title: Metachromatic leukodystrophy: natural course of cerebral MRI changes in relation to clinical course.
abstract: OBJECTIVE
  Metachromatic Leukodystrophy (MLD) is a rare disorder leading to demyelination and neurological impairment. A natural history study within the German leukodystrophy network analyzed MRI changes with respect to the clinical course.
  
  
  METHODS
  113 MR images of 68 patients (33 late-infantile, 35 juvenile) were studied cross-sectionally and longitudinally. MRI and motor deterioration were assessed using standardized scoring systems.
  
  
  RESULTS
  The temporal and spatial patterns of MR severity scores differed between the late-infantile and juvenile form. Although early (involving central white matter, corpus callosum) and late signs (involving pons, cerebellum, cerebral atrophy) were similar, high MRI scores (mean 18, SD 1.2, p < 0.001) were evident in the juvenile form already at the onset of first symptoms and even in presymptomatic patients. The progression rate of the MRI score was clearly higher and more uniform in the late-infantile (on average 8 per year, p < 0.0001) than in the juvenile patients (on average 0.4 per year, p < 0.08). In late-infantile patients, MRI changes correlated highly with motor deterioration (rho = 0.73, p < 0.001), this was less remarkable in the juvenile form (rho = 0.50, p < 0.01). Severe motor dysfunction was associated with U-fiber involvement and cerebellar changes (p < 0.05).
  
  
  CONCLUSIONS
  MRI showed a typical spatial pattern, which evolved gradually and uniformly during disease progression in late-infantile MLD. In juvenile MLD MRI changes were already observed at disease onset and temporal patterns were more variable. As therapeutic options for MLD are evolving, these findings are not only important for patient counseling but also for the evaluation of therapeutic interventions.
authors.affiliation: Department of Pediatric Neurology & Developmental Medicine and Experimental Pediatric Neuroimaging, University Children's Hospital, Hoppe-Seyler-Strasse 1, 72076, Tübingen, Germany. samuel.groeschel@med.uni-tuebingen.de
authors.forename: Samuel
authors.initials: S
authors.lastname: Groeschel
authors.forename: Christiane
authors.initials: C
authors.lastname: Kehrer
authors.forename: Corinna
authors.initials: C
authors.lastname: Engel
authors.forename: Christine
authors.initials: C
authors.lastname: I Dali
authors.forename: Annette
authors.initials: A
authors.lastname: Bley
authors.forename: Robert
authors.initials: R
authors.lastname: Steinfeld
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Grodd
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Krägeloh-Mann
mesh_terms: D000293:Adolescent; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D007966:Leukodystrophy, Metachromatic / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods; D009043:Motor Activity / Q000502:physiology; D011859:Radiography; D012720:Severity of Illness Index