The PET Sandwich: Using Serial FDG-PET Scans with Interval Burst Suppression to Assess Ictal Components of Disease

A Correction to this article was published on 06 May 2020

An Invited Editorial Commentary to this article was published on 06 April 2020

This article has been updated



Determining the cause of refractory seizures and/or interictal continuum (IIC) findings in the critically ill patient remains a challenge. These electrographic abnormalities may represent primary ictal pathology or may instead be driven by an underlying infectious, inflammatory, or neoplastic pathology that requires targeted therapy. In these cases, it is unclear whether escalating antiepileptic therapy will be helpful or harmful. Herein, we report the use of serial [F-18] fluorodeoxyglucose positron emission tomography (FDG-PET) coupled with induced electrographic burst suppression to distinguish between primary and secondary ictal pathologies. We propose that anesthetic suppression of hypermetabolic foci suggests clinical responsiveness to escalating antiepileptic therapy, whereas non-suppressible hypermetabolic foci are suggestive of non-ictal pathologies that likely require multimodal therapy.


We describe 6 patients who presented with electrographic findings of seizure or IIC abnormalities, severe neurologic injury, and clinical concern for confounding pathologies. All patients were continuously monitored on video electroencephalography (cvEEG). Five patients underwent at least two sequential FDG-PET scans of the brain: one in a baseline state and the second while under electrographic burst suppression. FDG-avid loci and EEG tracings were compared pre- and post-burst suppression. One patient underwent a single FDG-PET scan while burst-suppressed.


Four patients had initially FDG-avid foci that subsequently resolved with burst suppression. Escalation of antiepileptic therapy in these patients resulted in clinical improvement, suggesting that the foci were related to primary ictal pathology. These included clinical diagnoses of electroclinical status epilepticus, new-onset refractory status epilepticus, stroke-like migraine attacks after radiotherapy, and epilepsy secondary to inflammatory cerebral amyloid angiopathy. Conversely, two patients with high-grade EEG abnormalities had FDG-avid foci that persisted despite burst suppression. The first presented with a poor examination, fever, and concern for encephalitis. Postmortem pathology confirmed suspicion of herpes simplex virus encephalitis. The second patient presented with concern for checkpoint inhibitor-induced autoimmune encephalitis. The persistence of the FDG-avid focus, despite electrographic burst suppression, guided successful treatment through escalation of immunosuppressive therapy.


In appropriately selected patients, FDG-PET scans while in burst suppression may help dissect the underlying pathophysiologic cause of IIC findings observed on EEG and guide tailored therapy.

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Change history

  • 06 May 2020

    In the original article, Figure 5 has incorrect EEG images and the corrected version is shown below.


  1. 1.

    Sivaraju A, Gilmore EJ. Understanding and managing the ictal-interictal continuum in neurocritical care. Curr Treat Options Neurol. 2016;18:8.

    Article  Google Scholar 

  2. 2.

    Johnson EL, Kaplan PW. Population of the ictal-interictal zone: the significance of periodic and rhythmic activity. Clin Neurophysiol Pract. 2017;2:107–18.

    Article  Google Scholar 

  3. 3.

    de Bruijn MAAM, van Sonderen A, van Coevorden-Hameete MH, et al. Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABA. Neurology. 2019;92:e2185–e96.

    Article  Google Scholar 

  4. 4.

    Waziri A, Claassen J, Stuart RM, et al. Intracortical electroencephalography in acute brain injury. Ann Neurol. 2009;66:366–77.

    Article  Google Scholar 

  5. 5.

    Claassen J, Perotte A, Albers D, et al. Nonconvulsive seizures after subarachnoid hemorrhage: multimodal detection and outcomes. Ann Neurol. 2013;74:53–64.

    Article  Google Scholar 

  6. 6.

    Kim JA, Rosenthal ES, Biswal S, et al. Epileptiform abnormalities predict delayed cerebral ischemia in subarachnoid hemorrhage. Clin Neurophysiol. 2017;128:1091–9.

    CAS  Article  Google Scholar 

  7. 7.

    Raichle ME, Gusnard DA. Appraising the brain's energy budget. Proc Natl Acad Sci USA. 2002;99:10237–9.

    CAS  Article  Google Scholar 

  8. 8.

    Engel J, Kuhl DE, Phelps ME. Patterns of human local cerebral glucose metabolism during epileptic seizures. Science. 1982;218:64–6.

    Article  Google Scholar 

  9. 9.

    Siclari F, Prior JO, Rossetti AO. Ictal cerebral positron emission tomography (PET) in focal status epilepticus. Epilepsy Res. 2013;105:356–61.

    Article  Google Scholar 

  10. 10.

    Schur S, Allen V, White A, et al. Significance of FDG-PET hypermetabolism in children with intractable focal epilepsy. Pediatr Neurosurg. 2018;53:153–62.

    Article  Google Scholar 

  11. 11.

    Hajek M, Antonini A, Leenders KL, Wieser HG. Epilepsia partialis continua studied by PET. Epilepsy Res. 1991;9:44–8.

    CAS  Article  Google Scholar 

  12. 12.

    Sarikaya I. PET studies in epilepsy. Am J Nucl Med Mol Imaging. 2015;5:416–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Franck G, Sadzot B, Salmon E, et al. Study of cerebral metabolism and blood flow in partial complex epilepsy and status epilepticus in man using positron emission tomography. Rev Electroencephalogr Neurophysiol Clin. 1986;16:199–21616.

    CAS  Article  Google Scholar 

  14. 14.

    Subramaniam T, Jain A, Hall LT, et al. Lateralized periodic discharges frequency correlates with glucose metabolism. Neurology. 2019;92:e670–e4.

    Article  Google Scholar 

  15. 15.

    Struck AF, Westover MB, Hall LT, Deck GM, Cole AJ, Rosenthal ES. Metabolic correlates of the ictal-interictal continuum: FDG-PET during continuous EEG. Neurocrit Care. 2016;24:324–31.

    CAS  Article  Google Scholar 

  16. 16.

    Kampe KK, Rotermund R, Tienken M, et al. Diagnostic value of positron emission tomography combined with computed tomography for evaluating critically ill neurological patients. Front Neurol. 2017;8:33.

    Article  Google Scholar 

  17. 17.

    Morbelli S, Djekidel M, Hesse S, et al. Role of (18)F-FDG-PET imaging in the diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15:1009–10.

    Article  Google Scholar 

  18. 18.

    Probasco JC, Solnes L, Nalluri A, et al. Abnormal brain metabolism on FDG-PET/CT is a common early finding in autoimmune encephalitis. Neurol Neuroimmunol Neuroinflamm. 2017;4:e352.

    Article  Google Scholar 

  19. 19.

    Trevino-Peinado C, Arbizu J, Irimia P, Riverol M, Martínez-Vila E. Monitoring the effect of immunotherapy in autoimmune limbic encephalitis using 18F-FDG PET. Clin Nucl Med. 2015;40:e441–3.

    Article  Google Scholar 

  20. 20.

    Singhal T, Solomon I, Akbik F, Smirnakis S, Vaitkevicius H. Ventral striatal and septal area hypermetabolism on FDG-PET in herpes simplex viral encephalitis. J Neurovirol. 2019;21:118–20.

    Google Scholar 

  21. 21.

    Kaisti KK, Metsahonkala L, Teras M, et al. Effects of surgical levels of propofol and sevoflurane anesthesia on cerebral blood flow in healthy subjects studied with positron emission tomography. Anesthesiology. 2002;96:1358–70.

    CAS  Article  Google Scholar 

  22. 22.

    Jeong YB, Kim JS, Jeong SM, Park JW, Choi IC. Comparison of the effects of sevoflurane and propofol anaesthesia on regional cerebral glucose metabolism in humans using positron emission tomography. J Int Med Res. 2006;34:374–84.

    CAS  Article  Google Scholar 

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Author information




HV designed the study. FA and HV wrote the manuscript with critical review from AD, MR, TS, and JL. MR provided qualitative and quantitative PET imaging data. All authors were involved in clinical care of the patients and interpretation of the supporting data.

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Correspondence to Henrikas Vaitkevicius.

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Akbik, F., Robertson, M., Das, A.S. et al. The PET Sandwich: Using Serial FDG-PET Scans with Interval Burst Suppression to Assess Ictal Components of Disease. Neurocrit Care 33, 657–669 (2020).

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  • Ictal–interictal continuum
  • Burst suppression
  • Electroclinical seizures