, Volume 59, Issue 3, pp 237–245 | Cite as

Evaluation of deep gray matter volume, cortical thickness and white matter integrity in patients with typical absence epilepsy: a study using voxelwise-based techniques

  • D. G. Corrêa
  • N. Ventura
  • N. Zimmermann
  • T. M. Doring
  • G. Tukamoto
  • J. Leme
  • M. Pereira
  • I. D’Andrea
  • C. Rêgo
  • S. V. Alves-Leon
  • E. L. Gasparetto
Functional Neuroradiology



The objective of this study was to evaluate the cortical thickness and the volume of deep gray matter structures, measured from 3D T1-weighted gradient echo imaging, and white matter integrity, by diffusion tensor imaging (DTI) in patients with typical absence epilepsy (AE).


Patients (n = 19) with typical childhood AE and juvenile AE, currently taking antiepileptic medication, were compared with control subjects (n = 19), matched for gender and age. 3D T1 magnetization-prepared rapid gradient echo-weighted imaging and DTI along 30 noncolinear directions were performed using a 1.5-T MR scanner. FreeSurfer was used to perform cortical volumetric reconstruction and segmentation of deep gray matter structures. For tract-based spatial statistics analysis of DTI, a white matter skeleton was created, along with a permutation-based inference with 5000 permutations. A threshold of p < 0.05 was used to identify abnormalities in fractional anisotropy (FA). The mean, radial, and axial diffusivities were also projected onto the mean FA skeleton.


Patients with AE presented decreased FA and increased mean diffusivity and radial diffusivity values in the genu and the body of the corpus callosum and right anterior corona radiata, as well as decreased axial diffusivity in the left posterior thalamic radiation, inferior cerebellar peduncle, right cerebral peduncle, and right corticospinal tract. However, there were no significant differences in cortical thickness or deep gray matter structure volumes between patients with AE and controls.


Abnormalities found in white matter integrity may help to better understand the pathophysiology of AE and optimize diagnosis and treatment strategies.


Absence epilepsy Magnetic resonance imaging Cortical thickness Diffusion tensor imaging 


Compliance with ethical standards

We declare that all human and animals studies have been approved by the ethical review board of the Clementino Fraga Filho University Hospital and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. We declare that all patients and/or their legal guardians gave informed consent prior to inclusion in this study.

Conflict of interest

We declare that we have no conflict of interest.


  1. 1.
    Engel J Jr (2001) A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia 42:796–803CrossRefPubMedGoogle Scholar
  2. 2.
    Engel J Jr (2006) Report of the ILAE classification core group. Epilepsia 47:1558–1568CrossRefPubMedGoogle Scholar
  3. 3.
    Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde BW, Engel J, French J, Glauser TA, Mathern GW, Moshé SL, Nordli D, Plouin P, Scheffer IE (2010) Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 51:676–685CrossRefPubMedGoogle Scholar
  4. 4.
    Guilhoto LM, Manreza ML, Yacubian EM (2003) Syndromic classification of patients with typical absence seizures. Arq Neuropsiquiatr 61:580–587CrossRefPubMedGoogle Scholar
  5. 5.
    Chang BS, Lowenstein DH (2003) Epilepsy. N Engl J Med 349:1257–1266CrossRefPubMedGoogle Scholar
  6. 6.
    Holmes GL, McKeever M, Adamson M (1987) Absence seizures in children: clinical and electroencephalographic features. Ann Neurol 21:268–273CrossRefPubMedGoogle Scholar
  7. 7.
    Panayiotopoulos CP (2008) Typical absence seizures and related epileptic syndromes: assessment of current state and directions for future research. Epilepsia 49:2131–2139CrossRefPubMedGoogle Scholar
  8. 8.
    Wirrell EC (2003) Natural history of absence epilepsy in children. Can J Neurol Sci 30:184–188CrossRefPubMedGoogle Scholar
  9. 9.
    Seidenbecher T, Staak R, Pape HC (1998) Relations between cortical and thalamic cellular activities during absence seizures in rats. Eur J Neurosci 10:1103–1312CrossRefPubMedGoogle Scholar
  10. 10.
    Meeren HK, Pijn JP, Van Luijtelaar EL, Coenen AM, Lopes da Silva FH (2002) Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats. J Neurosci 22:1480–1495PubMedGoogle Scholar
  11. 11.
    Blumenfeld H (2005) Consciousness and epilepsy: why are patients with absence seizures absent? Prog Brain Res 150:271–286CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Meeren H, van Luijtelaar G, Lopes da Silva F, Coenen A (2005) Evolving concepts on the pathophysiology of absence seizures: the cortical focus theory. Arch Neurol 62:371–376CrossRefPubMedGoogle Scholar
  13. 13.
    Holmes MD, Brown M, Tucker DM (2004) Are “generalized” seizures truly generalized? Evidence of localized mesial frontal and frontopolar discharges in absence. Epilepsia 45:1568–1579CrossRefPubMedGoogle Scholar
  14. 14.
    Gaillard WD, Chiron C, Cross JH, Harvey AS, Kuzniecky R, Hertz-Pannier L, Vezina LG, ILAE, Committee for Neuroimaging, Subcommittee for Pediatric (2009) Guidelines for imaging infants and children with recent-onset epilepsy. Epilepsia 50:2147–2153CrossRefPubMedGoogle Scholar
  15. 15.
    Chan CH, Briellmann RS, Pell GS, Scheffer IE, Abbott DF, Jackson GD (2006) Thalamic atrophy in childhood absence epilepsy. Epilepsia 47:399–405CrossRefPubMedGoogle Scholar
  16. 16.
    Pardoe H, Pell GS, Abbott DF, Berg AT, Jackson GD (2008) Multi-site voxel-based morphometry: methods and a feasibility demonstration with childhood absence epilepsy. NeuroImage 42:611–616CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Caplan R, Levitt J, Siddarth P, Wu KN, Gurbani S, Sankar R, Shields WD (2009) Frontal and temporal volumes in childhood absence epilepsy. Epilepsia 50:2466–2472CrossRefPubMedGoogle Scholar
  18. 18.
    Betting LE, Mory SB, Lopes-Cendes I, Li LM, Guerreiro MM, Guerreiro CA, Cendes F (2006) MRI volumetry shows increased anterior thalamic volumes in patients with absence seizures. Epilepsy Behav 8:575–580CrossRefPubMedGoogle Scholar
  19. 19.
    Betting LE, Mory SB, Li LM, Lopes-Cendes I, Guerreiro MM, Guerreiro CA, Cendes F (2006) Voxel-based morphometry in patients with idiopathic generalized epilepsies. NeuroImage 32:498–502CrossRefPubMedGoogle Scholar
  20. 20.
    Sundgren PC, Dong Q, Gómez-Hassan D, Mukherji SK, Maly P, Welsh R (2004) Diffusion tensor imaging of the brain: review of clinical applications. Neuroradiology 46:339–350CrossRefPubMedGoogle Scholar
  21. 21.
    Luo C, Xia Y, Li Q, Xue K, Lai Y, Gong Q, Zhou D, Yao D (2011) Diffusion and volumetry abnormalities in subcortical nuclei of patients with absence seizures. Epilepsia 52:1092–1099CrossRefPubMedGoogle Scholar
  22. 22.
    Yang T, Guo Z, Luo C, Li Q, Yan B, Liu L, Gong Q, Yao D, Zhou D (2012) White matter impairment in the basal ganglia-thalamocortical circuit of drug-naïve childhood absence epilepsy. Epilepsy Res 99:267–273CrossRefPubMedGoogle Scholar
  23. 23.
    Stoeter P, Dellani PR, Vucurevic G (2008) Diffusion tensor imaging of cerebral white matter. Clin Neuroradiol 18:155–162CrossRefGoogle Scholar
  24. 24.
    Fischl B, Dale AM (2000) Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci U S A 97:11050–11055CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, van der Kouwe A, Killiany R, Kennedy D, Klaveness S, Montillo A, Makris N, Rosen B, Dale AM (2002) Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33:341–355CrossRefPubMedGoogle Scholar
  26. 26.
    Desikan RS, Ségonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D, Buckner RL, Dale AM, Maguire RP, Hyman BT, Albert MS, Killiany RJ (2006) An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. NeuroImage 31:968–980CrossRefPubMedGoogle Scholar
  27. 27.
    Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, Bannister PR, De Luca M, Drobnjak I, Flitney DE, Niazy RK, Saunders J, Vickers J, Zhang Y, De Stefano N, Brady JM, Matthews PM (2004) Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage 23:208–219CrossRefGoogle Scholar
  28. 28.
    Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins KE, Ciccarelli O, Cader MZ, Matthews PM, Behrens TE (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. NeuroImage 31:1487–1505CrossRefPubMedGoogle Scholar
  29. 29.
    Smith SM, Nichols TE (2009) Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. NeuroImage 44:83–98CrossRefPubMedGoogle Scholar
  30. 30.
    Braga AM, Fujisao EK, Verdade RC, Paschoalato RP, Paschoalato RP, Yamashita S, Betting LE (2015) Investigation of the cingulate cortex in idiopathic generalized epilepsy. Epilepsia 56:1803–1811CrossRefPubMedGoogle Scholar
  31. 31.
    Marsh ED, Brooks-Kayal AR, Porter BE (2006) Seizures and antiepileptic drugs: does exposure alter normal brain development? Epilepsia 47:1999–2010CrossRefPubMedGoogle Scholar
  32. 32.
    Guerrini R, Belmonte A, Canapicchi R, Casalini C, Perucca E (1998) Reversible pseudoatrophy of the brain and mental deterioration associated with valproate treatment. Epilepsia 39:27–32CrossRefPubMedGoogle Scholar
  33. 33.
    Chahboune H, Mishra AM, DeSalvo MN, Staib LH, Purcaro M, Scheinost D, Papademetris X, Fyson SJ, Lorincz ML, Crunelli V, Hyder F, Blumenfeld H (2009) DTI abnormalities in anterior corpus callosum of rats with spike-wave epilepsy. NeuroImage 47:459–466CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Hagmann P, Jonasson L, Maeder P, Thiran JP, Wedeen VJ, Meuli R (2006) Understanding diffusion MR imaging techniques: from scalar diffusion-weighted imaging to diffusion tensor imaging and beyond. Radiographics 26:S205–S223CrossRefPubMedGoogle Scholar
  35. 35.
    Qiu D, Tan LH, Zhou K, Khong PL (2008) Diffusion tensor imaging of normal white matter maturation from late childhood to young adulthood: voxel-wise evaluation of mean diffusivity, fractional anisotropy, radial and axial diffusivities, and correlation with reading development. NeuroImage 41:223–232CrossRefPubMedGoogle Scholar
  36. 36.
    Bernhardt BC, Rozen DA, Worsley KJ, Evans AC, Bernasconi N, Bernasconi A (2009) Thalamo-cortical network pathology in idiopathic generalized epilepsy: insights from MRI-based morphometric correlation analysis. NeuroImage 46:373–381CrossRefPubMedGoogle Scholar
  37. 37.
    Kim JB, Suh SI, Seo WK, Oh K, Koh SB, Kim JH (2014) Altered thalamocortical functional connectivity in idiopathic generalized epilepsy. Epilepsia 55:592–600CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • D. G. Corrêa
    • 1
    • 2
  • N. Ventura
    • 1
    • 2
  • N. Zimmermann
    • 1
    • 3
  • T. M. Doring
    • 2
  • G. Tukamoto
    • 1
    • 2
  • J. Leme
    • 1
  • M. Pereira
    • 1
  • I. D’Andrea
    • 4
  • C. Rêgo
    • 4
  • S. V. Alves-Leon
    • 4
  • E. L. Gasparetto
    • 1
    • 2
  1. 1.Department of Radiology, Hospital Universitário Clementino Fraga FilhoFederal University of Rio de JaneiroRio de JaneiroBrazil
  2. 2.Clínica de Diagnóstico por Imagem (CDPI)Rio de JaneiroBrazil
  3. 3.Department of PsychologyPontifical Catholic University of Rio Grande do SulPorto AlegreBrazil
  4. 4.Department of Neurology, Epilepsy Center, Hospital Universitário Clementino Fraga FilhoFederal University of Rio de JaneiroRio de JaneiroBrazil

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