sirolimus and Intracranial-Arteriovenous-Malformations

Arteriovenous malformations (AVMs) of the brain and face present unique challenges for clinicians. Cerebral AVMs may induce hemorrhage or form aneurysms, while facial AVMs can cause significant disfigurement and pain. Moreover, facial AVMs often draw blood supply from arteries providing critical blood flow to other important structures of the head which may make them impossible to treat curatively. Medical adjuvants may be an important consideration in the management of these patients.. We conducted a systematic review of the literature to identify other instances of molecular target of rapamycin (mTOR) inhibitors used as medical adjuvants for the treatment of cranial and facial AVMs. We also present 2 cases from our own institution where patients were treated with partial embolization, followed by adjuvant therapy with rapamycin. After screening a total of 75 articles, 7 were identified which described use of rapamycin in the treatment of inoperable cranial or facial AVM. In total, 21 cases were reviewed. The median treatment duration was 12 months (3-24.5 months), and the highest recorded dose was 3.5 mg/m2. 76.2% of patients demonstrated at least a partial response to rapamycin therapy. In 2 patients treated at our institution, symptomatic and radiographic improvement were noted 6 months after initiation of therapy. Key Messages: Early results have been encouraging in a small number of patients with inoperable AVM of the head and face treated with mTOR inhibitors. Further study of medical adjuvants such as rapamycin may be worthwhile.

Topics: Adult; Arteriovenous Malformations; Combined Modality Therapy; Embolization, Therapeutic; Face; Female; Humans; Immunosuppressive Agents; Intracranial Arteriovenous Malformations; Sirolimus; TOR Serine-Threonine Kinases; Treatment Outcome; Young Adult

We describe a case of a premature infant with antenatally detected retroperitoneal arteriovenous malformation (AVM) with extensive intraspinal extension. Treatment of the malformation with embolectomy and sclerotherapy was not feasible in view of intraspinal extensions and small size of vessels of the lesion. During a trial of propranolol over 20 days, the lesion progressed in size, roughly doubling in volume and was accompanied with deranged coagulation parameters. Treatment was therefore switched to oral prednisolone and sirolimus. The steroid was stopped after 6 weeks and sirolimus was continued with serum drug level monitoring and serial imaging of the malformation. After 4 months of sirolimus, the AVM remained at the same size as at the start of treatment, thus we propose that the drug may have arrested the growth of the lesion. This case highlights the use of sirolimus in management of AVMs in infants.

Topics: Arteriovenous Malformations; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intracranial Arteriovenous Malformations; Prednisolone; Sclerotherapy; Sirolimus