Introduction to use of an acute seizure action plan for seizure clusters and guidance for implementation

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.

Section: Discussionmentioning

confidence: 99%

“…Patel and Becker, Introduction to Use of an Acute Seizure Action Plan for Seizure Clusters and Guidance for Implementation76 in this issue). Future studies are needed that examine new drug formulations and routes of administration, as well as drugs that have been used successfully off-label for the treatment of seizure clusters.…”

mentioning

confidence: 99%

Rescue therapies for seizure clusters: Pharmacology and target of treatments

Gidal

Detyniecki

2022

“…The potential benefits of an appropriate response include both stopping progression to status epilepticus and avoiding the need for transport to the hospital, and also improvements in patient safety, social function, and quality of life. 42,43 Current definitions of seizure clusters may fail to identify seizure clusters that do not meet a prespecified threshold and may fail to account for individual variability. 7 The development of an individualized seizure cluster definition that allows for the incorporation of customized variations in the number of seizures and duration, as well as the lived experience and impact, that are specific to the patient may be helpful to enhance awareness and recognition of seizure clusters.…”

Section: Customization and Standardizationmentioning

confidence: 99%

Recognizing seizure clusters in the community: The path to uniformity and individualization in nomenclature and definition

Haut

Nabbout

2022

Seizure emergencies experienced by patients with epilepsy include status epilepticus and seizure clusters. Although an accepted definition of status epilepticus exists, no clear consensus definition of seizure clusters has emerged; this is further complicated by the appearance in the literature of various empirically based definitions that have been developed for clinical trial study designs. In general, patients with intractable epilepsy have been shown to have a significant risk for acute episodes of increased seizure activity called seizure clusters (also referred to as acute repetitive seizures, among other terms) that differ from their usual seizure pattern. Duration (e.g., number of hours or days) is often included in the definition of a seizure cluster; however, the duration may vary among patients, with some seizure clusters lasting ≥24 h and requiring long‐acting treatment for this period. In addition to seizure cluster duration, the time between seizures and possible acceleration in seizure frequency during the cluster may be important variables. The recognition and treatment of seizure clusters require urgent action because episodes that are not quickly and appropriately treated may lead to injury or progress to status epilepticus or potentially death. Most seizure clusters occur outside a medical facility (in the community) and treatment is usually administered by nonmedical individuals; therefore, health care providers may benefit from a clear description of these potential seizure emergencies that they can then use to educate patients and caregivers on the prompt and appropriate identification of seizure clusters and administration of rescue therapy. Here we explore why greater uniformity is needed in the discussion of seizure clusters. This exploration examines epidemiologic studies of seizure clusters and status epilepticus, inconsistencies in nomenclature and definitions for seizure clusters, practical application of seizure cluster terminology, and the potential use of acute seizure action plans and patient‐specific individualized definitions in the clinical setting.

“…8 See Patel and Becker, Introduction to Use of an Acute Seizure Action Plan for Seizure Clusters and Guidance for Implementation in this supplement for more details regarding ASAPs. 68 In facilities that care for people with epilepsy who also have intellectual disabilities, direct, easyto-understand instructions for seizure cluster care like those found in an ASAP could improve recognition of patientspecific manifestations (e.g., types of seizures that are likely to represent the initial seizure in a cluster), shorten response times for treatment, and reinforce optimal response and care provided by multiple staff members, including support staff with limited medical training. In the community setting, some adult patients may be familiar with seizure first aid, but their care partners may benefit from written specific and comprehensive guidance.…”

Section: Management and Selfmanagement Of Seizure Clustersmentioning

confidence: 99%

“…SAPs provide instructions related to seizure care and management (rescue and daily medications) as well as detailed patient and contact information, whereas an ASAP is concisely focused on the rescue protocol and provides emergency procedures 8 . See Patel and Becker, Introduction to Use of an Acute Seizure Action Plan for Seizure Clusters and Guidance for Implementation in this supplement for more details regarding ASAPs 68 . In facilities that care for people with epilepsy who also have intellectual disabilities, direct, easy‐to‐understand instructions for seizure cluster care like those found in an ASAP could improve recognition of patient‐specific manifestations (e.g., types of seizures that are likely to represent the initial seizure in a cluster), shorten response times for treatment, and reinforce optimal response and care provided by multiple staff members, including support staff with limited medical training.…”

Section: Impact: Clinical Perspectivementioning

confidence: 99%

Consequences: Bench to home

Long

Dixon‐Salazar²

2022

Seizure clusters (also referred to as acute repetitive seizures) consist of several seizures interspersed with brief interictal periods. Seizure clusters can break down γ‐aminobutyric acidergic (GABAergic) inhibition of dentate granule cells, leading to hyperactivation. Functional changes to GABAA receptors, which play a vital neuroinhibitory role, can include altered GABAA receptor subunit trafficking and cellular localization, intracellular chloride accumulation, and dysregulation of proteins critical to chloride homeostasis. A reduction in neuroinhibition and potentiation of excitatory neurotransmission in CA1 pyramidal neurons represent pathological mechanisms that underlie seizure clusters. Benzodiazepines are well‐established treatments for seizure clusters; however, there remain barriers to appropriate care. At the clinical level, there is variability in seizure cluster definitions, such as the number and/or type of seizures associated with a cluster as well as the interictal duration between seizures. This can lead to delays in diagnosis and timely treatment. There are gaps in understanding between clinicians, their patients, and caregivers regarding acute treatment for seizure clusters, such as the use of rescue medications and emergency services. This lack of consensus to define seizure clusters in addition to a lack of education for appropriate treatment can affect quality of life for patients and place a greater burden on patient families and caregivers. For patients with seizure clusters, the sense of unpredictability can lead to continuous traumatic stress, during which patients and families live with a heightened level of anxiety. Clinicians can affect patient quality of life and clinical outcomes through improved seizure cluster education and treatment, such as the development and implementation of a personalized seizure action plan as well as prescriptions for suitable rescue medications indicated for seizure clusters and instructions for their proper use. In all, the combination of targeted therapy along with patient education and support can improve quality of life.