Effect of ketogenic diet in patients with Dravet syndrome_Journal of Epilepsy

Authors：

 DONG Xiaoli , LI Hua , ZHAO Liming , HU xiangshu , FEI Lingxia , GUO Jing , ZHANG peiqi , LI Kaihui , PENG Kai

The Epilepsy Centre of Guangdong 999 Brain Hospital, Guangzhou 510520, China;

Corresponding author：

DONG Xiaoli, Email: 965889556@qq.com

Keywords：

Ketogenic diet; Dravet syndrome; SCN1A; Children

DOI：

10.7507/2096-0247.20200080

Video：

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Objective To explore the effect of Ketogenic diet (KD) in patients with Dravet syndrome (DS).Methods The seizures, electroencephalogram (EEG) and cognitive function of 26 DS patients receiving treatment of KD from June 2015 to October 2019 in the Epilepsy Centre of Guangdong 999 Brain Hospital were analyzed retrospectively. Modified Johns Hopkins protocol was used to initiate KD, blood glucose and urinary ketone bodies were monitored in the patients. The effect was evaluated by Engel outcome scale. And the EEG, cognition, language and motor function of the patients were assessed.Results 26 DS patients (20 boys, 6 girls) received treatment of KD more than 4 weeks, the seizure of epilepsy were reduced above 50% in 15 patients (57.7%), 2 patients were seizure free. Among them, the effcet of KD can be observed in 7 patients within one week and 3 patients within two weeks, accounting for 66.7% (10/15). 26 cases (100%), 24 cases (92.3%), 20 cases (76.9%), 11 cases (42.3%) were reserved in 4, 12, 24, 28 weeks respectively. 26 patients achieved Engel Ⅰ ,Ⅱ,Ⅲ,Ⅳgrade effect, accounting for 38.5% (10/25), 54.2% (13/23), 65.0% (12/19), 81.8% (9/11) respectively according to Engel scale. The back ground rhythm of EEG showed obvious improvement in 14 patients wthin 16 patients who revieved EEG after KD. 17 patients assessed cognitive, language and motor function after KD, cognitive function was improved in 10 patients, language was enhanced in 11 patients, motor function of 8 patients was enhanced. The main adverse reactions of KD in the treatment process were mainly gastrointestinal symptoms and metabolic disorders.Conclusion KD treatment in DS has many advantages, such as fast acting, being effective in more than half of the DS patients and tolerable adverse reactions. Cognitive, language and motor function were improved in some patients. Drug resistant DS patients are suggested to receive KD treatment early.

Citation： DONG Xiaoli, LI Hua, ZHAO Liming, HU xiangshu, FEI Lingxia, GUO Jing, ZHANG peiqi, LI Kaihui, PENG Kai. Effect of ketogenic diet in patients with Dravet syndrome. Journal of Epilepsy, 2020, 6(6): 485-491. doi: 10.7507/2096-0247.20200080 Copy

1.	Dravet C. Les epilepsies graves de I’enfant. Vie Med, 1978, 8: 543-548.
2.	Dravet C. The core dravet syndrome phenotype. Epilepsia, 2011, 52(Suppl 2): 3-9.
3.	Bayat A, Hjalgrim H, Møller RS. The incidence of SCN1A-related Dravet syndrome in Denmark is 1:22, 000: a population-based study from 2004 to 2009. Epilepsia, 2015, 56(Suppl 1): 36-39.
4.	Claes L, Del-Favero J, Ceulemans B, et al. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet, 2001, 68: 1327-1332.
5.	Steel D, Symonds JD, Zuberi SM, et al. Dravet syndrome and its mimics: Beyond SCN1A. Epilepsia. 2017, 58(11): 1807-1816.
6.	Wheless JW. History of the ketogenic diet. Epilepsia, 2008, 49(Suppl. 8): 3-5.
7.	Cervenka MC, Kossoff EH. Dietary treatment of intractable epilepsy. Continuum (Minneap Minn), 2013, 19: 756-766.
8.	Caraballo RH, Cersósimo RO, Sakr D, et al. Ketogenic diet in patients with Dravet syndrome. Epilepsia, 2005, 46(11): 1539-1544.
9.	Laux L, Blackford R. The ketogenic diet in dravet syndrome. J Child Neurol, 2013, 28: 1041-1044.
10.	Dravet C, Bureau M, Oguni H, et al. Dravet syndrome(Severe myoclonic epilepsy in infancy). In: Bureau M, Genton P, Dravet C, et al//Editors. Epileptic Syndromes in Infancy, Childhood and Adolescence, 5th ed. Paris: John Libbey Eurotext, 2012: 125-156.
11.	Anwar A, Saleem S, Patel UK, et al. Dravet syndrome: an overview. Cureus, 2019, 11(6): e5006.
12.	Kossoff EH, Drward JL. The modified atkins diet. Epilepsia, 2008, 49(8): 37-41.
13.	Wheless JW. History of the ketogenic diet. Epilepsia, 2008, 49(Suppl 8): 3-5.
14.	Thammongkol S, Vears DF, Bicknell-Royle J, et al. Efficacy of the ketogenic diet: which epilepsies respond? Epilepsia, 2012, 53(1): 55.
15.	Yan Ni, Xin-Hua Wang, Lin-Mei Zhang, et al. Prospective study of the efficacy of a ketogenic diet in 20 patients with dravet syndrome. Seizure, 2018, 60: 144-148.
16.	Ko A, Da EJ, Kim SH, et al. The efficacy of ketogenic diet for specific genetic mutation in developmental andepileptic encephalopathy. Front Neurol, 2018, 9: 530.
17.	Inoue Y, Ohtsuka Y. STP-1 study group. Effectiveness of add-on stiripentol to clobazam and valproate in Japanese patients with dravet syndrome: additional supportive evidence. Epilepsy Res, 2014, 108: 725-731.
18.	Shi XY, Tomonoh Y, Wang WZ, et al. Efficacy of antiepileptic drugs for the treatment of dravet syndrome with different genotypes. Brain Dev, 2016, 38(1): 40-46.
19.	O’Connor SE, Ream MA, Richardson C, et al. The ketogenic diet for the treatment of pediatric status epilepticus. Pediatr Neurol, 2014, 50(1): 101-103.
20.	Dressler A, Trimmel-Schwahofer P, Reithofer E, et al. Efficacy and tolerability of the ketogenic diet in dravet syndrome:comparison with various standard antiepileptic drug regimen. Epilepsy Res, 2015, 109(1): 81-89.
21.	Nabbout R, Copioli C, Chipaux M, et al. Ketogenic diet also benefits dravet syndrome patients receiving stiripentol: a prospective pilot study. Epilepsia, 2011, 52(1): 54-57.
22.	Liao J, Qin J, Zhou S, et al. Prospective multicenter study on long-term ketogenic diet therapy for intractable childhood epilepsy. Chin J Pediatr, 2013, 51: 276-281.
23.	Suo C, Liao J, Lu X, et al. Efficacy and safety of the ketogenic diet in Chinese children. Seizure, 2013, 22(2): 174-178.
24.	Kossoff EH, Zupec-Kania BA, Ephane Auvin S, et al. Optimal clinical management of children receiving dietary therapies for epilepsy: updated recommendations of the International Ketogenic Diet Study Group. Child Neurol Soc Epilepsia Open, 2018, 3(2): 175-192.
25.	Ismayilova N, Leung MA, Kumar R, et al. Ketogenic diet therapy in infants less than two years of age for medically refractory epilepsy. Seizure, 2018, 57(1): 5-7.
26.	Kessler SK, Gallagher PR, Renée AS, et al. Early EEG improvement after ketogenic diet initiation. Epilepsy Res, 2011, 94(1): 94-101.
27.	Li B. Effects of ketogenic diet on the clinical and electroencephalographic features of children with drug therapy-resistant epilepsy. Exp Therap Med, 2012, 5(2): 611-615.
28.	Chiron C, Dulac O. The pharmacologic treatment of dravet syndrome. Epilepsia, 2011, 52(Suppl. 2): 72-75.
29.	Nagisa S, Tsuyoshi I. Electrical control in neurons by the ketogenic diet. Front Cell Neurosci, 2018, 12(2): 208.
30.	Rho JM. How does the ketogenic diet induce anti-seizure effects? Neurosci Lett, 2017, 637(1): 4-10.

1. Dravet C. Les epilepsies graves de I’enfant. Vie Med, 1978, 8: 543-548.
2. Dravet C. The core dravet syndrome phenotype. Epilepsia, 2011, 52(Suppl 2): 3-9.
3. Bayat A, Hjalgrim H, Møller RS. The incidence of SCN1A-related Dravet syndrome in Denmark is 1:22, 000: a population-based study from 2004 to 2009. Epilepsia, 2015, 56(Suppl 1): 36-39.
4. Claes L, Del-Favero J, Ceulemans B, et al. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet, 2001, 68: 1327-1332.
5. Steel D, Symonds JD, Zuberi SM, et al. Dravet syndrome and its mimics: Beyond SCN1A. Epilepsia. 2017, 58(11): 1807-1816.
6. Wheless JW. History of the ketogenic diet. Epilepsia, 2008, 49(Suppl. 8): 3-5.
7. Cervenka MC, Kossoff EH. Dietary treatment of intractable epilepsy. Continuum (Minneap Minn), 2013, 19: 756-766.
8. Caraballo RH, Cersósimo RO, Sakr D, et al. Ketogenic diet in patients with Dravet syndrome. Epilepsia, 2005, 46(11): 1539-1544.
9. Laux L, Blackford R. The ketogenic diet in dravet syndrome. J Child Neurol, 2013, 28: 1041-1044.
10. Dravet C, Bureau M, Oguni H, et al. Dravet syndrome(Severe myoclonic epilepsy in infancy). In: Bureau M, Genton P, Dravet C, et al//Editors. Epileptic Syndromes in Infancy, Childhood and Adolescence, 5th ed. Paris: John Libbey Eurotext, 2012: 125-156.
11. Anwar A, Saleem S, Patel UK, et al. Dravet syndrome: an overview. Cureus, 2019, 11(6): e5006.
12. Kossoff EH, Drward JL. The modified atkins diet. Epilepsia, 2008, 49(8): 37-41.
13. Wheless JW. History of the ketogenic diet. Epilepsia, 2008, 49(Suppl 8): 3-5.
14. Thammongkol S, Vears DF, Bicknell-Royle J, et al. Efficacy of the ketogenic diet: which epilepsies respond? Epilepsia, 2012, 53(1): 55.
15. Yan Ni, Xin-Hua Wang, Lin-Mei Zhang, et al. Prospective study of the efficacy of a ketogenic diet in 20 patients with dravet syndrome. Seizure, 2018, 60: 144-148.
16. Ko A, Da EJ, Kim SH, et al. The efficacy of ketogenic diet for specific genetic mutation in developmental andepileptic encephalopathy. Front Neurol, 2018, 9: 530.
17. Inoue Y, Ohtsuka Y. STP-1 study group. Effectiveness of add-on stiripentol to clobazam and valproate in Japanese patients with dravet syndrome: additional supportive evidence. Epilepsy Res, 2014, 108: 725-731.
18. Shi XY, Tomonoh Y, Wang WZ, et al. Efficacy of antiepileptic drugs for the treatment of dravet syndrome with different genotypes. Brain Dev, 2016, 38(1): 40-46.
19. O’Connor SE, Ream MA, Richardson C, et al. The ketogenic diet for the treatment of pediatric status epilepticus. Pediatr Neurol, 2014, 50(1): 101-103.
20. Dressler A, Trimmel-Schwahofer P, Reithofer E, et al. Efficacy and tolerability of the ketogenic diet in dravet syndrome:comparison with various standard antiepileptic drug regimen. Epilepsy Res, 2015, 109(1): 81-89.
21. Nabbout R, Copioli C, Chipaux M, et al. Ketogenic diet also benefits dravet syndrome patients receiving stiripentol: a prospective pilot study. Epilepsia, 2011, 52(1): 54-57.
22. Liao J, Qin J, Zhou S, et al. Prospective multicenter study on long-term ketogenic diet therapy for intractable childhood epilepsy. Chin J Pediatr, 2013, 51: 276-281.
23. Suo C, Liao J, Lu X, et al. Efficacy and safety of the ketogenic diet in Chinese children. Seizure, 2013, 22(2): 174-178.
24. Kossoff EH, Zupec-Kania BA, Ephane Auvin S, et al. Optimal clinical management of children receiving dietary therapies for epilepsy: updated recommendations of the International Ketogenic Diet Study Group. Child Neurol Soc Epilepsia Open, 2018, 3(2): 175-192.
25. Ismayilova N, Leung MA, Kumar R, et al. Ketogenic diet therapy in infants less than two years of age for medically refractory epilepsy. Seizure, 2018, 57(1): 5-7.
26. Kessler SK, Gallagher PR, Renée AS, et al. Early EEG improvement after ketogenic diet initiation. Epilepsy Res, 2011, 94(1): 94-101.
27. Li B. Effects of ketogenic diet on the clinical and electroencephalographic features of children with drug therapy-resistant epilepsy. Exp Therap Med, 2012, 5(2): 611-615.
28. Chiron C, Dulac O. The pharmacologic treatment of dravet syndrome. Epilepsia, 2011, 52(Suppl. 2): 72-75.
29. Nagisa S, Tsuyoshi I. Electrical control in neurons by the ketogenic diet. Front Cell Neurosci, 2018, 12(2): 208.
30. Rho JM. How does the ketogenic diet induce anti-seizure effects? Neurosci Lett, 2017, 637(1): 4-10.

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Effect of ketogenic diet in patients with Dravet syndrome

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