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Cortical Thinning Rates Indicate Epilepsy Is a Progressive Disorder


NEW ORLEANS—The faster pace of cortical thinning among those with non-lesional focal epilepsy compared with healthy controls indicates that epilepsy is a progressive rather than a static disease, researchers reported here at the American Epilepsy Society annual meeting.

Magnetic resonance imaging (MRI) scans for cortical thinning in epilepsy patients compared with healthy matched controls provided a reliable measure for establishing that the disease is in fact progressive.

"By directly comparing patients with healthy volunteers, we were able to differentiate epilepsy-induced progression from normal aging, and this is something that most previous studies struggled with," said Marian Galovic, MD, a PhD student at University College London. "We demonstrated widespread areas of progressive epilepsy-related atrophy that exceeded aging-related changes that we observed in healthy volunteers."

Researchers enrolled 190 patients who underwent 396 MRI scans and 141 age- and sex-matched controls who underwent 242 MRI scans. They all had at least two scans on the same scanner more than six months apart.

The research team found that those with epilepsy had an overall yearly global cortical thinning rate of .024 mm compared with a rate of  .011 mm for the healthy controls (p=.01). Using a machine learning model, researchers found that there was progressive atrophy — thinning at a rate faster than those in the control group — in 73 percent of those with epilepsy.

Researchers also described the distribution of progressive thinning in the cortex: It was most pronounced on the side of the epileptic focus but also affected areas beyond that location, frequently affecting the other hemisphere. They also found that the atrophy occurred at an overall faster rate with earlier onset of epilepsy and in those with hippocampal sclerosis.

A somewhat surprising finding, they reported, was that progressive atrophy was not associated with seizure frequency. The lack of a link to seizures was somewhat perplexing, and will require more investigation, Dr. Galovic said. This finding, researchers hypothesized, supports the notion that progressive atrophy in epilepsy is not entirely driven by the direct effects of detectable seizures, but rather represents the ongoing network disruption as an underlying pathogenic process in epilepsy, which could be a seizure-independent phenomenon. On the other hand, the lack of a link [to seizure activity] underscores the message that seizure counts reported by patients should be "viewed with caution."

"It can be an unreliable parameter," Dr. Galovic said. 

The broader point — that epilepsy is progressive — should lend urgency to the care of patients.

"If epilepsy is progressive, it has implications for how quickly we diagnose epilepsy and how rapidly it's treated," he said. "And we know that there are frequent delays in offering epilepsy surgery to people with refractory seizures. This would be big incentive to speed up these delays that tend to occur."

Dr. Galovic added: "The practical application of this, besides knowing that epilepsy is progressive, is to do further research, and longitudinal MRI could be a practical and reliable surrogate marker for progressive neurodegeneration in epilepsy or progression of the disease."

Jacqueline A. French, MD, FAAN, professor of neurology at the New York University Comprehensive Epilepsy Center, said that future insights could stem from the measurement of cortical thinning.

"This is an important finding, because we might find that the amount of thinning is related to other things, such as the likelihood of treatment resistance or the cause of the epilepsy," she said. "It is a good first step."

The study was funded by the Medical Research Council. Neither Drs. Galovic and French reported disclosures relevant to the study.


AES Abstract 2.184: Galovic M, Van Dooren V, Postma T, et al. Is epilepsy a progressive neurodegenerative disease? Evidence from a large multicentre longitudinal neuroimaging study.