Consequences: Bench to home

Abstract

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.

Global trends in research of glutamate in epilepsy during past two decades: A bibliometric analysis

“…Figures 7C , 8C show hotspots , such as “dentate gyrus,” “glioma,” “GABA,” “AE,” “GAD,” “activation,” “mutation,” “glia,” “lamotrigine,” and “zonisamide.” For many years, the dentate gyrus has been the focal point of research on the molecular, cellular, and network mechanisms that underlie epileptogenesis in TLE ( Dudek and Sutula, 2007 ). Two hypothesized mechanisms have received particular interest and experimental support: (1) selective loss of vulnerable interneurons within the hilus region and (2) the establishment of new recurrent excitatory circuits after sprouting mossy fibers ( Kapur et al, 2022 ; Ramos et al, 2022 ). Tumor-associated epilepsy and gliomas share pathophysiological mechanisms contributing to ictogenesis and tumor progression ( Huberfeld and Vecht, 2016 ).…”

“…(1) selective loss of vulnerable interneurons within the hilus region and (2) the establishment of new recurrent excitatory circuits after sprouting mossy fibers (Kapur et al, 2022;Ramos et al, 2022). Tumor-associated epilepsy and gliomas share pathophysiological mechanisms contributing to ictogenesis and tumor progression (Huberfeld and Vecht, 2016).…”

Rescue therapies for seizure clusters: Pharmacology and target of treatments

“…Rescue therapy is a critical component of seizure cluster management, both to reduce the risks of prolonged seizures and to prevent the progression to status epilepticus 1–3 . Moreover, effective rescue therapy is important to reduce the need for emergency services as well as the clinical and quality‐of‐life burdens of seizure clusters for patients, family members, and caregivers/care partners (please see Kapur et al, Consequences: Bench to Home 4 for further discussion on the impact of seizure clusters). Ideal rescue therapies should be easy and safe to administer, be effective at small doses (with a large therapeutic index), and exhibit rapid onset of action that can be sustained for several hours 5 …”

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

“…Others have suggested that the use of educational and quality‐of‐life measurements could be more appropriate 12 . More details regarding the impact of seizure clusters on patient and caregiver quality of life are discussed by Kapur et al in Consequences: Bench to Home in this supplement 13 . One study looked at health care utilization outcomes and scores on the Modified Impact on Families (MIF) questionnaire at 3 and 12 months in 54 patients with epilepsy who received an SAP and 48 patients who had standard care alone 14 .…”

“…12 More details regarding the impact of seizure clusters on patient and caregiver quality of life are discussed by Kapur et al in Consequences: Bench to Home in this supplement. 13 One study looked at health care utilization outcomes and scores on the Modified Impact on Families (MIF) questionnaire at 3 and 12 months in 54 patients with epilepsy who received an SAP and 48 patients who had standard care alone. 14 Differences in health care utilization were not seen between the groups; however, among patients with ≤12 seizures per year, seizure comfort scores on the MIF questionnaire at 12 months were significantly higher in the SAP group compared with the standard care group.…”