In the latest article in our Clinical-Problem Solving series, an 89-year-old man was brought to the emergency department by his wife and son for an evaluation of changes in cognition and personality. Six months earlier, he began needing help managing finances and operating his computer. He had poor memory for recent events and difficulty expressing himself.
Because most dementias eventually progress to global neurologic dysfunction, it is important to focus on the early clinical manifestations and the course of decline over time to obtain clues to the diagnosis.
Clinical Pearls
• What are the most frequent causes of dementia that progresses in weeks to months?
The most frequent causes of dementia that progresses in a matter of weeks to months are prion diseases, including sporadic Creutzfeldt-Jakob disease, acquired Creutzfeldt-Jakob disease, and genetic prion disease. Other conditions that may cause rapidly progressive dementia include other neurodegenerative dementias (such as frontotemporal dementia, corticobasal degeneration, progressive supranuclear palsy, dementia with Lewy bodies, and Alzheimer’s disease) and autoimmune encephalopathies. Less often, vascular, infectious, neoplastic, toxic, metabolic, and psychiatric conditions may cause rapidly progressive dementia.
• What is the characteristic clinical presentation in Creutzfeldt-Jacob disease?
Creutzfeldt-Jakob disease typically causes rapid cognitive decline and myoclonus, although it can produce a wide variety of neurologic symptoms, including visual, pyramidal, extrapyramidal, oculomotor, psychiatric, and sensory symptoms, as well as ataxia and insomnia.
Morning Report Questions
Q: How is Creutzfeldt-Jakob disease diagnosed?
A: An MRI finding of restricted diffusion confined to the gray matter of the cortex (known as a cortical ribbon sign), deep nuclei (the striatum or thalamus), or both in patients with rapidly progressive dementia is sensitive and specific for Creutzfeldt-Jakob disease. The characteristic EEG finding in this disease is generalized, periodic, biphasic or triphasic sharp-wave complexes of 1 to 2 Hz. Although this finding has high specificity for Creutzfeldt-Jakob disease, it is relatively insensitive. An elevated level of 14-3-3 protein in the CSF has been reported to have a sensitivity of up to 86% and a specificity of 68 to 74% for Creutzfeldt-Jakob disease overall, although results may vary according to the subtype. False positive results have been reported in patients with many other neurologic disorders. A definitive diagnosis of prion disease requires a positive result for protease-resistant PrPSc on pathological analysis of tissue from the brain, but brain biopsy is rarely performed because of the potential risk to those who are exposed to the tissue and the low likelihood that confirmation of the diagnosis will alter the plan of care.
Q: What are the forms of Creutzfeldt-Jakob disease and how is each acquired?
A: There are several forms of Creutzfeldt-Jakob disease, including sporadic, familial, iatrogenic, and variant. Sporadic Creutzfeldt-Jakob disease accounts for approximately 85% of cases, with an annual incidence of 1 case per 1 million people. In this form of the disease, it is unclear how the initial conformational change in the prion occurs. The familial form of the disease accounts for 10 to 15% of cases and results from any of several autosomal dominant mutations in the prion protein gene (PRNP). Iatrogenic Creutzfeldt-Jakob disease results from exposure to tissue from a person with the disease. These cases are rare (accounting for <1% of all cases of Creutzfeldt-Jakob disease), and most are traced to exposure to cadaveric human pituitary hormones or dural grafts. The variant form of Creutzfeldt-Jakob disease is a human prion disease caused by ingestion of the prion responsible for bovine spongiform encephalopathy. The majority of cases have occurred in the United Kingdom and France.
