ARTICLE IN BRIEF
Researchers say new data showing a link between abnormal electrical activity in the heart and periods of low oxygen levels during epileptic seizures could help shed light on sudden unexpected death in epilepsy.
SAN DIEGO—Abnormal electrical activity in the heart is linked with periods of low oxygen levels during epileptic seizures, according to new findings presented here at the American Neurological Association annual meeting.
Researchers say the findings could help shed light on what is happening during SUDEP (sudden unexpected death in epilepsy), in which people who have epilepsy die with no obvious cause of death.
In the study, researchers at the University of California, Davis analyzed 56 seizures in 17 consecutive patients. They found that two types of abnormal electrical activity in the heart were more likely during oxygen desaturation than non-desaturation periods.
They focused on the QT interval — the time it takes for the ventricles of the heart to take a beat and get prepared for the electrical impulse for the next beat, a process that normally takes just under half a second.
“We found that the QT intervals were both more likely to be abnormally long, and more likely to be abnormally short, in patients with seizures with significant oxygen desaturations,” said Lisa Bateman, MD, assistant professor of clinical neurology at the University of California, Davis.
“There were even changes in seizures without significant oxygen desaturations, but (it) was much more commonly seen in the seizures that were associated with more severe respiratory dysfunction. And that's significant because both long and short QT intervals are associated with potentially fatal cardiac arrhythmias.”
The 17 study participants had 56 seizures that were analyzed — 37 of them with oxygen desaturation and 19 without oxygen desaturation — during video EEG telemetry.
“There's a debate about the precise mechanism,” Dr. Bateman said. “Is it primarily related to the seizure, that for some reason in response to the seizure there's a total brain shutdown and that eventually leads to failure of breathing and failure of the heart? Is there actually a primary cardiac mechanism? There have been arrhythmias seen associated with seizures.” She noted one case of a patient suffering a fatal arrhythmia after a seizure while in an epilepsy monitoring unit.
It's also possible that respiratory distress is the primary culprit. In their work, UC Davis researchers found that one-third of patients with intractable, localization-related epilepsy suffer hypoxemia during seizures.
“The depth and duration of hypoxemia with the seizures, makes it more likely that there's going to be more significant cardiac dysfunction,” she said. “Potentially you could say the degree of your respiratory dysfunction puts you more at risk for more severe cardiac dysfunction and that becomes a final common pathway for why patients die.”
One diffuclty in putting the data to use might be identifying the patients who are likely to suffer from low oxygen during seizures.
“We don't know” who might suffer from that problem, she said. She added that there's evidence suggesting that men might be more likely to have the problem than women, as well as those with seizures based in the right temporal lobe, seizures that spread to the other side of the brain and seizures of longer duration. It's also likely that you'll suffer from low oxygen again during a subsequent seizure if it has already happened.
“All of these studies come from patients who are in an epilepsy monitoring unit,” Dr. Bateman said. “These are patients with medically intractable seizures and they're being worked up for surgery. We don't know until we actually see them have a seizure.
Commenting on the study, Arthur J. Moss, MD, professor of medicine (cardiology) at the University of Rochester Medical Center, noted that some of the causes of seizure disorders involve ion channelopathies that overlap with long QT syndrome (LQTS). The hypoxia following some seizures could certainly alter ventricular repolarization, he said.
“In the vulnerable cardiac patient with some intrinsic prolongation in ventricular repolarization that can occur in LQTS and some other inherited arrhythogenic disorders, the post-seizure hypoxia could be the straw that breaks the camel's back,” he continued. But, he added, I doubt that short QT interval or QT dispersion is playing a role. The number of patients in the current study is relatively small, he noted, but the authors may be on to at least one mechanism to explain SUDEP.
John Bodensteiner, MD, a pediatric neurologist in the Department of Neurology at Mayo Clinic in Rochester, MN, said he has seen children die of SUDEP and that the study might verify a suspicion.
“We've all thought that there might be an arrhythmia as the cause,” he said. “If you identify a patient as an at-risk person, you could theoretically decrease the risk.”
If this is done, there might be options for better treatment, he said. “Maybe those people should carry a pacemaker, or have a pacemaker placed,” he said, adding that medical therapy might be a possibility.
Elson So, MD, professor of neurology at the Mayo Clinic in Rochester, MN, who has studied SUDEP, said the study is an important step. “We do not know if a person with epilepsy with long QT in this setting will necessarily have a fatal arrhythmia, but it is important enough to know what seizure-related changes in the EKG could serve as a potential cause of SUDEP.”
He said generalized convulsive seizures and prolonged seizures in general carry higher risk for hypoxemia. Other than that, there is no good way to know ahead of time, without inpatient epilepsy monitoring, which patients will suffer hypoxemia during seizures.
Antiepileptic drugs (AED) are often tapered during inpatient monitoring to increase the likelihood of seizure occurrence and recording. An alternative would be to monitor patients who suffer frequent seizures at home with an oximetry monitor, said Dr. So, which would allow seizures to be recorded without having to withdraw the AED on an outpatient basis.
As more is learned, it may become worthwhile to more routinely monitor patients' oxygenation in the epilepsy unit, Dr. So said.
- Abnormally prolonged QT intervals — corrected for the heart rate — were more likely during desaturation periods than during the pre-seizure period (p<.0001). Abnormally shortened QT intervals were also more likely (p<.0001).
- Prolonged QT intervals were more likely during desaturation seizures than non-desaturation seizures, as were shortened QT intervals (p<.0001 for both).
- The range of QT intervals — the difference between the shortest and longest intervals — tended to be larger, and therefore more problematic, when the desaturations were more severe and the duration of the desaturation period was longer (p<.0001).