Clinical UM Guideline


Subject:  Ketogenic Diet for Treatment of Intractable Seizures
Guideline #:  CG-MED-05Current Effective Date:  10/14/2014
Status:ReviewedLast Review Date:  08/14/2014

Description

This document addresses the use of a ketogenic diet to treat seizures. The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet which has been used for the treatment of uncontrolled seizures.

Clinical Indications

Medically Necessary:

The use of a ketogenic diet for children and teenagers with seizures refractory to antiepileptic drugs is considered medically necessary.

Not Medically Necessary:

The use of a ketogenic diet for all other indications is considered not medically necessary.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

CPT 
99499Unlisted evaluation and management service [when specified as services related to ketogenic diet]
  
ICD-9 Diagnosis[For dates of service prior to 10/01/2015]
345.00-345.91Epilepsy and recurrent seizures
  
ICD-10 Diagnosis[For dates of service on or after 10/01/2015]
G40.011-G40.019Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, intractable
G40.111-G40.119Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, intractable
G40.211-G40.219Localization-related (focal) (partial) symptomatic epilepsy and epileptics syndromes with complex partial seizures, intractable
G40.311-G40.319Generalized idiopathic epilepsy and epileptic syndromes, intractable
G40.A11-G40.A19Absence epileptic syndrome, intractable
G40.B11-G40.B19Juvenile myoclonic epilepsy, intractable
G40.411-G40.419Other generalized epilepsy and epileptic syndromes, intractable
G40.803-G40.804Other epilepsy, intractable
G40.813-G40.814Lennox-Gastaut syndrome, intractable
G40.823-G40.824Epileptic spasms, intractable
G40.89Other seizures
G40.911-G40.919Epilepsy, unspecified, intractable
  
Discussion/General Information

The ketogenic diet is a high-fat, low-carbohydrate, low-protein diet that has been used to treat seizures. The diet has a 4:1 ratio of fats to carbohydrates. The composition of the diet induces ketosis, a physiologic state in which circulating ketone bodies are used as the primary fuel source in the absence of simple sugars. Ketosis is thought to inhibit seizures, although the mechanism is unknown. The ketogenic diet is quite restrictive, requiring the cooperation of the individual, family and an appropriately trained dietician. The diet may be initiated in the inpatient or outpatient setting. In the inpatient setting, children are admitted to the hospital and fasted for one to two days. The diet is then instituted gradually over a number of days. The main reason for hospitalization is to monitor the period of initial fasting, which exposes children to metabolic derangements and dehydration. In a study by Kossoff (2008), it was reported that individuals who responded to the diet, did so quickly (often within one to two weeks), but universally within the first two months. In children in whom the seizures are not improved after two months, the study suggests a regular diet could be reintroduced and other treatment options considered.

Published data shows that some children benefit from the ketogenic diet, as demonstrated by a significant reduction in seizure frequency. A 1998 meta-analysis (Blue Cross Blue Shield Association Technology Evaluation Center) suggested the ketogenic diet yielded complete cessation of seizures in 16% of children, greater than 90% reduction in 32%, and a greater than 50% reduction in 56 % of children. These results exceed any expected placebo effect or spontaneous remission of seizures.

A meta-analysis by Henderson and colleagues (2006) supports the current uncontrolled case series reporting on the therapeutic effect of the ketogenic diet in the treatment of seizures in pediatric epileptic individuals. The analysis of 1,084 pooled individuals demonstrated a greater than 50% seizure reduction in individuals who stayed on the ketogenic diet versus those who discontinued the diet.

Neal (2008) studied the effectiveness of a ketogenic diet on intractable seizures in a randomized controlled trial. Of 145 children initially enrolled, 103 completed the study and were included in the final analysis. Dropout reasons varied from changing their mind to diet intolerance. After 3 months of ketogenic diet, the mean percentage of seizures in the 54 children on the diet fell to 62% of baseline. For the 49 children in the control group, seizures increased to 137% of baseline. The authors were surprised by the increase in seizures of the control group. Their most probable explanation is an unusual increase in seizure frequency of three of the children in the control group. When that data was excluded, the seizure frequency increase in the control group over 3 months was only 12%.

The National Institute for Health and Clinical Excellence (NICE) (2012) Clinical Guideline on the diagnosis and management of epilepsy concluded that children and young people who have had seizures not responsive to appropriate anti-epileptic drugs should be referred to an epilepsy specialist for consideration of the use of a ketogenic diet. The efficacy and safety of the ketogenic diet in adults has not been well studied or proven.

The ketogenic diet has been initiated in an inpatient setting, primarily to monitor the individual during the initial fasting period, but also to provide the intense education required to maintain a ketogenic diet once discharged. However, recent studies have suggested that the diet can be safely initiated in the outpatient setting. In 2004, Vaisleib and colleagues reported on a case series of 37 individuals who underwent outpatient induction of the ketogenic diet, whose outcomes were compared retrospectively to those who underwent inpatient dietary induction. The mean age of the individuals was 6.6 years, with a range of 1.8 to 14 years. The authors reported that there was no evidence that inpatient initiation of the ketogenic diet was superior to outpatient initiation. Additional studies identified in the literature search focused on the long-term effects of the ketogenic diet on the growth and development of children (Kwiterovich, 2003; Liu, 2003; Marsh, 2006; Vining, 2002), and whether or not the less restrictive Atkins diet, which also produces a mild ketosis, is an option to the ketogenic diet (Kossoff, 2003; Tonekaboni, 2010).

In 2014, Taub and colleagues looked at the records of 276 children who had been initiated on the ketogenic diet. A total of 65 children achieved freedom from seizures for a minimum of one month. The median time to seizure freedom after initiation of ketogenic diet was 1.5 months. Seizures recurred in 53 children with a median time to seizure recurrence of 3 months. The recurrence of seizures was reported as an occasional breakthrough and not a return to baseline seizure frequency.

Although the use of a ketogenic diet is being studied for population groups other than children and teenagers, there is a paucity of peer-reviewed published literature that shows effectiveness in other age groups. Klein (2010) reported on twelve adult participants who underwent initiation of a ketogenic diet. Baseline of the treatment was considered four months. Treatment ranged from 4 days to 26 months. Three participants stopped treatment during the first 4 months. Nine participants continued past the 4 month baseline. Four participants stopped treatment after 7, 8, 24 and 25 months. Of the 12 initial participants, 10 had improved seizures, 1 did not change and 1 worsened. Four out of 12 participants had a greater than 75% reduction in seizures. Five out of 12 participants had a greater than 50% reduction in seizures. Compliance has been an issue with adults using the ketogenic diet. Of those participants who followed the diet past the 4 month baseline, 7 out of 12 participants were fully compliant with the diet, 2 out of 12 participants were moderately and mildly compliant. This study is limited by its small sample size.

Thakur and colleagues (2014) reported a retrospective chart review in which ten adults were started on ketogenic diet for super-refractory status epilepticus. Ninety percent of participants achieved ketosis. For those participants who achieved ketosis, status epilepticus stopped in all of them in a median of three days. Prospective trials are warranted to examine the efficacy of the use of ketogenic diet in adults.

References

Peer Reviewed Publications:

  1. Henderson CB, Filloux FM, Alder SC, et al. Efficacy of the ketogenic diet as a treatment option for epilepsy: Meta-analysis. J Child Neurol. 2006; 21(3):193-198.
  2. Klein P, Janousek J, Barber A, Weissberger R. Ketogenic diet treatment in adults with refractory epilepsy. Epilepsy Behav. 2010; 19(4):575-579.
  3. Kossoff EH, Krauss GL, McGrogan JR, et al. Efficacy of the Atkins diet as therapy for intractable epilepsy. Neurology. 2003; 61:1789-1791.
  4. Kossoff EH, Laux LC, Blackford R, et al. When do seizures usually improve with the ketogenic diet? Epilepsia. 2008; 49(2):329-333.
  5. Kwiterovich PO, Vining EP, Pyzik P. Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins, and apolipoproteins in children. JAMA. 2003; 290(7):912-920.
  6. Liu YM, Williams S, Basualdo-Hammond C, et al. A prospective study; growth and nutritional status of children treated with the ketogenic diet. J Am Diet Assoc. 2003; 103(6):707-712.
  7. Marsh EB, Freeman JM, Kossoff EH, et al. The outcome of children with intractable seizures: a 3- to 6-year follow-up of 67 children who remained on the ketogenic diet less than one year. Epilepsia. 2006; 47(2):425-430.
  8. Neal EG, Chaffe H, Schwartz RH, et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 2008; 7(6):500-506.
  9. Taub KS, Kessler SK, Bergqvist AG. Risk of seizure recurrence after achieving initial seizure freedom on the ketogenic diet. Epilepsia. 2014; 55(4):579-583.
  10. Thakur KT, Probasco JC, Hocker SE, et al. Ketogenic diet for adults in super-refractory status epilepticus. Neurology. 2014; 82(8):665-670.
  11. 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(6):492-497.
  12. Vaisleib II, Buchhalter JR, Zupanc ML. Ketogenic diet: Outpatient initiation, without fluid, or caloric restrictions. Pediatr Neurol. 2004; 31(3):198-202.
  13. Vining EP, Pyzik P, McGrogan J, et al. Growth of children on the ketogenic diet. Dev Med Child Neurol. 2002; 44(12):796-802.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Blue Cross Blue Shield Association. Ketogenic diet for the treatment of children with refractory epilepsy. TEC Assessment, 1998; 13(20).
  2. Levy RG, Cooper PN, Giri P. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database Syst Rev. 2012, (3):CD001903.
  3. National Institute for Health and Clinical Excellence. Clinical guidelines CG137. The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care. January 2012. Available at: http://publications.nice.org.uk/the-epilepsies-the-diagnosis-and-management-of-the-epilepsies-in-adults-and-children-in-primary-and-cg137. Accessed on July 3, 2014.
Websites for Additional Information
  1. National Institute of Neurological Disorders and Stroke (NINDS). NINDS Epilepsy Information Page. Available at http://www.ninds.nih.gov/disorders/epilepsy/epilepsy.htm. Accessed on July 3, 2014.
Index

Epilepsy
Ketogenic Diet

History
StatusDateAction
Reviewed08/14/2014Medical Policy & Technology Assessment Committee (MPTAC) review. Updated Discussion/General Information and References.
Reviewed08/08/2013MPTAC review. Updated Discussion/General Information.
Reviewed08/09/2012MPTAC review. Updated Discussion/General Information and References.
Reviewed08/18/2011MPTAC review. Updated Discussion/General Information and References.
Reviewed08/19/2010MPTAC review. No change in Clinical Indications.
Reviewed08/27/2009MPTAC review. Removed "Place of Service" section. Updated Discussion and References.
Revised08/28/2008MPTAC review. References, Coding and Web Sites updated. Added "not medically necessary" statement.
Revised08/23/2007MPTAC review. Deleted "highly motivated" from Clinical Indication statement. Rationale and References updated.
Reviewed09/14/2006MPTAC review. No change in position; References updated.
Revised09/22/2005MPTAC Revision based on Pre-merger Anthem and Pre-merger WellPoint Harmonization.