Analysis of factors influencing the efficacy of vagus nerve stimulation for the treatment of drug-resistant epilepsy in children and prediction model for efficacy evaluation

The International League Against Epilepsy (ILAE) Classification of the Epilepsies has been updated to reflect our gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for diagnosis of patients, but it is also critical for epilepsy research, development of antiepileptic therapies, and communication around the world. The new classification originates from a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It presents three levels, starting with seizure type, where it assumes that the patient is having epileptic seizures as defined by the new 2017 ILAE Seizure Classification. After diagnosis of the seizure type, the next step is diagnosis of epilepsy type, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and also an unknown epilepsy group. The third level is that of epilepsy syndrome, where a specific syndromic diagnosis can be made. The new classification incorporates etiology along each stage, emphasizing the need to consider etiology at each step of diagnosis, as it often carries significant treatment implications. Etiology is broken into six subgroups, selected because of their potential therapeutic consequences. New terminology is introduced such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self-limited and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the 21st century.

To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) appointed a Task Force to formulate a consensus definition of drug resistant epilepsy. The overall framework of the definition has two "hierarchical" levels: Level 1 provides a general scheme to categorize response to each therapeutic intervention, including a minimum dataset of knowledge about the intervention that would be needed; Level 2 provides a core definition of drug resistant epilepsy using a set of essential criteria based on the categorization of response (from Level 1) to trials of antiepileptic drugs. It is proposed as a testable hypothesis that drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This definition can be further refined when new evidence emerges. The rationale behind the definition and the principles governing its proper use are discussed, and examples to illustrate its application in clinical practice are provided.

Epilepsy is one of the most common serious brain conditions, affecting over 70 million people worldwide. Its incidence has a bimodal distribution with the highest risk in infants and older age groups. Progress in genomic technology is exposing the complex genetic architecture of the common types of epilepsy, and is driving a paradigm shift. Epilepsy is a symptom complex with multiple risk factors and a strong genetic predisposition rather than a condition with a single expression and cause. These advances have resulted in the new classification of epileptic seizures and epilepsies. A detailed clinical history and a reliable eyewitness account of a seizure are the cornerstones of the diagnosis. Ancillary investigations can help to determine cause and prognosis. Advances in brain imaging are helping to identify the structural and functional causes and consequences of the epilepsies. Comorbidities are increasingly recognised as important aetiological and prognostic markers. Antiseizure medication might suppress seizures in up to two-thirds of all individuals but do not alter long-term prognosis. Epilepsy surgery is the most effective way to achieve long-term seizure freedom in selected individuals with drug-resistant focal epilepsy, but it is probably not used enough. With improved understanding of the gradual development of epilepsy, epigenetic determinants, and pharmacogenomics comes the hope for better, disease-modifying, or even curative, pharmacological and non-pharmacological treatment strategies. Other developments are clinical implementation of seizure detection devices and new neuromodulation techniques, including responsive neural stimulation.