The clinical diagnosis during life rests mostly on the recognition of one of the clusters of typical clinical features, particularly the special rate of rapid progression of dementia—much more quickly than that of common degenerative diseases—coupled with stimulus-sensitive myoclonus and the characteristic MRI and EEG changes that occur in most patients (see below).
The disease is invariably fatal, usually in a few months and almost always less than a year from the onset. In approximately 10 percent of patients, the illness begins with almost stroke-like suddenness and runs its course rapidly, in a matter of a few weeks. At the other extreme, a small number of patients have reportedly survived for 2 to 10 years, but these reports should be accepted with caution; in some of them, the illness appears to have been superimposed on Alzheimer or Parkinson disease or some other chronic condition that predated the prion illness.
The routine CSF and other laboratory tests are normal—useful findings in that they exclude a number of chronic inflammatory causes of dementia such as neurosyphilis. In most patients, the EEG pattern is distinctive, changing over the course of the disease from one of diffuse and nonspecific slowing to one of stereotyped high-voltage slow(1to 2-Hz) and sharp-wave complexes on an increasingly slow and low-voltage background (see Fig. 2-5G). The high-voltage sharp waves, which give the appearance of periodicity (they have been called pseudoperiodic), are synchronous with the myoclonus, but may persist in its absence.
MRI of the brain has now been appreciated to show hyperintensity of the lenticular nuclei on T2-weighted and diffusion-weighted images in the basal ganglia and cortex when the disease is fully established (Fig. 32-5). Long contiguous segments of the cortex, as well as various parts of the basal ganglia, show these alterations in a pattern that is characteristic and mistakable only perhaps for the appearance of diffuse cerebral anoxia. According to Shiga and colleagues, these changes occur in 90 percent of cases (cortex more often than caudate or lenticular nuclei and sometimes both), making them potentially the most sensitive test for the disease but the proportion has been lower in our patients. Complicating the interpretation of the MRI findings in this disease have been reports from Japan of extensive white matter lesions in several autopsy-proven cases (Matsusue et al).
There are helpful confirmatory laboratory tests but they are not always necessary. Hsich and colleagues described the finding by immunoassay of peptide fragments of normal brain proteins, termed “14-3-3.” This test was useful in separating CJD from other chronic noninflammatory dementing diseases but it has been sometimes disappointing, giving both false-positive and false-negative results. A summary publication has indicated an overall sensitivity from pooled reports of 92 percent and specificity of 80 percent (report of the Guidelines Development Committee of the American Academy of Neurology). The 14-3-3 test has been supplanted by RT-QuIC (real-time quaking induced conversion), which is protein amplification technique based on seeding by recombinant prion protein (see McGuire et al). It can be used in CSF, brushings of nasal mucosal (see Orru et al), or other tissue. Prions have been detected in the urine of patients with variant CJD (see Moda et al).
The National Prion Disease Pathology Surveillance Center, which was established at Case Western Reserve University, is available to assist clinicians by performing, free of charge, a variety of specific diagnostic tests (accessible through http://www.cjdsurveillance.com).