What is the management approach for tuberous sclerosis?

Management of Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) requires coordinated multidisciplinary care delivered by a specialized team in an expert center, with regular surveillance and targeted interventions to address organ-specific manifestations and prevent complications that affect mortality and quality of life.

Multidisciplinary Approach

The management of TSC requires a coordinated team approach due to its multi-organ involvement:

• Core team members should include:

  • Nephrologist (crucial for kidney manifestations)
  • Neurologist (for seizures and brain lesions)
  • Pulmonologist (especially for females)
  • Dermatologist
  • Cardiologist
  • Geneticist

• Structured follow-up visits should be coordinated on the same day when possible 1

Surveillance Recommendations

Regular monitoring is essential to detect complications early:

Brain:

• MRI every 1-3 years if asymptomatic, until 25 years of age 2
• More frequent monitoring if symptomatic

Kidneys:

• Blood pressure and kidney function (GFR) measurement annually 2
• Abdominal ultrasound at diagnosis and every 1-3 years until age 12 2
• Renal MRI at diagnosis and every 1-3 years starting at age 12 2
• Complete clinical assessment including history, imaging, kidney function, proteinuria, and blood pressure at diagnosis 1

Lungs:

• Chest CT at age 18 for females and symptomatic males 2

Heart:

• Echocardiogram at diagnosis, especially if <3 years old, and repeated if positive until regression 2

Kidney Management

Kidney disease is the most common cause of death in adults with TSC 2:

• For angiomyolipomas:

  • First-line treatment: mTOR inhibitors (everolimus) at 10mg orally once daily for angiomyolipomas not requiring immediate surgery 3
  • Continue treatment for at least 12 months before assessing response 1
  • Monitor for adherence and confirm diagnosis if no response after 12 months 1

• For acute bleeding:

  • Radiological intervention (arterial embolization) is first-line for angiomyolipoma bleeding requiring intervention 1
  • Steroid prophylaxis is recommended when embolization is performed to prevent post-embolization syndrome 1
  • Nephrectomy should be avoided unless absolutely necessary 1

• For surgical intervention:

  • Nephron-sparing approaches are strongly recommended when surgery is needed 1
  • Tumor enucleation is preferred over resection with margins in cases without suspected malignancy 1

Brain Management

• For subependymal giant cell astrocytoma (SEGA):

  • Everolimus is indicated for SEGAs requiring intervention but cannot be curatively resected 3
  • Starting dose: 4.5 mg/m² orally once daily 3
  • Monitor blood trough concentrations to maintain 5-15 ng/mL 3

• For seizures:

  • Antiepileptic medications
  • Consider mTOR inhibitors, ketogenic diet, or epilepsy surgery for drug-resistant epilepsy 4

Special Considerations

• Kidney transplantation:

  • Nephrectomy should not typically be performed in TSC patients undergoing kidney transplantation 1
  • Consider nephrectomy only if:
    • Large ipsilateral kidney prevents transplantation
    • Suspicion of malignancy
    • High bleeding risk from angiomyolipoma
    • Symptomatic angiomyolipoma unresponsive to mTOR inhibition 1

• mTOR inhibitor management:

  • Stop or pause treatment during active severe infection or severe adverse effects 1
  • Monitor for adverse effects including non-infectious pneumonitis, stomatitis, and metabolic events 3
  • Adjust dosing for patients with hepatic impairment or those taking drugs that affect P-gp and CYP3A4 3

Common Pitfalls to Avoid

• Inadequate surveillance leading to delayed diagnosis and treatment of complications 2
• Inappropriate surgical interventions that can worsen the risk of chronic kidney disease 2
• Failure to recognize the changing manifestations of TSC with age, requiring different monitoring strategies 5
• Lack of transition planning from pediatric to adult care, which should be a key responsibility of the multidisciplinary team 1

By following these evidence-based recommendations and maintaining vigilant surveillance, the morbidity and mortality associated with TSC can be significantly reduced while improving quality of life for affected individuals.