Iván Sánchez Fernández1, Howard P Goodkin2, Rod C Scott3. 1. Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States; Department of Child Neurology, Hospital Sant Joan de Déu, Universidad de Barcelona, Barcelona, Spain. 2. Departments of Neurology and Pediatrics, University of Virginia, Charlottesville, VA, United States. 3. Neurosciences Unit, University College London Great Ormond Street Institute of Child Health, London, UK; Department of Neurological Sciences, University of Vermont, Burlington, VT, United States. Electronic address: Rodney.Scott@uvmhealth.org.
Abstract
PURPOSE: To summarize the pathophysiology of convulsive status epilepticus (SE) with a focus on practical implications for treatment. METHOD: Narrative review of the medical literature on the pathophysiology of convulsive SE. We considered both animal models of SE and clinical studies. RESULTS: Convulsive SE is an emergency in which prolonged convulsive seizures are associated with cardiorespiratory instability, hypoxia, hypoglycemia, and hyperthermia. Supportive treatment helps correct these physiological imbalances. When treatment is delayed, the ability of first line seizure suppressing medications to terminate the seizure can be reduced. Animal studies have suggested that GABAA receptor trafficking may contribute to the failure of the first line therapies and that NMDA receptor antagonists such as ketamine may become more effective as seizures last longer. Potential strategies to take advantage of these changes in pathophysiology include a rapid escalation from benzodiazepines to non-benzodiazepine antiepileptic drugs (AEDs), early polytherapy and use of NMDA antagonists such as ketamine for refractory convulsive SE. Despite the importance of a timely treatment of convulsive SE, major treatment delays are frequent in clinical practice. Policies to improve time to treatment, especially in convulsive SE that starts outside the hospital, may improve response to treatment and convulsive SE outcomes. CONCLUSIONS: Convulsive SE is a time-sensitive emergency in which the underlying pathophysiology may provide targets for improving treatment strategies. A timely transition from benzodiazepines to other AEDs may help reduce treatment resistance in convulsive SE.
PURPOSE: To summarize the pathophysiology of convulsive status epilepticus (SE) with a focus on practical implications for treatment. METHOD: Narrative review of the medical literature on the pathophysiology of convulsive SE. We considered both animal models of SE and clinical studies. RESULTS:Convulsive SE is an emergency in which prolonged convulsive seizures are associated with cardiorespiratory instability, hypoxia, hypoglycemia, and hyperthermia. Supportive treatment helps correct these physiological imbalances. When treatment is delayed, the ability of first line seizure suppressing medications to terminate the seizure can be reduced. Animal studies have suggested that GABAA receptor trafficking may contribute to the failure of the first line therapies and that NMDA receptor antagonists such as ketamine may become more effective as seizures last longer. Potential strategies to take advantage of these changes in pathophysiology include a rapid escalation from benzodiazepines to non-benzodiazepine antiepileptic drugs (AEDs), early polytherapy and use of NMDA antagonists such as ketamine for refractory convulsive SE. Despite the importance of a timely treatment of convulsive SE, major treatment delays are frequent in clinical practice. Policies to improve time to treatment, especially in convulsive SE that starts outside the hospital, may improve response to treatment and convulsive SE outcomes. CONCLUSIONS:Convulsive SE is a time-sensitive emergency in which the underlying pathophysiology may provide targets for improving treatment strategies. A timely transition from benzodiazepines to other AEDs may help reduce treatment resistance in convulsive SE.
Authors: James Peters; Nirosen Vijiaratnam; Joseph Z W Wong; Sonia Jitpiriyaroj; Ronil V Chandra; Peter A Kempster Journal: Epilepsy Behav Rep Date: 2019-11-15