The ketogenic diet is a high fat, low carbohydrate diet used as alternative treatment in drug-resistant epilepsy.
The International League Against Epilepsy (ILAE) defines refractory epilepsy as a clinical condition in which two appropriately chosen and tolerated antiepileptic drugs, either in monotherapy or in combination, fail to achieve seizure freedom.
The factors that contribute for an epilepsy to develop into a refractory condition are yet uncomprehended.
Genetics, brain lesions, and infectious and inflammatory disorders may increase the probability of drug-resistance.
Malpractice could trigger a ‘pseudo resistance’. An erroneous differential diagnosis between epilepsy and other paroxysmal movement disorders, an inaccurate diagnosis of epileptic seizures and syndromes, and a wrong administration of medication are all elements that may increase the frequency and the intensity of epileptic seizures.
Poor adherence to treatment also plays a key role. In my daily work with patients diagnosed with epilepsy, I had the opportunity to witness that a poor compliance of the treatment by the patients contributed to aggravate the prognosis and progression of the disorder. Poor adherence was associated with psychological and social factors, difficulty in accepting the illness, illiteracy or a low educational level, secondary effects, and inaccessibility to obtain the prescribed drugs.
Before going in depth into the main topic of this essay, I would like to emphasize the semantic difference between two medical terms: refractory and drug-resistant. When speaking of a refractory condition, we refer to a non- tractable illness and automatically reduce the alternative solutions offered to patients. On the other hand, when using the term drug-resistant, we refer to a condition that does not respond to pharmacological treatment but may respond to other non-pharmacological interventions. So, being this point cleared, I would like to use the term drug-resistant when referring to refractory epilepsy from now on.
The main theme of this text is precisely an alternative intervention for drug- resistant epilepsies: ketogenic diet.
The ketogenic diet is a high fat, adequate protein and low carbohydrate diet. Different variations of ketogenic diets have been tested. In the traditional version, 90% of the energy source comes from fats and 10% from protein; another version gets 70% of energy source from fats, 20% from carbohydrates and 10% from proteins; and in another version, 65% of the energy source comes from fats, 20-15% from proteins and 15-10% from carbohydrates, being this last option the best tolerated one.
As it can be seen, the ketogenic diet causes the amount of glucose to drop dramatically, turning ketone bodies (synthesized in fats metabolism) into the major source of energy for the brain. Ketone bodies stimulate GABA synthesis, which is the same function antiepileptic drugs perform in the brain. GABA, an inhibitory neurotransmitter, has anticonvulsant effects because it closes the ion channels in the post-synaptic neurons and enhances inhibitory transmission, reducing the electric, abnormal discharges that produce epileptic seizures.
The ketogenic therapy must be supervised by a multidisciplinary team. It consists of a physician, a dietician, a nurse and a neurologist. Patients that accomplish the requirements and are accepted in the programme, will undergo a rigid procedure. Firstly, they will receive information on the diet and how to prepare the meals, as well as the pros and cons they will face during the process. During the first days on the diet, the patient will be hospitalized for his tolerability to be monitored. The first results on seizure reduction are expected in a 12-week period. If progress is not evident, the diet will be suspended. However, if the diet is shown to be effective, the patient will have to commit to it for at least two years. Depending on each patient’s progress, the reduction of antiepileptic drugs will begin in 3 to 6 months from the beginning of the diet.
Many short and long-term side effects are associated with the ketogenic diet. The most common symptoms are constipation, diarrhea, nausea and vomit, fever, infections, kidney stones, acidosis, hyperlipidemia, hypoglycemia, hypercholesterolemia, weight loss, inadequate growth, malnutrition, sleepiness, sedation and lethargy.
However, the advantages outweigh the disadvantages. Several studies have reported 50-60% reduction in seizures, showing no significant difference in the efficacy of the treatment between focal or generalised seizures. Although, the diet seems to be more effective in certain refractory epileptic syndromes: Lennox-Gastaut, West, Doose, Dravet and Rett Syndromes, Tuberous Sclerosis, Febrile Infection Related Epilepsy Syndrome and Epilepsy-Autism Complex.
Seizure and anti-epileptic drug reduction combined with the ketogenic diet produce positive effects on mental functions. Many studies show an improvement in the level of alertness, sustained attention, working memory, vocabulary, processing speed and social interaction, as well as behaviour, impulse control and quality of sleep.
Although the ketogenic diet is a very ancient therapy, used even before pharmacological treatments boosted, its advantages are still questioned by many clinicians. Its effectiveness has been proved mostly in pediatric populations though drug-resistant epilepsy is extremely frequent among older adults too. More research on this topic is required in order to offer alternative treatments to patients and give them the possibility of improving their quality of life.
References
Anyanwu, C. and Motamedi, G. (2012). Management of pediatric refractory epilepsy. Journal of Pediatric Epilepsy, 1, 203-209. doi: 10.3233/PEP-12032
Armeno, M., Araujo, C., Sotomontesano, B. and Caraballo, R. (2018). Actualización sobre los efectos adversos durante la terapia con dieta cetogénica en la epilepsia refractaria pediátrica. Revista de Neurología, 66 (6), 193-200.
García-Peñas, J. (2018). Epilepsia, cognición y dieta cetogénica. Revista de Neurología, 66 (1), 71-75.
Rickertsen, T. and Danforth, S. (2014). Ketogenic diet for seizure management in children. Journal of Pediatric Epilepsy, 3, 25-31. doi: 10.3233/PEP-14070
Villanueva Haba, V. and Donaire Pedraza, A. (2012). Epilepsia refractaria a fármacos antiepilépticos. Politerapia racional. In J. Mercadé, J. Sancho, J. Mauri, F. López and X. Salas. (Eds.). Guía oficial de práctica clínica en epilepsia: Guías diagnósticas y terapéuticas de la Sociedad Española de Neurología. Madrid, Spain: Ediciones SEN.
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