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Creutzfeldt-Jakob Disease

Creutzfeldt-Jakob disease is usually a sporadic disease, although 5 to 15 percent of cases have an autosomal dominant pattern of inheritance. Regions of high incidence and prevalence resulting from the presence of families with CJD, are scattered throughout the world, most prominently in parts of Libya and North Africa and in Slovakia. CJD is not contagious, but person-to-person spread of the disease has occurred following transplantation of corneas or dural grafts obtained from infected individuals. Isolated cases also have been attributed to improperly decontaminated neurosurgical instruments and stereotactic intracerebral depth electrodes. Approximately 50 cases have been reported in patients with panhypopituitarism who received supplemental cadaveric human growth hormone therapy and in patients who received cadaveric human gonadotropins for treatment of bovine spongiform encephalopathy.

CJD typically presents as a rapidly progressive dementia with prominent associated myoclonus. Clinical manifestations are protean and often include combinations of severe and progressive dementia, pyramidal and extrapyramidal motor disturbances, and signs and symptoms of cerebellar dysfunction. Clinical and pathologic subtypes with predominant involvement of specific regions of the brain have been described (e.g., occipital, thalamic, and cerebellar types). Early signs of mental impairment may be manifested as slowness.

Laboratory tests are helpful in excluding other causes of rapidly progressing dementia. The CSF is typically unremarkable, although the protein level may be mildly elevated. A pleocytosis is unusual.

The pathologic hallmarks of CJD are spongiform changes (small round vacuoles) within the neuropil, neuronal loss, hypertrophy and proliferation of glial cells, and absence of significant inflammation or white matter involvement. Pathologic changes are strongest in the cortex but are often prominent in the basal ganglia, cerebellum, and thalamus. The brainstem and spinal cord are usually spared.

A recent summary of 300 cases of prion disease studied at the National Institutes of Health found that 79 percent of sporadic CJD cases were transmissible, 79 percent involved spongiform neuropathologic changes, and in 83 percent, protease-resistant prion proteins were detected in western immunoblots of brain tissue extracts. All iatrogenic CJD cases and all kuru cases were transmissible and had spongiform changes and positive immunoblots. Cases of familial CJD, GSS syndrome, and fatal familial insomnia showed more variable results.

CJD is invariably fatal, and no specific therapy has been proven effective.

Approximately a dozen cases of a variant form of CJD have been identified in the United Kingdom. It has been suggested that these cases are linked to bovine spongiform encephalopathy (BSE), perhaps as a result of human.