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Febrile Seizures

Febrile Seizures: Pathogenesis and clinical findings Factors that ↓ seizure threshold Immunizations (DTaP, MMR) activate host immune system Immune cells release pro-inflammatory interleukin (IL)-1β, IL-6 & TNF-α cytokines that reach the central nervous system Viral infections (primarily HHV-6 & H1N1) activate host immune system Immature nervous system in children between 6 Family history of febrile seizures months & 5 years old (peak 12-18 months old) (genetic predisposition) Hypothalamus releases prostaglandin E2 (PGE2) to ↑ body temperature Fever reaches ≥380C ↑ Voltage gated Na+ & Ca2+ channel excitability ↑ Susceptibility to fevers Fever ↑ metabolic rate & ↑ oxygen demand ↑ Respiratory rate Hyperventilation ↑ volume of CO2 exhaled ↓ Serum CO2 leads to respiratory alkalosis Inherited mutations in genes encoding the GABAA receptor subunit ↓ GABAA receptor expression ↓ GABAergic inhibition Inherited mutations in genes encoding the Na+ channels IL-1β ↑ glutamate release & ↓ GABAergic inhibition Pro-inflammatory mediators ↑ sensitivity of N-methyl-D-aspartate (NMDA) (glutamate) receptors on medial temporal lobe neurons Imbalances between excitatory glutamate & inhibitory gamma- aminobutyric acid (GABA) neurotransmission ↑ Neuronal Na+ channel activity Neurons become more excitable & generate action potentials more readily Large groups of neurons fire simultaneously (synchronize) in the medial temporal lobe (hippocampus) Activity spreads to other subcortical or cortical brain regions via synapses & gap junctions Excessive excitatory signaling disrupts normal brain activity Authors: Merry Faye Graff Catherine Beyak, Dasha Mori Reviewers: Michelle J. Chen, Calvin Howard Emily J. Doucette, Gary Klein* Jean K. Mah* * MD at time of publication Simple Febrile Seizure Complex Febrile Seizure Focal seizure, associated with a fever, that lasts > 15 minutes or has multiple recurrences in a 24-hour period Generalized seizure, associated with a fever, that lasts < 15 minutes & does not recur in a 24-hour period Generalized (bilateral cortical involvement) tonic-clonic seizure Temporary post-ictal Temporary post-ictal weakness or ↓ Threshold for future febrile seizures Prolonged (> 30 mins) or recurrent seizures without full return to consciousness in between (Febrile status epilepticus) Focal (localized) seizures Damages to neuronal circuits in affected regions drowsiness or confusion **See corresponding Calgary Guide slide paralysis (Todd’s paralysis) Epilepsy** Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 21, 2019; updated Mar 20, 2025 on www.thecalgaryguide.com