The spectrum of movement disorders in neurosyphilis: A systematic review

Neurosyphilis is a well-recognized mimicker and may present with diverse movement disorders resembling neurodegenerative or autoimmune syndromes. This systematic review aims to elucidate the comprehensive clinical, laboratory, imaging, and outcome spectrum of movement disorders in neurosyphilis.

This systematic review followed PRISMA guidelines with a protocol registered in PROSPERO (CRD420251135620). PubMed, Embase, Scopus, and Google Scholar were searched. Eligible studies included case reports, case series, and observational cohorts with confirmed or probable neurosyphilis and clinically diagnosed movement disorders. Data on demographics, clinical features, cerebrospinal fluid, neuroimaging, treatment, and outcomes were extracted.

We analyzed a total of 48 individual cases reported across 44 publications and two retrospective cohorts (n = 223, with 61 movement disorder patients). The mean age was 47 years (range 10-83), with 76.3% male and 76.3% human immunodeficiency virus negative. Movement disorder subtypes included ataxia (28.9%), parkinsonism (18.4%), choreiform disorders (15.8%), dyskinesias/dystonia (15.8%), and myoclonus (7.9%). The orofacial "candy sign" was noted in 7.9%. In 10 cases, complex presentations mimicked progressive supranuclear palsy, corticobasal degeneration, Creutzfeldt-Jakob disease, and autoimmune encephalitis. CSF serology was positive in 84.2% of cases. Imaging showed cerebral or cerebellar atrophy (34.2%), basal ganglia infarction (15.8%), white matter changes (15.8%), hydrocephalus (5.3%), or normal scans (18.4%). Penicillin was mainstay of therapy (57.9%). Outcomes included marked improvement in 44.7%, partial recovery in 34.2%, persistent decline in 15.8%, and death in 5.3%.

Neurosyphilis should be recognized as a treatable cause of secondary movement disorders. Ataxia and parkinsonism predominate, but frequent misdiagnosis delays therapy.