Skip to main content
Book cover

Epilepsy and the Ketogenic Diet pp 111–121Cite as

Indications and Contraindications of the Ketogenic Diet

  • Chapter

Part of the Nutrition and Health book series (NH)

Abstract

The ketogenic diet (KD) has historically been used in the treatment of medically refractory epilepsy. It is currently not recommended for new-onset seizures because antiepileptic drugs (AEDs) are easier to use and are effective in approx 70–80% of patients. The KD requires a significant commitment of time and effort by the patient, his or her family, the KD health-care team, and the institution that supports the KD program. Determining precisely when intractability occurs in a child with epilepsy continues to be a subject of discussion among epidemiologists (1–5). Generally, epilepsy centers will not offer the KD treatment until a patient has failed two or three standard AEDs. Most patients who start the KD have failed at least three times as many AEDs. The KD is not recommended to some patients until all other options have failed (6). Current treatments available to patients with intractable epilepsies include a plethora of conventional AEDs, the vagus nerve stimulator, epilepsy surgery, and the KD. The optimal hierarchy of these treatments in the course of intractable epilepsy should be continually reevaluated based on efficacy, side effects, and safety. For example, epilepsy surgery (the “gold standard” for lesional temporal lobe epilepsy) is often ineffective in nonlesional, nontemporal causes of epilepsy and may result in significant morbidity. The use of the KD prior to epilepsy surgery treatment in these patients has been suggested (7,8).

Keywords

  • Ketone Body
  • Inborn Error
  • Ketogenic Diet
  • Seizure Type
  • Refractory Epilepsy

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

This is a preview of subscription content, access via your institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-1-59259-808-3_8
  • Chapter length: 11 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   189.00
Price excludes VAT (USA)
  • ISBN: 978-1-59259-808-3
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   249.99
Price excludes VAT (USA)
Hardcover Book
USD   249.99
Price excludes VAT (USA)
Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Engel J Jr. Intractable epilepsy: definition and neurobiology. Epilepsia, 2001;42(Suppl 6):3.

    CrossRef  PubMed  Google Scholar 

  2. Dlugos DJ, et al. Response to first drug trial predicts outcome in childhood temporal lobe epilepsy. Neurology, 2001;57:2259–2264.

    CrossRef  PubMed  CAS  Google Scholar 

  3. Keranen T, Riekkinen P. Severe epilepsy: diagnostic and epidemiological aspects. Acta Neurol Scand Suppl 1988;117:7–14.

    CrossRef  PubMed  CAS  Google Scholar 

  4. Berg AT, et al. Predictors of intractable epilepsy in childhood: a case-control study. Epilepsia 1996;37:24–30.

    CrossRef  PubMed  CAS  Google Scholar 

  5. Camfield PR, Camfield CS. Antiepileptic drug therapy: when is epilepsy truly intractable? Epilepsia 1996;37(Suppl 1):S60–S65.

    CrossRef  Google Scholar 

  6. Lefevre F, Aronson N. Ketogenic diet for the treatment of refractory epilepsy in children: a systematic review of efficacy. Pediatrics 2000;105:E46.

    CrossRef  Google Scholar 

  7. Benbadis SR, Tatum WO. Advances in the treatment of epilepsy. Am Fam Phys 2001;64:91–98.

    CAS  Google Scholar 

  8. Wheless JW, Baumgartner J, Ghanbari C. Vagus nerve stimulation and the ketogenic diet. Neurol Clin 2001;19:371–407.

    CrossRef  PubMed  CAS  Google Scholar 

  9. Livingston S. The Diagnosis and Treatment of Convulsive Disorders in Children. Charles C. Thomas, Springfield, IL, 1954.

    Google Scholar 

  10. Keith HM. Convulsive Disorders in Children with Reference to Treatment with the Ketogenic Diet. Little, Brown, Boston, 1963.

    Google Scholar 

  11. Vining EPG, et al. A multicenter study of the efficacy of the ketogenic diet. Arch Neurol 1998;55:1433–1437.

    CrossRef  PubMed  CAS  Google Scholar 

  12. Kinsman SL, et al. Efficacy of the ketogenic diet for intractable seizure disorders: review of 58 cases. Epilepsia 1992;33:1132–1136.

    CrossRef  PubMed  CAS  Google Scholar 

  13. Freeman JM, et al. The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children. Pediatrics 1998;102:1358–1363.

    CrossRef  PubMed  CAS  Google Scholar 

  14. Maydell BV, et al. Efficacy of the ketogenic diet in focal versus generalized seizures. Pediatr Neurol 2001;25:208–212.

    CrossRef  PubMed  CAS  Google Scholar 

  15. Hemingway C, et al. The ketogenic diet: a 3- to 6-year follow-up of 150 children enrolled prospectively. Pediatrics 2001;108:898–905.

    CrossRef  PubMed  CAS  Google Scholar 

  16. Coppola G, et al. The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience. Epilepsy Res 2002;48:221–227.

    CrossRef  PubMed  Google Scholar 

  17. DiMario FJ Jr, Holland J. The ketogenic diet: a review of the experience at Connecticut Children’s Medical Center. Pediatr Neurol 2002;26:288–292.

    CrossRef  PubMed  Google Scholar 

  18. Hassan AM, et al. Ketogenic diet in the treatment of refractory epilepsy in childhood. Pediatr Neurol 1999;21:548–552.

    CrossRef  PubMed  CAS  Google Scholar 

  19. Katyal NG, et al. The ketogenic diet in refractory epilepsy: the experience of Children’s Hospital of Pittsburgh. Clin Pediatr 2000;39:153–159.

    CrossRef  CAS  Google Scholar 

  20. Nordli DR, Jr, et al. Experience with the ketogenic diet in infants. Pediatrics 2001;108:129–133.

    CrossRef  PubMed  Google Scholar 

  21. Persson B, Settergren G, Dahlquist G. Cerebral arterio-venous differences of acetoacetate and Dbetahydroxybutyrate in children. Acta Paediatr Scand 1972;61:273–278.

    CrossRef  PubMed  CAS  Google Scholar 

  22. Barborka CJ. Epilepsy in adults: results of treatment by ketogenic diet in one hundred cases. Arch Neurol Psychiatr 1930;23:904.

    CrossRef  Google Scholar 

  23. Sirven J, et al. The ketogenic diet for intractable epilepsy in adults: preliminary results. Epilepsia 1999;40:1721–1726.

    CrossRef  PubMed  CAS  Google Scholar 

  24. Gordon N. Medium-chain triglycerides in a ketogenic diet. Dev Med Child Neurol 1977;19:535–538.

    CrossRef  PubMed  CAS  Google Scholar 

  25. Huttenlocher PR. Ketonemia and seizures: metabolic and anticonvulsant effects of two ketogenic diets in childhood epilepsy. Pediatr Res 1976;10:536–540.

    CrossRef  PubMed  CAS  Google Scholar 

  26. Livingston S, Pauli LL. Ketogenic diet and epilepsy. Dev Med Child Neurol 1975;17:818–819.

    CrossRef  PubMed  CAS  Google Scholar 

  27. Berman W. The ketogenic diet, West and Lennox syndromes. Dev Med Child Neurol 1975;17:255.

    CrossRef  PubMed  CAS  Google Scholar 

  28. Freeman JM, Vining EPG. Seizures decrease rapidly after fasting: preliminary studies of the ketogenic diet. Arch Pediatr Adolesc Med 1999;153:946–949.

    PubMed  CAS  Google Scholar 

  29. Kossoff EH, et al. Efficacy of the ketogenic diet for infantile spasms. Pediatrics 2002;109:780–783.

    CrossRef  PubMed  Google Scholar 

  30. Bergqvist AG, et al. Treatment of acquired epileptic aphasia with the ketogenic diet. J Child Neurol 1999;14:696–701.

    CrossRef  PubMed  CAS  Google Scholar 

  31. Shafrir Y, Prensky AL. Acquired epileptiform opercular syndrome: a second case report, review of the literature, and comparison to the Landau-Kleffner syndrome. Epilepsia 1995;36:1050–1057.

    CrossRef  PubMed  CAS  Google Scholar 

  32. Haas RH, et al. Therapeutic effects of a ketogenic diet in Rett syndrome. Am J Med Genet 1986;24(Suppl 1):225–246.

    CrossRef  Google Scholar 

  33. Pulsifer MB, et al. Effects of ketogenic diet on development and behavior: preliminary report of a prospective study. Dev Med Child Neurol 2001;43:301–306.

    CrossRef  PubMed  CAS  Google Scholar 

  34. Freeman JM, Vining EPG. Ketogenic diet: a time-tested, effective, and safe method for treatment of intractable childhood enilepsv. Epilensia 1998:39:450–451.

    CrossRef  CAS  Google Scholar 

  35. Nordli DR Jr, DeVivo DC. The ketogenic diet revisited: back to the future. Epilepsia 1997;38:743–749.

    CrossRef  PubMed  Google Scholar 

  36. Kayano T, et al. Evidence for a family of human glucose transporter-like proteins. Sequence and gene localization of a protein expressed in fetal skeletal muscle and other tissues. J Biol Chem 1988:263:15245–1524g.

    PubMed  CAS  Google Scholar 

  37. Maher F, Vannucci SJ, Simpson IA. Glucose transporter proteins in brain. FASEB J 1994;8:1003–1011.

    PubMed  CAS  Google Scholar 

  38. DeVivo DC, et al. Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. N Engl J Med 1991;325:703–709.

    CrossRef  CAS  Google Scholar 

  39. Klepper J, Voit T. Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain-a review. Eur J Pediatr 2002;161:295–304.

    CrossRef  PubMed  CAS  Google Scholar 

  40. Clark DD, Sokoloff L. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. Raven, New York, 1994.

    Google Scholar 

  41. Vannucci RC, Vannucci SJ. Glucose metabolism in the developing brain. Semin Perinatol 2000;24:107–115.

    CrossRef  PubMed  CAS  Google Scholar 

  42. Cremer JE. Substrate utilization and brain development. J Cereb Blood Flow Metab 1982;2:394–407.

    CrossRef  PubMed  CAS  Google Scholar 

  43. Klepper J, et al. Glucose transporter protein syndrome. Neuropediatrics 1998;29:A9.

    Google Scholar 

  44. Klepper J, et al. GTPS: Defining a new syndrome. Neurology 1998;50:A6.

    Google Scholar 

  45. Brockmann K, et al. Autosomal dominant glut-1 deficiency syndrome and familial epilepsy. Ann Neurol 2001;50:476–485.

    CrossRef  PubMed  CAS  Google Scholar 

  46. Klepper J, et al. Defective glucose transport across brain tissue barriers:a newly recognized neurological syndrome. Neurochem Res 1999;24:587–594.

    CrossRef  PubMed  CAS  Google Scholar 

  47. Brockmann K, Korenke CG, von Moers A. Epilepsy with seizures after fasting and retardation:the first familial cases of glucose transporter protein (GLUT 1) deficiency. Eur J Paediatr Neurol 1999;3:A90–A91.

    CrossRef  Google Scholar 

  48. Klepper J, et al. Erythocyte 3-O-methyl-D glucose uptake assay for diagnosis of glucose transporter protein syndrome. J Clin Lab Anal 1999;13:116–121.

    CrossRef  PubMed  CAS  Google Scholar 

  49. Stewart WA, Gordon K, Camfield P. Acute pancreatitis causing death in a child on the ketogenic diet. J Child Neurol 2001;16:682.

    CrossRef  PubMed  CAS  Google Scholar 

  50. Chugani HT. Development of regional brain glucose metabolism in relation to behavior and plasticity. In: Dawson G, Fisher KW (eds.). Human Behavior and the Developing Brain. Guilford, New York 1994, pp. 153–175.

    Google Scholar 

  51. Robinson B. Lactic acidemia. Biochim Biophys Acta 1993;1182:231–244.

    CrossRef  PubMed  CAS  Google Scholar 

  52. Brown GK, et al. Pyruvate dehydrogenase deficiency. J Med Genet 1994;31:875–879.

    CrossRef  PubMed  CAS  Google Scholar 

  53. Robinson B, MacKay N, Petrova-Benedict R. Defects in the E2 lipoyltransacetylase and the X-lipoylcontaining components of the pyruvate dehydrogenase complex in patients with lactic acidemia. J Clin Invest 1990;85:1821–1824.

    CrossRef  PubMed  CAS  Google Scholar 

  54. Brown RM, Head RA, Brown GK. Pyruvate dehydrogenase E3 binding protein deficiency. Hum Genet 2002;110:187–191.

    CrossRef  PubMed  CAS  Google Scholar 

  55. Brown RM, Dahl HH, Brown GK. X-chromosome localization of the functional gene for the El alpha subunit of the human pyruvate dehydrogenase complex. Genomics 1989;4:174–181.

    CrossRef  PubMed  CAS  Google Scholar 

  56. Dahl HH. Pyruvate dehydrogenase El alpha deficiency: males and females differ yet again. Am J Hum Genet 1995;56:553–557.

    PubMed  CAS  Google Scholar 

  57. Stansbie D, Wallace SJ, Marsac C. Disorders of the pyruvate dehydrogenase complex. J Inher Metab Dis 1986;9:105–119.

    CrossRef  PubMed  CAS  Google Scholar 

  58. DeVivo DC. The expanding clinical spectrum of mitochondrial diseases. Brain Dev 1993;15:1–22.

    CrossRef  CAS  Google Scholar 

  59. DeVivo DC. Leigh syndrome:historical perspective and clinical variations. Biofactors 1998;7:269–271.

    CrossRef  CAS  Google Scholar 

  60. Canafoglia L. et al. Epileptic phenotypes associated with mitochondrial disorders. Neurology 2001:56:1340–1346.

    CrossRef  PubMed  CAS  Google Scholar 

  61. Chow CW, Thorburn DR. Morphological correlates of mitochondrial dysfunction in children. Hum Reprod 2000;15(Suppl 2):68–78.

    CrossRef  PubMed  Google Scholar 

  62. Di Rocco M, et al. Outcome of thiamine treatment in a child with Leigh disease due to thiamineresponsive pyruvate dehydrogenase deficiency. Eur J Paediatr Neurol 2000;4:115–117.

    CrossRef  PubMed  Google Scholar 

  63. Morten KJ, et al. Dichloroacetate stabilizes the mutant El alpha subunit in pyruvate dehydrogenase deficiency. Neurology 1999;53:612–616.

    CrossRef  PubMed  CAS  Google Scholar 

  64. Naito E, et al. Thiamine-responsive pyruvate dehydrogenase deficiency in two patients caused by a point mutation (F205L and L216F) within the thiamine pyrophosphate binding region. Biochim Biophys Acta 2002;1588:79–84.

    CrossRef  PubMed  CAS  Google Scholar 

  65. Falk RE, et al. Ketonic diet in the management of pyruvate dehydrogenase deficiency. Pediatrics 1976;58:713–721.

    PubMed  CAS  Google Scholar 

  66. Wexler ID, et al. Outcome of pyruvate dehydrogenase deficiency treated with ketogenic diets. Studies in patients with identical mutations. Neurology 1997;49:1655–1661.

    CrossRef  PubMed  CAS  Google Scholar 

  67. Du Bois EF. The control of protein in the diet. J Am Diet Assoc 1928;4:53–76.

    Google Scholar 

  68. Heinbecker P. Studies on the metabolism of Eskimos. J Biol Chem 1928;80:461–475.

    CAS  Google Scholar 

  69. Trumbo P, et al. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. J Am Diet Assoc 2002;102:1621–1630.

    CrossRef  PubMed  Google Scholar 

  70. Atkins RC. Dr Atkins’ New Diet Revolution, rev. ed. Avon, New York, 1998.

    Google Scholar 

  71. Vockley J, Singh RH, Whiteman DA. Diagnosis and management of defects of mitochondrial beta-oxidation. Curr Opin Clin Nutr Metab Care 2002;5:601–609.

    CrossRef  PubMed  CAS  Google Scholar 

  72. Vockley J, Whiteman DA. Defects of mitochondrial beta-oxidation: a growing group of disorders. Neuromuscular Dis 2002;12:235–246.

    CrossRef  Google Scholar 

  73. Vianey-Liaud C, et al. The inborn errors of mitochondrial fatty acid oxidation. J Inher Metab Dis 1987;10 (Suppl 1):159–200.

    CrossRef  PubMed  Google Scholar 

  74. Rinaldo P, Matern D, Bennett MJ. Fatty acid oxidation disorders. Annu Rev Physiol 2002;64:477–502.

    CrossRef  PubMed  CAS  Google Scholar 

  75. Rabier D, et al. Do criteria exist from urinary organic acids to distinguish beta-oxidation defects? J Inher Metab Dis 1995;18:257–260.

    CrossRef  PubMed  CAS  Google Scholar 

  76. Coates PM. New developments in the diagnosis and investigation of mitochondrial fatty acid oxidation disorders. Eur J Pediatr 1994;153 (7 Suppl 1):S49–S56.

    CrossRef  Google Scholar 

  77. Bennett MJ, Rinaldo P, Strauss AW. Inborn errors of mitochondrial fatty acid oxidation. Crit Rev Clin Lab Sci 2000;37:1–44.

    CrossRef  PubMed  CAS  Google Scholar 

  78. Schuurmans MM, et al. Influence of age and gender on the clinical expression of acute intermittent porphyria based on molecular study of porphobilinogen deaminase gene among Swiss patients. Mol Med 2001;7:535–542.

    PubMed  CAS  Google Scholar 

  79. Andersson C, Innala E, Backstrom T. Acute intermittent porphyria in women: clinical expression, use and experience of exogenous sex hormones. A population-based study in northern Sweden. J Intern Med 2003;254:176–183.

    CrossRef  PubMed  CAS  Google Scholar 

  80. Wikberg A, Andersson C, Lithner F. Signs of neuropathy in the lower legs and feet of patients with acute intermittent porphyria. J Intern Med 2000;248:27–32.

    CrossRef  PubMed  CAS  Google Scholar 

  81. Sykes RM. Acute intermittent porphyria, seizures, and antiepileptic drugs: a report on a 3-year-old Nigerian boy. Seizure 2001;10:64–66.

    CrossRef  PubMed  CAS  Google Scholar 

  82. Regan L, Gonsalves L, Tesar G. Acute intermittent porphyria. Psychosomatics 1999;40:521–523.

    CrossRef  PubMed  CAS  Google Scholar 

  83. Yano Y, Kondo M. Acute intermittent porphyria (AIP). Ryoikibetsu Shokogun Shirizu 1998;19(Pt 2):136–138.

    PubMed  Google Scholar 

  84. Zadra M, et al. Treatment of seizures in acute intermittent porphyria: safety and efficacy of gabapentin. Seizure 1998;7:415–416.

    CrossRef  PubMed  CAS  Google Scholar 

  85. Takeoka M, et al. Concomitant treatment with topiramate and ketogenic diet in pediatric epilepsy. Epilepsia 2002;43:1072–1075.

    CrossRef  PubMed  CAS  Google Scholar 

  86. Kossoff EH, et al. Kidney stones, carbonic anhydrase inhibitors, and the ketogenic diet. Epilepsia 2002;43:1168–1171.

    CrossRef  PubMed  Google Scholar 

Download references

Authors
  1. Anna Gunhild Christina Bergqvist
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Neurology, University of Wisconsin, Madison, WI, USA

    Carl E. Stafstrom MD, PhD

  2. The Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA

    Jong M. Rho MD

Rights and permissions

Reprints and Permissions

Copyright information

© 2004 Springer Science+Business Media New York

About this chapter

Cite this chapter

Bergqvist, A.G.C. (2004). Indications and Contraindications of the Ketogenic Diet. In: Stafstrom, C.E., Rho, J.M. (eds) Epilepsy and the Ketogenic Diet. Nutrition and Health. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-808-3_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-808-3_8

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-477-7

  • Online ISBN: 978-1-59259-808-3

  • eBook Packages: Springer Book Archive