Twelve landmarks in the treatment of status epilepticus.

Status epilepticus was a term which first appeared in the medical literature in 1824. In the 200 years that have passed since, treatment has undergone many changes. In this paper, 12 landmarks in the treatment of status epilepticus over this period are briefly described. This paper was presented at the 9th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures, in London in April 2024.

Is NORSE a meaningful clinical entity?

This article summarises the arguments for and against the proposition, debated at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures, that: 'NORSE is a meaningful clinical entity'. Here the two sides of the argument are briefly presented. This article is published as part of the special issue of Epilepsy & Behavior which are the proceedings of the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures.

Psychoanalytical concepts of epilepsy.

As part of the anniversary issue of Epilepsy & Behavior looking back as aspects of the history of epilepsy, this article reviews psychoanalytical concepts of the pathogenesis of seizures and the so-called epileptic personality (epileptic constitution). It addresses the question whether these theories are completely invalid or do they have insights that are worth rediscovering. Special Issue: Epilepsy & Behavior's 20th Anniversary.

The seventh London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures.

The 7th London-Innsbruck Colloquium on Status Epilepticus was held in London on 7-9 April 2019, with a faculty of 47 clinicians and scientists from 16 countries and a total of 401 delegates from 41 countries. This paper is an introduction to the proceedings of the colloquium, and outlines the recent developments in status epilepticus which formed the core of colloquium program in the areas of 1. basic science; 2. clinical description, etiology, and investigation; and 3. treatment. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

The anesthetic drug treatment of refractory and super-refractory status epilepticus around the world: Results from a global audit.

Multinational and multicenter registries collecting cases of refractory and super-refractory status epilepticus help to understand what the current practice in the treatment of such conditions is and can improve the rational therapy. We prospectively collected 776 cases of refractory status epilepticus requiring continuous intravenous anesthetic drugs in an intensive care unit setting, through online questionnaires compiled by the treating physicians in 50 countries. Initiation of an intravenous anaesthetic drug was relatively delayed in middle-income compared with high-income countries. There were marked regional differences in the choice of initial intravenous anaesthetic drug. Generally, midazolam was the most commonly used initial anesthetic drug (56%), followed by propofol (35%), in Europe, propofol was preferred over midazolam. In addition to anesthesia, 26% of cases received some form of immunosuppression (with corticosteroids and/or intravenous immunoglobulin). In this observational study, outcome was not affected by choice or sequence of anesthetic drugs, and nor was the use of barbiturate anesthetics associated with poorer outcome. The proportion of patients responding to cycles of different anaesthetic drugs was high even after failure of the earlier anesthetics, but the neurological outcome progressively worsened the longer anaesthetic drugs were needed and the longer the status epilepticus continued. However, even in the 158 patients who required three or more different anaesthetic trials, 49% had seizure control on tapering the third anesthetic, and 20% had a good neurological outcome anywhere. For these reasons we believe that it is important to persist with therapy in patients who are intractable initially, especially as etiology, not the number of duration of anesthesia, is the primary determinant of prognosis. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Regulatory aspects of status epilepticus.

In this article, we consider four aspects of the regulatory standing of status epilepticus and the difficulties these raise in relation to trials and licensing. These formed the basis of a discussion held at the 6th London?Innsbruck Colloquium on Status Epilepticus, held on April 6, 2017.

Etiologies and characteristics of refractory status epilepticus cases in different areas of the world: Results from a global audit.

To describe the demographics, etiologies, types of status epilepticus (SE), and outcomes in people with refractory and super-refractory SE from around the world, we prospectively collected cases of refractory SE (RSE) treated with continuous intravenous anesthetic drugs in an intensive care unit setting through online questionnaires using "active surveillance." We collected information about 776 cases of RSE in 50 countries over 4 years. Control of SE was achieved in 74% of the cases. Neurologic outcomes were poor in 41% of patients, and 24% died. Good outcome was associated with younger age and a history of epilepsy. Etiology strongly influenced the outcome. Patients from Asia were younger, more frequently presented with convulsive SE, and were more frequently affected by infectious etiologies when compared with patients from Europe and the Americas. Despite these differences, outcomes were similar in all countries. Demographics of patients with RSE in a global audit are similar to those in prior single center series, providing evidence of generalizability of those studies. Important differences exist among patients with RSE from different regions of the world, but these do not seem to significantly influence patient outcomes.

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. METHODS: Each AED is evaluated using five criteria: (1) efficacy, by seizure type (a: PGTCSs and b: SGTCSs); (2) adverse effects; (3) interactions; (4) adherence and dosing; and (5) mechanism of action (MOA). To ensure the inclusions of robust data, only efficacy data accepted by regulatory authorities were considered, and data related to adverse effects, interactions, adherence, and MOA were all extracted from UK Summaries of Product Characteristics (SPCs). RESULTS: (1a) There is class 1 evidence of the efficacy of only four AEDs in controlling PGTCSs (lamotrigine, levetiracetam, perampanel, and topiramate). (1b) There is no class 1 evidence of the efficacy of any AED in SGTCSs although some evidence from pooled/subgroup analyses or meta-analyses supports the use of the four AEDs (levetiracetam, perampanel, topiramate, and with less robust data for lamotrigine). (2) AEDs are associated with different, but to some extent overlapping, common adverse effect profiles but have differing idiosyncratic adverse effects. (3) Pharmacokinetic interactions are seen with most, but not all, AEDs and are most common with carbamazepine and phenytoin. (4) Good adherence is important for seizure control and is influenced by frequency of dosing, among other factors. (5) Mechanism of action is also a consideration in rationalising AED selection when switching or combining AEDs. CONCLUSION: Ultimately, the choice of AED depends on all these factors but particularly on efficacy and adverse effects. Different patients will weigh the various factors differently, and the role of the treating physician is to provide accurate information to allow patients to make informed choices.

Recent advances in status epilepticus.

PURPOSE OF REVIEW: This review discusses advances in the understanding of the mechanisms of status epilepticus and its current treatment approaches. Many of these have been topics at the 5th London-Innsbruck Colloquium on status epilepticus 2015. RECENT FINDINGS: A new definition and classification of status epilepticus was proposed, which is expected to improve treatment and stimulate research. A better understanding of the failure of seizure suppressing mechanisms and the initiation of self-sustaining seizures begins to translate into the clinical arena. Drugs, such as allopregnanolone, cannabinoids, sec-butylpropylacetamide and valnoctamide, may better target these seizure-perpetuating mechanisms. The concept of combinatorial treatments has further developed, but yet trials in humans are lacking. A new prognostic outcome-score and electroencephalography-criteria for nonconvulsive status epilepticus are ready for clinical use. Alternative routes, such as intranasal or buccal, have been explored in a number of trials suggesting that intramuscular midazolam is at least as effective as intravenous lorazepam and buccal or intranasal midazolam is at least as effective as rectal diazepam. SUMMARY: Despite progress in basic science, translation into the clinical field remains difficult. There is hope, that the two large phase III studies in the established and refractory status that started recruitment in 2015 will better inform the clinicians in this emergency situation.

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. We investigated seizure outcome and survival in people presenting with a single seizure and in those presenting with >2 seizures (epilepsy). RESULTS: 695 people (median follow-up 23.6 years) had unprovoked epileptic seizures. For seizure analysis we excluded 38 people with missing data leaving 657 (309 male, and 249 aged <18 years). Seizures recurred in 67%. The 354 people with epilepsy were only slightly more likely to have further seizure recurrence than the 302 people with a single seizure at presentation (HR 1.32, 95% CI 1.09 to 1.59). In 327 people with complete follow-up, 268 (82%, 95% CI 77% to 86%) were in terminal remission; (80%, (95% CI 73% to 85%) in those with epilepsy at presentation). Premature mortality was increased in people with epilepsy (standardised mortality ratio 1.67; 95% CI 1.40 to 1.99) and those with a single seizure at presentation (standardised mortality ratio 2.65; 95% CI 2.23 to 3.15). It is also high in those with early remission. CONCLUSIONS: People with epilepsy and with single seizures at presentation in the community generally have good prognosis for seizure control with prolonged follow-up. The risk of premature mortality is significantly increased in both groups.

A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus.

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 of SE is 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 (t1 at 5 min and t2 at 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 of SE, but as knowledge and understanding increase, time points can be defined for specific forms of SE based on scientific evidence and incorporated into the definition, without changing the underlying concepts. A new diagnostic classification system of SE is 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 of SE divided into those with prominent motor systems, those without prominent motor systems, and currently indeterminate conditions (such as acute confusional states with epileptiform EEG patterns). Axis 2 (etiology) is divided into subcategories of known and unknown causes. Axis 3 (EEG correlates) adopts the latest recommendations by consensus panels to use the following descriptors for the EEG: 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.

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. A survey was then carried out among a total of 110 adults with epilepsy. Participants were asked to complete questionnaires inquiring into their beliefs about the causes and range of treatments used for epilepsy. Each participant was allowed to choose more than one cause and more than one treatment method. The questionnaires were administered face to face by a clinical psychologist (HAA) to improve the quality of the responses. RESULTS: We found that most adults with epilepsy in Saudi Arabia believe that epilepsy is a condition with multifactorial causation and for which more than one treatment method should be applied. A test from God was the most commonly ascribed cause (83% as well as 40% who believed that some cases of the illness were a punishment from God). The belief in the concept of God's will helped many in the cohort to accept their illness as part of their destiny. Ninety-six percent of the patients believed that there were also medical causes (such as an illness, brain insult, inflammation, heredity, contagion), and a similar proportion believed that there were also religious causes. Smaller proportions believed epilepsy could be due to cultural (78%) or psychosocial causes (64%). Thirty-four percent of people believed that there could be sometimes no cause, but only 2% thought that epilepsy never had any identifiable cause. Most patients did not believe that one treatment alone would help. Ninety-three percent of patients believed in medical treatment, 93% in religious treatment, and 64% in traditional treatments, and 7% believed in changing lifestyle (eating balanced food and positive thinking). Seventy-eight percent of the sample believed that their epilepsy was a curable illness. Ninety-six percent believed that faith and practicing religious rituals helped in coping with epilepsy, and 92% believed that family support helped in coping with epilepsy. Nine percent of patients had stopped their medication for religious reasons or because of a sense of shame, and 7% had at one time been forced by their family to stop their medication. Ninety-two percent of the sample reported having enough family support. Ninety-five percent believed that Saudi society needs more awareness to understand epilepsy. CONCLUSION: In Saudi Arabia, religious and cultural beliefs about the causes and treatment of epilepsy exist alongside medical beliefs. The holding of religious beliefs, the practicing of religious rituals, and the presence of family support were found to be of great importance in coping with epilepsy, and their role needs to be fully appreciated in the medical management of the condition.

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.

The evolution of epilepsy theory and practice at the National Hospital for the Relief and Cure of Epilepsy, Queen Square between 1860 and 1910.

In the years between 1860 and 1910, a revolution in epilepsy theory and practice occurred. The National Hospital for the Relief and Cure of the Paralysed and the Epileptic at Queen Square in London was at the center of this revolution. A series of remarkable physicians and surgeons were appointed to the staff. The four greatest were John Hughlings Jackson, Sir David Ferrier, Sir Victor Horsley, and Sir William Gowers. Their lasting contribution to epilepsy is discussed. Other physicians who made notable contributions to epilepsy were Jabez Spence Ramskill, Charles Eduard Brown-Séquard, Charles Bland Radcliffe, Sir John Russell Reynolds, Sir Edward Henry Sieveking, Walter Stacy Colman, and William Aldren Turner. At the hospital in this period, amongst the lasting contributions to epilepsy were the following: the development of a new conceptual basis of epilepsy, the development of a theory of the physiological structure of the nervous system in relation to epilepsy, the demonstration and investigation of cortical localization of epileptic activity, the establishment of the principle of focal epilepsy and the description of focal seizure types, the discovery of the first effective drug treatment for epilepsy (bromide therapy, indeed one of the first effective drug treatments in the whole of neurology), and the performance of the first surgical operation for epilepsy. This paper is based on the 2013 Gowers Memorial Lecture, delivered in May 2013.

The concept of symptomatic epilepsy and the complexities of assigning cause in epilepsy.

The concept of symptomatic epilepsy and the difficulties in assigning cause in epilepsy are described. A historical review is given, emphasizing aspects of the history which are relevant today. The historical review is divided into three approximately semicentenial periods (1860-1910, 1910-1960, 1960-present). A definition of symptomatic epilepsy and this is followed by listing of causes of symptomatic epilepsy. The fact that not all the causes of idiopathic epilepsy are genetic is discussed. A category of provoked epilepsy is proposed. The complexities in assigning cause include the following: the multifactorial nature of epilepsy, the distinction between remote and proximate causes, the role of nongenetic factors in idiopathic epilepsy, the role of investigation in determining the range of causes, the fact that not all symptomatic epilepsy is acquired, the nosological position of provoked epilepsy and the view of epilepsy as a process, and the differentiation of new-onset and established epilepsy. The newly proposed ILAE classification of epilepsy and its changes in terminologies and the difficulties in the concept of acute symptomatic epilepsy are discussed, including the inconsistencies and gray areas and the distinction between idiopathic, symptomatic, and provoked epilepsies. Points to be considered in future work are listed.

Seizure precipitants (triggering factors) in patients with epilepsy.

AIM: adult epilepsy clinic population: (a) to identify the frequency of seizure precipitants (triggering factors) and their relative frequency in those with psychiatric disorders, and in those in remission or with active epilepsy, differences in frequency with regard to gender, seizure duration, number of drugs taken; (b) to determine which precipitants patients most commonly report; and (c) to identify differences in the distribution of precipitants among generalized, temporal, and extratemporal epilepsies. METHODS: Consecutive patients attending a tertiary-care epilepsy clinic were prospectively and an open personal interview to identify and characterize seizure precipitants. Information about the epilepsy and clinical characteristics of patients was collected during the interview and from medical records. RESULTS: Of 104 patients, 97% cited at least one precipitant. Stress, sleep deprivation, and fatigue were the most frequently reported precipitants. Patients with psychological comorbidities reported a greater percentage of seizures with seizure precipitants. Patients with idiopathic generalized epilepsy seemed to be more sensitive to seizures during awakening and sleep deprivation, patients with extratemporal epilepsy reported more frequent seizures during sleep. There were no differences in frequency or type of seizure precipitants with regard to gender, seizure duration or frequency, and the number of antiepileptic drugs taken. CONCLUSION: The findings may have implications for the better management of epilepsy by increasing a focus on nonpharmacological therapy. The implications of the findings for nosology and causation of epilepsy are also briefly discussed.