title: Cortical hypometabolism and crossed cerebellar diaschisis suggest subcortically induced disconnection in CADASIL: an 18F-FDG PET study.
abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small-vessel disease caused by mutations in the NOTCH3 gene. As in sporadic small-vessel disease, ischemic lesions are largely confined to subcortical structures, whereas the cortex is spared. CADASIL, therefore, may serve as a model to study subcortically induced remote effects. The purpose of this study was to evaluate with (18)F-FDG PET whether regional cerebral metabolic rate of glucose (rCMRglc) is altered in CADASIL patients and, if so, whether there is evidence of subcortically induced disconnection.
  
  
  METHODS
  Eleven CADASIL patients (7 women, 4 men; mean age, 55.8 +/- 6.7 y) without cortical lesions on brain MR images underwent PET after intravenous injection of 120 MBq (18)F-FDG, with calculation of rCMRglc according to a previously published method. For further processing, patient studies were registered to a template of a healthy control group and region-of-interest-based and voxelwise comparisons were performed.
  
  
  RESULTS
  In CADASIL patients, mean rCMRglc was significantly reduced in all cortical and subcortical structures, compared with the values in healthy volunteers. In the subcortical gray matter, metabolic rates, given as the percentage of the mean of healthy volunteers, were 49.7%, 65.3%, and 51.6% in the caudate, putamen, and thalamus, respectively. Among cortical structures, the values were 66.9%, 67.9%, 67.2%, and 76.5% for the frontal, parietal, temporal, and occipital lobes, respectively. On an individual level, most patients showed marked asymmetry and inhomogeneities of cortical glucose metabolism. In 6 (55%) CADASIL patients, there was evidence of crossed cerebellar diaschisis.
  
  
  CONCLUSIONS
  This study showed that cortical glucose metabolism is significantly lower in CADASIL patients than in healthy volunteers. The observed decrease in rCMRglc may in part be explained by a reduction of cerebral blood flow and neuronal loss. In addition, our data provide evidence of remote effects secondary to the functional disruption of subcortical fiber tracts in this particular type of small-vessel disease.
authors.affiliation: Department of Nuclear Medicine, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany. tatsch@nuk.med.uni-muenchen.de
authors.forename: Klaus
authors.initials: K
authors.lastname: Tatsch
authors.forename: Walter
authors.initials: W
authors.lastname: Koch
authors.forename: Rainer
authors.initials: R
authors.lastname: Linke
authors.forename: Gabriele
authors.initials: G
authors.lastname: Poepperl
authors.forename: Nils
authors.initials: N
authors.lastname: Peters
authors.forename: Markus
authors.initials: M
authors.lastname: Holtmannspoetter
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
mesh_terms: D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D015161:Dementia, Multi-Infarct / Q000000981:diagnostic imaging / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose