mellitus. Syphilitic meningitis was diagnosed initially on serology and cerebrospinal fluid (CSF) analysis. The patient had persistently raised non-treponemal titres on serum with negative CSF venereal disease research laboratory result, following treatment during 3 years of follow-up.
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Neurossífilis , Humanos , Neurossífilis/diagnóstico , Neurossífilis/tratamento farmacológico , Neurossífilis/complicações , Masculino , Treponema pallidum/isolamento & purificação , Treponema pallidum/imunologia , Diabetes Mellitus Tipo 2/complicações , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/líquido cefalorraquidianoRESUMO
Moyamoya angiopathy is a rare cerebrovascular condition characterized by insufficient cerebral blood flow resulting from arterial vessel narrowing or occlusion, potentially leading to cerebral ischemia due to inadequate oxygen and nutrient supply to the brain tissue. The development of collateral vessels in stenotic regions, inherently fragile and prone to rupture, may further precipitate intracerebral hemorrhage. Alongside focal neurological symptoms, the common clinical presentations of Moyamoya angiopathy encompass headaches, dizziness, cognitive impairments, seizures, and involuntary movements. When associated with an underlying systemic illness, including Down Syndrome, cranial radiation, neurofibromatosis type 1, or meningitis, the condition is termed Moyamoya syndrome; whereas when idiopathic and a genetic mutation are identified, it is referred to as Moyamoya disease. In this report, we present a case of the rare Moyamoya syndrome, which was attributed to syphilis and HIV infection and was identified during an investigation into the etiology of ischemic stroke in a young patient.
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Syphilis is a chronic infectious disease, which dates back to the XV century and is caused by the spirochete treponema pallidum, capable of invading the central nervous system in any of its stages- Its incidence has increased in parallel to the HIV/AIDS pandemic, and the synergism between both pathologies is such. that it has become a public health problem in recent years. Here we present the case of a 31-year-old female patient, who consulted for headache associated with decreased visual acuity and provided an unenhanced head CT showing hypodense lesions in both thalamic regions, serological tests for syphilis were reactive and those for HIV were not reactive. The brain MRI with spectroscopy was reported in favor of cerebral toxoplasmosis, which was later ruled out with a study of cerebrospinal fluid. Management with penicillin G sodium IV for 6 weeks was indicated, achieving complete imaging resolution of her lesions.
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Sexually transmitted infectious diseases could affect a variety of organs, generating significant symptomatology. In the elderly population, infectious causes for vision problems are not generally considered. We present the case of an elderly patient with blurred vision and darkening of visual fields. He underwent an unsuccessful biopsy of the temporal artery as his vision disturbances presented also with episodic headaches. He was found to have an elevated rapid plasma reagin (RPR) and venereal disease research laboratory (VDRL) test in his cerebrospinal fluid (CSF) analysis. He was treated for ocular syphilis with a total resolution of his vision loss.
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OBJECTIVES: Invasive lumbar puncture is the conventional method for diagnosing neurosyphilis (NS). We investigated a non-invasive alternative method to detect serum Treponema pallidum-specific antibodies against highly immunogenic antigens TP0171 (TP15), TP0435 (TP17), and TP0574 (TP47) by using luciferase immunosorbent assay. METHODS: A total of 816 HIV-negative patients suspected of NS from the Beijing and Guangzhou cohorts were retrospectively selected and tested for serum anti-TP15, TP17, and TP47 IgG antibodies. Two diagnostic prediction models were developed using stepwise logistic regression in the Beijing cohort, and evaluated in the Guangzhou cohort for external validation. RESULTS: Serum antibodies against TP15, TP17, and TP47 showed moderate capability for NS diagnosis in the Beijing cohort and the corresponding area under the receiver operating characteristic curves (AUCs) were 0.722 [95% confidence interval (CI): 0.680-0.762)], 0.780 (95% CI: 0.741-0.817), and 0.774 (95% CI: 0.734-0.811), respectively. An expanded NS prediction model integrated with anti-TP17 and anti-TP47 antibodies showed better performance than the base NS diagnostic model without anti-TP17 and anti-TP47 antibodies with the AUC of 0.874 (95% CI: 0.841-0.906) vs. 0.845 (95% CI: 0.809-0.881) (p = 0.007) in the development cohort, and 0.934 (95% CI: 0.909-0.960) vs. 0.877 (95% CI: 0.840-0.914) (p < 0.001) in validation cohort, respectively. Decision curve analysis revealed that the net benefit of the expanded model exceeded that of the base model when the threshold probability was between 0.10 and 0.95 in both the development and external validation cohorts. DISCUSSION: Serum antibodies against TP17 and TP47 exhibited promising diagnostic capability for NS and significantly enhanced the predictive accuracy of model for NS diagnosis. Our study highlights the potential of serum treponemal antibody detection as a non-invasive method for NS diagnosis to substitute invasive lumbar puncture in NS diagnosis.