Focal Cortical Dysplasia: Gene Mutations, Cell Signaling, and Therapeutic Implications

Annual Review of Pathology: Mechanisms of Disease

Volumn 12, Issue , 2017, Pages 547-571

  Iffland, Philip H ^a   Crino, Peter B ^b  

^a TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

Developmental biology; Focal cortical dysplasia electrophysiology; Inflammation; Molecular genetics; MTOR; MTORopathy; Transcriptome

Indexed keywords

CELL SURFACE RECEPTOR; MAMMALIAN TARGET OF RAPAMYCIN; NEUROPEPTIDE; NEUROTRANSMITTER; TRANSCRIPTOME;

BRAIN CORTEX; CELL LINEAGE; CORTICAL DYSPLASIA; DISEASE CLASSIFICATION; ELECTROENCEPHALOGRAPHY; ELECTROPHYSIOLOGY; GENE EXPRESSION PROFILING; GENE MUTATION; HISTOPATHOLOGY; HUMAN; INFLAMMATION; INTRACELLULAR SIGNALING; MOLECULAR GENETICS; NERVE CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; SLICE CULTURE; WHITE MATTER; ANIMAL; GENETICS; MALFORMATIONS OF CORTICAL DEVELOPMENT; MOLECULARLY TARGETED THERAPY; MUTATION; PATHOLOGY;

ANIMALS; HUMANS; MALFORMATIONS OF CORTICAL DEVELOPMENT; MOLECULAR TARGETED THERAPY; MUTATION; SIGNAL TRANSDUCTION;

EID: 85011270516     PISSN: 15534006     EISSN: 15534014     Source Type: Book Series    
DOI: 10.1146/annurev-pathol-052016-100138     Document Type: Review

References (128)

1. Crome L. 1957. Abnormal brain structure in mental deficiency. Med. World 86(3):217-23
2. Taylor DC, Falconer MA, Bruton CJ, Corsellis JA. 1971. Focal dysplasia of the cerebral cortex in epilepsy. J. Neurol. Neurosurg. Psychiatry 34(4):369-87
3. Crino PB. 2011. mTOR: a pathogenic signaling pathway in developmental brain malformations. Trends Mol. Med. 17(12):734-42
4. Krueger DA, Northrup H, Int. Tuberous Scler. Complex Consens. Group. 2013. Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr. Neurol. 49(4):255-65
5. Donkels C, Pfeifer D, Janz P, Huber S, Nakagawa J, et al. 2016. Whole transcriptome screening reveals myelination deficits in dysplastic human temporal neocortex. Cereb. Cortex 2016:bhv346
6. Muhlebner A, Groppel G, Dressler A, Reiter-Fink E, Kasprian G, et al. 2014. Epilepsy surgery in children and adolescents with malformations of cortical development-outcome and impact of the new ILAE classification on focal cortical dysplasia. Epilepsy Res. 108(9):1652-61
7. KimDW,Kim S, Park SH,Chung CK, Lee SK. 2012. Comparison of MRI features and surgical outcome among the subtypes of focal cortical dysplasia. Seizure 21(10):789-94
8. Rowland NC, Englot DJ, Cage TA, Sughrue ME, Barbaro NM, Chang EF. 2012. A meta-analysis of predictors of seizure freedom in the surgical management of focal cortical dysplasia. J. Neurosurg. 116(5):1035-41
9. Palmini A, Najm I, Avanzini G, Babb T, Guerrini R, et al. 2004. Terminology and classification of the cortical dysplasias. Neurology 62(6 Suppl. 3):S2-8
10. Blumcke I,ThomM,Aronica E, ArmstrongDD,VintersHV,et al. 2011. The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission. Epilepsia 52(1):158-74
11. Coras R, de Boer OJ, Armstrong D, Becker A, Jacques TS, et al. 2012. Good interobserver and intraobserver agreement in the evaluation of the new ILAE classification of focal cortical dysplasias. Epilepsia 53(8):1341-48
12. Orlova KA,Tsai V, BaybisM,Heuer GG, Sisodiya S, et al. 2010. Early progenitor cellmarker expression distinguishes type II from type I focal cortical dysplasias. J. Neuropathol. Exp. Neurol. 69(8):850-63
13. Santos MV, de Oliveira RS,Machado HR. 2014. Approach to cortical dysplasia associated with glial and glioneuronal tumors (FCD type IIIb). Childs Nerv. Syst. 30(11):1869-74
14. Martinoni M, Marucci G, de Biase D, Rubboli G, Volpi L, et al. 2015. BRAF V600E mutation in neocortical posterior temporal epileptogenic gangliogliomas. J. Clin. Neurosci. 22(8):1250-53
15. Sarnat H, Flores-Sarnat L, Crino P, Hader W, Bello-Espinosa L. 2012. Hemimegalencephaly: foetal tauopathy with mTOR hyperactivation and neuronal lipidosis. Folia Neuropathol. 50(4):330-45
16. Sarnat HB, Flores-Sarnat L. 2015. Infantile tauopathies: hemimegalencephaly; tuberous sclerosis complex; focal cortical dysplasia 2; ganglioglioma. Brain Dev. 37(6):553-62
17. Lamparello P, Baybis M, Pollard J, Hol EM, Eisenstat DD, et al. 2007. Developmental lineage of cell types in cortical dysplasia with balloon cells. Brain 130(Pt. 9):2267-76
18. Hanai S, Saito T, Nakagawa E, Arai A, Otsuki T, et al. 2010. Abnormal maturation of non-dysmorphic neurons in focal cortical dysplasia: immunohistochemical considerations. Seizure 19(5):274-79
19. Prabowo AS, Anink JJ, Lammens M, NellistM, Ouweland AM, et al. 2013. Fetal brain lesions in tuberous sclerosis complex: TORC1 activation and inflammation. Brain Pathol. 23(1):45-59
20. Tsai V, Parker WE, Orlova KA, Baybis M, Chi AW, et al. 2014. Fetal brain mTOR signaling activation in tuberous sclerosis complex. Cereb. Cortex 24(2):315-27
21. White R, Hua Y, Scheithauer B, Lynch DR, Henske EP, Crino PB. 2001. Selective alterations in glutamate and GABA receptor subunit mRNA expression in dysplastic neurons and giant cells of cortical tubers. Ann. Neurol. 49(1):67-78
22. Calcagnotto ME, Paredes MF, Tihan T, Barbaro NM, Baraban SC. 2005. Dysfunction of synaptic inhibition in epilepsy associated with focal cortical dysplasia. J. Neurosci. 25(42):9649-57
23. Kuchukhidze G,Wieselthaler-Holzl A, Drexel M, Unterberger I, Luef G, et al. 2015. Calcium-binding proteins in focal cortical dysplasia. Epilepsia 56(8):1207-16
24. Andre VM, Wu N, Yamazaki I, Nguyen ST, Fisher RS, et al. 2007. Cytomegalic interneurons: a new abnormal cell type in severe pediatric cortical dysplasia. J. Neuropathol. Exp. Neurol. 66(6):491-504
25. Taylor JP, Sater R, French J, Baltuch G, Crino PB. 2001. Transcription of intermediate filament genes is enhanced in focal cortical dysplasia. Acta Neuropathol. 102(2):141-48
26. Crino PB, Trojanowski JQ, Dichter MA, Eberwine J. 1996. Embryonic neuronal markers in tuberous sclerosis: single-cell molecular pathology. PNAS 93(24):14152-57
27. Oh HS, Lee MC, Kim HS, Lee JS, Lee JH, et al. 2008. Pathophysiologic characteristics of balloon cells in cortical dysplasia. Childs Nerv. Syst. 24(2):175-83
28. Crino PB, Miyata H, Vinters HV. 2002. Neurodevelopmental disorders as a cause of seizures: neuropathologic, genetic, and mechanistic considerations. Brain Pathol. 12(2):212-33
29. MizuguchiM, Yamanouchi H, Becker LE, Itoh M, Takashima S. 2002. Doublecortin immunoreactivity in giant cells of tuberous sclerosis and focal cortical dysplasia. Acta Neuropathol. 104(4):418-24
30. Thom M, Martinian L, Sisodiya SM, Cross JH,Williams G, et al. 2005. Mcm2 labelling of balloon cells in focal cortical dysplasia. Neuropathol. Appl. Neurobiol. 31(6):580-88
31. Ying Z, Gonzalez-Martinez J, Tilelli C, Bingaman W, Najm I. 2005. Expression of neural stem cell surface marker CD133 in balloon cells of human focal cortical dysplasia. Epilepsia 46(11):1716-23
32. Yasin SA, Latak K, Becherini F, Ganapathi A, Miller K, et al. 2010. Balloon cells in human cortical dysplasia and tuberous sclerosis: isolation of a pathological progenitor-like cell. Acta Neuropathol. 120(1):85-96
33. MaldonadoM, BaybisM, Newman D, Kolson DL, Chen W, et al. 2003. Expression of ICAM-1, TNFalpha, NF kappa B, andMAP kinase in tubers of the tuberous sclerosis complex. Neurobiol. Dis. 14(2):279-90
34. Iyer A, Prabowo A, Anink J, Spliet WG, van Rijen PC, Aronica E. 2014. Cell injury and premature neurodegeneration in focal malformations of cortical development. Brain Pathol. 24(1):1-17
35. Monuki ES, Walsh CA. 2001. Mechanisms of cerebral cortical patterning in mice and humans. Nat. Neurosci. 4(Suppl.):1199-206
36. Crino PB, Eberwine J. 1996. Molecular characterization of the dendritic growth cone: regulated mRNA transport and local protein synthesis. Neuron 17(6):1173-87
37. Crino PB, Trojanowski JQ, Eberwine J. 1997. Internexin, MAP1B, and nestin in cortical dysplasia as markers of developmental maturity. Acta Neuropathol. 93(6):619-27
38. Boer K, Lucassen PJ, Spliet WG, Vreugdenhil E, van Rijen PC, et al. 2009. Doublecortin-like (DCL) expression in focal cortical dysplasia and cortical tubers. Epilepsia 50(12):2629-37
39. Cepeda C, Andre VM, Levine MS, Salamon N, Miyata H, et al. 2006. Epileptogenesis in pediatric cortical dysplasia: the dysmature cerebral developmental hypothesis. Epilepsy Behav. 9(2):219-35
40. Crino PB, Duhaime AC, Baltuch G,White R. 2001. Differential expression of glutamate and GABA-A receptor subunit mRNA in cortical dysplasia. Neurology 56(7):906-13
41. Hammers A, Koepp MJ, Richardson MP, Labbe C, Brooks DJ, et al. 2001. Central benzodiazepine receptors in malformations of cortical development: a quantitative study. Brain 124(Pt. 8):1555-65
42. Ying Z, Najm IM. 2002. Mechanisms of epileptogenicity in focal malformations caused by abnormal cortical development. Neurosurg. Clin. N. Am. 13(1):27-33
43. Sukigara S, DaiH,Nabatame S,Otsuki T,Hanai S, et al. 2014. Expression of astrocyte-related receptors in cortical dysplasia with intractable epilepsy. J. Neuropathol. Exp. Neurol. 73(8):798-806
44. Zurolo E, Iyer AM, SplietWG, van Rijen PC, TroostD, et al. 2010. CB1 and CB2 cannabinoid receptor expression during development and in epileptogenic developmental pathologies. Neuroscience 170(1):28-41
45. Diaz-Alonso J, Aguado T, de Salas-Quiroga A, Ortega Z, Guzman M, Galve-Roperh I. 2015. CB1 cannabinoid receptor-dependent activation of mTORC1/Pax6 signaling drives Tbr2 expression and basal progenitor expansion in the developing mouse cortex. Cereb. Cortex 25(9):2395-408
46. Kovacs FE, Knop T, Urbanski MJ, Freiman I, Freiman TM, et al. 2012. Exogenous and endogenous cannabinoids suppress inhibitory neurotransmission in the human neocortex. Neuropsychopharmacology 37(5):1104-14
47. Gibson HE, Edwards JG, Page RS, Van Hook MJ, Kauer JA. 2008. TRPV1 channels mediate long-term depression at synapses on hippocampal interneurons. Neuron 57(5):746-59
48. Peters JH, McDougall SJ, Fawley JA, Smith SM, Andresen MC. 2010. Primary afferent activation of thermosensitive TRPV1 triggers asynchronous glutamate release at central neurons. Neuron 65(5):657-69
49. Xu GZ, Shu HF, Yue HY, Zheng DH, Guo W, Yang H. 2015. Increased expression of TRPC5 in cortical lesions of the focal cortical dysplasia. J. Mol. Neurosci. 55(3):561-69
50. Chen K, Zhang ZF, Liao MF, Yao WL,Wang J,Wang XR. 2015. Blocking PAR2 attenuates oxaliplatininduced neuropathic pain via TRPV1 and releases of substance P and CGRP in superficial dorsal horn of spinal cord. J. Neurol. Sci. 352(1-2):62-67
51. Aronica E, Boer K, Doorn KJ, Zurolo E, SplietWG, et al. 2009. Expression and localization of voltage dependent potassium channel Kv4.2 in epilepsy associated focal lesions. Neurobiol. Dis. 36(1):81-95
52. Yu S, Li S, Shu H, Zhang C, He J, et al. 2012. Upregulated expression of voltage-gated sodium channel Nav1.3 in cortical lesions of patients with focal cortical dysplasia type IIb. Neuroreport 23(7):407-11
53. Sisodiya SM, Lin WR, Squier MV, Thom M. 2001. Multidrug-resistance protein 1 in focal cortical dysplasia. Lancet 357(9249):42-43
54. Sisodiya SM, Heffernan J, Squier MV. 1999. Over-expression of P-glycoprotein in malformations of cortical development. Neuroreport 10(16):3437-41
55. TishlerDM, Weinberg KI,HintonDR, BarbaroN, Annett GM, Raffel C. 1995. MDR1 gene expression in brain of patients with medically intractable epilepsy. Epilepsia 36(1):1-6
56. Medici V, Frassoni C, Tassi L, Spreafico R, Garbelli R. 2011. Aquaporin 4 expression in control and epileptic human cerebral cortex. Brain Res. 1367:330-39
57. Ulu MO, Tanriverdi T, Oz B, Biceroglu H, Isler C, et al. 2010. The expression of astroglial glutamate transporters in patients with focal cortical dysplasia: an immunohistochemical study. Acta Neurochir. Wien. 152(5):845-53
58. Voss LJ, Jacobson G, Sleigh JW, Steyn-Ross A, Steyn-Ross M. 2009. Excitatory effects of gap junction blockers on cerebral cortex seizure-like activity in rats and mice. Epilepsia 50(8):1971-78
59. Luan G, GaoQ, Zhai F, Zhou J, Liu C, et al. 2015. Adenosine kinase expression in cortical dysplasia with balloon cells: analysis of developmental lineage of cell types. J. Neuropathol. Exp. Neurol. 74(2):132-47
60. Boer K, Troost D, Spliet WG, van Rijen PC, Gorter JA, Aronica E. 2008. Cellular distribution of vascular endothelial growth factor A (VEGFA) and B (VEGFB) and VEGF receptors 1 and 2 in focal cortical dysplasia type IIB. Acta Neuropathol. 115(6):683-96
61. Thom M, Harding BN, Lin WR, Martinian L, Cross H, Sisodiya SM. 2003. Cajal-Retzius cells, inhibitory interneuronal populations and neuropeptide Y expression in focal cortical dysplasia and microdysgenesis. Acta Neuropathol. 105(6):561-69
62. ColmersWF, El Bahh B. 2003. Neuropeptide Y and epilepsy. Epilepsy Curr. 3(2):53-58
63. Baybis M, Yu J, Lee A, Golden JA, Weiner H, et al. 2004. mTOR cascade activation distinguishes tubers from focal cortical dysplasia. Ann. Neurol. 56(4):478-87
64. Miyata H, Chiang AC, Vinters HV. 2004. Insulin signaling pathways in cortical dysplasia and TSCtubers: tissue microarray analysis. Ann. Neurol. 56(4):510-19
65. LjungbergMC, Bhattacharjee MB, Lu Y, Armstrong DL, Yoshor D, et al. 2006. Activation of mammalian target of rapamycin in cytomegalic neurons of human cortical dysplasia. Ann. Neurol. 60(4):420-29
66. Schick V, Majores M, Engels G, Hartmann W, Elger CE, et al. 2007. Differential Pi3K-pathway activation in cortical tubers and focal cortical dysplasias with balloon cells. Brain Pathol. 17(2):165-73
67. Grabiner BC, Nardi V, Birsoy K, Possemato R, Shen K, et al. 2014. A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity. Cancer Discov. 4(5):554-63
68. RensingN,Han L, Wong M. 2015. Intermittent dosing of rapamycin maintains antiepileptogenic effects in a mouse model of tuberous sclerosis complex. Epilepsia 56(7):1088-97
69. Aronica E, Boer K, Baybis M, Yu J, Crino P. 2007. Co-expression of cyclin D1 and phosphorylated ribosomal S6 proteins in hemimegalencephaly. Acta Neuropathol. 114(3):287-93
70. Samadani U, Judkins AR, Akpalu A, Aronica E, Crino PB. 2007. Differential cellular gene expression in ganglioglioma. Epilepsia 48(4):646-53
71. Liu J, Reeves C, Michalak Z, Coppola A, Diehl B, et al. 2014. Evidence for mTOR pathway activation in a spectrum of epilepsy-associated pathologies. Acta Neuropathol. Commun. 2:71
72. Zeng LH,Rensing NR,WongM. 2009. Themammalian target of rapamycin signaling pathway mediates epileptogenesis in a model of temporal lobe epilepsy. J. Neurosci. 29(21):6964-72
73. Hester MS, Hosford BE, Santos VR, Singh SP, Rolle IJ, et al. 2016. Impact of rapamycin on status epilepticus induced hippocampal pathology and weight gain. Exp. Neurol. 280:1-12
74. Hua Y, Crino PB. 2003. Single cell lineage analysis in human focal cortical dysplasia. Cereb. Cortex 13(6):693-99
75. Crino PB. 2007. Focal brain malformations: a spectrum of disorders along the mTOR cascade. Novartis Found. Symp. 288:260-72
76. Becker AJ, Urbach H, Scheffler B, Baden T, Normann S, et al. 2002. Focal cortical dysplasia of Taylor's balloon cell type: Mutational analysis of the TSC1 gene indicates a pathogenic relationship to tuberous sclerosis. Ann. Neurol. 52(1):29-37
77. Lim JS, Kim WI, Kang HC, Kim SH, Park AH, et al. 2015. Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy. Nat. Med. 21(4):395-400
78. Nakashima M, Saitsu H, Takei N, Tohyama J, Kato M, et al. 2015. Somatic Mutations in the MTOR gene cause focal cortical dysplasia type IIb. Ann. Neurol. 78(3):375-86
79. D'Gama AM, Geng Y, Couto JA, Martin B, Boyle EA, et al. 2015. Mammalian target of rapamycin pathway mutations cause hemimegalencephaly and focal cortical dysplasia. Ann. Neurol. 77(4):720-25
80. Scerri T, Riseley JR, GilliesG, Pope K, Burgess R, et al. 2015. Familial cortical dysplasia type IIA caused by a germline mutation in DEPDC5. Ann. Clin. Transl. Neurol. 2(5):575-80
81. Crino PB, Aronica E, Baltuch G, Nathanson KL. 2010. Biallelic TSC gene inactivation in tuberous sclerosis complex. Neurology 74(21):1716-23
82. Moon UY, Park JY, Park R, Cho JY, Hughes LJ, et al. 2015. Impaired Reelin-Dab1 signaling contributes to neuronal migration deficits of tuberous sclerosis complex. Cell Rep. 12(6):965-78
83. Baek ST, Copeland B, Yun EJ, Kwon SK, Guemez-Gamboa A, et al. 2015. An AKT3-FOXG1-reelin network underlies defective migration in human focal malformations of cortical development. Nat.Med. 21:1445-54
84. Tsai PT, Hull C, Chu Y, Greene-Colozzi E, Sadowski AR, et al. 2012. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature 488(7413):647-51
85. Crowell B, Lee GH, Nikolaeva I, Dal Pozzo V, D'Arcangelo G. 2015. Complex neurological phenotype in mutant mice lacking Tsc2 in excitatory neurons of the developing forebrain. eNeuro. https://doi.org/10.1523/ENEURO.0046-15.2015
86. Pun RY, Rolle IJ, LaSarge CL, Hosford BE, Rosen JM, et al. 2012. Excessive activation of mTOR in postnatally generated granule cells is sufficient to cause epilepsy. Neuron 75(6):1022-43
87. Roy A, Skibo J, Kalume F, Ni J, Rankin S, et al. 2015. Mouse models of human PIK3CA-related brain overgrowth have acutely treatable epilepsy. eLife. https://doi.org/10.7554/eLife.12703
88. Marsan E, Ishida S, Schramm A, Weckhuysen S, Muraca G, et al. 2016. Depdc5 knockout rat: a novel model of mTORopathy. Neurobiol. Dis. 89:180-89
89. Jansen LA, Mirzaa GM, Ishak GE, O'Roak BJ, Hiatt JB, et al. 2015. PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia. Brain 138 (Pt. 6):1613-28
90. Aronica E, Crino PB. 2011. Inflammation in epilepsy: clinical observations. Epilepsia 52(Suppl. 3):26-32
91. Boer K, SplietWG, vanRijen PC,Redeker S, TroostD, Aronica E. 2006. Evidence of activated microglia in focal cortical dysplasia. J. Neuroimmunol. 173(1-2):188-95
92. Shu HF, Zhang CQ, Yin Q, An N, Liu SY, Yang H. 2010. Expression of the interleukin 6 system in cortical lesions from patients with tuberous sclerosis complex and focal cortical dysplasia type IIb. J. Neuropathol. Exp. Neurol. 69(8):838-49
93. Iyer A, Zurolo E, SplietWG, van Rijen PC, Baayen JC, et al. 2010. Evaluation of the innate and adaptive immunity in type I and type II focal cortical dysplasias. Epilepsia 51(9):1763-73
94. Butler T, Ichise M, Teich AF, Gerard E, Osborne J, et al. 2013. Imaging inflammation in a patient with epilepsy due to focal cortical dysplasia. J. Neuroimaging 23(1):129-31
95. Lin YX, Lin K, Liu XX, Kang DZ, Ye ZX, et al. 2015. PI3K-AKT pathway polymerase chain reaction (PCR) array analysis of epilepsy induced by type II focal cortical dysplasia. Genet. Mol. Res. 14(3):9994-10000
96. Weichhart T, Saemann MD. 2009. The multiple facets of mTOR in immunity. Trends Immunol. 30(5):218-26
97. Byles V, Covarrubias AJ, Ben-Sahra I, Lamming DW, Sabatini DM, et al. 2013. The TSC-mTOR pathway regulates macrophage polarization. Nat. Commun. 4:2834
98. Chen J, Tsai V, Parker WE, Aronica E, Baybis M, Crino PB. 2012. Detection of human papillomavirus in human focal cortical dysplasia type IIB. Ann. Neurol. 72(6):881-92
99. Liu S, Lu L, Cheng X, Xu G, Yang H. 2014. Viral infection and focal cortical dysplasia. Ann. Neurol. 75(4):614-16
100. Vidone M, Alessandrini F, Marucci G, Farnedi A, Biase D, et al. 2014. Evidence of association of human papillomavirus with prognosis worsening in glioblastoma multiforme. Neuro. Oncol. 16(2):298-302
101. Hashida Y, Taniguchi A, Yawata T, Hosokawa S, Murakami M, et al. 2015. Prevalence of human cytomegalovirus, polyomaviruses, and oncogenic viruses in glioblastoma among Japanese subjects. Infect. Agent. Cancer 10:3
102. Coras R, Korn K, Bien CG, Kalbhenn T, Rossler K, et al. 2015. No evidence for human papillomavirus infection in focal cortical dysplasia IIb. Ann. Neurol. 77(2):312-19
103. Shapiro KA,McGuoneD,Deshpande V, Sadow PM, Stemmer-Rachamimov A, Staley KJ. 2015. Failure to detect human papillomavirus in focal cortical dysplasia type IIb. Ann. Neurol. 78(1):63-67
104. Husain RS, Ramakrishnan V. 2015. Global variation of human papillomavirus genotypes and selected genes involved in cervical malignancies. Ann. Glob. Health 81(5):675-83
105. Kloss S, Pieper T, Pannek H, Holthausen H, Tuxhorn I. 2002. Epilepsy surgery in children with focal cortical dysplasia (FCD): results of long-term seizure outcome. Neuropediatrics 33(1):21-26
106. Fauser S, Huppertz HJ, Bast T, Strobl K, Pantazis G, et al. 2006. Clinical characteristics in focal cortical dysplasia: a retrospective evaluation in a series of 120 patients. Brain 129(Pt. 7):1907-16
107. Blumcke I. 2009. Neuropathology of focal epilepsies: a critical review. Epilepsy Behav. 15(1):34-39
108. Kerber K, Dumpelmann M, Schelter B, Le Van P, Korinthenberg R, et al. 2014. Differentiation of specific ripple patterns helps to identify epileptogenic areas for surgical procedures. Clin. Neurophysiol. 125(7):1339-45
109. Jacobs J, Levan P, Chatillon CE, Olivier A, Dubeau F, Gotman J. 2009. High frequency oscillations in intracranial EEGs mark epileptogenicity rather than lesion type. Brain 132(Pt. 4):1022-37
110. Avoli M, Bernasconi A, Mattia D, Olivier A, Hwa GG. 1999. Epileptiform discharges in the human dysplastic neocortex: in vitro physiology and pharmacology. Ann. Neurol. 46(6):816-26
111. Mattia D, Olivier A, Avoli M. 1995. Seizure-like discharges recorded in human dysplastic neocortex maintained in vitro. Neurology 45(7):1391-95
112. Moshel YA, Elliott R, Teutonico F, Sellin J, Carlson C, et al. 2010. Do tubers contain function? Resection of epileptogenic foci in perirolandic cortex in children with tuberous sclerosis complex. Epilepsia 51(7):1242-51
113. Marusic P, Najm IM, Ying Z, Prayson R, Rona S, et al. 2002. Focal cortical dysplasias in eloquent cortex: functional characteristics and correlation with MRI and histopathologic changes. Epilepsia 43(1):27-32
114. Janszky J, Ebner A, Kruse B,Mertens M, Jokeit H, et al. 2003. Functional organization of the brain with malformations of cortical development. Ann. Neurol. 53(6):759-67
115. Cepeda C, Hurst RS, Flores-Hernandez J, Hernandez-Echeagaray E, Klapstein GJ, et al. 2003. Morphological and electrophysiological characterization of abnormal cell types in pediatric cortical dysplasia. J. Neurosci. Res. 72(4):472-86
116. Williams MR, DeSpenza T Jr., Li M, Gulledge AT, Luikart BW. 2015. Hyperactivity of newborn Pten knock-out neurons results from increased excitatory synaptic drive. J. Neurosci. 35(3):943-59
117. Bateup HS, Denefrio CL, Johnson CA, Saulnier JL, Sabatini BL. 2013. Temporal dynamics of a homeostatic pathway controlling neural network activity. Front. Mol. Neurosci. 6:28
118. Schwartzkroin PA, Wenzel HJ. 2012. Are developmental dysplastic lesions epileptogenic? Epilepsia 53(Suppl. 1):35-44
119. Cepeda C, Andre VM, Hauptman JS, Yamazaki I, Huynh MN, et al. 2012. Enhanced GABAergic network and receptor function in pediatric cortical dysplasia Type IIB compared with tuberous sclerosis complex. Neurobiol. Dis. 45(1):310-21
120. Khazipov R. 2016. GABAergic synchronization in epilepsy. Cold Spring Harb. Perspect. Med. 6(2):a022764
121. Barker-Haliski M, White HS. 2015. Glutamatergic mechanisms associated with seizures and epilepsy. Cold Spring Harb. Perspect. Med. 5(8):a022863
122. Ganguly K, Schinder AF, Wong ST, Poo M. 2001. GABA itself promotes the developmental switch of neuronal GABAergic responses from excitation to inhibition. Cell 105(4):521-32
123. Talos DM, Kwiatkowski DJ, Cordero K, Black PM, Jensen FE. 2008. Cell-specific alterations of glutamate receptor expression in tuberous sclerosis complex cortical tubers. Ann. Neurol. 63(4):454-65
124. TalosDM, SunH, Kosaras B, Joseph A, Folkerth RD, et al. 2012. Altered inhibition in tuberous sclerosis and type IIb cortical dysplasia. Ann. Neurol. 71(4):539-51
125. Andre VM, Cepeda C, Vinters HV, Huynh M, Mathern GW, Levine MS. 2010. Interneurons, GABAA currents, and subunit composition of the GABAA receptor in type I and type II cortical dysplasia. Epilepsia 51(Suppl. 3):166-70
126. Cepeda C, Chen JY, Wu JY, Fisher RS, Vinters HV, et al. 2014. Pacemaker GABA synaptic activity may contribute to network synchronization in pediatric cortical dysplasia. Neurobiol. Dis. 62:208-17
127. Deleted in proof
128. Gonzalez-Martinez JA, Ying Z, Prayson R, Bingaman W, Najm I. 2011. Glutamate clearance mechanisms in resected cortical dysplasia. J. Neurosurg. 114(4):1195-202