结节性硬化症脑部病灶的MRI特征与癫痫的关系
摘要
目的:本文旨在研究结节性硬化症脑部MRI病灶特征与癫痫之间的关系。
方法:首先通过病例回顾搜集患者的癫痫临床特征。然后利用医学图像分析软件对入选患者的T1加权相和FLAIR相的三维MRI图像进行自动分割处理,从而获取病灶范围。为了度量病灶负荷量,提出以下概念:病灶/全脑比例(TLBP),即全脑范围内的病灶体积占全脑体积的比例,以及皮质病灶/皮质比例(CLCP),即皮质范围内病灶体积所占皮质体积的比例。最后对癫痫临床特征以及MRI病灶负荷量进行分别统计描述,并计算其相互关系。
结果:24例患者入选本研究。研究发现:FLAIR相TLBP和CLCP皆与癫痫首发年龄反相关,同时癫痫首发年龄也受到新生儿窒息史的影响。有婴儿痉挛史的患儿相比无婴儿痉挛史的患儿有较高的FLAIR相TLBP和CLCP。在经历过婴儿痉挛的患儿中,继续痫性痉挛的患儿较转变为其他癫痫发作类型的患儿有较高的FLAIR相CLCP。在无婴儿痉挛史的患儿中,主要发作类型不同的患者之间病灶负荷量无显著差异。T1相病灶负荷量与癫痫首发年龄和发作类型均不相关。
结论:FLAIR相病灶负荷量与首发年龄以及发作类型这两个癫痫特征之间存在明显相关性,尤其是皮质区域的病灶负荷量在癫痫的评估中具有重要意义。T1相病灶负荷量和癫痫特征的关系仍有待进一步研究。
Purpose: The purpose of this study was to reveal the association between MRI brain lesion load and epileptic characteristics.
Methods: The epileptic characteristics were collected through retrospective chart review. Three-dimensional T1 and FLAIR MRI data were obtained and brain lesions were segmented with automatic algorithms of medical image processing softwares. The conceptions total lesion/brain proportion (TLBP), the proportion of total brain volume occupied by lesions, and Cortical lesion/cortex proportion (CLCP), the proportion of cortical volume occupied by lesions, were proposed as measurements of MRI lesion load. Afterward, the epileptic characteristics and MRI lesion load were statistically described and the association between them were tested.
Results: 24 patients were included. Both FLAIR-TLBP and FLAIR-CLCP were found inversely related to age at seizure onset, which was also influenced by perinatal asphyxia. Both FLAIR-TLBP and FLAIR-CLCP were significantly higher in patients with a history of infantile spasms than in those without. Epileptic spasms was distinguished from other seizure types originated from infantile spasms, when comparing the mean FLAIR-CLCP of the patients with continuous spasms after infancy with that of the patients with transformed seizure types. In patients without a history of infantile spasms, no difference of lesion load were found between groups with different dominant seizure phenotypes. T1 lesion load were related to neither age at seizure onset nor seizure types.
Conclusion: There was significant relation between FLAIR, especially cortical, lesion load and epileptic characteristics (age at seizure onset and the seizure types). The association between T1 lesion load and epileptic characteristics still need to be further studied.
方法:首先通过病例回顾搜集患者的癫痫临床特征。然后利用医学图像分析软件对入选患者的T1加权相和FLAIR相的三维MRI图像进行自动分割处理,从而获取病灶范围。为了度量病灶负荷量,提出以下概念:病灶/全脑比例(TLBP),即全脑范围内的病灶体积占全脑体积的比例,以及皮质病灶/皮质比例(CLCP),即皮质范围内病灶体积所占皮质体积的比例。最后对癫痫临床特征以及MRI病灶负荷量进行分别统计描述,并计算其相互关系。
结果:24例患者入选本研究。研究发现:FLAIR相TLBP和CLCP皆与癫痫首发年龄反相关,同时癫痫首发年龄也受到新生儿窒息史的影响。有婴儿痉挛史的患儿相比无婴儿痉挛史的患儿有较高的FLAIR相TLBP和CLCP。在经历过婴儿痉挛的患儿中,继续痫性痉挛的患儿较转变为其他癫痫发作类型的患儿有较高的FLAIR相CLCP。在无婴儿痉挛史的患儿中,主要发作类型不同的患者之间病灶负荷量无显著差异。T1相病灶负荷量与癫痫首发年龄和发作类型均不相关。
结论:FLAIR相病灶负荷量与首发年龄以及发作类型这两个癫痫特征之间存在明显相关性,尤其是皮质区域的病灶负荷量在癫痫的评估中具有重要意义。T1相病灶负荷量和癫痫特征的关系仍有待进一步研究。
Purpose: The purpose of this study was to reveal the association between MRI brain lesion load and epileptic characteristics.
Methods: The epileptic characteristics were collected through retrospective chart review. Three-dimensional T1 and FLAIR MRI data were obtained and brain lesions were segmented with automatic algorithms of medical image processing softwares. The conceptions total lesion/brain proportion (TLBP), the proportion of total brain volume occupied by lesions, and Cortical lesion/cortex proportion (CLCP), the proportion of cortical volume occupied by lesions, were proposed as measurements of MRI lesion load. Afterward, the epileptic characteristics and MRI lesion load were statistically described and the association between them were tested.
Results: 24 patients were included. Both FLAIR-TLBP and FLAIR-CLCP were found inversely related to age at seizure onset, which was also influenced by perinatal asphyxia. Both FLAIR-TLBP and FLAIR-CLCP were significantly higher in patients with a history of infantile spasms than in those without. Epileptic spasms was distinguished from other seizure types originated from infantile spasms, when comparing the mean FLAIR-CLCP of the patients with continuous spasms after infancy with that of the patients with transformed seizure types. In patients without a history of infantile spasms, no difference of lesion load were found between groups with different dominant seizure phenotypes. T1 lesion load were related to neither age at seizure onset nor seizure types.
Conclusion: There was significant relation between FLAIR, especially cortical, lesion load and epileptic characteristics (age at seizure onset and the seizure types). The association between T1 lesion load and epileptic characteristics still need to be further studied.
引文
[1] Moshel YA, Elliott R, Teutonico F, et al. Do tubers contain function? Resection of epileptogenic foci in perirolandic cortex in children with tuberous sclerosis complex [J]. Epilepsia. 2010, 51 (7): 1242-1251
[2] Chu-Shore CJ, Major P, Camposano S. The natural history of epilepsy in tuberous sclerosis complex [J]. Epilepsia. 2010, 51 (7): 1236-1241
[3] Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis [J]. Lancet. 2008, 372 (9639): 657–668
[4] Shepherd CW, Gomez MR, Lie JT, et al. Causes of death in patients with tuberous sclerosis [J]. Mayo Clin Proc. 1991, 66(8): 792–796
[5] Thiele EA. Managing epilepsy in tuberous sclerosis complex [J]. J Child Neurol. 2004, 19 (9): 680–686
[6] Holmes GL, Stafstrom CE, Tuberous Sclerosis Study Group. Tuberous Sclerosis complex and epilepsy: recent developments and future challenges [J]. Epilepsia. 2007, 48 (4): 617–630
[7] Braffman BH, Bilaniuk LT, Naidich TP, et al. MR imaging of tuberous sclerosis: pathogenesis of this phakomatosis, use of gadopentetate dimeglumine, and literature review [J]. Radiology. 1992, 183(1): 227-238
[8] Talos DM, Kwiatkowski DJ, Cordero K, et al. Cell-specific alterations of glutamate receptor expression in tuberous sclerosis complex cortical tubers [J]. Ann Neurol. 2008, 63 (4): 454–465
[9] Chu-Shore CJ, Major P, Montenegro M, et al. Cyst-like tubers are associated with TSC2 and epilepsy in tuberous sclerosis complex [J]. Neurology. 2009, 72 (13): 1165–1169
[10] DiMario FJ. Brain abnormalities in tuberous sclerosis complex [J]. J Child Neurol. 2004, 19 (5): 650–657
[11] Braffman BH, Bilaniuk LT, Naidich TP, et al. MR imaging of tuberous sclerosis: Pathogenesis of this phakomatosis, use of gadopentetate dimeglumine, and literature review [J]. Radiology. 1992, 183 (1): 227–238
[12] Cusmai R, Chiron C, Curatolo P, et al. Topographic comparative study of magnetic resonance imaging and electroencephalography electroencephalography in 34 children with tuberous sclerosis [J]. Epilepsia. 1990, 31 (6): 747–755
[13] Jambaque I, Cusmai R, Curatolo P, et al. Neuropsychological aspects of tuberous sclerosis in relation to epilepsy and MRI findings [J]. Dev Med Child Neurol. 1991, 33 (8): 698–705
[14] Webb DW, Thomson JL, Osborne JP. Cranial magnetic resonance imaging in patients with tuberous sclerosis and normal intellect [J]. Arch Dis Child. 1991, 66 (12): 1375–1377
[15] Shepherd CW, Houser OW, Gomez MR. MR findings in tuberous sclerosis complex and correlation with seizure development and mental impairment [J]. AJNR Am J Neuroradiol. 1995, 16 (1):149–155
[16] Takanashi J, Sugita K, Fujii K, et al. MR evaluation of tuberous sclerosis: Increased sensitivity with fluid-attenuated inversion recovery and relation to severity of seizures and mental retardation [J]. AJNR Am J Neuroradiol. 1995, 16 (9): 1923–1928
[17] Bolton PF, Griffiths PD. Association of tuberous sclerosis of temporal lobes with autism and atypical autism [J]. Lancet. 1997, 349 (9049): 392–395
[18] Griffiths PD, Bolton P, Verity C. White matter abnormalities in tuberous sclerosis complex [J]. Acta Radiol. 1998, 39 (5): 482–486
[19] Baron Y, Barkovich AJ. MR imaging of tuberous sclerosis in neonates and young infants [J]. AJNR Am J Neuroradiol. 1999, 20 (5): 907–916
[20] Seri S, Cerquiglini A, Pisani F, et al. Autism in tuberous sclerosis: Evoked potential evidence for a deficit in auditory sensory processing [J]. Clin Neurophysiol. 1999, 110 (10): 1825–1830
[21] Marti-Bonmati L, Menor F, Dosda R. Tuberous sclerosis: Differences between cerebral and cerebellar cortical tubers in a pediatric population [J]. AJNR Am J Neuroradiol. 2000, 21 (3):557–560
[22] Weber AM, Egelhoff JC, McKellop JM, et al. Autism and the cerebellum: Evidence from tuberous sclerosis [J]. J Autism Dev Disord. 2000, 30 (6): 511–517
[23] Walz NC, Byars AW, Egelhoff JC, et al. Supratentorial tuber location and autism in tuberous sclerosis complex [J]. J Child Neurol. 2002, 17 (11): 830–832
[24] Bolton PF, Park RJ, Higgins JN, et al. Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex [J]. Brain. 2002, 125 (pt6): 1247–1255
[25] Asano E, Chugani DC, Muzik O, et al. Multimodality imaging for improveddetection of epileptogenic foci in tuberous sclerosis complex [J]. Neurology. 2000, 54 (10):1976–1984
[26] Doherty C, Goh S, Poussaint TY, et al. Prognostic significance of tuber count and location in tuberous sclerosis complex [J]. J Child Neurol. 2005, 20 (10): 837-841
[27] Jansen FE, Braams O, Vincken KL, et al. Overlapping neurologic and cognitive phenotypes in patients with TSC1 or TSC2 mutations [J]. Neurology. 2008, 70 (12): 904–905
[28] Jansen FE, Vincken KL, Algra A, et al. Cognitive impairment in tuberous sclerosis complex is a multifactorial condition [J]. Neurology. 2008, 70 (12): 916–923
[29] Ridler K, Bullmore ET, De Vries PJ, et al. Widespread anatomical abnormalities of grey and white matter structure in tuberous sclerosis [J]. Psychol Med. 2001, 31 (8): 1437-1446
[30] Gallagher A, Grant EP, Madan N, et al. MRI findings reveal three different types of tubers in patients with tuberous sclerosis complex [J]. J Neurol. 2010, 257 (8): 1373-1381
[31] Chu-Shore CJ, Major P, Montenegro M, et al. Cyst-like tubers are associated with TSC2 and epilepsy in tuberous sclerosis complex [J]. Neurology. 2009, 72 (13): 1165–1169
[32] Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: Revised clinical diagnostic criteria [J]. J Child Neurol. 1998, 13 (12): 624-628
[33] Commission on classification and terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes [J]. Epilepsia. 30 (4):389–399
[34] Berg AT, Berkovic SF, Brodie MJ. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005–2009 [J]. Epilepsia. 2010, 51 (4): 676–685
[35] Smith SM. Fast robust automated brain extraction [J]. Hum Brain Mapp. 2002, 17 (3): 143–155.
[36] Pham DL. Spatial models for Fuzzy Clustering [J]. Comput Vis Image Und. 2001, 84 (11): 285-297, 2001.
[37] Bullmore ET, Brammer MJ, Rouleau G., et al. Computerised brain tissue classification of magnetic resonance images: a new approach to the problem ofpartial volume artefact [J]. NeuroImage. 1995, 2 (2): 133-147.
[38] DJ withey, ZJ Koles. A review of medical image segmentation: methods and available softwares [J]. Int J bioelectromagnetism. 2008, 10(3): 125-148
[39] Udupa JK, Samarasekera S. Fuzzy Connectedness and object definition: Theory, algorithms, and applications in image segmentation [J]. Graph Models. 1996, 58 (3): 246–261
[40] Alderliestena T, Niessena WJ, Vincken KL, et al. Objective and reproducible segmentation and quantification of tuberous sclerosis lesions in FLAIR brain MR images[J]. Proc SPIE. 2001, 4322: 1509-1518
[41] Datta S, Sajja BR, He RJ, et al. Segmentation and quantification of black holes in multiple sclerosis [J]. Neuroimage. 2006, 29 (2): 467–474
[42] Bagnato F, Butman JA, Gupta S, et al. In vivo detection of cortical plaques by MR imaging in patients with multiple sclerosis [J]. AJNR Am J Neuroradiol. 2006, 27 (10): 2161– 2167
[43] Talairach J, Tournoux P. Co-planar stereotaxic atlas of the human brain [M]. New York: Thieme Medical Publishers, 1988
[44] ICBM atlas created by the International Consortium on Brain Mapping (ICBM), automatic [EB/OL]. http://www.loni.ucla.edu/ICBM/ICBM_BrainTemplate.html
[45] Chu-Shore CJ, Frosch MP, Grant PE, et al. Progressive multifocal cystlike cortical tubers in tuberous sclerosis complex: Clinical and neuropathologic findings [J]. Epilepsia. 2009, 50 (12): 2648–2651
[46] Kwan P, Arzimanoglou K, Berg AT, et al. Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies [J]. Epilepsia. 2010, 51 (6): 1069–1077
[47] Engel J Jr. ILAE classification of epilepsy syndromes [J]. Epilepsy Res. 2006, 70 (Suppl 1): S5–S10
[48] Camfield P, Camfield C, Lortie A, et al. Infantile spasms in remission may reemerge as intractable epileptic spasms [J]. Epilepsia. 2003, 44 (12): 1592-1595.
[49] Talwar D, Baldwin MA, Hutzler R, et al. Epileptic spasms in older children: persistence beyond infancy [J]. Epilepsia. 1995, 36 (2): 151-155
[50] de Menezes MA, Rho JM. Clinical and electrographic features of epileptic spasms persisting beyond the second year of life [J]. Epilepsia. 2002, 43 (6): 623-630
[51] Devlin LA, Shepherd CH, Crawford H, et al. Tuberous sclerosis complex: clinicalfeatures, diagnosis, and prevalence within Northern Ireland [J]. Dev Med Child Neurol. 2006, 48 (6): 495–499.
[52] Jozwiak S, Shwarz RA, Janniger CK, et al. Usefulness of diagnostic criteria of tuberous sclerosis complex in pediatric patients [J]. J Child Neurol. 2000, 15 (10): 652–659.
[53] Webb DW, Fryer AE, Osborne JP. On the incidence of fits and mental retardation in tuberous sclerosis [J]. J Med Genet. 1991, 28 (6): 395–397.
[54] Curatolo P, De Luca D, Verdecchia M. Epilepsy in tuberous sclerosis complex [J]. Int Pediatr. 2000, 15 (3): 137-142
[55] Lee A, Maldonado M, Baybis M, et al. Markers of cellular proliferation are expressed in cortical tubers [J]. Ann Neurol. 2003, 53 (5): 668–673
[56] Grajkowska W, Kotulska K, Jurkiewicz E, et al. Brain lesions in tuberous sclerosis complex [J]. Folia Neuropathol. 2010, 48 (3): 139-149
[57] Wiznitzer M. Autism and tuberous sclerosis [J]. J Child Neurol. 2004, 19 (9): 675-679
[58] Lesser RP, Luders H, Wyllie E, et al. Mental deterioration in epilepsy [J]. Epilepsia. 1986, 27(suppl 2): S105–S123
[59] Miller SP, Tasch T, Sylvain M, et al. Tuberous sclerosis complex and neonatal seizures [J]. J Child Neurol. 1998, 13 (12): 619–623
[60] Jambaque I, Cusmai R, Curatolo P, et al. Neuropsychological aspects of tuberous sclerosis in relation to epilepsy and MRI findings [J]. Dev Med Child Neurol. 1991, 33 (8): 698-705
[61] Humphreym A, Williams J, Pinto E. A prospective longitudinal study of early cognitive development in tuberous sclerosis [J]. Eur Child Adolesc Psychiatry. 2004, 13 (3): 159–165
[62] Curatolo P, Bombardieri R, Verdecchia M, et al. Intractable seizures in tuberous sclerosis complex: From molecular pathogenesis to the rationale for treatment [J]. J Child Neurol. 2005, 20 (4): 318-325
[63] Bolton P, Park R, Griffiths P, et al. Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex [J]. Brain. 2002, 125 (Pt6): 1247–1255
[64] McGuire W. Perinatal asphyxia. Clinical Evidence. 2007, 11: 320
[65] Kagan KO, Schmidt M, Kuhn U, et al. Ventricular outflow obstruction, valve aplasia, bradyarrhythmia, pulmonary hypoplasia and non-immune fetal hydropsbecause of a large rhabdomyoma in a case of unknown tuberous sclerosis: a prenatal diagnosed cardiac rhabdomyoma with multiple symptoms [J]. BJOG.. 2004, 111 (12): 1478–1480
[66] Calhoun BC, Watson PT, Hegge F. Ultrasound diagnosis of an obstructive cardiac rhabdomyoma with severe hydrops and hypoplastic lungs. A case report [J]. J Reprod Med. 1991, 36 (4): 317–319
[67] Choi JM, Jaffe R, Maidman J, et al. Multiple cardiac rhabdomyomas detected in utero [J]. Fetal Diagn Ther. 2000, 15 (3): 174–176
[68] Khemiri M, Ouederni M, Barsaoui S. Neonatal heart failure revealing a cardiac rhabdomyoma with tuberous sclerosis [J]. Tunis Med. 2008, 86 (1): 75-77
[69] Jiang ZY, Pircova A, Sekarski N, et al. Transposition of the great arteries, pulmonary atresia, and multiple ventricular septal defects associated with multiple cardiac rhabdomyomas in a case of tuberous sclerosis [J]. Pediatr Cardiol. 2000, 21 (2): 165–169
[70] Garfinkle J, Shevell MI. Predictors of outcome in term infants with neonatal seizures subsequent to intrapartum ssphyxia [J]. J Child Neurol. 2011, 26 (1): 73-76
[71] Perlman M, Shah PS. Hypoxic-ischemic encephalopathy: challenges in outcome and prediction [J]. J Pediatr. 2011, 158 (2 Suppl): S51-S54
[72] Lai MC, Yang SN. Perinatal hypoxic-ischemic encephalopathy [J]. J Biomed Biotechnol. 2011, 2011: 609813.
[73] Kato T, Okumura A, Hayakawa F, et al. Prolonged EEG depression in term and near-term infants with hypoxic ischemic encephalopathy and later development of West syndrome [J]. Epilepsia. 2010, 51 (12): 2392-2396
[74] Fung C, Evans E, Shin D, et al. Hypoxic-ischemic brain injury exacerbates neuronal apoptosis and precipitates spontaneous seizures in glucose transporter isoform 3 heterozygous null mice [J]. J Neurosci Res. 2010, 88 (15): 3386-3398.
[75] Liauw L, van der Grond J, van den Berg-Huysmans AA, et al. Hypoxic-ischemic encephalopathy: diagnostic value of conventional MR imaging pulse sequences in term-born neonates [J]. Radiology. 2008, 247 (1): 204-212
[76] Sie LT, Barkhof F, Lafeber HN. Et al. Value of fluid-attenuated inversion recovery sequences in early MRI of the brain in neonates with a perinatal hypoxic-ischemic encephalopathy [J]. Eur Radiol. 2000, 10 (10): 1594-1601
[77] David A. Muzykewicz, Daniel J. Costello, Elkan F. Halpern, et al. Infantile spasmsin tuberous sclerosis complex: Prognostic utility of EEG. [J]. Epilepsia. 2009, 50 (2): 290–296
[78] Fukushima K, Inoue Y, Fujiwara T, et al. Long-term follow-up study of West syndrome associated with tuberous sclerosis [J]. Brain Dev. 2001, 23 (7): 698–704
[79] Pellock JM, Hrachovy R, Shinnar S, et al. Infantile spasms: a U.S. consensus report [J]. Epilepsia. 2010, 51 (10): 1–15
[80] Rando T, Bancale A, Baranello G, et al. Visual function in infants with West Syndrome: Correlation with EEG patterns [J]. Epilepsia. 2004, 45 (7): 781–786
[81] Goh S, Kwiatkowski DJ, Dorer DJ, et al. Infantile spasms and intellectual outcomes in children with tuberous sclerosis complex [J]. Neurology. 2005, 65 (2): 235-238.
[82] Curatolo P, Seri S, Verdecchia M, et al. Infantile spasms in tuberous sclerosis complex [J]. Brain Dev. 2001, 23 (7) 502–507
[83] Asato MR, Hardan AY. Neuropsychiatric problems in tuberous sclerosis complex [J]. J Child Neurol. 2004, 19 (4): 241-249
[84] Goldstein J, Slomski J. Epileptic spasms: a variety of etiologies and associated syndromes [J]. J Child Neurol. 2008, 23 (4): 407-414
[85] Ridler K, Suckling J, Higgins N, et al. Whole brain maps of lesion load in tuberous sclerosis complex [J]. J Child Neurol. 2004, 19 (9): 658–665
[86] Saada J, Hadjrabia S, Fermont L, et al. Prenatal diagnosis of cardiac rhabdomyomas: incidence of associated cerebral lesions of tuberous sclerosis complex [J]. Ultrasound Obstet Gynecol. 2009, 34 (2): 155–159
[87] Milunsky A, Shiml SH, Ito M, et al. Precise prenatal diagnosis of tuberous sclerosis by sequencing the TSC2 gene [J]. Prenat Diagn. 2005, 25 (7): 582–585.
[88] Sgro M, Barozzino T, Toi A, et al. Prenatal detection of cerebral lesions in a fetus with tuberous sclerosis [J]. Ultrasound Obstet Gynecol. 1999, 14 (5): 356–359.
[1] Moshel YA, Elliott R, Teutonico F, et al. Do tubers contain function? Resection of epileptogenic foci in perirolandic cortex in children with tuberous sclerosis complex. Epilepsia. 2010, 51 (7): 1242-1251.
[2] Chu-Shore CJ, Major P, Camposano S. The natural history of epilepsy in tuberous sclerosis complex. Epilepsia. 2010, 51 (7): 1236-1241.
[3] Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet. 2008, 372 (9639): 657–668.
[4] Shepherd CW, Gomez MR, Lie JT, et al. Causes of death in patients with tuberous sclerosis. Mayo Clin Proc. 1991, 66(8): 792–796.
[5] Thiele EA. Managing epilepsy in tuberous sclerosis complex. J Child Neurol. 2004, 19 (9): 680–686.
[6] Holmes GL, Stafstrom CE, Tuberous Sclerosis Study Group. Tuberous Sclerosis complex and epilepsy: recent developments and future challenges. Epilepsia. 2007, 48 (4): 617–630.
[7] Curatolo P. Tuberous Sclerosis Complex: From Basic Science to Clinical Phenotypes. Cambridge: Cambridge University Press. 2004: 26-45.
[8] Gallagher A, Chu-Shore CJ, Montenegro MA, et al. Associations between electroencephalographic and magnetic resonance imaging findings in tuberous sclerosis complex. Epilepsy Res. 2009, 87 (9): 197-202.
[9] Talos DM, Kwiatkowski DJ, Cordero K, et al. Cell-specific alterations of glutamate receptor expression in tuberous sclerosis complex cortical tubers. Ann Neurol. 2008, 63 (4): 454–465.
[10] Chu-Shore CJ, Major P, Montenegro M, et al. Cyst-like tubers are associated with TSC2 and epilepsy in tuberous sclerosis complex. Neurology. 2009, 72 (13): 1165–1169.
[11] Gallagher A, Grant EP, Madan N, et al. MRI findings reveal three differenttypes of tubers in patients with tuberous sclerosis complex. J Neurol. 2010, 257 (8): 1373-1381.
[12] Doherty C, Goh S, Poussaint TY, et al. Prognostic Significance of Tuber Count and Location in Tuberous Sclerosis Complex. J Child Neurol. 2005, 20 (10): 837-841.
[13] Husain AM, Foley CM, Legido A, et al. West Syndrome in Tuberous Sclerosis Complex. Pediatr Neurol. 2000, 23 (3): 233-235.
[14] Anisya-Vasanth AV, Satishchandra P, Nagaraja D, et al. Spectrum of epilepsy in tuberous sclerosis. Neurology India. 2004, 52 (2): 210-212.
[15] Jansen FE, Braams O, Vincken KL, et al. Overlapping neurologic and cognitive phenotypes in patients with TSC1 or TSC2 mutations. Neurology. 2008, 70 (12): 904–905.
[16] Jansen FE, Vincken KL, Algra A, et al. Cognitive impairment in tuberous sclerosis complex is a multifactorial condition. Neurology. 2008, 70 (12): 916–923.
[17] Ridler K, Suckling J, Higgins N, et al. Standardized Whole Brain Mapping of Tubers and Subependymal Nodules in Tuberous Sclerosis Complex. J Child Neurol. 2004, 19 (9): 658-665
[18] Curatolo P, Seri S, Verdecchia M, et al. Infantile spasms in tuberous sclerosis complex. Brain and Development. 2001, 23 (7): 502–507.
[19] Humphrey A, Williams J, Pinto E, et al. A prospective longitudinal study of early cognitive development in tuberous sclerosis. Eur Child Adolesc Psychiatry. 2004, 13 (3): 159-165.
[20] Henry TR, Duncan JS, Berkovic SF. Functional Imaging in the Epilepsies. Philadelphia: Lippincott Williams & Wilkins. 2000: 279-284.
[21] Jansen FE, Braun KPJ, Nieuwenhuizen OV, et al. Diffusion-weighted magnetic resonance imaging and identification of the epileptogenic tuber in patients with tuberous sclerosis. Arch Neurol. 2003, 60 (11): 1580-1584.
[22] Rugg-Gunn FJ, Eriksson SH, Symms MR, et al. Diffusion tensor imaging of cryptogenic and acquired partial epilepsies. Brain. 2001, 124 (pt 3): 627-636.
[23] Eriksson SH, Rugg-Gunn FJ, Symms MR, et al. Diffusion tensor imaging in patients with epilepsy and malformations of cortical development. Brain. 2001, 124 (pt 3): 617-626.
[24] Piao CF, Yu AH, Li KC, et al. Cerebral diffusion tensor imaging in tuberous sclerosis. Eur J Radiol. 2009, 71 (2): 249–252.
[25] Karadag D, Mentzel H-J, Gullmar D, et al. Diffusion tensor imaging in children and adolescents with tuberous sclerosis. Pediatr Radiol. 2005, 35 (10): 980–983.
[26] Saada J, Hadjrabia S, Fermont L, et al. Prenatal diagnosis of cardiac rhabdomyomas: incidence of associated cerebral lesions of tuberous sclerosis complex. Ultrasound Obstet Gynecol. 2009, 34 (2): 155–159.
[27] Sgro M, Barozzino T, Toi A, et al. Prenatal detection of cerebral lesions in a fetus with tuberous sclerosis. Ultrasound Obstet Gynecol. 1999, 14 (5): 356–359.
[28] Milunsky A, Shiml SH, Ito M, et al. Precise prenatal diagnosis of tuberous sclerosis by sequencing the TSC2 gene. Prenat Diagn. 2005, 25 (7): 582–585.
[29] Roach ES, Gomez MR, Northrup H. Tuberous Sclerosis Complex Consensus Conference: Revised Clinical Diagnostic Criteria. J Child Neurol . 1998, 13 (12): 624-628.
[30] Schachter SC. Antiepileptic drug therapy: general treatment principles and application for special patient populations. Epilepsia. 1999, 40 (Suppl 9): S20-S25.
[31] Hirtz D, Berg A, Bettis D, et al. Practice parameter: Treatment of the child with a first unprovoked seizure: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2003, 60 (2): 166-175.
[2] Chu-Shore CJ, Major P, Camposano S. The natural history of epilepsy in tuberous sclerosis complex [J]. Epilepsia. 2010, 51 (7): 1236-1241
[3] Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis [J]. Lancet. 2008, 372 (9639): 657–668
[4] Shepherd CW, Gomez MR, Lie JT, et al. Causes of death in patients with tuberous sclerosis [J]. Mayo Clin Proc. 1991, 66(8): 792–796
[5] Thiele EA. Managing epilepsy in tuberous sclerosis complex [J]. J Child Neurol. 2004, 19 (9): 680–686
[6] Holmes GL, Stafstrom CE, Tuberous Sclerosis Study Group. Tuberous Sclerosis complex and epilepsy: recent developments and future challenges [J]. Epilepsia. 2007, 48 (4): 617–630
[7] Braffman BH, Bilaniuk LT, Naidich TP, et al. MR imaging of tuberous sclerosis: pathogenesis of this phakomatosis, use of gadopentetate dimeglumine, and literature review [J]. Radiology. 1992, 183(1): 227-238
[8] Talos DM, Kwiatkowski DJ, Cordero K, et al. Cell-specific alterations of glutamate receptor expression in tuberous sclerosis complex cortical tubers [J]. Ann Neurol. 2008, 63 (4): 454–465
[9] Chu-Shore CJ, Major P, Montenegro M, et al. Cyst-like tubers are associated with TSC2 and epilepsy in tuberous sclerosis complex [J]. Neurology. 2009, 72 (13): 1165–1169
[10] DiMario FJ. Brain abnormalities in tuberous sclerosis complex [J]. J Child Neurol. 2004, 19 (5): 650–657
[11] Braffman BH, Bilaniuk LT, Naidich TP, et al. MR imaging of tuberous sclerosis: Pathogenesis of this phakomatosis, use of gadopentetate dimeglumine, and literature review [J]. Radiology. 1992, 183 (1): 227–238
[12] Cusmai R, Chiron C, Curatolo P, et al. Topographic comparative study of magnetic resonance imaging and electroencephalography electroencephalography in 34 children with tuberous sclerosis [J]. Epilepsia. 1990, 31 (6): 747–755
[13] Jambaque I, Cusmai R, Curatolo P, et al. Neuropsychological aspects of tuberous sclerosis in relation to epilepsy and MRI findings [J]. Dev Med Child Neurol. 1991, 33 (8): 698–705
[14] Webb DW, Thomson JL, Osborne JP. Cranial magnetic resonance imaging in patients with tuberous sclerosis and normal intellect [J]. Arch Dis Child. 1991, 66 (12): 1375–1377
[15] Shepherd CW, Houser OW, Gomez MR. MR findings in tuberous sclerosis complex and correlation with seizure development and mental impairment [J]. AJNR Am J Neuroradiol. 1995, 16 (1):149–155
[16] Takanashi J, Sugita K, Fujii K, et al. MR evaluation of tuberous sclerosis: Increased sensitivity with fluid-attenuated inversion recovery and relation to severity of seizures and mental retardation [J]. AJNR Am J Neuroradiol. 1995, 16 (9): 1923–1928
[17] Bolton PF, Griffiths PD. Association of tuberous sclerosis of temporal lobes with autism and atypical autism [J]. Lancet. 1997, 349 (9049): 392–395
[18] Griffiths PD, Bolton P, Verity C. White matter abnormalities in tuberous sclerosis complex [J]. Acta Radiol. 1998, 39 (5): 482–486
[19] Baron Y, Barkovich AJ. MR imaging of tuberous sclerosis in neonates and young infants [J]. AJNR Am J Neuroradiol. 1999, 20 (5): 907–916
[20] Seri S, Cerquiglini A, Pisani F, et al. Autism in tuberous sclerosis: Evoked potential evidence for a deficit in auditory sensory processing [J]. Clin Neurophysiol. 1999, 110 (10): 1825–1830
[21] Marti-Bonmati L, Menor F, Dosda R. Tuberous sclerosis: Differences between cerebral and cerebellar cortical tubers in a pediatric population [J]. AJNR Am J Neuroradiol. 2000, 21 (3):557–560
[22] Weber AM, Egelhoff JC, McKellop JM, et al. Autism and the cerebellum: Evidence from tuberous sclerosis [J]. J Autism Dev Disord. 2000, 30 (6): 511–517
[23] Walz NC, Byars AW, Egelhoff JC, et al. Supratentorial tuber location and autism in tuberous sclerosis complex [J]. J Child Neurol. 2002, 17 (11): 830–832
[24] Bolton PF, Park RJ, Higgins JN, et al. Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex [J]. Brain. 2002, 125 (pt6): 1247–1255
[25] Asano E, Chugani DC, Muzik O, et al. Multimodality imaging for improveddetection of epileptogenic foci in tuberous sclerosis complex [J]. Neurology. 2000, 54 (10):1976–1984
[26] Doherty C, Goh S, Poussaint TY, et al. Prognostic significance of tuber count and location in tuberous sclerosis complex [J]. J Child Neurol. 2005, 20 (10): 837-841
[27] Jansen FE, Braams O, Vincken KL, et al. Overlapping neurologic and cognitive phenotypes in patients with TSC1 or TSC2 mutations [J]. Neurology. 2008, 70 (12): 904–905
[28] Jansen FE, Vincken KL, Algra A, et al. Cognitive impairment in tuberous sclerosis complex is a multifactorial condition [J]. Neurology. 2008, 70 (12): 916–923
[29] Ridler K, Bullmore ET, De Vries PJ, et al. Widespread anatomical abnormalities of grey and white matter structure in tuberous sclerosis [J]. Psychol Med. 2001, 31 (8): 1437-1446
[30] Gallagher A, Grant EP, Madan N, et al. MRI findings reveal three different types of tubers in patients with tuberous sclerosis complex [J]. J Neurol. 2010, 257 (8): 1373-1381
[31] Chu-Shore CJ, Major P, Montenegro M, et al. Cyst-like tubers are associated with TSC2 and epilepsy in tuberous sclerosis complex [J]. Neurology. 2009, 72 (13): 1165–1169
[32] Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: Revised clinical diagnostic criteria [J]. J Child Neurol. 1998, 13 (12): 624-628
[33] Commission on classification and terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes [J]. Epilepsia. 30 (4):389–399
[34] Berg AT, Berkovic SF, Brodie MJ. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005–2009 [J]. Epilepsia. 2010, 51 (4): 676–685
[35] Smith SM. Fast robust automated brain extraction [J]. Hum Brain Mapp. 2002, 17 (3): 143–155.
[36] Pham DL. Spatial models for Fuzzy Clustering [J]. Comput Vis Image Und. 2001, 84 (11): 285-297, 2001.
[37] Bullmore ET, Brammer MJ, Rouleau G., et al. Computerised brain tissue classification of magnetic resonance images: a new approach to the problem ofpartial volume artefact [J]. NeuroImage. 1995, 2 (2): 133-147.
[38] DJ withey, ZJ Koles. A review of medical image segmentation: methods and available softwares [J]. Int J bioelectromagnetism. 2008, 10(3): 125-148
[39] Udupa JK, Samarasekera S. Fuzzy Connectedness and object definition: Theory, algorithms, and applications in image segmentation [J]. Graph Models. 1996, 58 (3): 246–261
[40] Alderliestena T, Niessena WJ, Vincken KL, et al. Objective and reproducible segmentation and quantification of tuberous sclerosis lesions in FLAIR brain MR images[J]. Proc SPIE. 2001, 4322: 1509-1518
[41] Datta S, Sajja BR, He RJ, et al. Segmentation and quantification of black holes in multiple sclerosis [J]. Neuroimage. 2006, 29 (2): 467–474
[42] Bagnato F, Butman JA, Gupta S, et al. In vivo detection of cortical plaques by MR imaging in patients with multiple sclerosis [J]. AJNR Am J Neuroradiol. 2006, 27 (10): 2161– 2167
[43] Talairach J, Tournoux P. Co-planar stereotaxic atlas of the human brain [M]. New York: Thieme Medical Publishers, 1988
[44] ICBM atlas created by the International Consortium on Brain Mapping (ICBM), automatic [EB/OL]. http://www.loni.ucla.edu/ICBM/ICBM_BrainTemplate.html
[45] Chu-Shore CJ, Frosch MP, Grant PE, et al. Progressive multifocal cystlike cortical tubers in tuberous sclerosis complex: Clinical and neuropathologic findings [J]. Epilepsia. 2009, 50 (12): 2648–2651
[46] Kwan P, Arzimanoglou K, Berg AT, et al. Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies [J]. Epilepsia. 2010, 51 (6): 1069–1077
[47] Engel J Jr. ILAE classification of epilepsy syndromes [J]. Epilepsy Res. 2006, 70 (Suppl 1): S5–S10
[48] Camfield P, Camfield C, Lortie A, et al. Infantile spasms in remission may reemerge as intractable epileptic spasms [J]. Epilepsia. 2003, 44 (12): 1592-1595.
[49] Talwar D, Baldwin MA, Hutzler R, et al. Epileptic spasms in older children: persistence beyond infancy [J]. Epilepsia. 1995, 36 (2): 151-155
[50] de Menezes MA, Rho JM. Clinical and electrographic features of epileptic spasms persisting beyond the second year of life [J]. Epilepsia. 2002, 43 (6): 623-630
[51] Devlin LA, Shepherd CH, Crawford H, et al. Tuberous sclerosis complex: clinicalfeatures, diagnosis, and prevalence within Northern Ireland [J]. Dev Med Child Neurol. 2006, 48 (6): 495–499.
[52] Jozwiak S, Shwarz RA, Janniger CK, et al. Usefulness of diagnostic criteria of tuberous sclerosis complex in pediatric patients [J]. J Child Neurol. 2000, 15 (10): 652–659.
[53] Webb DW, Fryer AE, Osborne JP. On the incidence of fits and mental retardation in tuberous sclerosis [J]. J Med Genet. 1991, 28 (6): 395–397.
[54] Curatolo P, De Luca D, Verdecchia M. Epilepsy in tuberous sclerosis complex [J]. Int Pediatr. 2000, 15 (3): 137-142
[55] Lee A, Maldonado M, Baybis M, et al. Markers of cellular proliferation are expressed in cortical tubers [J]. Ann Neurol. 2003, 53 (5): 668–673
[56] Grajkowska W, Kotulska K, Jurkiewicz E, et al. Brain lesions in tuberous sclerosis complex [J]. Folia Neuropathol. 2010, 48 (3): 139-149
[57] Wiznitzer M. Autism and tuberous sclerosis [J]. J Child Neurol. 2004, 19 (9): 675-679
[58] Lesser RP, Luders H, Wyllie E, et al. Mental deterioration in epilepsy [J]. Epilepsia. 1986, 27(suppl 2): S105–S123
[59] Miller SP, Tasch T, Sylvain M, et al. Tuberous sclerosis complex and neonatal seizures [J]. J Child Neurol. 1998, 13 (12): 619–623
[60] Jambaque I, Cusmai R, Curatolo P, et al. Neuropsychological aspects of tuberous sclerosis in relation to epilepsy and MRI findings [J]. Dev Med Child Neurol. 1991, 33 (8): 698-705
[61] Humphreym A, Williams J, Pinto E. A prospective longitudinal study of early cognitive development in tuberous sclerosis [J]. Eur Child Adolesc Psychiatry. 2004, 13 (3): 159–165
[62] Curatolo P, Bombardieri R, Verdecchia M, et al. Intractable seizures in tuberous sclerosis complex: From molecular pathogenesis to the rationale for treatment [J]. J Child Neurol. 2005, 20 (4): 318-325
[63] Bolton P, Park R, Griffiths P, et al. Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex [J]. Brain. 2002, 125 (Pt6): 1247–1255
[64] McGuire W. Perinatal asphyxia. Clinical Evidence. 2007, 11: 320
[65] Kagan KO, Schmidt M, Kuhn U, et al. Ventricular outflow obstruction, valve aplasia, bradyarrhythmia, pulmonary hypoplasia and non-immune fetal hydropsbecause of a large rhabdomyoma in a case of unknown tuberous sclerosis: a prenatal diagnosed cardiac rhabdomyoma with multiple symptoms [J]. BJOG.. 2004, 111 (12): 1478–1480
[66] Calhoun BC, Watson PT, Hegge F. Ultrasound diagnosis of an obstructive cardiac rhabdomyoma with severe hydrops and hypoplastic lungs. A case report [J]. J Reprod Med. 1991, 36 (4): 317–319
[67] Choi JM, Jaffe R, Maidman J, et al. Multiple cardiac rhabdomyomas detected in utero [J]. Fetal Diagn Ther. 2000, 15 (3): 174–176
[68] Khemiri M, Ouederni M, Barsaoui S. Neonatal heart failure revealing a cardiac rhabdomyoma with tuberous sclerosis [J]. Tunis Med. 2008, 86 (1): 75-77
[69] Jiang ZY, Pircova A, Sekarski N, et al. Transposition of the great arteries, pulmonary atresia, and multiple ventricular septal defects associated with multiple cardiac rhabdomyomas in a case of tuberous sclerosis [J]. Pediatr Cardiol. 2000, 21 (2): 165–169
[70] Garfinkle J, Shevell MI. Predictors of outcome in term infants with neonatal seizures subsequent to intrapartum ssphyxia [J]. J Child Neurol. 2011, 26 (1): 73-76
[71] Perlman M, Shah PS. Hypoxic-ischemic encephalopathy: challenges in outcome and prediction [J]. J Pediatr. 2011, 158 (2 Suppl): S51-S54
[72] Lai MC, Yang SN. Perinatal hypoxic-ischemic encephalopathy [J]. J Biomed Biotechnol. 2011, 2011: 609813.
[73] Kato T, Okumura A, Hayakawa F, et al. Prolonged EEG depression in term and near-term infants with hypoxic ischemic encephalopathy and later development of West syndrome [J]. Epilepsia. 2010, 51 (12): 2392-2396
[74] Fung C, Evans E, Shin D, et al. Hypoxic-ischemic brain injury exacerbates neuronal apoptosis and precipitates spontaneous seizures in glucose transporter isoform 3 heterozygous null mice [J]. J Neurosci Res. 2010, 88 (15): 3386-3398.
[75] Liauw L, van der Grond J, van den Berg-Huysmans AA, et al. Hypoxic-ischemic encephalopathy: diagnostic value of conventional MR imaging pulse sequences in term-born neonates [J]. Radiology. 2008, 247 (1): 204-212
[76] Sie LT, Barkhof F, Lafeber HN. Et al. Value of fluid-attenuated inversion recovery sequences in early MRI of the brain in neonates with a perinatal hypoxic-ischemic encephalopathy [J]. Eur Radiol. 2000, 10 (10): 1594-1601
[77] David A. Muzykewicz, Daniel J. Costello, Elkan F. Halpern, et al. Infantile spasmsin tuberous sclerosis complex: Prognostic utility of EEG. [J]. Epilepsia. 2009, 50 (2): 290–296
[78] Fukushima K, Inoue Y, Fujiwara T, et al. Long-term follow-up study of West syndrome associated with tuberous sclerosis [J]. Brain Dev. 2001, 23 (7): 698–704
[79] Pellock JM, Hrachovy R, Shinnar S, et al. Infantile spasms: a U.S. consensus report [J]. Epilepsia. 2010, 51 (10): 1–15
[80] Rando T, Bancale A, Baranello G, et al. Visual function in infants with West Syndrome: Correlation with EEG patterns [J]. Epilepsia. 2004, 45 (7): 781–786
[81] Goh S, Kwiatkowski DJ, Dorer DJ, et al. Infantile spasms and intellectual outcomes in children with tuberous sclerosis complex [J]. Neurology. 2005, 65 (2): 235-238.
[82] Curatolo P, Seri S, Verdecchia M, et al. Infantile spasms in tuberous sclerosis complex [J]. Brain Dev. 2001, 23 (7) 502–507
[83] Asato MR, Hardan AY. Neuropsychiatric problems in tuberous sclerosis complex [J]. J Child Neurol. 2004, 19 (4): 241-249
[84] Goldstein J, Slomski J. Epileptic spasms: a variety of etiologies and associated syndromes [J]. J Child Neurol. 2008, 23 (4): 407-414
[85] Ridler K, Suckling J, Higgins N, et al. Whole brain maps of lesion load in tuberous sclerosis complex [J]. J Child Neurol. 2004, 19 (9): 658–665
[86] Saada J, Hadjrabia S, Fermont L, et al. Prenatal diagnosis of cardiac rhabdomyomas: incidence of associated cerebral lesions of tuberous sclerosis complex [J]. Ultrasound Obstet Gynecol. 2009, 34 (2): 155–159
[87] Milunsky A, Shiml SH, Ito M, et al. Precise prenatal diagnosis of tuberous sclerosis by sequencing the TSC2 gene [J]. Prenat Diagn. 2005, 25 (7): 582–585.
[88] Sgro M, Barozzino T, Toi A, et al. Prenatal detection of cerebral lesions in a fetus with tuberous sclerosis [J]. Ultrasound Obstet Gynecol. 1999, 14 (5): 356–359.
[1] Moshel YA, Elliott R, Teutonico F, et al. Do tubers contain function? Resection of epileptogenic foci in perirolandic cortex in children with tuberous sclerosis complex. Epilepsia. 2010, 51 (7): 1242-1251.
[2] Chu-Shore CJ, Major P, Camposano S. The natural history of epilepsy in tuberous sclerosis complex. Epilepsia. 2010, 51 (7): 1236-1241.
[3] Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet. 2008, 372 (9639): 657–668.
[4] Shepherd CW, Gomez MR, Lie JT, et al. Causes of death in patients with tuberous sclerosis. Mayo Clin Proc. 1991, 66(8): 792–796.
[5] Thiele EA. Managing epilepsy in tuberous sclerosis complex. J Child Neurol. 2004, 19 (9): 680–686.
[6] Holmes GL, Stafstrom CE, Tuberous Sclerosis Study Group. Tuberous Sclerosis complex and epilepsy: recent developments and future challenges. Epilepsia. 2007, 48 (4): 617–630.
[7] Curatolo P. Tuberous Sclerosis Complex: From Basic Science to Clinical Phenotypes. Cambridge: Cambridge University Press. 2004: 26-45.
[8] Gallagher A, Chu-Shore CJ, Montenegro MA, et al. Associations between electroencephalographic and magnetic resonance imaging findings in tuberous sclerosis complex. Epilepsy Res. 2009, 87 (9): 197-202.
[9] Talos DM, Kwiatkowski DJ, Cordero K, et al. Cell-specific alterations of glutamate receptor expression in tuberous sclerosis complex cortical tubers. Ann Neurol. 2008, 63 (4): 454–465.
[10] Chu-Shore CJ, Major P, Montenegro M, et al. Cyst-like tubers are associated with TSC2 and epilepsy in tuberous sclerosis complex. Neurology. 2009, 72 (13): 1165–1169.
[11] Gallagher A, Grant EP, Madan N, et al. MRI findings reveal three differenttypes of tubers in patients with tuberous sclerosis complex. J Neurol. 2010, 257 (8): 1373-1381.
[12] Doherty C, Goh S, Poussaint TY, et al. Prognostic Significance of Tuber Count and Location in Tuberous Sclerosis Complex. J Child Neurol. 2005, 20 (10): 837-841.
[13] Husain AM, Foley CM, Legido A, et al. West Syndrome in Tuberous Sclerosis Complex. Pediatr Neurol. 2000, 23 (3): 233-235.
[14] Anisya-Vasanth AV, Satishchandra P, Nagaraja D, et al. Spectrum of epilepsy in tuberous sclerosis. Neurology India. 2004, 52 (2): 210-212.
[15] Jansen FE, Braams O, Vincken KL, et al. Overlapping neurologic and cognitive phenotypes in patients with TSC1 or TSC2 mutations. Neurology. 2008, 70 (12): 904–905.
[16] Jansen FE, Vincken KL, Algra A, et al. Cognitive impairment in tuberous sclerosis complex is a multifactorial condition. Neurology. 2008, 70 (12): 916–923.
[17] Ridler K, Suckling J, Higgins N, et al. Standardized Whole Brain Mapping of Tubers and Subependymal Nodules in Tuberous Sclerosis Complex. J Child Neurol. 2004, 19 (9): 658-665
[18] Curatolo P, Seri S, Verdecchia M, et al. Infantile spasms in tuberous sclerosis complex. Brain and Development. 2001, 23 (7): 502–507.
[19] Humphrey A, Williams J, Pinto E, et al. A prospective longitudinal study of early cognitive development in tuberous sclerosis. Eur Child Adolesc Psychiatry. 2004, 13 (3): 159-165.
[20] Henry TR, Duncan JS, Berkovic SF. Functional Imaging in the Epilepsies. Philadelphia: Lippincott Williams & Wilkins. 2000: 279-284.
[21] Jansen FE, Braun KPJ, Nieuwenhuizen OV, et al. Diffusion-weighted magnetic resonance imaging and identification of the epileptogenic tuber in patients with tuberous sclerosis. Arch Neurol. 2003, 60 (11): 1580-1584.
[22] Rugg-Gunn FJ, Eriksson SH, Symms MR, et al. Diffusion tensor imaging of cryptogenic and acquired partial epilepsies. Brain. 2001, 124 (pt 3): 627-636.
[23] Eriksson SH, Rugg-Gunn FJ, Symms MR, et al. Diffusion tensor imaging in patients with epilepsy and malformations of cortical development. Brain. 2001, 124 (pt 3): 617-626.
[24] Piao CF, Yu AH, Li KC, et al. Cerebral diffusion tensor imaging in tuberous sclerosis. Eur J Radiol. 2009, 71 (2): 249–252.
[25] Karadag D, Mentzel H-J, Gullmar D, et al. Diffusion tensor imaging in children and adolescents with tuberous sclerosis. Pediatr Radiol. 2005, 35 (10): 980–983.
[26] Saada J, Hadjrabia S, Fermont L, et al. Prenatal diagnosis of cardiac rhabdomyomas: incidence of associated cerebral lesions of tuberous sclerosis complex. Ultrasound Obstet Gynecol. 2009, 34 (2): 155–159.
[27] Sgro M, Barozzino T, Toi A, et al. Prenatal detection of cerebral lesions in a fetus with tuberous sclerosis. Ultrasound Obstet Gynecol. 1999, 14 (5): 356–359.
[28] Milunsky A, Shiml SH, Ito M, et al. Precise prenatal diagnosis of tuberous sclerosis by sequencing the TSC2 gene. Prenat Diagn. 2005, 25 (7): 582–585.
[29] Roach ES, Gomez MR, Northrup H. Tuberous Sclerosis Complex Consensus Conference: Revised Clinical Diagnostic Criteria. J Child Neurol . 1998, 13 (12): 624-628.
[30] Schachter SC. Antiepileptic drug therapy: general treatment principles and application for special patient populations. Epilepsia. 1999, 40 (Suppl 9): S20-S25.
[31] Hirtz D, Berg A, Bettis D, et al. Practice parameter: Treatment of the child with a first unprovoked seizure: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2003, 60 (2): 166-175.