1. Prevalence and Diagnosis: Among 1588 syphilis cases, 262 (16.5%) were reported as neurosyphilis. Only 30.2% (79) of these cases were confirmed through CSF tests.

2. Psychiatric Symptoms: 34.7% of neurosyphilis cases were initially diagnosed with schizophrenia, highlighting the challenge of differential diagnosis in psychiatric settings.

3. Standard Treatment: Of the reported neurosyphilis cases, 66.8% received standard treatment. Confirmed cases had a significantly higher rate of standard treatment compared to suspected cases.

4. Treatment Efficacy: BPRS scores indicated significant improvement in psychotic symptoms after standard treatment, particularly in confirmed neurosyphilis cases.

5. Diagnostic Challenges: The study underscores the difficulty in diagnosing neurosyphilis due to varied clinical manifestations and the need for improved diagnostic capabilities, especially in lower-grade hospitals. MRI plays a crucial role in diagnosing neurosyphilis, detecting various manifestations and brain abnormalities that often precede symptoms, emphasizing its importance in early detection.

Syphilis is a resurgent sexually transmitted disease worldwide, with 6.3 million new syphilis cases each year among people aged 15–49 [1, 2]. According to the American Centers for Disease Control and Prevention (CDC), 176,713 syphilis cases were reported in 2021. The rate of primary and secondary syphilis increased by 28.6% from 2020 to 2021 [3]. In China, 535,819 cases of syphilis (all stages) were reported, with the incidence rising from 30.93 to 38.37 cases per 100,000. This reflects an average annual growth rate of 4.41% during 2014–2019 [4]. Guangdong Province in South China is experiencing a syphilis epidemic. In 2019, 6276 cases were reported in Guangdong, accounting for 11.7% of national cases [5].

Treponema pallidum (T. pallidum), the causative agent of syphilis, can spread to the central nervous system hours to days after inoculation, leading to neurosyphilis at any stage of syphilis [6]. If untreated, 4%–10% of patients with syphilis develop neurosyphilis [7]. Neurosyphilis can cause severe neurological damage, manifesting as acute meningitis, cranial nerve abnormalities, or stroke due to central nervous system (CNS) arteritis, and may progress to chronic conditions like general paresis or tabes dorsalis, leading to dementia, motor dysfunction, and sensory loss. It can also affect the eyes and ears, resulting in visual impairment, hearing loss, or balance issues [8]. However, the true incidence of neurosyphilis is hard to determine due to frequent misdiagnoses, a lack of accurate microbiological tests, varied disease symptoms, and different clinical diagnostic criteria [9]. Between 2009 and 2021, 7486 cases of neurosyphilis were reported in China [10]. Insufficient detection of cerebrospinal fluid and the low sensitivity (30–50%) of non-specific antibody tests complicate diagnosis and treatment. Additionally, the standard 10–14 day hospital stay required for neurosyphilis treatment is often affected by hospital conditions, patient financial constraints, and preferences to avoid prolonged hospitalization, resulting in non-standard treatment. Our early cross-sectional study found that 48.3% of cases were misdiagnosed among 3805 patients with neurosyphilis and tertiary syphilis reported during 2009–2014, and only 27.1% of the correctly diagnosed cases of late neurosyphilis received standard treatment [11]. The diagnosis of neurosyphilis is generally difficult [12].

Numerous psychotic symptoms are caused by neurosyphilis, which can inform a differential diagnosis of patients with psychosis [7]. Recently, the incidence of syphilis, especially neurosyphilis, has increased [13]. This study aims to enhance the diagnosis and treatment of neurosyphilis in psychiatric hospitals. Given the frequent misdiagnosis resulting from overlapping psychiatric symptoms and a rising incidence of neurosyphilis, this research evaluates diagnostic and management practices in four municipal psychiatric hospitals in Guangdong Province from 2014 to 2018. The goal is to improve patient outcomes and reduce the overall impact of neurosyphilis.

Our study focused on neurosyphilis among syphilis cases attending the psychiatric hospital. Among all the syphilis patients screened, 16.5% were diagnosed with neurosyphilis, in which only one-third were confirmed and two-thirds were treated with standard therapy. The findings indicate that neurosyphilis might be frequently challenging in patients with mental disorders, complicating both diagnosis and treatment. Diagnosing and treating neurosyphilis is challenging due to inadequate cerebrospinal fluid testing in Grade II hospitals and the low sensitivity (30–50%) of non-specific antibody tests in Grade III hospitals. Complex clinical manifestations further complicate diagnosis. Treatment requires a 10–14-day hospital stay, which many Grade II hospitals cannot accommodate. Financial constraints and patient preferences to avoid extended hospitalization often result in incomplete or suboptimal care, worsening the condition’s management.

Psychotic symptoms resulting from neurosyphilis are varied and can contribute to differential diagnosis of many psychotic conditions [18, 19]. Rozwens et al. [19] reported that 27% of neurosyphilis patients exhibited psychiatric symptoms [20]. Similarly, among 149 HIV-negative Chinese patients with neurosyphilis, 46 out of 58 with general paresis presented with psychiatric presentations [20]. In this study, 34.7% neurosyphilis cases were diagnosed with schizophrenia, 19.1% organic, 16.8% bipolar, and 14.1% paranoid disorders on their first visit. Friedrich et al. [18] recommended routine screening tests in the psychiatric field. About 3% of prevalence rates of syphilis were reported among patients with psychosis [21]. We observed that the syphilis prevalence among patients with psychosis was 2.3% from 2014 to 2018, aligning with trends in Guangdong Province [22]. Most neurosyphilis cases involved males and individuals over 45 years old, mirroring the broader trend of increasing syphilis rates among older men, where the male-to-female ratio of syphilis was 1.8, with cases in men aged $\ge$50 years rising significantly from 13.8 per 100,000 in 2004 to 112.0 per 100,000 in 2019 [13].

Diagnosing neurosyphilis remains challenging because it can occur at any stage of syphilis infection and presents with diverse clinical manifestations, compounded by the lack of specific diagnostic tests. CSF examination is recommended in the presence of serologic positive of syphilis in the serum and a clinical syndrome that is consistent with neurosyphilis [17]. The US CDC defines confirmed neurosyphilis as (1) any syphilis stage and (2) a reactive CSF-VDRL [17]. Symptomatic neurosyphilis can present as meningitis, gumma, meningovascular involvement, brain parenchyma involvement, meningomyelitis, tabes dorsalis, or peripheral nervous system involvement. Magnetic resonance imaging (MRI) is crucial for diagnosing neurosyphilis. He C et al. [23] showed symptomatic neurosyphilis patients had more brain abnormalities on MRI, like infarcts and atrophy. These findings often precede symptoms, highlighting MRI’s importance in early detection. MRI is vital for diagnosing general paresis, a common neurosyphilis, by revealing brain changes despite a lack of definitive diagnosis and non-specific symptoms. It aids in timely and accurate diagnoses [24]. MRI’s advanced imaging technique, high-resolution vessel wall imaging (HR-VWI), accurately diagnosed neurosyphilis-related vascular complications, confirmed the cause, and monitored treatment [25]. However, in our study, out of 262 cases reported as neurosyphilis, 137 underwent lumbar puncture and CSF testing. The testing rates were significantly higher in Grade III hospitals (63.2%) compared to Grade II hospitals (43.9%), respectively (p 0.001). To uphold evidence-based medicine principles, it is crucial to emphasize discussions on valid cases of neurosyphilis supported by comprehensive diagnostic evaluations, including CSF testing where indicated. Improving adherence to diagnostic guidelines across hospital grades, enhancing healthcare provider awareness, and advocating for standardized testing protocols are essential steps toward achieving more reliable diagnoses and optimizing patient care outcomes in cases of suspected neurosyphilis. The ability of clinical diagnosis and laboratory of neurosyphilis, especially in low-level hospitals need to be improved.

Treatment guidelines recommend high-dose intravenous penicillin G or intramuscular procaine penicillin G plus oral probenecid for neurosyphilis for 10–14 days to achieve sufficient penicillin concentrations in the CSF [13, 14]. In this study, two-thirds of patients of reported neurosyphilis cases received standard treatment. Notably, 87.3% of confirmed cases received standard therapy compared to 57.9% of suspected cases, resulting in significant improvement in psychotic symptoms as reflected by decreased BPRS scores, particularly in confirmed cases [18]. These results underscore the critical importance of accurate diagnosis and adherence to standard treatment protocols in managing neurosyphilis to improve both syphilis cure rates and associated mental health outcomes.

This study primarily focused on the prevalence and treatment of neurosyphilis in select neurological hospitals in Guangdong but had several limitations. It included only two secondary and two tertiary hospitals out of 21 cities, excluding primary psychiatric hospitals. Additionally, potential missed diagnoses of neurosyphilis in mental patients with syphilis and incomplete classification of syphilis stages due to limited clinical data were not analyzed.

The diagnosis and treatment of neurosyphilis in psychiatric hospitals in Guangdong, China, remains challenging. Only one-third of reported neurosyphilis cases were confirmed and two-thirds received standard therapy. Correct diagnosis and standard treatment is of clinical significance not only for curing syphilis but also for improving mental disorders caused by neurosyphilis. Enhancing diagnostic accuracy through greater use of CSF tests and implementing standardized treatment protocols are critical for effectively managing neurosyphilis and its associated mental health complications in psychiatric hospitals worldwide.

In Guangdong’s psychiatric field, given the need to manage syphilis and its associated mental health issues from neurosyphilis effectively, accurate diagnosis and standardized treatment are crucial. However, diagnosing and treating neurosyphilis in local psychiatric hospitals remain challenging, calling for enhanced clinical skills, updated tools, and strict protocol adherence to improve patient care and control the disease.

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Conception–YW; Design–WK; Supervision–WK; Data Collection and/or Processing–YW, ZH, HZhe, XQ, CL, LZ; Analysis and/or Interpretation–HZha; Writing–YW, ZH, HZhe, XQ, CL, LZ; Critical Review–LZ, WK, HZha. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

The study was conducted in accordance with the Declaration of Helsinki, and was approved by the Institutional Ethics Committee of Southern Medical University Dermatology Hospital (GDDHLS-20181202). Since our study is based on a retrospective analysis of data retrieved from a historical database, all data used were de-identified to ensure privacy and comply with ethical standards, therefore, obtaining informed consent from participants was not applicable or necessary for this research.

This research received no external funding.

The authors declare no conflict of interest.