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Neuropathological spectrum of cortical dysplasia in children with severe focal epilepsies

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Abstract

Cortical dysplasias comprise a variable spectrum of clinical, neuroradiological and histopathological findings. We report about a cohort of 25 pediatric patients (mean age 8.1±4.8 years) with severe drug-resistant early onset focal epilepsies (mean duration 2.1±0.4 years), mental/psychomotor retardation, and multilobar epileptogenesis. Compared to age-matched biopsy controls, microscopical inspection of neurosurgically resected specimens revealed dysplastic neurons with/without balloon cells in only 7 patients. According to Palmini’s classification system, these lesions were categorized as focal cortical dysplasia (FCD) type II. All other patients presented with rather subtle but statistically significant neuroanatomical abnormalities. We identified increased numbers of ectopic neurons in white matter and cortical gliosis. However, most intriguing was our finding of a microcolumnar arrangement of cortical neurons in layer III. These microcolumns can be statistically defined as vertical lining of more than eight neurons (two times standard deviation of cell countings obtained from controls). In addition, neuronal perikarya were significantly smaller in epilepsy patients. Although histological abnormalities occurring during postnatal maturation of the brain challenge any neuropathological classification in this group of young patients, we propose that these findings are classified according to FCD type I. Our observations support a concept compatible with regional loss of high-order brain organization.

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Acknowledgements

The authors thank Dr. Riederer (Institut de Biologie Cellulaire et de Morphologie, Université Lausanne, Lausanne) for donation of antibodies; Ms. Gutmann and Ms. Rings (Department of Neuropathology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany) are kindly acknowledged for their technical support. The study was supported by the DFG BL421/1-1 and the ELAN-Fond of the University Hospital Erlangen-Nuremberg.

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Authors and Affiliations

  1. Department of Neuropathology and Neuropathological Reference Center for Epilepsy Surgery, University of Erlangen-Nuremberg, Krankenhausstr. 8–10, 91054, Erlangen, Germany

    Michelle Hildebrandt & Ingmar Blümcke

  2. Neuropediatric Clinic and Clinic for Neurorehabilitation—Epilepsy Center for Children and Adolescents, Behandlungszentrum Vogtareuth, Krankenhausstr. 20, 83569, Vogtareuth, Germany

    Tom Pieper & Hans Holthausen

  3. Department of Radiology, Olgaspital, Bismarckstr. 8, 70176, Stuttgart, Germany

    Peter Winkler

  4. Clinic for Neurosurgery and Neuroradiology, Behandlungszentrum Vogtareuth, Krankenhausstr. 20, 83569, Vogtareuth, Germany

    Dieter Kolodziejczyk

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  1. Michelle Hildebrandt
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  2. Tom Pieper
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Correspondence to Ingmar Blümcke.

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Hildebrandt, M., Pieper, T., Winkler, P. et al. Neuropathological spectrum of cortical dysplasia in children with severe focal epilepsies. Acta Neuropathol 110, 1–11 (2005). https://doi.org/10.1007/s00401-005-1016-6

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