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| Fatal Familian Insomnia | Inheritance
In1992 was presented the pedigree as well as the clinical and neuropathologic findings in 5 new cases. Women and men were affected in a pattern consistent with autosomal dominant inheritance.
The age of onset varied between 37 and 61 years; the course averaged 13 months, with a range of 7 to 25 months.
Pathogenesis
In the research of fatal familial insomnia by Lugaresi 1986, pathologic changes were distinguished from those seen in the thalamic form of Creutzfeldt-Jakob disease, in which there is always cortical spongiosis and the gliosis is not confined to the thalamus.
The distinct location of the pathologic changes in FFI permitted more precise clinicopathologic correlations than had been possible in cases of tumors and vascular lesions. These correlations betokened that the anterior and dorsomedial thalamus has a role in integrating and expressing sleep, autonomic functions, and neuroendocrine circadian rhythm.
It was concluded that the kindred probably had the same disorder because of the identical pattern of inheritance, pathologic changes, and signs and symptoms.
In 1995 was succeeded in transmitting fatal familial insomnia to mice, thus placing FFI within the group of infectious cerebral amyloidoses.
Valuable information on the pathogenesis of fatal familial insomnia was provided by the descriptions of sporadic fatal insomnia by Mastrianni in1999 and Parchi (1999), which were described a 44-year-old man with insomnia, dysautonomia, and ataxia, followed toward the end of the fatal 16-month course by hallucinations and myoclonus.
Histopathologic analysis showed lesions that were indistinguishable in type and regional distribution from those of fatal familial insomnia; the amount, distribution, and molecular mass of the pathologic isoform of the prion protein (PrP(Sc)) in the brain were similar to those in fatal familial insomnia.
Nevertheless, a rigorous analysis of the PRNP gene failed to identify the mutation at codon 178 (D178N) that is associated with FFI.
Mastrianni argued that their patient had a sporadic form of fatal insomnia. Such a conclusion was supported by the description of 5 such patients by Parchi.
Mastrianni also demonstrated experimental transmission of sporadic fatal insomnia to mice.
Mice vaccinated with brain homogenates from subjects with fatal familial insomnia or sporadic fatal insomnia had lesions of similar types and distributions in their brains.
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