Rescue therapies in epilepsy

Purpose of review The purpose of this review is to provide a succinct evaluation of the current rescue medications and action plans available to our patients with seizure clusters in the outpatient setting. Recent findings The main themes of the recent findings are that rescue medications and seizure action plans (SAPs) are underutilized, particularly in the adult population. The safety and efficacy of intranasal midazolam and intranasal diazepam is comparable with rectal diazepam for the treatment of seizure clusters. Additionally, this intranasal formulation has the benefit of a more socially acceptable route of administration and ease of use. The implication of these findings is a greater variety and awareness in the rescue medications available to our patients suffering from seizure clusters

Rescue therapies for seizure clusters: Pharmacology and target of treatments

The primary goal of treatment for seizure clusters is cessation of the cluster to avoid progression to more severe conditions, such as prolonged seizures and status epilepticus. Rescue therapies are key components of treatment plans for patients with seizure clusters. Three rescue therapies are approved in the United States for the treatment of seizure clusters: diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray. This review characterizes the pharmacological function of rescue therapies for seizure clusters, as well as describing γ‐aminobutyric acid A (GABAA) receptor functions. GABAA receptors are heteropentamers, consisting primarily of α1‐6, β1‐3, γ2, and δ subunits in the central nervous system. These subunits can traffic to and from the membrane to regulate membrane potential. Benzodiazepines, such as diazepam and midazolam, are positive allosteric modulators of GABAA receptors, the activation of which leads to an increase in intracellular chloride, hyperpolarization of the cell membrane, and a reduction in excitation. GABAA receptor subunit mutations, dysregulation of trafficking, and degradation are associated with epilepsy. Although benzodiazepines are effective GABAA receptor modulators, individual formulations have unique profiles in practice. Diazepam rectal gel is an effective rescue therapy for seizure clusters; however, adults and adolescents may have social reservations regarding its administration. Intranasal delivery of midazolam or diazepam is a promising alternative to rectal administration because these formulations offer easy, socially acceptable administration and exhibit a rapid onset. Off‐label benzodiazepines, such as orally disintegrating lorazepam and intranasal use of an intravenous formulation of midazolam via nasal atomizer, are less well characterized regarding bioavailability and tolerability compared with approved agents

Epilepsy Seizure Clusters: Therapeutic Advances and Emergency Plans

Many patients with epilepsy experience seizure clusters, which have consequences such as problems at school or work and decreased quality of life. However, according to the Seizure Cluster Burden of Illness US Study, only one-third of patients report having a seizure emergency plan. Research also suggests that patients and caregivers often respond differently to emergency situations than their clinicians recommend. Multiple options are available for the acute treatment of seizure clusters, and newer nasal spray formulations can easily be used. Seizure Action Plans and Acute Emergency Seizure Action Plans provide direction that may alleviate fear and hospitalization, benefitting the patient and caregiver and the health care system

Consciousness of seizures and consciousness during seizures: Are they related?

Recent advances have been made in the network mechanisms underlying impairment of consciousness during seizures. However, less is known about patient awareness of their own seizures. Studying patient reports or documentation of their seizures is currently the most commonly utilized mechanism to scientifically measure patient awareness of seizures. The purpose of this review is to summarize the available evidence regarding the accuracy of patient seizure counts and identify the variables that may influence unreliable seizure reporting. Several groups looking at patient documentation of seizures during continuous EEG monitoring show that patients do not report as many as 50% of their seizures. These studies also suggest that seizures accompanied by loss of consciousness, arising from the left hemisphere or the temporal lobe, or occurring during sleep are associated with significantly reduced reporting. Baseline memory performance does not appear to have a major influence on the accuracy of seizure report. Further prospective studies using validated ictal behavioral testing as well as using correlation with newer electrophysiological and neuroimaging techniques for seizure localization are needed to more fully understand the mechanisms of underreporting of seizures. Better methods to alert caregivers about unrecognized seizures and to improve seizure documentation are under investigation. This article is part of a Special Issue entitled Epilepsy and Consciousness. •We summarized past studies assessing the accuracy of patient's seizure documentation.•Work to date has shown that patients fail to report 30–50% of their seizures.•Impairment of consciousness is an important factor that influences seizure report.•Seizure location and preictal vigilance state may also affect the reliability of seizure counts

Cannabidiol for Epilepsy: New Hope on the Horizon?

Epilepsy is a common neurologic disorder; it is estimated that ∼50million people are affected worldwide. About one third of those patients are drug resistant, defined as failure to stop all seizures despite adequate trials of at least 2 appropriate medications. There has been an enormous interest in developing antiepileptic drugs with novel mechanisms of action. This review discusses the evidence supporting the anticonvulsant properties of cannabis in humans, focusing on cannabidiol. We begin by exploring the early and somewhat anecdotal evidence that was recently replaced by high-quality data from randomized controlled studies, which subsequently led to the US Food and Drug Administration approval of a purified cannabidiol extract for the treatment of 2 highly refractory pediatric epilepsy syndromes (Dravet and Lennox-Gastaut)

The unmet need for rapid epileptic seizure termination (REST)

•Rapid epileptic seizure termination (REST) treatment aims to abort an ongoing seizure.•Current outpatient rescue medications have not been sufficiently studied as REST treatment.•Successful REST medication requires IV-like pharmacokinetics.•Novel drug delivery systems suitable for REST treatment are in development. Approximately 40% of epilepsy patients will continue to experience breakthrough seizures despite stable antiepileptic drug regimens. Rescue treatments have demonstrated efficacy and safety for select seizure emergencies. Outpatient administered intranasal and rectally delivered medications are regulatory approved for acute repetitive seizures (ARS), and injectable benzodiazepines are indicated for parenteral treatment of established status epilepticus. Despite these advances, no studies have been shown to abort an ongoing seizure following patient or caregiver home administration of therapy at the first clinical sign of seizure onset. Such treatment would require rapid systemic absorption without intravenous access, and evidence of seizure cessation within minutes of administration that is superior to placebo (eg, seizure self-regulation). Rapid epileptic seizure termination (REST) treatment may apply to multiple seizure emergencies beyond ARS, including focal or generalized seizures preceded by an aura, flurries of absence or myoclonic seizures, or prolonged focal and generalized seizures at high risk of progression to status epilepticus. Novel investigational drug delivery systems have demonstrated feasibility of intraictal delivery and seizure cessation by two minutes. Ongoing randomized trials of REST treatment for diverse seizure emergencies hold the potential to decrease bouts of mental and physical incapacitation in patients with drug-resistant epilepsy

Seizure clusters: A common, understudied and undertreated phenomenon in refractory epilepsy

Epilepsy is widely prevalent globally and has emerged as a well-studied neurological condition in the recent past. Seizure clusters, a type of seizures, and several aspects pertaining to the etiopathogenesis and management of clusters are yet to be elucidated. This review is an attempt to recapitulate the current understanding of seizure clusters based on the research that has been performed on seizure clusters. This article will provide a comprehensive review of various aspects of clusters, and discusses definitions, prevalence, risk factors, impact on quality of life, approved treatment modalities, and recent advances in management

Assessment of Treatment Side Effects and Quality of Life in People with Epilepsy

Epilepsy impairs quality of life in physical, psychological, cognitive, social, and occupational domains. In people who are not seizure free, depression and adverse medication effects have a predominant role in determining quality of life. The assessment of these factors and other comorbidities is essential for maximizing quality of life in epilepsy. There are multiple tools available to assess medication effects and quality of life in a structured format. Such tools can provide superior assessments and allow clinicians to have a greater impact on their patients' quality of life