Skip to main content Accessibility help
×
Home
  • Print publication year: 2019
  • Online publication date: October 2019

Chapter 3 - Pathology of the Epilepsies

Summary

The pathology of epilepsy is a complex and evolving field, reflecting both rapid developments in diagnostic and therapeutic techniques, and the continued difficulties in translating electrical and functional phenomena into traditional categories of morphological disease. A seizure is an acute neurological event due to sudden excessive disorderly discharge of neurons.1 Lesions that are presumed to cause seizures can be either structural, definable by morphological techniques such as radiology and anatomic pathology, or functional, definable by clinical localization, electrophysiology, and, in some cases, functional imaging defining a focus. Causality is inferred by correlation of morphological findings and location with clinical and electrophysiological data and, in some cases, by the cessation of subsequent seizures after removal of the lesion or focus. Epilepsy is intermittent recurrence of seizures. The finding of structural lesions in some forms of epilepsy suggests and supports causality, but our understanding of the chain between the definable structural lesion and the recurrence of seizures is often less clear.2 Causality may be particularly difficult to determine in conditions producing multiple structural lesions such as tuberous sclerosis, where one lesion is epileptogenic and other similar lesions are not. Even determining how a particular electrically active focus propagates to evolve into a particular seizure or series of intractable seizures is also incompletely understood. To add to the difficulty, seizures or epilepsy itself can be causal, resulting in progressive brain damage and self-perpetuating seizures, particularly in some forms of temporal lobe epilepsy. Moreover, some treatments for epilepsy themselves have been associated with some forms of brain damage.

1.Scharfman, HE. Epilepsy. In: Zigmond, MJ, Rowland, LP, Coyle, JT, eds., Neurobiology of Brain Disorders: Biological Basis of Neurological and Psychiatric Disorders. Waltham, MA: Academic Press; 2015:236261.
2.Thom, M, Sisodiya, S. Epilepsy. In: Love, S, Perry, A, Ironside, JW, Budka, H, eds., Greenfield’s Neuropathology. 9th edn. Boca Raton, FL: CRC Press; 2015:683739.
3.Marras, CE, Granata, T, Franzini, A, et al. Hemispherotomy and functional hemispherectomy: indications and outcome. Epilepsy Res. 2010;89(1):104112.
4.Blumcke, I, Aronica, E, Miyata, H, et al. International recommendation for a comprehensive neuropathologic workup of epilepsy surgery brain tissue: a consensus Task Force report from the ILAE Commission on Diagnostic Methods. Epilepsia. 2016;57(3):348358.
5.Blumcke, I, Thom, M, Aronica, E, et al. International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a Task Force report from the ILAE Commission on Diagnostic Methods. Epilepsia. 2013;54(7):13151329.
6.Blumcke, I, Kistner, I, Clusmann, H, et al. Towards a clinico-pathological classification of granule cell dispersion in human mesial temporal lobe epilepsies. Acta Neuropathol. 2009;117(5):535544.
7.Squier, W. Grey matter lesions. In: Golden, J, Harding, BN, eds., Developmental Neuropathology. Basel, Switzerland: ISN Neuropath Press; 2004:171175.
8.Loman, AM, ter Horst, HJ, Lambrechtsen, FA, Lunsing, RJ. Neonatal seizures: aetiology by means of a standardized work-up. Eur J Paediatr Neurol. 2014;18(3):360367.
9.Ronen, GM, Penney, S, Andrews, W. The epidemiology of clinical neonatal seizures in Newfoundland: a population-based study. J Pediatr. 1999;134(1):7175.
10.Barkovich, AJ, Guerrini, R, Kuzniecky, RI, Jackson, GD, Dobyns, WB. A developmental and genetic classification for malformations of cortical development: update 2012. Brain. 2012;135(Pt 5):13481369.
11.Barkovich, AJ. Current concepts of polymicrogyria. Neuroradiology. 2010;52(6):479487.
12.Blumcke, I, Thom, M, Aronica, E, et al. The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission. Epilepsia. 2011;52(1):158174.
13.Mirzaa, GM, Poduri, A. Megalencephaly and hemimegalencephaly: breakthroughs in molecular etiology. Am J Med Genet C Semin Med Genet. 2014;166C(2):156172.
14.Islam, MP, Roach, ES. Tuberous sclerosis complex. Handb Clin Neurol. 2015;132:97109.
15.Stafstrom, CE, Staedtke, V, Comi, AM. Epilepsy mechanisms in neurocutaneous disorders: tuberous sclerosis complex, neurofibromatosis type 1, and Sturge-Weber syndrome. Front Neurol. 2017;8:87.
16.Adriaensen, ME, Schaefer-Prokop, CM, Stijnen, T, et al. Prevalence of subependymal giant cell tumors in patients with tuberous sclerosis and a review of the literature. Eur J Neurol. 2009;16(6):691696.
17.Comi, AM. Sturge-Weber syndrome. Handb Clin Neurol. 2015;132:157168.
18.Shirley, MD, Tang, H, Gallione, CJ, et al. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013;368(21):19711979.
19.Erturk Cetin, O, Isler, C, Uzan, M, Ozkara, C. Epilepsy-related brain tumors. Seizure. 2017;44:9397.
20.Soffietti, R, Ruda, R, Reardon, D. Rare glial tumors. Handb Clin Neurol. 2016;134:399415.
21.Blumcke, I, Aronica, E, Urbach, H, Alexopoulos, A, Gonzalez-Martinez, JA. A neuropathology-based approach to epilepsy surgery in brain tumors and proposal for a new terminology use for long-term epilepsy-associated brain tumors. Acta Neuropathol. 2014;128(1):3954.
22.Chassoux, F, Daumas-Duport, C. Dysembryoplastic neuroepithelial tumors: where are we now? Epilepsia. 2013;54 (Suppl 9):129134.
23.Ida, CM, Rodriguez, FJ, Burger, PC, et al. Pleomorphic xanthoastrocytoma: natural history and long-term follow-up. Brain Pathol. 2015;25(5):575586.
24.Rasmussen, T, Olszewski, J, Lloyd-Smith, D. Focal seizures due to chronic localized encephalitis. Neurology. 1958;8(6):435445.
25.Bien, CG, Granata, T, Antozzi, C, et al. Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement. Brain. 2005;128(Pt 3):454471.
26.Varadkar, S, Bien, CG, Kruse, CA, et al. Rasmussen’s encephalitis: clinical features, pathobiology, and treatment advances. Lancet Neurol. 2014;13(2):195205.
27.Brenton, JN, Goodkin, HP. Antibody-mediated autoimmune encephalitis in childhood. Pediatr Neurol. 2016;60:1323.
28.Bauer, J, Bien, CG. Neuropathology of autoimmune encephalitides. Handb Clin Neurol. 2016;133:107120.