Pediatric Drugs

, Volume 10, Issue 5, pp 299–313

Current Management of Tuberous Sclerosis Complex

Therapy In Practice

Abstract

Tuberous sclerosis complex (TSC) is an important cause of epilepsy, autism, and renal and pulmonary disease in children and adults. The clinical course of TSC and the prognosis and appropriate therapy for TSC patients are often different than that for individuals with epilepsy, renal tumors, or interstitial lung disease from other causes. This article reviews the current therapeutic recommendations for medical and surgical management of neurologic, renal, and pulmonary manifestations of TSC. In addition, recent clinical trials using inhibitors of the mammalian target of rapamycin (mTOR) have demonstrated regression of astrocytomas, angiofibromas, and angiomyoliomas, as well as improved pulmonary function in persons with TSC.

References

  1. 1.
    Curatolo P, editor. Tuberous sclerosis complex: from basic science to clinic phenotypes. London: Mac Keith Press, 2003Google Scholar
  2. 2.
    Crino P, Nathanson K, Henske E. The tuberous sclerosis complex. N Engl J Med 2006; 355(13): 1345–56PubMedCrossRefGoogle Scholar
  3. 3.
    Yates J. Tuberous sclerosis. Eur J Hum Genet 2006; 14(10): 1065–73PubMedCrossRefGoogle Scholar
  4. 4.
    European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 1993; 75(7): 1305–15CrossRefGoogle Scholar
  5. 5.
    van Slegtenhorst M, deHoogt R, Hermans C, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 1997; 277(5327): 805–8PubMedCrossRefGoogle Scholar
  6. 6.
    Zhang Y, Gao X, Saucedo L, et al. Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nature Cell Biol 2003; 5(6): 578–81PubMedCrossRefGoogle Scholar
  7. 7.
    Ma L, Teruya-Feldstein J, Bonner P, et al. Identification of S664 TSC2 phosphorylation as a marker for Erk-mediated mTOR activation in tuberous sclerosis and human cancer. Cancer Res 2007; 67(15): 7106–12PubMedCrossRefGoogle Scholar
  8. 8.
    Ravikumar B, Vacher C, Berger Z, et al. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet 2004; 36(6): 585–95PubMedCrossRefGoogle Scholar
  9. 9.
    Paccalin M, Pain-Barc S, Pluchon C, et al. Activated mTOR and PKR kinases in lymphocytes correlate with memory and cognitive decline in Alzheimer’s disease. Dement Geriatr Cogn Disord 2006; 22(4): 320–6PubMedCrossRefGoogle Scholar
  10. 10.
    Xu L, Alafuzoff I, Soininen H, et al. Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer’s disease brain. FEBS J 2005; 272(16): 4211–20CrossRefGoogle Scholar
  11. 11.
    Cao Y, Espinola J, Fossale E, et al. Autophagy is disrupted in a knock-in mouse model of juvenile neuronal ceroid lipofuscinosis. J Biol Chem 2006; 281(29): 20483–93PubMedCrossRefGoogle Scholar
  12. 12.
    Gong R, Park CS, Abbassi NR, et al. Roles of glutamate receptors and the mammalian target of rapamycin (mTOR) signaling pathway in activity-dependent dendritic protein synthesis in hippocampal neurons. J Biol Chem 2006 Jul; 281(27): 18802–15PubMedCrossRefGoogle Scholar
  13. 13.
    Raab-Graham KF, Haddick PCG, Jan YN, et al. Activity- and mTOR-dependent suppression of Kv1.1 channel mRNA translation in dendrites. Science 2006 Oct 6; 314(5796): 144–8PubMedCrossRefGoogle Scholar
  14. 14.
    Tavazoie SF, Alvarez VA, Ridenour DA, et al. Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2. Nat Neurosci 2005 Dec; 8(12): 1727–34PubMedCrossRefGoogle Scholar
  15. 15.
    Inoki K, Guan K. Complexity of the TOR signaling network. Trends Cell Biol 2006; 16(4): 206–12PubMedCrossRefGoogle Scholar
  16. 16.
    Sehgal S, Baker H, Vézina C. Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation and characterization. J Antibiot 1975; 28(10): 727–32PubMedCrossRefGoogle Scholar
  17. 17.
    Augustine J, Bodziak K, Hricik D. Use of sirolimus in solid organ transplantation. Drugs 2007; 67(3): 369–91PubMedCrossRefGoogle Scholar
  18. 18.
    Morice M, Serruys P, Sousa J, et al. A randomized comparison of a sirolimuseluting stent with a standard stent for coronary revascularization. N Engl J Med 2002; 346(23): 1773–80PubMedCrossRefGoogle Scholar
  19. 19.
    Easton J, Houghton P. mTOR and cancer therapy. Oncogene 2006; 25(48): 6436–46PubMedCrossRefGoogle Scholar
  20. 20.
    Bolton P, Park R, Higgins J, et al. Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex. Brain 2002; 125(6): 1247–55PubMedCrossRefGoogle Scholar
  21. 21.
    Jozwiak S, Goodman M, Lamm S. Poor mental development in patients with tuberous sclerosis complex: clinical risk factors. Arch Neurol 1998; 55(3): 379–84PubMedCrossRefGoogle Scholar
  22. 22.
    Joinson C, O’Callaghan F, Osborne J, et al. Learning disability and epilepsy in an epidemiological sample of individuals with tuberous sclerosis complex. Psychol Med 2003; 33(2): 335–44PubMedCrossRefGoogle Scholar
  23. 23.
    Goh S, Kwiatkowski D, Dorer D, et al. Infantile spasms and intellectual outcomes in children with tuberous sclerosis complex. Neurology 2005; 65(2): 235–8PubMedCrossRefGoogle Scholar
  24. 24.
    Jambaqué I, Chiron C, Dumas C, et al. Mental and behavioural outcome of infantile epilepsy treated by vigabatrin in tuberous sclerosis patients. Epilepsy Res 2000; 38(2–3): 151–60PubMedCrossRefGoogle Scholar
  25. 25.
    Curatolo P, Verdecchia M, Bombardieri R. Tuberous sclerosis complex: a review of neurological aspects. Eur J Paediatr Neurol 2002; 6(1): 15–23PubMedCrossRefGoogle Scholar
  26. 26.
    Thiele E. Managing epilepsy in tuberous sclerosis complex. J Child Neurol 2004; 19(9): 680–6PubMedGoogle Scholar
  27. 27.
    Hancock E, Osborne J. Vigabatrin in the treatment of infantile spasms in tuberous sclerosis: literature review. J Child Neurol 1999; 14(2): 71–4PubMedCrossRefGoogle Scholar
  28. 28.
    Lawden M, Eke T, Degg C, et al. Visual field defects associated with vigabatrin therapy. J Neurol Neurosurg Psychiatry 1999; 67(6): 716–22PubMedCrossRefGoogle Scholar
  29. 29.
    Manuchehri K, Goodman S, Siviter L, et al. A controlled study of vigabatrin and visual abnormalities. Br J Ophthalmol 2000; 84(5): 499–505PubMedCrossRefGoogle Scholar
  30. 30.
    Gross-Tsur V, Banin E, Shahar E, et al. Visual impairment in children with epilepsy treated with vigabatrin. Annal Neurol 2000; 48(1): 60–4PubMedCrossRefGoogle Scholar
  31. 31.
    Vanhatalo S, Nousiainen I, Eriksson K, et al. Visual field constriction in 91 Finnish children treated with vigabatrin. Epilepsia 2002; 42(7): 748–56CrossRefGoogle Scholar
  32. 32.
    Hyman M, Whittemore V. National Institutes of Health consensus conference: tuberous sclerosis complex. Arch Neurol 2000; 57(5): 662–5PubMedCrossRefGoogle Scholar
  33. 33.
    Mackay M, Weiss S, Adams-Webber T, et al. Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society. Neurology 2004; 62(10): 1668–81PubMedCrossRefGoogle Scholar
  34. 34.
    Parisi P, Bombardieri R, Curatolo P. Current role of vigabatrin in infantile spasms. Eur J Paediatr Neurol 2007; 11(6): 331–6PubMedCrossRefGoogle Scholar
  35. 35.
    Rowley S, O’Callaghan F, Osborne J. Ophthalmic manifestations of tuberous sclerosis: a population based study. Br J Ophthalmol 2001; 85(4): 420–3PubMedCrossRefGoogle Scholar
  36. 36.
    Verrotti A, Manco R, Matricardi S, et al. Antiepileptic drugs and visual function. J Pediatr Neurol 2007; 36(6): 353–60CrossRefGoogle Scholar
  37. 37.
    Bundic J, Westall C, Panton C, et al. Characteristic retinal atrophy with secondary “inverse” optic atrophy identifies vigabatrin toxicity in children. Ophthalmology 2004; 111(10): 1935–42CrossRefGoogle Scholar
  38. 38.
    Clarke A, Hancock E, Kingswood C, et al. End-stage renal failure in adults with the tuberous sclerosis complex. Nephrol Dial Transplant 1999; 14(4): 988–91PubMedCrossRefGoogle Scholar
  39. 39.
    Overby PJ, Kossoff EH. Treatment of infantile spasms. Curr Treat Options Neurol 2006; 8(6): 457–64PubMedCrossRefGoogle Scholar
  40. 40.
    Chiron C, Dumas C, Jambaqué I, et al. Randomized trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis. Epilepsy Res 1997; 26(2): 389–95PubMedCrossRefGoogle Scholar
  41. 41.
    Mikati M, Lepejian G, Holmes G. Medical treatment of patients with infantile spasms. Clin Neuropharmacol 2002; 25(2): 61–70PubMedCrossRefGoogle Scholar
  42. 42.
    Hishitani T, Hoshino K, Ogawa K, et al. Rapid enlargement of cardiac rhabdomyoma during corticotropin therapy for infantile spasms. Can J Cardiol 1997; 13(1): 72–4PubMedGoogle Scholar
  43. 43.
    Buoni S, Zannolli R, Strambi M, et al. Combined treatment with vigabatrin and topiramate in West syndrome. J Child Neurol 2004; 19(5): 385–6PubMedCrossRefGoogle Scholar
  44. 44.
    Deray M, Resnick T, Luis A. Complete pocket reference for the treatment of epilepsy. 2nd ed. Miami (FL): CPR Educational Services, 2004Google Scholar
  45. 45.
    Franz D, Tudor C, Leonard J. Topiramate as therapy for tuberous sclerosis complex-associated seizures [abstract]. Epilepsia 2000; 41Suppl. 7: 87Google Scholar
  46. 46.
    Lamb E, Stevens P, Nashef L. Topiramate increases biochemical risk of nephrolithiasis. Ann Clin Biochem 2004; 41(2): 166–9PubMedCrossRefGoogle Scholar
  47. 47.
    Glauser TA. Behavioral and psychiatric adverse events associated with antiepileptic drugs commonly used in pediatric patients. J Child Neurol 2004; 19Suppl. 1: S25–38PubMedGoogle Scholar
  48. 48.
    Franz D, Tudor C, Leonard J, et al. Lamotrigine therapy of epilepsy in tuberous sclerosis. Epilepsia 2001; 42(7): 935–40PubMedCrossRefGoogle Scholar
  49. 49.
    Collins J, Tudor C, Leonard J, et al. Levetiracetam as adjunctive antiepileptic therapy for patients with tuberous sclerosis complex: a retrospective open-label trial. J Child Neurol 2006; 21(1): 53–7PubMedCrossRefGoogle Scholar
  50. 50.
    Lenz G, Avruch J. Glutamatergic regulation of the p70S6 kinase in primary mouse neurons. J Biol Chem 2005 Nov; 280(46): 38121–4PubMedCrossRefGoogle Scholar
  51. 51.
    Wang Y, Barbaro M, Baraban S. A role for the mTOR pathway in surface expression of AMPA receptors. Neurosci Lett 2006; 401(2006): 35–9PubMedCrossRefGoogle Scholar
  52. 52.
    Pellock J, Faught E, Leppik I, et al. Felbamate: consensus of current clinical experience. Epilepsy Res 2006; 71(2–3): 89–101PubMedCrossRefGoogle Scholar
  53. 53.
    Takayanagi M, Yamamoto K, Nakagawa H, et al. Two successful cases of bromide therapy for refractory symptomatic localization-related epilepsy. Brain Dev 2002; 24(3): 194–6PubMedCrossRefGoogle Scholar
  54. 54.
    Winterkorn E, Pulsifer M, Thiele E. Cognitive prognosis of patients with tuberous sclerosis complex. Neurology 2007; 68(1): 62–4PubMedCrossRefGoogle Scholar
  55. 55.
    Dulac O, Tuxhorn I. Infantile spasms and West syndrome. In: Roger J, Bureau M, Dravet C, et al., editors. Epileptic syndromes in infancy, childhood and adolescence. 4th ed. London: John Libby Eurotext, 2005: 53–73Google Scholar
  56. 56.
    Talwar D, Arora M, Sher P. EEG changes and seizure exacerbation in young children treated with carbamazepine. Epilepsia 1994; 35(6): 1154–9PubMedCrossRefGoogle Scholar
  57. 57.
    Jaworski J, Sheng M. The growing role of mTOR in neuronal development and plasticity. Mol Neurobiol 2006; 34(3): 205–19PubMedCrossRefGoogle Scholar
  58. 58.
    von der Brelie C, Waltereit R, Zhang L, et al. Impaired synaptic plasticity in a rat model of tuberous sclerosis. Eur J Neurosci 2006; 23(3): 686–92PubMedCrossRefGoogle Scholar
  59. 59.
    Kwon C, Luikart B, Powell C, et al. Pten regulates neuronal arborization and social interaction in mice. Neuron 2006 May; 50: 377–88PubMedCrossRefGoogle Scholar
  60. 60.
    Zeng LH, Gutmann D, Wong M. Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex. Ann Neurol 2008; 63(4): 444–53PubMedCrossRefGoogle Scholar
  61. 61.
    Meikle L, Pollizi K, Egnor A, et al. Response of a nueronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitor: effects on mTORC1 and Akt signalling lead to improved survival and function. J Neuroscience 2008; 28(21): 5422–32CrossRefGoogle Scholar
  62. 62.
    Ehninger D, Han S, Shilyansky C, et al. Reversal of learning deficits in a Tsc2(+/−) mouse model of tuberous sclerosis. Nat Med. Epub 2008 Jun 22Google Scholar
  63. 63.
    Forgacs B, Merhav H, Lappin J, et al. Successful conversion to rapamycin for calcineurin inhibitor-related neurotoxicity following liver transplantation. Transplant Proc 2005; 37(4): 1912–4PubMedCrossRefGoogle Scholar
  64. 64.
    Sindhi R, Seward J, Mazariegos G, et al. Replacing calcineurin inhibitors with mTOR inhibitors in children. Pediatr Transplant 2005; 9(3): 391–7PubMedCrossRefGoogle Scholar
  65. 65.
    Stafstrom CE, Bough KJ.The ketogenic diet for the treatment of epilepsy: a challenge for nutritional neuroscientists. Nutr Neurosci 2003; 6(2): 67–79PubMedCrossRefGoogle Scholar
  66. 66.
    Cota D, Proulx K, Smith KA, et al. Hypothalamic mTOR signaling regulates food intake. Science 2006 May; 312(5775): 927–30PubMedCrossRefGoogle Scholar
  67. 67.
    Kossoff E, Thiele E, Pfeifer H, et al. Tuberous sclerosis complex and the ketogenic diet. Epilepsia 2005; 46(10): 1684–6PubMedCrossRefGoogle Scholar
  68. 68.
    Coppola G, Klepper J, Ammendola E, et al. The effects of the ketogenic diet in refractory partial seizures with reference to tuberous sclerosis. Eur J Paediatr Neurol 2006; 10(3): 148–51PubMedCrossRefGoogle Scholar
  69. 69.
    Martinez C, Pyzik P, Kossoff E. Discontinuing the ketogenic diet in seizure-free children: recurrence and risk factors. Epilepsia 2007; 48(1): 187–90PubMedCrossRefGoogle Scholar
  70. 70.
    Kossoff E, McGrogan J, Bluml R, et al. A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy. Epilepsia 2006; 47(2): 421–4PubMedCrossRefGoogle Scholar
  71. 71.
    Pfeifer H, Thiele E. Low-glycemic-index treatment: a liberalized ketogenic diet for treatment of intractable epilepsy. Neurology 2005; 65(11): 1810–2PubMedCrossRefGoogle Scholar
  72. 72.
    Parain D, Penniello M, Berquen P, et al. Vagal nerve stimulation in tuberous sclerosis complex patients. Pediatr Neurol 2001; 25(3): 213–6PubMedCrossRefGoogle Scholar
  73. 73.
    Jansen F, van Huffelen A, Algra A, et al. Epilepsy surgery in tuberous sclerosis: a systematic review. Epilepsia 2007; 48(8): 1466–84CrossRefGoogle Scholar
  74. 74.
    Chandra P, Salamon N, Huang J, et al. FDG-PET/MRI coregistration and diffusion-tensor imaging distinguish epileptogenic tubers and cortex in patients with tuberous sclerosis complex: a preliminary report. Epilepsia 2006; 47(9): 1543–9PubMedCrossRefGoogle Scholar
  75. 75.
    Kagawa K, Chugani DC, Asano E, et al. Epilepsy surgery outcome in children with tuberous sclerosis complex evaluated with alpha-[11C] methyl-L-tryptophan positron emission tomography (PET). J Child Neurol 2005 May; 20(5): 429–38PubMedCrossRefGoogle Scholar
  76. 76.
    Madhavan D, Schaffer S, Yankovsky A, et al. Surgical outcome in tuberous sclerosis complex: a multicenter survey. Epilepsia 2007; 48(8): 1625–8PubMedCrossRefGoogle Scholar
  77. 77.
    Franz DN, Leonard J, Tudor C, et al. Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol 2006 Feb; 59: 490–8PubMedCrossRefGoogle Scholar
  78. 78.
    Weiner H, Carlson C, Ridgway E, et al. Epilepsy surgery in young children with tuberous sclerosis: results of a novel approach. Pediatrics 2006; 117(5): 1494–502PubMedCrossRefGoogle Scholar
  79. 79.
    Koh S, Jayakar P, Dunoyer C, et al. Epilepsy surgery in children with tuberous sclerosis complex: presurgical evaluation and outcome. Epilepsia 2000; 41(9): 1206–13PubMedCrossRefGoogle Scholar
  80. 80.
    Hunt A, Shepherd C. A prevalence study of autism in tuberous sclerosis. J Autism Dev Disord 1993 Jun; 23(2): 323–39PubMedCrossRefGoogle Scholar
  81. 81.
    Wiznitzer M, Autism and tuberous sclerosis, J Child Neurol 2004 Sep 19; (9): 675–9Google Scholar
  82. 82.
    Prather P, de Vries PJ. Behavioral and cognitive aspects of tuberous sclerosis complex. J Child Neurol 2004; 19(9): 666–74PubMedGoogle Scholar
  83. 83.
    Pulsifer M, Winterkorn E, Thiele E. Psychological profile of adults with tuberous sclerosis complex. Epilepsy Behav 2007; 10(3): 402–6PubMedCrossRefGoogle Scholar
  84. 84.
    Connor DF, Meltzer BM. Pediatric psychopharmacology: fast facts. New York: WW Norton and Company, 2006Google Scholar
  85. 85.
    Muzykewicz DA, Newberry P, Danforth N, et al. Psychiatric comorbid conditions in a clinic population of 241 patients with tuberous sclerosis complex. Epilepsy Behav 2007; 11(4): 506–13PubMedCrossRefGoogle Scholar
  86. 86.
    Dhillon S, Scott L, Plosker G. Escitalopram: a review of its use in the management of anxiety disorders. CNS Drugs 2006; 20(9): 763–90PubMedCrossRefGoogle Scholar
  87. 87.
    Hunt A. Development, behaviour and seizures in 300 cases of tuberous sclerosis. J Intellect Disabil Res 1993; 37(1): 41–51PubMedCrossRefGoogle Scholar
  88. 88.
    Hunt A, Stores G. Sleep disorder and epilepsy in children with tuberous sclerosis: a questionnaire-based study. Dev Med Child Neurol 1994; 36(2): 108–15PubMedCrossRefGoogle Scholar
  89. 89.
    O’Callaghan F, Clarke A, Hancock E, et al. Use of melatonin to treat sleep disorders in tuberous sclerosis. Dev Med Child Neurol 1999; 41(2): 123–6PubMedCrossRefGoogle Scholar
  90. 90.
    Hancock E, O’Callaghan F, Osborne J. Effect of melatonin dosage on sleep disorder in tuberous sclerosis complex. J Child Neurol 2005; 20(1): 78–80PubMedCrossRefGoogle Scholar
  91. 91.
    O’Callaghan FJ, Clarke AC, Jaffe H, et al. Tuberous sclerosis complex and Wolff-Parkinson-White syndrome. Arch Dis Child 1998; 78(2): 159–62PubMedCrossRefGoogle Scholar
  92. 92.
    Cuccia V, Zuccaro G, Sosa F, et al. Subependymal giant cell astrocytoma in children with tuberous sclerosis. Childs Nerv Syst 2003; 19(4): 232–43PubMedGoogle Scholar
  93. 93.
    Goh S, Butler W, Thiele E. Subependymal giant cell tumors in tuberous sclerosis complex. Neurology 2004; 63(8): 1457–61PubMedCrossRefGoogle Scholar
  94. 94.
    Russel D, Rubinstein L. Pathology of tumors in the central nervous system. 4th ed. Baltimore (MD): Williams & Wilkins, 1977: 47–8, 165-6Google Scholar
  95. 95.
    Braffman B, Bilaniuk L, Naidich T, et al. MR imaging of tuberous sclerosis: pathogenesis of this phakomatosis, use of gadopentetate dimeglumine, and literature review. Radiology 1992; 183(1): 227–38PubMedGoogle Scholar
  96. 96.
    Torres O, Roach E, Delgado M, et al. Early diagnosis of subependymal giant cell astrocytoma in patients with tuberous sclerosis. J Child Neurol 1998; 13(4): 173–7PubMedCrossRefGoogle Scholar
  97. 97.
    Yamamoto K, Yamada K, Nakahara T, et al. Rapid regrowth of solitary subependymal giant cell astrocytoma: case report. Neurol Med Chir 2002; 42(5): 224–7CrossRefGoogle Scholar
  98. 98.
    Levine N, Collins J, Franz D, et al. Gradual formation of an operative corridor by balloon dilation for resection of subependymal giant cell astrocytomas in children with tuberous sclerosis: specialized minimal access technique of balloon dilation. Minim Invasive Neurosurg 2006; 49(5): 317–20PubMedCrossRefGoogle Scholar
  99. 99.
    Bissler J, McCormack F, Young L, et al. Efficacy and safety of sirolimus for angiomyolipomata in patients with tuberous sclerosis complex and lymphangioleiomyomatosis. N Engl J Med 2008; 358: 140–51PubMedCrossRefGoogle Scholar
  100. 100.
    Vignot S, Faivre S, Aguirre D, et al. mTOR-targeted therapy of cancer with rapamycin derivatives. Ann Oncol 2005; 16(5): 525–37PubMedCrossRefGoogle Scholar
  101. 101.
    Ewalt D, Sheffield E, Sparagana S, et al. Renal lesion growth in children with tuberous sclerosis complex. J Urol 1998; 160(1): 141–5PubMedCrossRefGoogle Scholar
  102. 102.
    Bissler J, Kingswood J. Renal angiomyolipomata. Kidney International 2004; 66(3): 924–34PubMedCrossRefGoogle Scholar
  103. 103.
    Casper K, Donnelly L, Chen B, et al. Tuberous sclerosis complex: renal imaging findings. Radiology 2002; 225(2): 451–6PubMedCrossRefGoogle Scholar
  104. 104.
    Yamakado K, Tanaka N, Nakagawa T, et al. Renal angiomyolipoma: relationships between tumor size, aneurysm formation, and rupture. J Urol 2002; 225(1): 78–82Google Scholar
  105. 105.
    Chesa Ponce N, Artiles Hernández J, Ponce Socorro J, et al. Wunderlich’s syndrome as the first manifestation of a renal angiomyolipoma. Arch Esp Urol 1995; 48(3): 305–8PubMedGoogle Scholar
  106. 106.
    Schillinger F, Montagnac R. Chronic renal failure and its treatment in tuberous sclerosis. Nephrol Dial Transplant 1996; 11(3): 481–5PubMedCrossRefGoogle Scholar
  107. 107.
    Minervini A, Giubilei G, Masieri L, et al. Simple enucleation for the treatment of renal angiomyolipoma. BJU Int 2007; 99(4): 887–91PubMedCrossRefGoogle Scholar
  108. 108.
    Nelson C, Sanda M. Contemporary diagnosis and management of renal angiomyolipoma. J Urol 2002; 168(4): 1315–25PubMedCrossRefGoogle Scholar
  109. 109.
    Williams J, Racadio J, Johnson N, et al. Embolization of renal angiomyolipomata in patients with tuberous sclerosis complex. Am J Kidney Dis 2006; 47(1): 95–102PubMedCrossRefGoogle Scholar
  110. 110.
    Bissler J, Racadio J, Donnelly L, et al. Reduction of postembolization syndrome after ablation of renal angiomyolipoma. Am J Kidney Dis 2002; 39(5): 966–71PubMedCrossRefGoogle Scholar
  111. 111.
    Herry I, Neukirch C, Debray M, et al. Dramatic effect of sirolimus on renal angiomyolipomas in a patient with tuberous sclerosis complex. Eur J Intern Med 2007; 18(1): 76–7PubMedCrossRefGoogle Scholar
  112. 112.
    Wienecke R, Fackler I, Linsenmaier U, et al. Antitumoral activity of rapamycin in renal angiomyolipoma associated with tuberous sclerosis complex. Am J Kidney Dis 2006; 48(3): e27–9PubMedCrossRefGoogle Scholar
  113. 113.
    Chapman AB. Autosomal dominant polycystic kidney disease: time for a change? J Am Soc Nephrol 2007 May; 18(5): 1399–407PubMedCrossRefGoogle Scholar
  114. 114.
    Johnson S. Lymphangioleiomyomatosis. Eur Respir J 2006; 27(5): 1056–65PubMedGoogle Scholar
  115. 115.
    Moss J, Avila N, Barnes P, et al. Prevalence and clinical characteristics of lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex. Am J Respir Crit Care Med 2001; 164(4): 669–71PubMedGoogle Scholar
  116. 116.
    McCormack F. Lymphangioleiomyomatosis. MedGenMed 2006; 8(1): 15PubMedGoogle Scholar
  117. 117.
    Franz D, Brody A, Meyer C, et al. Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis. Am J Respir Crit Care Med 2001; 164(4): 661–8PubMedGoogle Scholar
  118. 118.
    Shen A, Iseman M, Waldron J, et al. Exacerbation of pulmonary lymphangioleiomyomatosis by exogenous estrogens. Chest 1987; 91(5): 782–5PubMedCrossRefGoogle Scholar
  119. 119.
    Oberstein EM, Fleming LE, Gomez-Marin O, et al. Pulmonary lymphangioleiomyomatosis (LAM): examining oral contraceptive pills and the onset of disease. J Womens Health 2003 Jan–Feb; 12(1): 81–5CrossRefGoogle Scholar
  120. 120.
    Denoo X, Hermans G, Degives R, et al. Successful treatment of pulmonary lymphangioleiomyomatosis with progestins: a case report. Chest 1999 Jan; 115(1): 276–9PubMedCrossRefGoogle Scholar
  121. 121.
    Eliasson AH, Phillips YY, Tenholder MF. Treatment of lymphangioleiomyomatosis: a meta-analysis. Chest 1989 Dec; 96(6): 1352–5PubMedCrossRefGoogle Scholar
  122. 122.
    Moses MA, Harper J, Folkman J. Doxycycline treatment for lymphangioleiomyomatosis with urinary monitoring for MMPs. N Engl J Med 2006 Jun 15; 354(24): 2621–2PubMedCrossRefGoogle Scholar
  123. 123.
    Taillé C, Debray M, Crestani B. Sirolimus treatment for pulmonary lymphangioleiomyomatosis. Ann Intern Med 2007; 146(9): 687–8PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.Tuberous Sclerosis ClinicUniversity of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical CenterCincinnatiUSA
  2. 2.Department of NeurologyUniversity of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical CenterCincinnatiUSA

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