Aetiology of cognitive impairment in children with frontal lobe epilepsy Braakman HMH, Vaessen MJ, Jansen JFA, Debeij-van Hall MHJA, de Louw A, Hofman PAM, Vles JSH, Aldenkamp AP, Backes WH. Aetiology of cognitive impairment in children with frontal lobe epilepsy. Acta Neurol Scand: DOI: 10.1111/ane.12283. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objectives – Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE), but its aetiology is unknown. MRI scans often reveal no structural brain abnormalities that could explain the cognitive impairment. This does not exclude more subtle morphological abnormalities that can only be detected by automated morphometric techniques. Aims – With these techniques, we investigate the relationship between cortical brain morphology and cognitive functioning in a cohort of children with FLE and healthy controls. Materials and Methods – Thirty-four children aged 8–13 years with FLE of unknown cause and 41 healthy age-matched controls underwent neuropsychological assessment and structural brain MRI. Patients were grouped as cognitively impaired or unimpaired. Intracranial volume, white matter volume, lobular cortical volume, cortical thickness and volumes of cortex structures were compared between patients and controls, and potential correlations with cognitive status were determined. Results – The group of cognitively impaired children with FLE had significantly smaller left temporal cortex volumes, specifically middle temporal grey matter volume and entorhinal cortex thickness. In addition, cognitively impaired children with FLE had smaller volumes of structures in the left and right frontal cortex, right temporal cortex and the left subcortical area. Conclusion – Cognitively impaired children with FLE have smaller volumes of various cortex structures within the frontal lobes and in extra-frontal regions, most notably temporal cortex volumes. These findings might well explain the broad scale of cognitive domains affected in children with FLE complicated by cognitive impairment and highlight that FLE impacts on areas beyond the frontal lobe. H. M. H. Braakman 1,2,3 , M. J. Vaessen 2,3,4 , J. F. A. Jansen 2,4 , M. H. J. A. Debeij-van Hall 3 , A. de Louw 3 , P. A. M. Hofman 2,3,4 , J. S. H. Vles 1,2,3 , A. P. Aldenkamp 1,2,3 , W. H. Backes 2,4 1 Department of Neurology, Maastricht University Medical Centre, Maastricht, the Netherlands; 2 Research School for Mental Health & Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands; 3 Department of Research and Development, Epilepsy Centre Kempenhaeghe, Heeze, the Netherlands; 4 Department of Radiology, Maastricht University Medical Centre, Maastricht, the Netherlands Key words: all epilepsy/seizures; MRI; volumetric MRI; neuropsychological assessment; all paediatric H. M. H. Braakman, Department of Neurology, Maastricht University Medical Centre, P. Debyelaan 25, 6202 AZ Maastricht, the Netherlands Tel.: +31 43 3877056 Fax: +31-43-3877055 e-mail: hilde.braakman@gmail.com Accepted for publication July 10, 2014 Introduction Frontal lobe epilepsy (FLE) in childhood is fre- quently complicated by cognitive impairment. These cognitive impairments often cover a broad range of cognitive domains and frequently result in a need for special education (1, 2). The aetiology of cognitive deficits in children with FLE is unknown, and correlations with clinical epilepsy characteristics remain inconclu- sive (1, 2). MRI scans often reveal no structural brain abnormalities that may explain the cogni- tive impairment, as FLE in childhood is usually of unknown cause (2). However, the cognitive impairment may still be related to more subtle morphological abnormalities that remain unno- ticed on a visual MRI assessment. With sophisti- cated software programs to analyse brain morphology, this relationship can be investi- gated. In previous studies, atrophy of various brain structures, including the hippocampus, thalamus, amygdala and mammillary bodies, has, 1 Acta Neurol Scand DOI: 10.1111/ane.12283 © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA