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Why consider the Modified Atkins Diet for the treatment of refractory epilepsy Yvette McMurtrie Client Services Coordinator Epilepsy Queensland, Brisbane, Australia T he majority of people with epilepsy become seizure free with antiepileptic medications, but approximately 20-30% will have refractory epilepsy, for which seizures persist despite accurate diagnosis and carefully monitored treatment (Berg et al., 2001). The Ketogenic Diet (KD) was originally developed in the USA in the early 1920s and has recently become increasingly accepted internationally. It is considered an important alternative to drug therapy for children with medically intractable seizures (Freeman et al., 2007). The KD, however, remains restrictive and prescriptive, requiring careful monitoring by a dietician. Use in adults has been attempted but in view of its restrictions has been extremely difficult and has been noted that even when a benefit is seen, adults are not able to continue with the KD in the immediate term (Cross, 2010). The Modified Atkins Diet (MAD) has been used to treat intractable or refractory epilepsy since 2003 (Kossoff et al., 2008) and the results are promising. An average of 56% of patients experienced greater than 50% seizure reduction and an average of 16% of patients experienced greater than 90% seizure reduction. This demonstrates that the MAD is remarkably similar to the KD in effectiveness. The MAD is also generally thought to be easier to stick to and have fewer side effects than the KD (Cervenka et al., 2012). The MAD was created at the John Hopkins hospital in an attempt to create a more palatable and less restrictive dietary treatment. The MAD induces ketosis without fluid, energy or protein restriction (Kossoff et al., 2010). The MAD can be initiated in an out-patient setting and is possibly suitable for both children and adults. So how do the diets differ? Essentially both the KD and MAD are high fat diets with very little energy coming from carbohydrate. On the MAD, daily carbohydrates are limited initially to 10g/ day in children with planned increase after one month to 15g, then 20-30 g as tolerated based on seizure control. Adults are started on 15 g/day and can be increased to 20-30g/day after one month. A high fat intake is encouraged. Unlike the KD, however, fasting or food weighing is not required. Calories and fluids are also not restricted on MAD the way they are on KD. The ratios of energy coming from different nutrients in the Ketogenic and Modified Atkins Diets are outlined in figure 1. Research does indicate that the diet is most effective in Doose, Dravet and West syndrome (Oguni et al., 2002; Caraballo et al.,2005; Kossoff et al., 2008). In these syndromes diet therapy could possibly be considered earlier in the management rather than later. Kossoff et al., (2010) found that children with Doose (Myoclonic Astatic Epilepsy) had an almost 100% responder rate with more that 90% reduction in seizures. There have not, however, been many studies in adults with other syndromes and thus the diet may be just as effective in these. Patients on the MAD experience fewer serious side effects than on the KD. Most of the side effects were manageable and patients were more likely to be able to tolerate being on the diet for a longer period. The MAD is generally considered less restrictive on lifestyle (Kossoff et al, 2010). There are no studies to date, however, that examine the long term side effects of the MAD. Similar to the KD, families and adults alike on MAD report not only seizure reduction as a beneficial side effect of the diet but also improved concentration, Figure 1. Diet compositions: ratio, grams of fat, protein and carbohydrate. (Epilepsia © ILAE) Typical Western Diet 18 Traditional Ketogenic Diet Modified Atkins Diet Fat Fat Fat Protein Protein Protein Carbohydrate Carbohydrate Carbohydrate THE EPILEPSY REPORT JULY 2013 alertness and behaviour (Weber et al., 2009) and this is before medications were reduced. Weber also found that children were more awake during the day and slept better at night. Independent from its effect on seizure frequency and severity, MAD may also be beneficial in patients with clinical obesity or those desiring weight loss (Smith et al.,2011). Some adult patients on MAD experienced adverse side effects of elevated LDL cholesterol levels. However, Cervenka et al.(2012) found that on carnitine supplements, combined with dietary counselling to avoid saturated fat and increase consumption of unsaturated fat, the levels of LDL and total cholesterol returned to normal. It is essential to note though that References Barzegar M., Irandoust P., Ebrahimi Mameghani M. (2010) A Modified Atkins Diet for Intractable Childhood Epilepsy. Iran J Child Neurology. Vol 4 (3). pp. 15 – 20. Berg A., Shinnar S., Levy S., Testa F., Smith-Rapaport S., Beckerman B. (2001) Early development of intractable epilepsy in children: a prospective study. Neurology. Vol 56 pp1445-1452. Bergqvist AGC, Schall JI, Stallings VA, Zemel BS. (2008) Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet. American Journal of Clinical Nutrition Vol 88;1678-84. Bodenant M., Moreau C., Sejourne C., Auvin S., Delval A., Cuisset J. (2008) Interest of the ketogenic diet in refractory status epilepticus in adults Rev Neurol (Paris). Vol 164 (2) pp148-56. Carrette E., Vonck K., De Herdt V., Dewaele I., Raedt R., Goossens L., Van Zandijcke M., Wadman W., Thadani V., Boon P. (2008) A Pilot Trial with Modified Atkins’ Diet in Adult Patients with Refractory Epilepsy. Clinical Neurology and Neurosurgery. Vol 110. pp. 797 – 803. Cervenka M., Terao N., Bosarge J., Henry B., Klees A., Morrison P., Kossoff E. (2012) E-mail Management of the Modified Atkins Diet for Adults with Epilepsy is Feasible and Effective. Epilepsia. Vol 53(4) pp. 1 – 5. Cross J. H. (2010) Dietary Therapies – An Old Idea With a New Lease of Life. Seizure. Vol 19. pp. 671 – 674. Cross J. H., Neal E. G. (2010) Efficacy of Dietary Treatments for Epilepsy. Journal of Human Nutrition and Dietetics. Vol 23. pp. 113 – 119. Dutton S., Escayg A. (2008) Genetic Influences on Ketogenic Diet Efficacy. Epilepsia. Vol 49 (8). pp. 67 - 69. Hartman A., Vining E. (2007) Clinical Aspects of the Ketogenic Diet. Epilepsia. Vol 48 (1). pp. 31 – 42. Jung D, Kang H, Kim H. (2008) Long-term outcome of the ketogenic diet for childhood intractable epilepsy due to focal malformation of cortical development. Pediatrics, Vol 122:330-3. Kang H., Lee H., You S., Kang D., Ko T., Kim H. (2007) Use of a Modified Atkins Diet in Intractable Childhood Epilepsy. Epilepsia. Vol 48 (1). pp. 182 – 186. neither the MAD nor KD can be considered a ‘natural treatment’. They have side effects like any medication. Further, the KD requires a high level of dietary supervision, commitment and resources, the MAD less so, but still a challenge. Although a varied diet can be provided within the requirements, both are still very limiting on lifestyle. For this reason dietary therapy should only be considered for drug resistant epilepsy, that is, after two appropriate medications have failed and only undertaken with strict medical supervision (Cross, 2010). Response (or seizure reduction) to the diet at three months predicted the response to the diet at 12 months for most patients (Smith et al.,2011). Therefore a three month trial of MAD may be sufficient to determine whether or not it is an efficacious and sustainable therapy. Even though results for MAD and the KD are good, very few patients achieve complete long term seizure freedom. Treatment is also ongoing and requires a sustained commitment. An additional drawback of dietary therapy in both adults and children is the lack of dietician expertise and perceived complicated nature of using the diet by the average neurologist without KD and MAD experience (Kossoff & Doward, 2008). Despite increasing evidence of efficacy and an increasing awareness amongst families, there is still a lack of choice for either the family or the health professional owing to a lack of resources required. Waiting lists for MAD or KD services are long. Kessler S., Neal E., Camfield C., Kossoff E. (2011) Dietary Therapies for Epilepsy. Epilepsy & Behaviour. Vol 22. pp. 17–22. Kim Y., Vaidya V., Khusainov T., Kim H., Kim S., Lee E., Lee Y., Lee J., Kang H. (2011) Various Indications for a Modified Atkins Diet in Intractable Childhood Epilepsy. Brain & Development. Vol 10 pp 1-6 Kossoff E., Borsage J., Comi A. (2010) A Pilot Study of the Modified Atkins Diet for SturgeWeber Syndrome. Epilepsy Research. Vol 92. pp. 240 – 243. Kossoff E., Bosarge J., Miranda M., WiemerKruel A., Kang H., Kim H. (2010) Will Seizure Control Improve by Switching from the Modified Atkins Diet to the Traditional Ketogenic Diet? Epilepsia. Vol 51 (12). pp. 2496 – 2499. Kossoff E., Dorward J. (2008) The Modified Atkins Diet. Epilepsia. Vol 49 (8). pp. 37 – 41. Kossoff EK, Hedderick E, Turner Z, Freeman JM. (2008) A case-control evaluation of the ketogenic diet versus ACTH for new onset infantile spasms. Epilepsia. 49(9)1504-09. Kossoff E., Laux L., Blackford R., Morrison P., Pyzik P., Hamdy R., Turner Z., Nordli D. (2008) When Do Seizures Usually Improve with the Ketogenic Diet? Epilepsia. Vol 49 (2). pp. 329 – 333. Kossoff E., McGrogan J., Bluml R., Pillas D., Rubenstein J., Vining E. (2006) A Modified Atkins Diet is Effective for the Treatment of Intractable Pediatric Epilepsy. Epilepsia. Vol 47 (2). pp. 421 – 424. Kossoff E., Turner Z., Bluml R., Pyzik P., VIning E. (2007) A Randomized, Crossover Comparison of Daily Carbohydrate Limits Using the Modified Atkins Diet. Epilepsy & Behaviour. Vol 10. pp. 432 – 436. Miranda M., Mortensen M., Povlsen J., Nielsen H., Beniczky S. (2011) 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. Vol 20. pp. 151 – 155. Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, Whitney A, Cross JH.( 2008)The Ketogenic diet for the treatment of childhood epilepsy: a randomized controlled trial. Lancet Neurology. 7(6):500-6 Jun Neal EG, Chaffe H, Schwartz RHm Lawson MS, Edwards N, Fitzsimmons G, Whitney A, Cross JH. Growth of children in classical and medium-chain triglyceride ketogenic diet. Pediatrics, 2008, 122;e334-40 Payne N., Cross H., Sander J., Sisodiya S. (2011) The Ketogenic and Related Diets in Adolescents and Adults – A Review. Epilepsia. Vol 52 (11). pp. 1941 – 1948. Porta N., Vallee L., Boutry E., Fontaine M., Dessein A., Joriot S., Cuisset J., Cuvellier J., Auvin S. (2009) Comparison of Seizure Reduction and Serum Fatty Acid Levels After Receiving the Ketogenic and Modified Atkins Diet. Seizure. Vol 18. pp. 359 - 364. Sirven J., Whedon B., Caplan D., Liporace J., Glosser D., O’Dwyer J., Sperling M. (1999) The Ketogenic Diet for Intractable Epilepsy in Adults: Preliminary Results. Epilepsia. Vol 40 (12). pp. 1721 – 1726. Smith M., Politzer N., MacGarvie D., McAndrews M., Del Campo M. (2011) Efficacy and Tolerability of the Modified Atkins Diet in Adults with Pharmacoresistant Epilepsy: A Prospective Observational Study. Epilepsia. Vol 52 (4). pp. 775 – 780. Vining E. P. G. (2008) Long-term Health Consequences of Epilepsy Diet Treatments. Epilepsia. Vol 49 (8). pp. 27 – 29. Weber S., Molgaard C., Taudorf K., Uldall P. (2009) Modified Atkins Diet to Children and Adolescents with Medical Intractable Epilepsy. Seizure. Vol 18. pp. 237 – 240. Wheless J. (2004) Nonpharmacologic Treatment of the Catastrophic Epilepsies of Childhood. Epilepsia. Vol 45 (5). pp. 17 – 22. Wheless J. (2008) History of the Ketogenic Diet. Epilepsia. Vol 49 (8). pp. 3 – 5. THE EPILEPSY REPORT JULY 2013 19