Exogenous Ketone Esters for Drug Resistant Epilepsy

Epilepsy is a common neurological disorder among children with significant neurobiological, cognitive, psychological, and social consequences. Seizures can usually be controlled by anti-seizure medications (ASMs) in up to two-thirds of children with epilepsy. However, this leaves a significant part of epileptic children whose seizures are not controlled by pharmacotherapy. Currently, available alternatives for drug-resistant epilepsy (DRE) include surgery, vagus nerve stimulation, and ketogenic diet (KD).

KD has been classically used for treating children with DRE. However, KD requires strict dietary restriction, which may not be applicable or acceptable for many patients, and is associated with several adverse effects, commonly including gastrointestinal (e.g., constipation, nausea, vomiting), cardiovascular (e.g., dyslipidemia), renal/genitourinary (e.g., renal calculi), and growth problems. Exogenous ketone esters (EKE) could be a more convenient and superior alternative to KD for children with DRE.

Inclusion criteria

• Drug-resistant epilepsy
• Seizure frequency ≥ 7 per week

Exclusion criteria

• Failure to obtain informed consent
• Recent intake of exogenous ketones, ketogenic diet, or any dietary restrictions/modifications
• Severe disease conditions, including hepatic, renal, respiratory, cardiac, gastrointestinal, endocrinal, and immune systems
• Hypo-/hyperglycemia
• Metabolic acidosis
• Ketosis (βHB > 2 mmol/L)
• GIT disorders, including gastritis/peptic ulcer, diarrhea/constipation, and irritable bowel disease
• Malnutrition/obesity
• Limitations to oral feeding (e.g., severe gastroesophageal reflux)
• Inborn errors of metabolism
• Chromosomal disorders
• Surgically-remediable epilepsy
• Allergies or any other contraindication to ketone supplements
• Inapplicable recording of seizures
• Incompliance to anti-seizure medications and/or irregular follow-up
• Recent propofol therapy
• Intake of carbonic-anhydrase inhibitors