EEG findings in patients with angelman syndrome. Notched slow waves and age-specific characteristics of the main EEG patterns

Angelman syndrome (AS) is a genetic disorder caused by a mutation in the maternal copy of the UBE3A gene and characterized by typical clinical manifestations (such as mental retardation, difficulty walking, and laughter) and specific changes on the electroencephalogram (EEG).
The aim of this study was to analyze age-specific characteristics of the main EEG patterns, including high-amplitude frontal delta activity with spikes, slow-wave delta-theta activity with spikes in the posterior regions, and diffuse continuous rhythmic theta activity. In addition to that, we assessed the frequency of a rare and highly specific for AS EEG pattern: notched slow waves.
We have identified and described additional criteria for EEG during sleep: high index of pathological slow-wave activity and the ratio of pathological slow-wave activity index to epileptiform activity index during sleep. We also analyzed all EEG patterns at the age most significant for the detection of this syndrome (up to 3 years) and their age-specific dynamics.
We covered the frequency and characteristics of EEG patterns rare in AS patients, such as three-phase bifrontal delta waves, reactive pathological activity in the posterior areas, EEG patterns of focal seizures originating from the posterior areas, benign epileptiform discharges of childhood, and migrating continuous slow-wave activity.
We analyzed the differences between main EEG patterns in AS and frontal and occipital intermittent rhythmic delta activity (fIRDA and OIRDA patterns).

1. Абатуров А.Е., Петренко Л.Л., Кривуша Е.Л. Синдром Ангельмана. Часть 2 (клиника и диагностика). Здоровье ребенка 2015;6(66). [Abaturov A.E., Petrenko L.L., Krivusha E.L. Angelman syndrome. Part 2 (clinical manifestations and diagnosis). Zdorovye rebenka = Child Health 2015;6(66). (In Russ.)].

2. Михайлова Н.В., Савинов С.В., Акчурина Я.Е. и др. Синдром Ангельмана как иллюстрация дифференцированного подхода к диагностике причин аутизма, задержки психомоторного развития и ДЦП. Нейрохирургия и неврология Казахстана 2017;1(46). [Mikhaylova N.V., Savinov S.V., Akchurina Ya.E. et al. Angelman syndrome as an illustration of a differentiated approach to the diagnosis of the causes of autism, delayed psychomotor development and cerebral palsy. Neyrokhirurgiya i nevrologiya Kazakhstana = Neurosurgery and Neurology of Kazakhstan 2017;1(46). (In Russ.)].

3. Мухин К.Ю. Синдром Ангельмана. В кн.: Эпилептические энцефалопатии и схожие синдромы у детей. М.: АртСервис Лтд, 2011. C. 520–533. [Mukhin K.Yu. Angelman syndrome. In: Epileptic encephalopathies and similar syndromes in children. Moscow: ArtServis Ltd, 2011. Pp. 520–533. (In Russ.)].

4. Battaglia A., Carey J.C., Thompson J.A., Filloux F.M. EEG studies in the Wolf– Hirschhorn (4p-) syndrome. EEG Clin Neurophysiol 1996;99(4):324.

5. Bird L.M. Angelman syndrome: review of clinical and molecular aspects. Appl Clin Genet 2014;7:93–104.

6. Boyd S.G., Harden A., Patton M.A. The EEG in early diagnosis of the Angelman (happy puppet) syndrome. Eur J Pediatr 1988;147(5):508–13. DOI: 10.1007/BF00441976.

7. Den Bakker H., Sidorov M.S., Fan Z. et al. Abnormal coherence and sleep composition in children with Angelman syndrome: a retrospective EEG study. Mol Autism 2018;9:32. DOI: 10.1186/s13229-018-0214-8.

8. Fariello R.G., Orrison W., Blanco G., Reyes P.F. Neuroradiological correlates of frontally predominant intermittent rhythmic delta activity (FIRDA). Electroencephalogr Clin Neurophysiol 1982;54(2):194–202. DOI: 10.1016/0013-4694(82)90161-4.

9. Korff C.M., Kelley K.R., Nordli D.R.Jr. Notched delta, phenotype, and Angelman syndrome. J Clin Neurophysiol 2005;22(4):238–43. DOI: 10.1097/01.wnp.0000167930.90824.0f.

10. Laan L.A., Renier W.O., Arts W.F.M. et al. Evolution of epilepsy and EEG findings in Angelman syndrome. Epilepsia 1997;38:195–9. DOI: 10.1111/j.1528-1157.1997.tb01097.x.

11. Laan L.A., Vein A.A. A Rett patient with a typical Angelman EEG. Epilepsia 2002;43(12):1590–2. DOI: 10.1046/j.1528-1157.2002.30802.x.

12. Matsumoto A., Kumagai T., Miura K. et al. Epilepsy in Angelman syndrome associated with chromosome 15q deletion. Epilepsia 1992;33:1083–90. DOI: 10.1111/j.1528-1157.1992.tb01763.x.

13. Minassian B.A., DeLorey T.M., Olsen R.W. et al. Angelman syndrome: correlations between epilepsy phenotypes and genotypes. Ann Neurol 1998;43(4): 485–93. DOI: 10.1002/ana.410430412.

14. Riviello J.J.Jr., Foley C.M. The epileptiform significance of intermittent rhythmic delta activity in childhood. J Child Neurol 1992;7(2):156–60. DOI: 10.1177/088307389200700204.

15. Rubin D.I., Patterson M.C., Westmoreland B.F., Klass D.W. Angelman’s syndrome: clinical and electroencephalographic findings. Electroencephalogr Clin Neurophysiol 1997;102(4):299–302. DOI: 10.1016/s0013-4694(96)96105-2.

16. Valente K.D., Andrade J.Q., Grossmann R.M. et al. Angelman syndrome: difficulties in EEG pattern recognition and possible misinterpretations. Epilepsia 2003;44:1051–63. DOI: 10.1046/j.1528-1157.2003.66502.x.

17. Van der Drift J., Magnus O. The value of the EEG in the differential diagnosis of cases with cerebral lesion. Electroencephalogr Clin Neurophysiol 1959;11:733–46.

18. Vendrame M., Loddenkemper T., Zarowski M. et al. Analysis of EEG patterns and genotypes in patients with Angelman syndrome. Epilepsy Behav 2012;23(3):261–5. DOI: 10.1016/j.yebeh.2011.11.027.

19. Viani F., Romeo A., Viri M. et al. Seizure and EEG patterns in Angelman’s syndrome. J Child Neurol 1995;10:467–71. DOI: 10.1177/088307389501000609.

20. Watemberg N., Gandelman R., Neufeld M.Y. et al. Clinical correlates of frontal intermittent rhythmic delta activity in children. J Child Neurol 2003;18:525–9. DOI: 10.1177/08830738030180080601.

21. Watemberg N., Linder I., Dabby R. et al. Clinical correlates of occipital intermittent rhythmic delta activity (OIRDA) in children. Epilepsia 2007;48(2):330–4. DOI: 10.1111/j.1528-1167.2006.00937.x.

22. Williams C.A., Beaudet A.L., Clayton-Smith J. et al. Angelman syndrome 2005: updated consensus for diagnostic criteria. Am J Med Genet A 2006;140(5):413–8. DOI: 10.1002/ajmg.a.31074.

23. Yum M.S., Lee E.H., Kim J.H. et al. Implications of slow waves and shifting epileptiform discharges in Angelman syndrome. Brain Dev 2013;35(3):245–51. DOI: 10.1016/j.braindev.2012.04.006.