title: Cerebral gray and white matter changes and clinical course in metachromatic leukodystrophy.
abstract: OBJECTIVE
  Metachromatic leukodystrophy (MLD) is a rare metabolic disorder leading to demyelination and rapid neurologic deterioration. As therapeutic options evolve, it seems essential to understand and quantify progression of the natural disease. The aim of this study was to assess cerebral volumetric changes in children with MLD in comparison to normal controls and in relation to disease course.
  
  
  METHODS
  Eighteen patients with late-infantile MLD and 42 typically developing children in the same age range (20-59 months) were analyzed in a cross-sectional study. Patients underwent detailed genetic, biochemical, electrophysiologic, and clinical characterization. Cerebral gray matter (GM) and white matter (WM) volumes were assessed by multispectral segmentation of T1- and T2-weighted MRI. In addition, the demyelinated WM (demyelination load) was automatically quantified in T2-weighted images of the patients, and analyzed in relation to the clinical course.
  
  
  RESULTS
  WM volumes of patients did not differ from controls, although their growth curves were slightly different. GM volumes of patients, however, were on average 10.7% (confidence interval 6.0%-14.9%, p < 0.001) below those of normally developing children. The demyelination load (corrected for total WM volume) increased with disease duration (p < 0.003) and motor deterioration (p < 0.001).
  
  
  CONCLUSIONS
  GM volume in patients with MLD is reduced when compared with healthy controls, already at young age. This supports the notion that, beside demyelination, neuronal dysfunction caused by neuronal storage plays an additional role in the disease process. The demyelination load may be a useful noninvasive imaging marker for disease progression and may serve as reference for therapeutic intervention.
authors.affiliation: Department of Pediatric Neurology & Developmental Medicine, University Children's Hospital, Tübingen, Germany. Samuel.groeschel@med.uni-tuebingen.de
authors.forename: Samuel
authors.initials: S
authors.lastname: Groeschel
authors.forename: Christine
authors.initials: C
authors.lastname: í Dali
authors.forename: Philipp
authors.initials: P
authors.lastname: Clas
authors.forename: Judith
authors.initials: J
authors.lastname: Böhringer
authors.forename: Morten
authors.initials: M
authors.lastname: Duno
authors.forename: Christian
authors.initials: C
authors.lastname: Krarup
authors.forename: Christiane
authors.initials: C
authors.lastname: Kehrer
authors.forename: Marko
authors.initials: M
authors.lastname: Wilke
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Krägeloh-Mann
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology; D002540:Cerebral Cortex / Q000473:pathology*; D002648:Child; D016001:Confidence Intervals; D003430:Cross-Sectional Studies; D003711:Demyelinating Diseases / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007966:Leukodystrophy, Metachromatic / Q000235:genetics / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000209:etiology / Q000473:pathology; D009186:Myelin Sheath / Q000473:pathology; D009431:Neural Conduction / Q000502:physiology; D012044:Regression Analysis; D013433:Sulfoglycosphingolipids / Q000652:urine; D055815:Young Adult
chemical_list: D013433:Sulfoglycosphingolipids