A panencephalopathic type of Creutzfeldt-Jakob disease with selective lesions of the thalamic nuclei in 2 Swiss patients

Creutzfeldt-Jakob disease (CJD), a subacute spongiform encephalopathy, is generally included among the group of human and animal diseases which is transmissible by a non-conventional agent, the prion, whose expression is conditioned by the host's genome. The process leading to neuropathological changes is still unknown. We report the neuropathological findings in 2 cases of the 'panencephalopathic' variant of CJD, which is relatively common in Japan, but extremely rare in Europe and North America. When compared with the classical form this variant is characterized by a relatively long clinical course with persistent vegetative state and primary involvement of the white matter presenting in the form of demyelination and gemistocytic gliosis. The selective involvement of certain thalamic nuclei is a particular pathological feature in both our cases. There was practically complete neuronal loss with diffuse gliosis of the anteroventral (AV) and dorsomedial (DM) nuclei, while the neuronal loss in the pulvinar remained moderate; the other nuclei were apparently spared. A similar involvement of the thalamus has been reported in fatal familial insomnia, a recently described prion disease in which these lesions are predominant. A comparable distribution has also been observed in other degenerative neurological diseases such as Steele-Richardson-Olszewski disease, Alzheimer disease, and thalamic dementia (selective thalamic atrophy or with multisystemic degeneration). The AV and DM nuclei, commonly referred to as 'limbic thalamus' represent phylogenetically the most recent thalamic structures and would appear to play an important role in the superior functions in man as memory, attention and awareness. In our cases thalamic lesions are selective, bilateral, and symmetric, not explained by Wallerian degeneration. These lesions may be due to the primary pathogenetic properties of the infectious agent. The rapid clinical evolution in a persistent vegetative state could be consequential to precocious and severe disfunction of the limbic thalamus.