Sleep abnormalities with REM disorder in experimental Creutzfeldt-Jakob disease in cats: a new pathological feature

Alterations in sleep organization were studied during the clinical phase of experimental Creutzfeldt-Jakob disease (CJD) in cats. Twenty months after intracerebral inoculation of a CJD agent, cats developed clinical signs including behavioral changes, diminished grooming activity, dysmetria, startle reflex, myoclonus, and unusual sleep abnormalities. Rapid eye movement (REM) sleep displayed a new and irreversible organization, with a continuous and constant pseudoperiodic pattern of rapid eye movements, synchronous with diffuse bursts of cortical abnormalities and with ponto-geniculo-occipital (PGO) wave activity. Computer analysis revealed a constant morphology of cortical bursts and their temporal relationship with ocular episodes. Induction of PGO wave activity with benzoquinolizine derivative Ro 4-1284 demonstrated the PGO-dependent nature of the cortical alterations. Abnormal unresponsive states were observed during REM sleep phases and arousal thresholds were increased in CJD cats during REM sleep. The percentages of wakefulness and slow-wave sleep were reversed in these animals. Preliminary neuropathological observations included discrete to minimal spongiosis of cerebral gray matter and a remarkably focalized intracytoplasmic vacuolation in neurons of the raphé system. Our findings suggest that particular neuronal systems involved in sleep regulation are impaired in CJD cats.