Botulinum toxin to improve vessel graft patency in cerebral revascularization surgery: report of 3 cases

Abstract

Surgical revascularization continues to play an important role in the management of complex intracranial aneurysms and ischemic cerebrovascular disease. Graft spasm is a common complication of bypass procedures and can result in ischemia or graft thrombosis. The authors here report on the first clinical use of botulinum toxin to prevent graft spasm following extracranial-intracranial (EC-IC) bypass. This technique was used in 3 EC-IC bypass surgeries, 2 for symptomatic carotid artery occlusions and 1 for a ruptured basilar tip aneurysm. In all 3 cases, the harvested graft was treated ex vivo with botulinum toxin before the anastomosis was performed. Post-bypass vascular imaging demonstrated patency and the absence of spasm in all grafts. Histopathological analyses of treated vessels did not show any immediate endothelial or vessel wall damage. Postoperative angiograms were without graft spasm in all cases. Botulinum toxin may be a reasonable option for preventing graft spasm and maintaining patency in cerebral revascularization procedures.

EC‐IC bypass for cerebral revascularization following skull base tumor resection: Current practices and innovations

“…Many techniques have been used to reduce vessel spasm, including calcium channel antagonists, pressure distension technique, and PTA. Recently, our group published the first report of botulinum toxin use for blood vessel neuromodulation to improve vessel graft patency in cerebral revascularization . Although definitive conclusions are yet to be determined, this study does suggest that botulinum toxin may be a reasonable option for preventing graft spasm and maintaining patency.…”

Convection-enhanced delivery of botulinum toxin serotype A into the nonhuman primate cisterna magna and hippocampus

“…7 In a recent human clinical study, 100 U of BoNT/A was used ex vivo to improve vessel graft patency in cerebral revascularization surgery. 43 All of these studies employed the strategy of using a neurotoxin to target a unique tissue receptor, block harmful physiological processes, and treat CNS disease.…”

Role of botulinum neurotoxin–A in cerebral revascularization graft vasospasm prevention: current state of knowledge

“…26,28,29 The first translational application of BTX-A for cerebrovascular bypass graft spasm prevention in humans was only recently published. 63…”

“…[2][3][4] The proposed ex-vivo perivascular toxin application by soaking the graft in a reconstituted BTX-A solution intraoperatively during cerebral bypass does not involve injections. 63 Moreover, after approximately 30 minutes of soaking in BTX-A solution, the graft is thoroughly flushed and washed to remove any residual toxin, thus minimizing risks of local and systemic spread.…”

“…While more extensive studies determining optimal dosing and exposure times for BTX-A use are certainly necessary, the concentration of the toxin proposed in cerebral revascularization grafts is only 10 IU/ml. 63 As a comparison, recommended doses of BTX-A used in injection form for spastic disorders reaches up to 100 IU/ml, with total dosages of 360 IU per treatment session. 3 Similar to numerous currently practiced unlabeled BTX-A and other off-label medication uses, 12,13 BTX-A use in graft vasospasm is unlabeled and will likely remain so given the costly and time-consuming nature of obtaining FDA approval for new indications of currently approved drugs.…”