[Skip to Content]
[Skip to Content Landing]
Views 1,131
Citations 0
Original Investigation
July 1, 2019

Progressive Cortical Thinning in Patients With Focal Epilepsy

Author Affiliations
  • 1Department of Clinical and Experimental Epilepsy, University College London Queen Square Institute of Neurology, London, United Kingdom
  • 2Magnetic Resonance Imaging Unit, Epilepsy Society, Chalfont St Peter, Buckinghamshire, United Kingdom
  • 3Department of Neurology, Kantonsspital St Gallen, St Gallen, Switzerland
  • 4Department of Child Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands
  • 5Centre for Medical Image Computing, University College London, London, United Kingdom
  • 6Institute of Neurology, University of Catanzaro, Catanzaro, Italy
JAMA Neurol. Published online July 1, 2019. doi:10.1001/jamaneurol.2019.1708
Key Points

Question  Is epilepsy a progressive neurodegenerative disease?

Findings  In this case-control study of 331 adults with 678 magnetic resonance imaging scans, widespread progressive cortical thinning distinct from normal aging was detected in 146 of 190 individuals with epilepsy (76.8%). Cortical thinning was most pronounced in individuals with epilepsy older than 55 years and during the first 5 years after the onset of seizures.

Meaning  People with focal epilepsy may develop progressive cortical atrophy that can affect widespread cortical areas.


Importance  It is controversial whether epilepsy is a static or progressive disease. Evidence of progressive gray matter loss in epilepsy would support early diagnosis, rapid treatment, and early referral for surgical interventions.

Objective  To demonstrate progressive cortical thinning in patients with focal epilepsy distinct from cortical thinning associated with normal aging.

Design, Setting, and Participants  A case-control neuroimaging study was conducted from August 3, 2004, to January 26, 2016, among 190 patients with focal epilepsy at a tertiary epilepsy referral center (epilepsy data) and 3 independent comparison cohorts matched for age and sex (healthy volunteer data; n = 141).

Exposures  Two or more high-resolution T1-weighted magnetic resonance imaging scans at least 6 months apart (mean [SD] interval, 2.5 [1.6] years).

Main Outcomes and Measures  Global and vertexwise rate of progressive cortical thinning.

Results  A total of 190 people with focal epilepsy (99 women and 91 men; mean [SD] age, 36 [11] years; 396 magnetic resonance imaging scans) were compared with 141 healthy volunteers (76 women and 65 men; mean [SD] age, 35 [17] years; 282 magnetic resonance imaging scans). Widespread highly significant progressive cortical thinning exceeding normal aging effects, mainly involving the bilateral temporal lobes, medial parietal and occipital cortices, pericentral gyri, and opercula, was seen in 146 individuals with epilepsy (76.8%; 95% CI, 58%-95%). The mean (SD) annualized rate of global cortical thinning in patients with epilepsy was twice the rate of age-associated thinning observed in healthy volunteers (0.024 [0.061] vs 0.011 [0.029] mm/y; P = .01). Progression was most pronounced in adults older than 55 years and during the first 5 years after the onset of seizures. Areas of accelerated cortical thinning were detected in patients with early onset of epilepsy and in patients with hippocampal sclerosis. Accelerated thinning was not associated with seizure frequency, history of generalized seizures, or antiepileptic drug load and did not differ between patients with or without ongoing seizures. Progressive atrophy in temporal (n = 101) and frontal (n = 28) lobe epilepsy was most pronounced ipsilaterally to the epileptic focus but also affected a widespread area extending beyond the focus and commonly affected the contralateral hemisphere. For patients with temporal lobe epilepsy, accelerated cortical thinning was observed within areas structurally connected with the ipsilateral hippocampus.

Conclusions and Relevance  Widespread progressive cortical thinning exceeding that seen with normal aging may occur in patients with focal epilepsy. These findings appear to highlight the need to develop epilepsy disease-modifying treatments to disrupt or slow ongoing atrophy. Longitudinal cortical thickness measurements may have the potential to serve as biomarkers for such studies.