NR AXNB
AU Giaccone,G.; Mangieri,M.; Priano,L.; Limido,L.; Brioschi,A.; Albani,G.; Pradotto,L.; Fociani,P.; Orsi,L.; Mortara,P.; Tagliavini,F.; Mauro,A.
TI Sporadic Fatal Insomnia with Unusual Biochemical and Neuropathological Findings
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.121
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Sporadic fatal insomnia (SFI) is a rare subtype of human prion disease, whose clinical and neuropathological phenotype is very similar to familial fatal insomnia (FFI). SFI patients reported until now were all homozygous for methionine at codon 129 of PRNP with deposition of type 2 PrPres (Parchi classification) in the brain. Here we describe a 56-year-old woman who died after a 10-month illness characterized by progressive drowsiness, cognitive deterioration, autonomic impairment and myoclonus. Polysomnography demonstrated a pattern similar to that described in FFI cases with loss of circadian pattern of sleep-wake cycle. A remarkable finding was that 20 years before the onset of symptoms, the patient had undergone surgery for a colloid cyst of the third ventricle, and two ventricular shunts were placed, one correctly in the left ventricle, while the second ended in the right thalamus. The PRNP gene showed no mutation and methionine homozygosity at codon 129. The neuropathologic examination revealed neuronal loss, gliosis, and spongiosis that were mild in the cerebral cortex, while relevant in the caudate nucleus, putamen, thalamus, hypothalamus and inferior olives. In the thalamus, the mediodorsal nuclei were more severely affected than the ventral ones. PrPres immunoreactivity was consistent in the striatum, thalamus and hypothalamus, patchy and of low intensity in the cerebral cortex and absent in the cerebellum. Western blot analysis confirmed this topographic distribution of PrPres. The bands corresponding to di- glycosylated, monoglycosylated and non-glycosylated PrPres were equally represented. The nonglycosylated PrPres band had an electrophoretic mobility identical to that of type 1 by Parchi classification, in the multiple cortical and subcortical regions examined. These findings demonstrate the existence of further rare molecular subtypes of human prion diseases, whose characterization may provide clues for the elucidation of the relation between biochemical characteristics of PrPres and clinico-pathological features of these disorders.
AD G. Giaccone, M. Mangieri, L. Limido, F. Tagliavini, Fondazione IRCCS Istituto Neurologico Carlo Besta, Italy; L. Priano, A. Brioschi, G. Albani, L. Pradotto, A. Mauro, IRCCS Istituto Auxologico Italiano, Italy; P. Fociani, Università di Milano, Ospedale Luigi Sacco, Italy; L. Orsi, P. Mortara, Università di Torino, Dipartimento di Neuroscienze, Italy
SP englisch
PO Schottland