Skip to main content

Advertisement

SpringerLink
Log in

Management of CNS-related Disease Manifestations in Patients With Tuberous Sclerosis Complex

  • PEDIATRIC NEUROLOGY (HS SINGER, SECTION EDITOR)
  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Opinion statement

Historically, before the advent of modern imaging and genetic testing, Tuberous Sclerosis Complex (TSC) was more of a diagnostic challenge and less of a treatment challenge. This is because the natural history of TSC was poorly understood and TSC-specific treatments were non-existent. In the current era, diagnosis is more straightforward but management is much more complex. Disease manifestations vary by age, severity, and organ system. Management issues in the first few months of life, including neurologic manifestations, are very different than late childhood, adolescence, and adulthood. With increasing numbers of TSC diagnoses being made prenatally or shortly after birth, the opportunity for interventions that may improve long-term developmental and epilepsy outcomes now may precede the onset of neurological clinical symptoms. Familiarity and anticipation of these neurologic complications and rapid response to their emergence is crucial. Periodic imaging surveillance for development of subependymal giant cell astrocytoma (SEGA), preferably by magnetic resonance imaging (MRI) every 1–3 years, is now standard of care. Early SEGA detection provides opportunity to initiate pharmacologic treatment with everolimus if appropriate, thereby negating the need for invasive surgery. Routine electroencephalography (EEG) in asymptomatic infants for the first year or two of life is becoming increasingly accepted, with treatment initiation of vigabatrin dependent on concerning EEG findings instead of waiting until onset of clinical seizures, the traditional approach. Effective SEGA treatment and optimal seizure control remain principal during the first few decades of life for the clinical neurologist involved in the management of TSC. However, during the same period and extending through adulthood, assessment of TSC-associated neuropsychiatric disorder (TAND) is also key to the best clinical outcome and quality of life for affected individuals and their surrounding family and caregivers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Bourneville D-M. Encéphalite ou sclérose tubéreuse des circonvolutions cérébrales. Encéphalite ou sclérose tubéreuse des circonvolutions cérébrales [Encephalitis or tuberous sclerosis of the cerebral convolutions]. Archives de Neurologie, Paris. 1881;1:390–412.

    Google Scholar 

  2. Von Recklinghausen F. Ein Herz von einem Nuegeborene welches mehrere theils nachaussen, theils nachden Höhlein prominirende Tumoren (Myomen) trug. Ein Herz von einem Nuegeborene welches mehrere theils nachaussen, theils nachden Höhlein prominirende Tumoren (Myomen) trug [A heart of a newborn with partial external and internal prominent tumors (fibroids)]. Monatschr Gebursheklkd. 1862;20:1–2.

    Google Scholar 

  3. O'Callaghan F, Shiell A, Osborne J, Martyn C. Prevalence of tuberous sclerosis estimated by capture-recapture analysis. Lancet. 1998;352:318–9.

    Article  Google Scholar 

  4. European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell. 1993;75:1305–15.

    Article  Google Scholar 

  5. van Slegtenhorst M, deHoogt R, Hermans C, Henske E, Short M, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science. 1997;277:805–8.

    Article  PubMed  Google Scholar 

  6. Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J. Rheb binds and regulates the mTOR kinase. Curr Biol. 2005;15:702–13.

    Article  PubMed  CAS  Google Scholar 

  7. Franz D, Belousova E, Sparagana S, Bebin E, Frost M, et al. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associate702-71d with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2012;381:125–32. This article provides definitive evidence of the benefit of everolimus for the treatment of SEGA in a randomized, double-blinded placebo-controlled design. All of the patients in the treatment group demonstrated some degree of benefit, whereas tumor progression was only observed in the placebo group. Class I evidence.

    Article  PubMed  Google Scholar 

  8. Franz DN, Leonard J, Tudor C, Chuck G, Care M, et al. Rapamycin Causes Regression of Astrocytomas in Tuberous Sclerosis Complex. Ann Neurol. 2006;59:490–8.

    Article  PubMed  CAS  Google Scholar 

  9. Krueger D, Care M, Agricola K, Tudor C, Mays M, et al. Everolimus long-term safety and efficacy in subependymal giant-cell astrocytoma. Neurology. 2012;80:574–80. This article provides most up to date evidence of long-term safety and efficacy of everolimus for medical management of SEGA. Treatment continues to be well-tolerated and prevents tumor progression median treatment duration of 34.2 months. Class III evidence.

    Article  Google Scholar 

  10. Krueger DA, Care MM, Holland K, Agricola K, Tudor C, et al. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. 2010;363:1801–11.

    Article  PubMed  CAS  Google Scholar 

  11. Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, et al. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2013;[Epub ahead of print].

  12. Bissler JJ, McCormack FX, Young LR, Elwing JM, Chuck G, et al. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med. 2008;358:140–51.

    Article  PubMed  CAS  Google Scholar 

  13. Dabora SL, Franz DN, Ashwal S, Sagalowsky A, DiMario Jr FJ, et al. Multicenter phase 2 trial of sirolimus for tuberous sclerosis: Kidney angiomyolipomas and other tumors regress and VEGF- D levels decrease. PLoS ONE. 2011;6.

  14. Davies DM, De Vries PJ, Johnson SR, McCartney DL, Cox JA, et al. Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: a phase 2 trial. Clin Cancer Res. 2011;17:4071–81.

    Article  PubMed  CAS  Google Scholar 

  15. McCormack F, Inoue Y, Moss J, Singer L, Strange C, et al. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011;364:1595–606.

    Article  PubMed  CAS  Google Scholar 

  16. Foster R, Bint L, Halbert A. Topical 0.1% rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: a pilot study of four patients. Australas J Dermatol. 2012;53:52–6.

    Article  PubMed  Google Scholar 

  17. Haemel A, O'Brian A, Teng J. Topical rapamycin: a novel approach to facial angiofibromas in tuberous sclerosis. Arch Dermatol. 2010;146:715–8.

    Article  PubMed  Google Scholar 

  18. Koenig M, Hebert A, Roberson J, Samueals J, Slopis J, et al. Topical rapamycin therapy to alleviate the cutaneous manifestations of tuberous sclerosis complex: a double-blind, randomized, controlled trial to evaluate the safety and efficacy of topical applied rapamycin. Drugs R&D. 2012;12:121–6.

    Article  CAS  Google Scholar 

  19. Mutizwa M, Berk D, Anadkat M. Treatment of facial angiofibromas with topical application of oral rapamycin solution (1mgmL(−1) ) in two patients with tuberous sclerosis. Br J Dermatol. 2011;165:922–3.

    Article  PubMed  CAS  Google Scholar 

  20. Demir H, Ekici F, Yazal Erdem A, Emir S, Tunç B. Everolimus: a challenging drug in the treatment of multifocal inoperable cardiac rhabdomyoma. Pediatrics. 2012;130:e243–7.

    Article  PubMed  Google Scholar 

  21. Tiberio D, Franz D, Phillips J. Regression of a cardiac rhabdomyoma in a patient receiving everolimus. Pediatrics. 2011;127:e1335–7.

    Article  PubMed  Google Scholar 

  22. Krueger D, Wilfong A, Holland-Bouley K, Anderson A, Agricola K, et al. Everolimus treatment of refractory epilepsy in tuberous sclerosis complex. Ann Neurol. 2013. doi:10.1002/ana.23960.

  23. Adams R, Victor M. Principles of neurology. New York: McGraw-Hill; 1985. p. 1186.

  24. Menkes J, Maria B. Neurocutaneous syndromes. In: Menkes J, Sarnat H, editors. Child Neurology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2000. p. 865–72.

    Google Scholar 

  25. Zhou J, Shrikhande G, Xu J, McKay R, Burns D, et al. Tsc1 mutant neural stem/progenitor cells exhibit migration deficits and give rise to subependymal lesions in the lateral ventricle. Genes Dev. 2011;25:1595–600.

    Article  PubMed  CAS  Google Scholar 

  26. Way S, McKenna III J, Mietzsch U, Reith R, Wu H, et al. Loss of Tsc2 in radial glia models the brain pathology of tuberous sclerosis complex in the mouse. Hum Mol Gen. 2009;18:1252–65.

    Article  PubMed  CAS  Google Scholar 

  27. Carlson B, Houser O, Gomez M. Brain imaging in the tuberous sclerosis complex. In: Gomez M, Sampson J, Whittemore V, editors. Tuberous sclerosis complex. 3rd ed. New York: Oxford University Press; 1999. p. 85–100.

    Google Scholar 

  28. Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol. 1998;13:624–8.

    Article  PubMed  CAS  Google Scholar 

  29. Inoue Y, Nemoto Y, Murata R, Tashiro T, Shakudo M, et al. CT and MR imaging of cerebral tuberous sclerosis. Brain Dev. 1998;20:209–21.

    Article  PubMed  CAS  Google Scholar 

  30. Kalantari BN, Salamon N. Neuroimaging of tuberous sclerosis: spectrum of pathologic findings and frontiers in imaging. Am J Roentgenol. 2008;190:W304–9.

    Article  Google Scholar 

  31. Crino P, Mehta R, Vinters H. Pathogenesis of TSC in the brain. In: Kwiatkowsi D, Whittemore V, Thiele E, editors. Tuberous sclerosis complex: genes, clinical features, and therapeutics. Weinheim: Wiley-Blackwell; 2010. p. 285–309.

    Google Scholar 

  32. Kim SK, Wang KC, Cho BK, Jung HW, Lee YJ, et al. Biological behavior and tumorigenesis of subependymal giant cell astrocytomas. J Neuro-Oncol. 2001;52:217–25.

    Article  CAS  Google Scholar 

  33. Adriaensen ME, Schaefer-Prokop CM, Stijnen T, Duyndam DA, Zonnenberg BA, et al. Prevalence of subependymal giant cell tumors in patients with tuberous sclerosis and a review of the literature. Eur J Neurol. 2009;16:691–6.

    Article  PubMed  CAS  Google Scholar 

  34. Phi JH, Park SH, Chae JH, Hong KH, Park SS, et al. Congenital subependymal giant cell astrocytoma: clinical considerations and expression of radial glial cell markers in giant cells. Child Nerv Syst. 2008;24:1499–503.

    Article  Google Scholar 

  35. Raju GP, Urion DK, Sahin M. Neonatal Subependymal Giant Cell Astrocytoma: new case and review of literature. Pediatr Neurol. 2007;36:128–31.

    Article  PubMed  Google Scholar 

  36. Shepherd CW, Scheithauer B, Gomez MR. Brain tumors in tuberous sclerosis. A clinicopathologic study of the Mayo Clinic experience. Ann N Y Acad Sci. 1991;615:378–9.

    Article  PubMed  CAS  Google Scholar 

  37. Buccoliero A, Franchi A, Castiglione F, Gheri C, Mussa F, et al. Subependymal giant cell astrocytoma (SEGA): is it an astrocytoma? Morphological, immunohistochemical and ultrastructural study. Neuropathology. 2009;29:25–30.

    Article  PubMed  Google Scholar 

  38. Cuccia V, Zuccaro G, Sosa F, Monges J, Lubienieky F, et al. Subependymal giant cell astrocytoma in children with tuberous sclerosis. Child Nerv Syst. 2003;19:232–43.

    Google Scholar 

  39. The International Tuberous Sclerosis Complex Consensus Group. “Recommendations for surveillance and management in tuberous sclerosis complex: 2012 update of the International Tuberous Sclerosis Complex Consensus Conference.” Presented at the 2013 International Research Conference on Tuberous Sclerosis Complex and Related Disorders, Washington, DC, June 20–23, 2014.

  40. Thiele EA. Managing epilepsy in tuberous sclerosis complex. J Child Neurol. 2004;19:680–6.

    PubMed  Google Scholar 

  41. Jóźwiak S, Kotulska K, Domańska-Pakieła D, Łojszczyk B, Syczewska M, et al. Antiepileptic treatment before the onset of seizures reduces epilepsy severity and risk of mental retardation in infants with tuberous sclerosis complex. Eur J Paediat Neurol. 2011;15:424–31. This paradigm shifting article introduces a prospective, preventative approach towards seizure control rather than the traditional reactionary approach of waiting until after the onset of clinical seizures in infants with TSC. As a result, those infants treated prospectively demonstrated improved long-term seizure control and developmental progress. Class III evidence.

    Article  Google Scholar 

  42. Curatolo P, Verdecchia M, Bombardieri R. Tuberous sclerosis complex: a review of neurological aspects. Eur J Paediat Neurol. 2002;6:15–23.

    Article  Google Scholar 

  43. de Vries P. Neurodevelopmental, Psychiatric and Cognitive Aspects of Tuberous Sclerosis Complex. In: Kwiatkowsi DJ, Whittemore VH, Thiele EA, editors. Tuberous Sclerosis Complex. Weinheim: Wiley-Blackwell; 2010. p. 229–68.

    Chapter  Google Scholar 

  44. Leclezio L, de Vries P. The Tuberous Sclerosis Complex Associated Neuropsychiatrif Disorders (TAND) Checklist- Pilot validation of a new screening tool for neurophsyciatric manifestations of TSC. Washington, DC.2013.

  45. De Vries P, Humphrey A, McCartney D, Prather P, Bolton P, et al. Consensus clinical guidelines for the assessment of cognitive and behavioral problems in Tuberous Sclerosis. Eur Child Adolesc Psychiatr. 2005;14:183–90.

    Article  Google Scholar 

  46. Stafstrom CE, Bough KJ. The Ketogenic Diet for the Treatment of Epilepsy: a challenge for nutritional neuroscientists. Nutr Neurosci. 2003;6:67–79.

    Article  PubMed  CAS  Google Scholar 

  47. Kossoff E, Thiele E, Pfeifer H, McGrogan J, Freeman J. Tuberous sclerosis complex and the ketogenic diet. Epilepsia. 2005;46:1684–6.

    Article  PubMed  Google Scholar 

  48. Coppola G, Klepper J, Ammendola E, Fiorillo M, Corte R, et al. The effects of the ketogenic diet in refractory partial seizures with reference to tuberous sclerosis. Eur J Paediat Neurol. 2006;10:148–51.

    Article  Google Scholar 

  49. Larson AM, Pfeifer HH, Thiele EA. Low glycemic index treatment for epilepsy in tuberous sclerosis complex. Epilepsy Res. 2012;99(1–2):180–2

    Google Scholar 

  50. Agricola K, Tudor C, Krueger D, Franz D. Nursing implications for the lifelong management of tuberous sclerosis complex. J Neurosci Nurs. 2013(in press).

  51. Meikle L, Pollizzi K, Egnor A, Kramvis I, Lane H, et al. Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. J Neurosci. 2008;28:5422–32.

    Article  PubMed  CAS  Google Scholar 

  52. Meikle L, Talos D, Onda H, Pollizzi K, Rotenberg A, et al. A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival. J Neurosci. 2007;27:5546–58.

    Article  PubMed  CAS  Google Scholar 

  53. Muncy J, Butler IJ, Koenig M. Rapamycin reduces seizure frequency in tuberous sclerosis complex. J Child Neurol. 2009;24:477.

    Article  PubMed  Google Scholar 

  54. Zeng L, Rensing N, Wong M. The mammalian target of rapamycin signaling pathway mediates epileptogenesis in a model of temporal lobe epilepsy. J Neurosci. 2009;29:6964–72.

    Article  PubMed  CAS  Google Scholar 

  55. Zeng LH, Xu L, Gutmann DH, Wong M. Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex. Ann Neurol. 2008;63:444–53.

    Article  PubMed  CAS  Google Scholar 

  56. McDaniel S, Rensing N, Thio L, Yamada K, Wong M. The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway. Epilepsia. 2011;52:e7–11.

    Article  PubMed  CAS  Google Scholar 

  57. Ehninger D, Han S, Shilyansky C, Zhou Y, Li W, et al. Reversal of learning deficits in a Tsc2+/− mouse model of tuberous sclerosis. Nat Med. 2008;14:843–8.

    Article  PubMed  CAS  Google Scholar 

  58. Ehninger D, Silva AJ. Rapamycin for treating Tuberous sclerosis and Autism spectrum disorders. Trends Mol Med. 2011;17:78–87.

    Article  PubMed  CAS  Google Scholar 

  59. Go C, Mackay M, Weiss S, Stephens D, Addams-Webber T, et al. Evidence-based guideline update: medical treatment of infantile spasms. Neurology. 2012;78:1974–80.

    Article  PubMed  CAS  Google Scholar 

  60. Camposano SE, Major P, Halpern E, Thiele EA. Vigabatrin in the treatment of childhood epilepsy: a retrospective chart review of efficacy and safety profile. Epilepsia. 2008;49:1186–91.

    Article  PubMed  CAS  Google Scholar 

  61. Greiner H, Lynch E, Fordyce S, Agricola K, Tudor C, et al. Vigabatrin for childhood partial-onset epilepsies. Pediat Neurol. 2012;46:83–8.

    Article  PubMed  Google Scholar 

  62. Kinirons P, Cavalleri G, O'Rourke D, Doherty C, Reid I, et al. Vigabatrin retinopathy in an Irish cohort: lack of correlation with dose. Epilepsia. 2006;47:311–7.

    Article  PubMed  CAS  Google Scholar 

  63. Jammoul F, Wang Q, Nabbout R, Coriat C, Duboc A, et al. Taurine deficiency is a cause of vigabatrin-induced retinal phototoxicity. Ann Neurol. 2009;65:98–107.

    Article  PubMed  CAS  Google Scholar 

  64. Collins J, Tudor C, Leonard J, Chuck G, Franz D. Levetiracetam as adjunctive antiepileptic therapy for patients with tuberous sclerosis complex: a retrospective open-label trial. J Child Neurol. 2006;21:53–7.

    Article  PubMed  Google Scholar 

  65. Franz D, Leonard J, Tudor C, Chuck G, Egelhoff J. Levetiracetam therapy of epilepsy in tuberous sclerosis. J Child Neurol. 2001;16:679.

    Google Scholar 

  66. Franz D, Leonard J, Tudor C, Chuck G, Egelhoff J. Oxcarbazepine therapy of epilepsy in tuberous sclerosis. J Child Neurol. 2001;16:680.

    Google Scholar 

  67. Franz D, Tudor C, Leonard J. Topiramate as therapy for tuberous sclerosis complex-associated seizures. Epilepsia. 2000;41:87.

    Google Scholar 

  68. Franz D, Tudor C, Leonard J, Egelhoff J, Byars A, et al. Lamotrigine therapy of epilepsy in tuberous sclerosis. Epilepsia. 2001;42:935–40.

    Article  PubMed  CAS  Google Scholar 

  69. Franz DN, Tudor C, Leonard J, Egelhoff JC, Byars A, et al. Lamotrigine therapy of epilepsy in tuberous sclerosis. Epilepsia. 2001;42:935–40.

    Article  PubMed  CAS  Google Scholar 

  70. Chung T, Lynch E, Fiser C, Nelson D, Agricola K, et al. Psychiatric comorbidity and treatment response in patients with tuberous sclerosis complex. Ann Clin Psychiatr. 2011;23:263–9.

    Google Scholar 

  71. Krueger DA, Franz DN. Current management of tuberous sclerosis complex. Pediatr Drugs. 2008;10:299–313.

    Article  Google Scholar 

  72. Jozwiak J, Jozwiak S, Oldak M. Molecular activity of sirolimus and its possible application in tuberous sclerosis treatment. Med Res Rev. 2006;26:160–80.

    Article  PubMed  CAS  Google Scholar 

  73. Wheless J, Ramsay R, Collins S. Vigabatrin. Neurotherapeutics. 2007;4:163–72.

    Article  PubMed  CAS  Google Scholar 

  74. Berhouma M. Management of subependymal giant cell tumors in tuberous sclerosis complex: the neurosurgeon's perspective. World J Pediatr. 2010;6:103–10.

    Article  PubMed  Google Scholar 

  75. de Ribaupierre S, Dorfmüller G, Bulteau C, Fohlen M, Pinard J, et al. Subependymal giant-cell astrocytomas in pediatric tuberous sclerosis disease: when should we operate? Neurosurgery. 2007;60:83–9.

    Article  PubMed  Google Scholar 

  76. Moavero R, Pinci M, Bombardieri R, Curatolo P. The management of subependymal giant cell tumors in tuberous sclerosis: a clinician's perspective. Child Nervous Syst. 2011;27:1203–10.

    Article  Google Scholar 

  77. Sun P, Kohrman M, Liu J, Guo A, Rogerio J, et al. Outcomes of resecting subependymal giant cell astrocytoma (SEGA) among patients with SEGA-related tuberous sclerosis complex: a national claims database analysis. Curr Med Res Opin. 2012;28:657–63.

    Article  PubMed  Google Scholar 

  78. Franz D, Agricola KD, Tudor C, Krueger D. Everolimus for tumor recurrence after surgical resection for subependymal giant cell astrocytoma assocaited with tuberous sclerosis complex. J Child Neurol. 2012;28:602–7.

    Article  PubMed  Google Scholar 

  79. Connolly MB, Hendson G, Steinbok P. Tuberous sclerosis complex: a review of the management of epilepsy with emphasis on surgical aspects. Child Nerv Syst. 2006;22:896–908.

    Article  Google Scholar 

  80. Koh S, Jayakar P, Dunoyer C, Whiting SE, Resnick TJ, et al. Epilepsy surgery in children with tuberous sclerosis complex: presurgical evaluation and outcome. Epilepsia. 2000;41:1206–13.

    Article  PubMed  CAS  Google Scholar 

  81. Weiner HL, Ferraris N, LaJoie J, Miles D, Devinsky O. Epilepsy surgery for children with tuberous sclerosis complex. J Child Neurol. 2004;19:687–9.

    PubMed  Google Scholar 

  82. Elliott RE, Carlson C, Kalhorn SP, Moshel YA, Weiner HL, et al. Refractory epilepsy in tuberous sclerosis: vagus nerve stimulation with or without subsequent resective surgery. Epilepsy Behav. 2009;16:454–60.

    Article  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Darcy A. Krueger has received compensation for consulting work, participation on advisory boards, and various promotional activities for Novartis. He has also received compensation for participation on advisory boards for Lundbeck Pharmaceuticals. D. A. Krueger receives research grant support from the National Institutes of Health, Department of Defense, the Tuberous Sclerosis Alliance, Lundbeck Pharmaceuticals, and Novartis.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Departments of Pediatrics and Neurology, University of Cincinnati College of Medicine and Division of Child Neurology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue ML #2015, Cincinnati, OH, 45229, USA

    Darcy A. Krueger MD, PhD

Authors
  1. Darcy A. Krueger MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Darcy A. Krueger MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Krueger, D.A. Management of CNS-related Disease Manifestations in Patients With Tuberous Sclerosis Complex. Curr Treat Options Neurol 15, 618–633 (2013). https://doi.org/10.1007/s11940-013-0249-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11940-013-0249-2

Keywords

Search

Navigation