NR ACWT
AU Cortelli,P.; Perani,D.; Parchi,P.; Grassi,F.; Montagna,P.; De Martin,M.; Castellani,R.J.; Tinuper,P.; Gambetti,P.; Lugaresi,E.; Fazio,F.
TI Cerebral metabolism in fatal familial insomnia: relation to duration, neuropathology, and distribution of protease-resistant prion protein.
QU Neurology 1997 Jul; 49(1): 126-33
PT journal article
AB We used [18F]-2-fluoro-2-deoxy-D-glucose (FDG) and PET to study regional cerebral glucose utilization in seven patients with fatal familial insomnia (FFI), an inherited prion disease with a mutation at codon 178 of the prion protein gene. Four patients were methionine/methionine homozygotes at codon 129 (symptom duration, 8.5 +/- 1 months) and three were methionine/valine (MET/VAL129) heterozygotes (symptom duration, 35 +/- 11 months). A severely reduced glucose utilization of the thalamus and a mild hypometabolism of the cingulate cortex were found in all FFI patients. In six subjects the brain hypometabolism also affected the basal and lateral frontal cortex, the caudate nucleus, and the middle and inferior temporal cortex. Comparison between homozygous or heterozygous patients at codon 129 showed that the hypometabolism was more widespread in the MET/VAL129 group, which had a significantly longer symptom duration at the time of [18F] FDG PET study. Comparison between neuropathologic and [18F] FDG PET findings in six patients showed that areas with neuronal loss were also hypometabolic. However, cerebral hypometabolism was more widespread than the histopathologic changes and significantly correlated with the presence of protease-resistant prion protein (PrPres). Our findings indicate that hypometabolism of the thalamus and cingulate cortex is the hallmark of FFI, while the involvement of other brain regions depends on the duration of symptoms and some unknown factors specific to each patient. The present data also support the notion that PrPres formation is the cause of neuronal dysfunction in prion diseases.
IN Durch die Messung der Verteilung radioaktiv markierter Glukose und durch Positronenemmisionstomographie wurden die Hirnstoffwechselaktivitäten bei Patienten mit der fatalen familiären Schlaflosigkeit untersucht. Als typisch erwies sich eine stark verminderte Aktivität im Thalamus sowie ein etwas verminderter Zuckerverbrauch im Cinglum (vom Stirnlappen zu den Schläfenlappen verlaufende Assoziationsfasern). Individuell unterschiedlich waren auch andere Hirnregionen betroffen. Bezüglich des Codons 129 heterozygote Patienten zeigten mit 35 +/- 11 Monaten deutlich längere Krankheitsphasen als die Methionin-homozygoten mit 8,5 +/- 1 Monaten. Außerdem betraf bei ihnen die verminderte Hirnaktivität größere Hirnbereiche. Die Bereiche mit vermindertem Zellstoffwechsel enthielten die Bereiche mit erkennbaren Neuronenverlusten, waren jedoch ausgedehnter und entsprachen der Verteilung proteaseresistenter Prionproteinansammlungen.
ZR 36
MH Adult; Cerebral Cortex/*metabolism/*radionuclide imaging; Female; Human; Male; Middle Age; PrPc Proteins/*metabolism; Prion Diseases/genetics/*metabolism; Support, Non-U.S. Gov't; Tomography, Emission-Computed
AD Neurological Institute, University of Bologna, Italy.
SP englisch
PO USA