Fatal familial insomnia: a new Austrian family

We present clinical, pathological and molecular features of the first Austr ian family with fatal familial insomnia. Detailed clinical data are availab le in five patients and autopsy in four patients. Age at onset of disease r anged between 20 and 60 years, and disease duration between 8 and 20 months . Severe loss of weight was an early symptom in ail five patients, Four pat ients developed insomnia and/or autonomic dysfunction, and all five patient s developed motor abnormalities. Analysis of the prion protein (PrP) gene r evealed the codon 178 point mutation and methionine homozygosity at positio n 129, In all brains, neuropathology showed widespread cortical astrogliosi s, widespread brainstem nuclei and tract degeneration, and olivary 'pseudoh ypertrophy' with vacuolated neurons, in addition to neuropathological featu res described previously, such as thalamic and olivary degeneration. Wester n blotting of one brain and immunocytochemistry in four brains revealed qua ntitative and regional dissociation between PrPres (the protease resistant form of PrP) deposition and histopathology, In the cerebellar cortex of one patient, PrPres deposits were prominent in the molecular layer and display ed a peculiar patchy and strip-like pattern with perpendicular orientation to the surface. In another patient, a single vacuolated neuron in the infer ior olivary nuclei contained prominent intravacuolar granular PrPres deposi ts, resembling changes of brainstem neurons in bovine spongiform encephalop athy.