This patient most likely has sporadic Creutzfeldt-Jakob disease (CJD). She has a compatible clinical presentation, with acute onset of rapidly progressive dementia, ataxic gait, and myoclonus. In addition, the cerebrospinal fluid (CSF) demonstrates elevated 14-3-3 protein. Brain biopsy would be required for definitive diagnosis. Sporadic CJD is the most common form of human prion disease, with onset usually in the seventh decade of life. Myoclonus is seen in 90% of patients. In the appropriate clinical setting, the CSF test for the 14-3-3 protein is relatively specific and sensitive for this diagnosis. Other disorders that increase CSF 14-3-3 protein, such as acute stroke or multiple sclerosis, are rarely confused with CJD clinically.

Patients with Alzheimer disease have a more insidious and chronic presentation of dementia and other neurologic findings than seen in this patient.

Kuru was the first prion disease recognized to be transmissible and was linked to cannibalism among tribes of Papua, New Guinea. Common initial manifestations of kuru include headaches and joint pain. Subsequent symptoms include ataxia, dysarthria, and tremors. Myoclonus and dementia are generally seen only late in the illness. The incidence of kuru has decreased with the cessation of the practice of cannibalism.

Neurosyphilis may be asymptomatic or may manifest as syphilitic meningitis, meningovascular syphilis, tabes dorsalis (demyelination of the posterior columns of the spinal cord), or general paresis. General paresis is a chronic meningoencephalitis that results in gradual, progressive loss of cortical function. The CSF is nearly always abnormal, with a lymphocytic pleocytosis and increased protein.