Catatonia and epilepsy: An underappreciated relationship.

Catatonia is currently conceived in the major diagnostic manuals as a syndrome with a range of possible psychiatric and general medical underlying conditions. It features diverse clinical signs, spanning motor, verbal and behavioural domains and including stupor, catalepsy, mutism, echolalia, negativism and withdrawal. The existing literature suggests that seizure activity may underlie catatonia in approximately 2% of cases. There are three possible temporal relationships between catatonia and seizure activity: (1) ictal catatonia, in which catatonia is a presentation of non-convulsive status epilepticus; (2) postictal catatonia, in which catatonia follows a seizure, and (3) interictal catatonia, in which catatonia and seizures occur in the same individual without any clear temporal relationship between them. Electroencephalographic (EEG) abnormalities are common in catatonia, even in those cases with a presumed primary psychiatric origin, and often consist of generalised background slowing. Paradoxically, electroconvulsive therapy is an effective treatment for catatonia. There are several converging pieces of evidence suggesting that there may be underlying seizure activity in more cases of catatonia than has hitherto been recognised, though identification of these seizures may require intracranial EEG recording.

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.

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. He also described the epileptic voice sign, wrote psychobiographies of among others Abraham Lincoln and Napoleon Bonaparte, and published a book of poetry. He held many important positions in American professional societies and yet was embroiled in controversy.

What is status epilepticus and what do we know about its epidemiology?

Epidemiological studies across medical conditions share many similar difficulties relating, for instance, to selection bias, defining a population frame, statistical power and adequate documentation. However, in the case of status epilepticus there are, in addition to these, a variety of specific issues that pose significant hurdles to accurate investigation - not least defining status epilepticus itself and determining whether it is simply a severe manifestation of epilepsy or should be considered a distinct entity in its own right. In this paper, we present a historical overview of how opinions about status epilepticus have changed with time, outline some of the issues unique to the study of status epilepticus and provide personal perspectives on certain controversies within this important area of epileptology. This article focuses on adult status epilepticus as paediatric status epilepticus has been covered in a separate Seizure special edition. With a focus on status epilepticus in adults, we review salient population based studies, exploring their advantages and limitations. While it can be difficult to draw conclusions from these studies, it does seem that status epilepticus is more common in African-Americans, males and in either young children or older adults. Given demographic changes resulting in an ageing population, the incidence of status epilepticus is therefore likely to rise. We illustrate how the majority of work performed to date has been in convulsive status epilepticus and demonstrate that more needs to be done to better understand nonconvulsive status epilepticus as well as to further refine the boundaries of status epilepticus as a whole. Despite status epilepticus being common and associated with significant morbidity, our knowledge of the true epidemiology of this condition remains far from complete.

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".

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 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".

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. DATA SOURCE: This systemic review and meta-analysis on studies focused on the mortality of convulsive status epilepticus was conducted by searching MEDLINE, Embase, PsychINFO, CINAHL Plus, and the Cochrane Database of Systematic Reviews between January 1, 1990, and June 30, 2017. STUDY SELECTION: Studies were excluded if they had fewer than 30 participants (<20 for refractory SE), were limited to SE of single specific etiology or an evaluation of a single treatment modality, or were studies of nonconvulsive SE. DATA EXTRACTION AND SYNTHESIS: Data were abstracted and their quality was assessed via a modified Newcastle-Ottawa scale independently by 2 reviewers (A.N. and T.D.G.) using the Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines. Data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES: The main outcome measure was in-hospital mortality or 30-day case fatality expressed as proportional mortality. RESULTS: Sixty-one studies were included in the analysis. The pooled mortality ratios were 15.9% (95% CI, 12.7-19.2) for adult studies, 13.0% (95% CI, 7.2-19.0) for all-age population studies, 3.6% (95% CI, 2.0%-5.2%) for pediatric studies, and 17.3% (95% CI, 9.8-24.7) for refractory SE studies, with very high between-study heterogeneity. We found no evidence of a change in prognosis over time nor by the definition of SE used. CONCLUSIONS AND RELEVANCE: The mortality of convulsive SE is higher in adults than in children and there was no evidence for improved survival over time. Although there are many explanations for these findings, they can be explained by aetiology of SE being the major determinant of mortality. However, there are potential confounders, including differences in case ascertainment and study heterogeneity. This meta-analysis highlights the need for strict international guidelines for the study of this condition.

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.