eMedicine Specialties > Neurology > Pediatric Neurology

Tuberous Sclerosis: Follow-up

Author: David Neal Franz, MD, Professor, Departments of Pediatrics and Neurology, University of Cincinnati College of Medicine; Director, Tuberous Sclerosis Clinic, Cincinnati Children's Hospital Medical Center
Coauthor(s): Tracy A Glauser, MD, Professor, Departments of Pediatrics and Neurology, University of Cincinnati College of Medicine, Children's Comprehensive Epilepsy Program, Children's Hospital Medical Center of Cincinnati
Contributor Information and Disclosures

Updated: Feb 14, 2007

Follow-up

Further Inpatient Care

  • Patients with TSC may experience frequent exacerbations of their seizures that may require inpatient adjustment of AEDs.
  • Patients with TSC may have retroperitoneal hemorrhage and/or hematuria from larger (>4-6 cm) AMLs. These sometimes can be catastrophic and require emergent supportive care. Once the patient's condition is stabilized, embolization rather than resection is the preferred method of treatment for AMLs that have bled. Patients with end-stage renal disease may require inpatient treatment for dialysis or management of hypertension or electrolyte disturbance.
  • Patients with LAM may require acute inpatient treatment for pneumothorax, chylothorax, or dyspnea. Lung transplantation may be undertaken for end-stage pulmonary disease.

Complications

  • Death - Usually either sudden unexplained death in epilepsy or related to an accident involving a seizure
  • Injuries, especially facial - From seizures resulting in falls
  • Dose-related, idiosyncratic, or long-term adverse effects of AEDs
  • Renal, cardiac, or metabolic complications from the ketogenic diet
  • Inappropriate surgery or therapies - Clinicians unfamiliar with TSC frequently make recommendations that are unwarranted given the unique nature of the hamartomas associated with the disorder. For example, nephrectomies (even bilateral) may be undertaken to rule out the extremely low possibility of a renal cell carcinoma rather than performing serial MRI and follow-up. Patients may not receive embolization to prevent potentially fatal hemorrhage from arterial aneurysms associated with large AMLs. Invariably benign hamartomas of the liver, spleen, or other viscera are needlessly biopsied or resected on the fear that they may reflect malignancies. Children with TSC and infantile spasms are treated with agents other than vigabatrin owing to misplaced anxiety on the part of their neurologists.

Prognosis

  • The prognosis of patients with TSC is not as grim as has been typically thought. Higher numbers of tubers, earlier onset and intractability of seizures, and infantile spasms are associated with (but do not guarantee) worse cognitive and behavioral outcomes (see Images 19-20). Cardiac lesions almost always spontaneously regress, although supportive care may be necessary for a time. Pulmonary and renal lesions affect prognosis on the basis of their extent and severity.

Miscellaneous

Medicolegal Pitfalls

  • Failure to inform the patient's family of the risk for severe idiosyncratic reactions from 3 commonly used antiepileptic medications for seizure in patients with TSC
    • Vigabatrin - Visual field constriction
    • Valproate - Hepatotoxicity, pancreatitis
    • Lamotrigine - Stevens-Johnson syndrome, toxic epidermal necrolysis
  • Failure to inform the patient's family of the risk for severe adverse effects, including death, from the use of either ACTH or oral steroids
  • Failure to identify and provide treatment for seizures, renal AMLs, or LAM. This could result in patients presenting later and with greater morbidity from these conditions.
  • Failure to instruct the family on what to do if they notice signs and symptoms indicating severe adverse effects or idiosyncratic reactions
  • Failure to recognize signs and symptoms of TSC, which could result in failure to select an appropriate AED with proven efficacy. This could increase the risk for uncontrolled seizures that in turn increase the risk for injury and death. It also could result in inappropriate management or surgery, or failure to screen for known complications of the condition.
  • Failure to communicate the genetic basis of TSC to the patient and family, and to provide the option of genetic counseling. This could result in additional pregnancies that are affected with TSC, which the parents might not otherwise have undertaken.
 


More on Tuberous Sclerosis

Overview: Tuberous Sclerosis
Differential Diagnoses & Workup: Tuberous Sclerosis
Treatment & Medication: Tuberous Sclerosis
Follow-up: Tuberous Sclerosis
Multimedia: Tuberous Sclerosis
References
[ CLOSE WINDOW ]

References

  1. Asano E, Chugani DC, Muzik O, et al. Autism in tuberous sclerosis complex is related to both cortical and subcortical dysfunction. Neurology. Oct 9 2001;57(7):1269-77. [Medline].

  2. Asano E, Chugani DC, Muzik O, et al. Multimodality imaging for improved detection of epileptogenic foci in tuberous sclerosis complex. Neurology. May 23 2000;54(10):1976-84. [Medline].

  3. Avellino AM, Berger MS, Rostomily RC, et al. Surgical management and seizure outcome in patients with tuberous sclerosis. J Neurosurg. Sep 1997;87(3):391-6. [Medline].

  4. Beltramello A, Puppini G, Bricolo A, et al. Does the tuberous sclerosis complex include intracranial aneurysms? A case report with a review of the literature. Pediatr Radiol. Mar 1999;29(3):206-11. [Medline].

  5. Boehler A, Speich R, Russi EW, Weder W. Lung transplantation for lymphangioleiomyomatosis. N Engl J Med. Oct 24 1996;335(17):1275-80. [Medline].

  6. Bolton PF, Griffiths PD. Association of tuberous sclerosis of temporal lobes with autism and atypical autism. Lancet. Feb 8 1997;349(9049):392-5. [Medline].

  7. Bowen J, Beasley SW. Rare pulmonary manifestations of tuberous sclerosis in children. Pediatr Pulmonol. Feb 1997;23(2):114-6. [Medline].

  8. Bruni O, Cortesi F, Giannotti F, Curatolo P. Sleep disorders in tuberous sclerosis: a polysomnographic study. Brain Dev. Jan-Feb 1995;17(1):52-6. [Medline].

  9. Christophe C, Sekhara T, Rypens F, et al. MRI spectrum of cortical malformations in tuberous sclerosis complex. Brain Dev. Dec 2000;22(8):487-93. [Medline].

  10. Chugani DC, Chugani HT, Muzik O, et al. Imaging epileptogenic tubers in children with tuberous sclerosis complex using alpha-[11C]methyl-L-tryptophan positron emission tomography. Ann Neurol. Dec 1998;44(6):858-66. [Medline].

  11. Crino, PB, Nathanson, KL, Henske, EP. The tuberous sclerosis complex. New England Journal of Medicine. Sep 28 2006;355(13):1345-56. [Medline].

  12. Dabora SL, Jozwiak S, Franz DN, et al. Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am J Hum Genet. Jan 2001;68(1):64-80. [Medline].

  13. El-Hashemite N, Zhang H, Walker V, et al. Perturbed IFN-gamma-Jak-signal transducers and activators of transcription signaling in tuberous sclerosis mouse models: synergistic effects of rapamycin-IFN-gamma treatment. Cancer Res. May 15 2004;64(10):3436-43. [Medline].

  14. Enbergs A, Borggrefe M, Kurlemann G, et al. Ventricular tachycardia caused by cardiac rhabdomyoma in a young adult with tuberous sclerosis. Am Heart J. Dec 1996;132(6):1263-5. [Medline].

  15. Flanagan N, O''Connor WJ, McCartan B, et al. Developmental enamel defects in tuberous sclerosis: a clinical genetic marker?. J Med Genet. Aug 1997;34(8):637-9. [Medline].

  16. Franz DN. Diagnosis and management of tuberous sclerosis complex. Semin Pediatr Neurol. Dec 1998;5(4):253-68. [Medline].

  17. Franz DN, 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. Aug 15 2001;164(4):661-8. [Medline].

  18. Franz DN, Tudor C, Leonard J, et al. Lamotrigine therapy of epilepsy in tuberous sclerosis. Epilepsia. Jul 2001;42(7):935-40. [Medline].

  19. Franz, DN, Leonard, J, Tudor, C. Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Annals of Neurology. March 2006;59(3):490-498. [Medline].

  20. Gates J, Jordan JE. Tuberous sclerosis in old age. South Med J. Aug 1978;71(8):974-6. [Medline].

  21. Glauser TA. Topiramate. Epilepsia. 1999;40 Suppl 5:S71-80. [Medline].

  22. Goodman M, Lamm SH, Engel A, et al. Cortical tuber count: a biomarker indicating neurologic severity of tuberous sclerosis complex. J Child Neurol. Feb 1997;12(2):85-90. [Medline].

  23. Hancock E, Osborne JP. Vigabatrin in the treatment of infantile spasms in tuberous sclerosis: literature review. J Child Neurol. Feb 1999;14(2):71-4. [Medline].

  24. Harding B, Copp AJ. Malformations: tuberous sclerosis. In: Greenfield's Neuropathology. 6th ed. Arnold Edward;1997:497-502.

  25. Harrison JE, Bolton PF. Annotation: tuberous sclerosis. J Child Psychol Psychiatry. Sep 1997;38(6):603-14. [Medline].

  26. Henske EP, Wessner LL, Golden J, et al. Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors. Am J Pathol. Dec 1997;151(6):1639-47. [Medline].

  27. Holley DG, Martin GR, Brenner JI, et al. Diagnosis and management of fetal cardiac tumors: a multicenter experience and review of published reports. J Am Coll Cardiol. Aug 1995;26(2):516-20. [Medline].

  28. Hyman MH, Whittemore VH. National Institutes of Health consensus conference: tuberous sclerosis complex. Arch Neurol. May 2000;57(5):662-5. [Medline].

  29. Inoki K, Ouyang H, Li Y, Guan KL. Signaling by target of rapamycin proteins in cell growth control. Microbiol Mol Biol Rev. Mar 2005;69(1):79-100. [Medline].

  30. Jost CJ, Gloviczki P, Edwards WD, et al. Aortic aneurysms in children and young adults with tuberous sclerosis: report of two cases and review of the literature. J Vasc Surg. Mar 2001;33(3):639-42. [Medline].

  31. Jozwiak S, Pedich M, Rajszys P, Michalowicz R. Incidence of hepatic hamartomas in tuberous sclerosis. Arch Dis Child. Nov 1992;67(11):1363-5. [Medline].

  32. Kandt RS, Haines JL, Smith M, et al. Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease. Nat Genet. Sep 1992;2(1):37-41. [Medline].

  33. Kenerson H, Dundon TA, Yeung RS. Effects of rapamycin in the Eker rat model of tuberous sclerosis complex. Pediatr Res. Jan 2005;57(1):67-75. [Medline].

  34. Koprowski C, Rorke LB. Spinal cord lesions in tuberous sclerosis. Pediatr Pathol. Oct-Dec 1983;1(4):474-80. [Medline].

  35. Langkau N, Martin N, Brandt R. TSC1 and TSC2 mutations in tuberous sclerosis, the associated phenotypes and a model to explain observed TSC1/ TSC2 frequency ratios. Eur J Pediatr. Jul 2002;161(7):393-402. [Medline].

  36. Louis DN, Scheithauer BW, Budka H. Meningiomas. In: Pathology and Genetics of Tumours of the Nervous System. London: Oxford University Press;2000:176-84.

  37. Maeda M, Tartaro A, Matsuda T, Ishii Y. Cortical and subcortical tubers in tuberous sclerosis and FLAIR sequence. J Comput Assist Tomogr. Jul-Aug 1995;19(4):660-1. [Medline].

  38. Mak BC, Yeung RS. The tuberous sclerosis complex genes in tumor development. Cancer Invest. 2004;22(4):588-603. [Medline].

  39. Miller SP, Tasch T, Sylvain M, et al. Tuberous sclerosis complex and neonatal seizures. J Child Neurol. Dec 1998;13(12):619-23. [Medline].

  40. Nobukini T, Thomas G. The mTOR/S6K signalling pathway: the role of the TSC1/2 tumour suppressor complex and the proto-oncogene Rheb. Novartis Found Symp. 2004;262:148-54; discussion 154-9, 265-8. [Medline].

  41. Pui MH, Kong HL, Choo HF. Bone changes in tuberous sclerosis mimicking metastases. Australas Radiol. Feb 1996;40(1):77-9. [Medline].

  42. Roach ES, DiMario FJ, Kandt RS, Northrup H. Tuberous Sclerosis Consensus Conference: recommendations for diagnostic evaluation. National Tuberous Sclerosis Association. J Child Neurol. Jun 1999;14(6):401-7. [Medline].

  43. Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol. Dec 1998;13(12):624-8. [Medline].

  44. Sampson JR, Attwood D, al Mughery AS, Reid JS. Pitted enamel hypoplasia in tuberous sclerosis. Clin Genet. Jul 1992;42(1):50-2. [Medline].

  45. Sener N. Tuberous sclerosis: diffusion MRI findings in the brain. Eur Radiol. Jan 2002;12(1):138-43. [Medline].

  46. Seri S, Cerquiglini A, Pisani F, et al. Frontal lobe epilepsy associated with tuberous sclerosis: electroencephalographic-magnetic resonance image fusioning. J Child Neurol. Jan 1998;13(1):33-8. [Medline].

  47. Shepherd CW, Houser OW, Gomez MR. MR findings in tuberous sclerosis complex and correlation with seizure development and mental impairment. AJNR Am J Neuroradiol. Jan 1995;16(1):149-55. [Medline].

  48. Takanashi J, Sugita K, Fujii K, Niimi H. MR evaluation of tuberous sclerosis: increased sensitivity with fluid- attenuated inversion recovery and relation to severity of seizures and mental retardation. AJNR Am J Neuroradiol. Oct 1995;16(9):1923-8. [Medline].

  49. Van Slegtenhorst M, Nellist M, Nagelkerken B. Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet. 7(6):1053-7. [Medline].

  50. Webb DW, Fryer AE, Osborne JP. Morbidity associated with tuberous sclerosis: a population study. Dev Med Child Neurol. Feb 1996;38(2):146-55. [Medline].

  51. Webb DW, Thomas RD, Osborne JP. Cardiac rhabdomyomas and their association with tuberous sclerosis. Arch Dis Child. Mar 1993;68(3):367-70. [Medline].

  52. Weber AM, Egelhoff JC, McKellop JM, Franz DN. Autism and the cerebellum: evidence from tuberous sclerosis. J Autism Dev Disord. Dec 2000;30(6):511-7. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

tuberous sclerosis complex, Bourneville disease. Bourneville's disease, epiloia, Vogt triad, Vogt's triad, angiomyolipoma, lymphangiomyomatosis, polycystic kidney disease, renal cell carcinoma, intractable epilepsy, medically refractory epilepsy, mental retardation, adenoma sebaceum, hamartoma, subependymal nodule, subependymal giant cell astrocytoma, SEGA

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

David Neal Franz, MD, Professor, Departments of Pediatrics and Neurology, University of Cincinnati College of Medicine; Director, Tuberous Sclerosis Clinic, Cincinnati Children's Hospital Medical Center
David Neal Franz, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Medical Association, Child Neurology Society, Children's Oncology Group, and Ohio State Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Tracy A Glauser, MD, Professor, Departments of Pediatrics and Neurology, University of Cincinnati College of Medicine, Children's Comprehensive Epilepsy Program, Children's Hospital Medical Center of Cincinnati
Tracy A Glauser, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

Medical Editor

Robert Baumann, MD, Program Director, Professor, Departments of Neurology and Pediatrics, University of Kentucky
Robert Baumann, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American College of Epidemiology, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.