EDITORIAL Myoclonic atonic epilepsy Another generalized epilepsy syndrome that is “not so” generalized

John M. Zempel, MD, Myoclonic atonic/astatic epilepsy (MAE), first described have shown predominant thalamic activation PhD well by Doose1 (pronounced dough sah: http://www. and default mode network deactivation.6–8 Even Tadaaki Mano, MD, PhD youtube.com/watch?v5hNNiWXV2wF0), is a general- Lennox-Gastaut syndrome, a devastating epileptic ized electroclinical syndrome with early onset charac- encephalopathy with EEG findings of runs of slow terized by myoclonic, atonic/astatic, generalized spike and wave and paroxysmal higher frequency Correspondence to tonic-clonic, and absence seizures (but not tonic activity, has fMRI correlates that are more focal than Dr. Zempel: [email protected] seizures) in association with generalized spike-wave expected in a syndrome with widespread EEG (GSW) discharges. Thought to have a genetic com- abnormalities.9,10 Neurology® 2014;82:1486–1487 ponent that has proven to be complicated,2 MAE EEG-fMRI is maturing as a research and clinical sometimes occurs in children who have otherwise technique. Recording scalp EEG in an electrically been developing normally and has variable outcome. hostile environment is not an easy task. Substantial MAE is typically treated with antiseizure medications technical artifacts, such as changing imaging gradients that are used for generalized epilepsy syndromes, with and ballistocardiogram (ECG-linked artifact observed perhaps a best response to valproate, felbamate, or the in the scalp electrodes), contaminate the EEG signal. ketogenic diet.3,4 However, the relatively distinctive EEG discharges in In this issue of Neurology®, Moeller et al.5 report patients with epilepsy have partially circumvented on the fMRI correlates of GSW discharges as mea- this problem. EEG-fMRI even has applicability to sured with simultaneous EEG during sleep in chil- young pediatric populations6–8 and was performed dren with a clinical diagnosis of MAE. They were by Moeller et al.5 with chloral hydrate–induced able to obtain blood oxygen level–dependent sleep in mostly young children (ages 3–13 years, (BOLD) fMRI signal changes in most individual but mostly 3–5). participants. This study, like other EEG-fMRI stud- Clinically, EEG-fMRI is advancing in both tech- ies of the generalized epilepsies, shows that fMRI nology and utilization across many types of epilepsy. activations involve selective brain networks that are EEG-fMRI localization is used increasingly in focal more localized than the widespread EEG discharges epilepsies, where more precise localization may lead associated with generalized epilepsies. Group fMRI to successful surgical treatment.11 EEG-fMRI may analysis showed BOLD signal increases in the thala- eventually have clinical utility in the generalized epi- mus, putamen, and premotor cortex, with BOLD lepsies, for both treatment and diagnosis. The signal decreases in nodes of the default mode response to treatment with valproate, for example, network (posterior cingulate/precuneus and lateral is related to the generator of the GSW discharge.12 parietal cortex/inferior parietal lobule). In addition EEG-fMRI may be particularly helpful diagnostically to the common brain networks highlighted in other by providing a biomarker for distinguishing subtypes generalized epilepsy syndromes with thalamic of these often overlapping generalized epilepsy syn- activation and posterior cingulate/precuneus deacti- dromes. The BOLD signal fingerprint may provide vation, children with MAE have prominent activa- both syndrome- and patient-specific information as tion of nodes of the motor network, consistent the underlying causes of the many related generalized with the motor features of the common myoclonic syndromes are better understood.13 atonic/astatic seizures seen in this distinctive electro- clinical syndrome. AUTHOR CONTRIBUTIONS More generally, the results of this study are in John M. Zempel: drafting/revising the manuscript, study concept or design. Tadaaki Mano: study concept or design, study supervision. line with a broadly developing theme in the study of childhood generalized epilepsy syndromes. STUDY FUNDING EEG-fMRI studies of childhood absence epilepsy No targeted funding reported.

See page 1508 From the Department of Neurology and Pediatrics (J.M.Z.), Washington University School of Medicine, St. Louis, MO; and Gifu University of Medical Science (T.M.), Seki, Gifu, Japan. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the editorial.

1486 © 2014 American Academy of Neurology DISCLOSURE 8. Carney PW, Masterton RA, Harvey AS, Scheffer IE, The authors report no disclosures relevant to the manuscript. Go to Berkovic SF, Jackson GD. The core network in absence Neurology.org for full disclosures. epilepsy: differences in cortical and thalamic BOLD response. Neurology 2010;75:904–911. REFERENCES 9. Pillay N, Archer JS, Badawy RA, Flanagan DF, 1. Doose H. Myoclonic-astatic epilepsy. Epilepsy Res Suppl Berkovic SF, Jackson G. Networks underlying paroxysmal 1992;6:163–168. fast activity and slow spike and wave in Lennox-Gastaut 2. Tang S, Pal DK. Dissecting the genetic basis of myoclonic- syndrome. Neurology 2013;81:665–673. astatic epilepsy. Epilepsia 2012;53:1303–1313. 10. Siniatchkin M, Coropceanu D, Moeller F, Boor R, 3. Zupanc ML, Roell Werner R, Schwabe MS, et al. Efficacy Stephani U. EEG-fMRI reveals activation of brainstem of felbamate in the treatment of intractable pediatric epi- and thalamus in patients with Lennox-Gastaut syndrome. lepsy. Pediatr Neurol 2010;42:396–403. – 4. Kelley SA, Kossoff EH. Doose syndrome (myoclonic- Epilepsia 2011;52:766 774. astatic epilepsy): 40 years of progress. Dev Med Child 11. An D, Fahoum F, Hall J, Olivier A, Gotman J, Dubeau F. Neurol 2010;52:988–993. Electroencephalography/functional magnetic resonance 5. Moeller F, Groening K, Moehring J, et al. EEG-fMRI in imaging responses help predict surgical outcome in focal – myoclonic astatic epilepsy (Doose syndrome). Neurology epilepsy. Epilepsia 2013;54:2184 2194. 2014;82:1508–1513. 12. Szaflarski JP, Kay B, Gotman J, Privitera MD, 6. Moeller F, Siebner HR, Wolff S, et al. Simultaneous EEG- Holland SK. The relationship between the localization fMRI in drug-naive children with newly diagnosed of the generalized spike and wave discharge generators absence epilepsy. Epilepsia 2008;49:1510–1519. and the response to valproate. Epilepsia 2013;54: 7. Bai X, Vestal M, Berman R, et al. Dynamic time course of 471–480. typical childhood absence seizures: EEG, behavior, and 13. Moeller F, Stephani U, Siniatchkin M. Simultaneous EEG functional magnetic resonance imaging. J Neurosci 2010; and fMRI recordings (EEG-fMRI) in children with epi- 30:5884–5893. lepsy. Epilepsia 2013;54:971–982.

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