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. 2002 Dec;73(6):648–655. doi: 10.1136/jnnp.73.6.648

Voxel based morphometry of grey matter abnormalities in patients with medically intractable temporal lobe epilepsy: effects of side of seizure onset and epilepsy duration

S Keller 1, U Wieshmann 1, C Mackay 1, C Denby 1, J Webb 1, N Roberts 1
PMCID: PMC1757338  PMID: 12438464

Abstract

Objectives: To investigate the use of whole brain voxel based morphometry (VBM) and stereological analysis to study brain morphology in patients with medically intractable temporal lobe epilepsy; and to determine the relation between side, duration, and age of onset of temporal lobe epilepsy, history of childhood febrile convulsions, and grey matter structure.

Methods: Three dimensional magnetic resonance images were obtained from 58 patients with left sided seizure onset (LSSO) and 58 patients with right sided seizure onset (RSSO), defined using EEG and foramen ovale recordings in the course of presurgical evaluation for temporal lobectomy. Fifty eight normal controls formed a comparison group. VBM was used to characterise whole brain grey matter concentration, while the Cavalieri method of modern design stereology in conjunction with point counting was used to estimate hippocampal and amygdala volume. Age and sex were used as confounding covariates in analyses.

Results: LSSO and RSSO patients showed significant reductions in volume (using stereology) and grey matter concentration (using VBM) of the hippocampus, but not of the amygdala, in the presumed epileptogenic zone when compared with controls, but hippocampal (and amygdala) volume and grey matter concentration were not related to duration or age of onset of epilepsy. LSSO and RSSO patients with a history of childhood febrile convulsions had reduced hippocampal volumes in the presumed epileptogenic zone compared with patients without such a history. Left amygdala volume was also reduced in LSSO patients with a history of childhood convulsions. VBM results indicated bilateral thalamic, prefrontal, and cerebellar GMC reduction in patients, which correlated with duration and age of onset of epilepsy.

Conclusions: Hippocampal sclerosis is not necessarily the consequence of recurrent temporal lobe seizures. A major cause of hippocampal sclerosis appears to be an early aberrant neurological insult, such as childhood febrile seizures. Secondary brain abnormalities exist in regions outside the presumed epileptogenic zone and may result from recurrent seizures.

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Selected References

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  1. Ashburner J., Friston K. J. Voxel-based morphometry--the methods. Neuroimage. 2000 Jun;11(6 Pt 1):805–821. doi: 10.1006/nimg.2000.0582. [DOI] [PubMed] [Google Scholar]
  2. Baron J. C., Chételat G., Desgranges B., Perchey G., Landeau B., de la Sayette V., Eustache F. In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer's disease. Neuroimage. 2001 Aug;14(2):298–309. doi: 10.1006/nimg.2001.0848. [DOI] [PubMed] [Google Scholar]
  3. Bernasconi N., Bernasconi A., Andermann F., Dubeau F., Feindel W., Reutens D. C. Entorhinal cortex in temporal lobe epilepsy: a quantitative MRI study. Neurology. 1999 Jun 10;52(9):1870–1876. doi: 10.1212/wnl.52.9.1870. [DOI] [PubMed] [Google Scholar]
  4. Bernasconi N., Bernasconi A., Caramanos Z., Andermann F., Dubeau F., Arnold D. L. Morphometric MRI analysis of the parahippocampal region in temporal lobe epilepsy. Ann N Y Acad Sci. 2000 Jun;911:495–500. doi: 10.1111/j.1749-6632.2000.tb06752.x. [DOI] [PubMed] [Google Scholar]
  5. Bernasconi N., Bernasconi A., Caramanos Z., Dubeau F., Richardson J., Andermann F., Arnold D. L. Entorhinal cortex atrophy in epilepsy patients exhibiting normal hippocampal volumes. Neurology. 2001 May 22;56(10):1335–1339. doi: 10.1212/wnl.56.10.1335. [DOI] [PubMed] [Google Scholar]
  6. Cendes F., Andermann F., Gloor P., Lopes-Cendes I., Andermann E., Melanson D., Jones-Gotman M., Robitaille Y., Evans A., Peters T. Atrophy of mesial structures in patients with temporal lobe epilepsy: cause or consequence of repeated seizures? Ann Neurol. 1993 Dec;34(6):795–801. doi: 10.1002/ana.410340607. [DOI] [PubMed] [Google Scholar]
  7. Davies K. G., Hermann B. P., Dohan F. C., Jr, Foley K. T., Bush A. J., Wyler A. R. Relationship of hippocampal sclerosis to duration and age of onset of epilepsy, and childhood febrile seizures in temporal lobectomy patients. Epilepsy Res. 1996 Jun;24(2):119–126. doi: 10.1016/0920-1211(96)00008-3. [DOI] [PubMed] [Google Scholar]
  8. DeCarli C., Hatta J., Fazilat S., Fazilat S., Gaillard W. D., Theodore W. H. Extratemporal atrophy in patients with complex partial seizures of left temporal origin. Ann Neurol. 1998 Jan;43(1):41–45. doi: 10.1002/ana.410430110. [DOI] [PubMed] [Google Scholar]
  9. Duncan J. S. Imaging and epilepsy. Brain. 1997 Feb;120(Pt 2):339–377. doi: 10.1093/brain/120.2.339. [DOI] [PubMed] [Google Scholar]
  10. Good C. D., Johnsrude I. S., Ashburner J., Henson R. N., Friston K. J., Frackowiak R. S. A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage. 2001 Jul;14(1 Pt 1):21–36. doi: 10.1006/nimg.2001.0786. [DOI] [PubMed] [Google Scholar]
  11. Guerreiro C., Cendes F., Li L. M., Jones-Gotman M., Andermann F., Dubeau F., Piazzini A., Feindel W. Clinical patterns of patients with temporal lobe epilepsy and pure amygdalar atrophy. Epilepsia. 1999 Apr;40(4):453–461. doi: 10.1111/j.1528-1157.1999.tb00740.x. [DOI] [PubMed] [Google Scholar]
  12. Ho S. S., Consalvo D., Gilliam F., Faught E., Bilir E., Morawetz R., Kuzniecky R. I. Amygdala atrophy and seizure outcome after temporal lobe epilepsy surgery. Neurology. 1998 Nov;51(5):1502–1504. doi: 10.1212/wnl.51.5.1502. [DOI] [PubMed] [Google Scholar]
  13. Keller Simon S., Mackay Clare E., Barrick Thomas R., Wieshmann Udo C., Howard Matthew A., Roberts Neil. Voxel-based morphometric comparison of hippocampal and extrahippocampal abnormalities in patients with left and right hippocampal atrophy. Neuroimage. 2002 May;16(1):23–31. doi: 10.1006/nimg.2001.1072. [DOI] [PubMed] [Google Scholar]
  14. Lindvall O., Nilsson B. Cerebellar atrophy following phenytoin intoxication. Ann Neurol. 1984 Aug;16(2):258–260. doi: 10.1002/ana.410160218. [DOI] [PubMed] [Google Scholar]
  15. Liu R. S., Lemieux L., Bell G. S., Bartlett P. A., Sander J. W., Sisodiya S. M., Shorvon S. D., Duncan J. S. A longitudinal quantitative MRI study of community-based patients with chronic epilepsy and newly diagnosed seizures: methodology and preliminary findings. Neuroimage. 2001 Jul;14(1 Pt 1):231–243. doi: 10.1006/nimg.2001.0773. [DOI] [PubMed] [Google Scholar]
  16. Mackay C. E., Webb J. A., Eldridge P. R., Chadwick D. W., Whitehouse G. H., Roberts N. Quantitative magnetic resonance imaging in consecutive patients evaluated for surgical treatment of temporal lobe epilepsy. Magn Reson Imaging. 2000 Dec;18(10):1187–1199. doi: 10.1016/s0730-725x(00)00220-4. [DOI] [PubMed] [Google Scholar]
  17. Mathern G. W., Babb T. L., Leite J. P., Pretorius K., Yeoman K. M., Kuhlman P. A. The pathogenic and progressive features of chronic human hippocampal epilepsy. Epilepsy Res. 1996 Dec;26(1):151–161. doi: 10.1016/s0920-1211(96)00052-6. [DOI] [PubMed] [Google Scholar]
  18. Meiners L. C., Witkamp T. D., de Kort G. A., van Huffelen A. C., van der Graaf Y., Jansen G. H., van der Grond J., van Veelen C. W. Relevance of temporal lobe white matter changes in hippocampal sclerosis. Magnetic resonance imaging and histology. Invest Radiol. 1999 Jan;34(1):38–45. doi: 10.1097/00004424-199901000-00006. [DOI] [PubMed] [Google Scholar]
  19. Moran N. F., Lemieux L., Kitchen N. D., Fish D. R., Shorvon S. D. Extrahippocampal temporal lobe atrophy in temporal lobe epilepsy and mesial temporal sclerosis. Brain. 2001 Jan;124(Pt 1):167–175. doi: 10.1093/brain/124.1.167. [DOI] [PubMed] [Google Scholar]
  20. Nishio S., Morioka T., Hisada K., Fukui M. Temporal lobe epilepsy: a clinicopathological study with special reference to temporal neocortical changes. Neurosurg Rev. 2000 Jun;23(2):84–89. doi: 10.1007/pl00021698. [DOI] [PubMed] [Google Scholar]
  21. Roberts N., Garden A. S., Cruz-Orive L. M., Whitehouse G. H., Edwards R. H. Estimation of fetal volume by magnetic resonance imaging and stereology. Br J Radiol. 1994 Nov;67(803):1067–1077. doi: 10.1259/0007-1285-67-803-1067. [DOI] [PubMed] [Google Scholar]
  22. Salmenperä T., Kälviäinen R., Partanen K., Mervaala E., Pitkänen A. MRI volumetry of the hippocampus, amygdala, entorhinal cortex, and perirhinal cortex after status epilepticus. Epilepsy Res. 2000 Jul;40(2-3):155–170. doi: 10.1016/s0920-1211(00)00121-2. [DOI] [PubMed] [Google Scholar]
  23. Salmenperä T., Kälviäinen R., Partanen K., Pitkänen A. Hippocampal and amygdaloid damage in partial epilepsy: a cross-sectional MRI study of 241 patients. Epilepsy Res. 2001 Jul;46(1):69–82. doi: 10.1016/s0920-1211(01)00258-3. [DOI] [PubMed] [Google Scholar]
  24. Salmenperä T., Kälviäinen R., Partanen K., Pitkänen A. Hippocampal damage caused by seizures in temporal lobe epilepsy. Lancet. 1998 Jan 3;351(9095):35–35. doi: 10.1016/S0140-6736(05)78092-2. [DOI] [PubMed] [Google Scholar]
  25. Saykin A. J., Johnson S. C., Flashman L. A., McAllister T. W., Sparling M., Darcey T. M., Moritz C. H., Guerin S. J., Weaver J., Mamourian A. Functional differentiation of medial temporal and frontal regions involved in processing novel and familiar words: an fMRI study. Brain. 1999 Oct;122(Pt 10):1963–1971. doi: 10.1093/brain/122.10.1963. [DOI] [PubMed] [Google Scholar]
  26. Tasch E., Cendes F., Li L. M., Dubeau F., Andermann F., Arnold D. L. Neuroimaging evidence of progressive neuronal loss and dysfunction in temporal lobe epilepsy. Ann Neurol. 1999 May;45(5):568–576. doi: 10.1002/1531-8249(199905)45:5<568::aid-ana4>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  27. Theodore W. H., Bhatia S., Hatta J., Fazilat S., DeCarli C., Bookheimer S. Y., Gaillard W. D. Hippocampal atrophy, epilepsy duration, and febrile seizures in patients with partial seizures. Neurology. 1999 Jan 1;52(1):132–136. doi: 10.1212/wnl.52.1.132. [DOI] [PubMed] [Google Scholar]
  28. Van Paesschen W., Duncan J. S., Stevens J. M., Connelly A. Longitudinal quantitative hippocampal magnetic resonance imaging study of adults with newly diagnosed partial seizures: one-year follow-up results. Epilepsia. 1998 Jun;39(6):633–639. doi: 10.1111/j.1528-1157.1998.tb01432.x. [DOI] [PubMed] [Google Scholar]
  29. Woermann F. G., Free S. L., Koepp M. J., Ashburner J., Duncan J. S. Voxel-by-voxel comparison of automatically segmented cerebral gray matter--A rater-independent comparison of structural MRI in patients with epilepsy. Neuroimage. 1999 Oct;10(4):373–384. doi: 10.1006/nimg.1999.0481. [DOI] [PubMed] [Google Scholar]
  30. Woermann F. G., Free S. L., Koepp M. J., Sisodiya S. M., Duncan J. S. Abnormal cerebral structure in juvenile myoclonic epilepsy demonstrated with voxel-based analysis of MRI. Brain. 1999 Nov;122(Pt 11):2101–2108. doi: 10.1093/brain/122.11.2101. [DOI] [PubMed] [Google Scholar]
  31. Woermann F. G., van Elst L. T., Koepp M. J., Free S. L., Thompson P. J., Trimble M. R., Duncan J. S. Reduction of frontal neocortical grey matter associated with affective aggression in patients with temporal lobe epilepsy: an objective voxel by voxel analysis of automatically segmented MRI. J Neurol Neurosurg Psychiatry. 2000 Feb;68(2):162–169. doi: 10.1136/jnnp.68.2.162. [DOI] [PMC free article] [PubMed] [Google Scholar]

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