A 60-year-old male with history of alcohol use disorder presented nine years after initial penile lesion. He experienced seven months of prodromal symptoms with lightheadedness, nausea, fatigue, and brain fog. Two months prior to presentation, he experienced acute decline (severe cognitive decline, dysarthria, weight loss, and ataxia). Initially treated as Wernicke’s encephalopathy. At time of presentation, he exhibited episodic rhythmic right-hand flexion and involuntary saccades to the right, perseveration, aphasia, horizontal nystagmus, Argyll Robertson pupils, broad-based gait, and startle myoclonus.

MRI demonstrated asymmetric cortical ribboning along the left hemisphere on diffusion-weighted imaging. EEG revealed lateralized periodic discharges, maximally over the left frontocentral region (F3>F7>C3). Lumbar puncture showed lymphocytic pleocytosis. Syphilis serology was positive in serum (RPR titer 1:256) and CSF (VDRL 1:32, IgG index 8). Five days later, CSF RT-QuIC returned positive (t-Tau/p-Tau ratio 220, total-Tau 4198), supporting a diagnosis of CJD. Limited improvement after five days of intravenous penicillin G. He was discharged to hospice, passing away four days later. Pending autopsy.