Literature Review

Patients with focal epilepsy have progressive cortical thinning



Many patients with focal epilepsy may have widespread progressive cortical thinning to an extent greater than that associated with normal aging, according to research published online July 1 in JAMA Neurology. Methods for preventing this thinning are unknown. “Our findings appear to highlight the need for longitudinal studies to develop disease-modifying treatments for epilepsy,” said Marian Galovic, MD, a doctoral student at University College London, and colleagues.

To date, neurologists have not found a definitive answer to the question of whether epilepsy is a static or progressive disease. Few longitudinal studies have examined patients with structural neuroimaging to determine whether the brain changes over time. The studies that have taken this approach have had small populations or have lacked control populations.

Comparing brain changes in patients and controls

Dr. Galovic and colleagues analyzed data for consecutive patients with focal epilepsy who underwent follow-up at the National Hospital for Neurology and Neurosurgery in London. The data were collected from Aug. 3, 2004, to Jan. 26, 2016. The researchers chose individuals who had at least 2 high-resolution T1-weighted MRI scans performed on the same scanner more than 6 months apart. They excluded patients with brain lesions other than hippocampal sclerosis, those with inadequate MRI scan quality, and those for whom clinical data were missing. To match these patients with controls, Dr. Galovic and colleagues chose three longitudinal data sets with data for healthy volunteers between ages 20 and 70 years. Each control participant had two high-resolution T1-weighted scans taken more than 6 months apart. The investigators matched patients and controls on age and sex. The automated and validated Computational Anatomy Toolbox (CAT12) estimated cortical thickness.

Dr. Galovic’s group included 190 patients with focal epilepsy, who had had 396 MRI scans, and 141 healthy controls, who had had 282 MRI scans, in their analysis. Age, sex, and image quality did not differ significantly between the two groups. Mean age was 36 years for patients and 35 years for controls. The proportion of women was 52.1% among patients and 53.9% among controls.

The rate of atrophy was doubled in patients

Approximately 77% of people with epilepsy had progressive cortical thinning that was distinct from that associated with normal aging. The mean overall annual rate of global cortical thinning was higher among patients with epilepsy (0.024) than among controls (0.011). The mean annual rate of cortical thinning increased among people with epilepsy who were older than 55 years. This rate was 0.021 in patients aged 18 to less than 35 years, compared with 0.023 in patients aged 35 to less than 55 years. Seizure frequency, number of antiepileptic drugs (AEDs) taken, and history of secondarily generalized seizures did not differ between age groups.

Compared with healthy controls, patients with focal epilepsy had widespread areas of greater progressive atrophy. Bilaterally affected areas included the lateral and posterior temporal lobes, posterior cingulate gyri, occipital lobes, pericentral gyri, and opercula. The distribution of progressive thinning in all patients with epilepsy was similar to regions connected to both hippocampi. Healthy controls had no areas of greater cortical thinning, compared with patients with epilepsy.

Progressive thinning in the left postcentral gyrus was greater in patients with left temporal lobe epilepsy (TLE) than in those with right TLE. Cortical thinning was more progressive in patients with right frontal lobe epilepsy (FLE) than in those with left FLE, particularly in right parietotemporal and right frontal areas.

Dr. Galovic and colleagues found no association between the rate of cortical thinning and seizure frequency, history of secondarily generalized seizures, or number of AEDs taken between MRIs. They found no difference in the rate of atrophy between patients with epilepsy with ongoing seizures and those without. The annual mean rate of cortical thinning was higher in people with a short duration of epilepsy (i.e., less than 5 years), compared with patients with a longer duration of epilepsy (i.e., 5 years or more).

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