Self Management of Fatal Familial Insomnia. Part 1: What Is FFI?

Joyce Schenkein, PhD; Pasquale Montagna, MD

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In This Article

Does Insomnia Cause Death?

The precise cause of death in FFI patients is unclear. Although neural degeneration predicts long-term death, as in all prion diseases,[14] it is also possible that some functions that are disrupted or unbalanced by the ongoing disease (such as sleep and autonomic function) may terminate life even before critical degeneration. This might particularly be suggested by the rapid disease course of the Met-Met patients who, upon autopsy, show the least pathology, as measured either by apoptosis, neural degeneration, or PrPres distribution. This important possibility suggests that aggressive symptomatic treatment of insomnia may extend life.

The benefits of sleep are well documented in both humans and animals. In animal studies, total sleep deprivation resulted in death (within 4-6 days for puppies[15] and 2-4 weeks for rats[16]). Death is preceded by weight loss despite increased food intake, debilitation, a decline in thyroid hormone, elevated sympathetic activation, and poor resistance to infection.[17] Compared with yoked controls, glucose utilization decreases in the hypothalamus, thalamus, and limbic system. Hypocretin levels increase in the lateral hypothalamus[18] leading to wakefulness, stimulation of hypothalamic-pituitary axis, and sympathetic activation. A drop in body temperature 2-3 standard deviations below baseline is an irreversible harbinger of death.[17]

Postmortem analysis of sleep-deprived puppies describes capillary hemorrhages in the cerebral grey matter and chromatolysis and vacuolation in the cytoplasm of cells in the cerebral cortex, particularly the frontal lobe.[15] Rats show significantly lower liver and spleen weights and higher adrenal weight,[16] suggesting a stress response. Everson found no structural damage in the brains of these rats.[17] However, others have reported degenerative changes in the supraoptic nucleus (SON) of the anterior hypothalamus.[19] The SON, an integration site for surrounding hypothalamic nuclei, orchestrates many homeostatic mechanisms such as blood pressure, vascular resistance, and body temperature. If SON function is impaired in sleep deprivation, then subsequent changes in internal state may be a secondary consequence of the insomnia rather than a primary one.[19]

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