Development of a self-management tool for individuals with seizure clusters: Trial design and methodological report.

Background: Despite advances in anti-seizure medications (ASMs) for people with epilepsy (PWE), adverse outcomes, negative health events (NHEs), and breakthrough seizures remain common. Rescue medication (RM) can better manage repetitive seizures, but barriers to RM use persist. Self-management for PWE and a history of NHEs (SMART) is an evidence-based epilepsy self-management program aimed at reducing barriers and maximizing facilitators to self-care in high-risk PWE.

Benzodiazepine rescue medication administration for seizure clusters: Real-world retrospective outcomes.

Objective: Benzodiazepine rescue medications are established as therapy for acute termination of seizure clusters. A post-hoc analysis of a clinical trial of seizure cluster treatment with diazepam nasal spray found a potential longer-term impact over a year of treatment. In this retrospective analysis, we tested the hypothesis that benzodiazepine-treated seizure clusters are associated with prolonged time to the next seizure cluster compared with untreated seizure clusters in a patient-reported real-world database.

Immediate Treatment of Seizure Clusters: A Conceptual Roadmap to Expedited Seizure Management.

Some patients with epilepsy continue to have seizures despite daily treatment with antiseizure medications. This includes seizure clusters (also known as acute repetitive seizures), which are an increase in seizure frequency that is different from the usual seizure pattern for that patient. In the literature, the term "rescue" is used for pharmacologic treatment for seizure clusters, but clarity regarding timing or whether a caregiver or patient should wait until a moment of life-threatening urgency before administering the medication is lacking.

Treatment of prolonged seizure with diazepam nasal spray: An exploratory post hoc cohort analysis.

Background: Benzodiazepines are used in first-line rescue therapy as immediate-use seizure medication for the treatment of seizure clusters and prolonged seizures. Their use varies across clinical practices and conditions, and they can be used promptly when indicated. Clinical studies have demonstrated seizure termination within 2 min when diazepam nasal spray is used to treat seizure clusters within 5 min, but the response when treating longer duration seizures in a cluster remains to be characterized.

Short-Term Impact of Seizures and Mitigation Opportunities.

Purpose Of Review: The burden of epilepsy is complex and consists of elements directly related to acute seizures as well as those associated with living with a chronic neurologic disorder. The purpose of this systematic review was to characterize short-term burdens of seizures and to explore the potential value of acute treatments to mitigate these burdens apart from reducing the risk of status epilepticus.

Recent Findings: A systematic literature search was conducted using PubMed to identify articles published from January 1, 2017, to June 22, 2023, that described short-term burdens and acute treatments of seizures.

Diazepam nasal spray administration is effective to control seizure clusters irrespective of time of day.

Introduction: Neurologic circadian influences, including sleep/wake transitions, processes (e.g., hormonal variation), and behavioral patterns (e.

Anticipatory anxiety of seizures in epilepsy: A common, complex, and underrecognized phenomenon?

The diagnosis of epilepsy is associated with loss of predictability, which invariably results in the fear of when and if future seizures will occur. For a subset of patients with epilepsy (PWE), there may be a pathological persistent fear of seizure occurrence, resulting in limitations to daily activities through avoidant behaviors. Paradoxically, the research of anticipatory anxiety of seizures (AAS; also referred to as seizure phobia) has been practically nonexistent and, not surprisingly, this condition remains underrecognized by clinicians.

Benzodiazepines for the Treatment of Seizure Clusters.

Patients with epilepsy may experience seizure clusters, which are described by the US Food and Drug Administration (FDA) as intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient's usual seizure pattern. Untreated seizure clusters may increase the risk for status epilepticus, as well as decrease quality of life and increase burden on patients and care partners. Benzodiazepine therapies are the mainstay for acute treatment of seizure clusters and are often administered by nonmedical care partners outside a healthcare facility.

Taking a Newer, Faster, Intranasal Route: A Narrative Review of Transitioning to a Less-Invasive Rescue Treatment for Seizure Clusters.

In the US, 3 rescue treatment options are approved for patients with seizure clusters (ie, acute repetitive seizures), which are intermittent increases of seizure activity. This narrative PubMed review of these 3 treatments examines newer intranasal options that are well suited for adolescent and adult patients who may desire a transition from rectal treatment. Diazepam rectal gel is indicated for patients ≥2 years, diazepam nasal spray for those ≥6 years, and midazolam nasal spray for those ≥12 years.

Safety and effectiveness of diazepam nasal spray in male and female patients: Post hoc analysis of data from a phase 3 safety study.

Sex differences in drug pharmacokinetics include variations in the expression of the cytochrome P450 enzymes, which are involved in the metabolism of benzodiazepines. It is unclear whether sex influences outcomes associated with intranasally administered drugs. A post hoc analysis of sex differences was conducted to evaluate the effectiveness and safety of diazepam nasal spray, which included examining changes in the number of days between seizure clusters over time (SEIzure interVAL [SEIVAL]).

Alternative Approaches for Addressing Acute Agitation in Schizophrenia and Bipolar Disorder.

The prompt effective treatment of acute agitation among patients with schizophrenia or bipolar disorder can alleviate distressing symptoms for the patient and decrease the risk of escalation to aggression and the potential for serious harm to the patient, health care providers, and others. A commonly used approach for the management of acute agitation has been the intramuscular administration of antipsychotic medications and/or benzodiazepines. However, US Food and Drug Administration-approved treatments with alternative routes of delivery now include inhaled loxapine powder and, more recently, dexmedetomidine sublingual film.

Analyses of patients who self-administered diazepam nasal spray for acute treatment of seizure clusters.

For acute treatment of seizure clusters in patients with epilepsy, intranasal administration of acute seizure therapies has been shown to provide accessibility and ease of use to care partners as well as the potential for self-administration by patients. Diazepam nasal spray (Valtoco®) was approved by the US Food and Drug Administration for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in patients with epilepsy aged ≥6 years. Self-administration consistent with the prescribing information is feasible and was reported by a subgroup of patients (n = 27 of 163) in a long-term phase 3 safety study.

Role of Rho-Associated Kinase in the Pathophysiology of Cerebral Cavernous Malformations.

Cerebral cavernous malformations (CCMs) are vascular lesions characterized by a porous endothelium. The lack of a sufficient endothelial barrier can result in microbleeds and frank intracerebral hemorrhage. A primary mechanism for lesion development is a sequence variant in at least 1 of the 3 CCM genes (, , and ), which influence various signaling pathways that lead to the CCM phenotype.

Rapid Rescue Treatment with Diazepam Nasal Spray Leads to Faster Seizure Cluster Termination in Epilepsy: An Exploratory Post Hoc Cohort Analysis.

Introduction: Although prompt treatment of status epilepticus is standard of care, the effect of timing of rescue therapy administration for seizure clusters in epilepsy remains unknown. Seizure clusters are a rare but clinically important condition, and benzodiazepines are the cornerstone rescue therapy for seizure clusters in epilepsy. We characterized temporal patterns from a large dataset of treated seizure clusters in the safety study of diazepam nasal spray.

Intracerebral electrographic activity following a single dose of diazepam nasal spray: A pilot study.

Objective: Rescue benzodiazepine medication can be used to treat seizure clusters, which are intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient's usual seizure pattern. The NeuroPace RNS® System is a device that detects abnormal electrographic activity through intracranial electrodes and administers electrical stimulation to control seizures. Reductions in electrographic activity over days to weeks have been associated with the longer-term efficacy of daily antiseizure medications (ASMs).

Practical Questions About Rescue Medications for Acute Treatment of Seizure Clusters in Children and Adolescents with Epilepsy in the USA: Expanding Treatment Options to Address Unmet Needs.

Epilepsy is a common pediatric neurological condition, affecting approximately 470,000 children in the USA and having a prevalence of 0.9% in the global population of approximately 2.6 billion children.

Optimizing Absorption for Intranasal Delivery of Drugs Targeting the Central Nervous System Using Alkylsaccharide Permeation Enhancers.

Intranasal delivery of drugs offers several potential benefits related to ease of delivery, rapid onset, and patient experience, which may be of particular relevance to patients with central nervous system (CNS) conditions who experience acute events. Intranasal formulations must be adapted to address anatomical and physiological characteristics of the nasal cavity, including restricted dose volume, limited surface area, and barriers to mucosal absorption, in addition to constraints on the absorption window due to mucociliary clearance. Development of an effective formulation may utilize strategies including the addition of excipients to address the physicochemical properties of the drug within the constraints of nasal delivery.

Acute seizure therapies in people with epilepsy: Fact or fiction? A U.S. Perspective.

Patients with epilepsy (PWE) may experience seizure emergencies including acute repetitive seizures despite chronic treatment with daily antiseizure medications. Seizures may adversely impact routine daily activities and/or healthcare utilization and may impair the quality of life of patients with epilepsy and their caregivers. Seizures often occur at home, school, or work in a community setting.

Safety of Diazepam Nasal Spray in Pediatric Patients With Developmental Epileptic Encephalopathies: Results From a Long-term Phase 3 Safety Study.

Pediatric developmental epileptic encephalopathies are often refractory to treatment despite stable antiseizure therapy. The safety profile of diazepam nasal spray (Valtoco) as rescue therapy for seizure clusters was described in a long-term safety study. This post hoc analysis assessed safety and effectiveness within a subpopulation of patients with developmental epileptic encephalopathies.

Use of intranasal rescue therapy for seizure clusters in students with epilepsy: Nurses' knowledge, perceptions, and practice.

School nurses play a crucial role in the prompt, appropriate response to epilepsy-related seizure emergencies among students in the school setting. Two intranasal benzodiazepine rescue therapies are now approved and offer potential benefits of being easy to use and socially acceptable. In July 2021, a survey was sent to 49,314 US school nurses to assess knowledge, perceptions, and practice with seizure rescue therapy.

Treatment of Seizure Clusters in Epilepsy: A Narrative Review on Rescue Therapies.

Epilepsy is a common neurological disorder in the United States, affecting approximately 1.2% of the population. Some people with epilepsy may experience seizure clusters, which are acute repetitive seizures that differ from the person's usual seizure pattern.

Acute Abortive Therapies for Seizure Clusters in Long-Term Care.

Objectives: To describe acute seizure treatment for the long-term care setting, emphasizing rescue (acute abortive) medications for on-site management of acute unexpected seizures and seizure clusters.

Design: Narrative review.

Setting And Participants: People with seizures in long-term care, including group residences.