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Longitudinal Changes in Diffusion Properties in White Matter Pathways of Children With Tuberous Sclerosis Complex

  • Author Footnotes
    1 These authors equally contributed to this work.
    Fiona M. Baumer
    Footnotes
    1 These authors equally contributed to this work.
    Affiliations
    Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Author Footnotes
    1 These authors equally contributed to this work.
    Jae W. Song
    Footnotes
    1 These authors equally contributed to this work.
    Affiliations
    Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Paul D. Mitchell
    Affiliations
    Clinical Research Center, Boston Children's Hospital, Boston, Massachusetts
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  • Rudolph Pienaar
    Affiliations
    Department of Radiology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts

    Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts

    Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Mustafa Sahin
    Affiliations
    Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
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  • P. Ellen Grant
    Affiliations
    Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts

    Department of Radiology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts

    Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts

    Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
    Search for articles by this author
  • Emi Takahashi
    Correspondence
    Communications should be addressed to: Dr. Takahashi; Division of Newborn Medicine; Boston Children's Hospital; 1 Autumn St. #456; Boston, MA 02115 and Dr. Fiona Baumer; Department of Neurology; Boston Children's Hospital; Harvard Medical School; 300 Longwood Avenue; Boston, MA 02115.
    Affiliations
    Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts

    Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts

    Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
    Search for articles by this author
  • Author Footnotes
    1 These authors equally contributed to this work.

      Abstract

      Background

      Abnormal white matter development in patients with tuberous sclerosis complex, a multisystem hamartomatous disorder caused by aberrant neural proliferation and axonal maturation, may be associated with poorer neurocognitive outcomes. The purpose of this study is to identify predictors of longitudinal changes in diffusion properties of white matter tracts in patients with tuberous sclerosis complex.

      Methods

      Diffusion magnetic resonance imaging was carried out in 17 subjects with tuberous sclerosis complex (mean age, 7.2 ± 4.4 years) with at least two magnetic resonance imaging scans (mean number of days between scans, 419.4 ± 105.4). There were 10 males; 5 of 17 had autism spectrum disorder and 10 of 17 had epilepsy. Regions of interest were placed to delineate the internal capsule/corona radiata, cingulum, and corpus callosum. The outcomes were mean change in apparent diffusion coefficient and fractional anisotropy. Data were analyzed using Pearson's correlation and multiple linear regression analyses.

      Results

      Gender was a significant predictor of mean change in apparent diffusion coefficient in the left internal capsule, right and left cingulum bundles, and corpus callosum and a significant predictor of mean change in fractional anisotropy in the corpus callosum. Epilepsy was a significant predictor of mean change in apparent diffusion coefficient in the left internal capsule. Autism spectrum disorder was not predictive of diffusion changes in any of the studied pathways.

      Conclusion

      Clinical variables, including gender and epilepsy, have an effect on the development of white matter pathways. These variables should be taken into consideration when counseling tuberous sclerosis complex patients and in future imaging studies in this population.

      Keywords

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      References

        • Ehninger D.
        • Silva A.J.
        Rapamycin for treating Tuberous sclerosis and Autism spectrum disorders.
        Trends Mol Med. 2011; 17: 78-87
        • Han J.M.
        • Sahin M.
        TSC1/TSC2 signaling in the CNS.
        FEBS Lett. 2011; 585: 973-980
        • Joinson C.
        • O'Callaghan F.J.
        • Osborne J.P.
        • Martyn C.
        • Harris T.
        • Bolton P.F.
        Learning disability and epilepsy in an epidemiological sample of individuals with tuberous sclerosis complex.
        Psychol Med. 2003; 33: 335-344
        • Curatolo P.
        • Cusmai R.
        • Cortesi F.
        • Chiron C.
        • Jambaque I.
        • Dulac O.
        Neuropsychiatric aspects of tuberous sclerosis.
        Ann N Y Acad Sci. 1991; 615: 8-16
        • Winterkorn E.B.
        • Pulsifer M.B.
        • Thiele E.A.
        Cognitive prognosis of patients with tuberous sclerosis complex.
        Neurology. 2007; 68: 62-64
        • de Vries P.J.
        • Hunt A.
        • Bolton P.F.
        The psychopathologies of children and adolescents with tuberous sclerosis complex (TSC): a postal survey of UK families.
        Eur Child Adolesc Psychiatry. 2007; 16: 16-24
        • Wong V.
        Study of the relationship between tuberous sclerosis complex and autistic disorder.
        J Child Neurol. 2006; 21: 199-204
        • Curatolo P.
        • Porfirio M.C.
        • Manzi B.
        • Seri S.
        Autism in tuberous sclerosis.
        Eur J Paediatr Neurol. 2004; 8: 327-332
        • Jansen F.E.
        • van Huffelen A.C.
        • Algra A.
        • van Nieuwenhuizen O.
        Epilepsy surgery in tuberous sclerosis: a systematic review.
        Epilepsia. 2007; 48: 1477-1484
        • Jansen F.E.
        • Vincken K.L.
        • Algra A.
        • et al.
        Cognitive impairment in tuberous sclerosis complex is a multifactorial condition.
        Neurology. 2008; 70: 916-923
        • Mori S.
        • Zhang J.
        Principles of diffusion tensor imaging and its applications to basic neuroscience research.
        Neuron. 2006; 51: 527-539
        • Karadag D.
        • Mentzel H.J.
        • Güllmar D.
        • et al.
        Diffusion tensor imaging in children and adolescents with tuberous sclerosis.
        Pediatr Radiol. 2005; 35: 980-983
        • Firat A.K.
        • Karakaş H.M.
        • Erdem G.
        • Yakinci C.
        • Biçak U.
        Diffusion weighted MR findings of brain involvement in tuberous sclerosis.
        Diagn Interv Radiol. 2006; 12: 57-60
        • Garaci F.G.
        • Floris R.
        • Bozzao A.
        • et al.
        Increased brain apparent diffusion coefficient in tuberous sclerosis.
        Radiology. 2004; 232: 461-465
        • Makki M.I.
        • Chugani D.C.
        • Janisse J.
        • Chugani H.T.
        Characteristics of abnormal diffusivity in normal-appearing white matter investigated with diffusion tensor MR imaging in tuberous sclerosis complex.
        AJNR Am J Neuroradiol. 2007; 28: 1662-1667
        • Simao G.
        • Raybaud C.
        • Chuang S.
        • Go C.
        • Snead O.C.
        • Widjaja E.
        Diffusion tensor imaging of commissural and projection white matter in tuberous sclerosis complex and correlation with tuber load.
        AJNR Am J Neuroradiol. 2010; 31: 1273-1277
        • Peng S.S.
        • Lee W.T.
        • Wang Y.H.
        • Huang K.M.
        Cerebral diffusion tensor images in children with tuberous sclerosis: a preliminary report.
        Pediatr Radiol. 2004; 34: 387-392
        • Peters J.M.
        • Sahin M.
        • Vogel-Farley V.K.
        • et al.
        Loss of white matter microstructural integrity is associated with adverse neurological outcome in tuberous sclerosis complex.
        Acad Radiol. 2012; 19: 17-25
        • van Eeghen A.M.
        • Ortiz-Terán L.
        • Terán L.O.
        • et al.
        The neuroanatomical phenotype of tuberous sclerosis complex: focus on radial migration lines.
        Neuroradiology. 2013; 55: 1007-1014
        • Arulrajah S.
        • Ertan G.
        • Jordan L.
        • et al.
        Magnetic resonance imaging and diffusion-weighted imaging of normal-appearing white matter in children and young adults with tuberous sclerosis complex.
        Neuroradiology. 2009; 51: 781-786
        • Lewis W.W.
        • Sahin M.
        • Scherrer B.
        • et al.
        Impaired language pathways in tuberous sclerosis complex patients with autism spectrum disorders.
        Cereb Cortex. 2013; 23: 1526-1532
        • Widjaja E.
        • Simao G.
        • Mahmoodabadi S.Z.
        • et al.
        Diffusion tensor imaging identifies changes in normal-appearing white matter within the epileptogenic zone in tuberous sclerosis complex.
        Epilepsy Res. 2010; 89: 246-253
        • Amarreh I.
        • Dabbs K.
        • Jackson D.C.
        • et al.
        Cerebral white matter integrity in children with active versus remitted epilepsy 5 years after diagnosis.
        Epilepsy Res. 2013; 107: 263-271
        • Widjaja E.
        • Kis A.
        • Go C.
        • Raybaud C.
        • Snead O.C.
        • Smith M.L.
        Abnormal white matter on diffusion tensor imaging in children with new-onset seizures.
        Epilepsy Res. 2013; 104: 105-111
        • Shukla D.K.
        • Keehn B.
        • Lincoln A.J.
        • Müller R.A.
        White matter compromise of callosal and subcortical fiber tracts in children with autism spectrum disorder: a diffusion tensor imaging study.
        J Am Acad Child Adolesc Psychiatry. 2010; 49 (1278.e1261-1262): 1269-1278
        • Billeci L.
        • Calderoni S.
        • Tosetti M.
        • Catani M.
        • Muratori F.
        White matter connectivity in children with autism spectrum disorders: a tract-based spatial statistics study.
        BMC Neurol. 2012; 12: 148
        • Ikuta T.
        • Shafritz K.M.
        • Bregman J.
        • et al.
        Abnormal cingulum bundle development in autism: a probabilistic tractography study.
        Psychiatry Res. 2014; 221: 63-68
        • Roach E.S.
        • Gomez M.R.
        • Northrup H.
        Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria.
        J Child Neurol. 1998; 13: 624-628
        • Northrup H.
        • Krueger D.A.
        • Group ITSCC
        Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference.
        Pediatr Neurol. 2013; 49: 243-254
        • Tuch D.S.
        • Reese T.G.
        • Wiegell M.R.
        • Wedeen V.J.
        Diffusion MRI of complex neural architecture.
        Neuron. 2003; 40: 885-895
        • D'Arceuil H.
        • Liu C.
        • Levitt P.
        • Thompson B.
        • Kosofsky B.
        • de Crespigny A.
        Three-dimensional high-resolution diffusion tensor imaging and tractography of the developing rabbit brain.
        Dev Neurosci. 2008; 30: 262-275
        • Takahashi E.
        • Dai G.
        • Rosen G.D.
        • et al.
        Developing neocortex organization and connectivity in cats revealed by direct correlation of diffusion tractography and histology.
        Cereb Cortex. 2011; 21: 200-211
        • Takahashi E.
        • Folkerth R.D.
        • Galaburda A.M.
        • Grant P.E.
        Emerging cerebral connectivity in the human fetal brain: an MR tractography study.
        Cereb Cortex. 2012; 22: 455-464
        • Dennis E.L.
        • Jahanshad N.
        • McMahon K.L.
        • et al.
        Development of insula connectivity between ages 12 and 30 revealed by high angular resolution diffusion imaging.
        Hum Brain Mapp. 2014; 35: 1790-1800
        • Dennis E.L.
        • Jahanshad N.
        • McMahon K.L.
        • et al.
        Development of brain structural connectivity between ages 12 and 30: a 4-Tesla diffusion imaging study in 439 adolescents and adults.
        Neuroimage. 2013; 64: 671-684
        • Takahashi E.
        • Song J.W.
        • Folkerth R.D.
        • Grant P.E.
        • Schmahmann J.D.
        Detection of postmortem human cerebellar cortex and white matter pathways using high angular resolution diffusion tractography: a feasibility study.
        Neuroimage. 2013; 68: 105-111
        • Catani M.
        • Thiebaut de Schotten M.
        A diffusion tensor imaging tractography atlas for virtual in vivo dissections.
        Cortex. 2008; 44: 1105-1132
        • Tillema J.M.
        • Leach J.L.
        • Krueger D.A.
        • Franz D.N.
        Everolimus alters white matter diffusion in tuberous sclerosis complex.
        Neurology. 2012; 78: 526-531
        • Bava S.
        • Boucquey V.
        • Goldenberg D.
        • et al.
        Sex differences in adolescent white matter architecture.
        Brain Res. 2011; 1375: 41-48
        • Giorgio A.
        • Watkins K.E.
        • Chadwick M.
        • et al.
        Longitudinal changes in grey and white matter during adolescence.
        Neuroimage. 2010; 49: 94-103
        • Lebel C.
        • Beaulieu C.
        Longitudinal development of human brain wiring continues from childhood into adulthood.
        J Neurosci. 2011; 31: 10937-10947
        • Sancak O.
        • Nellist M.
        • Goedbloed M.
        • et al.
        Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype–phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex.
        Eur J Hum Genet. 2005; 13: 731-741
        • Au K.S.
        • Williams A.T.
        • Roach E.S.
        • et al.
        Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States.
        Genet Med. 2007; 9: 88-100
        • Numis A.L.
        • Major P.
        • Montenegro M.A.
        • Muzykewicz D.A.
        • Pulsifer M.B.
        • Thiele E.A.
        Identification of risk factors for autism spectrum disorders in tuberous sclerosis complex.
        Neurology. 2011; 76: 981-987
        • Kaczorowska M.
        • Jurkiewicz E.
        • Domańska-Pakieła D.
        • et al.
        Cerebral tuber count and its impact on mental outcome of patients with tuberous sclerosis complex.
        Epilepsia. 2011; 52: 22-27
        • Vignoli A.
        • La Briola F.
        • Turner K.
        • et al.
        Epilepsy in TSC: certain etiology does not mean certain prognosis.
        Epilepsia. 2013; 54: 2134-2142
        • Zaroff C.M.
        • Barr W.B.
        • Carlson C.
        • et al.
        Mental retardation and relation to seizure and tuber burden in tuberous sclerosis complex.
        Seizure. 2006; 15: 558-562
        • Kassiri J.
        • Snyder T.J.
        • Bhargava R.
        • Wheatley B.M.
        • Sinclair D.B.
        Cortical tubers, cognition, and epilepsy in tuberous sclerosis.
        Pediatr Neurol. 2011; 44: 328-332
        • Dwyer B.E.
        • Wasterlain C.G.
        Electroconvulsive seizures in the immature rat adversely affect myelin accumulation.
        Exp Neurol. 1982; 78: 616-628