title: Structural and metabolic brain abnormalities in preclinical cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy.
abstract: OBJECTIVE
  To assess, by using quantitative MRI metrics, structural and metabolic brain abnormalities in subjects with preclinical cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL).
  
  
  BACKGROUND
  Brain MRI abnormalities have been occasionally reported in preclinical CADASIL subjects. However, very little is known as to when the brain tissue damage starts to accumulate, what brain regions are primarily involved and whether the brain damage is significant in subjects who have no overt clinical manifestations of the disease.
  
  
  METHODS
  Twelve subjects (mean age 40 years; range 26-55 years; males/females 6/6) with genetically proven CADASIL and no clinical signs of the disease underwent conventional MRI and proton MR spectroscopic imaging ((1)H-MRSI) to measure white matter (WM) lesion volume (LV), global and regional cerebral volumes, and WM levels of N-acetylaspartate (NAA) normalised to creatine (Cr). MR values were compared with those of 13 age- and sex-matched healthy controls.
  
  
  RESULTS
  All preclinical CADASIL showed WM lesions (range 0.2 to 26 cm(3)). They were mostly distributed in the frontal and parietal regions, with the highest probability in the corona radiata. On (1)H-MRSI examination, NAA/Cr values were lower in preclinical CADASIL than in HC, particularly in the corona radiata (p<0.01). Normalised brain and cortical volumes were also lower in preclinical CADASIL than in HC (p<0.01), particularly in the frontal cortex.
  
  
  CONCLUSIONS
  The pathological process occurring in CADASIL leads to damage of WM and neocortex much before the evidence of clinical symptoms. At this preclinical stage, this seems to take place prevalently in the frontal brain region.
authors.affiliation: Department Neurological and Behavioural Sciences, University of Siena, Viale Bracci 2, 53100 Siena, Italy.
authors.forename: M L
authors.initials: ML
authors.lastname: Stromillo
authors.forename: M T
authors.initials: MT
authors.lastname: Dotti
authors.forename: M
authors.initials: M
authors.lastname: Battaglini
authors.forename: M
authors.initials: M
authors.lastname: Mortilla
authors.forename: S
authors.initials: S
authors.lastname: Bianchi
authors.forename: K
authors.initials: K
authors.lastname: Plewnia
authors.forename: L
authors.initials: L
authors.lastname: Pantoni
authors.forename: D
authors.initials: D
authors.lastname: Inzitari
authors.forename: A
authors.initials: A
authors.lastname: Federico
authors.forename: N
authors.initials: N
authors.lastname: De Stefano
mesh_terms: D000328:Adult; D000367:Age Factors; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D046589:CADASIL / Q000378:metabolism* / Q000473:pathology*; D002544:Cerebral Infarction / Q000378:metabolism* / Q000473:pathology*; D003401:Creatine / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D011522:Protons
chemical_list: D011522:Protons; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine