Brainstem Sparing in Human Prion Disease: Sleep and Autonomic Function in a Long Survival Case Report

Abstract Background: The prion diseases are characterized by sleep disruption, with FFI typically characterized also by severe autonomic dysfunction and sympathetic hyperactivity. We report the results of an extensive neurophysiological and autonomic assessment in a CJD patient carrying the D178 mutation with the uncommon homozygosity for valine at codon 129. Results: A 47years old female presented with a memory impairment followed by progressive cognitive deficits and ataxia. The clinical picture slowly worsened to a state of akinetic mutism in about 2 years, and the patient died six years after the onset of symptoms. Repeated PSG and long-term actigraphic recordings, showed a peculiar, previously undescribed, pattern characterized by conservation of a rudimental circadian and ultradian rhythm, despite dramatic sleep micro-structure deterioration. We also observed a normal autonomic physiological response to orthostatic challenge and normal dynamic autonomic modulation during wake and sleep. The post-mortem brain pathology study, showed that neuronal loss was substantial in the cerebral cortex, diencephalon and thalami, but not in brainstem nuclei. Conclusions: We hypothesize that, despite a dramatic neurological picture (i.e. akinetic mutism) and a severe sleep micro-structural alteration, the persistence of an autonomic modulation and the persistence of a rudimental circadian and ultradian oscillation, are related to the relatively conserved anatomo-functional integrity of foundamental neuronal systems in the brainstem.