Atypical Presentations of Neurosyphilis: The Great Imitator Revisited

Abstract

Background Syphilis is a complex disease with a wide range of clinical manifestations. Neurosyphilis, a complication affecting the central nervous system, can occur at any stage of the disease, particularly in untreated cases. While classical forms are well documented, atypical presentations remain underrecognized, leading to diagnostic delays. This study explored atypical neurosyphilis cases at the Agadir University Hospital Center, Agadir, Morocco, emphasizing early recognition and management. Methods This retrospective study included patients with neurosyphilis for over two years. Ethical approval was obtained from all participants. All patients had a positive Treponema pallidum hemagglutination assay (TPHA) and cerebrospinal fluid (CSF) analysis. The diagnosis was based on either a reactive CSF Venereal Disease Research Laboratory (VDRL) test, a positive CSF TPHA test, or CSF lymphocytic pleocytosis associated with neurological symptoms. Data on demographics, clinical presentation, diagnostic findings, treatment, and outcomes were analyzed. Results Over a two-year period, 157 patients were diagnosed with syphilis, including 29 cases of neurosyphilis. The mean latency between primary syphilis and the onset of neurological symptoms was 20 years (range: 2-33 years). Meningovascular neurosyphilis (11 cases), chronic meningoencephalitis (6 cases), and tabes dorsalis (4 cases) were the most frequent classical forms. Seven (24.1%) patients exhibited atypical syndromes, including visual impairment, cerebellar ataxia, parkinsonism, sixth cranial nerve palsy, and epilepsy. Investigations confirmed a diagnosis of neurosyphilis. Treatment with intravenous ceftriaxone or penicillin led to clinical improvement. Conclusion Atypical neurosyphilis presentation complicates diagnosis, particularly in non-endemic areas. This study highlights the need to consider neurosyphilis in patients with unexplained neurological disorders, particularly in high-risk populations.

Keywords: atypical cases; great imitator; neurosyphilis; prevention; treponema pallidum.

Figure 1. Neurosyphilis cases with the different presentations

Figure 2. (A) MRI of the brain (T2 sagittal section) showing right optic atrophy with enlargement of the optic nerve sheath (yellow arrow) and hyperintense signals in the right optic nerve (red arrow). (B) Fundus examination showing cupping and pallor of the optic disc (red arrow). (C) Humphrey visual field test showing total vision loss in both eyes.

Figure 3. A. Brain MRI (T2 sagittal section) shows diffuse atrophy, predominantly in the olivo-ponto-cerebellar region, as observed in the fourth patient case (blue arrow). B. Brain MRI (T2 FLAIR coronal section) showing bilateral hyperintense signals in the striatum in the fifth patient case (red arrows). C. Brain MRI (CISS sequence) showing leptomeningeal and VI cranial nerve involvement in the sixth patient case (yellow arrows).

CISS, constructive interference in steady state; FLAIR, fluid-attenuated inversion recovery

Figure 4. EEG showing paroxysmal generalized spike and spike-wave discharges, predominantly localized in the posterior regions (red arrows).