{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:56:37Z","timestamp":1784735797514,"version":"3.55.0"},"reference-count":83,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T00:00:00Z","timestamp":1554940800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"published-print":{"date-parts":[[2020,4]]},"DOI":"10.1007\/s00401-019-02003-1","type":"journal-article","created":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T20:03:54Z","timestamp":1555013034000},"page":"613-624","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["An update on the central nervous system manifestations of tuberous sclerosis complex"],"prefix":"10.1007","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1420-3314","authenticated-orcid":false,"given":"Jennifer A.","family":"Cotter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,4,11]]},"reference":[{"key":"2003_CR1","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/BF00688497","volume":"21","author":"C Arseni","year":"1972","unstructured":"Arseni C, Alexianu M, Horvat L, Alexianu D, Petrovici A (1972) Fine structure of atypical cells in tuberous sclerosis. Acta Neuropathol 21:185\u2013193","journal-title":"Acta Neuropathol"},{"key":"2003_CR2","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1097\/GIM.0b013e31803068c7","volume":"9","author":"KS Au","year":"2007","unstructured":"Au KS, Williams AT, Roach ES, Batchelor L, Sparagana SP, Delgado MR et al (2007) Genotype\/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States. Genet Med 9:88\u2013100. \nhttps:\/\/doi.org\/10.1097\/GIM.0b013e31803068c7","journal-title":"Genet Med"},{"key":"2003_CR3","doi-asserted-by":"publisher","first-page":"95","DOI":"10.5146\/tjpath.2012.01107","volume":"28","author":"BD Barrows","year":"2012","unstructured":"Barrows BD, Rutkowski MJ, Gultekin SH, Parsa AT, Tihan T (2012) Evidence of ambiguous differentiation and mTOR pathway dysregulation in subependymal giant cell astrocytoma. Turk Patoloji Derg 28:95\u2013103. \nhttps:\/\/doi.org\/10.5146\/tjpath.2012.01107","journal-title":"Turk Patoloji Derg"},{"key":"2003_CR4","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1016\/j.neuron.2013.03.017","volume":"78","author":"HS Bateup","year":"2013","unstructured":"Bateup HS, Johnson CA, Denefrio CL, Saulnier JL, Kornacker K, Sabatini BL (2013) Excitatory\/inhibitory synaptic imbalance leads to hippocampal hyperexcitability in mouse models of tuberous sclerosis. Neuron 78:510\u2013522. \nhttps:\/\/doi.org\/10.1016\/j.neuron.2013.03.017","journal-title":"Neuron"},{"key":"2003_CR5","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1038\/s41591-018-0139-y","volume":"24","author":"JD Blair","year":"2018","unstructured":"Blair JD, Hockemeyer D, Bateup HS (2018) Genetically engineered human cortical spheroid models of tuberous sclerosis. Nat Med 24:1568\u20131578. \nhttps:\/\/doi.org\/10.1038\/s41591-018-0139-y","journal-title":"Nat Med"},{"key":"2003_CR6","doi-asserted-by":"publisher","first-page":"95516","DOI":"10.18632\/oncotarget.20764","volume":"8","author":"A Bongaarts","year":"2017","unstructured":"Bongaarts A, Giannikou K, Reinten RJ, Anink JJ, Mills JD, Jansen FE et al (2017) Subependymal giant cell astrocytomas in tuberous sclerosis complex have consistent TSC1\/TSC2 biallelic inactivation, and no BRAF mutations. Oncotarget 8:95516\u201395529. \nhttps:\/\/doi.org\/10.18632\/oncotarget.20764","journal-title":"Oncotarget"},{"key":"2003_CR7","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1002\/ajmg.c.31648","volume":"178","author":"S Boronat","year":"2018","unstructured":"Boronat S, Barber I (2018) Less common manifestations in TSC. Am J Med Genet Part C Semin Med Genet 178:348\u2013354. \nhttps:\/\/doi.org\/10.1002\/ajmg.c.31648","journal-title":"Am J Med Genet Part C Semin Med Genet"},{"key":"2003_CR8","first-page":"69","volume":"1","author":"D Bourneville","year":"1880","unstructured":"Bourneville D (1880) Contribution \u00e0 l\u2019\u00e9tude de l\u2019idiotie. Arch Neurol (Paris) 1:69\u201391","journal-title":"Arch Neurol (Paris)"},{"key":"2003_CR9","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/nature26000","volume":"555","author":"D Capper","year":"2018","unstructured":"Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D et al (2018) DNA methylation-based classification of central nervous system tumours. Nature 555:469\u2013474. \nhttps:\/\/doi.org\/10.1038\/nature26000","journal-title":"Nature"},{"key":"2003_CR10","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1093\/jnen\/63.12.1236","volume":"63","author":"JA Chan","year":"2004","unstructured":"Chan JA, Zhang H, Roberts PS, Jozwiak S, Wieslawa G, Lewin-Kowalik J et al (2004) Pathogenesis of tuberous sclerosis subependymal giant cell astrocytomas: biallelic inactivation of TSC1 or TSC2 leads to mTOR activation. J Neuropathol Exp Neurol 63:1236\u20131242","journal-title":"J Neuropathol Exp Neurol"},{"key":"2003_CR11","doi-asserted-by":"publisher","first-page":"14152","DOI":"10.1073\/pnas.93.24.14152","volume":"93","author":"PB Crino","year":"1996","unstructured":"Crino PB, Trojanowski JQ, Dichter MA, Eberwine J (1996) Embryonic neuronal markers in tuberous sclerosis: single-cell molecular pathology. Proc Natl Acad Sci USA 93:14152\u201314157","journal-title":"Proc Natl Acad Sci USA"},{"key":"2003_CR12","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/j.pediatrneurol.2015.06.020","volume":"53","author":"VA Cuddapah","year":"2015","unstructured":"Cuddapah VA, Thompson M, Blount J, Li R, Guleria S, Goyal M (2015) Hemispherectomy for hemimegalencephaly due to tuberous sclerosis and a review of the literature. Pediatr Neurol 53:452\u2013455. \nhttps:\/\/doi.org\/10.1016\/j.pediatrneurol.2015.06.020","journal-title":"Pediatr Neurol"},{"key":"2003_CR13","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/s2352-4642(18)30099-3","volume":"2","author":"P Curatolo","year":"2018","unstructured":"Curatolo P, Franz DN, Lawson JA, Yapici Z, Ikeda H, Polster T et al (2018) Adjunctive everolimus for children and adolescents with treatment-refractory seizures associated with tuberous sclerosis complex: post hoc analysis of the phase 3 EXIST-3 trial. Lancet Child Adolesc Health 2:495\u2013504. \nhttps:\/\/doi.org\/10.1016\/s2352-4642(18)30099-3","journal-title":"Lancet Child Adolesc Health"},{"key":"2003_CR14","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1002\/ana.24357","volume":"77","author":"AM D\u2019Gama","year":"2015","unstructured":"D\u2019Gama AM, Geng Y, Couto JA, Martin B, Boyle EA, LaCoursiere CM et al (2015) Mammalian target of rapamycin pathway mutations cause hemimegalencephaly and focal cortical dysplasia. Ann Neurol 77:720\u2013725. \nhttps:\/\/doi.org\/10.1002\/ana.24357","journal-title":"Ann Neurol"},{"key":"2003_CR15","doi-asserted-by":"publisher","first-page":"3754","DOI":"10.1016\/j.celrep.2017.11.106","volume":"21","author":"AM D\u2019Gama","year":"2017","unstructured":"D\u2019Gama AM, Woodworth MB, Hossain AA, Bizzotto S, Hatem NE, LaCoursiere CM et al (2017) Somatic mutations activating the mTOR pathway in dorsal telencephalic progenitors cause a continuum of cortical dysplasias. Cell Rep 21:3754\u20133766. \nhttps:\/\/doi.org\/10.1016\/j.celrep.2017.11.106","journal-title":"Cell Rep"},{"key":"2003_CR16","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1097\/00005072-196120040-00008","volume":"20","author":"RL Davis","year":"1961","unstructured":"Davis RL, Nelson E (1961) Unilateral ganglioglioma in a tuberosclerotic brain. J Neuropathol Exp Neurol 20:571\u2013581","journal-title":"J Neuropathol Exp Neurol"},{"key":"2003_CR17","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/0022-510X(88)90244-4","volume":"87","author":"GA Leon de","year":"1988","unstructured":"de Leon GA, Zaeri N, Foley CM (1988) Olfactory hamartomas in tuberous sclerosis. J Neurol Sci 87:187\u2013194","journal-title":"J Neurol Sci"},{"key":"2003_CR18","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s13023-018-0901-8","volume":"13","author":"PJ Vries de","year":"2018","unstructured":"de Vries PJ, Belousova E, Benedik MP, Carter T, Cottin V, Curatolo P et al (2018) TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study. Orphanet J Rare Dis 13:157. \nhttps:\/\/doi.org\/10.1186\/s13023-018-0901-8","journal-title":"Orphanet J Rare Dis"},{"key":"2003_CR19","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/S1874-6047(10)28002-2","volume":"28","author":"CC Dibble","year":"2010","unstructured":"Dibble CC, Manning BD (2010) The TSC1\u2013TSC2 complex: a key signal-integrating node upstream of TOR. Enzymes 28:21\u201348","journal-title":"Enzymes"},{"key":"2003_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2018.08.005","author":"P Dragoumi","year":"2018","unstructured":"Dragoumi P, O\u2019Callaghan F, Zafeiriou DI (2018) Diagnosis of tuberous sclerosis complex in the fetus. Eur J Paediatr Neurol. \nhttps:\/\/doi.org\/10.1016\/j.ejpn.2018.08.005","journal-title":"Eur J Paediatr Neurol"},{"key":"2003_CR21","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1016\/0092-8674(93)90618-Z","volume":"75","author":"European Chromosome 16 Tuberous Sclerosis Consortium","year":"1993","unstructured":"European Chromosome 16 Tuberous Sclerosis Consortium (1993) Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 75:1305\u20131315","journal-title":"Cell"},{"key":"2003_CR22","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/82_2010_64","volume":"347","author":"ME Feldman","year":"2010","unstructured":"Feldman ME, Shokat KM (2010) New inhibitors of the PI3K\u2013Akt\u2013mTOR pathway: insights into mTOR signaling from a new generation of Tor Kinase Domain Inhibitors (TORKinibs). Curr Top Microbiol Immunol 347:241\u2013262. \nhttps:\/\/doi.org\/10.1007\/82_2010_64","journal-title":"Curr Top Microbiol Immunol"},{"key":"2003_CR23","first-page":"47","volume":"3","author":"I Ferrer","year":"1984","unstructured":"Ferrer I, Fabregues I, Coll J, Ribalta T, Rives A (1984) Tuberous sclerosis: a Golgi study of cortical tuber. Clin Neuropathol 3:47\u201351","journal-title":"Clin Neuropathol"},{"key":"2003_CR24","doi-asserted-by":"publisher","first-page":"e0158476","DOI":"10.1371\/journal.pone.0158476","volume":"11","author":"DN Franz","year":"2016","unstructured":"Franz DN, Belousova E, Sparagana S, Bebin EM, Frost MD, Kuperman R et al (2016) Long-term use of everolimus in patients with tuberous sclerosis complex: final results from the EXIST-1 study. PLoS One 11:e0158476. \nhttps:\/\/doi.org\/10.1371\/journal.pone.0158476","journal-title":"PLoS One"},{"key":"2003_CR25","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1002\/ana.20784","volume":"59","author":"DN Franz","year":"2006","unstructured":"Franz DN, Leonard J, Tudor C, Chuck G, Care M, Sethuraman G et al (2006) Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol 59:490\u2013498. \nhttps:\/\/doi.org\/10.1002\/ana.20784","journal-title":"Ann Neurol"},{"key":"2003_CR26","doi-asserted-by":"publisher","first-page":"2153","DOI":"10.1016\/S0140-6736(16)31419-2","volume":"388","author":"JA French","year":"2016","unstructured":"French JA, Lawson JA, Yapici Z, Ikeda H, Polster T, Nabbout R et al (2016) Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet 388:2153\u20132163. \nhttps:\/\/doi.org\/10.1016\/S0140-6736(16)31419-2","journal-title":"Lancet"},{"key":"2003_CR27","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1101\/gad.901101","volume":"15","author":"X Gao","year":"2001","unstructured":"Gao X, Pan D (2001) TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes Dev 15:1383\u20131392. \nhttps:\/\/doi.org\/10.1101\/gad.901101","journal-title":"Genes Dev"},{"key":"2003_CR28","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1002\/jcu.20857","volume":"39","author":"A Gedikbasi","year":"2011","unstructured":"Gedikbasi A, Oztarhan K, Ulker V, Aslan G, Gul A, Sener-Arslan E et al (2011) Prenatal sonographic diagnosis of tuberous sclerosis complex. J Clin Ultrasound 39:427\u2013430. \nhttps:\/\/doi.org\/10.1002\/jcu.20857","journal-title":"J Clin Ultrasound"},{"key":"2003_CR29","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1177\/0883073818767036","volume":"33","author":"T Gilboa","year":"2018","unstructured":"Gilboa T, Segel R, Zeligson S, Alterescu G, Ben-Pazi H (2018) Ganglioglioma, epilepsy, and intellectual impairment due to familial TSC1 deletion. J Child Neurol 33:482\u2013486. \nhttps:\/\/doi.org\/10.1177\/0883073818767036","journal-title":"J Child Neurol"},{"key":"2003_CR30","doi-asserted-by":"publisher","first-page":"925646","DOI":"10.1155\/2012\/925646","volume":"2012","author":"M Gusman","year":"2012","unstructured":"Gusman M, Servaes S, Feygin T, Degenhardt K, Epelman M (2012) Multimodal imaging in the prenatal diagnosis of tuberous sclerosis complex. Case Rep Pediatr 2012:925646. \nhttps:\/\/doi.org\/10.1155\/2012\/925646","journal-title":"Case Rep Pediatr"},{"key":"2003_CR31","first-page":"400","volume":"59","author":"EP Henske","year":"1996","unstructured":"Henske EP, Scheithauer BW, Short MP, Wollmann R, Nahmias J, Hornigold N et al (1996) Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions. Am J Hum Genet 59:400\u2013406","journal-title":"Am J Hum Genet"},{"key":"2003_CR32","first-page":"395","volume":"80","author":"B Itoua","year":"1999","unstructured":"Itoua B, Joubert E, Le Bras Y, Picot F, Gautier F, Wertel F et al (1999) What is it? Bourneville tuberous sclerosis associated with an arteriovenous malformation, a pituitary adenoma and 2 arachnoid cysts. J Radiol 80:395\u2013396","journal-title":"J Radiol"},{"issue":"151\u2013155","key":"2003_CR33","doi-asserted-by":"publisher","first-page":"e151","DOI":"10.1016\/j.jpeds.2016.01.027","volume":"172","author":"S Jozwiak","year":"2016","unstructured":"Jozwiak S, Kotulska K, Berkowitz N, Brechenmacher T, Franz DN (2016) Safety of everolimus in patients younger than 3 years of age: results from EXIST-1, a randomized, controlled clinical trial. J Pediatr 172(151\u2013155):e151. \nhttps:\/\/doi.org\/10.1016\/j.jpeds.2016.01.027","journal-title":"J Pediatr"},{"key":"2003_CR34","doi-asserted-by":"publisher","first-page":"406","DOI":"10.3171\/2011.12.PEDS11418","volume":"9","author":"JS Katz","year":"2012","unstructured":"Katz JS, Milla SS, Wiggins GC, Devinsky O, Weiner HL, Roth J (2012) Intraventricular lesions in tuberous sclerosis complex: a possible association with the caudate nucleus. J Neurosurg Pediatr 9:406\u2013413. \nhttps:\/\/doi.org\/10.3171\/2011.12.PEDS11418","journal-title":"J Neurosurg Pediatr"},{"key":"2003_CR35","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1203\/01.PDR.0000147727.78571.07","volume":"57","author":"H Kenerson","year":"2005","unstructured":"Kenerson H, Dundon TA, Yeung RS (2005) Effects of rapamycin in the Eker rat model of tuberous sclerosis complex. Pediatr Res 57:67\u201375. \nhttps:\/\/doi.org\/10.1203\/01.PDR.0000147727.78571.07","journal-title":"Pediatr Res"},{"key":"2003_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2018.06.007","author":"DA Krueger","year":"2018","unstructured":"Krueger DA, Capal JK, Curatolo P, Devinsky O, Ess K, Tzadok M et al (2018) Short-term safety of mTOR inhibitors in infants and very young children with tuberous sclerosis complex (TSC): multicentre clinical experience. Eur J Paediatr Neurol. \nhttps:\/\/doi.org\/10.1016\/j.ejpn.2018.06.007","journal-title":"Eur J Paediatr Neurol"},{"key":"2003_CR37","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1056\/NEJMoa1001671","volume":"363","author":"DA Krueger","year":"2010","unstructured":"Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P et al (2010) Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med 363:1801\u20131811. \nhttps:\/\/doi.org\/10.1056\/NEJMoa1001671","journal-title":"N Engl J Med"},{"key":"2003_CR38","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.pediatrneurol.2013.08.002","volume":"49","author":"DA Krueger","year":"2013","unstructured":"Krueger DA, Northrup H, International Tuberous Sclerosis Complex Consensus Group (2013) Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 49:255\u2013265. \nhttps:\/\/doi.org\/10.1016\/j.pediatrneurol.2013.08.002","journal-title":"Pediatr Neurol"},{"key":"2003_CR39","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1002\/jso.23822","volume":"111","author":"D Lee","year":"2015","unstructured":"Lee D, Cho YH, Kang SY, Yoon N, Sung CO, Suh YL (2015) BRAF V600E mutations are frequent in dysembryoplastic neuroepithelial tumors and subependymal giant cell astrocytomas. J Surg Oncol 111:359\u2013364. \nhttps:\/\/doi.org\/10.1002\/jso.23822","journal-title":"J Surg Oncol"},{"key":"2003_CR40","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1002\/gcc.20052","volume":"41","author":"L Lee-Jones","year":"2004","unstructured":"Lee-Jones L, Aligianis I, Davies PA, Puga A, Farndon PA, Stemmer-Rachamimov A et al (2004) Sacrococcygeal chordomas in patients with tuberous sclerosis complex show somatic loss of TSC1 or TSC2. Genes Chromosom Cancer 41:80\u201385. \nhttps:\/\/doi.org\/10.1002\/gcc.20052","journal-title":"Genes Chromosom Cancer"},{"key":"2003_CR41","doi-asserted-by":"publisher","first-page":"13373","DOI":"10.1038\/s41598-018-31075-4","volume":"8","author":"Y Li","year":"2018","unstructured":"Li Y, Barkovich MJ, Karch CM, Nillo RM, Fan CC, Broce IJ et al (2018) Regionally specific TSC1 and TSC2 gene expression in tuberous sclerosis complex. Sci Rep 8:13373. \nhttps:\/\/doi.org\/10.1038\/s41598-018-31075-4","journal-title":"Sci Rep"},{"key":"2003_CR42","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/2051-5960-2-71","volume":"2","author":"J Liu","year":"2014","unstructured":"Liu J, Reeves C, Michalak Z, Coppola A, Diehl B, Sisodiya SM et al (2014) Evidence for mTOR pathway activation in a spectrum of epilepsy-associated pathologies. Acta Neuropathol Commun 2:71. \nhttps:\/\/doi.org\/10.1186\/2051-5960-2-71","journal-title":"Acta Neuropathol Commun"},{"key":"2003_CR43","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1038\/leu.2016.326","volume":"31","author":"W Liu","year":"2017","unstructured":"Liu W, Yu WM, Zhang J, Chan RJ, Loh ML, Zhang Z et al (2017) Inhibition of the Gab2\/PI3K\/mTOR signaling ameliorates myeloid malignancy caused by Ptpn11 (Shp2) gain-of-function mutations. Leukemia 31:1415\u20131422. \nhttps:\/\/doi.org\/10.1038\/leu.2016.326","journal-title":"Leukemia"},{"key":"2003_CR44","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1007\/s004010050438","volume":"91","author":"MB Lopes","year":"1996","unstructured":"Lopes MB, Altermatt HJ, Scheithauer BW, Shepherd CW, VandenBerg SR (1996) Immunohistochemical characterization of subependymal giant cell astrocytomas. Acta Neuropathol 91:368\u2013375","journal-title":"Acta Neuropathol"},{"key":"2003_CR45","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1242\/dmm.012096","volume":"6","author":"L Magri","year":"2013","unstructured":"Magri L, Cominelli M, Cambiaghi M, Cursi M, Leocani L, Minicucci F et al (2013) Timing of mTOR activation affects tuberous sclerosis complex neuropathology in mouse models. Dis Model Mech 6:1185\u20131197. \nhttps:\/\/doi.org\/10.1242\/dmm.012096","journal-title":"Dis Model Mech"},{"key":"2003_CR46","doi-asserted-by":"publisher","first-page":"15816","DOI":"10.1038\/ncomms15816","volume":"8","author":"KR Martin","year":"2017","unstructured":"Martin KR, Zhou W, Bowman MJ, Shih J, Au KS, Dittenhafer-Reed KE et al (2017) The genomic landscape of tuberous sclerosis complex. Nat Commun 8:15816. \nhttps:\/\/doi.org\/10.1038\/ncomms15816","journal-title":"Nat Commun"},{"key":"2003_CR47","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1136\/jmg.2010.085092","volume":"48","author":"ML McMaster","year":"2011","unstructured":"McMaster ML, Goldstein AM, Parry DM (2011) Clinical features distinguish childhood chordoma associated with tuberous sclerosis complex (TSC) from chordoma in the general paediatric population. J Med Genet 48:444\u2013449. \nhttps:\/\/doi.org\/10.1136\/jmg.2010.085092","journal-title":"J Med Genet"},{"key":"2003_CR48","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1016\/j.celrep.2015.07.013","volume":"12","author":"UY Moon","year":"2015","unstructured":"Moon UY, Park JY, Park R, Cho JY, Hughes LJ, McKenna J 3rd et al (2015) Impaired Reelin-Dab1 signaling contributes to neuronal migration deficits of tuberous sclerosis complex. Cell Rep 12:965\u2013978. \nhttps:\/\/doi.org\/10.1016\/j.celrep.2015.07.013","journal-title":"Cell Rep"},{"key":"2003_CR49","first-page":"261","volume":"5","author":"E Nardelli","year":"1986","unstructured":"Nardelli E, De Benedictis G, La Stilla G, Nicolardi G (1986) Tuberous sclerosis: a neuropathological and immunohistochemical (PAP) study. Clin Neuropathol 5:261\u2013266","journal-title":"Clin Neuropathol"},{"key":"2003_CR50","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.neuron.2013.03.030","volume":"78","author":"EA Normand","year":"2013","unstructured":"Normand EA, Crandall SR, Thorn CA, Murphy EM, Voelcker B, Browning C et al (2013) Temporal and mosaic Tsc1 deletion in the developing thalamus disrupts thalamocortical circuitry, neural function, and behavior. Neuron 78:895\u2013909. \nhttps:\/\/doi.org\/10.1016\/j.neuron.2013.03.030","journal-title":"Neuron"},{"key":"2003_CR51","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.pediatrneurol.2013.08.001","volume":"49","author":"H Northrup","year":"2013","unstructured":"Northrup H, Krueger DA, International Tuberous Sclerosis Complex Consensus Group (2013) Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 49:243\u2013254. \nhttps:\/\/doi.org\/10.1016\/j.pediatrneurol.2013.08.001","journal-title":"Pediatr Neurol"},{"key":"2003_CR52","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.1016\/S0140-6736(05)78872-3","volume":"351","author":"FJ O\u2019Callaghan","year":"1998","unstructured":"O\u2019Callaghan FJ, Shiell AW, Osborne JP, Martyn CN (1998) Prevalence of tuberous sclerosis estimated by capture-recapture analysis. Lancet 351:1490. \nhttps:\/\/doi.org\/10.1016\/S0140-6736(05)78872-3","journal-title":"Lancet"},{"key":"2003_CR53","volume-title":"The embryonic human brain: an atlas of developmental stages","author":"R O\u2019Rahilly","year":"1994","unstructured":"O\u2019Rahilly R, M\u00fcller F (1994) The embryonic human brain: an atlas of developmental stages. Wiley-Liss, Hoboken"},{"key":"2003_CR54","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1007\/s00381-014-2383-x","volume":"30","author":"T Ouyang","year":"2014","unstructured":"Ouyang T, Zhang N, Benjamin T, Wang L, Jiao J, Zhao Y et al (2014) Subependymal giant cell astrocytoma: current concepts, management, and future directions. Childs Nerv Syst 30:561\u2013570. \nhttps:\/\/doi.org\/10.1007\/s00381-014-2383-x","journal-title":"Childs Nerv Syst"},{"key":"2003_CR55","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1038\/ejhg.2016.85","volume":"24","author":"IE Overwater","year":"2016","unstructured":"Overwater IE, Swenker R, van der Ende EL, Hanemaayer KB, Hoogeveen-Westerveld M, van Eeghen AM et al (2016) Genotype and brain pathology phenotype in children with tuberous sclerosis complex. Eur J Hum Genet 24:1688\u20131695. \nhttps:\/\/doi.org\/10.1038\/ejhg.2016.85","journal-title":"Eur J Hum Genet"},{"key":"2003_CR56","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1002\/ajmg.c.31651","volume":"178","author":"A Peron","year":"2018","unstructured":"Peron A, Au KS, Northrup H (2018) Genetics, genomics, and genotype-phenotype correlations of TSC: insights for clinical practice. Am J Med Genet Part C Semin Med Genet 178:281\u2013290. \nhttps:\/\/doi.org\/10.1002\/ajmg.c.31651","journal-title":"Am J Med Genet Part C Semin Med Genet"},{"key":"2003_CR57","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1111\/j.1750-3639.2012.00616.x","volume":"23","author":"AS Prabowo","year":"2013","unstructured":"Prabowo AS, Anink JJ, Lammens M, Nellist M, van den Ouweland AM, Adle-Biassette H et al (2013) Fetal brain lesions in tuberous sclerosis complex: TORC1 activation and inflammation. Brain Pathol 23:45\u201359. \nhttps:\/\/doi.org\/10.1111\/j.1750-3639.2012.00616.x","journal-title":"Brain Pathol"},{"key":"2003_CR58","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1042\/bst0310579","volume":"31","author":"V Ramesh","year":"2003","unstructured":"Ramesh V (2003) Aspects of tuberous sclerosis complex (TSC) protein function in the brain. Biochem Soc Trans 31:579\u2013583. \nhttps:\/\/doi.org\/10.1042\/bst0310579","journal-title":"Biochem Soc Trans"},{"key":"2003_CR59","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.pediatrneurol.2016.07.003","volume":"63","author":"ES Roach","year":"2016","unstructured":"Roach ES (2016) Applying the lessons of tuberous sclerosis: the 2015 Hower Award Lecture. Pediatr Neurol 63:6\u201322. \nhttps:\/\/doi.org\/10.1016\/j.pediatrneurol.2016.07.003","journal-title":"Pediatr Neurol"},{"key":"2003_CR60","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/nature17963","volume":"534","author":"VS Rodrik-Outmezguine","year":"2016","unstructured":"Rodrik-Outmezguine VS, Okaniwa M, Yao Z, Novotny CJ, McWhirter C, Banaji A et al (2016) Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature 534:272\u2013276. \nhttps:\/\/doi.org\/10.1038\/nature17963","journal-title":"Nature"},{"key":"2003_CR61","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1212\/CON.0000000000000562","volume":"24","author":"T Rosser","year":"2018","unstructured":"Rosser T (2018) Neurocutaneous disorders. Continuum (Minneap Minn) 24:96\u2013129. \nhttps:\/\/doi.org\/10.1212\/CON.0000000000000562","journal-title":"Continuum (Minneap Minn)"},{"key":"2003_CR62","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.pediatrneurol.2013.08.017","volume":"49","author":"J Roth","year":"2013","unstructured":"Roth J, Roach ES, Bartels U, Jozwiak S, Koenig MK, Weiner HL et al (2013) Subependymal giant cell astrocytoma: diagnosis, screening, and treatment. Recommendations from the International Tuberous Sclerosis Complex Consensus Conference 2012. Pediatr Neurol 49:439\u2013444. \nhttps:\/\/doi.org\/10.1016\/j.pediatrneurol.2013.08.017","journal-title":"Pediatr Neurol"},{"key":"2003_CR63","doi-asserted-by":"publisher","first-page":"e142","DOI":"10.1111\/epi.14529","volume":"59","author":"S Samueli","year":"2018","unstructured":"Samueli S, Dressler A, Groppel G, Scholl T, Feucht M (2018) Everolimus in infants with tuberous sclerosis complex-related West syndrome: first results from a single-center prospective observational study. Epilepsia 59:e142\u2013e146. \nhttps:\/\/doi.org\/10.1111\/epi.14529","journal-title":"Epilepsia"},{"key":"2003_CR64","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/sj.ejhg.5201402","volume":"13","author":"O Sancak","year":"2005","unstructured":"Sancak O, Nellist M, Goedbloed M, Elfferich P, Wouters C, Maat-Kievit A et al (2005) Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype\u2013phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex. Eur J Hum Genet 13:731\u2013741. \nhttps:\/\/doi.org\/10.1038\/sj.ejhg.5201402","journal-title":"Eur J Hum Genet"},{"key":"2003_CR65","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/s00401-011-0802-6","volume":"121","author":"G Schindler","year":"2011","unstructured":"Schindler G, Capper D, Meyer J, Janzarik W, Omran H, Herold-Mende C et al (2011) Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol 121:397\u2013405. \nhttps:\/\/doi.org\/10.1007\/s00401-011-0802-6","journal-title":"Acta Neuropathol"},{"key":"2003_CR66","doi-asserted-by":"publisher","first-page":"H231","DOI":"10.1152\/ajpheart.00665.2011","volume":"302","author":"C Schramm","year":"2012","unstructured":"Schramm C, Fine DM, Edwards MA, Reeb AN, Krenz M (2012) The PTPN11 loss-of-function mutation Q510E-Shp2 causes hypertrophic cardiomyopathy by dysregulating mTOR signaling. Am J Physiol Heart Circ Physiol 302:H231\u2013H243. \nhttps:\/\/doi.org\/10.1152\/ajpheart.00665.2011","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2003_CR67","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2018.05.039","author":"S Schubert-Bast","year":"2018","unstructured":"Schubert-Bast S, Rosenow F, Klein KM, Reif PS, Kieslich M, Strzelczyk A (2018) The role of mTOR inhibitors in preventing epileptogenesis in patients with TSC: current evidence and future perspectives. Epilepsy Behav. \nhttps:\/\/doi.org\/10.1016\/j.yebeh.2018.05.039","journal-title":"Epilepsy Behav"},{"key":"2003_CR68","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.neuroscience.2016.11.017","volume":"341","author":"K Switon","year":"2017","unstructured":"Switon K, Kotulska K, Janusz-Kaminska A, Zmorzynska J, Jaworski J (2017) Molecular neurobiology of mTOR. Neuroscience 341:112\u2013153. \nhttps:\/\/doi.org\/10.1016\/j.neuroscience.2016.11.017","journal-title":"Neuroscience"},{"key":"2003_CR69","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1177\/0883073807304014","volume":"22","author":"M Tatli","year":"2007","unstructured":"Tatli M, Guzel A (2007) Bilateral temporal arachnoid cysts associated with tuberous sclerosis complex. J Child Neurol 22:775\u2013779. \nhttps:\/\/doi.org\/10.1177\/0883073807304014","journal-title":"J Child Neurol"},{"key":"2003_CR70","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.14055","author":"I Toldo","year":"2018","unstructured":"Toldo I, Brasson V, Miscioscia M, Pelizza MF, Manara R, Sartori S et al (2018) Tuberous sclerosis-associated neuropsychiatric disorders: a paediatric cohort study. Dev Med Child Neurol. \nhttps:\/\/doi.org\/10.1111\/dmcn.14055","journal-title":"Dev Med Child Neurol"},{"key":"2003_CR71","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1002\/ana.410090211","volume":"9","author":"IK Trombley","year":"1981","unstructured":"Trombley IK, Mirra SS (1981) Ultrastructure of tuberous sclerosis: cortical tuber and subependymal tumor. Ann Neurol 9:174\u2013181. \nhttps:\/\/doi.org\/10.1002\/ana.410090211","journal-title":"Ann Neurol"},{"key":"2003_CR72","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1093\/cercor\/bhs310","volume":"24","author":"V Tsai","year":"2014","unstructured":"Tsai V, Parker WE, Orlova KA, Baybis M, Chi AW, Berg BD et al (2014) Fetal brain mTOR signaling activation in tuberous sclerosis complex. Cereb Cortex 24:315\u2013327. \nhttps:\/\/doi.org\/10.1093\/cercor\/bhs310","journal-title":"Cereb Cortex"},{"key":"2003_CR73","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1126\/science.277.5327.805","volume":"277","author":"M Slegtenhorst van","year":"1997","unstructured":"van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S et al (1997) Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 277:805\u2013808","journal-title":"Science"},{"key":"2003_CR74","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1159\/000017404","volume":"21","author":"HV Vinters","year":"1999","unstructured":"Vinters HV, Park SH, Johnson MW, Mischel PS, Catania M, Kerfoot C (1999) Cortical dysplasia, genetic abnormalities and neurocutaneous syndromes. Dev Neurosci 21:248\u2013259. \nhttps:\/\/doi.org\/10.1159\/000017404","journal-title":"Dev Neurosci"},{"key":"2003_CR75","first-page":"1","volume":"20","author":"F Recklinghausen von","year":"1862","unstructured":"von Recklinghausen F (1862) Ein Herz von einem Neugebore- nen, welches mehrere teils nach aussen, teils nach den H\u00f6hlen prominierende Tumoren (Myomen) trug. Verh Ges Geburtsh Monatschr Geburtsk 20:1\u20132","journal-title":"Verh Ges Geburtsh Monatschr Geburtsk"},{"key":"2003_CR76","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.jdermsci.2015.04.005","volume":"79","author":"M Wataya-Kaneda","year":"2015","unstructured":"Wataya-Kaneda M (2015) Mammalian target of rapamycin and tuberous sclerosis complex. J Dermatol Sci 79:93\u2013100. \nhttps:\/\/doi.org\/10.1016\/j.jdermsci.2015.04.005","journal-title":"J Dermatol Sci"},{"key":"2003_CR77","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s00401-010-0677-y","volume":"120","author":"SA Yasin","year":"2010","unstructured":"Yasin SA, Latak K, Becherini F, Ganapathi A, Miller K, Campos O et al (2010) Balloon cells in human cortical dysplasia and tuberous sclerosis: isolation of a pathological progenitor-like cell. Acta Neuropathol 120:85\u201396. \nhttps:\/\/doi.org\/10.1007\/s00401-010-0677-y","journal-title":"Acta Neuropathol"},{"key":"2003_CR78","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1136\/adc.2011.211995","volume":"96","author":"JR Yates","year":"2011","unstructured":"Yates JR, Maclean C, Higgins JN, Humphrey A, le Marechal K, Clifford M et al (2011) The Tuberous Sclerosis 2000 Study: presentation, initial assessments and implications for diagnosis and management. Arch Dis Child 96:1020\u20131025. \nhttps:\/\/doi.org\/10.1136\/adc.2011.211995","journal-title":"Arch Dis Child"},{"key":"2003_CR79","first-page":"1477","volume":"151","author":"RS Yeung","year":"1997","unstructured":"Yeung RS, Katsetos CD, Klein-Szanto A (1997) Subependymal astrocytic hamartomas in the Eker rat model of tuberous sclerosis. Am J Pathol 151:1477\u20131486","journal-title":"Am J Pathol"},{"key":"2003_CR80","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1101\/gad.16750211","volume":"25","author":"J Zhou","year":"2011","unstructured":"Zhou J, Shrikhande G, Xu J, McKay RM, Burns DK, Johnson JE et al (2011) Tsc1 mutant neural stem\/progenitor cells exhibit migration deficits and give rise to subependymal lesions in the lateral ventricle. Genes Dev 25:1595\u20131600. \nhttps:\/\/doi.org\/10.1101\/gad.16750211","journal-title":"Genes Dev"},{"key":"2003_CR81","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1172\/jci96342","volume":"128","author":"P Zordan","year":"2018","unstructured":"Zordan P, Cominelli M, Cascino F, Tratta E, Poliani PL, Galli R (2018) Tuberous sclerosis complex-associated CNS abnormalities depend on hyperactivation of mTORC1 and Akt. J Clin Investig 128:1688\u20131706. \nhttps:\/\/doi.org\/10.1172\/jci96342","journal-title":"J Clin Investig"},{"key":"2003_CR82","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1111\/epi.13923","volume":"58","author":"J Zou","year":"2017","unstructured":"Zou J, Zhang B, Gutmann DH, Wong M (2017) Postnatal reduction of tuberous sclerosis complex 1 expression in astrocytes and neurons causes seizures in an age-dependent manner. Epilepsia 58:2053\u20132063. \nhttps:\/\/doi.org\/10.1111\/epi.13923","journal-title":"Epilepsia"},{"key":"2003_CR83","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.mcn.2018.08.004","volume":"92","author":"AJ Zucco","year":"2018","unstructured":"Zucco AJ, Pozzo VD, Afinogenova A, Hart RP, Devinsky O, D\u2019Arcangelo G (2018) Neural progenitors derived from Tuberous Sclerosis Complex patients exhibit attenuated PI3K\/AKT signaling and delayed neuronal differentiation. Mol Cell Neurosci 92:149\u2013163. \nhttps:\/\/doi.org\/10.1016\/j.mcn.2018.08.004","journal-title":"Mol Cell Neurosci"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-019-02003-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00401-019-02003-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-019-02003-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T23:19:36Z","timestamp":1586474376000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00401-019-02003-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,11]]},"references-count":83,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["2003"],"URL":"https:\/\/doi.org\/10.1007\/s00401-019-02003-1","relation":{},"ISSN":["0001-6322","1432-0533"],"issn-type":[{"value":"0001-6322","type":"print"},{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,11]]},"assertion":[{"value":"28 December 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2019","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 April 2019","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 April 2019","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}