Genetics of Tuberous Sclerosis Medication

Updated: Sep 02, 2021
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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Medication Summary

Medical care is aimed at seizure control using various anticonvulsants. Future prospects are exciting. For example, everolimus appears to be of value in treating the subependymal giant-cell astrocytomas (SEGAs), with a documented reduction in tumor volume, decreased hydrocephalus and intracranial pressure, and a decrease in seizure frequency; this may be a better option than neurosurgery. [50, 49, 51, 55] It also appears to have a favorable effect on renal angiomyolipoma in these patients. [60] Use of mammalian target of rapamycin inhibitors as effective treatment of various aspects of tuberous sclerosis complex has been stressed. [61] However, adverse events may occur, the commonest with everolimus being infections; although such infections are rarely serious, one patient developed grade IV pleuropneumonia and Streptococcus pneumoniae sepsis, while a second patient died after developing Escherichia coli sepsis. [62]


Antineoplastic, Mtor Kinase Inhibitor

Class Summary

Immunosuppressant, which forms an inhibitory complex with the immunophilin FKBP12, which binds to and inhibits the ability of mTOR to phosphorylate downstream substrates, such as the S6Ks and 4EBPs.

Everolimus (Afinitor)

Rapamycin-derivative kinase inhibitor. Reduces cell proliferation and angiogenesis by inhibition of mTOR pathway. Indicated for subependymal giant cell astrocytoma (SEGA) associated with TS that cannot be treated with surgery. Topical application of mTOR inhibitors are of value for facial angiofibromas.


Anticonvulsant Agents

Class Summary

These agents are used to prevent seizures and to terminate clinical and electrical seizure activity. Effective management requires a detailed and accurate classification of seizure types. The goal of treatment is monotherapy, although multidrug therapy is sometimes needed in patients with refractory seizures.

Carbamazepine (Tegretol)

Useful in the treatment of partial and generalized tonic-clonic seizures. Administer a low dose initially, with gradual increases as needed for clinical effect. Therapeutic serum concentration is 4-12 mcg/mL.

Valproic acid (Depakene, Depakote)

Useful in the treatment of all seizure types. Although mechanism of action is not established, activity may be related to increased brain levels of GABA or enhanced GABA action. Valproate may potentiate postsynaptic GABA responses, affect potassium channel, or have a direct membrane-stabilizing effect. Therapeutic serum concentration is 50-100 mcg/mL.

Lamotrigine (Lamictal)

Useful in the treatment of partial seizures or secondarily generalized seizures. Dose depends on use as monotherapy or as an add-on agent. Dose must be increased slowly.