Fatal familial insomnia

Abstract

In 1986, we reported two anatomoclinical observations of a familial condition that we called "fatal familial insomnia" (FFI). We now present the pedigree as well as the clinical and neuropathologic findings in five new subjects. The pedigree includes 288 members from six generations. Men and women are affected in a pattern consistent with an autosomal dominant inheritance. The age of onset of the disease varies between 37 and 61 years; the course averages 13 months with a range of 7 to 25 months. Progressive insomnia (polygraphically proven in two cases); autonomic disturbances including hyperhidrosis, hyperthermia, tachycardia, and hypertension; and motor abnormalities including ataxia, myoclonus, and pyramidal dysfunction, were present in every case, but with variable severity and time of presentation. Sleep and autonomic disorders were the earliest signs in two subjects, motor abnormalities were dominant in one, and others had intermediate clinical patterns. Pathologically, all the cases had severe atrophy of the anterior ventral and mediodorsal thalamic nuclei. Other thalamic nuclei were less severely and inconsistently affected. In addition, most of the cases had gliosis of the cerebral cortex, a moderate degree of cerebellar atrophy with "torpedoes," and severe atrophy of the inferior olivary nuclei. One case also showed spongy degeneration of the cerebral cortex. We conclude that all the lesions were primary, and that FFI is a multisystem disease in which the different structures are primarily affected with different severity. The insomnia appears to correlate best with the major thalamic pathology. The possibility that FFI belongs to the group identified as prion diseases or diseases transmitted by unconventional agents is examined.

Fulminant corticobasal degeneration: Agrypnia excitata in corticobasal syndrome

“…The pattern of tau deposition within the thalamus, indicating the severity of involvement by CBD, partially overlaps with areas involved by FFI, namely the dorsomedial nucleus. The anteroventral nucleus, typically severely affected in FFI, 6 appeared relatively uninvolved in this case. Given the rarity of severe sleep disturbances in CBD, future studies of the relationship between thalamic involvement and sleep disorders in CBD will require a large multisite clinicopathologic study.…”

“…This system has been described previously. 6 Briefly, our system includes 32 light sources and 32 photodetectors offering a total of 128 NIRS channels with an average interoptode distance of 3 cm. As the patient stood up, blood pressure gradually decreased from 134/70 mm Hg to 90/54 after 10 minutes, at which point he experienced tremor of the right forearm and hand associated with weakness of both legs and mild dysarthria (video).…”

Fatal familial insomnia: Clinical features and early identification

“…The diagnostic importance of polysomnography in FFI noted in our study has been emphasized by other authors. 2,6,12,14 [ 18 F]FDG-PET studies were reported to support FFI diagnosis. 9 Selective thalamic changes were seen on PET in only two of our patients, whereas widespread cortical hypometabolism without clear preference for a particular cortical region was found in five patients.…”

Different Behavior toward Bovine Spongiform Encephalopathy Infection of Bovine Prion Protein Transgenic Mice with One Extra Repeat Octapeptide Insert Mutation

“…Infectious TSEs have been described in animals and humans, the prototypes of which are scrapie in sheep and goats (Adams, 1986), bovine spongiform encephalopathy (BSE) in cattle (Prusiner, 1998), and kuru (Alpers and Rail, 1971) or variant Creutzfeldt-Jakob disease (vCJD) in humans Hill et al, 1997). Spontaneous and inherited TSEs have been mainly identified in humans and include CJD (Beck et al, 1969), Gertsmann-Sträussler-Scheinker disease (Bendheim, 1984;Collinge et al, 1989), and fatal familial insomnia (Manetto et al, 1992;Medori et al, 1992;Dormont, 1994;Goldfarb et al, 1994a).…”