Respiratory Physiology of Seizures

Comonitoring of seizures and respiratory function with pulse oximetry has shown that ictal respiratory changes (IRCs) accompany tonic-clonic convulsions and even partial seizures, especially those of temporal lobe origin. IRCs occur in children and adults, and diminished central drive is frequent, although peripheral obstruction is observed occasionally. Case reports of sudden unexplained death in epilepsy (SUDEP) have suggested IRC as a mechanism. In a series of 15 witnessed SUDEP cases, overt convulsions with marked respiratory difficulty were observed in 12. For two cases, obstructive mechanisms may have predominated. One near-SUDEP case implicated central apnea, but another case implicated postictal laryngospasm. Inhibition of brainstem respiratory control circuits likely subserves IRCs. The pre-Botzinger complex in the rostral ventrolateral medulla is a key locus for respiratory rhythm generation, with expiratory control neurons near the nucleus ambiguous. Inputs to these neurons descend from the insula, hypothalamus, and reticular formation. Direct stimulation of limbic targets ill humans causes apnea. Animal models of focal seizures with IRCs and SUDEP have produced inconsistent results: some Support central mechanisms, whereas others implicate peripheral obstruction. Serotonin seems relevant in a mouse model of SUDEP. These models may elucidate how seizures embarrass respiration and possibly predispose patients to SUDEP.