FATAL FAMILIAL INSOMNIA - SLEEP, NEUROENDOCRINE AND VEGETATIVE ALTERATIONS

Fatal Familial Insomnia (FFI) is an autosomal dominant prion disease, characterized by prominent degeneration of the thalamus and involving impaired control of the sleep-wake cycle and of autonomic and endocrin e functions. Profound alterations in the sleep-wake cycle consist of p rogressive decrease or complete absence of sleep activity and loss of any intrinsic cyclic organization of residual sleep. Unbalanced sympat hergic activation with preserved parasympathetic drive, associated wit h chronic secondary hypertension and loss of the physiological nocturn al decrease in blood pressure constitute the characteristic autonomic changes. Neuroendocrine studies document hypercortisolism with abnorma l feed-back suppression of adrenocorticotrophic hormone, constantly el evated catecholamine levels and abnormal secretory patterns of growth hormone, prolactin and melatonin. Advanced stages of the disease are i nvariably characterized by the disappearance of any circadian autonomi c and neuroendocrine rhythmicity. FFI represents a model disease empha sizing the correlations among the different sleep, autonomic and neuro endocrine functions. Clinico-pathological correlations demonstrate the role of the thalamus as an integrative neural structure placed betwee n the limbic system and the hypothalamus and controlling the homeostat ic balance of the organism