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Journal of Veterinary Internal Medicine 2024Seizure emergencies (ie, status epilepticus [SE] and cluster seizures [CS]), are common challenging disorders with complex pathophysiology, rapidly progressive...
BACKGROUND
Seizure emergencies (ie, status epilepticus [SE] and cluster seizures [CS]), are common challenging disorders with complex pathophysiology, rapidly progressive drug-resistant and self-sustaining character, and high morbidity and mortality. Current treatment approaches are characterized by considerable variations, but official guidelines are lacking.
OBJECTIVES
To establish evidence-based guidelines and an agreement among board-certified specialists for the appropriate management of SE and CS in dogs and cats.
ANIMALS
None.
MATERIALS AND METHODS
A panel of 5 specialists was formed to assess and summarize evidence in the peer-reviewed literature with the aim to establish consensus clinical recommendations. Evidence from veterinary pharmacokinetic studies, basic research, and human medicine also was used to support the panel's recommendations, especially for the interventions where veterinary clinical evidence was lacking.
RESULTS
The majority of the evidence was on the first-line management (ie, benzodiazepines and their various administration routes) in both species. Overall, there was less evidence available on the management of emergency seizure disorders in cats in contrast to dogs. Most recommendations made by the panel were supported by a combination of a moderate level of veterinary clinical evidence and pharmacokinetic data as well as studies in humans and basic research studies.
CONCLUSIONS AND CLINICAL RELEVANCE
Successful management of seizure emergencies should include an early, rapid, and stage-based treatment approach consisting of interventions with moderate to preferably high ACVIM recommendations; management of complications and underlying causes related to seizure emergencies should accompany antiseizure medications.
Topics: Cats; Dogs; Animals; Humans; Emergencies; Cat Diseases; Dog Diseases; Status Epilepticus; Epilepsy; Anticonvulsants
PubMed: 37921621
DOI: 10.1111/jvim.16928 -
Brain : a Journal of Neurology Jul 2023Epileptogenesis in infants with tuberous sclerosis complex (TSC) is a gradual and dynamic process, leading to early onset and difficult-to-treat seizures. Several... (Review)
Review
Epileptogenesis in infants with tuberous sclerosis complex (TSC) is a gradual and dynamic process, leading to early onset and difficult-to-treat seizures. Several cellular, molecular and pathophysiologic mechanisms, including mammalian target of rapamycin (mTOR) dysregulation, GABAergic dysfunction and abnormal connectivity, may play a role in this epileptogenic process and may also contribute to the associated developmental encephalopathy. Disease-specific antiseizure medications or drugs targeting the mTOR pathway have proved to be effective in TSC-associated epilepsy. Pre-symptomatic administration of vigabatrin, a GABAergic drug, delays seizure onset and reduces the risk of a subsequent epileptic encephalopathy, such as infantile spasms syndrome or Lennox-Gastaut syndrome. Everolimus, a rapamycin-derived mTOR inhibitor, reduces seizure frequency, especially in younger patients. This evidence suggests that everolimus should be considered early in the course of epilepsy. Future trials are needed to optimize the use of everolimus and determine whether earlier correction of mTOR dysregulation can prevent progression to developmental and epileptic encephalopathies or mitigate their severity in infants with TSC. Clinical trials of several other potential antiseizure drugs (cannabidiol and ganaxolone) that target contributing mechanisms are also underway. This review provides an overview of the different biological mechanisms occurring in parallel and interacting throughout the life course, even beyond the epileptogenic process, in individuals with TSC. These complexities highlight the challenges faced in preventing and treating TSC-related developmental and epileptic encephalopathy.
Topics: Infant; Humans; Everolimus; Tuberous Sclerosis; Epilepsy; Seizures; Sirolimus; TOR Serine-Threonine Kinases; Anticonvulsants
PubMed: 36806388
DOI: 10.1093/brain/awad048 -
Drugs Jul 2023Fenfluramine (Fintepla) is an oral anti-seizure medication (ASM) with a novel mechanism of action consisting of activity in the serotonergic system coupled with positive... (Review)
Review
Fenfluramine (Fintepla) is an oral anti-seizure medication (ASM) with a novel mechanism of action consisting of activity in the serotonergic system coupled with positive allosteric modulation effects at sigma-1 receptors. Originally approved for use at high doses as an appetite suppressant, it was subsequently withdrawn after being linked to valvular heart disease (VHD) and pulmonary arterial hypertension (PAH), before being investigated for use at low doses as an adjunctive ASM in patients with developmental epileptic encephalopathies, including Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) who have pharmacoresistant seizures. In clinical trials, treatment with adjunctive fenfluramine markedly reduced convulsive seizure frequency in patients with DS that were sustained for up to 3 years, and reduced drop seizure frequency in patients with LGS that were sustained for up to 1 year. Notably, fenfluramine was also associated with clinically meaningful improvements in aspects of everyday executive functioning (EF) not entirely explainable by seizure reduction alone. Furthermore, it was generally well tolerated with, importantly, no reports of VHD or PAH. Thus, adjunctive fenfluramine is a novel and effective treatment for pharmacoresistant seizures associated with DS and LGS that may also improve aspects of everyday EF in some patients.
Topics: Humans; Lennox Gastaut Syndrome; Fenfluramine; Epilepsies, Myoclonic; Treatment Outcome; Seizures; Anticonvulsants
PubMed: 37316680
DOI: 10.1007/s40265-023-01881-w -
Journal of Neurology Oct 2023To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and related entities.
METHODS
Two reviewers independently searched PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials from December 2022 to February 2023. Studies on the efficacy and safety of ASM monotherapies or adjunctive therapies for IGEs and related entities-including juvenile myoclonic epilepsy, childhood absence epilepsy (CAE), juvenile absence epilepsy, or generalized tonic-clonic seizures alone (GTCA)-were included. Efficacy outcomes were the proportions of patients remaining seizure free for 1, 3, 6, and 12 months; safety outcomes were the proportions of any treatment-emergent adverse event (TEAE) and TEAEs leading to discontinuation. Network meta-analyses were performed in a random-effects model to obtain odds ratios and 95% confidence intervals. Rankings of ASMs were based on the surface under the cumulative ranking curve (SUCRA). This study is registered with PROSPERO (No. CRD42022372358).
RESULTS
Twenty-eight randomized controlled trials containing 4282 patients were included. As monotherapies, all ASMs were more effective than placebo, and valproate and ethosuximide were significantly better than lamotrigine. According to the SUCRA for efficacy, ethosuximide ranked first for CAE, whereas valproate ranked first for other types of IGEs. As adjunctive therapies, topiramate ranked best for GTCA as well as overall for IGEs, while levetiracetam ranked best for myoclonic seizures. For safety, perampanel ranked best (measured by any TEAE).
CONCLUSIONS
All of the studied ASMs were more effective than placebo. Valproate monotherapy ranked best overall for IGEs, whereas ethosuximide ranked best for CAE. Adjunctive topiramate and levetiracetam were most effective for GTCA and myoclonic seizures, respectively. Furthermore, perampanel had the best tolerability.
Topics: Humans; Child; Valproic Acid; Topiramate; Network Meta-Analysis; Levetiracetam; Ethosuximide; Anticonvulsants; Epilepsy, Generalized; Seizures; Randomized Controlled Trials as Topic
PubMed: 37378757
DOI: 10.1007/s00415-023-11834-8