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The predictive value of hypometabolism in focal epilepsy: a prospective study in surgical candidates

  • José Tomás
  • Francesca Pittau
  • Alexander Hammers
  • Sandrine Bouvard
  • Fabienne Picard
  • Maria Isabel Vargas
  • Francisco Sales
  • Margitta Seeck
  • Valentina GaribottoEmail author
Original Article
  • 286 Downloads
Part of the following topical collections:
  1. Neurology

Abstract

Purpose

FDG PET is an established tool in presurgical epilepsy evaluation, but it is most often used selectively in patients with discordant MRI and EEG results. Interpretation is complicated by the presence of remote or multiple areas of hypometabolism, which leads to doubt as to the true location of the seizure onset zone (SOZ) and might have implications for predicting the surgical outcome. In the current study, we determined the sensitivity and specificity of PET localization prospectively in a consecutive unselected cohort of patients with focal epilepsy undergoing in-depth presurgical evaluation.

Methods

A total of 130 patients who underwent PET imaging between 2006 and 2015 matched our inclusion criteria, and of these, 86 were operated on (72% with a favourable surgical outcome, Engel class I). Areas of focal hypometabolism were identified using statistical parametric mapping and concordance with MRI, EEG and intracranial EEG was evaluated. In the surgically treated patients, postsurgical outcome was used as the gold standard for correctness of localization (minimum follow-up 12 months).

Results

PET sensitivity and specificity were both 95% in 86 patients with temporal lobe epilepsy (TLE) and 80% and 95%, respectively, in 44 patients with extratemporal epilepsy (ETLE). Significant extratemporal hypometabolism was observed in 17 TLE patients (20%). Temporal hypometabolism was observed in eight ETLE patients (18%). Among the 86 surgically treated patients, 26 (30%) had hypometabolism extending beyond the SOZ. The presence of unilobar hypometabolism, included in the resection, was predictive of complete seizure control (p = 0.007), with an odds ratio of 5.4.

Conclusion

Additional hypometabolic areas were found in one of five of this group of nonselected patients with focal epilepsy, including patients with “simple” lesional epilepsy, and this finding should prompt further in-depth evaluation of the correlation between EEG findings, semiology and PET. Hypometabolism confined to the epileptogenic zone as defined by EEG and MRI is associated with a favourable postoperative outcome in both TLE and ETLE patients.

Keywords

FDG PET Temporal epilepsy Extratemporal epilepsy Prognosis Predictive value Seizure onset zone 

Abbreviations

FDG

18F-Fluorodeoxyglucose

PET

Positron emission tomography

MRI

Magnetic resonance imaging

TLE

Temporal lobe epilepsy

ETLE

Extratemporal lobe epilepsy

EEG

Electroencephalography

SOZ

Seizure onset zone

SPM

Statistical parametric mapping

Notes

Acknowledgments

J.T. was supported by the “Egas Moniz” grant of the Neurology Portuguese Society. M.S. was supported by SNF 113766, SNF 180365, SNF 163398. Statistical help was provided by the Clinical Research Center, Geneva University Hospitals (Prof. Thomas Perneger). The reference database was provided by the CERMEP-Imagerie du vivant, Lyon, France.

Author contributions

J.T., M.S. and V.G. contributed to the concept and study design. M.S. and F.Picard. were responsible for patient management. J.T., F.Pittau, F.Picard, M.I.V., M.S. and V.G. contributed to data acquisition and analysis. J.T. and V.G. drafted the manuscript, tables and figures. F.Pittau, A.H., S.B., F.Picard, M.I.V., F.S. and M.S. contributed to critical revision of the manuscript. All authors approved the final version.

Compliance with ethical standards

This study was approved by the Geneva Cantonal Ethics Commission, and was in accordance with the principles of the Declaration of Helsinki and its further amendments.

Conflicts of interests

None.

References

  1. 1.
    Fiest KM, Sauro KM, Wiebe S, Patten SB, Kwon CS, Dykeman J, et al. Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies. Neurology. 2017;88(3):296–303.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Pittau F, Grouiller F, Spinelli L, Seeck M, Michel CM, Vulliemoz S. The role of functional neuroimaging in pre-surgical epilepsy evaluation. Front Neurol. 2014;5:31.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Rosenow F, Luders H. Presurgical evaluation of epilepsy. Brain. 2001;124(Pt 9):1683–700.PubMedGoogle Scholar
  4. 4.
    Engel J Jr, Brown WJ, Kuhl DE, Phelps ME, Mazziotta JC, Crandall PH. Pathological findings underlying focal temporal lobe hypometabolism in partial epilepsy. Ann Neurol. 1982;12(6):518–28.PubMedGoogle Scholar
  5. 5.
    Henry TR, Roman DD. Presurgical epilepsy localization with interictal cerebral dysfunction. Epilepsy Behav. 2011;20(2):194–208.PubMedGoogle Scholar
  6. 6.
    Nelissen N, Van Paesschen W, Baete K, Van Laere K, Palmini A, Van Billoen H, et al. Correlations of interictal FDG-PET metabolism and ictal SPECT perfusion changes in human temporal lobe epilepsy with hippocampal sclerosis. Neuroimage. 2006;32(2):684–95.PubMedGoogle Scholar
  7. 7.
    Foldvary N, Lee N, Hanson MW, Coleman RE, Hulette CM, Friedman AH, et al. Correlation of hippocampal neuronal density and FDG-PET in mesial temporal lobe epilepsy. Epilepsia. 1999;40(1):26–9.PubMedGoogle Scholar
  8. 8.
    Rathore C, Dickson JC, Teotónio R, Ell P, Duncan JS. The utility of 18F-fluorodeoxyglucose PET (FDG PET) in epilepsy surgery. Epilepsy Res. 2014;108(8):1306–14.PubMedGoogle Scholar
  9. 9.
    LoPinto-Khoury C, Sperling MR, Skidmore C, Nei M, Evans J, Sharan A, et al. Surgical outcome in PET-positive, MRI-negative patients with temporal lobe epilepsy. Epilepsia. 2012;53(2):342–8.PubMedGoogle Scholar
  10. 10.
    Carne RP, O'Brien TJ, Kilpatrick CJ, MacGregor LR, Hicks RJ, Murphy MA, et al. MRI-negative PET-positive temporal lobe epilepsy: a distinct surgically remediable syndrome. Brain. 2004;127(Pt 10):2276–85.PubMedGoogle Scholar
  11. 11.
    Chassoux F, Landré E, Mellerio C, Turak B, Mann MW, Daumas-Duport C, et al. Type II focal cortical dysplasia: electroclinical phenotype and surgical outcome related to imaging. Epilepsia. 2012;53(2):349–58.PubMedGoogle Scholar
  12. 12.
    Wong CH, Bleasel A, Wen L, Eberl S, Byth K, Fulham M, et al. Relationship between preoperative hypometabolism and surgical outcome in neocortical epilepsy surgery. Epilepsia. 2012;53(8):1333–40.PubMedGoogle Scholar
  13. 13.
    Guedj E, Bonini F, Gavaret M, Trébuchon A, Aubert S, Boucekine M, et al. 18FDG-PET in different subtypes of temporal lobe epilepsy: SEEG validation and predictive value. Epilepsia. 2015;56(3):414–21.PubMedGoogle Scholar
  14. 14.
    Kumar A, Juhász C, Asano E, Sood S, Muzik O, Chugani HT. Objective detection of epileptic foci by 18F-FDG PET in children undergoing epilepsy surgery. J Nucl Med. 2010;51(12):1901–7.Google Scholar
  15. 15.
    Lee JJ, Kang WJ, Lee DS, Lee JS, Hwang H, Kim KJ, et al. Diagnostic performance of 18F-FDG PET and ictal 99mTc-HMPAO SPET in pediatric temporal lobe epilepsy: quantitative analysis by statistical parametric mapping, statistical probabilistic anatomical map, and subtraction ictal SPET. Seizure. 2005;14(3):213–20.PubMedGoogle Scholar
  16. 16.
    Leiderman DB, Albert P, Balish M, Bromfield E, Theodore WH. The dynamics of metabolic change following seizures as measured by positron emission tomography with fludeoxyglucose F 18. Arch Neurol. 1994;51(9):932–6.PubMedGoogle Scholar
  17. 17.
    Archambaud F, Bouilleret V, Hertz-Pannier L, Chaumet-Riffaud P, Rodrigo S, Dulac O, et al. Optimizing statistical parametric mapping analysis of 18F-FDG PET in children. EJNMMI Res. 2013;3(1):2.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Trebossen R, Comtat C, Brulon V, Bailly P, Meyer ME. Comparison of two commercial whole body PET systems based on LSO and BGO crystals respectively for brain imaging. Med Phys. 2009;36(4):1399–409.PubMedGoogle Scholar
  19. 19.
    Vargas MI, Becker M, Garibotto V, Heinzer S, Loubeyre P, Gariani J, et al. Approaches for the optimization of MR protocols in clinical hybrid PET/MRI studies. MAGMA. 2013;26(1):57–69.PubMedGoogle Scholar
  20. 20.
    Bancaud J. Surgery of epilepsy based on stereotactic investigations – the plan of the SEEG investigation. Acta Neurochir Suppl (Wien). 1980;30:25–34.Google Scholar
  21. 21.
    Engel J Jr, Van Ness P, Rasmussen TB, Ojemann LM. Outcome with respect to epileptic seizures. In: Engel J Jr (editor) Surgical treatment of the epilepsies. 2nd ed. New York: Raven Press; 1993. p. 609–21.Google Scholar
  22. 22.
    Theodore WH, Sato S, Kufta C, Balish MB, Bromfield EB, Leiderman DB. Temporal lobectomy for uncontrolled seizures: the role of positron emission tomography. Ann Neurol. 1992;32(6):789–94.PubMedGoogle Scholar
  23. 23.
    Kim SK, Lee DS, Lee SK, Kim YK, Kang KW, Chung CK, et al. Diagnostic performance of [18F]FDG-PET and ictal [99mTc]-HMPAO SPECT in occipital lobe epilepsy. Epilepsia. 2001;42(12):1531–40.PubMedGoogle Scholar
  24. 24.
    Meyer PT, Cortés-Blanco A, Pourdehnad M, Levy-Reis I, Desiderio L, Jang S, et al. Inter-modality comparisons of seizure focus lateralization in complex partial seizures. Eur J Nucl Med. 2001;28(10):1529–40.PubMedGoogle Scholar
  25. 25.
    Salanova V, Markand O, Worth R. Focal functional deficits in temporal lobe epilepsy on PET scans and the intracarotid amobarbital procedure: comparison of patients with unitemporal epilepsy with those requiring intracranial recordings. Epilepsia. 2001;42(2):198–203.PubMedGoogle Scholar
  26. 26.
    Lee SK, Lee SY, Kim KK, Hong KS, Lee DS, Chung CK. Surgical outcome and prognostic factors of cryptogenic neocortical epilepsy. Ann Neurol. 2005;58(4):525–32.PubMedGoogle Scholar
  27. 27.
    Uijl SG, Leijten FS, Arends JB, Parra J, van Huffelen AC, Moons KG. The added value of [18F]-fluoro-D-deoxyglucose positron emission tomography in screening for temporal lobe epilepsy surgery. Epilepsia. 2007;48(11):2121–9.PubMedGoogle Scholar
  28. 28.
    Kim SK, Na DG, Byun HS, Kim SE, Suh YL, Choi JY, et al. Focal cortical dysplasia: comparison of MRI and FDG-PET. J Comput Assist Tomogr. 2000;24(2):296–302.PubMedGoogle Scholar
  29. 29.
    Mendes Coelho VC, Morita ME, Amorim BJ, Ramos CD, Yasuda CL, Tedeschi H, et al. Automated online quantification method for (18)F-FDG positron emission tomography/CT improves detection of the epileptogenic zone in patients with pharmacoresistant epilepsy. Front Neurol. 2017;8:453.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Wong CH, Bleasel A, Wen L, Eberl S, Byth K, Fulham M, et al. The topography and significance of extratemporal hypometabolism in refractory mesial temporal lobe epilepsy examined by FDG-PET. Epilepsia. 2010;51(8):1365–73.PubMedGoogle Scholar
  31. 31.
    Takaya S, Hanakawa T, Hashikawa K, Ikeda A, Sawamoto N, Nagamine T, et al. Prefrontal hypofunction in patients with intractable mesial temporal lobe epilepsy. Neurology. 2006;67(9):1674–6.PubMedGoogle Scholar
  32. 32.
    Lieb JP, Dasheiff RM, Engel J Jr. Role of the frontal lobes in the propagation of mesial temporal lobe seizures. Epilepsia. 1991;32(6):822–37.PubMedGoogle Scholar
  33. 33.
    Alkonyi B, Juhász C, Muzik O, Asano E, Saporta A, Shah A, et al. Quantitative brain surface mapping of an electrophysiologic/metabolic mismatch in human neocortical epilepsy. Epilepsy Res. 2009;87(1):77–87.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Jeong JW, Asano E, Kumar Pilli V, Nakai Y, Chugani HT, Juhász C. Objective 3D surface evaluation of intracranial electrophysiologic correlates of cerebral glucose metabolic abnormalities in children with focal epilepsy. Hum Brain Mapp. 2017;38:3098–112.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Ryvlin P, Mauguière F, Sindou M, Froment JC, Cinotti L. Interictal cerebral metabolism and epilepsy in cavernous angiomas. Brain. 1995;118(Pt 3):677–87.PubMedGoogle Scholar
  36. 36.
    Spencer S, Huh L. Outcomes of epilepsy surgery in adults and children. Lancet Neurol. 2008;7(6):525–37.PubMedGoogle Scholar
  37. 37.
    Tellez-Zenteno JF, Hernández Ronquillo L, Moien-Afshari F, Wiebe S. Surgical outcomes in lesional and non-lesional epilepsy: a systematic review and meta-analysis. Epilepsy Res. 2010;89(2-3):310–8.PubMedGoogle Scholar
  38. 38.
    Radtke RA, Hanson MW, Hoffman JM, Crain BJ, Walczak TS, Lewis DV, et al. Temporal lobe hypometabolism on PET: predictor of seizure control after temporal lobectomy. Neurology. 1993;43(6):1088–92.PubMedGoogle Scholar
  39. 39.
    Knowlton RC, Laxer KD, Ende G, Hawkins RA, Wong ST, Matson GB, et al. Presurgical multimodality neuroimaging in electroencephalographic lateralized temporal lobe epilepsy. Ann Neurol. 1997;42(6):829–37.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Dupont S, Semah F, Clémenceau S, Adam C, Baulac M, Samson Y. Accurate prediction of postoperative outcome in mesial temporal lobe epilepsy: a study using positron emission tomography with 18fluorodeoxyglucose. Arch Neurol. 2000;57(9):1331–6.PubMedGoogle Scholar
  41. 41.
    Struck AF, Hall LT, Floberg JM, Perlman SB, Dulli DA. Surgical decision making in temporal lobe epilepsy: a comparison of [(18)F]FDG-PET, MRI, and EEG. Epilepsy Behav. 2011;22(2):293–7.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Higo T, Sugano H, Nakajima M, Karagiozov K, Iimura Y, Suzuki M, et al. The predictive value of FDG-PET with 3D-SSP for surgical outcomes in patients with temporal lobe epilepsy. Seizure. 2016;41:127–33.PubMedGoogle Scholar
  43. 43.
    Choi JY, Kim SJ, Hong SB, Seo DW, Hong SC, Kim BT, et al. Extratemporal hypometabolism on FDG PET in temporal lobe epilepsy as a predictor of seizure outcome after temporal lobectomy. Eur J Nucl Med Mol Imaging. 2003;30(4):581–7.PubMedGoogle Scholar
  44. 44.
    Kim DW, Lee SK, Moon HJ, Jung KY, Chu K, Chung CK. Surgical treatment of nonlesional neocortical epilepsy: long-term longitudinal study. JAMA Neurol. 2017;74(3):324–31.PubMedGoogle Scholar
  45. 45.
    Desarnaud S, Mellerio C, Semah F, Laurent A, Landre E, Devaux B, et al. (18)F-FDG PET in drug-resistant epilepsy due to focal cortical dysplasia type 2: additional value of electroclinical data and coregistration with MRI. Eur J Nucl Med Mol Imaging. 2018;45(8):1449–60.PubMedGoogle Scholar
  46. 46.
    Kim DW, Lee SK, Yun CH, Kim KK, Lee DS, Chung CK, et al. Parietal lobe epilepsy: the semiology, yield of diagnostic workup, and surgical outcome. Epilepsia. 2004;45(6):641–9.PubMedGoogle Scholar
  47. 47.
    Kogias E, Klingler JH, Urbach H, Scheiwe C, Schmeiser B, Doostkam S, et al. 3 tesla MRI-negative focal epilepsies: presurgical evaluation, postoperative outcome and predictive factors. Clin Neurol Neurosurg. 2017;163:116–20.PubMedGoogle Scholar
  48. 48.
    Sarikaya I. PET studies in epilepsy. Am J Nucl Med Mol Imaging. 2015;5(5):416–30.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Galovic M, Koepp M. Advances of molecular imaging in epilepsy. Curr Neurol Neurosci Rep. 2016;16(6):58.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Hammers A, Koepp MJ, Brooks DJ, Duncan JS. Periventricular white matter flumazenil binding and postoperative outcome in hippocampal sclerosis. Epilepsia. 2005;46(6):944–8.PubMedGoogle Scholar
  51. 51.
    Yankam Njiwa J, Bouvard S, Catenoix H, Mauguiere F, Ryvlin P, Hammers A. Periventricular [(11)C]flumazenil binding for predicting postoperative outcome in individual patients with temporal lobe epilepsy and hippocampal sclerosis. Neuroimage Clin. 2013;3:242–8.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Theodore WH, Martinez AR, Khan OI, Liew CJ, Auh S, Dustin IM, et al. PET of serotonin 1A receptors and cerebral glucose metabolism for temporal lobectomy. J Nucl Med. 2012;53(9):1375–82.PubMedGoogle Scholar
  53. 53.
    Lam J, DuBois JM, Rowley J, González-Otárula KA, Soucy JP, Massarweh G, et al. In vivo metabotropic glutamate receptor type 5 abnormalities localize the epileptogenic zone in mesial temporal lobe epilepsy. Ann Neurol. 2019;85(2):218–28.PubMedGoogle Scholar
  54. 54.
    Kagawa K, Chugani DC, Asano E, Juhász C, Muzik O, Shah A, et al. Epilepsy surgery outcome in children with tuberous sclerosis complex evaluated with alpha-[11C]methyl-L-tryptophan positron emission tomography (PET). J Child Neurol. 2005;20(5):429–38.PubMedGoogle Scholar
  55. 55.
    Bauer M, Karch R, Zeitlinger M, Liu J, Koepp MJ, Asselin MC, et al. In vivo P-glycoprotein function before and after epilepsy surgery. Neurology. 2014;83(15):1326–31.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • José Tomás
    • 1
    • 2
  • Francesca Pittau
    • 1
    • 3
  • Alexander Hammers
    • 4
    • 5
  • Sandrine Bouvard
    • 6
  • Fabienne Picard
    • 1
    • 3
  • Maria Isabel Vargas
    • 3
    • 7
  • Francisco Sales
    • 2
  • Margitta Seeck
    • 1
    • 3
  • Valentina Garibotto
    • 3
    • 8
    Email author
  1. 1.EEG and Epilepsy Unit, Neurology DepartmentUniversity Hospitals of GenevaGenevaSwitzerland
  2. 2.Neurology DepartmentCoimbra Hospital and University CentreCoimbraPortugal
  3. 3.Faculty of Medicine of Geneva UniversityGenevaSwitzerland
  4. 4.The Neurodis FoundationCERMEP Imagerie du VivantLyonFrance
  5. 5.King’s College London & Guy’s and St Thomas’ PET Centre, Division of Imaging Sciences and Biomedical EngineeringKing’s College LondonLondonUK
  6. 6.Translational and Integrative Group in Epilepsy Research, Lyon Neuroscience Research Center, INSERM - U1028, CNRS - UMR5292University Claude Bernard Lyon 1LyonFrance
  7. 7.Neuroradiology Division, Diagnostic DepartmentUniversity Hospitals of GenevaGenevaSwitzerland
  8. 8.Nuclear Medicine and Molecular Imaging Division, Diagnostic DepartmentUniversity Hospitals of GenevaGenevaSwitzerland

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