Neuroradiology ~ Cerebral
Treatment of Cerebral Vasospasm
Interventional Neuroradiology service at Massachusetts General
and the MGH Brain Aneurysm & AVM Center.
With recent improvements in endovascular approaches to the intracranial
vasculature, several strategies have been developed to treat vasospasm
using endovascular techniques. Initially, transluminal balloon angioplasty
was demonstrated to be efficacious with some excellent success in
carefully selected patients with large vessel spasm (Zubkov, 1984).
Since then, advancements have been made in balloon and catheter technologies
which have made this technique more widely applicable and safer. The
original balloons used were relatively stiff latex balloons. Soft,
silicone balloons became available in the late 1980's. The softer
silicone balloons dramatically reduce the risk of catastrophic vessel
rupture. More recently, 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
not able to cooperate and the procedure 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, Dion, 1993, 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 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 and 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 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 8 to 10 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 are 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 with good results (Kaku 1992).
- Brothers MF, Holgate RC, Intracranial
angioplasty for treatment of vasospasm after subarachnoid hemorrhage:
technique and modifications to improve branch access. AJNR 11:239-247,
- 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).
- Dion et al, Neuroradiology 32:232-236
- 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
- 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,
- 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,
- Marks MP. Steinberg GK. Lane B.
Intraarterial papaverine for the treatment of vasospasm. AJNR.
- 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,