"Brain Pacemaker" For Epilepsy May Affect Breathing During Sleep

So far, the unexpected effect appears small, and not harmful. But the finding, in the November 28 issue of Neurology, may help doctors identify and treat patients who are susceptible to the breathing disruptions, called sleep apnea, before they begin using the device. The discovery could even aid scientists in unraveling the mystery of why the brain-stimulating device works.

"Vagus nerve stimulation is a very promising treatment for epilepsy, and many of our patients have been helped by it," says lead author and U-M assistant professor of neurology Beth Malow, M.D., M.S. "But we still need to understand it fully, including what conditions it may exacerbate. This first sign of an effect on breathing during sleep must be studied further in larger groups of patients, so that we can address with care any confirmed effect."

The study was funded by the National Institute of Neurological Disorders and Stroke and by Cyberonics, Inc., the manufacturer of the vagus nerve stimulation, or VNS, device. Currently approved for use in epilepsy and used by more than 8,000 Americans and Europeans, the device is also now being tested in the U.S. for treating depression. VNS uses an implanted battery and wires to directly stimulate the vagus nerve, a long brain-to-body communication channel in the neck. The electrical signal pulses on and off in intervals, frequencies and intensities that can be adjusted by a physician using a "wand" connected to a computer.

The study focuses on four U-M epilepsy patients who chose to have vagus nerve stimulating devices implanted in their chests after medication failed to control their seizures. All four came to the U-M's Michael S. Aldrich Sleep Disorders Laboratory for overnight sleep tests, both before and after their device was implanted.

All four were taking part in a trial to assess how VNS affects daytime sleepiness - a study that found a positive effect from low to medium VNS intensities. But the nighttime breathing problem was spotted during overnight monitoring of their airflow, blood oxygen and effort. All four had far more breathing decreases or interruptions when the device was on than when it was off.

All four had an overall lower airflow and breathing effort after getting their devices than before, an effect seen during almost every "on" cycle of their devices. Most of the breathing events, though, were not severe or long-lasting enough to be classed as apneas (an 80 percent or greater decrease in breathing for more than 10 seconds), or hypopneas (a breathing interruption for more than 10 seconds together with a partial awakening, or a decrease in blood oxygen).

One male patient, who had a preexisting but undiagnosed case of obstructive sleep apnea, experienced 11 apneas or hypopneas per total hour of sleep, including the time when the device was sending signals and the time when it wasn't. He had had only four such events per hour in the sleep test before he got his device.

The other patients, who had not had signs of sleep apnea in their baseline tests, also experienced an increase in apneas and hypopneas, although these remained below five times an hour, within the normal range. When Malow and her colleagues, including neurologist Jonathan Edwards, M.D., calculated the rate of interruptions during just the time when the device was stimulating their vagus nerve, it came out to 19 per hour.

Malow adds that follow-up studies of two patients showed that fine-tuning of their VNS devices may help reduce breathing disruptions. Both the patient with existing apnea and one of the others showed a decrease in apneas and hypopneas when the stimulus frequency of the electrical signal was decreased.

"In those with mild sleep apnea, decreasing the stimulus frequency or lengthening the time between stimulations may keep the problem from worsening," Malow explains. "And, as in the initial studies on VNS in depression, lower stimulus parameters may actually increase effectiveness. But more study is needed to tell for sure."

Malow notes that VNS patients who experience sleep apnea may also be helped by the conventional treatments for the condition, including adjustments to sleeping position, weight loss, and use of a device known as CPAP that keeps the throat open during sleep using increased air pressure.

The new finding adds to the building knowledge about sleep and epilepsy. Recently, Malow and her colleagues published results of a study that showed a third of epilepsy patients who aren't helped by medication may have sleep apnea, compared with about 24 percent of all men and 9 percent of all women. This frequent coexistence of the two conditions may signal some interaction between the parts of the brain affected by epilepsy, and areas that control breathing.

The new finding, and the research that grows out of it, may be most significant to the 20 to 30 percent of epilepsy patients who may be eligible for VNS treatment. But regardless of which treatment they choose, Malow hopes people with epilepsy will be aware of the symptoms and risks of sleep apnea.

"Most sleep apnea cases go undiagnosed, but if untreated the disorder can affect daytime performance, blood pressure, and heart and lung function," Malow explains. "In patients with epilepsy, sleep apnea may exacerbate seizures or daytime sleepiness, and treatment may improve seizure control and alertness during the day."

Nighttime snoring or wakefulness, and daytime sleepiness or fatigue, are all signs of a problem. But only testing at a fully equipped sleep laboratory can diagnose the condition for sure and lead to effective treatment that may address not only the apnea but even seizures too.