title: Neuroradiologic correlates of clinical disability and progression in the X-linked leukodystrophy Pelizaeus-Merzbacher disease.
abstract: OBJECTIVE
  To determine whether quantitative measure of magnetic resonance imaging data from patients with the inherited leukodystrophy, Pelizaeus-Merzbacher disease (PMD) correlates with clinical severity or progression.
  
  
  METHODS
  In our current work we have analyzed the clinical phenotypes and MRI scans of 51 male patients with PMD and 10 female carriers for whom the PLP1 genotype had been determined. In addition, we developed a 32-point functional disability scoring (FDS) system for PMD, and validated it for inter-rater reliability. Using conventional T1- and T2-weighted MRI images of the whole brain, we measured white matter and total brain volume (WMV and TBV), inter-caudate ratio (ICR), and corpus callosum area.
  
  
  RESULTS
  There was a significant positive correlation of FDS with white matter fraction (WMV/TBV) and corpus callosum area. Also, when applying a median split based on FDS, patients with lower FDS showed reduced white matter fraction and corpus callosum area, and increased ICR compared to patients with relatively higher FDS, regardless of age.
  
  
  CONCLUSIONS
  Although this patient population is heterogeneous, with multiple genetic and molecular mechanisms causing PMD, these data imply that white matter atrophy is a major pathological determinant of the clinical disability in most patients. Development of reliable non-invasive quantitative biomarkers of disease activity would be useful not only for following the natural history of the disease, but also raising the potential for evaluating future therapies.
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, United States; Department of Neurosciences & Neurology, University of Toledo College of Medicine, Toledo, OH 43614, United States.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Laukka
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Stanley
authors.forename: James Y
authors.initials: JY
authors.lastname: Garbern
authors.forename: Angela
authors.initials: A
authors.lastname: Trepanier
authors.forename: Grace
authors.initials: G
authors.lastname: Hobson
authors.forename: Tori
authors.initials: T
authors.lastname: Lafleur
authors.forename: Alexander
authors.initials: A
authors.lastname: Gow
authors.forename: John
authors.initials: J
authors.lastname: Kamholz
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003337:Corpus Callosum / Q000473:pathology; D006233:Persons with Disabilities; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D018991:Myelin Proteolipid Protein / Q000235:genetics; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009422:Nervous System Diseases / Q000209:etiology*; D020371:Pelizaeus-Merzbacher Disease / Q000150:complications* / Q000235:genetics; D055815:Young Adult
chemical_list: D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human
keywords: Clinical disability; Genetics; Magnetic resonance imaging; Pelizaeus–Merzbacher disease; Proteolipid protein; White matter atrophy