title: The neuroanatomical phenotype of tuberous sclerosis complex: focus on radial migration lines.
abstract: BACKGROUND
  The contribution of radial migration lines (RMLs) to the neuroanatomical and neurocognitive phenotype of tuberous sclerosis complex (TSC) is unclear. The aim of this study was to perform a comprehensive evaluation of the neuroradiological phenotype of TSC, distinguishing RMLs from normal-appearing white matter (NAWM) using diffusion tensor imaging (DTI) and volumetric fluid-attenuated inversion recovery imaging.
  
  
  METHODS
  Magnetic resonance images of 30 patients with TSC were evaluated. The frequencies of RMLs, tubers, and subependymal nodules (SENs) were determined for every hemispheric lobe. Cerebellar lesions and subependymal giant cell tumors were counted. DTI metrics were obtained from the NAWM of every hemispheric lobe and from the largest RML and tuber. Analyses of variance and correlations were performed to investigate the associations between neuroanatomical characteristics and relationships between RML frequency and neurocognitive outcomes. NAWM DTI metrics were compared with measurements of 16 control patients.
  
  
  RESULTS
  A mean of 47 RMLs, 27 tubers, and 10 SENs were found per patient, and the frequencies of these lesions were strongly correlated (p < 0.001). RML fractional anisotropy and mean diffusivity were strongly inversely correlated (p = 0.003). NAWM DTI metrics were similar to the controls (p = 0.26). RML frequency was strongly associated with age of seizure onset (p = 0.003), intelligence outcomes (p = 0.01), and level of autistic features (p = 0.007).
  
  
  CONCLUSIONS
  A detailed neuroradiological phenotype is presented, showing that RMLs are the most frequent neuroanatomical lesion, are responsible for white matter DTI abnormalities, and are strongly associated with age of seizure onset, intelligence outcomes, and level of autistic features.
authors: Department of Neurology, Carol and James Herscot Center for Tuberous Sclerosis Complex, Massachusetts General Hospital, 175 Cambridge Street, Boston, MA, 02114, USA. avaneeghen@partners.org.|ENCORE, Expertise Centre for Neurodevelopmental Disorders, Department of Neuroscience, Erasmus Medical Centre, Rotterdam, The Netherlands. avaneeghen@partners.org.
authors: Agnies M
authors: AM
authors: van Eeghen
authors: Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.
authors: Laura Ortiz
authors: LO
authors: Terán
authors: Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.
authors: Jason
authors: J
authors: Johnson
authors: Department of Psychiatry, Psychological Assessment Center, Massachusetts General Hospital, Boston, MA, USA.
authors: Margaret B
authors: MB
authors: Pulsifer
authors: Department of Neurology, Carol and James Herscot Center for Tuberous Sclerosis Complex, Massachusetts General Hospital, 175 Cambridge Street, Boston, MA, 02114, USA.
authors: Elizabeth A
authors: EA
authors: Thiele
authors: Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.
authors: Paul
authors: P
authors: Caruso
mesh_terms: D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000473:pathology*; D002648:Child; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014402:Tuberous Sclerosis / Q000473:pathology*; D055815:Young Adult
references: Pediatr Radiol. 2005 Oct;35(10):980-3
references: 16170442
references: J Child Neurol. 2004 Sep;19(9):650-7
references: 15563010
references: Epilepsy Res. 2009 Dec;87(2-3):197-202
references: 19783123
references: Eur J Radiol. 2009 Aug;71(2):249-52
references: 18538521
references: Neurology. 2008 Mar 18;70(12):916-23
references: 18032744
references: Epilepsia. 2010 Jul;51(7):1236-41
references: 20041940
references: Radiology. 2004 Aug;232(2):461-5
references: 15215545
references: Neuropathology. 2008 Dec;28(6):577-90
references: 18410267
references: Acad Radiol. 2012 Jan;19(1):17-25
references: 22142677
references: Epilepsy Behav. 2007 Dec;11(4):506-13
references: 17936687
references: Pediatrics. 2006 May;117(5):1494-502
references: 16651302
references: Arch Neurol. 2003 Nov;60(11):1580-4
references: 14623730
references: Dev Med Child Neurol. 2013 Feb;55(2):146-53
references: 23205844
references: Epilepsia. 2009 Jan;50(1):147-54
references: 19125835
references: J Autism Dev Disord. 1994 Oct;24(5):659-85
references: 7814313
references: Diagn Interv Radiol. 2006 Jun;12(2):57-60
references: 16752348
references: Br J Psychiatry. 1999 Nov;175:444-51
references: 10789276
references: Eur Radiol. 2002 Jan;12(1):138-43
references: 11868090
references: Pediatr Radiol. 2004 May;34(5):387-92
references: 15029464
references: Am J Phys Anthropol. 2002 Aug;118(4):341-58
references: 12124914
references: Radiology. 2009 Apr;251(1):206-15
references: 19190250
references: Epilepsia. 2009 Dec;50(12):2605-10
references: 19490046
references: Trends Mol Med. 2011 Dec;17(12):734-42
references: 21890410
references: AJNR Am J Neuroradiol. 2010 Aug;31(7):1273-7
references: 20203114
references: Nat Neurosci. 2010 Feb;13(2):163-72
references: 20062052
references: Psychol Med. 2001 Nov;31(8):1437-46
references: 11722158
references: Acta Neuropathol. 2012 May;123(5):685-93
references: 22327361
references: Genes Dev. 2010 Oct 15;24(20):2317-29
references: 20876733
references: Epilepsy Res. 2010 May;89(2-3):246-53
references: 20129760
references: Neurology. 2011 Mar 15;76(11):981-7
references: 21403110
references: Brain Dev. 2001 Nov;23(7):508-15
references: 11701246
references: J Child Neurol. 2006 Feb;21(2):99-105
references: 16566871
references: Epilepsy Behav. 2010 Jul;18(3):262-6
references: 20554253
references: J Neurochem. 2006 Jan;96(2):407-13
references: 16300636
references: AJNR Am J Neuroradiol. 1995 Jan;16(1):149-55
references: 7900584
references: Epilepsia. 2007 Aug;48(8):1460-9
references: 17441991
references: J Child Neurol. 2004 Sep;19(9):643-9
references: 15563009
references: AJNR Am J Neuroradiol. 2007 Oct;28(9):1662-7
references: 17893226
references: Pediatr Neurol. 2010 Feb;42(2):101-6
references: 20117745
references: Neuroradiology. 2009 Nov;51(11):781-6
references: 19603155