Electroencephalogram features in children with congenital hyperinsulinism treated according to the international protocol in Russian Federation

BACKGROUND: Congenital hyperinsulinism (CHI) is a rare life-threatening disease characterised by persistent hypoglycaemia as a result of inappropriate insulin secretion, which can lead to irreversible neurological defects in infants.

AIM: To evaluate neurophysiological characteristics of central nervous system in children with congenital hyperinsulinism treated according to the international protocol in Russian Federation.

MATERIALS AND METHODS: Our retrospective, prospective cohort study included 73 patients who received treatment for CHI according to the current international protocol at different departments of the Almazov National Medical Research Centre from 2017 to 2022. All patients underwent a comprehensive examination, including electroencephalography (EEG).

RESULTS: Among 73 patients with CHI, 35% (23) had focal form of the disease, 65% had non-focal form (49% (39) — diffuse form, 16% (11) — atypical form). All patients with focal form of CHI had a recovery as an outcome.

Analysing the EEG data we found that paroxysmal activity was recorded in 23 patients (32%), 50 patients did not have paroxysmal activity (68%). Diffuse changes were observed in 47 patients (64%), whereas 26 patients (36%) were absent of it. By constructing Kaplan-Meier curves we found that the alpha rhythm is formed significantly (p=0.026) earlier in patients with a focal form of CHI.

CONCLUSION: CHI patients treated according to the international guidelines in Russian Federation show rather positive neurological outcome. We established that alpha rhythm earliest formation is associated with focal form of CHI.

1. Gϋemes M, Rahman SA, Kapoor RR, et al. Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management. Rev Endocr Metab Disord. 2020;21(4):577-597. doi: https://doi.org/10.1007/s11154-020-09548-7.

2. Melikian MA. Vrozhdennyi giperinsulinizm: molekuliarnaia osnova, klinicheskie osobennosti i personalizirovannoe lechenie [dissertation]. Moscow; 2019. (In Russ.).

3. Warren RE, Frier BM. Hypoglycaemia and cognitive function. Diabetes, Obes Metab. 2005;7(5):493-503. doi: https://doi.org/10.1111/j.1463-1326.2004.00421.x

4. Puchalski ML, Russell TL, Karlsen KA. Neonatal hypoglycemia: Is there a sweet spot? Crit Care Nurs Clin North Am. 2018;30(4):467-480. doi: https://doi.org/10.1016/j.cnc.2018.07.004

5. Mohseni S. Neurologic damage in hypoglycemia. Handb Clin Neurol. 2014;(126):513-532. doi: https://doi.org/10.1016/B978-0-444-53480-4.00036-9

6. Yorifuji T, Horikawa R, Hasegawa T, et al. Clinical practice guidelines for congenital hyperinsulinism. Clin Pediatr Endocrinol. 2017;26(3):127-152. doi: https://doi.org/10.1297/cpe.26.127

7. Shield JPH. Fluorine-18 L-3,4-dihydroxyphenylalanine positron emission tomography: improving surgery and outcome in focal hyperinsulinism. Horm Res Paediatr. 2006;66(1):43-44. doi: https://doi.org/10.1159/000093472

8. Giri D, Hawton K, Senniappan S. Congenital hyperinsulinism: recent updates on molecular mechanisms, diagnosis and management. J Pediatr Endocrinol Metab. 2021;66(1):43-44. doi: https://doi.org/10.1515/jpem-2021-0369

9. Eisermann M, Kaminska A, Moutard ML, et al. Normal EEG in childhood: from neonates to adolescents. Neurophysiol Clin. 2013;43(1):35-65. doi: https://doi.org/10.1016/j.neucli.2012.09.091

10. Kaminska A, Eisermann M, Plouin P. Child EEG (and maturation). Handb Clin Neurol. 2019;(160):125-142. doi: https://doi.org/10.1016/B978-0-444-64032-1.00008-4

11. Pearl PL, Beal J, Eisermann M, et al. Normal EEG in Wakefulness and Sleep. New York NY: Oxford University Press; 2017. doi: https://doi.org/10.1093/med/9780190228484.003.0007

12. Lopes da Silva FH, Niedermeyer E, Schomer DL, et al. Niedermeyer’s Electroencephalography: Basic Principles Clinical Applications and Related Fields. Seventh edition. New York NY: Oxford University Press; 2018. doi: https://doi.org/10.1093/med/9780190228484.001.0001

13. Marshall PJ, Bar-Haim Y, Fox NA. Development of the EEG from 5 months to 4 years of age. Clin Neurophysiol. 2002;113(8):1199-1208. doi: https://doi.org/10.1016/S1388-2457(02)00163-3

14. Obshchestvennaia organizatsiia «Rossiĭskaia assotsiatsiia endokrinologov». Natsional’nye klinicheskie rekomendatsii. Diagnostika i lechenie vrozhdennogo giperinsulinizma u deteĭ. Moscow: 2021. (In Russ.).

15. Beniczky S, Hirsch LJ, Kaplan PW, et al. Unified EEG terminology and criteria for nonconvulsive status epilepticus. Epilepsia. 2013;54(6):28-29. doi: https://doi.org/10.1111/epi.12270

16. Rich JT, Neely JG, Paniello RC, et al. A practical guide to understanding Kaplan-Meier curves. Otolaryngol Head Neck Surg. 2010;143(3):331-336. doi: https://doi.org/10.1016/j.otohns.2010.05.007

17. Bin-Abbas BS, Al-Mulhim AN, Sakati NA, Al-Ashwal AA. Persistent hyperinsulinemic hypoglycemia of infancy in 38 children. Saudi Med J. 2003;24(8):890-894.

18. Rother KI, Matsumoto JMS, Rasmussen NH, Schwenk WF. Subtotal pancreatectomy for hypoglycemia due to congenital hyperinsulinism: long-term follow-up of neurodevelopmental and pancreatic function. Pediatr Diabetes. 2001;2(3):115-122. doi: https://doi.org/10.1034/j.1399-5448.2001.002003115.x

19. Dacou-Voutetakis C, Psychou F, Maniati-Christidis M. Persistent hyperinsulinemic hypoglycemia of infancy: long term results. J Pediatr Endocrinol Metab. 1998;11(S1):131-141. doi: https://doi.org/10.1515/JPEM.1998.11.S1.131

20. Mazor-Aronovitch K, Gillis D, Lobel D, et al. Long-term neurodevelopmental outcome in conservatively treated congenital hyperinsulinism. Eur J Endocrinol. 2007;157(4):491-497. doi: https://doi.org/10.1530/EJE-07-0445

21. Roeper M, Salimi Dafsari R, Hoermann H, et al. Risk Factors for adverse neurodevelopment in transient or persistent congenital hyperinsulinism. Front Endocrinol (Lausanne). 2020;(11). doi: https://doi.org/10.3389/fendo.2020.580642

22. Helleskov A, Melikyan M, Globa E, et al. Both low blood glucose and insufficient treatment confer risk of neurodevelopmental impairment in congenital hyperinsulinism: A multinational cohort study. Front Endocrinol (Lausanne). 2017;(8). doi: https://doi.org/10.3389/fendo.2017.00156

23. Laimon W, Aboelenin HM, El Tantawi NT. Clinical characteristics, outcome, and predictors of neurological sequelae of persistent congenital hyperinsulinism: A single tertiary center experience. Pediatr Diabetes. 2021;22(3):388-399. doi: https://doi.org/10.1111/pedi.13186

24. Bahi-Buisson N, Roze E, Dionisi C, et al. Neurological aspects of hyperinsulinism-hyperammonaemia syndrome. Dev Med Child Neurol. 2008;50(12):945-949. doi: https://doi.org/10.1111/j.1469-8749.2008.03114.x

25. Sun H-S, Feng Z-P, Miki T, et al. Enhanced neuronal damage after ischemic insults in mice lacking Kir6.2-Containing ATP-Sensitive K + Channels. J Neurophysiol. 2006;95(4):2590-2601. doi: https://doi.org/10.1152/jn.00970.2005