title: Loss of white matter microstructural integrity is associated with adverse neurological outcome in tuberous sclerosis complex.
abstract: OBJECTIVE
  Tuberous sclerosis complex (TSC) is a genetic neurocutaneous syndrome in which cognitive and social-behavioral outcomes for patients vary widely in an unpredictable manner. The cause of adverse neurologic outcome remains unclear. The aim of this study was to investigate the hypothesis that disordered white matter and abnormal neural connectivity are associated with adverse neurologic outcomes.
  
  
  METHODS
  Structural and diffusion magnetic resonance imaging was carried out in 40 subjects with TSC (age range, 0.5-25 years; mean age, 7.2 years; median age, 5 years), 12 of whom had autism spectrum disorders (ASD), and in 29 age-matched controls. Tractography of the corpus callosum was used to define a three-dimensional volume of interest. Regional averages of four diffusion scalar parameters of the callosal projections were calculated for each subject. These were the average fractional anisotropy (AFA) and the average mean, radial, and axial diffusivity.
  
  
  RESULTS
  Subjects with TSC had significantly lower AFA and higher average mean, radial, and axial diffusivity values compared to controls. Subjects with TSC and ASD had significantly lower AFA values compared to those without ASD and compared to controls. Subjects with TSC without ASD had similar AFA values compared to controls.
  
  
  CONCLUSIONS
  Diffusion tensor scalar parameters provided measures of properties of the three-dimensional callosal projections. In TSC, changes in these parameters may reflect microstructural changes in myelination, axonal integrity, or extracellular environment. Alterations in white matter microstructural properties were associated with TSC, and larger changes were associated with TSC and ASD, thus establishing a relationship between altered white matter microstructural integrity and brain function.
authors.affiliation: Department of Neurology, Children's Hospital Boston and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Jurriaan M
authors.initials: JM
authors.lastname: Peters
authors.forename: Mustafa
authors.initials: M
authors.lastname: Sahin
authors.forename: Vanessa K
authors.initials: VK
authors.lastname: Vogel-Farley
authors.forename: Shafali S
authors.initials: SS
authors.lastname: Jeste
authors.forename: Charles A
authors.initials: CA
authors.lastname: Nelson
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Gregas
authors.forename: Sanjay P
authors.initials: SP
authors.lastname: Prabhu
authors.forename: Benoit
authors.initials: B
authors.lastname: Scherrer
authors.forename: Simon K
authors.initials: SK
authors.lastname: Warfield
mesh_terms: D000293:Adolescent; D000328:Adult; D001927:Brain Diseases / Q000175:diagnosis* / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014402:Tuberous Sclerosis / Q000150:complications* / Q000175:diagnosis*; D055815:Young Adult