mTOR Inhibitor Therapy for Arteriovenous Malformations: Review and Angiographic Findings in Patient with PTEN Syndrome

Purpose: The purposes were to review the mechanism of action, indications, and off-label usage of mammalian target of rapamycin (mTOR) inhibitors in managing arteriovenous malformations (AVMs) and to recognize angiographic changes after therapy in the presented index case. Cellular metabolism and proliferation are mediated by intracellular signaling cascades involving protein kinase B (Akt) and mTOR. Murine models demonstrate that AVMs express high levels of these intracellular kinases, leading to abnormal proliferation. mTOR inhibitors directly disrupt cellular signaling cascades, which exerts an antiproliferative effect on cells with high Akt and mTOR expression. These drugs have shown efficacy and safety in treating patients with AVMs; this case demonstrates their efficacy as an adjunct to percutaneous and endovascular therapies.

Materials and Methods: This is a case presentation of a 37-year-old man with classic stigmata of Bannayan-Riley-Ruvalcaba syndrome, including extensive AVMs of the left upper extremity producing severe lymphedema, ulceration, and bleeding.

Results: Pretherapy angiographic evaluation of the left upper extremity noted extensive AVMs arising from the upper extremity arteries with engorged draining veins. The patient underwent multiple transcatheter and percutaneous therapy sessions, including alcohol and liquid embolic administration, which improved the angiographic appearance but did not halt the progression of edema, ulceration, and bleeding. As adjunct therapy, mTOR therapy with sirolimus was initiated and maintained at a serum level of 5 to 10 ng/mL for 3 months. Repeat angiography noted a marked reduction in lymphedema, as well as pruning of the AVMs.

Conclusions: The treatment of patients with AVMs is a challenging undertaking requiring multiple therapeutic modalities. mTOR inhibitors show potential for adjunct therapy for interventional radiology physicians tre