Performance of PET imaging for the localization of epileptogenic zone in patients with epilepsy: a meta-analysis

Abstract

Objectives

The aim of this meta-analysis was to estimate the clinical use value of 11C-FMZ and 18F-FDG in PET for the localization of epileptogenic zone and to provide evidence for practitioners’ clinical decision-making.

Methods

We searched PubMed and Embase in a time frame from inception to May 31, 2020. Studies utilizing FMZ or FDG-PET or FDG-PET/MRI used in patients with epilepsy, with EEG or surgical outcomes as the gold standard and corresponding outcomes such as concordance rates of PET or PET/MRI scan compared with reference standard, absolute numbers of participants with true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) results in FDG or FMZ PET. Pooled concordance rates, overall sensitivity, and specificity of 11C-FMZ-PET and 18F-FDG-PET were calculated.

Results

In total, 44 studies met the inclusion criteria. The pooled concordance rates of FDG-PET, FMZ-PET, and FDG-PET/MRI coregistration compared with reference standard were 0.67 (95% CI: 0.60–0.73), 0.75 (95% CI: 0.57–0.93), and 0.93 (95% CI: 0.89–0.97), respectively. The concordance rate of 18F-FDG-PET in patients with temporal lobe epilepsy (TLE) was 0.79 (0.63; 0.92). The overall sensitivity and specificity of 18F-FDG-PET were 0.66 (95% CI: 0.58–0.73) and 0.71 (95% CI: 0.63–0.78), respectively. 11C-FMZ-PET displayed an overall sensitivity of 0.62 (95% CI: 0.49–0.73) and specificity of 0.73 (95% CI: 0.59–0.84).

Conclusions

Both 11C-FMZ PET and 18F-FDG PET are the choice of modalities for the localization of epileptogenic zone, especially when coregistered with MRI.

Key Points

11 C-FMZ-PET may be more helpful than 18 F-FDG-PET in the localization of epilepsy foci.

• Coregistration of FDG-PET and MRI is recommended in the localization of epileptogenic zone.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Abbreviations

11C-FMZ:

11C-flumazenil

18F-FDG:

18F-2-fluoro-2-deoxy-D-glucose

AEDs:

Antiepileptic drugs

AMT:

a-Methyl-L-tryptophan

AUCs:

Area under the sROC curves

CIs:

Confidence intervals

EEG:

Electroencephalograph

FLE:

Frontal lobe epilepsy

FN:

False negative

FP:

False positive

LR:

Likelihood ratio

MRI:

Magnetic resonance imaging

NMDA:

N-Methyl-d-aspartate

OR:

Odds ratio

PET:

Positron emission tomography

PRISMA:

The Preferred Reporting Items for Systematic Review and Meta-analysis

QUADAS:

Quality assessment of diagnostic accuracy studies

SPECT:

Single-photon emission computed tomography

sROC:

Summarized receiver operating characteristic curves

TLE:

Temporal lobe epilepsy

TN:

True negative

TP:

True positive

References

  1. 1.

    Bertoglio D, Verhaeghe J, Dedeurwaerdere S, Grohn O (2017) Neuroimaging in animal models of epilepsy. Neuroscience 358:277–299. https://doi.org/10.1016/j.neuroscience.2017.06.062

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Thijs RD, Surges R, O'Brien TJ, Sander JW (2019) Epilepsy in adults. Lancet 393:689–701. https://doi.org/10.1016/S0140-6736(18)32596-0

    Article  PubMed  Google Scholar 

  3. 3.

    Fisher RS, Cross JH, French JA et al (2017) Operational classification of seizure types by the International League Against Epilepsy: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 58:522–530. https://doi.org/10.1111/epi.13670

    Article  PubMed  Google Scholar 

  4. 4.

    Ngugi AK, Kariuki SM, Bottomley C, Kleinschmidt I, Sander JW, Newton CR (2011) Incidence of epilepsy: a systematic review and meta-analysis. Neurology 77:1005–1012. https://doi.org/10.1212/WNL.0b013e31822cfc90

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Fiest KM, Sauro KM, Wiebe S et al (2017) Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies. Neurology 88:296–303. https://doi.org/10.1212/WNL.0000000000003509

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Fisher RS, Cross JH, D'Souza C et al (2017) Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia 58:531–542. https://doi.org/10.1111/epi.13671

    Article  PubMed  Google Scholar 

  7. 7.

    Manford M (2017) Recent advances in epilepsy. J Neurol 264:1811–1824. https://doi.org/10.1007/s00415-017-8394-2

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Wang Y, Chen Z (2019) An update for epilepsy research and antiepileptic drug development: toward precise circuit therapy. Pharmacol Ther 201:77–93. https://doi.org/10.1016/j.pharmthera.2019.05.010

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Whiting P, Gupta R, Burch J et al (2006) A systematic review of the effectiveness and cost-effectiveness of neuroimaging assessments used to visualise the seizure focus in people with refractory epilepsy being considered for surgery. Health Technol Assess 10:iii–128. https://doi.org/10.3310/hta10040

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Duncan JS, Sander JW, Sisodiya SM, Walker MC (2006) Adult epilepsy. Lancet 367:1087–1100. https://doi.org/10.1016/S0140-6736(06)68477-8

    Article  PubMed  Google Scholar 

  11. 11.

    Jette N, Sander JW, Keezer MR (2016) Surgical treatment for epilepsy: the potential gap between evidence and practice. Lancet Neurol 15:982–994. https://doi.org/10.1016/S1474-4422(16)30127-2

    Article  PubMed  Google Scholar 

  12. 12.

    Haneef Z, Stern J, Dewar S, Engel J Jr (2010) Referral pattern for epilepsy surgery after evidence-based recommendations: a retrospective study. Neurology 75:699–704. https://doi.org/10.1212/WNL.0b013e3181eee457

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Englot DJ, Ouyang D, Garcia PA, Barbaro NM, Chang EF (2012) Epilepsy surgery trends in the United States, 1990-2008. Neurology 78:1200–1206. https://doi.org/10.1212/WNL.0b013e318250d7ea

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Dewar SR, Pieters HC (2015) Perceptions of epilepsy surgery: a systematic review and an explanatory model of decision-making. Epilepsy Behav 44:171–178. https://doi.org/10.1016/j.yebeh.2014.12.027

    Article  PubMed  Google Scholar 

  15. 15.

    Pitkanen A, Loscher W, Vezzani A et al (2016) Advances in the development of biomarkers for epilepsy. Lancet Neurol 15:843–856. https://doi.org/10.1016/S1474-4422(16)00112-5

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Krumholz A, Shinnar S, French J, Gronseth G, Wiebe S (2015) Evidence-based guideline: management of an unprovoked first seizure in adults: report of the guideline development Subcommittee of the American Academy of neurology and the American Epilepsy Society. Neurology 85:1526–1527. https://doi.org/10.1212/WNL.0000000000001487

    Article  PubMed  Google Scholar 

  17. 17.

    Middlebrooks EH, Ver Hoef L, Szaflarski JP (2017) Neuroimaging in Epilepsy. Curr Neurol Neurosci Rep 17:32. https://doi.org/10.1007/s11910-017-0746-x

    Article  PubMed  Google Scholar 

  18. 18.

    Juhász C, Nagy F, Watson C et al (1999) Glucose and [11C]flumazenil positron emission tomography abnormalities of thalamic nuclei in temporal lobe epilepsy. Neurology 53:2037–2045. https://doi.org/10.1212/wnl.53.9.2037

    Article  PubMed  Google Scholar 

  19. 19.

    Juhász C, Chugani DC, Muzik O et al (2000) Electroclinical correlates of flumazenil and fluorodeoxyglucose PET abnormalities in lesional epilepsy. Neurology 55:825–835. https://doi.org/10.1212/wnl.55.6.825

    Article  PubMed  Google Scholar 

  20. 20.

    Theodore WH, Sato S, Kufta CV, Gaillard WD, Kelley K (1997) FDG-positron emission tomography and invasive EEG: seizure focus detection and surgical outcome. Epilepsia 38:81–86. https://doi.org/10.1111/j.1528-1157.1997.tb01081.x

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Rocher AB, Chapon F, Blaizot X, Baron JC, Chavoix C (2003) Resting-state brain glucose utilization as measured by PET is directly related to regional synaptophysin levels: a study in baboons. NeuroImage 20:1894–1898. https://doi.org/10.1016/j.neuroimage.2003.07.002

    Article  PubMed  Google Scholar 

  22. 22.

    Arnold S, Schlaug G, Niemann H et al (1996) Topography of interictal glucose hypometabolism in unilateral mesiotemporal epilepsy. Neurology 46:1422–1430. https://doi.org/10.1212/wnl.46.5.1422

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Savic I, Ingvar M, Stone-Elander S (1993) Comparison of [11C]flumazenil and [18F]FDG as PET markers of epileptic foci. J Neurol Neurosurg Psychiatry 56:615–621. https://doi.org/10.1136/jnnp.56.6.615

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Bankstahl M, Bankstahl JP (2017) Recent advances in radiotracer imaging hold potential for future refined evaluation of epilepsy in veterinary neurology. Front Vet Sci 4:218. https://doi.org/10.3389/fvets.2017.00218

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    la Fougère C, Rominger A, Förster S, Geisler J, Bartenstein P (2009) PET and SPECT in epilepsy: a critical review. Epilepsy Behav 15:50–55. https://doi.org/10.1016/j.yebeh.2009.02.025

    Article  PubMed  Google Scholar 

  26. 26.

    Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535. https://doi.org/10.1136/bmj.b2535

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Galovic M, Koepp M (2016) Advances of molecular imaging in epilepsy. Curr Neurol Neurosci Rep 16:58. https://doi.org/10.1007/s11910-016-0660-7

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE (1979) Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol 6:371–388. https://doi.org/10.1002/ana.410060502

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Hodolic M, Topakian R, Pichler R (2016) 18F-fluorodeoxyglucose and 18F-flumazenil positron emission tomography in patients with refractory epilepsy. Radiol Oncol 50:247–253. https://doi.org/10.1515/raon-2016-0032

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Laufs H, Richardson MP, Salek-Haddadi A et al (2011) Converging PET and fMRI evidence for a common area involved in human focal epilepsies. Neurology 77:904–910. https://doi.org/10.1212/WNL.0b013e31822c90f2

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Centeno M, Vollmar C, Stretton J et al (2014) Structural changes in the temporal lobe and piriform cortex in frontal lobe epilepsy. Epilepsy Res 108:978–981. https://doi.org/10.1016/j.eplepsyres.2014.03.001

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Yankam Njiwa J, Gray KR, Costes N, Mauguiere F, Ryvlin P, Hammers A (2015) Advanced [18F]FDG and [11C]flumazenil PET analysis for individual outcome prediction after temporal lobe epilepsy surgery for hippocampal sclerosis. Neuroimage Clin 7:122–131. https://doi.org/10.1016/j.nicl.2014.11.013

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Szelies B, Weber-Luxenburger G, Pawlik G et al (1996) MRI-guided flumazenil- and FDG-PET in temporal lobe epilepsy. Neuroimage 3:109–118. https://doi.org/10.1006/nimg.1996.0013

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Szelies B, Weber-Luxenburger G, Mielke R et al (2000) Interictal hippocampal benzodiazepine receptors in temporal lobe epilepsy: comparison with coregistered hippocampal metabolism and volumetry. Eur J Neurol 7:393–400. https://doi.org/10.1046/j.1468-1331.2000.00077.x

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Padma MV, Simkins R, White P et al (2004) Clinical utility of 11C-flumazenil positron emission tomography in intractable temporal lobe epilepsy. Neurol India 52:457–462

    CAS  PubMed  Google Scholar 

  36. 36.

    Komoto D, Iida K, Higaki T et al (2015) Diagnostic performance of positron emission tomography for the presurgical evaluation of patients with non-lesional intractable partial epilepsy: comparison among 18F-FDG, 11C-flumazenil, and 11C-flumazenil binding potential imaging using statistical imaging analysis. Hiroshima J Med Sci 64:51–57

    CAS  PubMed  Google Scholar 

  37. 37.

    Debets RM, Sadzot B, van Isselt JW et al (1997) Is 11C-flumazenil PET superior to 18FDG PET and 123I-iomazenil SPECT in presurgical evaluation of temporal lobe epilepsy? J Neurol Neurosurg Psychiatry 62:141–150. https://doi.org/10.1136/jnnp.62.2.141

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Vivash L, Gregoire MC, Lau EW et al (2013) 18F-flumazenil: a γ-aminobutyric acid A-specific PET radiotracer for the localization of drug-resistant temporal lobe epilepsy. J Nucl Med 54:1270–1277. https://doi.org/10.2967/jnumed.112.107359

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank the National Natural Science Foundation of China, Capital’s Funds for Health Improvement and Research (CFH), and CAMS Innovation Fund for Medical Sciences (CIFMS) for the financial support.

Funding

This work was sponsored in part by the National Natural Science Foundation of China (Grant No. 81571713), Capital’s Funds for Health Improvement and Research (CFH) (Grant No. 2016-2-40115), and CAMS Innovation Fund for Medical Sciences (CIFMS) (Grant Nos. 2016-I2M-4-003, 2017-I2M-3-001, 2018-I2M-3-001).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Li Huo.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Li Huo (huoli@pumch.cn).

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was not required for this study because this was a meta-analysis using the studies in published literature and did not analyze specific human subjects.

Ethical approval

Institutional Review Board approval was not required because this was a meta-analysis using the studies in published literature and did not analyze specific human subjects.

Study subjects or cohorts overlap

Information of study’s subjects or cohorts was extracted from previously published studies which were cited in the article.

Methodology

• meta-analysis

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 535 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Niu, N., Xing, H., Wu, M. et al. Performance of PET imaging for the localization of epileptogenic zone in patients with epilepsy: a meta-analysis. Eur Radiol (2021). https://doi.org/10.1007/s00330-020-07645-4

Download citation

Keywords

  • Humans
  • Fluorodeoxyglucose F18
  • Carbon-11
  • Positron emission tomography
  • Epilepsy