Introduction: PTEN hamartoma tumor syndromes (PHTS) result from germline mutations to the PTEN tumor suppressor gene which can manifest in the brain as arteriovenous malformations or dural arteriovenous fistulae (dAVF). This syndrome includes Cowden’s syndrome, Lhermitte–Duclos disease and Bannayan–Riley–Ruvalcaba syndrome. These lesions are often not amenable to surgical ligation or endovascular embolization due to collateral formation and re-establishment of abnormal fistulae. A more systemic approach may be needed to curb abnormal endothelial proliferation in patients with PTEN mutation associated dAVFs.
Methods: Three patients with PHTS who underwent a cerebral angiogram which demonstrated dAVFs and subsequently received Onyx (ev3, Irvine, California) and coil embolization were included. Patient 3 received concurrent treatment with mTOR inhibition; Patient 1 and Patient 2 did not.
Results: Patient 1, a 38-year-old woman with Cowden’s syndrome and a dAVF had continued recurrence 2 months after the last embolization despite a good angiographic result and underwent craniotomy for surgical ligation of the dAVF. The patient developed venous hypertension and hydrocephalus and did not recover neurologically despite ventriculo-peritoneal shunt placement.
Patient 2, a 45-year-old man with Cowden’s syndrome and a Cognard type III dAVF underwent a sub-occipital craniotomy for ligation of the residual dAVF, despite a good angiographic result following embolization. Post-operative worsening seizures and poor neurologic status resulted in care being withdrawn and the patient died.
Patient 3, a 20-year-old man with Bannayan–Riley–Ruvalcaba syndrome and a Cognard Type IIA dAVF demonstrated a small, stable dAVF without evidence of venous hypertension at 22 months following last embolization. He began 2mg/daily rapamycin (mTOR inhibitor) treatment to limit vascular proliferation two years before treatment and maintained this regimen following treatment.
Conclusions: PI3K/Akt/mTOR pathway inhibition is a safe and effective adjunct to surgical and endovascular management of cranial dAVF in PHTS patients and may improve treatment durability.
Patient Care: Patients suffering from vascular malformations associated with PTEN mutations often undergo multiple embolizations. Adjunctive adminstration of an MTOR inhibitor may improve treatment durability improving treatment outcomes and quality of care.
Learning Objectives: By the conclusion of this session, participants should be able to:
1) Recognize PTEN hamartoma tumor syndromes (PHTS) result from germline mutations to the PTEN tumor suppressor gene which can manifest in the brain as arteriovenous malformations or dural arteriovenous fistulae.
2) Consider PTEN mutation associated arteriovenous malformations and dural arteriovenous fistulae are often not amenable to surgical ligation or endovascular embolization due to collateral formation and re-establishment of abnormal fistulae.
3) Be aware that PI3K/Akt/mTOR pathway inhibition is a safe and effective adjunct to surgical and endovascular management of cranial dAVF in PHTS patients and may improve treatment durability by mitigating curb abnormal endothelial proliferation.