Mechanisms of Neurosyphilis-Induced Dementia: Insights into Pathophysiology.

Abstract

Neurosyphilis-induced dementia represents a severe manifestation of tertiary syphilis, characterized by cognitive and neuropsychiatric impairments. This condition arises from the progression of syphilis to the central nervous system, where the spirochete causes damage through invasion, chronic inflammation, and neurodegeneration. The pathophysiology involves chronic inflammatory responses, direct bacterial damage, and proteinopathies. Treponema pallidum triggers an inflammatory cascade, resulting in neuronal injury and synaptic dysfunction. Abnormal protein accumulations, including TAR DNA-binding protein 43 (TDP-43) and tau, contribute to neuronal loss and cognitive decline. Seizures, psychiatric symptoms, and motor deficits further complicate the progression of dementia. Diagnosis includes clinical assessment, cerebrospinal fluid analysis, and neuroimaging. Diagnostic tests include CSF-VDRL, FTA-ABS, and neuroimaging techniques such as MRI and PET scans, which help detect structural changes and confirm neurosyphilis. Management of neurosyphilis-induced dementia involves antibiotic therapy and psychotropic medications to address both infectious and symptomatic components. While penicillin remains the cornerstone of treatment, psychotropic agents, including haloperidol, risperidone, quetiapine, and divalproex sodium, can manage psychiatric symptoms. However, careful monitoring is required due to potential side effects and interactions with ongoing treatment. Overall, early diagnosis and comprehensive management are crucial for mitigating the cognitive and neuropsychiatric impairments associated with neurosyphilis-induced dementia.