Neurosyphilis and Parkinsonism: Overlapping Pathophysiology and Emerging Therapeutic Insights

Neurosyphilis, caused by Treponema pallidum, is a complex neurological condition arising from untreated syphilis and can present with diverse manifestations, including Parkinsonism-like motor dysfunction. Its pathophysiology involves Blood-Brain Barrier (BBB) disruption, dopaminergic neuronal loss, and neuroinflammatory cascades that resemble mechanisms seen in idiopathic Parkinson's Disease (PD).

A literature review from PubMed, ScienceDirect, Scopus, and Google Scholar (2014- 2025) explored studies on neurosyphilis, dopaminergic degeneration, BBB dysfunction, neuroinflammation, diagnostics, and treatments, including antibiotics, neuroprotective agents, nanocarriers, and vaccines. A narrative synthesis was conducted due to the variation in study designs.

The decreased BBB permeability, extracellular matrix degradation, TLR activation, reactive microglia, and neuronal cell death are mechanisms linking syphilis and idiopathic PD. Neurologists differentiate between neurosyphilis and idiopathic PD through neuroimaging and cerebrospinal fluid analysis (CSF). Treatment for neurosyphilis primarily involves penicillin, with alternatives such as ceftriaxone and doxycycline. Emerging evidence suggests that β-lactam antibiotics and nanoparticle systems targeting neuroinflammatory pathways may offer neuroprotective effects.

These findings exhibit considerable mechanistic overlap between neurosyphilis and PD, particularly concerning BBB dysfunction, dopaminergic neurodegeneration, and neuroinflammation. These common pathways lead to symptoms similar to those of PD and complicate clinical manifestation. Neuroimaging and CSF analyses are still very important for making an accurate diagnosis. Further study is needed to clarify disease mechanisms and to evaluate novel therapeutic approaches.

Neurosyphilis may present with Parkinsonian features due to PD-like neurodegenerative mechanisms. Early diagnosis and timely antimicrobial therapy are crucial to prevent irreversible neurological damage, while emerging neuroprotective strategies warrant further investigation.