Epilepsia

Epilepsy was defined conceptually in 2005 as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. This definition is usually practically applied as having two unprovoked seizures >24 h apart. The International League Against Epilepsy (ILAE) accepted recommendations of a task force altering the practical definition for special circumstances that do not meet the two unprovoked seizures criteria. The task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring >24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome. Epilepsy is considered to be resolved for individuals who either had an age‐dependent epilepsy syndrome but are now past the applicable age or who have remained seizure‐free for the last 10 years and off antiseizure medicines for at least the last 5 years. “Resolved” is not necessarily identical to the conventional view of “remission or “cure.” Different practical definitions may be formed and used for various specific purposes. This revised definition of epilepsy brings the term in concordance with common use.

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The International League Against Epilepsy (ILAE) Commission on Classification and Terminology has revised concepts, terminology, and approaches for classifying seizures and forms of epilepsy. Generalized and focal are redefined for seizures as occurring in and rapidly engaging bilaterally distributed networks (generalized) and within networks limited to one hemisphere and either discretely localized or more widely distributed (focal). Classification of generalized seizures is simplified. No natural classification for focal seizures exists; focal seizures should be described according to their manifestations (e.g., dyscognitive, focal motor). The concepts of generalized and focal do not apply to electroclinical syndromes. Genetic, structural–metabolic, and unknown represent modified concepts to replace idiopathic, symptomatic, and cryptogenic. Not all epilepsies are recognized as electroclinical syndromes. Organization of forms of epilepsy is first by specificity: electroclinical syndromes, nonsyndromic epilepsies with structural–metabolic causes, and epilepsies of unknown cause. Further organization within these divisions can be accomplished in a flexible manner depending on purpose. Natural classes (e.g., specific underlying cause, age at onset, associated seizure type), or pragmatic groupings (e.g., epileptic encephalopathies, self‐limited electroclinical syndromes) may serve as the basis for organizing knowledge about recognized forms of epilepsy and facilitate identification of new forms.

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.

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.

The Commission on Classification and Terminology and the Commission on Epidemiology of the International League Against Epilepsy (ILAE) have charged a Task Force to revise concepts, definition, and classification of status epilepticus (SE). The proposed new definition ofSEis as follows:Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t₁). It is a condition, which can have long‐term consequences (after time point t₂), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. This definition is conceptual, with two operational dimensions: the first is the length of the seizure and the time point (t₁) beyond which the seizure should be regarded as “continuous seizure activity.” The second time point (t₂) is the time of ongoing seizure activity after which there is a risk of long‐term consequences. In the case of convulsive (tonic–clonic)SE, both time points (t₁at 5 min and t₂at 30 min) are based on animal experiments and clinical research. This evidence is incomplete, and there is furthermore considerable variation, so these time points should be considered as the best estimates currently available. Data are not yet available for other forms ofSE, but as knowledge and understanding increase, time points can be defined for specific forms ofSEbased on scientific evidence and incorporated into the definition, without changing the underlying concepts. Anew diagnostic classification systemofSEis proposed, which will provide a framework for clinical diagnosis, investigation, and therapeutic approaches for each patient. There are four axes: (1) semiology; (2) etiology; (3) electroencephalography (EEG) correlates; and (4) age. Axis 1 (semiology) lists different forms ofSEdivided into those with prominent motor systems, those without prominent motor systems, and currently indeterminate conditions (such as acute confusional states with epileptiformEEGpatterns). Axis 2 (etiology) is divided into subcategories of known and unknown causes. Axis 3 (EEGcorrelates) adopts the latest recommendations by consensus panels to use the following descriptors for theEEG: name of pattern, morphology, location, time‐related features, modulation, and effect of intervention. Finally, axis 4 divides age groups into neonatal, infancy, childhood, adolescent and adulthood, and elderly.

Purpose:  We report a multicenter, double‐blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization‐related epilepsy.

Methods:  Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3‐month blinded phase; then all received unblinded stimulation.

Results:  One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and “most severe” seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure‐free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation‐associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events.

Discussion:  Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.

Purpose: The estimated prevalence of mental health disorders in those with epilepsy in the general population varies owing to differences in study methods and heterogeneity of epilepsy syndromes. We assessed the population‐based prevalence of various psychiatric conditions associated with epilepsy using a large Canadian national population health survey.

Methods: The Canadian Community Health Survey (CCHS 1.2) was used to explore numerous aspects of mental health in persons with epilepsy in the community compared with those without epilepsy. The CCHS includes administration of the World Mental Health Composite International Diagnostic Interview to a sample of 36,984 subjects. Age‐specific prevalence of mental health conditions in epilepsy was assessed using logistic regression.

Results: The prevalence of epilepsy was 0.6%. Individuals with epilepsy were more likely than individuals without epilepsy to report lifetime anxiety disorders or suicidal thoughts with odds ratio of 2.4 (95% CI = 1.5–3.8) and 2.2 (1.4–3.3), respectively. In the crude analysis, the odds of lifetime major depression or panic disorder/agoraphobia were not greater in those with epilepsy than those without epilepsy, but the association with lifetime major depression became significant after adjustment for covariates.

Conclusions: In the community, epilepsy is associated with an increased prevalence of mental health disorders compared with the general population. Epilepsy is also associated with a higher prevalence of suicidal ideation. Understanding the psychiatric correlates of epilepsy is important to adequately manage this patient population.

Although no randomized studies have demonstrated a positive impact of therapeutic drug monitoring (TDM) on clinical outcome in epilepsy, evidence from nonrandomized studies and everyday clinical experience does indicate that measuring serum concentrations of old and new generation antiepileptic drugs (AEDs) can have a valuable role in guiding patient management provided that concentrations are measured with a clear indication and are interpreted critically, taking into account the whole clinical context. Situations in which AED measurements are most likely to be of benefit include (1) when a person has attained the desired clinical outcome, to establish an individual therapeutic concentration which can be used at subsequent times to assess potential causes for a change in drug response; (2) as an aid in the diagnosis of clinical toxicity; (3) to assess compliance, particularly in patients with uncontrolled seizures or breakthrough seizures; (4) to guide dosage adjustment in situations associated with increased pharmacokinetic variability (e.g., children, the elderly, patients with associated diseases, drug formulation changes); (5) when a potentially important pharmacokinetic change is anticipated (e.g., in pregnancy, or when an interacting drug is added or removed); (6) to guide dose adjustments for AEDs with dose‐dependent pharmacokinetics, particularly phenytoin.