Multitracer study with positron emission tomography in Creutzfeldt-Jakob disease.
During the period February 1997 to April 2000, 15 patients with clinical symptoms of Creutzfeldt-Jakob disease (CJD) were referred to Uppsala University PET Centre. Positron emission tomography (PET) was performed to detect characteristic signs of the disease, e.g. neuronal death and/or astrocytosis in the brain. The examinations were performed in one session starting with oxygen-15 labelled water scan to measure regional cerebral blood flow, followed by imaging with the monoamine oxidase B inhibitor N-[(11)C-methyl]- L-deuterodeprenyl (DED) to assess astrocytosis in the brain and finally imaging with fluor-18 2-fluorodeoxyglucose (FDG) to assess regional cerebral glucose metabolism (rCMR(glu)) [corrected]. Nine of the patients fulfilled the clinical criteria of probable CJD. In eight of them, FDG and DED imaging revealed, in comparison with normal controls, a typical pattern characterized by a pronounced regional decrease (<2SD) in glucose brain metabolism, indicative of neuronal dysfunction; this was accompanied by a similar increase (>2SD) in DED binding, indicating astrocytosis. These changes were most pronounced in the cerebellum and the frontal, occipital and parietal cortices, whereas the pons, the thalamus and the putamen were less affected and the temporal cortex appeared unaffected. The cerebral blood flow showed a pattern similar to that observed with FDG. In the ninth patient, analysis with DED was not possible. The diagnosis of definite CJD according to international consensus criteria was confirmed in six of these patients. In one patient with probable CJD, protease-resistant prion protein (PrPres) could not be demonstrated. In two patients with probable CJD, autopsy was not allowed. Computed tomography and magnetic resonance imaging, performed in four and seven of these nine patients respectively, showed unspecific, mainly atrophic changes. In six other patients, the PET examinations gave a different pattern. In three of them, high rCMR(glu) was noticed in parts of the brain, particularly in the temporal lobes and basal ganglia, which could suggest encephalitis. One of the patients had Sjögren's syndrome, one had paraneoplastic limbic encephalitis and the third recovered spontaneously. In the other three patients, the DED binding was normal despite a hypometabolic glucose pattern. In conclusion, the PET findings obtained using DED and FDG paralleled neuropathological findings indicating neuronal dysfunction and astrocytosis, changes that are found in CJD.
Engler
Henry
H
Department of Neurology, Uppsala University Hospital, Uppsala, Sweden. henry.engler@pet.uu.se
Lundberg
Per Olov
PO
Ekbom
Karl
K
Nennesmo
Inger
I
Nilsson
Anna
A
Bergström
Mats
M
Tsukada
Hideo
H
Hartvig
Per
P
Långström
Bengt
B
D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002560:Cerebrovascular Circulation; D007562:Creutzfeldt-Jakob Syndrome / Q000150:complications / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005500:Follow-Up Studies; D005911:Gliosis / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000493:pharmacokinetics; D010104:Oxygen Radioisotopes / Q000493:pharmacokinetics; D011868:Radioisotopes / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*; D014867:Water / Q000378:metabolism
D002250:Carbon Radioisotopes; D008996:Monoamine Oxidase Inhibitors; D010104:Oxygen Radioisotopes; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D014867:Water; D019788:Fluorodeoxyglucose F18; D005947:Glucose