Snapshot A 55-year-old man is brought to the emergency department by his wife after falling down and having a generalized tonic-clonic seizure. Over the course of the past few months, she felt he has been having abnormal behavior. He was previously admitted to the inpatient psychiatric service after having delusions and violent outbursts. On physical exam, the patient was nonparticipatory due to being postictal. A noncontrast CT head was unremarkable. He was admitted to the neurology service for evaluation of his seizures. He was placed on video electroencephalogram and it was remarkable for biphasic synchronous sharp wave complexes. An MRI brain demonstrated cortical ribboning with caudate head signal changes. Cerebrospinal fluid analysis was remarkable for the presence of 14-3-3 protein. Introduction Definition human prion disease that leads to a rapid progressively dementia Types spontaneous Creutzfeldt-Jakob disease (CJD) most common form results in the spontaneous formation of prions for unknown reasons familial CJD spotaneous formation of prions secondary to autosomal dominant mutations acquired CJD iatrogenic transmission (e.g., neurosurgical transmission) dietary exposure Pathogenesis Abnormal prion isoform leads to prion misfolding within neurons Presentation Symptoms/physical exam rapidly progressive mental deterioration poor concentration, memory, and executive function myoclonus provoked by startle (thus "startle myoclonus') Imaging MRI brain findings cortical ribboning signal intensity in the putamen and head of the caudate on T2 and FLAIR Studies Electroencephalogram synchronous sharp wave complexes (has a very high specificity) Lumbar puncture presence of 14-3-3 protein a negative study does not exclude CJD Neuropathology spongiform vacuolation abnormal accumulation of abnormal prion protein Differential Alzheimer disease (AD) differentiating factors AD does not rapidly progress like CJD Treatment There is no effective treatment for this fatal disease Complications Aspiration and pneumonia secondary to dysphagia (most common cause of death) Prognosis Typically death occurs within 1-2 years of symptom onset