A small proportion of all series is familial—varying from 5 percent reported by Cathala and associates to 15 percent of 1,435 cases analyzed by Masters and coworkers (1979). The occurrence of familial cases that are not in the same household may indicate a genetic susceptibility to infection. A small number of conjugal cases have also been reported suggesting the possibility of common exposure. However, the only clearly demonstrated mechanism of spread of the usual type of CJD is iatrogenic, having occurred in a few cases after transplantation of corneas or dural grafts from infected individuals, after implantation of infected electroencephalographic depth electrodes, and after the injection of human growth hormone or gonadotropins that had been prepared from pooled cadaveric sources (see Gibbs et al 1985). At least one neurosurgeon is known to have acquired the disease. Of some interest is the finding by Zanusso and colleagues of the infectious prion protein in the nasal mucosa of all nine patients studied with the sporadic disease. This suggests a route for entry into the nervous system of the aberrant prion and also a potential diagnostic test. The tonsils of patients affected with variant CJD may also show immunostaining for prions (see Hill et al).
Attention has been drawn to an outbreak of prion disease among cows in the British Isles (“mad cow disease,” bovine spongiform encephalopathy, BSE). Cows elsewhere have sporadically been found to be infected. The mini-epidemic began in 1986, with putative transmission of the disease to 24 humans. These patients were younger (average age of onset 27 years) than those with typical CJD (average age of onset 65 years) and manifested psychiatric and sensory symptoms as the first sign of illness; they did not exhibit the usual EEG findings even as the illness advanced to its later stages (Will et al). This has been called “new variant Creutzfeldt-Jakob disease (vCJD).” One reason for including a lengthy explanation of this illness is the potential for cases to appear in future years. It was shown that the prion strain in affected patients is identical to the one from affected cattle and different from the prion agent that causes sporadic CJD. The mode of transmission, presumed to be the ingestion of infected meat, is reminiscent of the propagation of kuru in New Guinea by ceremonial ingestion of brain tissue from infected individuals that opened the era of understanding of prion disease.
Prion (spongiform) encephalopathy of all types has now been firmly associated with the conversion of a normal cellular protein, PrPc to an abnormal isoform, PrPsc. The transformation involves a change in the physical conformation of the protein in which its helical proportion diminishes and the proportion of the b pleated sheet increases (see reviews by Prusiner). The current understanding is that the “infectivity” of prions and their propagation in brain tissue result from the susceptibility of the native PrP to alter its shape as a result of physical contiguity to the abnormal protein, a so-called conformational disease. Conformationally altered prions have a tendency to aggregate, and this may be the mode of cellular destruction that leads to neuronal disease. In contrast, familial cases of prion disease are thought to be the result of one of several gene aberrations residing in the region that code for PrPc.