Factors associated with cerebrospinal fluid abnormalities suggestive of neurosyphilis in HIV-negative patients with secondary syphilis: a retrospective study

Objective To identify clinical and laboratory factors associated with cerebrospinal fluid (CSF) abnormalities suggestive of neurosyphilis (NS) among HIV-negative patients with secondary syphilis. Methods We conducted a retrospective analysis of 805 HIV-negative patients diagnosed with secondary syphilis who underwent lumbar puncture (Lp) at a tertiary referral center in Shanghai, China, between 2009 and 2022. NS was defined based on CSF-VDRL reactivity and/or CSF abnormalities (elevated protein or pleocytosis) in the absence of alternative causes. Logistic regression models were used to identify factors associated with NS. Results Among 805 participants, 402 (49.9%) met the study definition of NS. In multivariable analysis, age 39 years adjusted OR (aOR) = 2.72, 95% CI 2.01–3.68, male patients (aOR = 2.14, 95% CI 1.58–2.90), presence of oral mucosal patches (aOR = 2.21, 95% CI 1.38–3.55), and CD4 + T cell counts 500 cells/μL (aOR = 1.46, 95% CI 1.02–2.10) were independently associated with NS. Conclusion In HIV-negative patients with secondary syphilis undergoing Lp, several demographic, clinical, and immunological factors were associated with CSF abnormalities suggestive of NS. These findings may assist clinicians in identifying patients who could benefit from further neurological evaluation. However, given the broad case definition and potential selection bias, the results should be interpreted with caution. Prospective studies using standardized NS definitions are warranted.