WASHINGTON (FRONTLINE MEDICAL NEWS) – It has long been hypothesized that sudden unexpected death in epilepsy (SUDEP) is the result of damage to areas of the brain that control breathing and heart rate, but two studies presented at the American Epilepsy Society annual meeting identified specific areas where structural changes correlate with SUDEP, suggesting the potential for screening.

In one of two studies that evaluated MRI images in patients who subsequently died of SUDEP and compared them to patients with epilepsy or normal healthy individuals, brainstem volume loss was not only greater in those with SUDEP but there was a correlation between greater volume loss and a shorter period of survival, reported Susanne G. Mueller, MD , a radiologist affiliated with the Center for Imaging of Neurodegenerative Diseases at the San Francisco Veterans Affairs Medical Center.

“This is the first evidence that brainstem damage, one of the mechanisms that has been shown to cause SUDEP in animals, could also play a role in people with epilepsy,” Dr. Mueller reported. Although more work is needed, volume loss observed on MRI “could be used as a potential biomarker to assess the individual SUDEP risk in epilepsy patients.”

In one of two populations studied, investigators analyzed MRI scans from 27 SUDEP patients taken prior to death. Focusing on brainstem areas involved in autonomic function, deformation morphometry generated profile maps that isolated areas of volume loss. The changes suggested that focal epilepsy produced structural changes in the mesencephalic region of the lower brainstem. Damage to nuclei involved in control of heart rate variability and other autonomic functions would be consistent with increased risk of SUDEP.

“We can just report what we see on imaging. These data do not tell us the cause of SUDEP, but they do show correlations that are consistent with current theories,” Dr. Mueller explained.

In a second study that compared 18 patients with focal epilepsy to 11 controls, greater volume loss in patients with epilepsy correlated negatively with heart rate variability, a relationship not seen in the controls. The volume loss in periventricular gray and medulla oblongata nuclei was most closely associated with heart rate variability, which is considered a surrogate for altered autonomic function, Dr. Mueller reported.

Similar conclusions were reached in a different study conducted at a separate institution. In this study, MRI scans from 237 patients with epilepsy and 110 healthy controls were evaluated. Four of the epilepsy patients subsequently died of SUDEP.

Overall, although a variety of structural differences were observed between epilepsy patients and healthy controls, SUDEP patients were found to have significantly decreased volumes in the caudate, putamen, and nucleus accumbens, reported Allan George, associate research coordinator at the Comprehensive Epilepsy Center of New York University Langone Medical Center, New York.

“These are all areas that can be involved in autonomic function potentially involved in SUDEP,” Mr. George said. Like Dr. Mueller, Mr. George cautioned that clinically viable algorithms that would allow MRI to assess SUDEP risk may be years away, but these studies provide preliminary evidence that structural changes on MRI could eventually serve as a SUDEP biomarker.

There was limited overlap between the areas of structural change potentially associated with SUDEP in the studies presented by Dr. Mueller and Mr. George, but Dr. Mueller said that SUDEP might not stem from a single epilepsy-induced brain abnormality. She reported that more MRI scans to trace structural changes in SUDEP patients are likely to identify more areas of interest. Acquiring a large number of MRI scans is a challenge, but Dr. Mueller envisions a registry where routine scans could be submitted. This would permit this research to be conducted on a larger scale.

“There is a similar initiative to collect MRI brain images of patients with Alzheimer’s disease,” said Dr. Mueller, noting that this provides a precedent for the type of research needed in epilepsy. If a similar program could be undertaken in epilepsy, Dr. Mueller believes it might substantially accelerate the effort to understand and recognize risk of SUDEP.

Mr. George’s study was funded by FACES (Finding a CURE for Epilepsy/Seizures). Dr. Mueller’s study was funded by grants from UCSF, the Epilepsy Foundation, and the National Institutes of Health. Dr. Mueller and Mr. George reported no potential conflicts of interest related to this topic.

SOURCE: Mueller S et al., AES 2017 abstract 3.205 and George A et al., AES 2017 abstract 3.214


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