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Respiratory Physiology of Seizures

Blum, Andrew S.

Journal of Clinical Neurophysiology: October 2009 - Volume 26 - Issue 5 - p 309-315
doi: 10.1097/WNP.0b013e3181b7f14d
Invited Review

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-Bötzinger 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 in 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.

From the Department of Neurology, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, U.S.A.

Presented at the Neurophysiology of SUDEP symposium at the annual meeting of the American Clinical Neurophysiology Society, Savannah, Georgia, February 15, 2008.

Address correspondence and reprint requests to Andrew S. Blum, M.D., Ph.D., The Warren Alpert Medical School of Brown University, 110 Lockwood Street, Suite 342, Providence, RI 02903, U.S.A.; e-mail:

Copyright © 2009 American Clinical Neurophysiology Society