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Creutzfeldt-Jakob disease (CJD), the most common form of human prion diseases, is a rare and rapidly progressive neurological fatality. Several factors contribute to its challenges in diagnosis. For example, delayed and variable presentations, low awareness of the disease, limited testing sites, and the need for tissue pathology for confirmatory diagnosis. We report a rare sporadic case of CJD that mimics psychiatric disorders and stroke, involves a permanent pacemaker, and needs repeated cerebrospinal fluid (CSF) collections. Our patient has had multiple hospitalizations for his different chief complaints along with his rapidly deteriorating mental status each time. After ruling out common etiologies based on his presentations, we arrive at our diagnosis by combining the classic clinical features, characteristic electroencephalogram (EEG), and 14-3-3 protein in CSF. Magnetic resonance imaging (MRI) revealed cortical ribbon pattern, but this was not seen in the initial radiology report. In conclusion, it is imperative to consider CJD in differential diagnosis in patients with variable neuro-psychiatric manifestations after excluding other potential causes, especially in patients with recurrent hospitalizations due to rapidly declining mental state. In addition, effectively obtaining and interpreting critical supporting studies allow timely diagnosis to offer family condolences and perhaps, clinical research opportunities to further investigate disease therapeutic options.

Case report: challenges in making the diagnosis of sporadic Creutzfeldt-Jakob disease