The epilepsies in childhood are classified as primary (or idiopathic) and secondary (or symptomatic). The primary epilepsies account for two thirds of all childhood epilepsies and are presumed to be genetically determined. In the remaining one third of cases, a neuropathologic lesion can be identified. This paper summarizes the etiologies of the symptomatic epilepsies. They are classified according to the pathologic processes; malformative, metabolic, neoplastic and phakomatoses, hypoxic-ischemic, infectious, and of unknown pathologic process. (J Child Neurol 1998;13:361-371).
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References
1.
Sutula T.: The pathologies of the epilepsies: Insights into the causes and consequences of epileptic syndromes, in Dodson WE, Pellock JM (eds): Pediatric Epilepsy: Diagnoses and Therapy. New York, Demos Publications , 1993, pp 37-43.
2.
Lothman EW: Pathophysiology of seizures and epilepsy in the mature and immature brain: Cells, synapses, and circuits, in Dodson WE, Pellock JM (eds): Pediatric Epilepsy: Diagnosis and Therapy. New York, Demos Publications, 1993, pp 1-15.
3.
DeLorenzo RJ: Ion channels, membranes, and molecules in understanding epilepsy and neuronal excitability, in Dodson WE, Pellock JM (eds): Pediatric Epilepsy: Diagnosis and Therapy. New York, Demos Publications , 1993, pp 17-25.
4.
Engel J. Jr: New concepts of the epileptic focus in Wieser HG, Speckmann EJ, Engel J Jr (eds): Current Problems in Epilepsy, vol. 3. The Epileptic Focus. London, John Libbey, 1987, pp 83-94.
5.
a. International League Against Epilepsy, Commission 1989. Epilepsia1989;30:389-399.
6.
Hauser WA: Seizure disorders: The changes with age. Epilepsia1992;33(Suppl):S6-514.
7.
Lyon G., Gastaut H.: Considerations on the significance attributed to unusual cerebral histological findings recently described in eight patients with primary generalized epilepsy . Epilepsia1985; 26:365-367.
8.
Barth PG: Disorders of neuronal migration. Can J Neurol Sci1987;14:1-16.
9.
Hatten ME, Mason CA: Mechanisms of glial-guided neuronal migration in vitro and in vivo . Experientia1990;46:907-916.
10.
Rakic P.: Specification of cerebral cortical areas. Science1988;241:170-176.
11.
Walsh C., Cepko CL: Cell lineage and cell migration in the developing cerebral cortex . Experientia1990;46:940-947.
12.
Shaw CM, Alvord EC: Hydrocephalus, in Duckett S (ed): Pediatric Neuropathology. Baltimore, Williams & Wilkins, 1995, pp 179-184.
13.
Hanaway J., Lee SL, Netsky MG: Pachygyria: Relation of findings to modem embryologic concepts. Neurology1968;18:791-799.
14.
Stewart RM, Richman DP, Caviness VS Jr: Lissencephaly and pachygyria: An architecture and topographical analysis . Acta Neuropathol1975;31:1-12.
15.
Miller JQ: Lissencephaly in two siblings. Neurology1963 ; 13:841-850.
16.
Dieker H., Edwards RH, Zurhein G., et al: The lissencephalic syndrome. Birth Defects1969;5:53-64.
Dobyns WB, Curry CJR, Hoyme HE, et al: Clinical and molecular diagnosis of Miller-Dieker Syndrome. Am J Hum Genet1991;48:584-594.
19.
Van Allen M., Clarren SK: A spectrum of gyral anomalies in Miller-Dieker (Lissencephaly) Syndrome. J Pediatr1983;102:559-564.
20.
Volpe JJ: Neurology of the Newborn. Philadelphia, WB Saunders, 1995.
21.
Dobyns WB, Truwit CL: Lissencephaly and other malformations of cortical development: Update . Neuropediatrics1995;26:132-147.
22.
Williams RS , Ferrante RJ, Caviness VS Jr: The cellular pathology of microgyria. A golgi analysis. Acta Neuropathol1976;36:269-283.
23.
Chan CC, Egbert PR, Herrick MK, Urich H.: Oculocerebral malformations a reappraisal of Walker's "lissencephaly ." Arch Neurol1980;37:104-108.
24.
Gelot A., Billette de Villemeur T., Bordarier C., et al: Developmental aspects of type II lissencephaly: Comparative study of dysplastic lesions in fetal and post-natal brains. Acta Neuropathol1995;89:72-84.
25.
Lyon G., Raymond G., Mogami K., et al: Disorder of cerebellar foliation in Walker's lissencephaly and Neu-Laxova syndrome. J Neuropathol Exp Neurol1993;52:633-639.
26.
Towfighi J. , Sassni JW, Suzuki K., Ladda RL: Cerebro-ocular dysplasia-muscular dystrophy (COD-MD) syndrome. Acta Neuropathol1984;65:110-123.
27.
Leyton QH, Renkawek K., Renier WO, et al: Neuropathological findings in muscle-eye-brain disease (MEB-D) . Acta Neuropathol1991;83:55-60.
28.
Dobyns WB: Classification of the cerebro-ocular muscular syndrome—commentary . Brain Dev1993;15:242-244.
29.
Fukuyama Y. , Osawa M., Suzuki J.: Congenital progressive muscular dystrophy of the Fukuyama type; clinical, genetic and pathological considerations. Brain Dev1981;3:1-29.
30.
Gressens P. , Lammens M., Piccard JJ, Evrard P.: Ethanol induced disturbances of glioneogenesis and neurogenesis in the developing murine brain: An in vitro and in vivo immunohistochemical and ultrastructural study. Alcohol1992;27:219-226.
31.
Spohr HL, Willms J., Steinhausen C.: Prenatal alcohol exposure and long term developmental consequences . Lancet1993;341:907-910.
32.
Clarren SL, Alvord EC, Sumi I.: Brain malformations related to prenatal exposure to ethanol. J Pediatr1978;26:132-147.
33.
Bankl H., Jellinger K.: Central nervous system injuries following fetal carbon monoxide poisoning . Beitr Pathol Anat1967;135:350-376.
34.
Freide RL, Mikolasek J.: Postencephalitis porencephaly, hydranencephaly or polymicrogyria. A review . Acta Neuropathol1978;43:161-168.
35.
Taylor DC, Falconer MA, Bruton CJ, Corsellis JAN: Focal dysplasia of the cerebral cortex in epilepsy. J Neurol Neurosurg Psychiatry1971;34:369-387.
36.
Robinson RO : Familial schizencephaly. Dev Med Child Neurol1991;33:1010-1012.
37.
Barckovich AJ, Kjos BO: Schizencephaly: Correlation of clinical findings with MR characteristics. AJNRNeuroradiol1992; 13:85-94.
38.
Vinters HV, Fisher RS, Comford ME, et al: Morphological substrates of infantile spasms: Studies based on surgically resected cerebral tissue. Childs Nerv Syst1992;8:8-18.
39.
Mischel PS, Nguyen LP, Vinters HV: Cerebral cortical dysplasia associated with pediatric epilepsy. Review of neuropathologic features and proposal for a grading system. J Neuropathol Exp Neurol1995;54:137-153.
40.
Palmini A., Andermann F., Olivier A., et al: Focal neuronal migration disorders and intractable partial epilepsy: A study of 30 patients. Ann Neurol1991;30:712-749.
41.
Daumas-Duport C.: Patterns of tumor growth and problems associated with histological typing of low grade gliomas, in Apuzzo MLJ (ed): Benign Cerebral Glioma, vol 1. Park Ridge, American Association of Neurological Surgeons, 1995, pp 125-148.
42.
Kuzniecky R. , Andermann F., Guerrini R.: Infantile spasms: An early epileptic manifestation in some patients with the congenital bilateral perisylvian syndrome. J Child Neurol1994 ;9:420-423.
43.
Foix C., Chavany JA, Marie J.: Diplegie facio-linguo-masticatrice d'origine cortico-sous-cortical sans paralysie des members. Rev Neurol1926 ;33:214-219.
44.
Pinard JM, Mathe J., Chirin C., et al: Subcortical laminar hetero-topic and lissencephaly in two families: A single X-linked dominant gene. J Neurol Neurosurg Psychiatry1994;57:914-920.
45.
Maloof J., Sledz K., Hogg JP, et al: Unilateral megalencephaly and tuberous sclerosis: Related disorders?J Child Neurol1994;9:443-446.
46.
Bignami A., Palladini G., Zappella M.: Unilateral megalencephaly with nerve cell hypertrophy: An anatomical and quantitative histochemical study. Brain Res1968;9:103-114.
Meenke HJ, Janz D.: The significance of microdysgenesis in primary generalized epilepsy: An answer to the considerations of Lyon and Gastaut. Epilepsia1985;26:368-371.
49.
Hardiman O., Burke T., Phillips J.: Microdysgenesis in resected temporal neocortex: Incidence and clinical significance in focal epilepsy. Neurology1988;38:1041-1047.
50.
Armstrong DD, Bruton CJ: Postscript: What terminology is appropriate for tissue pathology? How does it predict outcome? in Engel J Jr (ed): Surgical Treatment of the Epilepsies. New York, Raven Press, 1987, pp 541-552.
51.
Wolf HK, Wellmer J., Muller M., et al: Glioneuronal malformative lesions and dysembryoplastic neuroepithelial tumors in patients with chronic pharmacoresistant epilepsies. J Neuropathol Exp Neurol1995;54:245-254.
52.
Costantino A., Vinters HV: A pathologic correlate of the "steal" phenomenon in a patient with cerebral arteriovenous malformation. Stroke1985;17:103-106.
53.
Bleck TP, Morrell F., Bergen D., et al: Neuropathologic analysis of tissue excised during cortigraphically guided seizure focus resections. Epilepsia1985;26:535.
54.
Drigo P., Mammi I., Battistella PA, et al: Familial cerebral, hepatic and retinal cavernous angiomas: A new syndrome. Childs Nerv Syst1994;10:205-209.
55.
Lemire RL, Loeser JD, Leech RW, Alvord EC Jr (eds): Normal and abnormal development of the human nervous system. Hagerstown, MD , Harper and Row, 1975, pp 331-334.
56.
deVolder AG , Gadisseaux JF, Michel CJ, et al: Brain glucose utilization in band heterotopia: Synaptic activity of double cortex. Pediatr Neurol1994;11:290-294.
57.
Lyon G, Adams RD, Kolodny EH (eds): Neurology of Hereditary Metabolic Diseases of Children, ed 2. New York, McGraw Hill, 1996, pp 303-309.
58.
Cervos-Navarro J, Urich H (eds): Metabolic and Degenerative Diseases of the Central Nervous System. San Diego, Academic Press, 1995 pp 601-602, 683-684, 689-706.
59.
Chintagumpala M., Armstrong D., Nelson T., et al: Mixed glial tumors, gangliogliomas and dysembryoplastic neuroepithelial tumors in children . Pediatr Neurosurg1996;24:306-313.
60.
Bhattacharjee MD, Armstrong DL, Vogel H., Cooley LD: Cytogenetic analysis of 120 primary pediatric brain tumors with review of the literature. Cancer Genet Cytogenet1997;97:39-53.
61.
Louis DN, Seizinger BR, Cavenee WK: Molecular genetics, basis of cerebral glioma, in Apuzzo MLJ (ed): Benign Cerebral Glioma . Park Ridge, American Association of Neurologic Surgeons , 1995, pp 163-180.
62.
Russell DS, Rubinstein LJ: Pathology of Tumors of the Nervous System. Baltimore , Williams & Wilkins, 1989.
63.
Lang FF, Epstein FJ, Ransohoff J., et al: Central nervous system gangliogliomas. Part 2: Clinical outcome . J Neurosurg1993;79:867-873.
64.
Jaffy PB, Mundt AJ, Baunoch D., et al: The clinical significance of extracellular matrix in gangliogliomas . J Neuropathol Exp Neurol1996;55:1246-1252.
65.
Sloviter RS : Calcium-binding protein (calbindin-D28k) and parvalbumin immunocytochemistry: Localization in the rat hippocampus with specific reference to the selective vulnerability of hippocampal neurons to seizure activity. J Comp Neurol1989;280:183-196.
66.
Daumas-Duport, Scheithauer BW, Chodkiewicz JP, et al: Dysembryoplastic neuroepithelial tumor: A surgically curable tumor of young patients with intractable partial seizures. Neurosurgery1988;23:545-555.
67.
Taratuto AL , Monges L., Lylyk P., Leiguarda R.: Superficial cerebral astrocytoma attached to dura: Report of six cases in infants. Cancer1985;54:2506-2512.
68.
Rodriguez ML, Chandrarma P.: The pathology of benign cerebral astrocytomas, in Apuzzo MLJ (ed): Benign Cerebral Glioma , vol 1. Park Ridge, American Association of Neurological Surgeons, 1995, pp 55-83.
69.
Van den Berg SR: Desmoplastic infantile ganglioglioma and desmoplastic cerebral astrocytoma of infancy. Brain Pathol1993;3:275-281.
70.
Van den Berg SR, May EE, Rubinstein LJ, et al: Desmoplastic supratentorial subepithelial tumors of infancy with divergent patiential desmoplastic infantile gangliogliomas: Report of tumors in infancy with distinctive embryonal tumor with favorable prognosis. J Neurosurg1987;66:58-71.
71.
Sawyer JR, Thomas EL, Roloson GJ, et al: Telomeric associations evolving to ring chromosomes in a recurrent pleomorphic xanthoastrocytoma. Cancer Genet Cytogenet1990;60:152-157.
72.
Macaulay RJB , Jay V., Hoffman HJ, Becker LE: Increased mitotic activity as a negative prognostic indicator in pleomorphic zanthoastrocytoma . Neurosurgery1993;79:761-768.
73.
Kepes JJ, Rubinstein LJ, Eng LJ: Pleomorphic xanthoastrocytoma: A distinctive meningocerebral glioma of young subjects with relatively favorable prognosis: A study of 12 cases . Cancer1979;44:1839-1852.
74.
Nakamura Y. , Becker LE: Subependymal giant-cell tumor: Astrocytic or neuronal?Acta Neuropathol1983 ;60:271-277.
75.
Fujiwara S. , Takaki T., Hikata T., Nishio S.: Subependymal giant cell astrocytoma associated with tuberous sclerosis: Do subependymal nodules grow?Childs Nerv Syst1989;5:40-44.
76.
Norman MG, Schoene WC: The ultrastructure of Sturge Weber disease. Acta Neuropathol1977;37:199-204.
77.
Hoffman HJ, Hendrick EB, Dennis M., Armstrong D.: Hemispherectomy for Sturge Weber syndrome. Childs Brain1979;5:233-248.
78.
Richardson EP Jr: Pathology of tuberous sclerosis, neuropathologic aspects. Ann N YAcad Sci1991;615:128-139.
79.
Armstrong DD : Neonatal encephalopathies, in Duckett S (ed): Pediatric Neuropathology. Baltimore, Williams & Wilkins, 1995, pp 334-351.
80.
Azzarelli B. , Meade P., Muller J.: Hypoxic lesions in areas of primary myelination. A distinct pattern in cerebral palsy. Childs Brain1980;7:132-145.
81.
Lanska MJ, Lanska DJ, Horwitz SJ, Aram DM: Presentation, clinical course, and outcome of childhood stroke. Pediatr Neurol1991;7:333-341.
82.
Jellinger K. : Giant cell granulomatous angiitis of the central nervous system. J Neurol1977;215:175-190.
83.
Yamashita M. , Oka K., Tanaka K.: Histopathology of the vascular networks in Moya Moya disease. Stroke1983;14:50-58.
84.
Lorente de No R.: Studies on the structure of the cerebral cortex. II: Continuation of the study of the ammonic system. J Psychol Neurol1934;46:113-177.
85.
Kotagal S., Peterson PL, Martens ME, et al: Impaired NADH-CoQ reductase activity in a child with Moyamoya syndrome. Pediatr Neurol1988;4:241-244.
86.
Calciolari G., Perlman JM, Volpe JJ: Seizures in the neonatal intensive care unit of the 1980's, types, etiologies, timing. Clin Pediatr1988;27:119-123.
87.
Mizrahi E., Kellaway P.: Characterization and classification of neonatal seizures. Neurology1987;37:1837-1844.
88.
Bell WE, McCormick WF, Markowitz M (eds): Neurologic Infections in Children. Philadelphia, WB Saunders, 1981, pp 283-468.
89.
Perlman JM, Argyle C.: Lethal cytomegalovirus infection in preterm infants, clinical, radiological and neuropathological findings. Ann Neurol1992;31:64-68.
90.
Hsu HW, Grady GF, Masguire JH, et al: Newborn screening for congenital toxoplasma infections; five year experience in Massachusetts, USA. ScandInfect Dis1992;84:59-64.
91.
Lowichik A., Siegel JD: Parasitic infections of the central nervous system in children. Part 1: Congenital infections and meningoencephalitis. J Child Neurol1995;10:4-17.
92.
Scaravilli F.: Parasitic and fungal infections, in Adams JH, Duchen LW (eds): Greenfield's Neuropathology. New York, Oxford University Press, 1992, pp 400~446.
93.
Bruton CJ: The Neuropathology of Temporal Lobe Epilepsy. Oxford, Oxford University Press, Maudsley Monographs #31, 1988.
94.
Sommer W.: Erkrankung des Ammonshoms als aetiologisches Moment der Epilepsie . Arch Psychiat Nervenkr1880;10:631-675.
95.
Bratz E.: Ammonshombefunde bei Epileptikern. Arch Psychiat Nervenkr1899;32:820-835.
96.
Margerison JH, Corsellis JAN: Epilepsy and the temporal lobes: A clinical, electroencephalographic and neuropathological study of the brain in epilepsy, with particular reference to the temporal lobes. Brain1966;89:499-530.
97.
Falconer MA , Taylor DC: Surgical treatment of drug-resistant epilepsy due to mesial temporal sclerosis. Arch Neurol1968;19:353-361.
98.
Earle KM, Baldwin M., Penfield W.: Incisural sclerosis and temporal lobe seizures produced by hippocampal herniation at birth. Arch Neurol Psychiatry1953;69:27-42.
99.
Gastaut H., Toga M., Roger J., Gibson WC: A correlation of clinical, electroencephalographic and anatomical findings in nine autopsied cases of "temporal lobe epilepsy." Epilepsia1959;1:56-85.
100.
Mathieson G. : Pathologic aspects of epilepsy with special reference to the surgical pathology of focal cerebral seizures. Adv Neurol1975;8:107-138.
101.
Babb TL, Brown WJ: Pathological findings in epilepsy, in Engel J Jr (ed): Surgical Treatment of the Epilepsies. New York, Raven Press, 1987, pp 511-540.
102.
Armstrong DD: The neuropathology of temporal lobe epilepsy . J Neuropathol Exp Neurol1993;52:433-443.
103.
Armstrong DD , Bruton CJ: Postscript: What terminology is appropriate for tissue pathology? How does it predict outcome? in Engel J Jr (ed): Surgical Treatment of the Epilepsies. New York, Raven Press, 1987, pp 541-552.
104.
Mathern GW , Pretorius JK, Babb TL: Influence of the type of initial precipitating injury and at what age it occurs on course and outcome in patients with temporal lobe seizures. J Neurosurg1995;24:259-288.
105.
Cascino GD , Jack CR, Parisi JT, et al: Magnetic resonance imaging based volume studies in temporal lobe epilepsy: Pathologic correlations. Ann Neurol1991;30:31-36.
106.
Houser CR: Granule cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy. Brain Res1990;535:195-204.
107.
Green RC, Blume HW, Kupferschmid SB, Mesulam M.: Alterations of hippocampal acetylcholinesterase in human temporal lobe epilepsy . Ann Neurol1989;26:347-351.
108.
Robbins RJ , Brines ML, Kim JH: A selective loss of somatostatin in the hippocampus of patients with temporal lobe epilepsy. Ann Neurol1991;29:325-332.
109.
Sloviter RS , Sollas AL, Barbaro NM, Laxer KD: Calcium-binding protein (calbinden-D28K) and parvalbumin immunochemistry in the normal and epileptic human hippocampus . J Comp Neurol1991;308:381-396.
110.
Zhu Z. , Armstrong DL, Grossman RG, Hamilton WJ: Tyrosine hydroxylase-immunoreactive neurons in the temporal lobe in complex partial seizures. Ann Neurol1990;27:564-572.
111.
de Lanerolle NC, Kim JH, Robbins RJ, Spencer DD: Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy. Brain Res1989;495:387-395.
112.
Geddes JW, Cahan LD, Cooper SM, et al: Altered distribution of excitatory amino acid receptors in temporal lobe epilepsy. Exp Neurol1990;108:214-220.
113.
Munoz DG: The distribution of chromogranin A-like immunoreactivity in the human hippocampus coincides with the pattern of resistance to epilepsy-induced neuronal damage . Ann Neurol1990;27:266-275.
114.
Represa A. , Robain O., Tremblay E., Ben-Ari Y: Hippocampal plasticity in childhood epilepsy. Neurosci Lett1989;99:351-355.
