Journal http://jcn.sagepub.com/ of Child Neurology
Use of the Modified Atkins Diet in Lennox Gastaut Syndrome Suvasini Sharma, Puneet Jain, Sheffali Gulati, Naveen Sankhyan and Anuja Agarwala J Child Neurol published online 20 March 2014 DOI: 10.1177/0883073814527162 The online version of this article can be found at: http://jcn.sagepub.com/content/early/2014/03/20/0883073814527162
Published by: http://www.sagepublications.com
Additional services and information for Journal of Child Neurology can be found at: Email Alerts: http://jcn.sagepub.com/cgi/alerts Subscriptions: http://jcn.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Mar 20, 2014 What is This?
Downloaded from jcn.sagepub.com at UNIV OF SOUTHERN CALIFORNIA on April 3, 2014
Original Article
Use of the Modified Atkins Diet in Lennox Gastaut Syndrome
Journal of Child Neurology 1-4 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073814527162 jcn.sagepub.com
Suvasini Sharma, MD, DM1,2, Puneet Jain, MD, DM1,2, Sheffali Gulati, MD1, Naveen Sankhyan, MD, DM1,3, and Anuja Agarwala, MSc4
Abstract There is scanty data regarding the efficacy and tolerability of the modified Atkins diet in children with Lennox-Gastaut syndrome. This study was a retrospective review of children with Lennox-Gastaut syndrome treated with the modified Atkins diet from May 2009 and March 2011. The diet was initiated in those children who persisted to have daily seizures despite the use of at least 3 appropriate antiepileptic drugs. Twenty-five children were started on a modified Atkins diet, restricting carbohydrate intake to 10 g/d. After 3 months, 2 patients were seizure-free, and 10/25 children had >50% reduction in seizure frequency. At 6 months, of 11 patients on the diet, 3 were seizure free and 8 had >50% reduction in seizure frequency. At 1 year, all 9 children on diet had >50% reduction in seizure frequency. The side effects of the diet were mild. The modified Atkins diet was found to be effective and well tolerated in children with Lennox-Gastaut syndrome. Keywords ketogenic diet, refractory epilepsy, ketosis, nonpharmacologic therapy, modified Atkins diet, Lennox-Gastaut syndrome Received October 19, 2013. Received revised December 17, 2013. Accepted for publication February 13, 2014.
Lennox-Gastaut syndrome is a severe form of childhood epileptic encephalopathy. The characteristic features of Lennox-Gastaut syndrome include intractable seizures including tonic, atypical absence, atonic and myoclonic seizures. Associated cognitive deterioration/stagnation is common and fluctuates with the seizure frequency. The electroencephalogram (EEG) reveals generalized slow spike-wave discharges with paroxysmal fast activity.1 The medical treatment of this syndrome with antiepileptic drugs is challenging.1-5 The ketogenic diet can be an useful therapeutic option alternative and can be used early in the management.6 The modified Atkins diet is a less restrictive alternative to the traditional ketogenic diet. This diet is started on an outpatient basis without a fast, allows unlimited protein and fat, and does not restrict calories or fluids. Many recent studies in children have demonstrated its efficacy and safety in refractory epilepsy.7-20 There is paucity of data regarding the efficacy and tolerability of the modified Atkins diet in children with Lennox-Gastaut syndrome. The studies exploring the efficacy of the modified Atkins diet in children with refractory epilepsy have enrolled children with heterogeneous etiologies and epilepsy syndromes. Relatively few children with Lennox-Gastaut syndrome have been included in these studies and separate outcomes in terms of seizure reduction in children with Lennox-Gastaut syndrome have not been specified. This retrospective study was thus
carried out to determine the efficacy and tolerance of the modified Atkins diet in children with Lennox-Gastaut syndrome managed at our institution.
Methods Setting and Participants This study was carried out in the Department of Pediatrics at a tertiary care and referral centre in north India. This was a follow-up study of children with Lennox-Gastaut syndrome started on the modified Atkins diet. These children were part of a randomized controlled trial of the use of the modified Atkins diet in refractory childhood
1
Division of Pediatric Neurology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India 2 Division of Pediatric Neurology, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children’s Hospital, New Delhi, India 3 Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India 4 Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India Corresponding Author: Sheffali Gulati, MD, Division of Pediatric Neurology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110 029 India. Email: [email protected]
Downloaded from jcn.sagepub.com at UNIV OF SOUTHERN CALIFORNIA on April 3, 2014
2
Journal of Child Neurology
epilepsy.19 The records of children with Lennox-Gastaut syndrome started on the modified Atkins diet at our institution from May 2009 to November 2012 were reviewed. The diagnosis of Lennox-Gastaut syndrome was based on presence of polymorphic seizures, including tonic, typical absence, atonic and myoclonic seizures, associated cognitive deterioration or stagnation, and generalized slow spike-wave discharges with paroxysmal fast activity on electroencephalogram.1,2 The diet was initiated in children aged 2 to 14 years who persisted to have daily seizures despite the use of at least 3 appropriate antiepileptic drugs. Children with known or suspected inborn errors of metabolism or systemic illnesses were excluded.
Modified Atkins Diet Administration The details of the modified Atkins diet administration at our center have been described earlier.19 The diet was started on an outpatient basis with carbohydrate intake restriction to 10 g/d. The carbohydrate content of various food items was explained to the parents, and exchange lists were provided. The intake of fat (eg, cream, butter, oils, ghee) was actively encouraged. Protein intake was not restricted. There was no calorie restriction. A list of recipes based on common locally available foods with prespecified carbohydrate contents (2.5 g, 5 g, etc) was provided. The antiepileptic drugs were continued unchanged for the first 3 months, and then reduced as per seizure control. The baseline seizure frequency was recorded during a 4-week observation period, during which parents were asked to maintain a daily seizure log, recording seizure type, duration, and frequency. Seizure frequency was assessed by the parent-maintained seizure records on the basis of a chart with various categories of seizure (infantile spasms, absence, myoclonic, atonic, tonic, tonic-clonic, and focal). Patients were reviewed as outpatients monthly for the initial 3 months followed by 3-monthly intervals. They underwent detailed evaluation including history pertaining to seizures, and the adverse effects. Urinary ketones were checked using urine dipstick at each hospital visit. Parents were asked to check urine ketones by reagent sticks daily for the first week on the diet and twice weekly thereafter. Renal and hepatic function tests with fasting lipid profile were performed at baseline and 6-monthly. The data was extracted per a predesigned proforma. The characteristics recorded included age at initiation of diet and onset of epilepsy, sex, dietary habits (vegetarian/nonvegetarian, intake of eggs), seizure frequency and semiology, duration of epilepsy, etiology, number of antiepileptic drugs used before and at diet initiation, presence of developmental delay, autistic features and hyperactivity, and adverse effects of the diet (vomiting, lethargy, poor appetite, refusal to feed, and constipation).
Outcomes The seizure frequency was assessed in accordance with the parental seizure records. At the end of 3, 6, and 12 months, the average seizures per week in the preceding 28 days was compared with the average weekly seizure frequency at the time of initiation of the diet. This was expressed as a percentage change in the seizure frequency as compared to the baseline. The seizure outcome was classified as follows: 50% seizure reduction as compared to baseline, with 2 children (8%) becoming seizure free (Table 2). At 6 months, more than half of the children discontinued diet. More than 50% seizure reduction was seen in all the remaining children (11) at 6 months, with 3 children becoming seizure free. One year after diet initiation, 2 more children discontinued the diet. Eight of the remaining 9 had >90% seizure reduction at 6 months. The reasons for discontinuation included unsatisfactory seizure control (13) and feeling that the diet was too restrictive (3). The urine ketones measurements at a 3-month follow-up after initiation of diet were as follows: trace (5 mg/dL), 2/25 (8%); small (15 mg/dL), 4/25 (16%); moderate (40 mg/dL), 13/25 (52%); and large (80-160 mg/dL), 6/25 (24%). The adequate ketosis (urine ketones 40 mg/dL) was not significantly different in children with 50% seizure reduction at 3 months (69.2% vs 83.3%, p ¼ .65). The diet was well tolerated in the study population. The adverse effects experienced were mild and did not warrant discontinuation of diet in any child. The adverse effects reported included constipation (44%), vomiting (16%), and anorexia (16%). A subjective improvement in alertness and interaction was reported by the parents in 12 (48%) children. None of the children had deranged renal or hepatic functions and lipid profile on the diet.
Discussion The realistic management goals in children with LennoxGastaut syndrome include lowering the frequency of disabling seizures like drop attacks, minimizing daytime seizures, and minimizing the adverse effects of antiepileptic drugs. Despite many suggested treatment protocols,1-5 these goals are difficult to achieve in most children. The pharmaco-resistance of the seizures in Lennox-Gastaut syndrome makes dietary therapy an attractive alternative. The classic ketogenic diet has been shown to be beneficial in the management of these children. A recent review explored the efficacy of a ketogenic diet in Lennox-Gastaut syndrome and found that 47% to 51% children had >50% reduction in seizure frequency at 6 months after initiation of ketogenic diet.6 In a small group of children, we found that modified Atkins diet was also effective in reducing the seizure frequency. Fortyeight percent children at 3 months and 44% children at 6
months had >50% seizure reduction as compared to the baseline. The response rates achieved with the ketogenic diet or the modified Atkins diet appear better than those achieved by lamotrigine or topiramate as add-on therapies.21 The newer antiepileptic drug rufinamide has been shown to be effective in children with Lennox-Gastaut syndrome. With rufinamide as an adjunctive therapy in children with Lennox-Gastaut syndrome, Lee et al22 reported that 34.8% children had >50% seizure reduction at 6 months. In another study, by Kim et al,23 35.9% achieved a >50% reduction in seizure frequency at 3 months. These response rates were inferior to those achieved in this study with the modified Atkins diet.21 Although initiating and monitoring drug therapy has obvious advantage of convenience, the option of diet should be considered in all individuals with drug-refractory, nonsurgically amenable epilepsies, including those with Lennox-Gastaut syndrome. The modified Atkins diet has been reported to be better tolerated than a ketogenic diet.19,24 In this study population also, modified Atkins diet was well tolerated. None of the children had disabling adverse effects. We found several advantages with the use of the modified Atkins diet. Apart from the outpatient initiation and ease of administration, the counseling time was reduced to 30–45 minutes. This is an ideal treatment option for resource-constrained settings with a paucity of trained dieticians. The drawbacks of our study include the small number of children studied and the potential inaccuracy of parental reporting of seizure frequency. The second factor is especially important in Lennox-Gastaut syndrome, which is characterized by frequent and multiple types (including nonconvulsive seizures) of seizures. Despite these, it would be prudent to conclude that the modified Atkins diet appears to be a feasible, effective, and welltolerated alternative in children with Lennox-Gastaut syndrome. Future research could include a randomized controlled trial to assess the effectiveness of early administration of the diet in children with Lennox-Gastaut syndrome, effect of the diet on specific seizure types, study of the interaction of coadministered antiepileptic drugs, and the effect of the diet on cognition and behavior. These could require multicentric studies. Author Contributions SS, NS, and PJ provided clinical care to the patients under the supervision of SG. The diet administration was assisted by AA. PJ and SS drafted the manuscript, which was read and approved by all the authors. The authors are also grateful to the EEG technicians, Mrs Sushila and Mr Suresh.
Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Suvasini Sharma was financially supported as a Senior Research Associate in
Downloaded from jcn.sagepub.com at UNIV OF SOUTHERN CALIFORNIA on April 3, 2014
4
Journal of Child Neurology
the ‘‘Scientists pool scheme’’ of the Council for Scientific and Industrial Research (CSIR), Govt. of India, for this study. There was no other funding source for the study.
Ethical Approval The study was part of a randomized controlled trial of the use of the modified Atkins diet in refractory childhood epilepsy (Reference 19; ethical approval Ref. No. P-07/2.02.2009).
References 1. Arzimanoglou A, French J, Blume WT, et al. Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. Lancet Neurol. 2009;8:82-93. 2. Panayiotopoulos C. A Clinical Guide to Epileptic Syndromes and Their Treatment. 2nd ed. London: Springer; 2011. 3. Arzimanoglou A, Guerrini R, Aicardi J. Aicardi’s Epilepsy in Children. 4th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2012. 4. Montouris GD. Rational approach to treatment options for Lennox-Gastaut syndrome. Epilepsia. 2011;52(suppl 5):10-20. 5. Ferrie CD, Patel A. Treatment of Lennox-Gastaut syndrome (LGS). Eur J Paediatr Neurol. 2009;13:493-504. 6. Lemmon ME, Terao NN, Ng Y-T, et al. Efficacy of the ketogenic diet in Lennox-Gastaut syndrome: a retrospective review of one institution’s experience and summary of the literature. Dev Med Child Neurol. 2012;54:464-468. 7. Kossoff EH, Krauss GL, McGrogan JR, Freeman JM. Efficacy of the Atkins diet as therapy for intractable epilepsy. Neurology. 2003;61:1789-1791. 8. Kossoff EH, McGrogan JR, Bluml RM, et al. A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy. Epilepsia. 2006;47:421-424. 9. Kossoff EH, Turner Z, Bluml RM, et al. A randomized, crossover comparison of daily carbohydrate limits using the modified Atkins diet. Epilepsy Behav. 2007;10:432-436. 10. Kang H-C, Lee HS, You SJ, et al. Use of a modified Atkins diet in intractable childhood epilepsy. Epilepsia. 2007;48:182-186. 11. Porta N, Valle´e L, Boutry E, et al. Comparison of seizure reduction and serum fatty acid levels after receiving the ketogenic and modified Atkins diet. Seizure. 2009;18:359-364.
12. Weber S, Mølgaard C, Karentaudorf, Uldall P. Modified Atkins diet to children and adolescents with medical intractable epilepsy. Seizure. 2009;18:237-240. 13. Kossoff EH, Borsage JL, Comi AM. A pilot study of the modified Atkins diet for Sturge-Weber syndrome. Epilepsy Res. 2010;92: 240-243. 14. Tonekaboni SH, Mostaghimi P, Mirmiran P, et al. Efficacy of the Atkins diet as therapy for intractable epilepsy in children. Arch Iran Med. 2010;13:492-497. 15. Miranda MJ, Mortensen M, Povlsen JH, et al. Danish study of a modified Atkins diet for medically intractable epilepsy in children: can we achieve the same results as with the classical ketogenic diet? Seizure. 2011;20:151-155. 16. Kossoff EH, Dorward JL, Turner Z, Pyzik PL. Prospective study of the modified Atkins diet in combination with a ketogenic liquid supplement during the initial month. J Child Neurol. 2011;26: 147-151. 17. Ito Y, Oguni H, Ito S, et al. A modified Atkins diet is promising as a treatment for glucose transporter type 1 deficiency syndrome. Dev Med Child Neurol. 2011;53:658-663. 18. Kumada T, Miyajima T, Oda N, et al. Efficacy and tolerability of modified Atkins diet in Japanese children with medicationresistant epilepsy. Brain Dev. 2012;34:32-38. 19. Sharma S, Sankhyan N, Gulati S, Agarwala A. Use of the modified Atkins diet for treatment of refractory childhood epilepsy: a randomized controlled trial. Epilepsia. 2013;54:481-486. 20. Sharma S, Sankhyan N, Gulati S, Agarwala A. Use of the modified Atkins diet in infantile spasms refractory to first-line treatment. Seizure. 2012;21:45-48. 21. Hancock EC, Cross JH. Treatment of Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2013;2:CD003277. 22. Lee EH, Yum MS, Ko TS. Effectiveness and tolerability of rufinamide in children and young adults with Lennox-Gastaut syndrome: a single center study in Korea. Clin Neurol Neurosurg. 2013;115:926-929. 23. Kim SH, Eun SH, Kang HC, et al. Rufinamide as an adjuvant treatment in children with Lennox-Gastaut syndrome. Seizure. 2012;21:288-291. 24. Kossoff EH, Dorward JL. The modified Atkins diet. Epilepsia. 2008;49(suppl 8):37-41.
Downloaded from jcn.sagepub.com at UNIV OF SOUTHERN CALIFORNIA on April 3, 2014
Use of the Modified Atkins Diet in Lennox Gastaut Syndrome Suvasini Sharma, Puneet Jain, Sheffali Gulati, Naveen Sankhyan and Anuja Agarwala J Child Neurol published online 20 March 2014 DOI: 10.1177/0883073814527162 The online version of this article can be found at: http://jcn.sagepub.com/content/early/2014/03/20/0883073814527162
Published by: http://www.sagepublications.com
Additional services and information for Journal of Child Neurology can be found at: Email Alerts: http://jcn.sagepub.com/cgi/alerts Subscriptions: http://jcn.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Mar 20, 2014 What is This?
Downloaded from jcn.sagepub.com at UNIV OF SOUTHERN CALIFORNIA on April 3, 2014
Original Article
Use of the Modified Atkins Diet in Lennox Gastaut Syndrome
Journal of Child Neurology 1-4 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073814527162 jcn.sagepub.com
Suvasini Sharma, MD, DM1,2, Puneet Jain, MD, DM1,2, Sheffali Gulati, MD1, Naveen Sankhyan, MD, DM1,3, and Anuja Agarwala, MSc4
Abstract There is scanty data regarding the efficacy and tolerability of the modified Atkins diet in children with Lennox-Gastaut syndrome. This study was a retrospective review of children with Lennox-Gastaut syndrome treated with the modified Atkins diet from May 2009 and March 2011. The diet was initiated in those children who persisted to have daily seizures despite the use of at least 3 appropriate antiepileptic drugs. Twenty-five children were started on a modified Atkins diet, restricting carbohydrate intake to 10 g/d. After 3 months, 2 patients were seizure-free, and 10/25 children had >50% reduction in seizure frequency. At 6 months, of 11 patients on the diet, 3 were seizure free and 8 had >50% reduction in seizure frequency. At 1 year, all 9 children on diet had >50% reduction in seizure frequency. The side effects of the diet were mild. The modified Atkins diet was found to be effective and well tolerated in children with Lennox-Gastaut syndrome. Keywords ketogenic diet, refractory epilepsy, ketosis, nonpharmacologic therapy, modified Atkins diet, Lennox-Gastaut syndrome Received October 19, 2013. Received revised December 17, 2013. Accepted for publication February 13, 2014.
Lennox-Gastaut syndrome is a severe form of childhood epileptic encephalopathy. The characteristic features of Lennox-Gastaut syndrome include intractable seizures including tonic, atypical absence, atonic and myoclonic seizures. Associated cognitive deterioration/stagnation is common and fluctuates with the seizure frequency. The electroencephalogram (EEG) reveals generalized slow spike-wave discharges with paroxysmal fast activity.1 The medical treatment of this syndrome with antiepileptic drugs is challenging.1-5 The ketogenic diet can be an useful therapeutic option alternative and can be used early in the management.6 The modified Atkins diet is a less restrictive alternative to the traditional ketogenic diet. This diet is started on an outpatient basis without a fast, allows unlimited protein and fat, and does not restrict calories or fluids. Many recent studies in children have demonstrated its efficacy and safety in refractory epilepsy.7-20 There is paucity of data regarding the efficacy and tolerability of the modified Atkins diet in children with Lennox-Gastaut syndrome. The studies exploring the efficacy of the modified Atkins diet in children with refractory epilepsy have enrolled children with heterogeneous etiologies and epilepsy syndromes. Relatively few children with Lennox-Gastaut syndrome have been included in these studies and separate outcomes in terms of seizure reduction in children with Lennox-Gastaut syndrome have not been specified. This retrospective study was thus
carried out to determine the efficacy and tolerance of the modified Atkins diet in children with Lennox-Gastaut syndrome managed at our institution.
Methods Setting and Participants This study was carried out in the Department of Pediatrics at a tertiary care and referral centre in north India. This was a follow-up study of children with Lennox-Gastaut syndrome started on the modified Atkins diet. These children were part of a randomized controlled trial of the use of the modified Atkins diet in refractory childhood
1
Division of Pediatric Neurology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India 2 Division of Pediatric Neurology, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children’s Hospital, New Delhi, India 3 Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India 4 Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India Corresponding Author: Sheffali Gulati, MD, Division of Pediatric Neurology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110 029 India. Email: [email protected]
Downloaded from jcn.sagepub.com at UNIV OF SOUTHERN CALIFORNIA on April 3, 2014
2
Journal of Child Neurology
epilepsy.19 The records of children with Lennox-Gastaut syndrome started on the modified Atkins diet at our institution from May 2009 to November 2012 were reviewed. The diagnosis of Lennox-Gastaut syndrome was based on presence of polymorphic seizures, including tonic, typical absence, atonic and myoclonic seizures, associated cognitive deterioration or stagnation, and generalized slow spike-wave discharges with paroxysmal fast activity on electroencephalogram.1,2 The diet was initiated in children aged 2 to 14 years who persisted to have daily seizures despite the use of at least 3 appropriate antiepileptic drugs. Children with known or suspected inborn errors of metabolism or systemic illnesses were excluded.
Modified Atkins Diet Administration The details of the modified Atkins diet administration at our center have been described earlier.19 The diet was started on an outpatient basis with carbohydrate intake restriction to 10 g/d. The carbohydrate content of various food items was explained to the parents, and exchange lists were provided. The intake of fat (eg, cream, butter, oils, ghee) was actively encouraged. Protein intake was not restricted. There was no calorie restriction. A list of recipes based on common locally available foods with prespecified carbohydrate contents (2.5 g, 5 g, etc) was provided. The antiepileptic drugs were continued unchanged for the first 3 months, and then reduced as per seizure control. The baseline seizure frequency was recorded during a 4-week observation period, during which parents were asked to maintain a daily seizure log, recording seizure type, duration, and frequency. Seizure frequency was assessed by the parent-maintained seizure records on the basis of a chart with various categories of seizure (infantile spasms, absence, myoclonic, atonic, tonic, tonic-clonic, and focal). Patients were reviewed as outpatients monthly for the initial 3 months followed by 3-monthly intervals. They underwent detailed evaluation including history pertaining to seizures, and the adverse effects. Urinary ketones were checked using urine dipstick at each hospital visit. Parents were asked to check urine ketones by reagent sticks daily for the first week on the diet and twice weekly thereafter. Renal and hepatic function tests with fasting lipid profile were performed at baseline and 6-monthly. The data was extracted per a predesigned proforma. The characteristics recorded included age at initiation of diet and onset of epilepsy, sex, dietary habits (vegetarian/nonvegetarian, intake of eggs), seizure frequency and semiology, duration of epilepsy, etiology, number of antiepileptic drugs used before and at diet initiation, presence of developmental delay, autistic features and hyperactivity, and adverse effects of the diet (vomiting, lethargy, poor appetite, refusal to feed, and constipation).
Outcomes The seizure frequency was assessed in accordance with the parental seizure records. At the end of 3, 6, and 12 months, the average seizures per week in the preceding 28 days was compared with the average weekly seizure frequency at the time of initiation of the diet. This was expressed as a percentage change in the seizure frequency as compared to the baseline. The seizure outcome was classified as follows: 50% seizure reduction as compared to baseline, with 2 children (8%) becoming seizure free (Table 2). At 6 months, more than half of the children discontinued diet. More than 50% seizure reduction was seen in all the remaining children (11) at 6 months, with 3 children becoming seizure free. One year after diet initiation, 2 more children discontinued the diet. Eight of the remaining 9 had >90% seizure reduction at 6 months. The reasons for discontinuation included unsatisfactory seizure control (13) and feeling that the diet was too restrictive (3). The urine ketones measurements at a 3-month follow-up after initiation of diet were as follows: trace (5 mg/dL), 2/25 (8%); small (15 mg/dL), 4/25 (16%); moderate (40 mg/dL), 13/25 (52%); and large (80-160 mg/dL), 6/25 (24%). The adequate ketosis (urine ketones 40 mg/dL) was not significantly different in children with 50% seizure reduction at 3 months (69.2% vs 83.3%, p ¼ .65). The diet was well tolerated in the study population. The adverse effects experienced were mild and did not warrant discontinuation of diet in any child. The adverse effects reported included constipation (44%), vomiting (16%), and anorexia (16%). A subjective improvement in alertness and interaction was reported by the parents in 12 (48%) children. None of the children had deranged renal or hepatic functions and lipid profile on the diet.
Discussion The realistic management goals in children with LennoxGastaut syndrome include lowering the frequency of disabling seizures like drop attacks, minimizing daytime seizures, and minimizing the adverse effects of antiepileptic drugs. Despite many suggested treatment protocols,1-5 these goals are difficult to achieve in most children. The pharmaco-resistance of the seizures in Lennox-Gastaut syndrome makes dietary therapy an attractive alternative. The classic ketogenic diet has been shown to be beneficial in the management of these children. A recent review explored the efficacy of a ketogenic diet in Lennox-Gastaut syndrome and found that 47% to 51% children had >50% reduction in seizure frequency at 6 months after initiation of ketogenic diet.6 In a small group of children, we found that modified Atkins diet was also effective in reducing the seizure frequency. Fortyeight percent children at 3 months and 44% children at 6
months had >50% seizure reduction as compared to the baseline. The response rates achieved with the ketogenic diet or the modified Atkins diet appear better than those achieved by lamotrigine or topiramate as add-on therapies.21 The newer antiepileptic drug rufinamide has been shown to be effective in children with Lennox-Gastaut syndrome. With rufinamide as an adjunctive therapy in children with Lennox-Gastaut syndrome, Lee et al22 reported that 34.8% children had >50% seizure reduction at 6 months. In another study, by Kim et al,23 35.9% achieved a >50% reduction in seizure frequency at 3 months. These response rates were inferior to those achieved in this study with the modified Atkins diet.21 Although initiating and monitoring drug therapy has obvious advantage of convenience, the option of diet should be considered in all individuals with drug-refractory, nonsurgically amenable epilepsies, including those with Lennox-Gastaut syndrome. The modified Atkins diet has been reported to be better tolerated than a ketogenic diet.19,24 In this study population also, modified Atkins diet was well tolerated. None of the children had disabling adverse effects. We found several advantages with the use of the modified Atkins diet. Apart from the outpatient initiation and ease of administration, the counseling time was reduced to 30–45 minutes. This is an ideal treatment option for resource-constrained settings with a paucity of trained dieticians. The drawbacks of our study include the small number of children studied and the potential inaccuracy of parental reporting of seizure frequency. The second factor is especially important in Lennox-Gastaut syndrome, which is characterized by frequent and multiple types (including nonconvulsive seizures) of seizures. Despite these, it would be prudent to conclude that the modified Atkins diet appears to be a feasible, effective, and welltolerated alternative in children with Lennox-Gastaut syndrome. Future research could include a randomized controlled trial to assess the effectiveness of early administration of the diet in children with Lennox-Gastaut syndrome, effect of the diet on specific seizure types, study of the interaction of coadministered antiepileptic drugs, and the effect of the diet on cognition and behavior. These could require multicentric studies. Author Contributions SS, NS, and PJ provided clinical care to the patients under the supervision of SG. The diet administration was assisted by AA. PJ and SS drafted the manuscript, which was read and approved by all the authors. The authors are also grateful to the EEG technicians, Mrs Sushila and Mr Suresh.
Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Suvasini Sharma was financially supported as a Senior Research Associate in
Downloaded from jcn.sagepub.com at UNIV OF SOUTHERN CALIFORNIA on April 3, 2014
4
Journal of Child Neurology
the ‘‘Scientists pool scheme’’ of the Council for Scientific and Industrial Research (CSIR), Govt. of India, for this study. There was no other funding source for the study.
Ethical Approval The study was part of a randomized controlled trial of the use of the modified Atkins diet in refractory childhood epilepsy (Reference 19; ethical approval Ref. No. P-07/2.02.2009).
References 1. Arzimanoglou A, French J, Blume WT, et al. Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. Lancet Neurol. 2009;8:82-93. 2. Panayiotopoulos C. A Clinical Guide to Epileptic Syndromes and Their Treatment. 2nd ed. London: Springer; 2011. 3. Arzimanoglou A, Guerrini R, Aicardi J. Aicardi’s Epilepsy in Children. 4th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2012. 4. Montouris GD. Rational approach to treatment options for Lennox-Gastaut syndrome. Epilepsia. 2011;52(suppl 5):10-20. 5. Ferrie CD, Patel A. Treatment of Lennox-Gastaut syndrome (LGS). Eur J Paediatr Neurol. 2009;13:493-504. 6. Lemmon ME, Terao NN, Ng Y-T, et al. Efficacy of the ketogenic diet in Lennox-Gastaut syndrome: a retrospective review of one institution’s experience and summary of the literature. Dev Med Child Neurol. 2012;54:464-468. 7. Kossoff EH, Krauss GL, McGrogan JR, Freeman JM. Efficacy of the Atkins diet as therapy for intractable epilepsy. Neurology. 2003;61:1789-1791. 8. Kossoff EH, McGrogan JR, Bluml RM, et al. A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy. Epilepsia. 2006;47:421-424. 9. Kossoff EH, Turner Z, Bluml RM, et al. A randomized, crossover comparison of daily carbohydrate limits using the modified Atkins diet. Epilepsy Behav. 2007;10:432-436. 10. Kang H-C, Lee HS, You SJ, et al. Use of a modified Atkins diet in intractable childhood epilepsy. Epilepsia. 2007;48:182-186. 11. Porta N, Valle´e L, Boutry E, et al. Comparison of seizure reduction and serum fatty acid levels after receiving the ketogenic and modified Atkins diet. Seizure. 2009;18:359-364.
12. Weber S, Mølgaard C, Karentaudorf, Uldall P. Modified Atkins diet to children and adolescents with medical intractable epilepsy. Seizure. 2009;18:237-240. 13. Kossoff EH, Borsage JL, Comi AM. A pilot study of the modified Atkins diet for Sturge-Weber syndrome. Epilepsy Res. 2010;92: 240-243. 14. Tonekaboni SH, Mostaghimi P, Mirmiran P, et al. Efficacy of the Atkins diet as therapy for intractable epilepsy in children. Arch Iran Med. 2010;13:492-497. 15. Miranda MJ, Mortensen M, Povlsen JH, et al. Danish study of a modified Atkins diet for medically intractable epilepsy in children: can we achieve the same results as with the classical ketogenic diet? Seizure. 2011;20:151-155. 16. Kossoff EH, Dorward JL, Turner Z, Pyzik PL. Prospective study of the modified Atkins diet in combination with a ketogenic liquid supplement during the initial month. J Child Neurol. 2011;26: 147-151. 17. Ito Y, Oguni H, Ito S, et al. A modified Atkins diet is promising as a treatment for glucose transporter type 1 deficiency syndrome. Dev Med Child Neurol. 2011;53:658-663. 18. Kumada T, Miyajima T, Oda N, et al. Efficacy and tolerability of modified Atkins diet in Japanese children with medicationresistant epilepsy. Brain Dev. 2012;34:32-38. 19. Sharma S, Sankhyan N, Gulati S, Agarwala A. Use of the modified Atkins diet for treatment of refractory childhood epilepsy: a randomized controlled trial. Epilepsia. 2013;54:481-486. 20. Sharma S, Sankhyan N, Gulati S, Agarwala A. Use of the modified Atkins diet in infantile spasms refractory to first-line treatment. Seizure. 2012;21:45-48. 21. Hancock EC, Cross JH. Treatment of Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2013;2:CD003277. 22. Lee EH, Yum MS, Ko TS. Effectiveness and tolerability of rufinamide in children and young adults with Lennox-Gastaut syndrome: a single center study in Korea. Clin Neurol Neurosurg. 2013;115:926-929. 23. Kim SH, Eun SH, Kang HC, et al. Rufinamide as an adjuvant treatment in children with Lennox-Gastaut syndrome. Seizure. 2012;21:288-291. 24. Kossoff EH, Dorward JL. The modified Atkins diet. Epilepsia. 2008;49(suppl 8):37-41.
Downloaded from jcn.sagepub.com at UNIV OF SOUTHERN CALIFORNIA on April 3, 2014
