Table 4.

Surveillance and management recommendations for patients already diagnosed with definite or possible TSC (16, 21).

Organ system or specialty area	Recommendation
Genetics	• Offer genetic testing for family counseling or when TSC diagnosis is in question but cannot be clinically confirmed.
Brain	• Obtain brain MRI 1–3 yearly in asymptomatic TSC patients aged under 25 years to monitor for new occurrence of SEGA. • Patients with asymptomatic large/growing SEGA, with or without ventricular enlargement should undergo MRI scans more frequently and the patients and their families should be educated regarding the potential of new symptoms. Patients with asymptomatic SEGA in childhood should continue to be imaged periodically as adults to ensure there is no growth. • For acutely symptomatic SEGA, neurosurgical resection, with or without cerebral spinal fluid diversion (shunt) is advocated. • For asymptomatic but growing SEGA, either surgical resection or medical treatment with mTOR inhibitors may be used. In determining the best treatment option, discussion should include the risks of complication and adverse outcomes, cost, length of treatment, and potential impact on TSC-associated comorbidities. • At least annual screening for TAND features at each clinical visit, using the TAND checklist (26). Comprehensive formal evaluation for TAND at key developmental time points: infancy (0–3 years), preschool (3–6 years), primary school (6–9 years), adolescence (12–16 years), early adulthood (18–25 years), and as needed thereafter. Management strategies should be based on the TAND profile of each patient and should be based on evidence-based good practice guidelines/practice parameters for individual disorders (e.g., autism spectrum disorder, attention deficit hyperactivity disorder, anxiety disorder). Always consider the need for an individual educational program (IEP). Sudden change in behavior should prompt medical/clinical evaluation to look at potential medical causes (e.g., SEGA, seizures, renal disease). • Routine electroencephalograph (EEG) should be performed in individuals with known or suspected seizure activity. The frequency of routine EEG should be determined by clinical need rather than a specific defined interval. Prolonged video EEG, 24 h or longer, is appropriate when seizure occurrence is unclear or when unexplained sleep, behavioral changes, or other alteration in cognitive or neurological function is present. • Vigabatrin is the recommended first-line therapy for infantile spasms. ACTH can be used if treatment with vigabatrin is unsuccessful. Anticonvulsant therapy of other seizure types in TSC should generally follow that of other epilepsies. • Epilepsy surgery should be considered for medically refractory TSC patients, but special consideration should be given to children at younger ages experiencing neurological regression and is best if performed at epilepsy centers with experience and expertise in TSC.
Kidney	• Obtain MRI of the abdomen to assess for the progression of angiomyolipoma and renal cystic disease every 1–3 years throughout the lifetime of the patient. • Assess renal function (including determination of glomerular filtration rate) and blood pressure at least annually. • First-line therapy for renal AMLs presenting with acute hemorrhage is embolization followed by corticosteroids, with nephrectomy to be avoided if possible. • First-line therapy for asymptomatic, growing AMLs measuring larger than 3 cm in diameter is treatment with an mTOR inhibitor. Selective embolization or kidney-sparing resection are acceptable second-line therapy for asymptomatic AMLs.
Lung	• Perform clinical screening for lymphangioleiomyomatosis (LAM) symptoms, including exertional dyspnoea and shortness of breath, at each clinic visit. Counseling regarding smoking risk and estrogen use should be reviewed at each clinic visit for individuals at risk of LAM. • Obtain HRCT every 5–10 years in asymptomatic individuals at risk of LAM if there is no evidence of lung cysts on their baseline HRCT. Individuals with lung cysts detected on HRCT should have annual pulmonary function testing (pulmonary function testing and 6-min walk) and HRCT interval reduced to every 2–3 years. • mTOR inhibitors may be used to treat LAM patients with moderate to severe lung disease or rapid progression. TSC patients with LAM are candidates for lung transplantation but TSC comorbidities may impact transplant suitability.
Skin	• Perform a detailed clinical dermatologic inspection/exam annually. • Rapidly changing, disfiguring, or symptomatic TSC-associated skin lesions should be treated as appropriate for the lesion and clinical context, using approaches such as surgical excision, laser(s), or possibly topical mTOR inhibitor. • Facial angiofibromas (And some other skin lesions) respond to systemic or topical mTOR inhibitor; which can prevent more severe disease later if started early (27, 28).
Teeth	• Perform a detailed clinical dental inspection/exam at minimum every 6 months and panoramic radiographs by age 7, if not performed previously. • Symptomatic or deforming dental lesions, oral fibromas, and bony jaw lesions should be treated with surgical excision or curettage when present.
Heart	• Obtain an echocardiogram every 1–3 years in asymptomatic pediatric patients until regression of cardiac rhabdomyomas is documented. More frequent or advanced diagnostic assessment may be required for symptomatic patients. • Obtain electrocardiogram (ECG) every 3–5 years in asymptomatic patients of all ages to monitor for conduction defects. More frequent or advanced diagnostic assessment such as ambulatory and event monitoring may be required for symptomatic patients.
Eye	• Annual ophthalmologic evaluation in patients with previously identified ophthalmologic lesions or vision symptoms at the baseline evaluation. • NB this frequency may not be necessary for most patients and the recommendation may be changed in the forthcoming 2019 revision of the International TSC Clinical Guidelines. • More frequent assessment, including those treated with vigabatrin, is of limited benefit and not recommended unless new clinical concerns arise.