Northrup H, Aronow ME, Bebin EM et al (2021) Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations. Pediatr Neurol 123:50–66
de Vries PJ, Whittemore VH, Leclezio L et al (2015) Tuberous sclerosis associated neuropsychiatric disorders (TAND) and the TAND Checklist. Pediatr Neurol 52(1):25–35
Curatolo P, Moavero R, de Vries PJ (2015) Neurological and neuropsychiatric aspects of tuberous sclerosis complex. Lancet Neurol 14(7):733–745
de Vries PJ, Wilde L, de Vries MC, Moavero R, Pearson DA, Curatolo P (2018) A clinical update on tuberous sclerosis complex-associated neuropsychiatric disorders (TAND). Am J Med Genet C Semin Med Genet 178(3):309–320
Article PubMed PubMed Central Google Scholar
Nabbout R, Belousova E, Benedik MP et al (2019) Epilepsy in tuberous sclerosis complex: Findings from the TOSCA Study. Epilepsia Open 4(1):73–84
Curatolo P, Nabbout R, Lagae L et al (2018) Management of epilepsy associated with tuberous sclerosis complex: Updated clinical recommendations. Eur J Paediatr Neurol 22(5):738–748
Zhang H, Cicchetti G, Onda H et al (2003) Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR. J Clin Invest 112(8):1223–1233
Article CAS PubMed PubMed Central Google Scholar
Marcotte L, Crino PB (2006) The neurobiology of the tuberous sclerosis complex. Neuromolecular Med 8(4):531–546
Article CAS PubMed Google Scholar
Saxton RA, Sabatini DM (2017) mTOR Signaling in Growth, Metabolism, and Disease. Cell 169(2):361–371
Article CAS PubMed Google Scholar
Tee AR, Fingar DC, Manning BD, Kwiatkowski DJ, Cantley LC, Blenis J (2002) Tuberous sclerosis complex‑1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci U S A 99(21):13571–13576
Article CAS PubMed PubMed Central Google Scholar
Marsan E, Baulac S (2018) Review: Mechanistic target of rapamycin (mTOR) pathway, focal cortical dysplasia and epilepsy. Neuropathology and Applied Neurobiology 44(1):6–17
Article CAS PubMed Google Scholar
Wienecke R, Fackler I, Linsenmaier U, Mayer K, Licht T, Kretzler M (2006) Antitumoral activity of rapamycin in renal angiomyolipoma associated with tuberous sclerosis complex. Am J Kidney Dis 48(3):e27–e29
Franz DN, Leonard J, Tudor C et al (2006) Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol 59(3):490–498
Article CAS PubMed Google Scholar
Sugimoto R, Nakao A, Yamane M et al (2008) Sirolimus amelioration of clinical symptoms of recurrent lymphangioleiomyomatosis after living-donor lobar lung transplantation. J Heart Lung Transplant 27(8):921–924
Bissler JJ, McCormack FX, Young LR et al (2008) Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. New England Journal of Medicine 358(2):140–151
Article CAS PubMed PubMed Central Google Scholar
Krueger DA, Care MM, Holland K et al (2010) Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med 363(19):1801–1811
Article CAS PubMed Google Scholar
Franz DN, Agricola K, Mays M et al (2015) Everolimus for subependymal giant cell astrocytoma: 5‑year final analysis. Ann Neurol 78(6):929–938
Article CAS PubMed PubMed Central Google Scholar
Becker LL, Agricola K, Ritter DM, Care MM, Krueger DA, Franz DN (2025) Long-Term Efficacy and Safety of Mammalian Target of Rapamycin Inhibitor Treatment for Subependymal Giant Cell Astrocytoma in Tuberous Sclerosis. Pediatr Neurol 168:90–95
Cavalheiro S, da Costa MDS, Richtmann R (2021) Everolimus as a possible prenatal treatment of in utero diagnosed subependymal lesions in tuberous sclerosis complex: a case report. Childs Nerv Syst 37(12):3897–3899
Arroyo MS, Krueger DA, Broomall E, Stevenson CB, Franz DN (2017) Acute Management of Symptomatic Subependymal Giant Cell Astrocytoma With Everolimus. Pediatr Neurol 72:81–85
Franz DN, Belousova E, Sparagana S et al (2013) Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 381(9861):125–132
Article CAS PubMed Google Scholar
Franz DN, Belousova E, Sparagana S et al (2016) Long-Term Use of Everolimus in Patients with Tuberous Sclerosis Complex: Final Results from the EXIST‑1 Study. PLoS One 11(6):e0158476
Article PubMed PubMed Central Google Scholar
Bissler JJ, Kingswood JC, Radzikowska E et al (2013) Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 381(9869):817–824
Article CAS PubMed Google Scholar
Bissler JJ, Kingswood JC, Radzikowska E et al (2017) Everolimus long-term use in patients with tuberous sclerosis complex: Four-year update of the EXIST‑2 study. PLoS One 12(8):e0180939
Article PubMed PubMed Central Google Scholar
McCormack FX, Inoue Y, Moss J et al (2011) Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med 364(17):1595–1606
Article CAS PubMed PubMed Central Google Scholar
Nathan N, Wang JA, Li S et al (2015) Improvement of tuberous sclerosis complex (TSC) skin tumors during long-term treatment with oral sirolimus. J Am Acad Dermatol 73(5):802–808
Article CAS PubMed PubMed Central Google Scholar
Franz DN, Budde K, Kingswood JC et al (2018) Effect of everolimus on skin lesions in patients treated for subependymal giant cell astrocytoma and renal angiomyolipoma: final 4‑year results from the randomized EXIST‑1 and EXIST‑2 studies. J Eur Acad Dermatol Venereol 32(10):1796–1803
Article CAS PubMed Google Scholar
Wataya-Kaneda M, Ohno Y, Fujita Y et al (2018) Sirolimus Gel Treatment vs Placebo for Facial Angiofibromas in Patients With Tuberous Sclerosis Complex: A Randomized Clinical Trial. JAMA Dermatol 154(7):781–788
Article PubMed PubMed Central Google Scholar
Koenig MK, Bell CS, Hebert AA et al (2018) Efficacy and Safety of Topical Rapamycin in Patients With Facial Angiofibromas Secondary to Tuberous Sclerosis Complex: The TREATMENT Randomized Clinical Trial. JAMA Dermatol 154(7):773–780
Article PubMed PubMed Central Google Scholar
Ritter DM, Schneider K, Ezeakudo N, et al. Maternal Sirolimus Treatment Reverses Cardiac Rhabdomyoma-Induced Hydrops Fetalis in a Twin Gestation With Tuberous Sclerosis Complex. Am J Med Genet A 2025: e64175.
Ebrahimi-Fakhari D, Stires G, Hahn E, Krueger D, Franz DN (2021) Prenatal Sirolimus Treatment for Rhabdomyomas in Tuberous Sclerosis. Pediatr Neurol 125:26–31
French JA, Lawson JA, Yapici Z 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(10056):2153–2163
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