The varied neuropsychiatric presentations of Creutzfeldt-Jakob disease.

Received May 29, 1998; revised October 16, 1998; accepted October 23, 1998. From the Department of Psychiatry, Mayo Clinic, Rochester, Minnesota. Address reprint requests to Dr. Rummans, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905. Copyright 1999 The Academy of Psychosomatic Medicine. Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative dementing illness with an incidence of roughly one case per million annually. CJD results from a prion infection of the central nervous system with both cortical and subcortical manifestations. Prion diseases, also referred to as spongiform encephalopathies because of their characteristic pathologic appearance, include several human diseases with CJD being the most common. A prion is a protein that acts as the infectious agent, differing from a virus as it does not include any nucleic acid. CJD mainly occurs sporadically but is both heritable and transmissible, although the mode of transmission is unknown. Ten to fifteen percent of cases occur in a familial pattern. Human-to-human transmission is rare with only iatrogenic cases being reported. Clinically, CJD usually occurs in middle or late life with a few reports of younger presentations. Clinical features are quite varied, as outlined in Table 1, but often include dementia, disturbances of gait, incoordination, rigidity, and myoclonus. The onset of illness may be gradual, but the progression of disease is rapid, ending in death usually within 1 year. Diagnosis of CJD may be difficult, with routine blood counts, chemistries, and cerebrospinal fluid (CSF) usually being normal. Both CT and MRI may be normal or reveal cerebral atrophy late in the course of the disease. Classic EEG changes are those of periodic (1–2 cycles/second) discharges of large (triphasic) sharp wave or “burst suppression” high-voltage activity. Although EEG is generally considered a useful tool for the diagnosis of CJD, some cases have been reported where the EEG is nonspecific. CSF evaluation may reveal CJD-specific proteins or genetic testing may reveal mutations in the prion protein. However, neither of these evaluations is routinely performed and they are difficult to obtain. Pathologic examination reveals a degenerative picture with gross atrophy, neuronal loss, gliosis, and vacuoles developing in neurons, giving a characteristic spongy appearance. There have been only a few case reports with little attention in the literature given to the psychiatric manifestations of CJD. In fact, there is a well-described prodromal phase of the disease in which symptoms may be vague and can include weight loss, fatigue, dizziness, headache, disorders of sleep, impaired judgment, and unusual behavior. An unusually intense emotional response to the environment as well as delusions, hallucinations, and agitation may be interpreted as a depressive or psychotic illness. In review of 232 experimentally transmitted cases of sporadic CJD, approximately one-third of the cases at the outset manifested mental deterioration only, with some form of “emotional abnormality” found in the majority of cases. Ten percent of patients with CJD are admitted to psychiatric wards. The following case illustrates how diagnosing CJD is difficult for psychiatrists, neurologists, and internists alike because of the variability and complexity of its presentation.