Objective:

To highlight neurosyphilis as a reversible mimic of neurodegenerative and autoimmune cognitive disorders and emphasize the importance of diagnostic vigilance in patients with atypical disease progression.

 

Background:

Neurosyphilis is an uncommon but treatable cause of cognitive and behavioral decline that can resemble neurodegenerative and neuroinflammatory conditions. In patients with established dementia, acute or subacute deterioration is frequently attributed to expected disease progression, increasing the risk of diagnostic anchoring, delayed recognition of reversible etiologies, and exposure to inappropriate or delayed therapies.

Design/Methods:

Not applicable

Results:

A 77-year-old male with Alzheimer’s dementia, PTSD, hypertension, and hyperlipidemia presented with acute neuropsychiatric deterioration, including paranoia, impulsivity, wandering, irritability, and aggression, culminating in misidentification of a family member as an intruder. Examination revealed preserved long-term memory with impaired short-term recall, limited insight, gait ataxia, and a broad-based stance—features atypical for Alzheimer’s disease progression and concerning for alternative etiologies, including infectious and neuroinflammatory processes. Serum rapid plasma reagin was reactive. Cerebrospinal fluid analysis demonstrated elevated protein and pleocytosis with normal glucose; CSF-VDRL was non-reactive, highlighting known limitations in sensitivity. Despite this, the constellation of clinical findings and serologic evidence supported a diagnosis of late neurosyphilis. The patient was treated with a 14-day course of intravenous penicillin G, resulting in improvement in agitation and behavioral symptoms, though baseline cognitive deficits persisted.

Conclusions:

Neurosyphilis remains an important reversible differential diagnosis in patients with atypical cognitive decline and can closely mimic both neurodegenerative and autoimmune conditions. This case underscores the limitations of relying on a single diagnostic modality and highlights the need to avoid anchoring bias. Early recognition is essential to prevent misdiagnosis, inappropriate immunotherapy, and unnecessary morbidity, while optimizing patient outcomes.