Anne T. Berg

Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009.

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.

Epileptic Seizures and Epilepsy: Definitions Proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)

The International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) have come to consensus definitions for the terms epileptic seizure and epilepsy. An epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epileptic seizure.

Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies.

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 Protective Efficacy of Polyvalent Pneumococcal Polysaccharide Vaccine

BACKGROUND Although the protective efficacy of pneumococcal polysaccharide vaccine has been demonstrated in randomized trials in young African gold miners, there has been controversy about its efficacy in older Americans at risk for serious pneumococcal infections. To assess the vaccines protective efficacy against invasive pneumococcal infections, we conducted a hospital-based case-control study of the efficacy of pneumococcal vaccine in adults with a condition recognized to be an indication for receiving the vaccine. METHODS From 1984 to 1990, adults in whom Streptococcus pneumoniae was isolated from any normally sterile site were identified by prospective surveillance in the microbiology laboratories of 11 large hospitals; those with an indication for pneumococcal vaccine were enrolled as case patients. For each case patient, one control was matched according to age, underlying illness, and site of hospitalization. We contacted all providers of medical care to ascertain each subjects history of immunization with pneumococcal vaccine. Isolates of S. pneumoniae were serotyped by an investigator unaware of the subjects vaccination history. RESULTS Thirteen percent of the 1,054 case patients and 20 percent of the 1,054 matched controls had received pneumococcal vaccine (P less than 0.001). When vaccine was given in either its 14-valent or its 23-valent form, its aggregate protective efficacy (calculated as a percentage: 1 minus the odds ratio of having been vaccinated times 100) against infections caused by the serotypes represented in the vaccine was 56 percent (95 percent confidence interval, 42 percent to 67 percent; P less than 0.00001) for all 983 patients infected with a serotype represented in the vaccine, 61 percent for a subgroup of 808 immunocompetent patients (95 percent confidence interval, 47 percent to 72 percent; P less than 0.00001), and 21 percent for a subgroup of 175 immunocompromised patients (95 percent confidence interval, -55 percent to 60 percent; P = 0.48). The vaccine was not efficacious against infections caused by serotypes not represented in the vaccine (protective efficacy, -73 percent; 95 percent confidence interval, -263 percent to 18 percent; P = 0.15). CONCLUSIONS Polyvalent pneumococcal vaccine is efficacious in preventing invasive pneumococcal infections in immunocompetent patients with indications for its administration. This vaccine should be used more widely.

Standards for epidemiologic studies and surveillance of epilepsy

Worldwide, about 65 million people are estimated to have epilepsy. Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy. However, different definitions and epidemiologic methods complicate the tasks of these studies and their interpretations and comparisons. The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population‐based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health. We discuss: (1) conceptual and operational definitions of epilepsy, (2) data resources and recommended data elements, and (3) methods and analyses appropriate for epidemiologic studies or the surveillance of epilepsy. Variations in these are considered, taking into account differing resource availability and needs among countries and differing purposes among studies.

The risk of seizure recurrence following a first unprovoked seizure: a quantitative review.

Knowledge of the recurrence risk following a first unprovoked seizure and the predictors of that risk are necessary for rational treatment decisions. Published estimates of recurrence risk range from 23 % to 71%. In a meta-analysis of 16 reports, three methodologic factors explained much of the reported variation: (1) study inclusion criteria, ie, whether patients were enrolled at the time of their first seizure or if patients with prior seizures were included; (2) retrospective versus prospective ascertainment of patients; (3) the interval between the first seizure and the time at which risk was assessed. The average recurrence risk across the 16 studies was 51%. The risk was 40% and 52% in prospective and retrospective studies that employed first-seizure methods and 67% in non-first seizure studies. At or near 2 years following the first seizure, the recurrence risk was 36% and 47% in prospective and retrospective first-seizure studies. The distribution of prognostic factors was also important. Seizure etiology and the EEG were the strongest predictors of recurrence distinguishing between patient subgroups, with recurrence risks as low as 24% and as high as 65%. Partial seizures were associated with an increased recurrence risk, but not consistently. There is considerable agreement among studies concerning the recurrence risk following a first seizure, and much of the discrepancies among studies can be explained by differences in study methods and distributions of important prognostic factors.

The epidemiology of epilepsy. Past, present, and future.

Much has been learned from epidemiologic studies about the frequency, causes, natural history, and prognosis of epilepsy and other seizure disorders. This knowledge has resulted in significant changes in the clinical management of individuals who have seizures and epilepsy. Recent changes in the known causal factors and diagnostic technologic advances, among other factors, will affect the epidemiology and prognosis of epilepsy. Continued epidemiologic monitoring of this common neurologic condition is necessary to ensure an accurate understanding of the current forms of the disorder.

Early development of intractable epilepsy in children: A prospective study

Background: Little is known about early prediction of intractable epilepsy (IE) in children. Such information could help guide the early use of new therapies in selected patients. Methods: Children with newly diagnosed epilepsy (n = 613) were prospectively identified from child neurology practices in Connecticut (1993–1997) and followed-up for the occurrence of IE (failure of >2 drugs, >1 seizure/month, over 18 months). Etiology and epilepsy syndromes were classified per International League Against Epilepsy guidelines. Results: The median follow-up is 4.8 years, and 599 (97.7%) have been followed for more than 18 months. Sixty children (10.0%) have met the criteria for IE, including 34.6% with cryptogenic/symptomatic generalized, 2.7% with idiopathic, 10.7% with other localization–related, and 8.2% with unclassified epilepsy (p < 0.0001). After multivariable adjustment for epilepsy syndrome, initial seizure frequency (p < 0.0001), focal EEG slowing (p = 0.02), and acute symptomatic or neonatal status epilepticus (p = 0.001) were associated with an increased risk of IE, and age at onset between 5 and 9 years was associated with a lowered risk (p = 0.03). The absolute number of seizures and unprovoked or febrile status epilepticus were not associated substantially with IE. Conclusions: Approximately 10% of children meet criteria for IE early in the course of their epilepsy. Cryptogenic/symptomatic generalized syndromes carry the highest risk and idiopathic syndromes the lowest. Half of IE occurs in children with nonidiopathic localization-related syndromes. Initial seizure frequency is highly predictive of IE. By contrast, absolute number of seizures and unprovoked or febrile status epilepticus are not.

Predicting long-term seizure outcome after resective epilepsy surgery The Multicenter Study

Background: In a seven-center prospective observational study of resective epilepsy surgery, the authors examined probability and predictors of entering 2-year remission and the risk of subsequent relapse. Methods: Patients aged 12 years and over were enrolled at time of referral for epilepsy surgery, and underwent standardized evaluation, treatment, and follow-up procedures. The authors defined seizure remission as 2 years completely seizure-free after hospital discharge with or without auras, and relapse as any seizures after 2-year remission. The authors examined type of surgery, seizure, clinical and demographic variables, and localization study results with respect to prediction of seizure remission or relapse, using χ2 and proportional hazards analysis. Results: Of 396 operated patients, 339 were followed over 2 years, and 223 (66%) experienced 2-year remission, not significantly different between medial temporal (68%) and neocortical (50%) resections. In multivariable models, only absence of generalized tonic-clonic seizures and presence of hippocampal atrophy were significantly and independently associated with remission, and only in the medial temporal resection group. Fifty-five patients relapsed after 2-year remission, again not significantly different between medial temporal (25%) and neocortical (19%) resections. Only delay to remission predicted relapse, and only in medial temporal patients. Conclusion: Hippocampal atrophy and a history of absence of generalized tonic clonic seizures were the sole predictors of 2-year remission, and only for medial temporal resections.

Practice parameter: evaluating a first nonfebrile seizure in children: Report of the Quality Standards Subcommittee of the American Academy of Neurology, the Child Neurology Society, and the American Epilepsy Society.

Objective: The Quality Standards Subcommittee of the American Academy of Neurology develops practice parameters as strategies for patient management based on analysis of evidence. For this practice parameter, the authors reviewed available evidence on evaluation of the first nonfebrile seizure in children in order to make practice recommendations based on this available evidence. Methods: Multiple searches revealed relevant literature and each article was reviewed, abstracted, and classified. Recommendations were based on a three-tiered scheme of classification of the evidence. Results: Routine EEG as part of the diagnostic evaluation was recommended; other studies such as laboratory evaluations and neuroimaging studies were recommended as based on specific clinical circumstances. Conclusions: Further studies are needed using large, well-characterized samples and standardized data collection instruments. Collection of data regarding appropriate timing of evaluations would be important.