The clinical analysis of ketogenic diet therapy in children with rapidly progressive Dravet syndrome_Journal of Epilepsy

Authors：

NI Yan , ZHOU Shuizhen , ZHANG Yunjian , LI Yijie , GONG Xiaoyan , LU Zhongying , WANG Yi ,  YU Lifei

Department of Neurology, National Children’s Medical Center, ChIldren’s Hospital of Fudan University, Shanghai 201102, China;

Corresponding author：

YU Lifei, Email: yulifei7711@163.com

Keywords：

Dravet syndrome; Ketogenic diet; Intractable epilepsy; Status epilepticus

DOI：

10.7507/2096-0247.202207012

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Objiective To explore the efficacy and safety of ketogenic diet therapy (KDT) in the rapidly progressive stage of childhood developmental epileptic encephalopathy Dravet syndrome (DS). Methods The clinical data of all patients who added KDT in the Children’s Hospital of Fudan University from 2011 to 2022 were retrospectively collected, and the age of <6 years was used as the criterion for the rapid progression of the disease. The clinica data, genotype and the efficacy of KDT were analyzed in DS patients who met the criteria. Results A total of 32 patients met the criteria for rapid disease progress, including 22 males and 10 females. The age at onset was (5.69±2.10) months. All patients had multiple seizure phenotypes and monthly seizures despite reasonable Antiseizure medications treatment. After 3, 6, 12, and ≥24 months, 93.8% (30/32), 87.5% (28/32), 53.1% (17/32), 34.4% (11/32) remained on the KDT, while 76.7% (23/30), 75.0% (21/28), 70.6% (12/17), 54.5% (6/11) showed >50% reduction in seizure. Status epileptius (SE) was reduced by 100% at 3 months, 71.0% at 6 months, 86.0% at 12 months. After 12 months, 14 patients experienced efficacy degradation. After 3 months, the EEG background rhythm showed improvement in 75.0% patients, interictal epileptic discharges was decreased in 54.5% patients and cognitive function was improved in 78.6% patients. At the initial stage of KDT, 62.5% (20/32) patients had transisent adverse reactions, including diarrhea, vomiting, fatigue, lethargy, hypoglycemia, and metabolic acidosis, but no mid- and long-term adverse reactions were found. Conclusion KDT is an efficective and safe treatment for DS. KDT can effectively control seizures, reduce the incidence of Status SE and shorten the duration of SE. With the prolongation of the KDT course, some patients experienced a degraded effect. KDT can improve abnormal EEG and cognitive function in DS patients. Pharmoco-resistant DS patients are suggested to receive KDT in the early stage of disease progression.

Citation： NI Yan, ZHOU Shuizhen, ZHANG Yunjian, LI Yijie, GONG Xiaoyan, LU Zhongying, WANG Yi, YU Lifei. The clinical analysis of ketogenic diet therapy in children with rapidly progressive Dravet syndrome. Journal of Epilepsy, 2022, 8(6): 517-523. doi: 10.7507/2096-0247.202207012 Copy

1.	Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia, 2017, 58(4): 512-521.
2.	Dravet C. Dravet syndrome history. Dev Med Child Neurol, 2011, 53: 1-6.
3.	Dravet C. The core Dravet syndrome phenotype. Epilepsia, 2011, 52(Suppl 2): 3-9.
4.	Caraballo RH, Cersosimo RO, Sakr D, et al. Ketogenic diet in patients with Dravet syndrome. Epilepsia, 2005, 46(9): 1539-1544.
5.	Caraballo RH. Nonpharmacologic treatments of Dravet syndrome: Focus on the ketogenic diet. Epilepsia, 2011, 52(1): 79-82.
6.	Laux L, Blackford R. The ketogenic diet in Dravet Syndrome. J Child Neurol, 2013, 28(8): 1041-1044.
7.	Tian XJ, Chen JY, Zhang J, et al. The efficacy of ketogenic diet in 60 chinese patients with Dravet Syndrome. Frontiers in Neurology, 2019, 10: 625.
8.	Nabbout R, Copioli C, Chipaux M, et al. Ketogenic diet also benefits Dravet syndrome patients receiving stiripentol: a prospective pilot study. Epilepsia, 2011, 52(7): E54-E7.
9.	Liu FY, Peng J, Zhu CH, et al. Efficacy of the ketogenic diet in Chinese children with Dravet syndrome: a focus on neuropsychological development. Epilepsy Behav, 2019, 92: 98-102.
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12.	Cross JH, Caraballo RH, Nabbout R, et al. Dravet syndrome: treatment options and management of prolonged seizures. Epilepsia, 2019, 60(Suppl 1): S39-S48.
13.	刘家雯, 丁鑫, 朱艳伟, 等. 生酮饮食治疗药物难治性Dravet综合征的疗效和安全性的前瞻性对照研究. 中华实用儿科临床杂志, 2019, 34(15): 1160-1165.
14.	Anwar A, Saleem S, Patel UK, et al. Dravet Syndrome: an overview. Cureus, 2019, 11(6): e5006.
15.	Sakauchi M, Oguni H, Kato I, et al. Retrospective multiinstitutional study of the prevalence of early death in Dravet syndrome. Epilepsia, 2011, 52(6): 1144-1149.
16.	Coppola G, Veggiotti P, Cusmai R, et al. The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience. Epilepsy Res, 2002, 48(3): 221-227.
17.	Ashrafi M, Hosseini S, Zamani G, et al. The efficacy of the ketogenic diet in infants and young children with refractory epilepsies using a formula-based powder. Acta Neurologica Belgica, 2017, 117(1): 175-182.
18.	Takayama R, Fujiwara T, Shigematsu H, et al. Long-term course of Dravet syndrome: a study from an epilepsy center in Japan. Epilepsia, 2014, 55(4): 528-538.
19.	Catterall WA. Sodium channels, inherited epilepsy, and antiepileptic drugs. Annu Rev Pharmacol Toxicol, 2014, 54: 317-338.
20.	Dalic L, Mullen SA, Roulet Perez E, et al. Lamotrigine can be beneficial in patients with Dravet syndrome. Dev Med Child Neurol, 2015, 57(2): 200-202.
21.	Snoeijen-Schouwenaars FM, Veendrick MJ, van Mierlo P, et al. Carbamazepine and oxcarbazepine in adult patients with Dravet syndrome: friend or foe? Seizure, 2015, 29(1): 114-118.
22.	Zhang Y, Xu J, Zhang K, et al. The anticonvulsant effects of ketogenic diet on epileptic seizures and potential mechanisms. Curr Neuropharmacol, 2018, 16(1): 66-70.
23.	Groesbeck DK, Bluml RM, Kossoff EH. Long-term use of the ketogenic diet in the treatment of epilepsy. Dev Med Child Neurol, 2006, 48(12): 978-981.

1. Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia, 2017, 58(4): 512-521.
2. Dravet C. Dravet syndrome history. Dev Med Child Neurol, 2011, 53: 1-6.
3. Dravet C. The core Dravet syndrome phenotype. Epilepsia, 2011, 52(Suppl 2): 3-9.
4. Caraballo RH, Cersosimo RO, Sakr D, et al. Ketogenic diet in patients with Dravet syndrome. Epilepsia, 2005, 46(9): 1539-1544.
5. Caraballo RH. Nonpharmacologic treatments of Dravet syndrome: Focus on the ketogenic diet. Epilepsia, 2011, 52(1): 79-82.
6. Laux L, Blackford R. The ketogenic diet in Dravet Syndrome. J Child Neurol, 2013, 28(8): 1041-1044.
7. Tian XJ, Chen JY, Zhang J, et al. The efficacy of ketogenic diet in 60 chinese patients with Dravet Syndrome. Frontiers in Neurology, 2019, 10: 625.
8. Nabbout R, Copioli C, Chipaux M, et al. Ketogenic diet also benefits Dravet syndrome patients receiving stiripentol: a prospective pilot study. Epilepsia, 2011, 52(7): E54-E7.
9. Liu FY, Peng J, Zhu CH, et al. Efficacy of the ketogenic diet in Chinese children with Dravet syndrome: a focus on neuropsychological development. Epilepsy Behav, 2019, 92: 98-102.
10. Wirrell EC, Hood V, Knupp KG, et al. International consensus on diagnosis and management of Dravet syndrome. Epilepsia, 2022, 63(7): 1761-1777.
11. Wirrell EC, Laux L, Donner E, et al. Optimizing the diagnosis and management of Dravet Syndrome: recommendations from a North American Consensus Panel. Pediatr Neurol, 2017, 68: 18-34.
12. Cross JH, Caraballo RH, Nabbout R, et al. Dravet syndrome: treatment options and management of prolonged seizures. Epilepsia, 2019, 60(Suppl 1): S39-S48.
13. 刘家雯, 丁鑫, 朱艳伟, 等. 生酮饮食治疗药物难治性Dravet综合征的疗效和安全性的前瞻性对照研究. 中华实用儿科临床杂志, 2019, 34(15): 1160-1165.
14. Anwar A, Saleem S, Patel UK, et al. Dravet Syndrome: an overview. Cureus, 2019, 11(6): e5006.
15. Sakauchi M, Oguni H, Kato I, et al. Retrospective multiinstitutional study of the prevalence of early death in Dravet syndrome. Epilepsia, 2011, 52(6): 1144-1149.
16. Coppola G, Veggiotti P, Cusmai R, et al. The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience. Epilepsy Res, 2002, 48(3): 221-227.
17. Ashrafi M, Hosseini S, Zamani G, et al. The efficacy of the ketogenic diet in infants and young children with refractory epilepsies using a formula-based powder. Acta Neurologica Belgica, 2017, 117(1): 175-182.
18. Takayama R, Fujiwara T, Shigematsu H, et al. Long-term course of Dravet syndrome: a study from an epilepsy center in Japan. Epilepsia, 2014, 55(4): 528-538.
19. Catterall WA. Sodium channels, inherited epilepsy, and antiepileptic drugs. Annu Rev Pharmacol Toxicol, 2014, 54: 317-338.
20. Dalic L, Mullen SA, Roulet Perez E, et al. Lamotrigine can be beneficial in patients with Dravet syndrome. Dev Med Child Neurol, 2015, 57(2): 200-202.
21. Snoeijen-Schouwenaars FM, Veendrick MJ, van Mierlo P, et al. Carbamazepine and oxcarbazepine in adult patients with Dravet syndrome: friend or foe? Seizure, 2015, 29(1): 114-118.
22. Zhang Y, Xu J, Zhang K, et al. The anticonvulsant effects of ketogenic diet on epileptic seizures and potential mechanisms. Curr Neuropharmacol, 2018, 16(1): 66-70.
23. Groesbeck DK, Bluml RM, Kossoff EH. Long-term use of the ketogenic diet in the treatment of epilepsy. Dev Med Child Neurol, 2006, 48(12): 978-981.

Journal of Epilepsy

The clinical analysis of ketogenic diet therapy in children with rapidly progressive Dravet syndrome

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