Seizure Clusters Research Articles

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

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

Malformation of the Cortical Development Associated with Severe Clusters of Epileptic Seizures

Three cases of the malformation of the cortical development are described: a mixed breed dog and a Border Collie pup with a focal and diffuse cortical dysplasia, respectively, and a kitten with lissencephaly. All cases presented with intractable epilepsy and were euthanized, due to the cluster of epileptic seizures. The gross examination at necropsy revealed the morphologic alteration of the telencephalic region in two cases. Histopathologically, a disorganization of the cortical lamination with the presence of megalic neurons, was found in the focal cortical dysplasia case. An altered organization of the white and gray matter, with a loss of the normal neuronal distribution and altered neurons, characterized the diffuse cortical dysplasia case. In the lissencephalic cat, there was no recognizable organization of the brain with areas of neuroglial tissue forming nodules in the leptomeningeal space. We strongly support the hypothesis that, as in humans, as well as in the veterinary patients, malformations of the cortical development could be the cause of refractory epilepsy.

The gut-brain axis: effect of antibiotics on canine drug-resistant idiopathic epilepsy

Approximately thirty percent of the dogs with idiopathic epilepsy develop multidrug resistance. Therefore, the search for new non-drug treatment alternatives is important. There is a growing interest in the gut-brain axis and its role in the pathogenesis of epilepsy. The gut microbiota can influence brain function by different neural, endocrine, immune and metabolic pathways, but this process is not yet fully understood. In this study, five client-owned dogs with drug-resistant, idiopathic epilepsy received amoxicillin-clavulanic acid as add-on orally (mean duration 32 days (range 21-64 days)). The mean isolated epileptic seizure frequency of these five dogs was 3.3/ week (range 2.5-6.5) with a mean cluster seizure frequency of 0.9/week (range 0.4-1.5). During the amoxicillin-clavulanic acid treatment, three dogs showed complete seizure freedom, one dog showed an 80% decrease of both isolated epileptic seizure and cluster seizure frequency, and one dog showed an increase in isolated epileptic seizure and cluster seizure frequency of 54% and 38%, respectively. In the two-month follow-up period after cessation of the antibiotic administration, the mean isolated epileptic seizure and cluster seizure frequency increased again to 1.5 seizures/week (range 0.9-2.8) and 0.4 clusters/week (range 0.4-0.6), respectively. The preliminary results in this study highlight the need for future research into the role of the canine gut-brain axis in idiopathic epilepsy.

Phenotypic characterization of idiopathic epilepsy and epilepsy of unknown cause in Irish Setters.

Canine epileptic seizures are common neurological symptom presenting to veterinary practice. Idiopathic epilepsy (IE) with a suspected genetic background has been reported in several dog breeds. Although it has been reported in the Irish Setter (IS), the phenotypic characteristics have not yet been described. The aim of this study was to characterize the phenotype of IE in this breed and to trace its mode of inheritance. Owners of IS were requested to fill in a questionnaire via the Dutch Irish Setter Club concerning the epileptic seizures in their dogs. The data was assessed retrospectively using descriptive statistics. Forty-eight privately owned IS dogs fulfilling tier I criteria for IE according to the International Veterinary Epilepsy Task Force of both sexes were included in the study. The mean age of seizure onset was 41 months. Five of the dogs included in the study had an onset of seizures >6 years of age. These dogs were classified with epilepsy of unknown cause (EUC). Primary generalized tonic-clonic seizures were the most common type of seizure and were seen in almost all dogs. Cluster seizures were reported in 54% of the studied population. Most owners reported pre- (56%) and post-ictal (97%) signs in their dogs. A pedigree analysis of one subpopulation was performed and traced the lineage of 13 affected IS. A segregation analysis of this population rejected a simple autosomal recessive inheritance pattern. The present study supports the occurrence of IE and EUC in the IS. The results provide clinical insight into epileptic seizures in this breed and may be a starting point for further, including genetic, analysis.

Flexible realistic simulation of seizure occurrence recapitulating statistical properties of seizure diaries.

A realistic seizure diary simulator is currently unavailable for many research needs, including clinical trial analysis and evaluation of seizure detection and seizure-forecasting tools. In recent years, important statistical features of seizure diaries have been characterized. These include (1) heterogeneity of individual seizure frequencies, (2) the relation between average seizure rate and standard deviation, (3) multiple risk cycles, (4) seizure clusters, and (5) limitations on inter-seizure intervals. The present study unifies these features into a single model. Our approach, Cyclic Heterogeneous Overdispersed Clustered Open-source L-relationship Adjustable Temporally limited E-diary Simulator (CHOCOLATES) is based on a hierarchical model centered on a gamma Poisson generator with several modifiers. This model accounts for the aforementioned statistical properties. The model was validated by simulating 10000 randomized clinical trials (RCTs) of medication to compare with 23 historical RCTs. Metrics of 50% responder rate (RR50) and median percent change (MPC) were evaluated. We also used CHOCOLATES as input to a seizure-forecasting tool to test the flexibility of the model. We examined the area under the receiver-operating characteristic (ROC) curve (AUC) for test data with and without cycles and clusters. The model recapitulated typical findings in 23 historical RCTs without the necessity of introducing an additional "placebo effect." The model produced the following RR50 values: placebo: 17 ± 4%; drug 38 ± 5%; and the following MPC values: placebo: 13 ± 6%; drug 40 ± 4%. These values are similar to historical data: for RR50: placebo, 21 ± 10%, drug: 43 ± 13%; and for MPC: placebo: 17 ± 10%, drug: 41 ± 11%. The seizure forecasts achieved an AUC of 0.68 with cycles and clusters, whereas without them the AUC was 0.51. CHOCOLATES represents the most realistic seizure occurrence simulator to date, based on observations from thousands of patients in different contexts. This tool is open source and flexible, and can be used for many applications, including clinical trial simulation and testing of seizure-forecasting tools.

What was Happening in the Brain of a 13-Year-Old with Cluster Seizures: Real-Ish-Time Assessment of Optic Nerve Sheath Diameter (ONSD)

What was Happening in the Brain of a 13-Year-Old with Cluster Seizures: Real-Ish-Time Assessment of Optic Nerve Sheath Diameter (ONSD)

Psychosocial outcomes of repeated treatment of seizure clusters with midazolam nasal spray: Results of a phase 3, open-label extension trial

ObjectiveTo evaluate treatment satisfaction, level of anxiety, confidence about traveling with midazolam nasal spray (MDZ‐NS), and health-related quality of life in patients with seizure clusters and their caregivers after repeated, intermittent use of MDZ-NS in the outpatient setting. MethodsWe analyzed the psychosocial outcome data from a phase 3, open-label extension trial (ARTEMIS-2; P261-402; NCT01529034) in patients 12 years of age and older with seizure clusters on a stable regimen of antiseizure medications. Caregivers administered MDZ‐NS 5 mg when patients experienced a seizure cluster. A second dose could be given if seizures did not terminate within 10 min or recurred from 10 min to 6 h. Treatment Satisfaction Questionnaire for Medication (TSQM), the Intranasal Therapy Impact Questionnaire (ITIQ), and the Short Form-12 Health Survey version 2 (SF-12v2) were self-administered by patients and/or caregivers at prespecified visits. ResultsOf the one hundred and seventy-five patients enrolled in ARTEMIS-2, 161 (92.0%) received ≥ 1 dose of MDZ‐NS and had a post-treatment seizure-related assessment and were included in the Efficacy Evaluable Set in this analysis, with a total of 1,998 treated seizure clusters over a median duration of 16.8 months. All TSQM scales showed improvement from the baseline of the double-blind ARTEMIS-1 trial (NCT01390220) to the last visit in ARTEMIS-2, indicating greater satisfaction with MDZ-NS across all domains, with a mean change from baseline of 8.8, 6.1, 4.3, and 6.2 for effectiveness (n = 135), side effects (n = 139), convenience (n = 139), and global satisfaction (n = 138), respectively. Change from baseline in TSQM scores generally increased with repeated MDZ-NS use. In both patients and caregivers, anxiety generally lessened with repeated MDZ-NS use, with a mean improvement in ITIQ scores in patients’ anxiety since receiving MDZ-NS from 2.5 (n = 138) to 3.5 (n = 145) from visit 1 to the last visit (and from 2.6 [n = 156] to 3.6 [n = 160] for caregivers), respectively. From visit 1 (screening and enrollment in ARTEMIS-2) to visit 10 (after 16 seizure cluster episodes treated with MDZ-NS), the proportions of patients and caregivers who answered “strongly agree” or “agree” for confidence about traveling with an intranasal spray remained ≥ 79% and generally increased over repeated MDZ-NS use. Small positive mean changes in SF-12v2 scores from baseline to the last visit were observed in both patients and caregivers, respectively, for the domains of physical functioning (0.9, 1.1), role-physical (2.4, 0.3), bodily pain (1.7, 0.3), general health (0.6, 1.2), and role-emotional (2.1, 0.3), and in the physical health component (1.6, 1.0). ConclusionPatients and caregivers perceived MDZ-NS favorably, with improvement from baseline on perceived effectiveness, side effects, convenience, and global satisfaction in the TSQM. This is supported by progressively lower anxiety and higher confidence levels about traveling with MDZ-NS over repeated intermittent use in the ITIQ. The positive mean changes observed in SF-12v2 scores from baseline to the last visit were small in magnitude. Limitations of this exploratory analysis include the open-label trial design and that these questionnaires have not been directly validated in epilepsy to identify clinically important changes; however, this does not mean these findings are not clinically meaningful. Overall, MDZ-NS is a socially acceptable drug device for outpatient treatment of seizure clusters that has the potential to improve quality of life and overall independence.

Convulsioni e gastroenterite: un caso che insegna

The article reports a case of convulsions with gastroenteritis (CWG) and briefly reviews the related literature. A 2-year-old girl presented with four short episodes of focal afebrile seizures within 12 hours. She had fever with vomiting in the previous 2 days and she developed diarrhoea during her hospital stay, after the fifth seizure. She had no significant past medical history and showed neither neurological signs nor signs of dehydration. Serum electrolytes were normal, cerebrospinal fluid examination was negative for meningoencephalitis and contrast-enhanced CT Brain scan showed no evidence of intracranial lesion. Stool investigation was positive for rotavirus. Therefore, the diagnosis of CWG was made. Repeated convulsions were handled with continuous intravenous infusion of midazolam. The main cause of CWGs in viral gastroenteritis is due to rotavirus or norovirus. The convulsions are usually focal seizure clusters, with secondary generalization. CWGs are associated with a benign prognosis.

PCDH19-related epilepsy in mosaic males: The phenotypic implication of genotype and variant allele frequency.

To analyze the genotypes and phenotypes of mosaic male patients with PCDH19-related epilepsy (PCDH19-RE) and explore the correlation between genotype, variant allele frequency (VAF), and phenotypic severity. Clinical data and peripheral blood samples of 11 male mosaic patients were collected and analyzed in our study. The VAF of the PCDH19 gene from peripheral blood was quantified using amplicon-based deep sequencing. Additional 20 mosaic male patients with PCDH19-RE were collected from the published literature, with 10 patients whose VAFs of the PCDH19 gene were available for analytic purposes. In our cohort of 11 patients, 10 variants were identified, and four were novel. The VAF of the PCDH19 gene from peripheral blood ranged from 27 to 90%. The median seizure onset age was 6 months (range: 4-9 months). Clinical manifestations included cluster seizures (100%), fever sensitivity (73%), focal seizures (91%), developmental delay/intellectual disability (DD/ID, 82%), and autistic features (45%). Thirty-one mosaic male patients collected from our cohort and the literature developed seizures mostly (87%) within one year of age. Variant types included missense variants (42%), truncating variants (52%), splice variants (3%), and whole PCDH19 deletion (3%). Among 21 patients with a definite VAF from our cohort and the literature, nine had a low VAF ( ≤ 50%) and 12 had a high VAF (> 50%). Seventy-five percent of variants from the high VAF group were missense, whereas 89% of those from the low VAF group were truncations. The median seizure onset age was 6 months in the low VAF group and 9 months in the high VAF group (p = 0.018). Forty-four percent (4/9) of patients from the low VAF group achieved seizure-free for ≥1 year, whereas none of the 12 patients from the high VAF group did (p = 0.021). DD/ID was present in 83% (10/12) of the high VAF group and 56% (5/9) of the low VAF group (p = 0.331). The predominant variant types were truncating and missense variants. Missense variants tended to have higher VAFs. Patients with a high VAF were more likely to have a more severe epileptic phenotype. Our findings shed light on the phenotypic implications of VAF in mosaic males with PCDH19-RE.

Implications of Seizure-Cluster Treatment on Healthcare Utilization: Use of Approved Rescue Medications.

People with epilepsy may experience seizure clusters despite a stable regimen of antiseizure medications. Such clusters have the potential to last ≥24 hours, typically occur in the community setting, and may progress to medical emergencies, such as status epilepticus, if untreated. Thus, long-acting rescue therapy for seizure clusters is needed that can be administered by nonmedical individuals outside a hospital. Benzodiazepines are the foundation of rescue therapy for seizure clusters. The approved outpatient treatments (ie, diazepam, midazolam) have differing profiles that may affect multiple aspects of health-care utilization. The current labeling of these medications allows for a second dose if needed to control the cluster. Although no head-to-head studies directly comparing rescue treatments have been conducted, differences between studies with generally similar designs may provide context for the potential importance of second doses of rescue therapy on health-care utilization. For this analysis, large, long-term, open-label studies of approved seizure-cluster treatments designed for use by nonmedical caregivers were reviewed, and the percentage of seizure clusters for which a second dose was used or that were not controlled at 6, 12, and 24 hours was examined. Available data on hospitalizations were also collected. The 3 identified studies meeting the inclusion criteria were for use of diazepam rectal gel, intranasal midazolam, and diazepam nasal spray. Across these studies, the use of a second dose ranged from <40% at 6 hours to <13% at 24 hours. Hospitalizations and serious treatment-emergent adverse events were reported variably across these studies. These results demonstrate the importance of second doses of rescue therapy for seizure clusters for optimizing health-care utilization. Need for second doses should be included as one component. In turn, when second doses are needed, they have the potential to curtail emergency department use and hospitalization and to prevent further seizure clusters.

A Survey on Epilepsy and Work: Profiles and Challenges

Abstract Objective Epilepsy can have a chronic course in a subgroup of people and may impact the ability to study, marry or earn a living thereby increasing significantly the burden of the illness. For a person with epilepsy (PWE), beyond seizure control, being participative and productive in life is a crucial factor for a good quality of life. The aim of the study was to explore factors that help and/or hinder PWE find work / employment. Materials and Methods Data was collected via a self-reported structured questionnaire from PWE in the age group 21 to 60 years, who had completed their education, and had a confirmed diagnosis of epilepsy for at least a year with no known psychiatric ailment or psychiatric morbidity. Binomial logistic regression was used to determine factors that impact employment. Results Sixty-three percent of our cohorts (n = 119/190) were employed. Factors that supported employment were higher education, late age of epilepsy onset, and better maternal education. The odds of being employed decreased significantly with increasing seizure frequency (odds ratio [OR] = 0.749; 95% confidence interval [CI] = 0.586–0.957) and occurrence of cluster seizures (OR = 0.348; 95% CI = 0.163–0.742; p &lt; 0.05). Conclusion PWE can secure employment when their seizure frequency is low and epilepsy onset is after the age of 5 years. However, high job stress and cognitive and emotional difficulties are barriers and reasons for resignation from work. PWEs and their caregivers need to be empowered with psychoeducation and receive counselling support for their mood and cognitive issues to help them reach their full work potential.

Prevalence and Predictors of Seizure Clusters in Pediatric Patients With Epilepsy: The Harvard-Yale Pediatric Seizure Cluster Study

BackgroundDetermine the prevalence of seizure clusters (two or more seizures in six hours), use of rescue medications, and adverse outcomes associated with seizure clusters in pediatric patients with a range of epilepsy severities, and identify risk factors predictive of seizure clusters. MethodsProspective observational two-center study, including phone call and seizure diary follow-up for 12 months in patients with epilepsy aged one month to 18 years. We classified patients into three risk groups based on seizures within the prior year: high, seizure cluster (two or more seizures within one day); intermediate, at least one seizure but no days with two or more seizures; low, no seizures. ResultsOne-third (32.3%; high risk, 72.4%; intermediate risk, 30.4%; low risk, 3.1%) of 297 patients had a seizure cluster during the study, including half (46.2%) of the patients with active seizures at baseline (intermediate- and high-risk groups combined). Emergency room visits or injuries were no more likely due to a seizure cluster than an isolated seizure. Rescue medications were utilized in 15.8% of patients in the high-risk group and 19.2% in the intermediate-risk group. History of status epilepticus (adjusted odds ratio [aOR], 2.13; confidence interval [CI], 1.09 to 4.16]), seizure frequency greater than four per month (aOR, 4.27; CI, 1.92 to 9.50), and high-risk group status (aOR, 6.42; CI, 2.97 to 13.87) were associated with greater odds of seizure cluster. ConclusionsSeizure clusters are common in pediatric patients with epilepsy. High seizure frequency was the strongest predictor of clusters. Rescue medications were underutilized. Future studies should evaluate the applicability and effectiveness of these medications for optimization of pediatric seizure cluster treatment and reduction of seizure-related emergency department visits, injuries, and mortality.

Approach to initial management of canine generalised epileptic seizures in primary-care veterinary practices in the United Kingdom.

To investigate how primary care clinicians in the UK approach initial management of canine generalised epileptic seizures, including factors potentially associated with prescription and choice of anti-seizure drugs. Electronic health records concerning 3,150,713 consultations (917,373 dogs) were collected from 224 veterinary practices by the Small Animal Veterinary Surveillance Network. Free-text clinical narratives were reviewed to identify those consistent with generalised epileptic seizure activity, including only those recording the first presentation for seizures. Dogs older than 6 years were excluded. Five hundred and seventeen cases were included. Sixty-seven dogs (13.0%) received anti-seizure drugs at first presentation; this was significantly more likely in dogs presented withcluster seizures (odds ratio 13.8, 95% confidence interval 7.3 to 26.1). Phenobarbital (n=36) and imepitoin (n=29) were the most frequently chosen anti-seizure drugs. Presentation for a single epileptic seizure occurred in 321 dogs; seven were prescribed anti-seizure drugs. Eighty-six dogs were presented with cluster seizures; 38 were prescribed anti-seizure drugs, most frequently imepitoin (n= 19) and phenobarbital (n=17). Of the dogs presenting with a single seizure and at least 6-month follow-up (n=165), 33 (20%) did not have subsequent seizures recorded. Primary care clinicians rarely prescribed anti-seizure drugs following a single epileptic seizure in accordance with International Veterinary Epilepsy Task Force recommendations. Less than half of dogs initially presenting with cluster seizures were prescribed anti-seizure drugs. Imepitoin was frequently selected in the treatment of cluster seizures despite no authorisation for this purpose. These findings may ultimately contribute to improved cohesion in the management of canine epileptic seizures between primary care and referral institutions.

Consequences: Bench to home.

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.

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

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.

Future opportunities for research in rescue treatments.

Clinical studies of rescue medications for seizure clusters are limited and are designed to satisfy regulatory requirements, which may not fully consider the needs of the diverse patient population that experiences seizure clusters or utilize rescue medication. The purpose of this narrative review is to examine the factors that contribute to, or may influence the quality of, seizure cluster research with a goal of improving clinical practice. We address five areas of unmet needs and provide advice for how they could enhance future trials of seizure cluster treatments. The topics addressed in this article are: (1) unaddressed end points to pursue in future studies, (2) roles for devices to enhance rescue medication clinical development programs, (3) tools to study seizure cluster prediction and prevention, (4) the value of other designs for seizure cluster studies, and (5) unique challenges of future trial paradigms for seizure clusters. By focusing on novel end points and technologies with value to patients, caregivers, and clinicians, data obtained from future studies can benefit the diverse patient population that experiences seizure clusters, providing more effective, appropriate care as well as alleviating demands on health care resources.

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

It is important for patients with epilepsy and their caregivers, including care partners, to understand the patient's seizure clusters and what to do when they occur. In many instances, seizure clusters are unique to each patient. The knowledge gained from understanding a patient's seizure cluster or seizure pattern provides a foundation for taking prompt action to prevent worsening to prolonged seizures, status epilepticus, and potentially death. Seizure action plans (SAPs), which are similar to the disease-related treatment action plans for other conditions, can be developed by a health care provider (HCP) in conjunction with the patient with epilepsy and/or caregivers, and SAPs are specifically customized for the individual patient and his or her seizure management. However, the current literature lacks unified guidance on how to design SAPs that will help prepare patients and caregivers for rapidly determining and initiating appropriate treatment of acute seizure emergencies in the community and at home. Here, we examine the current usage and value of SAPs for pediatric and adult patients with epilepsy, and we introduce the concept of the acute SAP (ASAP) for use specifically during seizure emergencies, such as seizure clusters. This type of standardized, simplified, and customized plan can rapidly and concisely provide patients and caregivers with a practical protocol to treat a seizure cluster consistently, appropriately, and in a timely manner. Details on potential content and formats of ASAPs are provided. Following this is a discussion of barriers to ASAP use that may affect HCPs or patients and caregivers, including lack of standardization, relevance, and personalization and pitfalls associated with technology. This leads into a discussion of guidance for developing, implementing, and updating ASAPs that suggests ways to address the barriers and ensure that the ASAP is best suited to the patient's needs.

Economic aspects of treating seizure clusters.

Seizure clusters may initiate a chain of events that have economic as well as clinical consequences. The potential economic consequences of seizure clusters must be weighed against the cost of medication to attenuate them. This is true both for individual patients and for society. Data needed for economic analyses include the chance that a cluster will progress to an adverse outcome, such as a need for emergency care, the costs of such an outcome, the cost of a rescue medication (RM), and the effectiveness of the RM. Indirect costs, such as lost employment for patients and caregivers, must also be considered. Several types of economic analyses can be used to determine costs and benefits of a medical intervention. There are studies comparing different RMs from an economic perspective, but there is little direct information on the costs of using an RM versus allowing clusters to run their course. However, the high expense of consequences of seizure clusters makes it likely that effective RMs will make economic as well as medical sense for many patients.

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.

Seizure clusters: Practical aspects and clinical strategies to care for patients in the community.

Seizure clusters: Practical aspects and clinical strategies to care for patients in the community.