Marian Galovic1,2,3,4, Victor Q H van Dooren1, Tjardo S Postma1,5, Sjoerd B Vos1,2,6, Lorenzo Caciagli1,2, Giuseppe Borzì1,7, Juana Cueva Rosillo1, Khue Anh Vuong1, Jane de Tisi1, Parashkev Nachev1, John S Duncan1,2, Matthias J Koepp1,2. 1. Department of Clinical and Experimental Epilepsy, University College London Queen Square Institute of Neurology, London, United Kingdom. 2. Magnetic Resonance Imaging Unit, Epilepsy Society, Chalfont St Peter, Buckinghamshire, United Kingdom. 3. Department of Neurology, Kantonsspital St Gallen, St Gallen, Switzerland. 4. Department of Neurology, University Hospital Zurich, Switzerland. 5. Department of Child Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands. 6. Centre for Medical Image Computing, University College London, London, United Kingdom. 7. Institute of Neurology, University of Catanzaro, Catanzaro, Italy.
Abstract
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.
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.
Authors: S Patodia; M Tachrount; A Somani; I Scheffer; T Yousry; X Golay; S M Sisodiya; M Thom Journal: Neuropathol Appl Neurobiol Date: 2020-07-15 Impact factor: 8.090
Authors: Ezequiel Gleichgerrcht; Simon S Keller; Daniel L Drane; Brent C Munsell; Kathryn A Davis; Erik Kaestner; Bernd Weber; Samantha Krantz; William A Vandergrift; Jonathan C Edwards; Carrie R McDonald; Ruben Kuzniecky; Leonardo Bonilha Journal: Ann Neurol Date: 2020-09-10 Impact factor: 10.422
Authors: Alexander C Whiting; Marcia Morita-Sherman; Manshi Li; Deborah Vegh; Brunno Machado de Campos; Fernando Cendes; Xiaofeng Wang; William Bingaman; Lara E Jehi Journal: Epilepsia Date: 2021-03-23 Impact factor: 5.864
Authors: Erik Kaestner; Anny Reyes; Zhong Irene Wang; Daniel L Drane; Vineet Punia; Bruce Hermann; Robyn M Busch; Carrie R McDonald Journal: Epilepsia Date: 2020-10-14 Impact factor: 5.864
Authors: Kristin E Wills; Hernán F J González; Graham W Johnson; Kevin F Haas; Victoria L Morgan; Saramati Narasimhan; Dario J Englot Journal: Epilepsy Behav Date: 2020-12-15 Impact factor: 2.937
Authors: Anny Reyes; Erik Kaestner; Emily C Edmonds; Anna Christina Macari; Zhong Irene Wang; Daniel L Drane; Vineet Punia; Robyn M Busch; Bruce P Hermann; Carrie R McDonald Journal: Epilepsia Date: 2020-12-01 Impact factor: 5.864
Authors: Thomas W Owen; Jane de Tisi; Sjoerd B Vos; Gavin P Winston; John S Duncan; Yujiang Wang; Peter N Taylor Journal: Eur J Neurosci Date: 2020-12-11 Impact factor: 3.698
Authors: Rodney Ogwang; Albert Ningwa; Pamela Akun; Paul Bangirana; Ronald Anguzu; Rajarshi Mazumder; Noriko Salamon; Oliver Johannes Henning; Charles R Newton; Catherine Abbo; Amos Deogratius Mwaka; Kevin Marsh; Richard Idro Journal: Front Neurol Date: 2021-06-03 Impact factor: 4.003