Effects of Vagus Nerve Stimulation on Sleep-related Breathing in Epilepsy Patients
Marzec M, Edwards J, Sagher O, Fromes G and Malow BA;
Commented by , 22 Aug 2003
Vagus nerve stimulation (VNS) is increasingly used in the management of drug refractory epilepsy. Though VNS is generally regarded as safe, there have been rare reports of sleep-related breathing disturbances.
To determine the effects of VNS on breathing during sleep in patients with drug refractory epilepsy.
Prospective study in 16 patients (age 21-58 years); 15 had complex partial seizures, one had juvenile myoclonic epilepsy. Patients with any sleep disorder other than treated obstructive sleep apnea were excluded.
Patients underwent polysomnograms before and 3 months after implantation of a vagal nerve stimulator. VNS parameters were set according to established guidelines.
Breathing effects were assessed by the apnea-hypopnea index (AHI), defined as the number of apnea and hypopnea episodes per hour of sleep.
After initiation of VNS therapy, 5 of 16 patients had an AHI above 5, compared with only one patient at baseline.
Apneas/hypopneas were more frequent during VNS-activation (on-time) than without VNS activation (off-time, p<0.02).
One patient had esophageal pressure monitoring, and showed pressure crescendos during VNS activation.
In one patient who had a continuous positive airway pressure trial, VNS-associated events occurred at low positive airway pressure levels but resolved when pressure levels were increased.
The first report of VNS-induced breathing impairment during sleep came from the same group (1) and concerned 4 patients, who are also included here.
Although there have been similar reports from other laboratories (2), this is the largest and most comprehensive study to date.
The message is clear: VNS affects respiration during sleep. The pattern is that of a consistent decrease in airflow with diminished but relatively preserved effort, often associated with tachypnea, which occurs during VNS activation. Overall, the findings are suggestive of compromised airway patency.
Mechanisms may include peripheral effects on vagus-innervated airway musculature as well as central effects on respiration. Interestingly, a recent study (3) found that atrial overdrive pacing reduces obstructive and central apneas in patients with sinus node dysfuction and associated sleep apneas, an effect ascribed to a reduction in vagal tone. Thus, VNS may reduce airway flow during sleep by increasing vagal tone, while atrial pacing may ameliorate sleep-disordered breathing by reducing vagal tone.
Although clinically significant changes in apnea-hypopnea index occurred in about one third of patients, the effect was mild in most cases and the clinical impact is unclear. Only 2 patients developed a AHI above 10 with VNS, and both had a history of obstructive sleep apnea.
After the first report in 2000, the VNS product labeling added a warning that “patients with obstructive sleep apnea may have increased apneic events during stimulation” and that care is needed when treating such patients.
Before considering a patient for VNS, it is wise to take a careful history for possible obstructive sleep apnea and, if appropriate, perform a polysomnographic investigation. Pre-existing obstructive sleep apnea should be treated before applying VNS. If obstructive sleep apnea develops during VNS, continuous positive airway pressure may be effective in managing the breathing disorder.
1. Malow BA, Edwards J, Marzec M et al, Effects of vagus nerve stimulation on respiration during sleep: A pilot study. Neurology 2000; 55:1450-4
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2. Deochand MC, Quint SR, Bernard EJ. et al, Sleep related respiratory function during vagal nerve stimulation. Epilepsia 2000; 41; 204
Murray BJ, Matheson JK, Scammel TE. Effects of vagus nerve stimulation on respiration during sleep. Neurology 2001; 57; 1523-4
Sorenson PG and Ferber RA. The effects of vagal nerve stimulation on respiration during sleep in pediatric patients with epilepsy, Sleep 2002; 25; A163-4
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3. Garrigue S, Bordier P, Jais P et al, Benefit of atrial pacing in sleep apnea syndrome. New Engl J Med 2002; 346; 404-12
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