Download PDF
Nervenheilkunde 2014; 33(05): 362-367
DOI: 10.1055/s-0038-1633407
Epilepsie
Schattauer GmbH

Ketogene Diät in der Therapie pharmakoresistenter Epilepsien

Indikationen und WirksamkeitKetogenic diet in the treatment of medically intractable epilepsiesIndications and efficacy
J. Kröll
1   Schweizerisches Epilepsie-Zentrum, Zürich
,
K. Otten
1   Schweizerisches Epilepsie-Zentrum, Zürich
,
M. Kurthen
1   Schweizerisches Epilepsie-Zentrum, Zürich
› Author Affiliations
Further Information

Publication History

eingegangen am: 15 January 2014

angenommen am: 29 January 2014

Publication Date:
02 February 2018 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die ketogene Diät (KD) ist eine seit mehr als hundert Jahren etablierte Therapie bei Kindern und Jugendlichen mit pharmakoresistenten Epilepsien. In den letzten Jahren hat das klinische Interesse an der KD durch Einführung weniger strenger und flexiblerer Therapieprotokolle wie der modifizierten Atkins-Diät (MAD) deutlich zugenommen. Aufgrund experimenteller Daten ergeben sich zunehmend Hinweise, dass die Wirksamkeit der Diät nicht auf eine antikonvulsive Wirkung beschränkt ist. Durch die Veränderung des zerebralen Energiestoffwechsels besitzt die KD auch ein mögliches neuroprotektives Potenzial, sodass im Rahmen wissenschaftlicher Studien zunehmend “neue” Indikationen der KD jenseits der Epilepsiebehandlung geprüft werden, z. B. der Einsatz bei neurodegenerativen Erkrankungen oder bei Hirntumoren.

Summary

For more than 100 years the ketogenic diet (KD) has been an established and well known treatment for children with pharmacoresistent epilepsies. During the last years the clinical interest in the ketogenic diet has significantly increased this due in part to the introduction of less strict and more flexible diet protocols like the modified Atkins diet (MAD). Experimental data also suggest that there is an additional potential impact beyond the diet’s anticonvulsive effect. Due to its influence on cerebral energy metabolism the KD probably possesses neuroprotective potential. This knowledge leading to an increasing number of clinical studies analyzing “new” indications, such as the treatment of neurodegenerative diseases or brain tumors.

Schlüsselwörter

Ketogene Diät - Indikationen - Effektivität - Nebenwirkungen - Wirkmechanismen

Keywords

Ketogenic diet - indications - efficacy - side-effects - modes of action
 

  • Literatur

  • 1 Wilder RM. The effects of ketonemia on the course of epilepsy. Mayo Clin Proc 1921; 02: 307-308.
    Search in Google Scholar
  • 2 Stafstrom CE, Rho JM. The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front Pharmacol 2012; 03: 59.
    Search in Google Scholar
  • 3 Seyfried BT, Kiebish M, Marsh J, Mukherjee P. Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet. J Cancer Res Ther 2009; 5 Suppl 1: S7-15.
    Search in Google Scholar
  • 4 Kossoff EH. et al. Optimal clinical management of children receiving the ketogenic diet: recommendations of the International Ketogenic Diet Study Group. Epilepsia 2009; 50: 304-317.
    CrossrefSearch in Google Scholar
  • 5 Huttenlocher PR, Wilbourn AJ, Signore JM. Medium-chain triglycerides as a therapy for intractable childhood epilepsy. Neurology 1971; 21: 1097-1103.
    CrossrefSearch in Google Scholar
  • 6 Schwartz RH, Eaton J, Bower BD, Green A. Ketogenic diets in the treatment of epilepsy: short-term clinical effects. Dev Med Child Neurol 1989; 31: 145-151.
    Search in Google Scholar
  • 7 Neal EG. et al. A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy. Epilepsia 2009; 50: 1109-1117.
    CrossrefSearch in Google Scholar
  • 8 Kossoff EH, Dorward JL. The modified Atkins diet. Epilepsia 2008; 49 Suppl 8: 37-41.
    Search in Google Scholar
  • 9 Auvin S. Should we routinely use modified Atkins diet instead of regular ketogenic diet to treat children with epilepsy?. Seizure 2012; 21: 237-240.
    CrossrefSearch in Google Scholar
  • 10 Chen W, Kossoff EH. Long-term follow-up of children treated with the modified Atkins diet. J Child Neurol 2012; 27: 754-758.
    CrossrefSearch in Google Scholar
  • 11 Kossoff EH, Rowley H, Sinha SR, Vining EP. A prospective study of the modified Atkins diet for intractable epilepsy in adults. Epilepsia 2008; 49: 316-319.
    CrossrefSearch in Google Scholar
  • 12 Smith M. et al. Efficacy and tolerability of the modified Atkins diet in adults with pharmacoresistant epilepsy: a prospective observational study. Epilepsia 2011; 52: 775-780.
    CrossrefSearch in Google Scholar
  • 13 Coppola G. et al. Low glycemic index diet in children and young adults with refractory epilepsy: first Italian experience. Seizure 2011; 20: 526-528.
    CrossrefSearch in Google Scholar
  • 14 Pfeifer HH, Thiele EA. Low-glycemic-index treatment: a liberalized ketogenic diet for treatment of intractable epilepsy. Neurology 2005; 65: 1810-1812.
    CrossrefSearch in Google Scholar
  • 15 Muzykewicz DA. et al. Efficacy, safety, and tolerability of the low glycemic index treatment in pediatric epilepsy. Epilepsia 2009; 50: 1118-1126.
    CrossrefPubMedSearch in Google Scholar
  • 16 Groesbeck DK, Bluml RM, Kossoff EH. Long-term use of the ketogenic diet in the treatment of epilepsy. Dev Med Child Neurol 2006; 48: 978-981.
    CrossrefSearch in Google Scholar
  • 17 Milder J, Patel M. Modulation of oxidative stress and mitochondrial function by the ketogenic diet. Epilepsy Res 2012; 100: 295-303.
    CrossrefSearch in Google Scholar
  • 18 Ma W, Berg J, Yellen G. Ketogenic diet metabolites reduce firing in central neurons by opening K(ATP) channels. J Neurosci 2007; 27: 3618-3625.
    CrossrefSearch in Google Scholar
  • 19 Tanner GR. et al. Single K ATP channel opening in response to action potential firing in mouse dentate granule neurons. J Neurosci 2011; 31: 8689-8696.
    CrossrefSearch in Google Scholar
  • 20 McDaniel SS. et al. The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway. Epilepsia 2011; 52: e7-11.
    CrossrefSearch in Google Scholar
  • 21 Bough KJ, Rho JM. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia 2007; 48: 43-58.
    CrossrefPubMedSearch in Google Scholar
  • 22 Danial NN, Hartman AL, Stafstrom CE, Thio LL. How does the ketogenic diet work? Four potential mechanisms. J Child Neurol 2013; 28: 1027-1033.
    CrossrefSearch in Google Scholar
  • 23 Masino SA, Rho JM. Mechanisms of Ketogenic Diet Action. In: Noebels JL. et al. (eds.). Jasper’s basic Mechanisms of the Epilepsies 4th edition. Bethesda (MD):: National Center for Biotechnology Information (US); 2012
    Search in Google Scholar
  • 24 Bergqvist AG. et al. Fasting versus gradual initiation of the ketogenic diet: a prospective, randomized clinical trial of efficacy. Epilepsia 2005; 46: 1810-1819.
    CrossrefPubMedSearch in Google Scholar
  • 25 Seo JH, Lee YM, Lee JS, Kang HC, Kim HD. Efficacy and tolerability of the ketogenic diet according to lipid:nonlipid ratios – comparison of 3:1 with 4:1 diet. Epilepsia 2007; 48: 801-805.
    CrossrefSearch in Google Scholar
  • 26 Kossoff EH. et al. A randomized, crossover comparison of daily carbohydrate limits using the modified Atkins diet. Epilepsy Behav 2007; 10: 432-436.
    CrossrefPubMedSearch in Google Scholar
  • 27 Neal EG. et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol 2008; 07: 500-506.
    CrossrefSearch in Google Scholar
  • 28 Lefevre F, Aronson N. Ketogenic diet for the treatment of refractory epilepsy in children: A systematic review of efficacy. Pediatrics 2000; 105: E46.
    CrossrefPubMedSearch in Google Scholar
  • 29 Keene DL. A systematic review of the use of the ketogenic diet in childhood epilepsy. Pediatr Neurol 2006; 35: 1-5.
    CrossrefSearch in Google Scholar
  • 30 Levy RG, Cooper PN, Giri P. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database Syst Rev 2012; 03: CD001903.
    Search in Google Scholar
  • 31 Klein P, Janousek J, Barber A, Weissberger R. Ketogenic diet treatment in adults with refractory epilepsy. Epilepsy Behav 2010; 19: 575-579.
    CrossrefPubMedSearch in Google Scholar
  • 32 Ramm-Pettersen A. et al. Good outcome in patients with early dietary treatment of GLUT-1 deficiency syndrome: results from a retrospective Norwegian study. Dev Med Child Neurol 2013; 55: 440-447.
    CrossrefPubMedSearch in Google Scholar
  • 33 Leen WG. et al. Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder. Brain 2010; 133: 655-670.
    CrossrefPubMedSearch in Google Scholar
  • 34 Klepper J. et al. Seizure control and acceptance of the ketogenic diet in GLUT1 deficiency syndrome: a 2-to 5-year follow-up of 15 children enrolled prospectively. Neuropediatrics 2005; 36: 302-308.
    Thieme ConnectPubMedSearch in Google Scholar
  • 35 De Vivo 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.
    CrossrefPubMedSearch in Google Scholar
  • 36 Klepper J, Leiendecker B. GLUT1 deficiency syndrome – 2007 update. Dev Med Child Neurol 2007; 49: 707-716.
    CrossrefPubMedSearch in Google Scholar
  • 37 Klepper J. GLUT1 deficiency syndrome in clinical practice. Epilepsy Res 2012; 100: 272-277.
    CrossrefSearch in Google Scholar
  • 38 De Giorgis V, Veggiotti P. GLUT1 deficiency syndrome 2013: current state of the art. Seizure 2013; 22: 803-811.
    CrossrefSearch in Google Scholar
  • 39 Byrne S. et al. Refractory absence epilepsy associated with GLUT-1 deficiency syndrome. Epilepsia 2011; 52: 1021-1024.
    CrossrefSearch in Google Scholar
  • 40 Arsov T. et al. Early onset absence epilepsy: 1 in 10 cases is caused by GLUT1 deficiency. Epilepsia 2012; 53: e204-e207.
    CrossrefSearch in Google Scholar
  • 41 Caraballo RH. et al. Ketogenic diet in patients with myoclonic-astatic epilepsy. Epileptic Disord 2006; 08: 151-155.
    Search in Google Scholar
  • 42 Oguni H. et al. Treatment and long-term prognosis of myoclonic-astatic epilepsy of early childhood. Neuropediatrics 2002; 33: 122-132.
    Thieme ConnectPubMedSearch in Google Scholar
  • 43 Kilaru S, Bergqvist AG. Current treatment of myoclonic astatic epilepsy: clinical experience at the Children’s Hospital of Philadelphia. Epilepsia 2007; 48: 1703-1707.
    CrossrefSearch in Google Scholar
  • 44 Caraballo RH. et al. Ketogenic diet in patients with Dravet syndrome. Epilepsia 2005; 46: 1539-1544.
    CrossrefSearch in Google Scholar
  • 45 Laux L, Blackford R. The ketogenic diet in Dravet syndrome. J Child Neurol 2013; 28: 1041-1044.
    CrossrefSearch in Google Scholar
  • 46 Mikaeloff Y. et al. Devastating epileptic encephalopathy in school-aged children (DESC): a pseudo encephalitis. Epilepsy Res 2006; 69: 67-79.
    CrossrefSearch in Google Scholar
  • 47 Sakuma H. et al. Acute encephalitis with refractory, repetitive partial seizures (AERRPS): a peculiar form of childhood encephalitis. Acta Neurol Scand 2010; 121: 251-256.
    CrossrefSearch in Google Scholar
  • 48 van Baalen A. et al. Febrile infection-related epilepsy syndrome without detectable autoantibodies and response to immunotherapy: a case series and discussion of epileptogenesis in FIRES. Neuropediatrics 2012; 43: 209-216.
    Thieme ConnectSearch in Google Scholar
  • 49 Kramer U. et al. Febrile infection-related epilepsy syndrome (FIRES): pathogenesis, treatment, and outcome: a multicenter study on 77 children. Epilepsia 2011; 52: 1956-1965.
    CrossrefSearch in Google Scholar
  • 50 Nabbout R. et al. Efficacy of ketogenic diet in severe refractory status epilepticus initiating fever induced refractory epileptic encephalopathy in school age children (FIRES). Epilepsia 2010; 51: 2033-2037.
    CrossrefPubMedSearch in Google Scholar
  • 51 Bodenant M. et al. (Interest of the ketogenic diet in a refractory status epilepticus in adults). Rev Neurol (Paris) 2008; 164: 194-199.
    CrossrefPubMedSearch in Google Scholar
  • 52 Kossoff EH, Nabbout R. Use of dietary therapy for status epilepticus. J Child Neurol 2013; 28: 1049-1051.
    CrossrefSearch in Google Scholar
  • 53 Strzelczyk A. et al. Intravenous initiation and maintenance of ketogenic diet: proof of concept in super-refractory status epilepticus. Seizure 2013; 22: 581-583.
    CrossrefPubMedSearch in Google Scholar
  • 54 Nam SH. et al. The role of ketogenic diet in the treatment of refractory status epilepticus. Epilepsia 2011; 52: e181-e184.
    CrossrefSearch in Google Scholar
  • 55 O’Connor SE. et al. The ketogenic diet for the treatment of pediatric status epilepticus. Pediatr Neurol 2014; 50: 101-103.
    CrossrefPubMedSearch in Google Scholar
  • 56 Kossoff EH. et al. A case-control evaluation of the ketogenic diet versus ACTH for new-onset infantile spasms. Epilepsia 2008; 49: 1504-1509.
    CrossrefPubMedSearch in Google Scholar
  • 57 Kossoff EH. et al. Tuberous sclerosis complex and the ketogenic diet. Epilepsia 2005; 46: 1684-1686.
    CrossrefPubMedSearch in Google Scholar
  • 58 Hemingway C. et al. The ketogenic diet: a 3-to 6-year follow-up of 150 children enrolled prospectively. Pediatrics 2001; 108: 898-905.
    CrossrefSearch in Google Scholar
  • 59 Freeman JM, Kossoff EH, Hartman AL. The ketogenic diet: one decade later. Pediatrics 2007; 119: 535-543.
    CrossrefPubMedSearch in Google Scholar
  • 60 Bergqvist AG. Long-term monitoring of the ketogenic diet: Do’s and Don’ts. Epilepsy Res 2012; 100: 261-266.
    CrossrefSearch in Google Scholar
  • 61 Kielb S, Koo HP, Bloom DA, Faerber GJ. Nephrolithiasis associated with the ketogenic diet. J Urol 2000; 164: 464-466.
    CrossrefSearch in Google Scholar
  • 62 Kang HC, Chung DE, Kim DW, Kim HD. Earlyand late-onset complications of the ketogenic diet for intractable epilepsy. Epilepsia 2004; 45: 1116-1123.
    CrossrefSearch in Google Scholar
  • 63 Kossoff EH. et al. Kidney stones, carbonic anhydrase inhibitors, and the ketogenic diet. Epilepsia 2002; 43: 1168-1171.
    CrossrefSearch in Google Scholar
  • 64 Sampath A. et al. Kidney stones and the ketogenic diet: risk factors and prevention. J Child Neurol 2007; 22: 375-378.
    CrossrefSearch in Google Scholar
  • 65 Kim JT. et al. Catch-up growth after long-term implementation and weaning from ketogenic diet in pediatric epileptic patients. Clin Nutr 2013; 32: 98-103.
    CrossrefSearch in Google Scholar
  • 66 Spulber G. et al. Growth dependence on insulinlike growth factor-1 during the ketogenic diet. Epilepsia 2009; 50: 297-303.
    CrossrefSearch in Google Scholar
  • 67 Best TH. et al. Cardiac complications in pediatric patients on the ketogenic diet. Neurology 2000; 54: 2328-2330.
    CrossrefSearch in Google Scholar
  • 68 Bank IM. et al. Sudden cardiac death in association with the ketogenic diet. Pediatr Neurol 2008; 39: 429-431.
    CrossrefSearch in Google Scholar
  • 69 Bergqvist AG. et al. Selenium deficiency associated with cardiomyopathy: a complication of the ketogenic diet. Epilepsia 2003; 44: 618-620.
    CrossrefSearch in Google Scholar
  • 70 Miranda MJ, Turner Z, Magrath G. Alternative diets to the classical ketogenic diet – Can we be more liberal?. Epilepsy Research 2012; 100: 278-85.
    CrossrefSearch in Google Scholar