nach oben

Acta Neuropathologica

Erschienen in:

11.04.2019 | Review

An update on the central nervous system manifestations of tuberous sclerosis complex

verfasst von: Jennifer A. Cotter

Erschienen in: Acta Neuropathologica | Ausgabe 4/2020

Einloggen, um Zugang zu erhalten

Abstract

The autosomal dominant disorder tuberous sclerosis complex (TSC) is characterized by an array of manifestations both within and outside of the central nervous system (CNS), including hamartomas and other malformations. TSC is caused by mutations in the TSC1 or TSC2 gene resulting in activation of the mechanistic target of rapamycin (mTOR) signaling pathway. Study of TSC has shed light on the critical role of the mTOR pathway in neurodevelopment. This update reviews the genetic basis of TSC, its cardinal phenotypic CNS features, and recent developments in the field of TSC and other mTOR-altered disorders.

Arseni C, Alexianu M, Horvat L, Alexianu D, Petrovici A (1972) Fine structure of atypical cells in tuberous sclerosis. Acta Neuropathol 21:185–193CrossRefPubMed

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 9:88–100. https://doi.org/10.1097/GIM.0b013e31803068c7 CrossRefPubMed

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 28:95–103. https://doi.org/10.5146/tjpath.2012.01107 CrossRefPubMed

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 78:510–522. https://doi.org/10.1016/j.neuron.2013.03.017 CrossRefPubMedPubMedCentral

Blair JD, Hockemeyer D, Bateup HS (2018) Genetically engineered human cortical spheroid models of tuberous sclerosis. Nat Med 24:1568–1578. https://doi.org/10.1038/s41591-018-0139-y CrossRefPubMedPubMedCentral

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 8:95516–95529. https://doi.org/10.18632/oncotarget.20764 CrossRefPubMedPubMedCentral

Boronat S, Barber I (2018) Less common manifestations in TSC. Am J Med Genet Part C Semin Med Genet 178:348–354. https://doi.org/10.1002/ajmg.c.31648 CrossRefPubMed

Bourneville D (1880) Contribution à l’étude de l’idiotie. Arch Neurol (Paris) 1:69–91

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 555:469–474. https://doi.org/10.1038/nature26000 CrossRefPubMedPubMedCentral

10.

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 63:1236–1242CrossRefPubMed

11.

Crino PB, Trojanowski JQ, Dichter MA, Eberwine J (1996) Embryonic neuronal markers in tuberous sclerosis: single-cell molecular pathology. Proc Natl Acad Sci USA 93:14152–14157CrossRefPubMedPubMedCentral

12.

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 53:452–455. https://doi.org/10.1016/j.pediatrneurol.2015.06.020 CrossRefPubMed

13.

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 2:495–504. https://doi.org/10.1016/s2352-4642(18)30099-3 CrossRefPubMed

14.

D’Gama 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 77:720–725. https://doi.org/10.1002/ana.24357 CrossRefPubMedPubMedCentral

15.

D’Gama 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 21:3754–3766. https://doi.org/10.1016/j.celrep.2017.11.106 CrossRefPubMedPubMedCentral

16.

Davis RL, Nelson E (1961) Unilateral ganglioglioma in a tuberosclerotic brain. J Neuropathol Exp Neurol 20:571–581CrossRefPubMed

17.

de Leon GA, Zaeri N, Foley CM (1988) Olfactory hamartomas in tuberous sclerosis. J Neurol Sci 87:187–194CrossRefPubMed

18.

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. https://doi.org/10.1186/s13023-018-0901-8 CrossRefPubMedPubMedCentral

19.

Dibble CC, Manning BD (2010) The TSC1–TSC2 complex: a key signal-integrating node upstream of TOR. Enzymes 28:21–48CrossRef

20.

Dragoumi P, O’Callaghan F, Zafeiriou DI (2018) Diagnosis of tuberous sclerosis complex in the fetus. Eur J Paediatr Neurol. https://doi.org/10.1016/j.ejpn.2018.08.005 CrossRefPubMed

21.

European Chromosome 16 Tuberous Sclerosis Consortium (1993) Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 75:1305–1315CrossRef

22.

Feldman ME, Shokat KM (2010) New inhibitors of the PI3K–Akt–mTOR pathway: insights into mTOR signaling from a new generation of Tor Kinase Domain Inhibitors (TORKinibs). Curr Top Microbiol Immunol 347:241–262. https://doi.org/10.1007/82_2010_64 CrossRefPubMed

23.

Ferrer I, Fabregues I, Coll J, Ribalta T, Rives A (1984) Tuberous sclerosis: a Golgi study of cortical tuber. Clin Neuropathol 3:47–51PubMed

24.

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. https://doi.org/10.1371/journal.pone.0158476 CrossRefPubMedPubMedCentral

25.

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 59:490–498. https://doi.org/10.1002/ana.20784 CrossRefPubMed

26.

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 388:2153–2163. https://doi.org/10.1016/S0140-6736(16)31419-2 CrossRefPubMed

27.

Gao X, Pan D (2001) TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes Dev 15:1383–1392. https://doi.org/10.1101/gad.901101 CrossRefPubMedPubMedCentral

28.

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 39:427–430. https://doi.org/10.1002/jcu.20857 CrossRefPubMed

29.

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 33:482–486. https://doi.org/10.1177/0883073818767036 CrossRefPubMed

30.

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. https://doi.org/10.1155/2012/925646 CrossRefPubMedPubMedCentral

31.

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 59:400–406PubMedPubMedCentral

32.

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 80:395–396PubMed

33.

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(151–155):e151. https://doi.org/10.1016/j.jpeds.2016.01.027 CrossRef

34.

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 9:406–413. https://doi.org/10.3171/2011.12.PEDS11418 CrossRefPubMed

35.

Kenerson H, Dundon TA, Yeung RS (2005) Effects of rapamycin in the Eker rat model of tuberous sclerosis complex. Pediatr Res 57:67–75. https://doi.org/10.1203/01.PDR.0000147727.78571.07 CrossRefPubMed

36.

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. https://doi.org/10.1016/j.ejpn.2018.06.007 CrossRefPubMed

37.

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 363:1801–1811. https://doi.org/10.1056/NEJMoa1001671 CrossRefPubMed

38.

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 49:255–265. https://doi.org/10.1016/j.pediatrneurol.2013.08.002 CrossRefPubMedPubMedCentral

39.

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 111:359–364. https://doi.org/10.1002/jso.23822 CrossRefPubMed

40.

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 41:80–85. https://doi.org/10.1002/gcc.20052 CrossRefPubMed

41.

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. https://doi.org/10.1038/s41598-018-31075-4 CrossRefPubMedPubMedCentral

42.

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. https://doi.org/10.1186/2051-5960-2-71 CrossRefPubMedPubMedCentral

43.

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 31:1415–1422. https://doi.org/10.1038/leu.2016.326 CrossRefPubMed

44.

Lopes MB, Altermatt HJ, Scheithauer BW, Shepherd CW, VandenBerg SR (1996) Immunohistochemical characterization of subependymal giant cell astrocytomas. Acta Neuropathol 91:368–375CrossRefPubMed

45.

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 6:1185–1197. https://doi.org/10.1242/dmm.012096 CrossRefPubMedPubMedCentral

46.

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. https://doi.org/10.1038/ncomms15816 CrossRefPubMedPubMedCentral

47.

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 48:444–449. https://doi.org/10.1136/jmg.2010.085092 CrossRefPubMed

48.

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 12:965–978. https://doi.org/10.1016/j.celrep.2015.07.013 CrossRefPubMedPubMedCentral

49.

Nardelli E, De Benedictis G, La Stilla G, Nicolardi G (1986) Tuberous sclerosis: a neuropathological and immunohistochemical (PAP) study. Clin Neuropathol 5:261–266PubMed

50.

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 78:895–909. https://doi.org/10.1016/j.neuron.2013.03.030 CrossRefPubMedPubMedCentral

51.

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 49:243–254. https://doi.org/10.1016/j.pediatrneurol.2013.08.001 CrossRefPubMedPubMedCentral

52.

O’Callaghan FJ, Shiell AW, Osborne JP, Martyn CN (1998) Prevalence of tuberous sclerosis estimated by capture-recapture analysis. Lancet 351:1490. https://doi.org/10.1016/S0140-6736(05)78872-3 CrossRefPubMed

53.

O’Rahilly R, Müller F (1994) The embryonic human brain: an atlas of developmental stages. Wiley-Liss, Hoboken

54.

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 30:561–570. https://doi.org/10.1007/s00381-014-2383-x CrossRefPubMed

55.

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 24:1688–1695. https://doi.org/10.1038/ejhg.2016.85 CrossRefPubMedPubMedCentral

56.

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 178:281–290. https://doi.org/10.1002/ajmg.c.31651 CrossRefPubMed

57.

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 23:45–59. https://doi.org/10.1111/j.1750-3639.2012.00616.x CrossRefPubMed

58.

Ramesh V (2003) Aspects of tuberous sclerosis complex (TSC) protein function in the brain. Biochem Soc Trans 31:579–583. https://doi.org/10.1042/bst0310579 CrossRefPubMed

59.

Roach ES (2016) Applying the lessons of tuberous sclerosis: the 2015 Hower Award Lecture. Pediatr Neurol 63:6–22. https://doi.org/10.1016/j.pediatrneurol.2016.07.003 CrossRefPubMed

60.

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 534:272–276. https://doi.org/10.1038/nature17963 CrossRefPubMedPubMedCentral

61.

Rosser T (2018) Neurocutaneous disorders. Continuum (Minneap Minn) 24:96–129. https://doi.org/10.1212/CON.0000000000000562 CrossRef

62.

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 49:439–444. https://doi.org/10.1016/j.pediatrneurol.2013.08.017 CrossRefPubMed

63.

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–e146. https://doi.org/10.1111/epi.14529 CrossRefPubMed

64.

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–phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex. Eur J Hum Genet 13:731–741. https://doi.org/10.1038/sj.ejhg.5201402 CrossRefPubMed

65.

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 121:397–405. https://doi.org/10.1007/s00401-011-0802-6 CrossRefPubMed

66.

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–H243. https://doi.org/10.1152/ajpheart.00665.2011 CrossRefPubMed

67.

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. https://doi.org/10.1016/j.yebeh.2018.05.039 CrossRefPubMed

68.

Switon K, Kotulska K, Janusz-Kaminska A, Zmorzynska J, Jaworski J (2017) Molecular neurobiology of mTOR. Neuroscience 341:112–153. https://doi.org/10.1016/j.neuroscience.2016.11.017 CrossRefPubMed

69.

Tatli M, Guzel A (2007) Bilateral temporal arachnoid cysts associated with tuberous sclerosis complex. J Child Neurol 22:775–779. https://doi.org/10.1177/0883073807304014 CrossRefPubMed

70.

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. https://doi.org/10.1111/dmcn.14055 CrossRefPubMed

71.

Trombley IK, Mirra SS (1981) Ultrastructure of tuberous sclerosis: cortical tuber and subependymal tumor. Ann Neurol 9:174–181. https://doi.org/10.1002/ana.410090211 CrossRefPubMed

72.

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 24:315–327. https://doi.org/10.1093/cercor/bhs310 CrossRefPubMed

73.

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 277:805–808CrossRefPubMed

74.

Vinters HV, Park SH, Johnson MW, Mischel PS, Catania M, Kerfoot C (1999) Cortical dysplasia, genetic abnormalities and neurocutaneous syndromes. Dev Neurosci 21:248–259. https://doi.org/10.1159/000017404 CrossRefPubMed

75.

von Recklinghausen F (1862) Ein Herz von einem Neugebore- nen, welches mehrere teils nach aussen, teils nach den Höhlen prominierende Tumoren (Myomen) trug. Verh Ges Geburtsh Monatschr Geburtsk 20:1–2

76.

Wataya-Kaneda M (2015) Mammalian target of rapamycin and tuberous sclerosis complex. J Dermatol Sci 79:93–100. https://doi.org/10.1016/j.jdermsci.2015.04.005 CrossRefPubMed

77.

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 120:85–96. https://doi.org/10.1007/s00401-010-0677-y CrossRefPubMed

78.

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 96:1020–1025. https://doi.org/10.1136/adc.2011.211995 CrossRefPubMed

79.

Yeung RS, Katsetos CD, Klein-Szanto A (1997) Subependymal astrocytic hamartomas in the Eker rat model of tuberous sclerosis. Am J Pathol 151:1477–1486PubMedPubMedCentral

80.

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 25:1595–1600. https://doi.org/10.1101/gad.16750211 CrossRefPubMedPubMedCentral

81.

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 128:1688–1706. https://doi.org/10.1172/jci96342 CrossRefPubMedPubMedCentral

82.

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 58:2053–2063. https://doi.org/10.1111/epi.13923 CrossRefPubMedPubMedCentral

83.

Zucco AJ, Pozzo VD, Afinogenova A, Hart RP, Devinsky O, D’Arcangelo G (2018) Neural progenitors derived from Tuberous Sclerosis Complex patients exhibit attenuated PI3K/AKT signaling and delayed neuronal differentiation. Mol Cell Neurosci 92:149–163. https://doi.org/10.1016/j.mcn.2018.08.004 CrossRefPubMedPubMedCentral

Titel: An update on the central nervous system manifestations of tuberous sclerosis complex
verfasst von: Jennifer A. Cotter
Publikationsdatum: 11.04.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Acta Neuropathologica / Ausgabe 4/2020
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-019-02003-1

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2020

An update on the CNS manifestations of neurofibromatosis type 2

An update on the central nervous system manifestations of familial tumor predisposition syndromes

An update on the central nervous system manifestations of neurofibromatosis type 1

Picalm reduction exacerbates tau pathology in a murine tauopathy model

An update on the central nervous system manifestations of DICER1 syndrome