Seminars in Pediatric Neurology
Volume 12, Issue 2 , Pages 72-87 , June 2005

Advances in the Pathophysiology of Developmental Epilepsies

  • Michael Wong, MD, PhD

      Affiliations

    • Departments of Neurology and Pediatrics and the Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO.
    • Division of Pediatric and Developmental Neurology and the Pediatric Epilepsy Center, St. Louis Children’s Hospital, St. Louis, MO.
    • Corresponding Author InformationAddress reprint requests to Michael Wong, MD, PhD, Department of Neurology, Box 8111, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110.

References 

  1. Haut SR , Veliskova J , Moshe SL . Susceptibility of immature and adult brains to seizure effects . Lancet Neurol . 2004;3:608–617
  2. Holmes GL , Ben-Ari Y . The neurobiology and consequences of epilepsy in the developing brain . Pediatr Res . 2001;49:320–325
  3. Holmes GL , Khazipov R , Ben-Ari Y . Seizure-induced damage in the developing human (relevance of experimental models) . Prog Brain Res . 2002;135:321–334
  4. Sanchez RM , Jensen FE . Maturational aspects of epilepsy mechanisms and consequences for the immature brain . Epilepsia . 2001;42:577–585
  5. Hauser WA , Annegers JR , Kurland LT . Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota (1935–1984) . Epilepsia . 1993;34:453–468
  6. Albala BJ , Moshe SL , Okada R . Kainic-acid induced seizures (a developmental study) . Brain Res . 1984;315:139–148
  7. Cavalheiro EA , Silva DF , Turski WA , et al.   The susceptibility of rats to pilocarpine-induced seizures is age-dependent . Brain Res . 1987;465:43–58
  8. Moshe SL , Albala BJ , Ackermann RF , Engel J . Increased seizure susceptibility of the immature brain . Brain Res . 1983;283:81–85
  9. Jensen FE , Applegate CD , Holzman D , et al.   Epileptogenic effect of hypoxia in the immature rodent brain . Ann Neurol . 1991;29:629–637
  10. Anderson AE , Hrachovy RA , Swann JW . Increased susceptibility to tetanus toxin-induced seizures in immature rats . Epilepsy Res . 1997;26:433–442
  11. Fueta Y , Avoli M . Effects of antiepileptic drugs on 4-aminopyridine-induced epileptiform activity in young and adult rat hippocampus . Epilepsy Res . 1992;12:207–215
  12. Gloveli T , Albrecht D , Heinemann U . Properties of low Mg2+ induced epileptiform activity in rat hippocampal and enthorhinal cortex slices during adolescence . Dev Brain Res . 1995;87:145–152
  13. Swann JW , Brady RJ . Penicillin-induced epileptogenesis in immature rat CA3 hippocampal pyramidal cells . Dev Brain Res . 1984;12:243–254
  14. Wang C , Jensen FE . Age dependence of NMDA receptor involvement in epileptiform activity in rat hippocampal slices . Epilepsy Res . 1996;23:105–113
  15. Hablitz JJ . Spontaneous ictal-like discharges and sustained potential shifts in the developing rat neocortex . J Neurophysiol . 1987;58:1052–1065
  16. Wong M , Yamada KA . Developmental characteristics of epileptiform activity in immature rat neocortex (a comparison of four in vitro seizure models) . Dev Brain Res . 2001;128:113–120
  17. Huttenlocher PR , deCourten C , Garey LJ , et al.   Synaptogenesis in human visual cortex (evidence for synapse elimination during normal development) . Neurosci Lett . 1982;33:247–252
  18. Rakic P , Bourgeois JP , Eckenhoff MF , et al.   Concurrent overproduction of synapses in diverse regions of primate cortex . Science . 1986;232:232–235
  19. Hua JY , Smith SJ . Neural activity and the dynamics of central nervous system development . Nat Neurosci . 2004;7:327–332
  20. Insel TR , Miller LP , Gelhard RE . The ontogeny of excitatory amino acid receptors in rat forebrain—I. N-methyl-D-aspartate and quisqualate receptors . Neuroscience . 1990;35:31–43
  21. Pellegrini-Giampietro DE , Bennett MV , Zukin RS . Differential expression of three glutamate receptors genes in developing rat brain (an in situ hybridization study) . Proc Natl Acade Sci U S A . 1991;88:4157–4161
  22. McDonald JW , Johnston MV , Young AB . Differential ontogenic development of three receptors comprising the NMDA receptor/channel complex in the rat hippocampus . Exp Neurol . 1990;110:237–247
  23. Monyer H , Burnashev N , Laurie DJ , et al.   Developmental and regional expression in the rat brain and functional properties of four NMDA receptors . Neuron . 1994;12:529–540
  24. Zhong J , Carrozz DP , Williams K , et al.   Expression of mRNAs encoding subunits of the NMDA receptor in developing rat brain . J Neurochem . 1995;64:531–539
  25. Flint AC , Maisch US , Weishaupt JH , et al.   NR2A subunit expression shortens NMDA receptor synaptic currents in developing neocortex . J Neurosci . 1997;17:2469–2476
  26. Pellegrini-Giampietro DE , Bennett MV , Zukin RS . Are Ca(2+)–permeable kainate/AMPA receptors more abundant in immature brain? . Neurosci Lett . 1992;144:65–69
  27. Sanchez RM , Koh S , Rio C , et al.   Decreased glutamate receptor 2 expression and enhanced epileptogenesis in immature rat hippocampus after perinatal hypoxia-induced seizures . J Neurosci . 2001;15:21:8154–8163
  28. Cherubini E , Rovira C , Gaiarsa JL , et al.   GABA mediated excitation in immature rat CA3 hippocampal neurons . Int J Dev Neurosci . 1990;8:481–490
  29. Plotkin MD , Snyder EY , Hebert SC , et al.   Expression of the Na-K-2Cl cotransporter is developmentally regulated in postnatal rat brains (a possible mechanism underlying GABA’s excitatory role in immature brain) . J Neurobiol . 1997;33:781–795
  30. Rivera C , Voipio J , Payne JA , et al.   The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation . Nature . 1999;397:251–255
  31. Baram TZ , Snead OC . Bicuculline induced seizures in infant rats (ontogeny of behavioral and electrocortical phenomena) . Dev Brain Res . 1990;57:291–295
  32. Chesnut TJ , Swann JW . Disinhibitory actions of the GABAA agonist muscimol in immature hippocampus . Brain Res . 1989;502:365–374
  33. Romano C , van den Pol AN , O’Malley KL . Enhanced early developmental expression of the metabotropic glutamate receptor mGluR5 in rat brain (protein, mRNA splice variants, and regional distribution) . J Comp Neurol . 1996;367:403–412
  34. Casabona G , Knopfel T , Kuhn R , et al.   Expression and coupling to polyphosphoinositide hydrolysis of group I metabotropic glutamate receptors in early postnatal and adult rat brain . Eur J Neurosci . 1997;9:12–17
  35. Turgeon SM , Albin RL . Postnatal ontogeny of GABAB binding in rat brain . Neuroscience . 1994;62:601–613
  36. Furuta A , Rothstein JD , Martin LJ . Glutamate transporter protein subtypes are expressed differentially during rat CNS development . J Neurosci . 1997;17:8363–8375
  37. Yan XX , Cariaga WA , Ribak CE . Immunoreactivity for GABA plasma membrane transporter, GAT-1, in the developing rat cerebral cortex (transient presence in the somata of neocortical and hippocampal neurons) . Dev Brain Res . 1997;99:1–19
  38. Hachiya Y , Takashima S . Development of GABAergic neurons and their transporter in human temporal cortex . Pediatr Neurol. . 2001;25:390–396
  39. Avishai-Eliner S , Yi SJ , Baram TZ . Developmental profile of messenger RNA for the corticotropin-releasing hormone receptor in the rat limbic system . Dev Brain Res . 1996;91:159–163
  40. Lee EY , Lee TS , Baik SH , et al.   Postnatal development of somatostatin- and neuropeptide Y-immunoreactive neurons in rat cerebral cortex (a double-labeling immunohistochemical study) . Int J Dev Neurosci . 1998;16:63–72
  41. Descombes S , Avoli M , Psarropoulou C . A comparison of the adenosine-mediated synaptic inhibition in the CA3 area of immature and adult rat hippocampus . Dev Brain Res . 1998;110:51–59
  42. Fujikawa DG , Itabashi HH , Wu A , et al.   Status epilepticus-induced neuronal loss in humans without systemic complications or epilepsy . Epilepsia . 2000;41:981–991
  43. Briellmann RS , Berkovic SF , Syngeniotis A , et al.   Seizure-associated hippocampal volume loss (a longitudinal magnetic resonance study of temporal lobe epilepsy) . Ann Neurol . 2002;51:641–644
  44. Fuerst D , Shah J , Shah A , et al.   Hippocampal sclerosis is a progressive disorder (a longitudinal volumetric MRI study) . Ann Neurol . 2003;53:413–416
  45. DeGiorgio CM , Correale JD , Gott PS , et al.   Serum neuron-specific enolase in human status epilepticus . Neurology . 1995;45:1134–1137
  46. Rabinowicz AL , Correale J , Boutros RB , et al.   Neuron-specific enolase is increased after single seizures during inpatient video/EEG monitoring . Epilepsia . 1996;37:122–125
  47. Bourgeois BFD , Prensky AL , Palkes HS , et al.   Intelligence in epilepsy (a prospective study in children) . Ann Neurol . 1983;14:438–444
  48. Farwell JR , Dodrill CB , Batzel LW . Neuropsychological abilities of children with epilepsy . Epilepsia . 1985;26:395–400
  49. Mathern GW , Leite JP , Pretorius J , et al.   Children with severe epilepsy (evidence of hippocampal neuron losses and aberrant mossy fiber sprouting during postnatal granule cell migration and differentiation) . Dev Brain Res . 1994;78:70–80
  50. Maytal J , Shinnar S , Moshe SL , et al.   Low morbidity and mortality of status epilepticus in children . Pediatrics . 1989;83:323–331
  51. Wong M , Ess K , Landt M . Cerebrospinal fluid neuron-specific enolase following seizures in children (role of etiology) . J Child Neurol . 2002;17:261–264
  52. Gurnett CA , Landt M , Wong M . Analysis of cerebrospinal fluid glial fibrillary acidic protein after seizures in children . Epilepsia . 2003;44:1455–1458
  53. Meldrum BS , Vigouroux RA , Brierley JB . Systemic factors and epileptic brain damage. Prolonged seizures in paralyzed, artificially ventilated baboons . Arch Neurol . 1973;29:82–87
  54. Wong M , Wozniak DF , Yamada KA . An animal model of generalized nonconvulsive status epilepticus (immediate characteristics and long-term effects) . Exp Neurol . 2003;183:87–99
  55. Schwob JE , Fuller T , Price JL , et al.   Widespread patterns of neuronal damage following systemic or intracerebral injections of kainic acid (a histological study) . Neuroscience . 1980;5:991–1014
  56. Turski WA , Cavalheiro EA , Schwarz M , et al.   Limbic seizures produced by pilocarpine in rats (behavioural, electroencephalographic and neuropathological study) . Behav Brain Res . 1983;9:315–335
  57. Sloviter RS . “Epileptic” brain damage in rats induced by sustained electrical stimulation of the perforant path. I. Acute electrophysiological and light microscopic studies . Brain Res Bull . 1983;10:675–697
  58. Cavazos JE , Das I , Sutula TP . Neuronal loss induced in limbic pathways by kindling (evidence for induction of hippocampal sclerosis by repeated brief seizures) . J Neurosci . 1994;14:3106–3121
  59. Bengzon J , Kokaia Z , Elmer E , et al.   Apoptosis and proliferation of dentate gyrus neurons after single and intermittent limbic seizures . Proc Natl Acad Sci U S A . 1997;94:10432–10437
  60. Sutula T , He XX , Cavazos J , et al.   Synaptic reorganization in the hippocampus induced by abnormal functional activity . Science . 1988;239:1147–1150
  61. Parent JM , Yu TW , Leibowitz RT , et al.   Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus . J Neurosci . 1997;17:3727–3738
  62. Swann JW , Al-Noori S , Jiang M , et al.   Spine loss and other dendritic abnormalities in epilepsy . Hippocampus . 2000;10:617–625
  63. Nitecka L , Tremblay E , Charton G , et al.   Maturation of kainic acid seizure-brain damage syndrome in the rat. II . Histopathological sequelae Neuroscience . 1984;13:1073–1094
  64. Sperber EF , Haas KZ , Stanton PK , et al.   Resistance of the immature hippocampus to seizure-induced synaptic reorganization . Dev Brain Res . 1991;60:88–93
  65. Carmant L , Liu Z , Werner SJ , et al.   Effect of kainic acid-induced status epilepticus on inositol-trisphosphate and seizure-induced brain damage in mature and immature animals . Dev Brain Res . 1995;89:67–72
  66. Hirsch E , Baram TZ , Snead OC . Ontogenic study of lithium-pilocarpine-induced status epilepticus in rats . Brain Res . 1992;583:120–126
  67. Sankar R , Shin DH , Liu H , et al.   Patterns of status epileptic-induced neuronal injury during development and long-term consequences . J Neurosci . 1998;18:8382–8393
  68. Tandon P , Yang Y , Stafstrom CE , et al.   Downregulation of kainate receptors in the hippocampus following repeated seizures in immature rats . Dev Brain Res . 2002;136:145–150
  69. Sankar R , Shin DH , Wasterlain CG . GABA metabolism during status epilepticus in the developing rat brain . Dev Brain Res . 1997;98:60–64
  70. Zhang G , Raol YH , Hsu FC , et al.   Effects of status epilepticus on hippocampal GABAA receptors are age-dependent . Neuroscience . 2004;125:299–303
  71. Friedman LK , Sperber EF , Moshe SL , et al.   Developmental regulation of glutamate and GABA(A) receptor gene expression in rat hippocampus following kainate-induced status epilepticus . Dev Neurosci . 1997;19:529–542
  72. Sullivan PG , Dube C , Dorenbos K , et al.   Mitochondrial uncoupling protein-2 protects the immature brain from excitotoxic neuronal death . Ann Neurol . 2003;53:711–717
  73. Patel M , Li QY . Age dependence of seizure-induced oxidative stress . Neuroscience . 2003;118:431–437
  74. Rizzi M , Perego C , Aliprandi M , et al.   Glia activation and cytokine increase in rat hippocampus by kainic acid-induced status epilepticus during postnatal development . Neurobiol Dis . 2003;14:494–503
  75. Storey TW , Rho JM , White SS , et al.   Age-dependent differences in flurothyl-induced c-fos and c-jun mRNA expression in the mouse brain . Dev Neurosci . 2002;24:294–299
  76. Tandon P , Yang Y , Das K , et al.   Neuroprotective effects of brain-derived neurotrophic factor in seizures during development . Neuroscience . 1999;91:293–303
  77. Liu Z , Gatt A , Werner SJ , et al.   Long-term behavioral deficits following pilocarpine seizures in immature rats . Epilepsy Res . 1994;19:191–204
  78. Priel MR , Ferreira dos Santos N , Cavalheiro EA . Developmental aspects of the pilocarpine model of epilepsy . Epilepsy Res . 1996;26:115–121
  79. Sankar R , Shin D , Mazarati AM , et al.   Epileptogenesis after status epilepticus reflects age- and model-dependent plasticity . Ann Neurol . 2000;48:580–589
  80. Stafstrom CE , Chronopoulos A , Thurber S , et al.   Age-dependent cognitive and behavioral deficits after kainic acid seizures . Epilepsia . 1993;34:420–432
  81. Stafstrom CE , Thompson JL , Holmes GL . Kainic acid seizures in the developing brain (status epilepticus and spontaneous recurrent seizures) . Dev Brain Res . 1992;65:227–236
  82. Koh S , Storey TW , Santos TC , et al.   Early-life seizures in rats increase susceptibility to seizure-induced brain injury in adulthood . Neurology . 1999;53:915–921
  83. Holmes GL , Gairsa JL , Chevassus-Au-Louis N , et al.   Consequences of neonatal seizures in the rat (morphological and behavioral effects) . Ann Neurol . 1998;44:845–857
  84. Huang L , Cilio MR , Silveira DC , et al.   Long-term effects of neonatal seizures (a behavioral, electrophysiological, and histological study) . Dev Brain Res . 1999;118:99–107
  85. Zhang G , Raol YS , Hsu FC , et al.   Long-term alterations in glutamate receptor and transporter expression following early-life seizures are associated with increased seizure susceptibility . J Neurochem . 2004;88:91–101
  86. Brewster A , Bender RA , Chen Y , et al.   Developmental febrile seizures modulate hippocampal gene expression of hyperpolarization-activated channels in an isoform- and cell-specific manner . J Neurosci . 2002;22:4591–4599
  87. Sutula T , Cascino G , Cavazos J , et al.   Mossy fiber reorganization in the epileptic human temporal lobe . Ann Neurol . 1989;26:321–330
  88. Yang Y , Tandon P , Liu Z , et al.   Synaptic reorganization following kainic acid-induced seizures during development . Dev Brain Res . 1998;107:169–177
  89. Liu Z , Yang Y , Silveira DC , et al.   Consequences of recurrent seizures during early brain development . Neuroscience . 1999;92:1443–1454
  90. Bender RA , Dube C , Gonzalez-Vega R , et al.   Mossy fiber plasticity and enhanced hippocampal excitability, without hippocampal cell loss or altered neurogenesis, in an animal model of prolonged febrile seizures . Hippocampus . 2003;13:399–412
  91. de Rogalski Landrot I , Minokoshi M , Silveira DC , et al.   Recurrent neonatal seizures (relationship of pathology to the electroencephalogram and cognition) . Dev Brain Res . 2001;129:27–38
  92. Gray WP , Sundstrom LE . Kainic acid increases the proliferation of granule cell progenitors in the dentate gyrus of the adult rat . Brain Res . 1998;790:52–59
  93. Sankar R , Shin D , Liu H , et al.   Granule cell neurogenesis after status epileptics in the immature rat brain . Epilepsia . 2000;41(suppl 6):S53–S56
  94. Porter BE , Maronski M , Brooks-Kayal AR . Fate of newborn dentate granule cells after early life status epilepticus . Epilepsia . 2004;45:13–19
  95. McCabe BK , Silveira DC , Cilio MR , et al.   Reduced neurogenesis after neonatal seizures . J Neurosci . 2001;21:2094–2103
  96. Scharfman HE , Goodman JH , Sollas AL . Granule-like neurons at the hilar/CA3 border after status epilepticus and their synchrony with area CA3 pyramidal cells (functional implications of seizure-induced neurogenesis) . J Neurosci . 2000;20:6144–6158
  97. Kullmann DM . The neuronal channelopathies . Brain . 2003;125:1177–1195
  98. Kullmann DM , Hanna MG . Neurological disorders caused by inherited ion-channel mutations . Lancet Neurol . 2002;1:157–166
  99. Pandey HK , Riggs JE . Channelopathies in pediatric neurology . Neurol Clin . 2003;21:765–777
  100. Suzuki T , Delgado-Escueta AV , Aguan K , et al.   Mutations in EFHC1 cause juvenile myoclonic epilepsy . Nat Genet . 2004;36:842–849
  101. Kalachikov S , Evgrafov O , Ross B , et al.   Mutations in LGI1 causes autosomal-dominant partial epilepsy with auditory features . Nat Genet . 2002;30:334–341
  102. Steinlein OK . Genes and mutations in human idiopathic epilepsy . Brain Dev . 2004;26:213–218
  103. Biervert C , Schroeder BC , Kubisch C , et al.   A potassium channel mutation in neonatal human epilepsy . Science . 1998;279:403–406
  104. Singh NA , Charlier C , Stauffer D , et al.   A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns . Nat Genet . 1998;18:25–29
  105. Charlier C , Singh NA , Ryan SG , et al.   A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family . Nat Genet . 1998;18:53–55
  106. Wang HS , Pan Z , Shi W , et al.   KCNQ2 and KCNQ3 potassium channel subunits (molecular correlates of the M-channel) . Science . 1998;282:1890–1893
  107. Lerche H , Biervert C , Alekov AK , et al.   A reduced K+ current due to a novel mutation in KCNQ2 causes neonatal convulsion . Ann Neurol . 1999;46:305–312
  108. Schroeder BC , Kubisch C , Stein V , et al.   Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy . Nature . 1998;396:687–690
  109. Castaldo P , Miraglia del Giudice E , Coppola G , et al.   Benign familial neonatal convulsions caused by altered gating of KCNQ2/KCNQ3 potassium channels . J Neurosci . 2002;22:1–6
  110. Okada M , Zhu G , Hirose S , et al.   Age-dependent modulation of hippocampal excitability by KCNQ-channels . Epilepsy Res . 2003;53:81–94
  111. Tatulian L , Delmas P , Abogadie FC , et al.   Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anti-convulsant drug retigabine . J Neurosci . 2001;21:5535–5545
  112. Scheffer IE , Berkovic SF . Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes . Brain . 1997;120:479–490
  113. Singh R , Scheffer IE , Crossland K , et al.   Generalized epilepsy with febrile seizures plus (a common childhood-onset genetic epilepsy syndrome) . Ann Neurol . 1999;45:75–81
  114. Singh R , Andermann E , Whitehouse WP , et al.   Severe myoclonic epilepsy of infancy (extended spectrum of GEFS+?) . Epilepsia . 2001;42:837–844
  115. Wallace RH , Wang DW , Singh R , et al.   Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B . Nat Genet . 1998;19:366–370
  116. Wallace RH , Scheffer IE , Barnett S , et al.   Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus . Am J Hum Genet . 2001;68:859–865
  117. Escayg A , MacDonald BT , Meisler MH , et al.   Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2 . Nat Genet . 2000;24:343–345
  118. Escayg A , Heils A , MacDonald BT , et al.   A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus and prevalence of variants in patients with epilepsy . Am J Hum Genet . 2001;68:866–873
  119. Sugawara T , Tsurubuchi Y , Agarwala KL , et al.   A missense mutation of the Na+ channel alpha II subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction . Proc Natl Acad Sci U S A . 2001;98:6384–6389
  120. Lossin C , Wang DW , Rhodes TH , et al.   Molecular basis of an inherited epilepsy . Neuron . 2002;34:877–884
  121. Alekov A , Rahman MM , Mitrovic N , et al.   A sodium channel mutation causing epilepsy in man exhibits subtle defects in fast inactivation and activation in vitro . J Physiol . 2000;529:533–539
  122. Spampanato J , Escayg A , Meisler MH , et al.   Functional effects of two voltage-gated sodium channel mutations that cause generalized epilepsy with febrile seizures plus type 2 . J Neurosci . 2001;21:7481–7490
  123. Spampanato J , Escayg A , Meisler MH , et al.   Generalized epilepsy with febrile seizures plus type 2 mutation W1204R alters voltage-dependent gating of Na(v)1.1 sodium channels . Neuroscience . 2003;116:37–48
  124. Cossette P , Loukas A , Lafreniere RG , et al.   Functional characterization of the D188V mutation in neuronal voltage-gated sodium channel causing generalized epilepsy with febrile seizures plus (GEFS) . Epilepsy Res . 2003;53:107–117
  125. Alekov AK , Rahman MM , Mitrovic N , et al.   Enhanced inactivation and acceleration of activation of the sodium channel associated with epilepsy in man . Eur J Neurosci . 2001;13:2171–2176
  126. Lossin C , Rhodes TH , Desai RR , et al.   Epilepsy-associated dysfunction in the voltage-gated neuronal sodium channel SCN1A . J Neurosci . 2003;23:11289–11295
  127. Baulac S , Huberfeld G , Gourfinkel-An I , et al.   First genetic evidence of GABA(A) receptor dysfunction in epilepsy (a mutation in the gamma2-subunit gene) . Nat Genet . 2001;28:46–48
  128. Harkin LA , Bowser DN , Dibbens LM , et al.   Truncation of the GABA(A)-receptor gamma2 subunit in a family with generalized epilepsy with febrile seizures plus . Am J Hum Genet . 2002;70:530–536
  129. Cossette P , Liu L , Brisebois K , et al.   Mutation of GABARA1 in an autosomal dominant form of juvenile myoclonic epilepsy . Nat Genet . 2002;31:183–189
  130. Wallace RH , Marini C , Petrou S , et al.   Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures . Nat Genet . 2001;28:49–52
  131. Fisher JL . A mutation in the GABAA receptor α1 subunit linked to human epilepsy affects channel gating properties . Neuropharm . 2004;46:629–637
  132. Chen Y , Lu J , Pan H , et al.   Association between genetic variation of CACNA1H and childhood absence epilepsy . Ann Neurol . 2003;54:239–243
  133. Khosravani H , Altier C , Simms B , et al.   Gating effects of mutations in the Cav3.2 T-type calcium channel associated with childhood absence epilepsy . J Biol Chem . 2004;279:9681–9684
  134. Haug K , Warnstedt M , Alekov AK , et al.   Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies . Nat Genet . 2003;33:527–532
  135. Barkovich AJ , Kuzinecky RI , Jackson GD , et al.   Classification system for malformations of cortical development (update 2001) . Neurology . 2001;57:2168–2178
  136. Leventer RJ , Phelan EM , Coleman LT , et al.   Clinical and imaging features of cortical malformations in childhood . Neurology . 1999;53:715–722
  137. Porter BE , Brooks-Kayal A , Golden JA . Disorders of cortical development and epilepsy . Arch Neurol . 2002;59:361–365
  138. Schwartzkroin PA , Roper SN , Wenzel HJ . Cortical dysplasia and epilepsy (animal models) . Adv Exp Med Biol . 2004;548:145–174
  139. Sisodiya SM . Malformations of cortical development (burdens and insights from important causes of human epilepsy) . Lancet Neurol . 2004;3:29–38
  140. Taylor DC , Falconer MA , Bruton CJ , et al.   Focal dysplasia of the cerebral cortex in epilepsy . J Neurol Neurosurg Psychiatry . 1971;34:369–387
  141. Spreafico R , Battaglia G , Arcelli P , et al.   Cortical dysplasia (an immunocytochemical study of three patients) . Neurology . 1998;50:27–36
  142. Crino PB , Duhaime AC , Baltuch G , et al.   Differential expression of glutamate and GABA-A receptor subunit mRNA in cortical dysplasia . Neurology . 2001;56:906–913
  143. Aronica E , Gorter JA , Jansen GH , et al.   Expression and cell distribution of group I and group II metabotropic glutamate receptor subtypes in taylor-type focal cortical dysplasia . Epilepsia . 2003;44:785–795
  144. Avoli M , Bernasconi A , Mattia D , et al.   Epileptiform discharges in the human dysplastic neocortex (in vitro physiology and pharmacology) . Ann Neurol . 1999;46:816–826
  145. D’Antuono M , Louvel J , Kohling R , et al.   GABAA receptor-dependent synchronization leads to ictogenesis in the human dysplastic cortex . Brain . 2004;127:1626–1640
  146. White R , Hua Y , Scheithauer B , et al.   Selective alterations in glutamate and GABA receptor subunit mRNA expression in dysplastic neurons and giant cells of cortical tubers . Ann Neurol . 2001;49:67–78
  147. Kobayashi T , Minowa O , Sugitani Y , et al.   A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice . Proc Natl Acad Sci U S A . 2001;98:8762–8767
  148. Uhlmann EJ , Wong M , Baldwin RL , et al.   Astrocyte-specific TSC1 conditional knockout mice exhibit abnormal neuronal organization and seizures . Ann Neurol . 2002;52:285–296
  149. Wong M , Ess KE , Uhlmann EJ , et al.   Impaired astrocyte glutamate transport in a mouse epilepsy model of tuberous sclerosis complex . Ann Neurol . 2003;54:251–256
  150. Fox JW , Lamperti ED , Eksioglu YZ , et al.   Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia . Neuron . 1998;21:1315–1325
  151. Reiner O , Carrozzo R , Shen Y , et al.   Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit-like repeats . Nature . 1993;364:717–721
  152. des Portes V , Pinard JM , Billuart P , et al.   A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome . Cell . 1998;92:51–61
  153. Gleeson JG , Allen KM , Fox JW , et al.   Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein . Cell . 1998;92:63–72
  154. Gleeson JG , Lin PT , Flanagan LA , et al.   Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons . Neuron . 1999;23:257–271
  155. Sapir T , Cahana A , Seger R , et al.   LIS1 is a microtubule-associated phosphoprotein . Eur J Biochem . 1999;265:181–188
  156. Hirotsune S , Fleck MW , Gambello MJ , et al.   Graded reduction of Pafah1b1 (Lis1) activity results in neuronal migration defects and early embryonic lethality . Nat Genet . 1998;19:333–339
  157. Fleck MW , Hirotsune S , Gambello MJ , et al.   Hippocampal abnormalities and enhanced excitability in a murine model of human lissencephaly . J Neurosci . 2000;20:2439–2450
  158. Lee KS , Schottler F , Collins JL , et al.   A genetic animal model of human neocortical heterotopia associated with seizures . J Neurosci . 1997;17:6236–6242
  159. Schottler F , Couture D , Rao A , et al.   Subcortical connections of normotopic and heterotopic neurons in sensory and motor cortices of the tish mutant rat . J Comp Neurol . 1998;395:29–42
  160. Chen ZF , Schottler F , Bertram E , et al.   Distribution and initiation of seizure activity in a rat brain with subcortical band heterotopia . Epilepsia . 2000;41:493–501
  161. Riggs HE , McGrath JJ , Schwartz HP . Malformation of the adult brain (albino rat) resulting from prenatal irradiation . J Neuropathol Exp Neurol . 1956;15:432–447
  162. Kondo S , Najm I , Kunieda T , et al.   Electroencephalographic characterization of an adult rat model of radiation-induced cortical dysplasia . Epilepsia . 2001;42:1221–1227
  163. Baraban SC , Schwartzkroin PA . Flurothyl seizure susceptibility in rats following prenatal methylazoxymethanol treatment . Epilepsy Res . 2000;39:87–102
  164. Robper SN , Eisenschenk S , King MA . Reduced density of parvalbumin- and calbindin D28k-immunoreactive neurons in experimental cortical dysplasia . Epilepsy Res . 1999;37:63–71
  165. Zhu WJ , Roper SN . Reduced inhibition in an animal model of cortical dysplasia . J Neurosci . 2000;20:8925–8931
  166. Calcagnotto ME , Paredes MF , Baraban SC . Heterotopic neurons with altered inhibitory synaptic function in an animal model of malformation-associated epilepsy . J Neurosci . 2002;22:7596–7605
  167. Rafiki A , Chevassus-au-Louis N , Ben-Ari Y , et al.   Glutamate receptors in dysplasic cortex (an in situ hybridization and immunohistochemistry study in rats with prenatal treatment with methylazoxymethanol) . Brain Res . 1998;782:142–152
  168. Castro PA , Cooper EC , Lowenstein DH , et al.   Hippocampal heterotopia lack functional Kv4.2 potassium channels in the methylazoxymethanol model of cortical malformations and epilepsy . J Neurosci . 2001;21:6626–6634
  169. Pentney AR , Baraban SC , Colmers WF . NPY sensitivity and postsynaptic properties of heterotopic neurons in the MAM model of malformation-associated epilepsy . J Neurophysiol . 2002;88:2745–2754
  170. Dixon-Salazar T , Silhavy JL , Marsh SE , et al.   Mutations in the AHI1 Gene, encoding Jouberin, cause Joubert syndrome with cortical polymicrogyria . Am J Hum Genet . 2004;75:979–987
  171. Jacobs KM , Gutnick MJ , Prince DA . Hyperexcitability in a model of cortical maldevelopment . Cereb Cortex . 1996;6:514–523
  172. Jacobs KM , Hwang BJ , Prince DA . Focal epileptogenesis in a rat model of polymicrogyria . J Neurophysiol . 1999;81:159–173
  173. Luhmann HJ , Karpuk N , Qu M , et al.   Characterization of neuronal migration disorders in neocortical structures. II. Intracellular in vitro recordings . J Neurophysiol . 1998;80:92–102
  174. Zilles K , Qu M , Schleicher A , et al.   Characterization of neuronal migration disorders in neocortical structures (quantitative receptor autoradiography of ionotropic glutamate, GABAA and GABA B receptors) . Eur J Neurosci . 1998;10:3095–3106
  175. Defazio RA , Hablitz JJ . Alterations in NMDA receptors in a rat model of cortical dysplasia . J Neurophysiol . 2000;83:315–321

 Supported in part by NIH K02NS045583.

PII: S1071-9091(05)00039-2

doi: 10.1016/j.spen.2005.03.002

Seminars in Pediatric Neurology
Volume 12, Issue 2 , Pages 72-87 , June 2005

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