Neurosyphilis may mimic inflammatory and demyelinating disorders, particularly when cerebrospinal fluid (CSF) abnormalities are minimal. We report a 17-year-old postpartum adolescent who developed progressive paraparesis, sensory deficits, gait instability, and headache 34 days after delivery following treatment for gestational syphilis during pregnancy. Brain magnetic resonance imaging demonstrated a solitary pontine T2-hyperintense lesion without significant enhancement, initially suggesting an inflammatory demyelinating process. CSF analysis revealed a protein concentration of 24.9 mg/dL and only 2 leukocytes/mm³. Despite these minimally inflammatory findings, CSF Venereal Disease Research Laboratory testing was reactive at a titer of 1:16, supporting the diagnosis of neurosyphilis in the appropriate clinical context. The patient experienced marked neurologic improvement following intravenous aqueous crystalline penicillin G therapy. This case highlights postpartum neurosyphilis as an uncommon demyelinating mimic and underscores the importance of syphilis testing in patients with unexplained focal neurologic syndromes despite near-normal CSF findings.
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