Epilepsy Surgery Shows Potential to Reverse Aging Effects of Temporal Lobe Epilepsy

Simon S. Keller, PhD

Findings from a study recently published in Neurology showed that epilepsy surgery was associated with reduced brain imaging defined age, suggesting that some morphological brain changes linked with accelerated aging in mesial temporal lobe epilepsy (mTLE) may be reversible.

"This is consistent with studies that found neuropsychological improvements following surgery and those calling for earlier surgical intervention where medical therapy is ineffective," senior author Simon S. Keller, PhD, Department of Pharmacology, University of Liverpool, and colleagues wrote. "Models of brain-predicted age may provide insight into the treatment and prognosis of epilepsy."

Investigators analyzed the structural T1-weighted (T1w) MR images obtained from 48 patients with refractory mTLE before and after temporal lobe surgery to estimate brain-age using a gaussian processes regression model. The Brain-Age-Gap-Estimation (BrainAGE), a measure of overall brain health, was used to test the effect of neurosurgery, comparing patients to 37 age- and sex-matched controls. Keller et al expected patients to have higher BrainAGE but that successful surgery would be associated with an overall decrease.

On average, patients with epilepsy showed an increased BrainAGE of 7.97 years compared with controls prior to surgery (95% CI, 5.26-10.8) and an increase of 2.8 years following surgery (95% CI, 0.05-5.78). Before surgery, BrainAGE differences were apparent between controls and sub-groups such as those who were seizure free (8.71 years [95% CI, 5.65-12.3]), persistent seizures (PS; 7.09 years [95% CI, 3.69-10.6]), left mTLE (6.73 years [95% CI, 3.58-9.66]), and right mTLE (10.2 [95% CI, 7.03-14.8]). BrainAGE differences between controls and patient subgroups after surgery were as follows: seizure free: 3.37 years (95% CI, 0.161-7.07); PS, 2.13 years (95% CI, –1.31 to 5.86); left mTLE, 0.16 years (95% CI, –2.78 to 3.17); right mTLE, 7.61 years (95% CI, 4.45-11.7).

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Though resection size did not differ between patient with left- and right-lateralized mTLE (t[44] = –0.03; P = .976), grouping patients by lateralization again revealed higher BrainAGE before surgery for both groups compared to controls (left mTLE: b = 3.72 [95% CI, 1.23-6.21]; right mTLE: b = 7.57 [95% CI, 4.62-10.52]) and a significant left vs right difference. Following surgery, however, individuals with right (b = 7.46 [95% CI, 3.83-11.09]), but not left (b = 0.25 [95% CI, –2.72 to 3.23]) mTLE had significantly higher BrainAGE compared to controls.

Investigators noted that the BrainAGE imaging biomarker may be used in to identify patients at high risk of sudden unexplained death in epilepsy (SUDEP), due to its ability to independently predict mortality. “Brain-age models may play both a prognostic and diagnostic role in the neurocognitive and psychiatric disorders associated with epilepsy, as these have proven to be useful in the context of psychiatric disease and impaired cognition,” the authors wrote. “Other advances in deep learning applied to brain images are beginning to play a role in clinical decision-making, such as the automatic classification and prognostics of TLE.”

REFERENCE

De Bezenac CE, Adan G, Weber B, Keller SS. Association of epilepsy surgery with changes in imaging defined brain age. Neurology. Published online July 14, 2021. doi: 10.1212/WNL.00000000000012289