Introduction: Neurological dysfunction is common in the acute care setting and espouses various etiologies which include infectious, inflammatory, and neurodegenerative in nature. Encephalopathy may be acute, chronic, or an acute manifestation of chronic illness. Risk factors of advanced age and existing co-morbidities are useful to determine underlying cause, however it is necessary to maintain a high index of suspicion in atypical scenarios. Termed “the great imitator”, complications of syphilis are increasingly rare due to the curative effectiveness of penicillin. Neurosyphilis is one of such complications which may occur anytime and should always be considered despite the possibility of confounding disease states. 

Case report: A 64-year-old male presented with several weeks of clinical decline and lethargy. He has a history of stroke, type 2 diabetes, and dementia. In November 2018, he presented with a painless penile ulcer identified as syphilitic chancre. RPR and FTA-ABS were positive. He was treated with a single dose of IM Benzathine Penicillin G 240,000IU and discharged home. A few months prior, patient was started on Donepezil for dementia. He remained at his neurological baseline until December 2021 when he was brought in for increased confusion, jerks and falls. Basic Labs were unremarkable. He was managed supportively and discharged from the ED. 

Two weeks after, he was brought in for unresponsiveness. Neurological function could not be fully assessed but showed intact reflexes. He was initially managed for aspiration pneumonia however began to spike fevers despite broad-spectrum antibiotics. A blood culture showed staph bacteremia. Patient’s neurological status remained poor with few episodes of agitation. Brain MRI showed profound atrophy. A repeat RPR and FTA-ABS were positive, HIV serology was unreactive. Patient was managed with staph-directed therapy and a 14-day course of IV Penicillin G. Unfortunately, his encephalopathy did not improve and he was ultimately transitioned to hospice care. 

Discussion: Neurosyphilis is a CNS infection due to Treponema pallidum. It develops 10 to 25 years after initial infection but may occur earlier, especially in immunocompromised patients. Early presentations include; asymptomatic, symptomatic meningitis, meningovascular syphilis, ocular, otosyphilis. General paresis, tabes dorsalis, or dementia are generally termed tertiary syphilis. Tertiary syphilis may mimic other neuropsychiatric diseases with features such as personality changes, forgetfulness, irritability, and sleep-wake cycle disorder. If left untreated, life expectancy is less than 5 years after symptom onset. Clinical features of neurosyphilis pose a diagnostic conundrum in the presence of other infectious foci like staph bacteremia, which may delay disease-focused therapy. Furthermore, the diagnosis of Alzheimer’s dementia should be one of exclusion, after other treatable causes of dementia have been ruled out.