Neurosyphilis with simultaneous brain and spinal cord involvement mimicking intracranial tumors: a case report

Neurosyphilis is a heterogeneous manifestation of Treponema pallidum infection with diverse clinical and radiological presentations. Concurrent involvement of the brain and spinal cord is rare and may mimic intracranial neoplasms, leading to diagnostic uncertainty. A 48-year-old woman presented with acute-onset limb numbness and diplopia. Brain and cervical spine magnetic resonance imaging (MRI) revealed multiple nodular and ring-enhancing lesions involving the brain parenchyma and cervical spinal cord, initially raising suspicion of lymphoma or metastatic tumors. Diffusion-weighted imaging (DWI) showed atypical hypointensity without diffusion restriction. Histopathological examination demonstrated perivascular inflammatory infiltration without evidence of malignancy. Serological testing confirmed a reactive serum rapid plasma reagin (RPR) titer with treponemal confirmation, and metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) detected Treponema pallidum deoxyribonucleic acid (DNA), supporting the diagnosis of neurosyphilis. HIV serology was negative. Due to a documented penicillin allergy (positive penicillin skin test), the patient received alternative antimicrobial therapy with fosfomycin (8 g/day intravenously) and minocycline (100 mg orally twice daily), resulting in marked clinical improvement and regression of lesions on follow-up imaging. This report describes a patient in whom neurosyphilis presented with concurrent brain and spinal cord lesions that radiologically resembled malignant central nervous system (CNS) tumors. Multifocal nodular and ring-enhancing lesions without diffusion restriction, combined with clinical improvement following antimicrobial therapy, were features observed in this case that contributed to the diagnostic re-evaluation. This case highlights the importance of including neurosyphilis in the differential diagnosis of tumor-like CNS lesions when imaging findings are atypical, while acknowledging that definitive diagnostic conclusions are limited by the single-case nature of this report.