Evidence from epidemiological, clinical, and biological research resulted in the immune hypothesis: the hypothesis that immune system dysfunction is involved in the pathophysiology of schizophrenia spectrum disorders (SSD). The promising implication of this hypothesis is the potential to use existing immunomodulatory treatment for innovative interventions for SSD. Here, we provide a selective historical review of important discoveries that have shaped our understanding of immune dysfunction in SSD. We first explain the basic principles of immune dysfunction, after which we travel more than a century back in time. Starting our journey with neurosyphilis-associated psychosis in the nineteenth century, we continue by evaluating the role of infections and autoimmunity in SSD and findings from assessment of immune function using new techniques, such as cytokine levels, microglia density, neuroimaging, and gene expression. Drawing from these findings, we discuss anti-inflammatory interventions for SSD, and we conclude with a look into the future.

UNASSIGNED: To investigate the role of the chemokines CXCL13, CXCL10 and CXCL8 in the diagnosis of ocular- and neurosyphilis by examining the serum, aqueous humour (AH) and cerebrospinal fluid (CSF) of patients with ocular syphilis.
UNASSIGNED: An observational descriptive study was performed prospectively at Tygerberg Academic Hospital in Cape Town, South Africa from 1 February 2018 till 31 January 2021 which enrolled 23 participants. 14 Patients were male and 9 female, 15 patients were HIV positive, and all patients were newly diagnosed with ocular syphilis. Upon diagnosis of ocular syphilis, the HIV status of each patient was determined, and 3 samples (AH, serum and CSF) were collected to measure the levels of CXCL13, CXCL10 and CXCL8 in each. All patients were treated with 14 days of intravenous Penicillin G and topical corticosteroid drops for uveitis.
UNASSIGNED: The mean concentrations of all 3 biomarkers were higher in the AH and CSF than in the serum. The mean concentrations of the 3 measured biomarkers were markedly different when comparing both AH and CSF levels to serum levels. The level of CXCL13 measured in the AH correlated well with the concentrations found in the CSF of patients with neurosyphilis. In patients with neurosyphilis, mean AH levels of CXCL13 and CXCL10 were markedly higher than in serum while mean CSF levels of CXCL10 were also markedly higher than in serum. Also, the AH/serum ratio of CXCL13 and CXCL10, as well as the CSF/serum ratio of CXCL10, was much higher in patients with neurosyphilis than without. In patients with HIV infection, mean AH CXCL13 levels were much higher than in patients without HIV infection.
UNASSIGNED: The levels of CXCL13, CXCL10 and CXCL8 in the AH of patients with neurosyphilis are similar to previously reported levels in the CSF of patients with neurosyphilis and can potentially be an adjunct in the diagnosis of ocular syphilis. Patients with ocular syphilis who tested negative for neurosyphilis with conventional CSF testing showed features of neurosyphilis when analysing the CSF chemokines.

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.

Neurosyphilis, a rare manifestation of Treponema pallidum spreading into the central nervous system, is a critical differential diagnosis due to its potentially severe neurologic effects if left untreated. We present a case of a 37-year-old woman who complained of bilateral vision loss and headaches originally concerning for idiopathic intracranial hypertension and uncontrolled diabetes. Comprehensive evaluations eventually led to a neurosyphilis diagnosis. Ophthalmologic examination revealed multifactorial visual symptoms with diabetic retinopathy contributing alongside neurosyphilis. Treatment was started promptly at the time of diagnosis and resulted in improvement in visual symptoms. This case emphasizes the importance of syphilis screening in appropriate age ranges, even in low-prevalence areas. Recognition of neurosyphilis as a potential diagnosis can impact patient outcomes and highlights the need for continued vigilance to identify the disease.

This is a case report of 51-year-old male patient with various symptoms including skin rashes, sensory disturbances, and non-cicatricial hair loss. Despite previous tests, the cause remained elusive until a dermatological examination revealed signs of syphilis. The patient\'s history, including his sexual relationships, became key in confirming the diagnosis, leading to treatment for neurosyphilis. With a rising incidence of syphilis in Denmark, this case highlights the importance of considering syphilis as a potential diagnosis across medical specialities because of the diverse and challenging clinical manifestations.

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UNASSIGNED: 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.
UNASSIGNED: Hospitalized patients with tabes dorsalis at Peking Union Medical College Hospital between January 2010 and December 2023 were reviewed.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.

OBJECTIVE: 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.
CONCLUSIONS: 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.

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.