Non-pharmacological Interventions for Intractable Epilepsy

Abstract

In 30% of epileptic individuals, intractable epilepsy represents a problem for the management of seizures and severely affects the patient's quality of life due to pharmacoresistance with commonly used antiseizure drugs (ASDs). Surgery is not the best option for all resistant patients due to its post-surgical consequences. Therefore, several alternative or complementary therapies have scientifically proven significant therapeutic potential for the management of seizures in intractable epilepsy patients with seizure-free occurrences. Various non-pharmacological interventions include metabolic therapy, brain stimulation therapy, and complementary therapy. Metabolic therapy works out by altering the energy metabolites and include the ketogenic diets (KD) (that is restricted in carbohydrates and mimics the metabolic state of the body as produced during fasting and exerts its antiepileptic effect) and anaplerotic diet (which revives the level of TCA cycle intermediates and this is responsible for its effect). Neuromodulation therapy includes vagus nerve stimulation (VNS), responsive neurostimulation therapy (RNS) and transcranial magnetic stimulation therapy (TMS). Complementary therapies such as biofeedback and music therapy have demonstrated promising results in pharmacoresistant epilepsies. The current emphasis of the review article is to explore the different integrated mechanisms of various treatments for adequate seizure control, and their limitations, and supportive pieces of evidence that show the efficacy and tolerability of these non-pharmacological options.

Keywords: ASDs, Antiepileptic drugs; ATP, Adenosine triphosphate; Anaplerotic diet; BBB, Blood-brain barrier; CKD, Classic ketogenic diet; CSF, Cerebrospinal fluid; EEG, Electroencephalography; EMG, Electromyography; GABA, Gamma-aminobutyric acid; Intractable epilepsy; KB, Ketone bodies; KD, Ketogenic diet; Ketogenic diet; LC, Locus coeruleus; LCFA, Long-chain fatty acids; MAD, Modified Atkin's diet; MCT, Medium-chain triglyceride; MEP, Maximal evoked potential; Music therapy; NTS, Nucleus tractus solitaries; PPAR, Peroxisome proliferator-activated receptor; PUFAs, Polyunsaturated fatty acids; RNS, Responsive neurostimulation; ROS, reactive oxygen species; SMR, Sensorimotor rhythm; TCA, Tricarboxylic acid cycle; TMS, Transcranial magnetic stimulation; Transcranial magnetic stimulation Biofeedback therapy; VNS, Vagus nerve stimulation; Vagus nerve stimulation.