The efficacy and safety of ketogenic diet in the treatment of drug-resistant epilepsy in children with malformations of cortical development_Journal of Epilepsy

Authors：

ZHANG Hongwei , ZHAO Fen , HU Wandong , ZHANG Huan , LIU Yong ,  JIN Ruifeng

Epilepsy Center, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan 250022, China;

Corresponding author：

JIN Ruifeng, Email: 13953174587@163.com

Keywords：

Ketogetic diet; Malformations of cortical development; Epilepsy; Efficacy

DOI：

10.7507/2096-0247.202307009

Video：

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Objective To explore the efficacy and safety of ketogenic diet (KD) in the treatment of drug-resistant epilepsy in children with malformations of cortical development (MCD). Methods The clinical data of 10 children with drug-resistant epilepsy caused by MCD treated in the Epilepsy Center of Children's Hospital affiliated to Shandong University from May 2021 to February 2023 were analyzed retrospectively. All of them received classical KD treatment for the first time. The patients were followed up at 1, 3, 6 and 12 months after KD treatment. The clinical efficacy was evaluated by Engel grade and the adverse reactions were recorded at the same time. Results There were 10 patients in this study, including 5 males and 5 females. The age of onset was 0.2~36.0 (10.3±11.1) months, 2.0~31.0 (9.7±8.5) months, and the age of starting KD was 3.0~50.0 (20.0±15.7) months. Cranial imaging showed that there were 2 cases of hemimegalencephaly, 1case of lissencephaly, 1 case of pachygyria combine polymicrogyria, and 6 cases of FCD,3 had gene abnormality (2 cases of DEPDC5 gene, 1 case of ARX gene). All children had different degrees of developmental retardation before KD treatment. The antiseizure medications taken before KD treatment were 2.0~5.0 (3.2±0.9). 5/10 (50%) children had a >50% reduction in seizure frequency at 3 months on the diet, 2/10 (20%) children had a seizure free response. The rate of development improvement was 50.0% (5/10) at 3 months. 5 cases had mild adverse reactions (50%), including 1 case of hypokalemia and 4 cases of gastrointestinal reactions, all of which were relieved after the reduction of the proportion of KD diet. None of the children stopped using KD. Conclusion KD therapy is a safe and effective method for the treatment of drug-resistant epilepsy in children caused by MCD, and some children can improve their developmental level.

Citation： ZHANG Hongwei, ZHAO Fen, HU Wandong, ZHANG Huan, LIU Yong, JIN Ruifeng. The efficacy and safety of ketogenic diet in the treatment of drug-resistant epilepsy in children with malformations of cortical development. Journal of Epilepsy, 2023, 9(6): 461-465. doi: 10.7507/2096-0247.202307009 Copy

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2.	Licchetta L, Vignatelli L, Toni F, et al. Long-term outcome of epilepsy and cortical malformations due to abnormal migration and postmigrational development: a cohort study. Neurology, 2022, 99 (1): e23-e32.
3.	Kossoff EH, Zupec-Kania BA, Auvin S, et al. Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open, 2018, 3 (2): 175-192.
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7.	Barkovich AJ, Kuzniecky RI, Dobyns WB, et al. A classification scheme for malformations of cortical development. Neuropediatrics, 1996, 27 (2): 59-63.
8.	Leventer RJ, Phelan EM, Coleman LT, et al. Clinical and imaging features of cortical malformations in childhood. Neurology, 1999, 53 (4): 715-22.
9.	Li H, Ji S, Dong B, Chen L. Seizure control after epilepsy surgery in early childhood: a systematic review and meta-analysis. Epilepsy Behav. 2021, 125: 108369.
10.	Dyńka D, Kowalcze K, Paziewska A. The role of ketogenic diet in the treatment of neurological diseases. Nutrients, 2022, 14 (23): 5003.
11.	Ułamek-Kozioł M, Czuczwar SJ, Januszewski S, et al. Ketogenic diet and epilepsy. Nutrients, 2019, 11 (10).
12.	Yang H, Shan W, Zhu F, et al. Ketone bodies in neurological diseases: focus on neuroprotection and underlying mechanisms. Front Neurol, 2019, 10: 585.
13.	Goswami JN, Sharma S. Current Perspectives on the role of the ketogenic diet in epilepsy management. Neuropsychiatr Dis Treat, 2019, 15: 3273-3285.
14.	McDaniel SS, Rensing NR, Thio LL, et al. The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway. Epilepsia, 2011, 52 (3): e7-e11.
15.	Genzer Y, Dadon M, Burg C, et al. Ketogenic diet delays the phase of circadian rhythms and does not affect AMP-activated protein kinase (AMPK) in mouse liver. Mol Cell Endocrinol, 2015, 417: 124-130.
16.	邓艳春, 乔晓枝. mTOR信号通路异常与癫痫. 中华神经科杂志, 2020, 53 (10): 829-835.
17.	Pasca L, Caraballo RH, De Giorgis V, et al. Ketogenic diet use in children with intractable epilepsy secondary to malformations of cortical development: a two- centre experience. Seizure, 2018, 57: 34-37.
18.	Jung DE, Kang HC, Kim HD. Long-term outcome of the ketogenic diet for intractable childhood epilepsy with focal malformation of cortical development. Pediatrics, 2008, 122 (2): e330-e333.
19.	Kang JW, Rhie SK, Yu R, et al. Seizure outcome of infantile spasms with focal cortical dysplasia. Brain Dev, 2013, 35 (8): 816-820.
20.	Ko A, Sim NS, Choi HS, et al. Efficacy of the ketogenic diet for pediatric epilepsy according to the presence of detectable somatic mTOR pathway mutations in the brain. J Clin Neurol, 2022, 18 (1): 71-78.
21.	van Berkel AA, IJff DM, Verkuyl JM. Cognitive benefits of the ketogenic diet in patients with epilepsy: a systematic overview. Epilepsy Behav, 2018, 87: 69-77.

1. Severino M, Geraldo AF, Utz N, et al. Definitions and classification of malformations of cortical development: practical guidelines. Brain, 2020, 143 (10): 2874-2894.
2. Licchetta L, Vignatelli L, Toni F, et al. Long-term outcome of epilepsy and cortical malformations due to abnormal migration and postmigrational development: a cohort study. Neurology, 2022, 99 (1): e23-e32.
3. Kossoff EH, Zupec-Kania BA, Auvin S, et al. Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open, 2018, 3 (2): 175-192.
4. Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia, 2010, 51 (6): 1069-1077.
5. Barkovich AJ, Guerrini R, Kuzniecky RI, et al. A developmental and genetic classification for malformations of cortical development: update 2012. Brain, 2012, 135 (Pt 5): 1348-69.
6. Juric-Sekhar G, Hevner RF. Malformations of cerebral cortex development: molecules and mechanisms. Annu Rev Pathol, 2019, 14: 293-318.
7. Barkovich AJ, Kuzniecky RI, Dobyns WB, et al. A classification scheme for malformations of cortical development. Neuropediatrics, 1996, 27 (2): 59-63.
8. Leventer RJ, Phelan EM, Coleman LT, et al. Clinical and imaging features of cortical malformations in childhood. Neurology, 1999, 53 (4): 715-22.
9. Li H, Ji S, Dong B, Chen L. Seizure control after epilepsy surgery in early childhood: a systematic review and meta-analysis. Epilepsy Behav. 2021, 125: 108369.
10. Dyńka D, Kowalcze K, Paziewska A. The role of ketogenic diet in the treatment of neurological diseases. Nutrients, 2022, 14 (23): 5003.
11. Ułamek-Kozioł M, Czuczwar SJ, Januszewski S, et al. Ketogenic diet and epilepsy. Nutrients, 2019, 11 (10).
12. Yang H, Shan W, Zhu F, et al. Ketone bodies in neurological diseases: focus on neuroprotection and underlying mechanisms. Front Neurol, 2019, 10: 585.
13. Goswami JN, Sharma S. Current Perspectives on the role of the ketogenic diet in epilepsy management. Neuropsychiatr Dis Treat, 2019, 15: 3273-3285.
14. McDaniel SS, Rensing NR, Thio LL, et al. The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway. Epilepsia, 2011, 52 (3): e7-e11.
15. Genzer Y, Dadon M, Burg C, et al. Ketogenic diet delays the phase of circadian rhythms and does not affect AMP-activated protein kinase (AMPK) in mouse liver. Mol Cell Endocrinol, 2015, 417: 124-130.
16. 邓艳春, 乔晓枝. mTOR信号通路异常与癫痫. 中华神经科杂志, 2020, 53 (10): 829-835.
17. Pasca L, Caraballo RH, De Giorgis V, et al. Ketogenic diet use in children with intractable epilepsy secondary to malformations of cortical development: a two- centre experience. Seizure, 2018, 57: 34-37.
18. Jung DE, Kang HC, Kim HD. Long-term outcome of the ketogenic diet for intractable childhood epilepsy with focal malformation of cortical development. Pediatrics, 2008, 122 (2): e330-e333.
19. Kang JW, Rhie SK, Yu R, et al. Seizure outcome of infantile spasms with focal cortical dysplasia. Brain Dev, 2013, 35 (8): 816-820.
20. Ko A, Sim NS, Choi HS, et al. Efficacy of the ketogenic diet for pediatric epilepsy according to the presence of detectable somatic mTOR pathway mutations in the brain. J Clin Neurol, 2022, 18 (1): 71-78.
21. van Berkel AA, IJff DM, Verkuyl JM. Cognitive benefits of the ketogenic diet in patients with epilepsy: a systematic overview. Epilepsy Behav, 2018, 87: 69-77.

Journal of Epilepsy

The efficacy and safety of ketogenic diet in the treatment of drug-resistant epilepsy in children with malformations of cortical development

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