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The knife-cut sign is a distinctive manifestation of herpes simplex virus (HSV) type 1 or HSV type 2 infection that has been described in at least 10 immunocompromised patients. It appears as an extremely painful linear erosion or fissure in an intertriginous area such as the body folds beneath the breast, or within the abdomen, or in the inguinal region. Also, concurrent HSV infection at other mucocutaneous sites, or viscera, or both have been observed. The patients had medical conditions (at least 9 patients) and/or immunosuppressive drug therapy (6 patients). The diagnosis of HSV infection was confirmed by viral culture (8 patients), biopsy (4 patients), direct fluorescence antibody testing (3 patients), immunohistochemistry staining (2 patients), polymerase chain reaction (2 patients), or Western blot serologic assay (1 patient). Knife-cut sign-associated HSV infection is potentially fatal; three patients died. However, clinical improvement or complete healing occurred in the patients who received oral valacyclovir (1 patient), or intravenous acyclovir (2 patients), or intravenous acyclovir followed by foscarnet (1 patient). In summary, HSV infection associated with a positive the knife-cut sign is a potentially fatal variant of HSV infection that occurs in the intertriginous areas of immunocompromised patients and usually requires intravenous antiviral therapy.

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. [ABSTRACT FROM AUTHOR]

Background The immunopathological mechanisms underlying neurosyphilis remain incompletely elucidated, and the diagnosis of neurosyphilis presents challenges. Methods We used an antibody microarray to detect 640 proteins in cerebrospinal fluid (CSF) samples collected from 6 patients with non-neurosyphilis and 10 with neurosyphilis. The levels of CSF CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9 in 46 patients with non-neurosyphilis, 51 with untreated neurosyphilis, and 31 posttreatment for neurosyphilis were quantified using enzyme-linked immunosorbent assay. The associations between the levels of these proteins and clinical parameters in neurosyphilis were evaluated using Spearman analysis, and the diagnostic performance of these proteins in neurosyphilis was assessed using receiver operating characteristic curve. Results A total of 102 differentially expressed proteins between neurosyphilis and non-neurosyphilis were identified. The levels of significantly elevated neutrophil-associated proteins (CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9) in neurosyphilis positively correlated with white blood cell counts, rapid plasma regain (RPR) titer, and protein concentration in CSF. The combination of CSF CXCL8, MMP9, and LCN2 yielded an area under the curve of 0.92 for diagnosing neurosyphilis, surpassing that of CSF RPR. Conclusions CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9 could be associated with central nervous system damage of neurosyphilis. The combination of CSF CXCL8, MMP9, and LCN2 is a promising biomarker for diagnosing neurosyphilis. [ABSTRACT FROM AUTHOR]

After the emergence of syphilis in Europe in 1495, it would take over 400 years to unpick the full course of the infection, including the involvement of the brain and spinal cord. This syndrome of mental and physical deterioration was called 'general paralysis of the insane' (GPI). Traditionally, the earliest clear description of GPI is attributed to Haslam in 1798. However, here I describe three clear cases and three highly suggestive cases, together with autopsy findings, published in 1794 by the Italian psychiatrist Vincenzo Chiarugi. Historically, Chiarugi's scholarship has been neglected in favour of English- and French-speaking physicians. His observations also give a rare clue regarding the prevalence of syphilis, suggesting a foothold in northern Italy in the late eighteenth century. [ABSTRACT FROM AUTHOR]

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Jia Zhou,1,* Wenwen Wang,1,* Qiyu Zhang,1,* Hanlin Zhang,1 Keyun Tang,1 Chenhui Mao,2 Mingli Li,3 Jun Li1 1Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, People’s Republic of China; 2Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Li, Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Disease, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-010-69151500, Fax +86-010-69151502, Email lijun35@hotmail.comPurpose: Syphilis, caused by Treponema pallidum, presents a diagnostic challenge due to its diverse clinical manifestations. Neurosyphilis has seen a resurgence in recent years, particularly among men who have sex with men and those living with HIV. Diagnosis of neurosyphilis in emergency settings is challenging due to its varied neurological presentations. This study aims to serve as a reference for dermatologists and neurologists in diagnosing and treating neurosyphilis.Patients and Methods: This retrospective study analyzed patients who presented with neuropsychiatric symptoms and were ultimately diagnosed with neurosyphilis. These patients were collected from the emergency department in Peking Union Medical College Hospital between January 2018 and November 2023. The medical history, clinical symptoms, laboratory examinations, cranial MRI characteristics, and treatment regimens of these patients were investigated.Results: Among the included 12 neurosyphilis patients, memory deterioration was observed in 8 out of the 12 neurosyphilis patients. Diagnosis often resulted in delays, with misdiagnoses mainly including Alzheimer’s disease, stroke, and epilepsy. Neuroimaging revealed various abnormalities, predominantly affecting ventricular and temporal regions. Treatment with penicillin-based regimens varied in compliance, with only a minority of patients adhering to guidelines. Treatment outcomes were inconsistent, with some patients experiencing irreversible neurological damage and fluctuating serum rapid plasma reagin (RPR) titers.Conclusion: Diagnosis of neurosyphilis in the emergency department remains challenging, necessitating awareness of its varied neurological presentations. Enhanced diagnostic strategies are imperative to accelerate treatment initiation and improve outcomes for affected individuals.Keywords: neurosyphilis, emergency department, neuropsychiatric symptoms, cerebrospinal fluid, serologic tests

Abstract 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.

Abstract 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

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.

Abstract 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.

Hong-Yan Li,1,2 Hao-Yu Wang,3 Yi-Fei Duan,2,4 Yu Gou,2,4 Xiao-Qin Liu,2,4 Zheng-Xiang Gao2,4 1West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan, People’s Republic of China; 3Department of Radiology, The First People’s Hospital of Liangshan Yi Autonomous Prefecture, Xichang, Sichuan, People’s Republic of China; 4Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Zheng-Xiang Gao, Email GAOZX84@163.comAbstract: 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.Keywords: neurosyphilis, case report, psychotic disorder, Treponema pallidum, syphilis

Zhou Zhu,1– 3,* Huizi Gong,4,* Mingjuan Liu,1– 3 Hanlin Zhang,1,2 Leyan Yang,1,2 Xinyi Zhang,5 Heyi Zheng,1,2 Yanfeng Li,6 Mingli Li,7 Jun Li1,2 1Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3 4+4 Medical Doctor Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Dermatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Departments of Internal Medicine and Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT, USA; 6Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 7Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingli Li, Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Email limingli@pumch.cn Jun Li, Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Email lijun35@hotmail.comBackground: 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.Keywords: tabes dorsalis, neurosyphilis, ataxia, cerebrospinal fluid

Yuanyuan Cheng,* Tengfei Qi,* Xin Gu Department of Sexually Transmitted Disease, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Gu, Department of Sexually Transmitted Disease, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, No. 1278 Baode Road, Shanghai, 200443, People’s Republic of China, Tel +86-18017336858, Email gx3014@163.comAbstract: 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.Keywords: recurrent secondary syphilis, perianal annular rash, neurosyphilis, definitive diagnosis

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Rapidly progressive dementia (RPD), characterized by a rapid cognitive decline leading to dementia, comprises a diverse range of disorders. Despite advancements in diagnosis and treatment, research on RPD primarily focuses on Western populations. Objective: This study aims to explore the etiology and demographics of RPD in Chinese patients. Methods: We retrospectively analyzed 323 RPD inpatients at Huashan Hospital from May 2019 to March 2023. Data on sociodemographic factors, epidemiology, clinical presentation, and etiology were collected and analyzed. Results: The median onset age of RPD patients was 60.7 years. Two-thirds received a diagnosis within 6 months of symptom onset. Memory impairment was the most common initial symptom, followed by behavioral changes. Neurodegenerative diseases accounted for 47.4% of cases, with central nervous system inflammatory diseases at 30.96%. Autoimmune encephalitis was the leading cause (16.7%), followed by Alzheimer's disease (16.1%), neurosyphilis (11.8%), and Creutzfeldt-Jakob disease (9.0%). Alzheimer's disease, Creutzfeldt-Jakob disease, and frontotemporal dementia were the primary neurodegenerative causes, while autoimmune encephalitis, neurosyphilis, and vascular cognitive impairment were the main non-neurodegenerative causes. Conclusions: The etiology of RPD in Chinese patients is complex, with neurodegenerative and non-neurodegenerative diseases equally prevalent. Recognizing treatable conditions like autoimmune encephalitis and neurosyphilis requires careful consideration and differentiation. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to outline a complete picture of Jarisch-Herxheimer reaction (JHR) in the central nervous system among HIV-negative neurosyphilis patients. Methods: A prospective study cohort of 772 cases with almost all stages of neurosyphilis depicted the features of JHR including occurrence rate, risk profiles, clinical manifestations, medical management and prognosis. Results: The total occurrence rate of JHR was 9.3% (95% CI, 7.3-11.4%), including 4.1% (95% CI, 2.7-5.6%) with severe JHR. The reaction started 5 h after treatment initiation, peaked after 8 h, and subsided after 18 h. Patients with severe JHR experienced a longer recovery time (26 h). Patients with general paresis (OR = 6.825), ocular syphilis (OR = 3.974), pleocytosis (OR = 2.426), or a high CSF-VDRL titre (per log2 titre increase, OR = 2.235) were more likely to experience JHR. Patients with general paresis had an 11.759-fold increased risk of severe JHR. Worsening symptoms included cognitive impairment, mania, nonsense speech, and dysphoria, while symptoms of hallucination, urination disorder, seizures, myoclonus, or aphasia appeared as new-onset symptoms. Neurosyphilis treatment did not need to be interrupted in most patients with JHR and could be reinstated in patients with seizures under supportive medication when JHR subsided. Conclusion: Severe JHR displayed a 4.1% occurrence rate and clinicians should pay particular attention to patients at a higher risk of JHR. The neurosyphilis treatment regime can be restarted under intensive observation for patients with severe JHR and, if necessary, supportive medication should be initiated and continued until the end of therapy. [ABSTRACT FROM AUTHOR]

Background: Meningovascular syphilis, a distinct classification of neurosyphilis, has gained attention for its association with cerebral ischemia, particularly among individuals living with HIV. This unique manifestation of syphilis affects the meningeal and vascular structures of the central nervous system, leading to cerebrovascular complications. In this case report, we present the case of a young man diagnosed with neurosyphilis and HIV after presenting with an ischemic stroke. We discuss the challenges associated with diagnosing neurosyphilis, given its frequent atypical presentations that can mimic other diseases. Furthermore, we explore the management approach for these coexisting conditions. Case Presentation: A right-handed male patient presented with a sudden paresis of the right upper and lower extremities, along with facial deviation to the left, and demonstrated low verbal output, limitation in constructing sentences, and conveying thoughts or ideas effectively. Upon admission, the patient's neurological examination revealed a FOUR coma scale of 16. He exhibited motor aphasia, right facial paralysis sparing the forehead, and right upper and lower extremity spastic hemiparesis with a strength of 3 out of 5 on the Medical Research Council scale. The Plantar reflex was positive on the affected side. Brain magnetic resonance imaging revealed left middle cerebral artery infarction (cortical and lenticulostriate territory acute infarction). Conclusion: This case highlights the need for treating physician to have a high index of suspicion towards meningovascular syphilis as a potential cause of stroke in young individuals. This is crucial, especially when there is also a concurrent HIV infection, as it requires specific treatment. [ABSTRACT FROM AUTHOR]

Objective: This is a retrospective analysis of clinical data from individuals diagnosed with neurosyphilis, aiming to enhance healthcare professionals' understanding of the disease and expedite early diagnosis and intervention. Methods: A retrospective analysis was conducted on the clinical records of 50 patients who received a diagnosis of symptomatic neurosyphilis and were admitted to the Neurology Department during the period spanning January 2012 to December 2022. Results: Clinical manifestations encompassed diverse phenotypes, with syphilitic meningitis accounting for 16% of cases, characterized by symptoms such as headache, blepharoptosis, paralysis, blurred vision, and tinnitus. Meningovascular syphilis presented in 36% of cases, exhibiting episodic loss of consciousness, limb numbness, and limb convulsion. Paralytic dementia manifested in 36% of cases, featuring symptoms such as memory loss, sluggish response, and slow movement. Tabes dorsalis was observed in 12% of cases, presenting with weakness, numbness, and staggering. Routine cerebrospinal fluid (CSF) analysis indicated abnormal white blood cell counts in 60% of patients, while biochemical testing revealed abnormal protein content in 52% of patients. Notably, statistically significant differences were observed between patients with interstitial and parenchymatous neurosyphilis (Z = 2.023, P = 0.044) in terms of CSF protein content. Electroencephalogram (EEG) results were abnormal in six patients, and imaging studies unveiled diverse findings in 46 patients. Conclusion: The study highlights the importance of neurological and/or ocular symptoms in diagnosing symptomatic neurosyphilis. Individuals with hypomnesia should be closely monitored for potential neurosyphilis. Integrating clinical manifestations, laboratory tests, EEG, and imaging can reduce misdiagnosis. This comprehensive approach shows promise in improving early identification and management of neurosyphilis. [ABSTRACT FROM AUTHOR]

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.

Purpose: To present a rare case of neurosyphilis, the tertiary form of syphilitic infection, following adequate but belated treatment and manifesting with a variety of clinical signs and further progression to tabetic neurosyphilis. Known as the "great imitator", neurosyphilis is often misdiagnosed and underestimated. Materials/methods: A 48-year-old male patient was admitted to the Neurology clinic of UMHAT "Dr Georgi Stranski" Pleven, Bulgaria, with progressive neurological deficit including numbness in the lower limbs, imbalance and wide-based gait. The T2W- MRI showed abnormally high longitudinal signals at Th12-L1 level, consistent with transverse myelitis. CSF analysis revealed leucocytic pleocytosis, elevated proteins and normal glucose. The nerve conduction studies confirmed sensory motor polyneuropathy. Results: After treatment with intravenous aqueous crystalline (IV) penicillin, 2 million intravenously every 4 hours for 20 days, the sensory symptoms reduced. The coordination disturbances persisted, but the gate showed moderate improvement. Conclusions: The diagnosis of syphilitic myelitis, known as tabes dorsalis, is always complex, not only because of its rarity but because of its unique clinical presentation with multiple clinical symptoms, mimicking other more common neurological disorders. Though confirmation of the diagnosis needs a lot of laboratory and neuroimaging studies, the option of effective specific treatment is worth all the efforts.

A rare case of neurosyphilis with oral condyloma lata and fingernail damage is reported. A 49-year-old male presented with a two-month history of copper-red macules on the palms of both hands and verrucous plaques on the tongue tip for 1 month, and dark shadows on the left eye for 1 week. Dermatological examination revealed uneven and partially thickened nail surfaces of the left thumb and right index finger. The palms were scattered with copper-red macules in the size of mung beans, surrounded by collar-like desquamation. Flat-topped verrucous plaques could be seen on the mucosa of the tongue tip. Hearing was slightly less in the left ear than in the right ear. Corrected visual acuity was 1.0 in the right eye and 0.8 in the left eye. Laboratory tests showed positive for both serum Treponema pallidum particle agglutination (TPPA) (>1∶1 280) and Tolulized red unheated serum test (TRUST) (1∶64). Moreover, the cerebrospinal fluid (CSF) was positive for TRUST(1∶1), TPPA(1∶640) and venereal disease research laboratory (VDRL) (1∶2). The presence of Treponema Pallidum (T. Pallium) in oral verrucous plaque was confirmed by metagenomics next-generation sequencing (mNGS) technology. The diagnosis was neurosyphilis, secondary syphilis (oral flat condyloma). After 2 weeks of treatment with aqua penicillin at a dose of 4 million U q4h, almost all clinical manifestations were improved. Serum TRUST titer was decreased to 1∶8 after 3 months. The follow-up is still ongoing.

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.

We review key concepts in the diagnosis, treatment, and follow-up of individuals with neurosyphilis. We describe the epidemiology of syphilis in the United States, highlight populations that are markedly affected by this infection, and attempt to estimate the burden of neurosyphilis. We describe the cardinal clinical features of early and late (tertiary) neurosyphilis and characterize the clinical significance of asymptomatic neurosyphilis in the antibiotic era. We review the indications for cerebrospinal fluid (CSF) examination and the performance characteristics of different CSF assays including treponemal and lipoidal antibodies, white cell count, and protein concentration. Future biomarkers and the role of imaging are briefly considered. We review preferred and alternative treatments for neurosyphilis and evidence for their use, including evidence for the use of enhanced intramuscular benzathine penicillin G to supplement intravenous penicillin. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Recurrent depression with psychotic features is an atypical presentation of neurosyphilis. This case emphasizes the polymorphic clinical presentation of neurosyphilis and how it mimics affective disorders with psychotic symptoms. [ABSTRACT FROM AUTHOR]

Key Clinical Message: With syphilis resurgence, physicians should be more vigilant to infection‐induced cerebral vasculitis in high‐risk patients presenting with neurological symptoms. In this case, neurosyphilis should not be missed. Thorough serologic screening and lumbar puncture are crucial for diagnosis, and further research is needed for safe and effective treatments in these populations. [ABSTRACT FROM AUTHOR]

A rare case of neurosyphilis with oral condyloma lata and fingernail damage is reported. A 49-year-old male presented with a two-month history of copper-red macules on the palms of both hands and verrucous plaques on the tongue tip for 1 month, and dark shadows on the left eye for 1 week. Dermatological examination revealed uneven and partially thickened nail surfaces of the left thumb and right index finger. The palms were scattered with copper-red macules in the size of mung beans, surrounded by collar-like desquamation. Flat-topped verrucous plaques could be seen on the mucosa of the tongue tip. Hearing was slightly less in the left ear than in the right ear. Corrected visual acuity was 1.0 in the right eye and 0. 8 in the left eye. Laboratory tests showed positive for both serum Treponema pallidum particle agglutination (TPPA) (>1:1 280 ) and Tolulized red unheated serum test (TRUST) (1 : 64). Moreover, the cerebrospinal fluid (CSF) was positive for TRUST (1 : 1), TPPA (1 : 640) and venereal disease research laboratory ( VDRL) (1 : 2). The presence of Treponema Pallidum (T. Pallium) in oral verrucous plaque was confirmed by metagenomics next-generation sequencing (mNGS) technology. The diagnosis was neurosyphilis, secondary syphilis( oral flat condyloma) . After 2 weeks of treatment with aqua penicillin at a dose of 4 miilion U q4h, almost all clinical manifestations were improved. Serum TRUST titer was decreased to 1 : 8 after 3 months. The follow-up is stiil ongoing. [ABSTRACT FROM AUTHOR]

Neurosyphilis (NS) is a central nervous system (CNS) infection caused by Treponema pallidum (T. pallidum). NS can occur at any stage of syphilis and manifests as a broad spectrum of clinical symptoms. Often referred to as "the great imitator," NS can be easily overlooked or misdiagnosed due to the absence of standard diagnostic tests, potentially leading to severe and irreversible organ dysfunction. In this study, proteomic and machine learning model techniques are used to characterize 223 cerebrospinal fluid (CSF) samples to identify diagnostic markers of NS and provide insights into the underlying mechanisms of the associated inflammatory responses. Three biomarkers (SEMA7A, SERPINA3, and ITIH4) are validated as contributors to NS diagnosis through multicenter verification of an additional 115 CSF samples. We anticipate that the identified biomarkers will become effective tools for assisting in diagnosis of NS. Our insights into NS pathogenesis in brain tissue may inform therapeutic strategies and drug discoveries for NS patients. [ABSTRACT FROM AUTHOR]

Background: Little is known about the etiology, clinical presentation, management, and outcome of central nervous system (CNS) infections in Indonesia, a country with a high burden of infectious diseases and a rising prevalence of HIV. Methods: We included adult patients with suspected CNS infections at two referral hospitals in a prospective cohort between April 2019 and December 2021. Clinical, laboratory, and radiological assessments were standardized. We recorded initial and final diagnoses, treatments, and outcomes during 6 months of follow-up. Results: Of 1051 patients screened, 793 were diagnosed with a CNS infection. Patients (median age 33 years, 62% male, 38% HIV-infected) presented a median of 14 days (IQR 7–30) after symptom onset, often with altered consciousness (63%), motor deficits (73%), and seizures (21%). Among HIV-uninfected patients, CNS tuberculosis (TB) was most common (60%), while viral (8%) and bacterial (4%) disease were uncommon. Among HIV-infected patients, cerebral toxoplasmosis (41%) was most common, followed by CNS TB (19%), neurosyphilis (15%), and cryptococcal meningitis (10%). A microbiologically confirmed diagnosis was achieved in 25% of cases, and initial diagnoses were revised in 46% of cases. In-hospital mortality was 30%, and at six months, 45% of patients had died, and 12% suffered from severe disability. Six-month mortality was associated with older age, HIV, and severe clinical, radiological and CSF markers at presentation. Conclusion: CNS infections in Indonesia are characterized by late presentation, severe disease, frequent HIV coinfection, low microbiological confirmation and high mortality. These findings highlight the need for earlier disease recognition, faster and more accurate diagnosis, and optimized treatment, coupled with wider efforts to improve the uptake of HIV services. [ABSTRACT FROM AUTHOR]

We evaluated the diagnostic clinical performance characteristics (DCPC) of cerebrospinal fluid (CSF) total protein (TP), white blood cell count (WBC), and lactate (LA) with different cutoff points as adjunct biomarkers of confirmed or presumptive symptomatic neurosyphilis (NS) and the impact of HIV infection. From 5,640 participants who underwent lumbar punctures, 236 participants were included, and classified as either people with HIV (PWH) or people without HIV (PWoH) according to the CDC criteria for confirmed NS (n = 42), presumptive NS (n = 74), systemic syphilis (SS) (n = 38), serological diagnosis of syphilis (n = 18), PWH without SS and NS (n = 10), and negative control (n = 72). In PWoH, for presumptive NS, the combination of CSF TP > 45 mg/dL and/or WBC > 5.0 cells/mm3 is valuable for screening, whereas in PWH, it is not recommended for either screening or case-finding NS, however the DCPC were better in the suppressed group. In PWoH, the value of CSF TP > 45 mg/dL is adequate for both screening and confirmation of presumptive NS, subject to prevalence. For WBC count > 20 cell/mm3, the positive predictive value (PPV) of the test is almost perfect, suggesting a confirmatory test. In PWH, CSF TP is an inadequate marker of NS. The WBC count, with cutoffs of > 10 or > 20 cells/mm3, was moderately applicable for screening. As conclusions: CSF WBC count and TP showed distinct DCPC in confirmed or presumptive NS, better in the former. These biomarkers could be included for presumptive NS diagnosis. DCPC of these biomarkers for the diagnosis of NS is greatly affected by HIV co-infection. [ABSTRACT FROM AUTHOR]

Syphilis is an infectious disease caused by the spirochete bacterium Treponema pallidum. Neurosyphilis results from the infection of the nervous system with Treponema pallidum, which can occur at any stage of syphilis. Neurosyphilis is often overlooked because of its rarity. Early‐stage neurosyphilis with brain mass formation is rare. We present a case of early‐stage neurosyphilis with prominent Epstein–Barr virus (EBV)‐positive monoclonal lymphoplasmacytic proliferation in an immunocompetent patient. A 36‐year‐old man presented with a chief complaint of a progressively worsening headache, a newly developed skin rash, and a fever. Magnetic resonance imaging showed a mass lesion, which measured 18 mm in diameter, in the left frontal lobe of the cerebrum. The patient underwent an emergency operation to remove the abscess. A pathological investigation revealed complex findings. There was an abscess in the cerebrum. Lymphoplasmacytic meningitis was also noted. In addition, a vaguely nodular lesion, which was composed of plasmacytoid and lymphoid cells, was observed around the abscess. Immunohistochemically, an anti‐Treponema pallidum antibody revealed numerous Treponemas around the abscess. In situ hybridization revealed that the plasmacytoid and lymphoid cells were Epstein–Barr encoding region (EBER)‐positive; κ‐positive cells were significantly more prevalent than λ‐positive cells, suggesting light‐chain restriction. Postoperatively, parenteral antibiotics were administered for four weeks. The patient has been free of recurrence for two years since the surgery. No association between neurosyphilis and EBV‐positive lymphoplasmacytic proliferation has ever been reported. Mass formation in early‐stage neurosyphilis is an exceptionally rare event. The present case indicates that in syphilis patients, lymphoproliferative disorders that lead to mass formation may be caused by concomitant EBV reactivation. Furthermore, when treating patients with mass lesions of the central nervous system, it is important to check their medical history and perform laboratory screening for infectious diseases to avoid overlooking syphilis infections. [ABSTRACT FROM AUTHOR]

Background: The incidence of syphilis has increased in high-income countries in the past few decades, especially among men who have sex with men. In the present study, we aimed to analyze the correlations between atypical syphilis manifestations and the demographic, clinical, and laboratory features of patients and to review unusual presentations of syphilis reported in the literature. Methods: We conducted a retrospective analysis of 307 patients with syphilis diagnosed between 1 January 2013 and 31 October 2023 at the sexually transmitted infection (STI) centers of the University of Genoa and University of Foggia with both typical and atypical manifestations of disease. Results: In our series, atypical manifestations were detected in 25.8% of the patients, especially in the secondary stage of the disease. Lesions with annular morphology and lesions presenting as itchy erythematous scaly plaques with a psoriasiform appearance were the most common atypical presentations of secondary syphilis. A statistical analysis revealed that homosexual orientation, syphilis reinfection, and venereal disease research laboratory (VDRL) titers > 1:32 were correlated with atypical manifestations. Conclusions: Our study demonstrates that the spectrum of syphilis manifestations, in all the stages of the disease, is wide; atypical manifestations often pose diagnostic challenges, may delay the provision of appropriate treatment, and facilitate the spread of the infection. [ABSTRACT FROM AUTHOR]

Syphilitic osteomyelitis, a rare complication of syphilis, should be considered in patients with lytic osseous lesions. A 25-year-old man presented with a progressive headache and a history of a painless penile chancre. Further investigation revealed a lytic osseous lesion in the left parietal bone, indicating syphilitic osteomyelitis. The patient was treated with penicillin and showed clinical and radiographic improvement after 2 weeks of therapy. Syphilitic osteitis and osteomyelitis management is not well established, and treatment duration varies. It is important to consider syphilitic osteitis in patients with bony pain to prevent permanent bony destruction. [Extracted from the article]

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.

Background and aim: Invasion of the central nervous system by Treponema pallidum can occur at any stage of syphilis. In the event that T. pallidum is not cleared promptly, certain individuals may experience progression to neurosyphilis, which manifests as cognitive and behavioral abnormalities, limb paralysis, and potentially fatal outcomes. Early identification or prevention of neurosyphilis is therefore crucial. The aim of this paper is to conduct a critical and narrative review of the latest information focusing exclusively to the pathogenesis and clinical management of neurosyphilis. Methodology: To compile this review, we have conducted electronic literature searches from the PubMed database relating to neurosyphilis. Priority was given to studies published from the past 10 years (from 2013 to 2023) and other studies if they were of significant importance (from 1985 to 2012), including whole genome sequencing results, cell structure of T. pallidum, history of genotyping, and other related topics. These studies are classic or reflect a developmental process. Results: Neurosyphilis has garnered global attention, yet susceptibility to and the pathogenesis of this condition remain under investigation. Cerebrospinal fluid examination plays an important role in the diagnosis of neurosyphilis, but lacks the gold standard. Intravenous aqueous crystalline penicillin G continues to be the recommended therapeutic approach for neurosyphilis. Considering its sustained prominence, it is imperative to develop novel public health tactics in order to manage the resurgence of neurosyphilis. Conclusion: This review gives an updated narrative description of neurosyphilis with special emphasis on its pathogenesis, susceptibility, diagnosis, treatment, and prevention. [ABSTRACT FROM AUTHOR]

Background: Neurosarcoidosis (NS) is a challenging diagnosis, particularly when cases occur in low-prevalence, non-endemic geographic regions. In the United States, the highest incidence is in the Midwest and Northeast, compared to our Southwest location. While it is well known that NS may clinically and neuroradiographically mimic meningeal carcinomatosis, autoimmune or infectious pachymeningitis, neurosyphilis, or tuberculosis, diagnosis may be particularly challenging if systemic signs of sarcoidosis are lacking or unconfirmed or if dural-based masses are present. We reviewed our Colorado experience with NS cases, focusing our study on cases where NS represented the first histological confirmation of disease. Methods: A search of departmental databases was conducted with the search term "neurosarcoidosis" to identify cases 1-2008 to 12-2019, inclusive of the given case numbers. Patients were only included if their clinical and neuroimaging features were unusual and only when a biopsy of the central nervous system (CNS) represented the first confirmed diagnosis of sarcoidosis. Results: A total of 17 cases were identified, of which the biopsy of the CNS was used for the initial confirmation of the disease in 9 of them. The most unusual findings were two patients with dural-based masses, one of which had pure NS as the cause of meningioma-like lesions and the second of which had coexistent meningioma and intimately admixed non-necrotizing granulomas of NS. Conclusion: NS with unusual features, especially in non-endemic areas, continues to yield diagnostic challenges for neurologists, neuroradiologists, and pathologists. [ABSTRACT FROM AUTHOR]

Glial fibrillary acidic protein (GFAP), an intracellular type III intermediate filament protein, provides structural support and maintains the mechanical integrity of astrocytes. It is predominantly found in the astrocytes which are the most abundant subtypes of glial cells in the brain and spinal cord. As a marker protein of astrocytes, GFAP may exert a variety of physiological effects in neurological diseases. For example, previous published literatures showed that autoimmune GFAP astrocytopathy is an inflammatory disease of the central nervous system (CNS). Moreover, the studies of GFAP in brain tumors mainly focus on the predictive value of tumor volume. Furthermore, using biomarkers in the early setting will lead to a simplified and standardized way to estimate the poor outcome in traumatic brain injury (TBI) and ischemic stroke. Recently, observational studies revealed that cerebrospinal fluid (CSF) GFAP, as a valuable potential diagnostic biomarker for neurosyphilis, had a sensitivity of 76.60% and specificity of 85.56%. The reason plasma GFAP could serve as a promising biomarker for diagnosis and prediction of Alzheimer's disease (AD) is that it effectively distinguished AD dementia from multiple neurodegenerative diseases and predicted the individual risk of AD progression. In addition, GFAP can be helpful in differentiating relapsing–remitting multiple sclerosis (RRMS) versus progressive MS (PMS). This review article aims to provide an overview of GFAP in the prediction of clinical progression in neuroinflammation, brain tumors, TBI, ischemic stroke, genetic disorders, neurodegeneration and other diseases in the CNS and to explore the potential therapeutic methods. [ABSTRACT FROM AUTHOR]

Background: The global shift in healthcare during the COVID-19 pandemic led to challenges in the care of people living with HIV. Methods: We conducted a retrospective study that aimed to delineate sociodemographic, clinical characteristics and outcomes, of people living with HIV diagnosed with ocular syphilis. Results: Fifty-three people living with HIV were identified with ocular syphilis. Thirty-eight (71.6%) presented ocular symptoms. Twenty-three (43.3%) underwent lumbar puncture, 5 (9.4%) were positive for neurosyphilis. Forty-seven (88.6%) received treatment, 32 (68%) received standard treatment with aqueous crystalline penicillin G, and 15 (31.9%) were treated with alternative regimens due to the impossibility of hospitalization. Six (11.3%) individuals were lost to follow-up and/or did not receive treatment. Eighteen (56.2%) out of 32 individuals in the aqueous crystalline penicillin G group experienced serological response, 5 (15.6%) experienced treatment failure, and 9 (28.1%) were lost to follow-up. In the alternative therapy group, 12 out of 15 individuals (80%) experienced serological response. One (6.7%) experienced treatment failure, and 2 (13.3%) were lost to follow-up. Conclusions: During the COVID-19 health emergency in Mexico, alternative treatments for ocular syphilis demonstrated favorable clinical outcomes amid challenges in accessing hospitalization. [ABSTRACT FROM AUTHOR]

C-X-C-motif chemokine ligand 13 (CXCL13) in cerebrospinal fluid (CSF) is increasingly used in clinical routines, although its diagnostic specificity and divergent cut-off values have been defined so far mainly for neuroborreliosis. Our aim was to evaluate the value of CSF-CXCL13 as a diagnostic and treatment response marker and its role as an activity marker in a larger disease spectrum, including neuroborreliosis and other neuroinflammatory and malignant CNS-disorders. Patients who received a diagnostic lumbar puncture (LP) (n = 1234) between July 2009 and January 2023 were included in our retrospective cross-sectional study. The diagnostic performance of CSF-CXCL13 for acute neuroborreliosis was highest at a cut-off of 428.92 pg/mL (sensitivity: 92.1%; specificity: 96.5%). In addition, CXCL13 levels in CSF were significantly elevated in multiple sclerosis with clinical (p = 0.001) and radiographic disease activity (p < 0.001). The clinical utility of CSF-CXCL13 appears to be multifaceted. CSF-CXCL13 is significantly elevated in patients with neuroborreliosis and shows a rapid and sharp decline with antibiotic therapy, but it is not specific for this disease and is also highly elevated in less common subacute neuroinfectious diseases, such as neurosyphilis and cryptococcal meningitis or in primary/secondary B-cell lymphoma. [ABSTRACT FROM AUTHOR]

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Accurately predicting neurosyphilis prior to a lumbar puncture (LP) is critical for the prompt management of neurosyphilis. However, a valid and reliable model for this purpose is still lacking. This study aimed to develop a nomogram for the accurate identification of neurosyphilis in patients with syphilis. The training cohort included 9,504 syphilis patients who underwent initial neurosyphilis evaluation between 2009 and 2020, while the validation cohort comprised 526 patients whose data were prospectively collected from January 2021 to September 2021. Neurosyphilis was observed in 35.8% (3,400/9,504) of the training cohort and 37.6% (198/526) of the validation cohort. The nomogram incorporated factors such as age, male gender, neurological and psychiatric symptoms, serum RPR, a mucous plaque of the larynx and nose, a history of other STD infections, and co-diabetes. The model exhibited good performance with concordance indexes of 0.84 (95% CI, 0.83–0.85) and 0.82 (95% CI, 0.78–0.86) in the training and validation cohorts, respectively, along with well-fitted calibration curves. This study developed a precise nomogram to predict neurosyphilis risk in syphilis patients, with potential implications for early detection prior to an LP. [ABSTRACT FROM AUTHOR]

Background. The incidence of syphilis throughout the world is increasing. Rates in pregnancy are similarly rising, presenting risks of an untreated syphilis infection that can be detrimental to the mother and fetus. Although routine screening for syphilis infections is recommended at the initial prenatal visit, there is a lack of universal agreement on rescreening pregnant people and approximately 50% of syphilis cases are asymptomatic in the general population. Furthermore, some symptoms of syphilis can overlap with nonspecific pregnancy-related symptoms. Meanwhile, Treponema pallidum can spread to various maternal and fetoplacental tissues quickly after infection and occur at any stage of syphilis. Case. A 26-year-old gravida 5 para 2 presented with a new onset headache and visual and auditory changes at 23 weeks of gestation. A computerized tomography scan revealed numerous ill-defined lytic lesions throughout the calvarium, suspicious for syphilitic osteitis. She tested positive for syphilis antibodies with a rapid plasma reagin (RPR) titer of 1 : 32. Cerebrospinal fluid evaluation from a lumbar puncture resulted in reactive fluorescent treponemal antibody (FTA) testing. She was diagnosed with secondary syphilis with osteitis and neuro and otic components. She completed 14 days of intravenous aqueous crystalline penicillin G with additional benzathine penicillin G 2.4 million units intramuscular weekly for two weeks. There was no evidence of congenital syphilis on neonatal examination. Conclusion. Syphilitic osteitis and neuro, otic, or ocular syphilis infections occur rarely in the nonpregnant population, and therefore, little data in pregnancy is available to inform outcomes in these specific disease states. It is of paramount importance to complete appropriate syphilis screening, recognize symptoms, and consider utilizing rescreen protocols to ensure prompt infection identification and treatment. For neuro, otic, and ocular syphilis, aqueous crystalline penicillin G (as opposed to benzathine penicillin G) is required to achieve treponemicidal concentrations in those physiologic compartments. There is no agreement as to the appropriate treatment regimen for the rare finding of syphilitic osteitis. [ABSTRACT FROM AUTHOR]

Key Clinical Message Recurrent depression with psychotic features is an atypical presentation of neurosyphilis. This case emphasizes the polymorphic clinical presentation of neurosyphilis and how it mimics affective disorders with psychotic symptoms.