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.
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.
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).
Both 11C-FMZ PET and 18F-FDG PET are the choice of modalities for the localization of epileptogenic zone, especially when coregistered with MRI.
• 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.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Area under the sROC curves
Frontal lobe epilepsy
Magnetic resonance imaging
Positron emission tomography
The Preferred Reporting Items for Systematic Review and Meta-analysis
Quality assessment of diagnostic accuracy studies
Single-photon emission computed tomography
Summarized receiver operating characteristic curves
Temporal lobe epilepsy
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
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
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
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
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
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
Manford M (2017) Recent advances in epilepsy. J Neurol 264:1811–1824. https://doi.org/10.1007/s00415-017-8394-2
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
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).
The scientific guarantor of this publication is Li Huo (firstname.lastname@example.org).
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.
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.
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.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
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
- Fluorodeoxyglucose F18
- Positron emission tomography