Fatal familial insomnia is a
prion disease in which a selective thalamic degeneration leads to total
sleep deprivation,
hypertension,
dysautonomia, adrenal overactivity, and impaired motor functions. With patients under continuous recumbency and polysomnographic control, we assessed the changes in the 24-hour patterns of blood pressure, heart rate, plasma
catecholamines,
corticotropin, and serum
cortisol in three patients at different stages of the disease. Six healthy volunteers were used as control subjects. A dominant 24-hour component was detected at rhythm analysis of all variables, both in patients and control subjects. In the patients, the amplitudes gradually decreased as the disease progressed, leading to the obliteration of any significant dirunal variation only in the preterminal stage. A shift in phase corresponded to the loss of the nocturnal fall in blood pressure in an early stage of the disease, when nocturnal
bradycardia was still preserved. Plasma
cortisol was high and became increasingly elevated, whereas
corticotropin remained within normal levels; abnormal nocturnal peaks appeared in their circadian patterns. The disrupted patterns of
cortisol and blood pressure preceded the development of
hypertension and severe
dysautonomia, which in turn were paralleled by increasing
catecholamine and heart rate levels. Our data demonstrate that in patients with
fatal familial insomnia the changes detectable in the rhythmic component of diurnal blood pressure variability result in a pattern of secondary
hypertension. Disturbances in thalamic, pituitary-adrenal, and autonomic functions seem to be involved in mediating these changes.