Prion Disease: A Challenging Diagnosis

Introduction: Human prion diseases are a group of rare encephalopathies resulting in rapidly progressive dementia and ultimately death. While there are no effective treatments for any form of prion disease, prompt and efficient diagnosis is essential to prevent the spread of the self-propagating protein, which may occur through aerosols, and avoid unnecessary or invasive testing. Diagnosis relies largely on physical examination, with many nonspecific findings, and laboratory testing, which has wide ranges of reported accuracy and high false positive rates with diseases such as Alzheimer’s dementia. Methods: Patients who underwent testing for prion disease were retrospectively identified from the electronic health records at a single-center university hospital. Presenting symptoms, as well as laboratory, radiographic, and electroencephalogram findings, were recorded and analyzed by group of final diagnosis, including prion disease, not prion disease, and undiagnosed. Results: There were 27 patients identified, two who had a final diagnosis of prion disease, 20 who had a formal diagnosis other than prion disease, and five who remained undiagnosed until death. There was a high degree of overlap in presenting symptoms. A high rate of false positive laboratory values, higher than previously reported, occurred for both the protein 14-3-3 and total Tau in cerebrospinal fluid. Magnetic resonance imaging ruled out prion disease most often. Testing with Rt-QuIC was the most diagnostic laboratory test. Both patients with a diagnosis of prion disease developed pneumonia and died of respiratory failure, and a total of nine patients required intubation for respiratory infections. Conclusion: Diagnosing prion disease remains a challenge due to nonspecific physical exam findings and symptoms and the high false positive rates of the laboratory algorithm. Testing with Rt-QuIC should be performed in patients that are critically ill or may have diseases known to cause high false positive rates of 14-3-3 or total Tau. Proper personal protective equipment should be used for any aerosol-generating procedure in patients who may have prion disease