Interventional Neuroradiology Endovascular Treatment of Cerebral Vasospasm
The Interventional Neuroradiology service at Massachusetts General Hospital and the MGH Brain Aneurysm & AVM Center.

Marked advances in instrumentation over the last decade have led to the development of several endovascular strategies to treat vasospasm. Transluminal balloon angioplasty was demonstrated to be efficacious in carefully selected patients with large vessel spasm (Zubkov, 1984). Since then, advancements in balloon and catheter technologies have made this technique more widely applicable and much safer. For example, the original balloons used were relatively stiff latex balloons. Soft, silicone balloons became available in the late 1980's, and they have dramatically reduced the risk of catastrophic vessel rupture. More recently, promising over-the-wire silicone balloon microcatheter systems have been introduced. Angioplasty of smaller vessels is known to be particularly hazardous, but these over-the-wire systems may allow a wider application of angioplasty techniques, particularly to the A1 and proximal M2.

Angioplasty is performed via a femoral artery approach, usually with a 6 or 7 French sheath. Ideally, the ruptured aneurysm is secured prior to angioplasty. Systemic heparinization is used to minimize the risk of thromboembolic events. Most patients are not able to cooperate for the procedure and it is best performed under general anesthesia. Only areas of vasospasm which correlate with symptoms should be targeted for treatment. This may change with the advent of imaging techniques capable of detecting sub-clinical ischemia.

A number of reasonably large series reporting the results of balloon angioplasty for the treatment of cerebral vasospasm after subarachnoid hemorrhage are now available in the literature (Brothers 1990, Takahashi, 1990, Higashida 1992, Eskridge 1994). The angiographic efficacy has been shown to be extremely high: 98-100% in most series. Clinical improvement has been noted in 65-70% of cases. Good results have been found to correlate with early and aggressive intervention after the failure of medical ("triple-H") therapy. Some authors suggest a temporal window of opportunity of 6-12 hours.

Reported complications resulting from balloon angioplasty for cerebral vasospasm following subarachnoid hemorrhage include perforation, aneurysm re-rupture, branch occlusion and hemorrhagic infarct. The complication rates are probably underestimated in the literature. Vessel rupture is reported in 2-5% of cases, rebleed from unclipped aneurysms is found in roughly 5% of cases. Importantly, the effect of angioplasty in the setting of cerebral vasospasm has been found to be lasting, and re-treatments are rarely, if ever, needed.

Another endovascular treatment strategy for vasospasm is intra-arterial infusion of papaverine. Papaverine is an alkaloid compound and is a powerful vasodilator. It acts directly on the smooth muscle cells of the arterial wall by trans-endothelial absorption. Favorable results in treating patients have also been reported with very low complication rates (Kaku 1992, Kassell 1992, Clouston 1995). Typically, papaverine is infused as a concentration of 3 mg/ml at 6-9 ml/min for a total dose of up to 300 mg per vascular territory. Since the absorption is trans-endothelial, it is not surprising that the best results have been obtained with an infusion close to the site of spasm. Because of reported ocular complications, a supra-ophthalmic position should be used if at all possible. An angiographic response is seen in 80-95% of cases. A clinical response is seen in 25-50% of cases.

As with angioplasty, the ruptured aneurysm is ideally secured prior to treatment and systemic heparinization is used routinely. The primary advantage of papaverine is its ability to treat distal spasm not safely approached with an angioplasty balloon. The main drawback of this form of therapy is its transient effect (24-48 hours). This typically necessitates multiple treatments, even as high as 6 to 8 in any given patient. The potential adverse effects of papaverine which have been reported include transient neurologic dysfunction, seizure, mydriasis, monoccular blindness, drug precipitation, increased intracranial pressure and even aggravation of spasm (Clyde 1996). Of these, by far the most common and troublesome in our experience is elevation of the intracranial pressure. Fortunately, this can usually be controlled (<20 mm H20) with a mannitol infusion (25-50 gm). However, on occasion, the infusion must be either slowed or even stopped. Other complications which can occur with this form of treatment include dissection and thromboembolism. The rate of serious complications is in the range of 5% or less of patients.

Balloon angioplasty and intra-arterial papaverine infusion should be viewed as complimentary approaches to the treatment of cerebral vasospasm. Both should be offered as soon as possible after the patient demonstrates a neurologic decline unresponsive to medical therapy. Probably, the most reasonable approach is to alleviate proximal, symptomatic spasm with angioplasty and proceed with papaverine infusion if there remains severe distal spasm. This approach has been reported to achieve good results (Kaku 1992).

References:

• Brothers MF, Holgate RC, Intracranial angioplasty for treatment of vasospasm after subarachnoid hemorrhage: technique and modifications to improve branch access. AJNR 11:239-247, (1990).
• Clouston JE. Numaguchi Y. Zoarski GH. Aldrich EF. Simard JM. Zitnay KM. Intraarterial papaverine infusion for cerebral vasospasm after subarachnoid hemorrhage. AJNR. 16(1):27-38, (1995).
• Clyde BL, Firlik AD, Kaufmann AM, Spearman MP, Yonas H. Paradoxical aggravation of vasospasm with papaverine infusion following aneurysmal subarachnoid hemorrhage: case report. J Neurosurg, 84:690-695 (1996).
• Eskridge JM, Newell DW, Mayberg MR, Winn HR. Update on transluminal angioplasty of vasospasm. Perspect Neurol Surg 1:120-126 (1990).
• Eskridge JM, Newell DW, Winn HR. Endovascular treatment of vasospasm. Neurosurg Clin N Am 5: 437-47 (1994)
• Higashida RT, Halbach VV, Dowd CF, et al Intravascular balloon dilatation therapy for intracranial arterial vasospasm: patient selection, technique and clinical results. Neurosurg Rev 15:89-95 (1992).
• Kaku Y. Yonekawa Y. Tsukahara T. Kazekawa K. Superselective intra-arterial infusion of papaverine for the treatment of cerebral vasospasm after subarachnoid hemorrhage. J Neurosurg 77(6):842-7, (1992).
• Kallmes DF. Jensen ME. Dion JE. Infusing doubt into the efficacy of papaverine. AJNR. 18(2):263-4, (1997).
• Kassell NF. Helm G. Simmons N. Phillips CD. Cail WS. Treatment of cerebral vasospasm with intra-arterial papaverine. J Neurosurg 77(6):848-52, (1992).
• Livingston K. Guterman LR. Hopkins LN. Intraarterial papaverine as an adjunct to transluminal angioplasty for vasospasm induced by subarachnoid Am J Neuroradiol. 14(2):346-7, (1993).
• Marks MP. Steinberg GK. Lane B. Intraarterial papaverine for the treatment of vasospasm. AJNR. 14(4):822-6, (1993).
• Mathis JM. DeNardo A. Jensen ME. Scott J. Dion JE. Transient neurologic events associated with intraarterial papaverine infusion for subarachnoid hemorrhage-induced vasospasm. AJNR 15(9):1671-4, (1994).
• Mathis JM. Jensen ME. Dion JE. Technical considerations on intra-arterial papaverine hydrochloride for cerebral vasospasm. Neuroradiology. 39(2):90-8, (1997).
• McAuliffe W, Townsend M, Eskridge JM, Newell DW, Grady S, Winn HR, Intracranial pressure changes induced during papaverine infusion for treatment of vasospasm. J Neurosurg 83:430-434 (1995).
• Takahashi A, Yoshoto T, Mizoi K, et al, Transluminal balloon angioplasty for vasospasm after subarachnoid hemorrhage. In: Cerebral Vasspam, edited by K Sano, K Takakura, NF Kassell and T Sasaki, pp. 429-432, U Tokyo Press, Tokyo, 1990.
• Tsukahara T. Yoshimura S. Kazekawa K. Hashimoto N. Intra-arterial papaverine for the treatment of cerebral vasospasm after subarachnoid hemorrhage. Autonomic Nervous System. 49 Suppl:S163-6, (1994).
• Zubkov YN, Nikiforov BM, Shustin VA, Balloon catheter technique for dilatation ofconstricted cerebral arteries after aneurysmal SAH. Acta Neurochir (Wien), 70:65-79, (1984).

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The Interventional Neuroradiology service at Massachusetts General Hospital and the MGH Brain Aneurysm/AVM Center.