Medical Adjuvants in the Treatment of Surgically Refractory Arteriovenous Malformations of the Head and Face: Case Report and Review of Literature

Abstract

<b><i>Background:</i></b> 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. <b><i>Summary:</i></b> 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/m<sup>2</sup>. 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. <b><i>Key Messages:</i></b> 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.

Most Promising Approaches to Improve Brain AVM Management: ARISE I Consensus Recommendations

“…MEK inhibitors: sirolimus (rapamycin), selumetinib, and trametinib 127,128 bAVM indicates brain arteriovenous malformation; SMAD4, mothers against decapentaplegic homolog 4; and VEGF, vascular endothelial growth factor.…”

ĮGIMTŲ KRAUJAGYSLIŲ MALFORMACIJŲ GYDYMAS mTOR INHIBITORIUMI: EFEKTYVUMAS, DOZAVIMAS, ŠALUTINIS POVEIKIS

“…Įvairių tyrimų duomenimis, arterioveninės malformacijos nereaguoja į gydymą su sirolimu [4,7]. Vis dėlto, literatūroje galima rasti atvejų aprašymų, parodančių, kad mTOR inhibitorių vartojimas gali užkirsti kelią patologijos recidyvavimui po intervencijos [8].…”

Hypoxia Promotes Angiogenic Effect in Extracranial Arteriovenous Malformation Endothelial Cells

“…Aside from this, non-steroid anti-inflammatory drugs, analgesics, and low molecular weight heparin are used as the treatment of AVM patients. [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Moreover, various studies have reported that angiogenesis induced under hypoxia was effectively compared and evaluated in normal and pathophysiological situations using the CD31 expression [ 14 , 15 ].…”