Abstract Background Prion diseases are rare, rapidly progressive, and universally fatal neurodegenerative disorders caused by misfolded prion proteins that induce structural changes in normal proteins, leading to neurotoxicity and neuronal loss. Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common subtype, accounting for approximately 90% of cases, with an annual incidence of one per million and a median survival of less than one year. Early symptoms are often vague, which can delay diagnosis. Case Presentation We describe a 55-year-old woman with a past medical history of asthma, diabetes, hypertension, dyslipidemia, and thyroid disease, who had adhered to a vegan diet. She initially presented to the emergency department with lightheadedness and blurry vision, previously attributed to vertigo. Her initial exam, labs, CT head, CT angiogram, and chest X-ray were unremarkable, and she was discharged with a presumptive diagnosis of presyncope. Subsequent outpatient MRI brain and nuclear medicine brain SPECT were also read as unremarkable. One month later, she returned with progressive debility, spasticity, double vision, delayed responses, and cognitive decline. Carbidopa-levodopa initiated for presumed Parkinson’s disease yielded no benefit. An EEG showed diffuse encephalopathy, and review of her prior MRI revealed subtle diffusion-weighted cortical ribboning. Lumbar puncture showed normal cell counts, mildly elevated protein, and pending CSF studies including 14-3-3, total tau protein, and RT-QuIC. The patient was discharged at her family’s request but soon returned with profound deterioration, including mutism and inability to ambulate. Repeat imaging revealed a superior sagittal sinus thrombosis, for which she was anticoagulated. Given her poor prognosis and suspected prion disease, the family elected for comfort care. She died within weeks of symptom onset. Posthumously, CSF biomarkers confirmed the diagnosis: markedly elevated 14-3-3 (42,389), total tau (7,194 pg/mL), and positive RT-QuIC assay. Discussion This case highlights the diagnostic challenges of sCJD, particularly in younger patients with atypical and nonspecific early presentations. The patient’s initial symptoms mimicked benign vestibular disorders, delaying recognition. Definitive diagnosis relied on RT-QuIC, which, despite excellent sensitivity and specificity, has a long turnaround time that limits real-time clinical utility. While no curative therapy exists, timely consideration of sCJD in rapidly progressive neurologic decline is essential for accurate prognostication, appropriate counseling, and potential trial enrollment. Conclusion sCJD remains a uniformly fatal disease with heterogeneous early manifestations. Maintaining a broad differential and recognizing subtle radiologic and clinical clues may facilitate earlier diagnosis, enabling families to prepare and, when available, consider investigational therapies. This abstract is funded by: None
Collins et al. (Fri,) studied this question.