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