What is the comprehensive management plan for individuals with tuberous sclerosis (TSC)?

From the Guidelines

The comprehensive management of tuberous sclerosis (TSC) requires a multidisciplinary approach tailored to each patient's specific manifestations, with a focus on regular surveillance, including brain MRI every 1-3 years, abdominal MRI annually, chest CT in adults, echocardiogram in children, ophthalmologic exams, and neuropsychiatric evaluations, as recommended by the most recent consensus statement 1.

Key Components of TSC Management

• Regular surveillance to monitor disease progression and identify potential complications early
• Use of mTOR inhibitors like everolimus for brain lesions, renal angiomyolipomas, and other manifestations
• Antiepileptic drugs such as vigabatrin for infantile spasms
• Management of dermatologic manifestations with topical rapamycin or laser therapy
• Treatment of pulmonary lymphangioleiomyomatosis with everolimus and bronchodilators
• Monitoring of kidney function and assessment of kidney structural lesions by imaging to enable early interventions

Surveillance and Monitoring

• Perform kidney imaging at the time of TSC diagnosis 1
• Assess angiomyolipoma-related complications, including pain, clinical bleeding risk, blood pressure, and biochemical tests to monitor kidney function at least annually 1
• Perform annual blood and urine tests in all adults with TSC to monitor kidney function and urinary protein excretion 1

Treatment

• Use everolimus as first-line treatment for subependymal giant cell astrocytomas (SEGAs) and seizures, starting at 4.5 mg/m² daily, titrated based on blood levels 1
• Treat renal angiomyolipomas larger than 3 cm with everolimus (10 mg daily for adults) or embolization to prevent hemorrhage 1
• Manage dermatologic manifestations with topical rapamycin (1 mg/ml applied twice daily) or laser therapy 1
• Treat pulmonary lymphangioleiomyomatosis with everolimus (2.5-10 mg daily) and bronchodilators 1

Disease Modification and Symptomatic Management

• Target the underlying mTOR pathway dysregulation in TSC to address both symptomatic management and disease modification
• Improve quality of life and prevent complications through a comprehensive and multidisciplinary approach

Recommendations for mTORC1 Inhibition Therapy

• Continue mTORC1 inhibition therapy for as long as the patient tolerates it, with regular monitoring of kidney function and assessment of kidney structural lesions by imaging 1
• Start with a reasonable dose of everolimus, such as 5mg in adults and 2.5mg/m² in children, and adjust based on side effects and efficacy 1
• Obtain everolimus trough levels where safety concerns arise, adherence problems are suspected, or lack of efficacy is observed 1
• Do not exceed everolimus target trough levels of >15ng/ml 1

From the Research

Comprehensive Management Plan for Tuberous Sclerosis

The management of tuberous sclerosis complex (TSC) requires a multidisciplinary approach, considering the various organ systems affected by the disorder. Key aspects of the comprehensive management plan include:

• Surgical intervention: Surgical resection is the procedure of choice for subependymal giant cell tumors (SGCT) 2.
• mTOR inhibitors: Biologically targeted pharmacotherapy with mTOR inhibitors, such as sirolimus and everolimus, provides a safe and efficacious treatment option for patients with SGCT and renal angiomyolipomas 2, 3, 4.
• Neurological and neuropsychiatric management: Treatment of epilepsy, attention-deficit/hyperactivity disorder, autism spectrum disorder, and intellectual disability is crucial, as these conditions are common in individuals with TSC 3, 5.
• Monitoring and continuity of care: Ongoing monitoring and continuity of clinical care are essential, particularly during the transition from childhood to adult services 3.
• Management of side effects: Awareness and management of adverse events associated with mTOR inhibitors are necessary to minimize their impact on patients 6.

Organ-Specific Management

• Renal angiomyolipomas: mTOR inhibitors have shown promising efficacy in reducing the size of renal angiomyolipomas and preventing potentially life-threatening hemorrhage 4.
• Subependymal giant cell astrocytomas: mTOR inhibitors are recommended as a treatment option for subependymal giant cell astrocytomas, in addition to surgical resection 2, 3.
• Neuropsychiatric manifestations: An individualized, multifaceted approach is necessary to manage neuropsychiatric symptoms, including attention-deficit/hyperactivity disorder, autism spectrum disorder, and intellectual disability 5.