The vast majority of patients are between 50 and
70 years old at the onset of the disease, although significantly younger
affected patients have been reported. The onset of familial cases is
significantly earlier than in other forms. The course of the illness may
last from a few weeks to several years, although in general it is rapidly
progressive. It is uniformly fatal, with the average length of survival from
onset of the disease being approximately 6 months. Affected patients present with
signs of dementia that often are accompanied by behavioral changes and
psychiatric anomalies. Characteristic electroencephalographic changes can be
detected (a slow background rhythm with superimposed periodic biphasic or
triphasic synchronous sharp-wave complexes), which are clinically often
accompanied by myoclonus and progressive motor dysfunction. Numerous other
neurologic symptoms such as pyramidal and extrapyramidal signs (muscular
rigidity), seizures, nystagmus, autonomic dysfunction, and signs of
cerebellar dysfunction (unsteady or atactic gait), may occur. Forgetfulness
or nervousness, supranuclear gaze paralysis, and loss of facial expression
may occur. Some neurologic features may subside in the terminal phase of the
disease. Autopsy reveals generalized brain atrophy; however, if the course
of the disease is rapid (i.e., death in less than 6 months), the macroscopic
changes may only be subtle. CJD is a spongiform encephalopathy resulting in
diffuse loss of neurons, reactive astrocytosis, and widespread vacuolization
of the neuropil. Electron microscopy locates the round vacuoles within the
neuroplasma and neuropil of the cortical gray matter. The vacuoles vary in
diameter from 1 to 50 μm and appear to contain membranous particles.