The enigmatic figure of Leon Pierce Clark and his contribution to epilepsy.

Leon Pierce Clark (1870-1933) was a prominent American neurologist and psychiatrist and an enigmatic figure. He made enduring contributions to status epilepticus and to epilepsy. In the 1910s and 1920s, his chief focus was on the psychological mechanisms of epilepsy and on the personality of those with idiopathic epilepsy which he interpreted from a psychoanalytical perspective.

Change in Mortality of Generalized Convulsive Status Epilepticus in High-Income Countries Over Time: A Systematic Review and Meta-analysis.

Importance: Status epilepticus (SE) is associated with significant morbidity and mortality. Since the late 1990s, a more aggressive management of prolonged convulsive seizures lasting longer than 5 minutes has been advocated.

Objective: To determine if convulsive SE mortality has decreased during a time of increasing advocacy for out-of-hospital treatment and escalating and earlier treatment protocols for prolonged seizures and SE.

Antiepileptic drug treatment of generalized tonic-clonic seizures: An evaluation of regulatory data and five criteria for drug selection.

Background: A generalized tonic-clonic seizure (GTCS) is the most severe form of common epileptic seizure and carries the greatest risk of harm. The aim of this review is to provide an evidence-based guide for the selection of antiepileptic drugs (AEDs) for patients with GTCSs. Eight AEDs are approved in Europe and the USA for the treatment of both primarily GTCSs (PGTCSs) and secondarily GTCSs (SGTCSs) and are considered in this paper.

Outcome of seizures in the general population after 25 years: a prospective follow-up, observational cohort study.

Objectives: We investigated long-term (to 25 years) seizure prognosis and survival in people with newly diagnosed epilepsy in the community. We explored whether prognosis is different in those with epilepsy (>2 unprovoked seizures) and those with a single seizure at presentation.

Methods: This is a prospective observational cohort study of people with newly diagnosed seizures.

The beliefs among patients with epilepsy in Saudi Arabia about the causes and treatment of epilepsy and other aspects.

Purpose: The current survey sought to identify the religious and cultural beliefs about the causes and treatment of epilepsy in people with epilepsy from Saudi Arabia and a number of other aspects relating to the possibility of cure, coping with the condition, and public awareness.

Methods: Study instruments were developed on the basis of the literature, a focus group of people with epilepsy, and feedback from people in the field with local knowledge. These were then piloted.

The use of the NDDI-E in Arabic to identify symptoms of depression of moderate or greater severity in people with epilepsy.

Aim: The aims of the current study were to translate and to validate the NDDI-E to the Arabic language to be used as a screening instrument to identify moderately severe symptoms of depression in people with epilepsy.

Methods: The English version of the NDDI-E was translated to Arabic and back translated to English by two independent translators. A total of 51 patients, aged 18-56years old, with a diagnosis of epilepsy, completed the Arabic versions of the Beck Depression Inventory (BDI-II) and the NDDI-E.

The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine-resistant convulsive status epilepticus: a meta-analysis of published studies.

Purpose: Systematic evaluation of published evidence-base of the efficacy of five antiepileptic drugs - lacosamide, levetiracetam, valproate, phenytoin and phenobarbital - in convulsive benzodiazepine-resistant status epilepticus.

Methods: Data sources included electronic databases, personal communication, and back tracing of references in pertinent studies. These were prospective and retrospective human studies presenting original data for participants with convulsive benzodiazepine-resistant status epilepticus.

The contribution of British general practice to our knowledge of epilepsy and its effects on people.

Introduction: British general practice is a good base for epidemiological research which is evidenced by the study of epilepsy.

Sources Of Data: A comprehensive search of PubMed using various keywords for articles on epilepsy research performed in British general practice.

Areas Of Agreement: Studies in the setting of general practice have contributed significantly to knowledge in the field of epilepsy, especially in relation to epidemiology, studies of prognosis and treatment patterns and psychosocial aspects.

Longitudinal cohort studies of the prognosis of epilepsy: contribution of the National General Practice Study of Epilepsy and other studies.

Longitudinal cohort studies of prognosis in epilepsy have been carried out since the late 1970s and these have transformed our understanding of prognosis in epilepsy. This paper reviews the contribution of such studies and focuses particularly on the National General Practice Study of Epilepsy, a prospective population-based cohort study of 1195 patients that was initiated in 1983. The National General Practice Study of Epilepsy and other studies have shown that: (i) epilepsy has an often good prognosis with 65-85% of cases eventually entering long-term remission, and an even higher proportion of cases entering a short-term remission; (ii) the likelihood of long-term remission of seizures is much better in newly diagnosed cases than in patients with chronic epilepsy; (iii) the early response to treatment is a good guide to longer term prognosis (although not inevitably so, as in a minority of cases seizure remission can develop after prolonged activity); (iv) the longer is the remission (and follow-up), the less likely is subsequent recurrence; (v) the longer an epilepsy is active, the poorer is the longer term outlook; (vi) that delaying treatment, even for many years, does not worsen long-term prognosis; (vii) the 'continuous' and 'burst' patterns are more common than the 'intermittent' seizure pattern; (viii) epilepsy has a mortality that is highest in the early years after diagnosis, and in the early years is largely due to the underlying cause, however, higher mortality rates than expected are observed throughout the course of an epilepsy; (ix) the prognosis of febrile seizures is generally good, with ~6-7% developing later epilepsy; and (x) clinical factors associated with outcome have been well studied, and those consistently found to predict a worse outcome include: the presence of neurodeficit, high frequency of seizures before therapy (seizure density), poor response to initial therapy, some epilepsy syndromes.

How phenobarbital revolutionized epilepsy therapy: the story of phenobarbital therapy in epilepsy in the last 100 years.

Phenobarbital (phenobarbitone) was first used as an antiepileptic drug 100 years ago, in 1912. This article tells the story of the discovery of its antiepileptic action, its early development, and the subsequent course of its clinical use over the 100-year period. The side effects, pharmacokinetics, and misuse of barbiturates are considered, along with the more recent clinical trials and the drug's current clinical utilization.

Treatment changes in a cohort of people with apparently drug-resistant epilepsy: an extended follow-up.

Background: The seizure response to the addition of a previously unused antiepileptic drug in a cohort of 155 people with refractory epilepsy was previously reported after a median of 18 months follow-up.

Methods: The authors followed 139 (90%) of the original cohort for a median follow-up of 6.9 years to determine the longer term outcome in people with refractory epilepsy.

Heredity in epilepsy: neurodevelopment, comorbidity, and the neurological trait.

The genetic bases of common, nonmendelian epilepsy have been difficult to elucidate. In this article, we argue for a new approach to genetic inquiry in epilepsy. In the latter part of the 19th century, epilepsy was universally acknowledged to be part of a wider "neurological trait" that included other neuropsychiatric conditions.

How refractory is refractory epilepsy? Patterns of relapse and remission in people with refractory epilepsy.

Background: Outcome studies in people with epilepsy have largely focused on the prognosis in the early stages and factors predictive of early remission. Few studies have examined prognosis in chronic refractory epilepsy.

Methods: We determined the pattern of remission and relapse of epilepsy in a cohort of people with refractory epilepsy (seizures in the past two years, at least five years after onset and who have been treated with at least 2 appropriate antiepileptic drugs during that time) to investigate whether any clinical or demographic features are predictive of seizure patterns.

The causes of epilepsy: changing concepts of etiology of epilepsy over the past 150 years.

This paper provides a survey of the changing concepts of the etiology of epilepsy from 1860 to 2010, focusing on the first two 50-year periods and outlining more briefly major developments in the past 50 years. Among the concepts reviewed in the first 100 years are: the division between predisposing and exciting causes, idiopathic and genuine epilepsy, organic epilepsy, the concept of "cause" being equivalent to "causal mechanism," Russell Reynolds etiological classification, the neurological taint and theories of degeneration, the self-perpetuating nature of seizures, reflex theories of etiology, autointoxication, heredity and eugenics, epilepsy due to brain disorders, the role of EEG and of hippocampal sclerosis, psychological theories of causation, and the multifactorial view of epilepsy etiology. In the past 50 years, the major advances in studying causation in epilepsy have been: clinical biochemistry, neuroimaging, molecular genetics, studies of mechanisms of epilepsy, better statistical methodologies and classification.

The etiologic classification of epilepsy.

The etiology of epilepsy is a major determinant of clinical course and prognosis, yet the current classifications of epilepsy do not list etiology in any detail. In this article, a classification (database) of the etiologies of epilepsy is proposed. In this scheme, the etiology of epilepsy is divided into four categories: idiopathic, symptomatic, provoked, and cryptogenic.

The long-term risk of premature mortality in people with epilepsy.

People with epilepsy have an increased risk of premature death. The risk is highest soon after onset of seizures. We report the findings of a long-term follow-up population-based study of people with epilepsy with regards to premature mortality.

Temporal trends in the mortality of people with epilepsy: a review.

Purpose: It is now generally accepted that people with epilepsy are at increased risk of premature death compared with peers in the general population. It has, however, not been clearly established how this risk changes over time, nor whether mortality rates have been changing over time.

Methods: We carried out a systematic review: (1) To determine the pattern of change of mortality risk relative to the general population in people with epilepsy in the course of their condition as measured by standardized mortality ratios (SMRs), by reviewing longitudinal prospective cohort studies.

Frequency and prognosis of convulsive status epilepticus of different causes: a systematic review.

We conducted a systematic review of all studies of status epilepticus (SE) with more than 30 patients published between January 1, 1990, and December 31, 2008, to determine the frequencies of the common underlying causes and the extent to which the underlying causes affect the prognosis of an episode of SE. The frequencies of underlying causes vary among studies and show marked geographic differences, but in most studies, the most common underlying causes were cerebrovascular disease and low antiepileptic drug levels. A relatively good prognosis of SE is found when the underlying cause is associated with low antiepileptic drug levels or alcohol abuse, and a relatively poor outcome occurs when the underlying cause is cerebrovascular disease, particularly in the case of SE due to acute cerebral anoxia, but in most conditions, the reported prognosis is variable.

Ischaemic stroke in adults and epilepsy.

Stroke is an important cause of symptomatic epilepsy especially in the elderly. Seizures in the setting of stroke will furthermore worsen the prognosis of stroke. Studies show that the frequency of seizures in stroke ranges between 2.