Patients with epilepsy can experience seizure clusters (acute repetitive seizures), defined as intermittent, stereotypic episodes of frequent seizure activity that are distinct from typical seizure patterns. There are three FDA-approved rescue medications, diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray, that can be administered to abort a seizure cluster in a nonmedical, community setting. Despite their effectiveness and safety, rescue medications are underutilized, and patient/caregiver experiences and perceptions of ease of use may constitute a substantial barrier to greater utilization.
The literature on rescue medications for seizure clusters is reviewed, including the effectiveness and safety, with an emphasis on ease and timing of treatment and associated outcomes. Barriers to greater utilization of rescue medication and the role of seizure action plans are discussed.
Intranasal rescue medications are easier to use and can be administered more rapidly than other routes (rectal, intravenous). Importantly, rapid administration of intranasal rescue medications has been associated with shorter durations of seizure activity as compared with rectal/intravenous routes. Intranasal rescue medications are also easy to use and socially acceptable. These factors potentially remove or reduce barriers to use and optimize the management of seizure clusters.

Seizure emergencies and potential emergencies, ranging from seizure clusters to prolonged seizure and status epilepticus, may affect adults with epilepsy despite stable antiseizure therapy. Seizure action plans (SAPs) are designed for patients and their caregivers/care partners to provide guidance on the individualized treatment plan, including response to potential seizure emergencies and appropriate use of rescue therapy. The use of pediatric SAPs is common (typically required by schools), however, most adults with epilepsy do not have a plan. Patient-centered action plans are integral to care for other chronic conditions and may offer insights applicable to the care of adults with epilepsy. This review analyzes the potential benefits of action plans for medical conditions by exploring their utility in conditions such as asthma, diabetes, chronic obstructive pulmonary disease, heart disease, and opioid overdose. Evidence across these conditions substantiates the value of action plans for patients, and the benefits of adult SAPs in epilepsy are emerging. Because wide implementation of SAPs has faced barriers, other conditions may provide insights that are relevant to implementing SAPs in epilepsy. Based on these analyses, we propose concrete steps to improve the use of SAPs among adults. A recent consensus statement promoting the use of formal SAPs in epilepsy and advances in rescue therapy delivery methods provides support to engage patients around the value of SAPs. The precedent for use of SAPs for pediatric epilepsy patients serves as the foundation to support increased usage in adults. Seizure action plans in the context of improved clinical outcomes are expected to reduce healthcare utilization, improve patient quality of life, and optimize epilepsy management.

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.

The number and type of therapies available to treat seizure clusters (SCs) or periods of increased seizure activity have risen in recent years. Gaps still exist on defining SCs, when to use them, and educating patients and families. The Epilepsy Foundation developed and published expert-derived consensus on preferred practices for rescue therapies (RTs), 79% of which were agreed upon by a larger group of healthcare professionals (HCPs). This paper describes insights from people with epilepsy (PWE) and families/caregivers (FCGs) on these practices to assess similarities and trends between PWE, FCGs, an expert panel, and HCPs.
Online survey including expert-derived preferred practices for RT was completed by a convenience sample of 176 PWE/FCGs. Respondents rated agreement with each preferred practice using a 0-8 point Likert scale. Results were examined by relationship to epilepsy, prior use of RTs, and comparison to the expert panel and larger group of HCPs.
41.5% of respondents were PWE and 54.6% were FCGs; 70% represented PWE age 18 and over or those who cared for adults with epilepsy. Levels of agreement were similar to those of HCPs - consensus was obtained on 79% of preferred practices. Differences were noted on which items achieved consensus and strength of consensus for some items. Differences between PWE and FCG, and between those who had and had not previously used a RT were found. A proposed definition of SCs did not reach consensus, but there was strong consensus for individualized seizure action plans and more RT education.

Disease-related treatment action plans for acute exacerbations providing information that may be helpful for self-management for patients and caregivers are commonly used for chronic conditions such as asthma and diabetes. However, among patients with epilepsy, a review of the literature suggested that the majority did not have an action plan in place for acute seizure treatment.
Currently, there is a lack of unified guidance on seizure action plans (SAPs) in the literature. In the authors\' opinion, available formats have limitations for practical use and may not be easily customizable to individual patients, and they are not often designed to provide simple-to-follow steps for rapid immediate steps to determine and initiate appropriate treatment of seizure emergencies. Our group reviewed current examples of SAPs and provided guidance on the development of acute seizure action plans (ASAPs) designed to facilitate rapid, appropriate acute care in the community and to be as useful as possible for a wide range of care partners, including those with limited experience.
This paper provides agreed upon expert opinion recommendations and considerations for goals, development process, types of content, and format for an ASAP.

Some of the most difficult issues in the care of people living with epilepsy (PWE) regard the definition, treatment, and communication of unexpected increase(s) in seizure frequency over a relatively short duration of time. In order to address this issue, the Epilepsy Foundation established the Rescue Therapy Project in Epilepsy to understand the gaps, needs, and barriers facing people with epilepsy who use or may benefit from rescue therapies (RTs) for \"seizure clusters\". The intent was to provide consensus-derived recommendations from a broad stakeholder group including PWE, their caregivers, epilepsy specialist physicians, nurses, pharmacists, and representatives of epilepsy & neurology advocacy and professional organizations.
During Phase 1, a group of epilepsy experts and stakeholders (N = 54) were divided into 3 workgroups that met by conference calls and in-person. Content of workgroups was developed into preferred practices related to RTs. In Phase 2, these recommendations were evaluated by a larger more diverse group of healthcare professionals, PWE, and caregivers. Agreement with recommended preferred practices at 80% or greater was set as the level to achieve consensus.
The preferred practices were centered around four core themes identified by the experts and key stakeholders: the importance of a common language; when RTs should be prescribed; assessing the need for RTs; and education/communication about RTs. Consensus from experts and key stakeholders was reached for 27 recommended preferred practices using the Delphi method. \"Rescue therapy\" or \"rescue medicine\" was the preferred term to describe what to name a treatment intervention in this context, and seizure action plans was the preferred term to communicate how to respond to a seizure or SCs and the use of RTs. In Phase 2, 23 of the recommendations reached final consensus, including the need for a common language, and the need to consider RTs and seizure action plans in all PWE in an individualized manner, several circumstances in which RTs should be prescribed, and the importance of education regarding RTs and SAPs.

Quality measures have highlighted the need for efficient treatment of status epilepticus. One strategy is prevention of refractory status epilepticus through individualized seizure action plans. As a quality improvement project, we implemented a standardized seizure action plan to improve the delivery of key information to families of children with seizures.
We implemented our standardized seizure action plan using plan-do-study-act cycles. The plans were distributed to caregivers of children (zero to 18 years) seen for seizures in outpatient neurology clinics. Families were given questionnaires at the beginning of each visit to gauge their understanding of their child\'s diagnosis, treatment, and comfort in emergency seizure management. Provider utilization rates and questionnaire responses were analyzed over time to assess the effectiveness of the action plan.
Provider utilization rates of the standardized seizure action plan improved from 0% to 58.1%. At baseline, 31.5% caregivers indicated that they did not know their child\'s epilepsy syndrome or seizure type, 29.6% did not know the emergency protocol at their child\'s school, 9.2% did not know when to consider a seizure an emergency or what to do if their child\'s seizure had become an emergency, and 17.5% were not comfortable administering rescue medication. Caregivers who received the action plan had improved responses at subsequent visits (P < 0.001), whereas those who did not receive the standardized form did not improve.
Standardizing provision of seizure action plans in pediatric neurology clinic can improve key elements of caregiver education regarding epilepsy diagnoses and seizure emergencies.

To assess how pediatric neurologists prescribe home seizure rescue medications to treat acute prolonged seizures and clusters of seizures in children.
A brief, email survey was sent to the members of the Pediatric Epilepsy Research Consortium assessing seizure rescue medication prescribing practices for patients of different age groups, cognitive abilities, and seizure type. Survey responses were anonymous.
Thirty-six respondents (of 76 surveyed; 47% response rate) completed the survey. Rectal diazepam was the most commonly chosen rescue medication for a prolonged convulsive seizure in a severely developmentally delayed 16-year-old (44%) and typical and delayed 7-year-old (44% and 61%, respectively), 3-year-old (78% and 86%, respectively), and 9-month-old (83%) patients. Most responders (69%) indicated that developmentally typical 16-year-olds would be prescribed intranasal midazolam. For clusters of seizures, clonazepam orally disintegrating tablets were the most frequent first-line option in all age groups, except developmentally delayed 3-year-old and 9-month-old children, for whom rectal diazepam was chosen more commonly. Medication dosing generally followed standard dosing guidelines with very few exceptions.
Rectal diazepam remains the most frequently used rescue medication for prolonged seizures for nearly all age groups, except in developmentally typical teenagers, for whom intranasal midazolam is used more often. Clonazepam orally disintegrating tablets are the most frequently used medication for treatment of clusters of seizures, except in younger patients. Further work is necessary to establish best practices for type and administration route of seizure rescue medications.

Seizure action plans help patients and caregivers better self-manage their epilepsy. We hypothesized that providing pediatric patients and their caregivers with a seizure action plan would reduce unplanned health care utilization and decrease the impact of epilepsy.
We developed a seizure action plan for use in pediatric epilepsy patients. A prospective cohort was randomly assigned to receive a seizure action plan in addition to standard epilepsy care or to standard epilepsy care alone. All caregivers were surveyed using the Modified Impact on Families (MIF) questionnaire at enrollment, 3 months, and 12 months. Health care utilization measures and Modified Impact on Families questionnaire scores were compared between the 2 groups.
Fifty-four patients received a seizure action plan and standard care, whereas 48 received standard care alone. The groups had similar demographics. There was a significantly higher proportion of overall clinic appointment no shows in the standard care group vs the seizure action plan group (P = .04); however, other significant differences in health care utilization were not found. Among patients with low seizure frequency (12 or fewer seizures per year), Seizure comfort scores on the Modified Impact on Families questionnaire were significantly higher at 12 months among the seizure action plan group compared to the standard care group.
Caregivers for patients with epilepsy receiving a seizure action plan were more comfortable regarding seizure care and missed fewer appointments. However, differences in health care utilization were not present. The seizure action plan appears to have more impact in patients who experience lower seizure frequencies. Further studies evaluating the impact as well as assessing caregivers\' perceptions of the seizure action plan using a larger sample are needed.

OBJECTIVE: To summarize definitions, prevalence, risk factors, consequences, and acute management of seizure clusters using rescue medications.
METHODS: We searched MEDLINE for studies that assessed definitions, clinical characteristics, outcomes, and use of rescue medication for aborting seizure clusters.
RESULTS: Different clinical and statistical definitions for seizure clusters have been proposed, including: ≥3 seizures in 24 h, ≥2 seizures in 24 h, and ≥2 seizures in 6 h. Most studies of seizure clusters have been conducted in tertiary epilepsy centers, with refractory epilepsy patients. Patients with severe and poorly controlled epilepsy are more likely to experience seizure clusters. Seizure clusters can result in increased health care utilization and have negative impact on the quality of life of patients and caregivers. Use of benzodiazepine rescue medications in acute management of seizure clusters can help avoid progression to status epilepticus and reduce emergency room visits. Rescue medications are underutilized in seizure clusters. Currently, rectal diazepam gel is the only FDA approved rescue medication for seizure clusters. In addition, buccal midazolam is approved in European countries for treatment of prolonged seizures. However, various non-rectal non-IV benzodiazepines are safe and effective in treating acute seizures and clusters. Most patients and caregivers preferred non-rectal routes.
CONCLUSIONS: Identifying patients that are at high risk for seizure clusters, providing them with formal action plans and educating them about use of rescue medication for seizure clusters can help ameliorate the outcomes in this group of epilepsy patients.