SEARCH RESULTS FOR: Status-Epilepticus

Status-Epilepticus

Status Epilepticus: Pathogenesis and clinical findings Authors: Katherine Liu Reviewers: Negar Tehrani Ephrem Zewdie Ran (Marissa) Zhang Carlos Camara-Lemarroy* * MD at time of publication Structural brain injury (stroke, trauma, hypoxia) Drugs that lower seizure threshold Antiseizure drug discontinuation Alcohol, barbiturate, benzodiazepine withdrawal Metabolic disturbance Infection See “Generalized Seizures” Altered excitability and communication between neuronal structures Isolated generalized seizures Ongoing seizure activity and repetitive neuronal firing Changes in receptor trafficking (seconds to minutes) Changes in neuromodulator expression in hippocampus (minutes to hours) Endocytosis of synaptic GABAA inhibitory receptors ↓ Number of inhibitory GABAA receptors Progressive resistance to benzodiazepines (drugs that upregulate GABA receptors) as seizure continues ↑ Expression of excitatory peptides (substance P, neurokinin B) Abbreviations: • GABA- γ-aminobutyric acid • NMDA- N-methyl-D-aspartic acid • AMPA- α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid NMDA and AMPA excitatory receptors mobilize to synaptic membrane ↑ Number of excitatory NMDA and AMPA receptors ↓ Expression of inhibitory peptide (dynorphin, galanin, somatostatin, neuropeptide Y) Seizure-induced failure of inhibitory mechanisms involved in seizure termination and increased neuronal excitability Status Epilepticus (SE) An abnormally prolonged seizure ≥ 5 minutes or 2+ sequential seizures without full recovery in between ↑↑ Glutamate release and activation of NMDA excitatory receptors ↑ Ca2+ entry into neurons Mitochondrial dysfunction ↑ Reactive oxygen species (nitric oxide) production Neuronal injury/death (↑ risk of developing chronic epilepsy) ↑ Autonomic activity Intense, sustained muscle contractions Persistent stimulus OR altered neuronal landscape (i.e., Immune mediated) Refractory SE: SE that does not respond to 1st or 2nd line therapy Prolonged seizures (≥30 mins) lead to failure of compensatory mechanisms Circulatory collapse ↓ Cerebral blood flow • Hypertension • Hyperglycemia • ↑ Cardiac output • ↑ Secretions • Hypotension • Hypoventilation Energy demands > ATP produced through oxidative phosphorylation Myocytes start utilizing anerobic glycolysis ↑ Lactic acid production ↑ Serum lactate Sustained muscle activity produces body heat Hyperpyrexia (axillary temperature ≥ 40° C) Myocyte injury Leakage of muscle contents into the circulation (Rhabdomyolysis) ↑ Serum creatine kinase Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 27, 2022 on www.thecalgaryguide.com