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(Stroke. 2002;33:313.)
© 2002 American Heart Association, Inc.

Comments, Opinions, and Reviews

Endovascular Treatment of Aneurysms in the Cavernous Sinus

A Systematic Review on Balloon Occlusion of the Parent Vessel and Embolization With Coils

Irene C. van der Schaaf, MSc; Eva H. Brilstra, MD; Eric Buskens, MD Gabriël J.E. Rinkel, MD

From the University Department of Neurology (I.C.v.d.S., E.H.B., G.J.E.R.), and the Julius Center for Patient Oriented Research, University of Utrecht (E.B.), Utrecht, the Netherlands.

Correspondence to E.H. Brilstra, MD, University Department of Neurology, PO Box 85500, 3508 GA Utrecht, The Netherlands. E-mail E.Brilstra{at}neuro.azu.nl

	Abstract

Top Abstract Introduction Materials and Methods Results Discussion References

 
Background and Purpose— Balloon occlusion of the parent vessel and endosaccular coiling are both frequently used for treatment of intracavernous aneurysms of the carotid artery. We performed a systematic review of studies reporting on these two treatment modalities to assess the rate of complications, rate of successful aneurysm occlusion, and clinical condition after treatment.

Methods— We performed a MEDLINE search for studies published between January 1974 and May 1999 and hand-searched recent volumes of 21 journals. Two authors independently extracted data by means of a standardized data extraction form.

Results— We found 35 studies reporting on 316 patients. Only 9 of the 35 studies reported on more than 5 patients; in only 9 studies (totaling 85 patients), well-defined outcome measures were used. Twenty-five studies (with 78% of all patients included in the review) reported on balloon occlusion. Complications during or in the first 24 hours after the balloon occlusion occurred in 4 of 247 patients (1.6%; 95% CI, 0.01% to 3.2%) and late ischemic complications in 5 of 148 patients (3.4%; 95% CI, 0.43% to 6.4%). Clinical follow-up was performed in 21 of 25 studies on treatment by means of balloon occlusion (148 [60%] of the 247 patients). None of the 68 patients treated by embolization with coils had a complication (0%; 95% CI, 0% to 4.3%). Of 157 aneurysms treated by balloon occlusion, 153 were completely thrombosed (97.5%; 95% CI, 95% to 100%). After coiling, 52 of 65 aneurysms (80%; 95% CI, 70% to 90%) were occluded by >90%.

Conclusions— Many studies included in this review had methodological weaknesses. The available data suggest that both balloon occlusion and endosaccular coiling are reasonably safe and result in occlusion of the aneurysm in the majority of patients. However, long-term outcomes have not yet been reported.

Key Words: aneurysm • balloon occlusion • cavernous sinus • endovascular therapy

	Introduction

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Intracavernous aneurysms of the carotid artery (ICAs) can produce symptoms through mass effect of the aneurysm on adjacent structures or through rupture, which leads to carotid cavernous fistula or occasionally to subarachnoid hemorrhage (SAH) if the aneurysm extends through the dura.

Little information exists on the natural course of intracavernous aneurysms. In 2 studies, totaling 90 patients, the risk of SAH was 0.4% per patient-year. The course of cranial neuropathy resulting from mass effect of the aneurysm was variable; symptoms often progressed but spontaneously disappeared in up to 20% of patients.^1,2

Given the relatively benign course of ICAs that are strictly intracavernous and the small chance of SAH if ICAs extend through the dura, any treatment should have a low risk of complications.

Surgical treatment of ICAs is difficult because of the surrounding cavernous sinus. In the past, therapeutic options have included ligation of the internal carotid artery and direct microsurgical exposure of the cavernous aneurysm.^3,4 Since 1974, ICAs have been treated by endovascular occlusion of the parent vessel with detachable balloons. In 1991, Guglielmi detachable coils for endosaccular packing of the aneurysm became available.

Many reports on endovascular treatment of intracavernous aneurysms by balloon occlusion or coiling have now been published, but a systematic review of the risks and effectiveness of the two endovascular treatment modalities is lacking.

	Materials and Methods

Top Abstract Introduction Materials and Methods Results Discussion References

 
Search Strategy
We performed a MEDLINE search for reports on endovascular treatment of carotid cavernous aneurysms, published between January 1974 and May 1999. We used the following key words: aneurysm, coil, therapy, endovascular, parent artery, Guglielmi, cavernous, and balloon in different permutations. In addition, we performed a hand search on the volumes of 1998 and the first 5 months of 1999 of 21 relevant general medical, radiological, neurological, and neurosurgical journals. Of all studies thus collected, we checked the reference lists for additional studies. This method of cross-reference checking was continued until no further publications were found.

Eligibility
The criteria for inclusion of studies in this review were publication after 1974 and treatment of cavernous carotid artery aneurysms by balloon occlusion of the internal carotid artery or by endosaccular occlusion with detachable coils. Studies on patients younger than 18 years, patients with mycotic, traumatic, bacterial, or dissecting aneurysms, and patients with an aneurysm associated with an arteriovenous malformation were not included. When no information was available on the type of aneurysm or on procedural complications, studies were excluded. A language other than English was not an exclusion criterion.

Data Extraction
Two investigators independently assessed eligibility of studies and extracted data by means of a standardized data extraction form. In the case of disagreement, both observers reviewed the article in question together until consensus was reached. We extracted data on (1) study design (Table 1), (2) baseline characteristics (Table 2), and (3) procedural complications, radiologic results, and clinical outcomes (Table 3). Additionally we recorded whether patients were treated by one or more radiologists and in one or more centers.

View this table: [in this window] [in a new window]   Table 1. Data on Design (in 35 Studies)

View this table: [in this window] [in a new window]   Table 2. Baseline Characteristics

View this table: [in this window] [in a new window]   Table 3. Complication Rate, Degree of Aneurysm Occlusion, and Clinical Outcome

For patients treated by balloon occlusion of the parent vessel, we additionally recorded whether the aneurysm was completely thrombosed and if it had become smaller at follow-up MRI.

For the assessment of outcome, we extracted data on symptoms and signs of mass effect from the aneurysm and on global functional health at follow-up. We used the Rankin scale to classify functional health. We dichotomized outcome in "good outcome" (independent for activities of daily living, Rankin score 0 to 2) and "poor outcome" (dependent for activities of daily living, Rankin score 3 to 5) or deceased. In the case of poor outcome, we recorded whether this was related to the procedure.

Data Analysis
All analyses were performed separately for the two treatment modalities.

We calculated the proportion and corresponding 95% confidence intervals of all extracted variables. In addition, we assessed the proportions of patients with improved, unchanged, or worse functional health compared with the health status before treatment and the proportions of patients with improved or resolved symptoms of mass effect after treatment.

By means of weighted linear regression analyses, we quantified the association between aneurysm size, aneurysm type, clinical condition, and mean age on the one hand and the following outcome measures on the other: proportion of early permanent complications, degree of thrombosis or proportion of >90% occluded aneurysms, improved diplopia, and clinical outcome.

For patients treated by balloon occlusion of the parent artery, we additionally assessed the association between aneurysm shape (saccular or fusiform) and the aforementioned outcome measures; for patients treated with coils, we assessed the association between neck size of the aneurysm and outcome measures.

	Results

Top Abstract Introduction Materials and Methods Results Discussion References

 
Study Characteristics
We found 74 studies reporting on endovascular treatment of intracavernous aneurysms. We excluded 39 studies for the following reasons: patients also reported in other publications (8 studies); insufficient data on procedural complications (6 studies); balloon occlusion of the aneurysm sac rather than occlusion of the parent vessel (8 studies); coiling of the internal carotid artery instead of endosaccular occlusion of the aneurysm (2 studies); study on aneurysms in a variety of locations, without individual data about patients with an intracavernous aneurysm (4 studies); uncertainty as to whether or not fistulas had originated from an aneurysm (4 studies); report on unsuccessful temporary balloon occlusion of the parent vessel (4 studies); and report on combined treatment (surgical and endovascular) (3 studies).

We included 35 studies in 5 languages. Twenty-five studies (247 patients, 78% of all patients included in this review) reported on treatment by balloon occlusion of the parent vessel^5–29 and 12 studies (68 patients, 24%) reported on endosaccular packing of the aneurysm with coils.^6,27,30–39 In 2 studies, authors reported on both balloon occlusion of the parent vessel and embolization with coils.

The data on study design are given in Table 1. Nine studies used well-defined outcome measures. In 5 studies, clinical outcome measures were used: the Glasgow Outcome Scale in 2 studies (3 patients), the Karnofski score in 1 study (2 patients), and the course of symptoms caused by mass effect in 2 studies (42 patients). Four studies reported on anatomic results (40 patients).

Twenty-six studies reported on treatment of <5 patients. Of the 68 patients treated with coils, 51 (75%) were derived from only 2 studies. The mean number of patients per study was 9 (median, 2 patients). One study reported on treatment by 1 radiologist (34 patients, 11%); 4 studies reported on treatment by several radiologists (111 patients, 35%). Two studies reported on patients from more than 1 hospital (41 patients, 13%).

Baseline Characteristics
Table 2 presents the baseline characteristics of patients treated by balloon occlusion of the parent vessel or by embolization with coils. No data were given on clinical condition at onset for the 16 patients who presented with SAH.

Of the 247 patients treated by balloon occlusion of the parent vessel, 5 patients had bilateral intracavernous aneurysms. In 3 patients, only the symptomatic aneurysm was treated and the asymptomatic bilateral aneurysm was left untreated. In one patient, one aneurysm was treated by occlusion of the parent vessel and the other by embolization with coils. In the fifth patient, both aneurysms were treated by balloon occlusion.

Sixty-nine patients were treated by means of embolization with coils. In one patient with bilateral intracavernous aneurysms, both aneurysms were treated with coils.

Complications, Data on Procedure, Effectiveness, and Clinical Outcome
Table 3 shows the percentages and type of complications, the radiologic results, clinical outcome, and for treatment by balloon occlusion of the parent vessel, data on the use of test occlusion and on the construction of an extracranial-intracranial (EC-IC) bypass.

Four of 247 patients (1.6%; 95% CI, 0.01% to 3.2%) treated by balloon occlusion had an early complication leading to permanent neurological deficit, and 5 of the 148 patients had a late and permanent ischemic complication (3.4%; 95% CI, 0.43% to 6.4%). Follow-up after the procedure was not available for 99 patients. There were no early or late permanent complications in patients treated by embolization with coils (0%; 95% CI, 0% to 4.3%).

An EC-IC bypass was constructed in 36 patients before balloon occlusion of the parent vessel: in 7 patients because the patient did not tolerate balloon test occlusion, in 11 patients because of presumed insufficiency of the collateral circulation, and in 2 patients as a precautionary measure. For 16 patients, the indications were not clear. It was not possible to evaluate the effect of the construction of an EC-IC bypass because data on outcome were often provided only for the entire group and not separately for the subgroup of patients with an EC-IC bypass.

Follow-up on deaths was available for almost all patients treated by endosaccular coiling; for patients treated by means of balloon occlusion, this information was lacking for half of the patients. Three patients (4.6%) treated by embolization with coils died; 1 patient who had epistaxis and was successfully treated had a series of strokes 1 month after treatment, probably caused by subacute bacterial endocarditis. He was successfully treated with antibiotics. The following month, he died of an unknown cause.³¹ One patient died after rupture of an additional aneurysm³¹ and one from secondary ischemia after SAH from another intradural aneurysm.⁶

Weighted Linear Regression
For treatment by balloon occlusion, weighted linear regression analyses did not show any relation that was statistically significant between aneurysm size, aneurysm type, clinical condition before treatment and mean age on the one hand and the proportion of early permanent complications, the degree of thrombosis of the aneurysm, improved diplopia, and clinical outcome on the other.

For treatment by embolization with coils, linear regression analysis showed a statistically significant inverse relation between the presence of additional aneurysms and the proportion of patients with good outcome (ßb=-0.08; 95% CI, -0.12 to -0.03). The value -0.08 indicates that for each percentage point of more patients with an additional aneurysm, the percentage of patients with good outcome decreases by 0.08%. The corresponding 95% CI implies that the data are compatible with a decrease of the percentage of patients with good outcome ranging from 0.03% to 0.12%. There was also a statistically significant association between the percentage of nongiant aneurysms and the percentage of aneurysms occluded by >90% (ßb=0.73; 95% CI, 0.47 to 0.99). Also, we found a relation between the presence of fistulas and improvement of diplopia (ßb=7.02; 95% CI, 1.71 to 12.32) and between increased age and improvement of diplopia (ßb=3.68; 95% CI, 0.71 to 6.7).

	Discussion

Top Abstract Introduction Materials and Methods Results Discussion References

 
Many studies that we reviewed had methodological weaknesses. The method of data collection was prospective in only a minority of studies, study period and duration of follow-up were not specified in some studies, criteria for inclusion were defined in less than half of all studies, and well-defined outcome measures were used in only a minority. Clinical follow-up in the first few days after balloon occlusion was available for less than two thirds of patients, and data on baseline characteristics and on clinical outcome were provided for less than half of all included patients. For patients with SAH, data on an important prognostic factor, clinical condition at onset, were not available. Adequate descriptions of symptoms before treatment were frequently lacking. Apart from the methodological weaknesses, most series have a low generalizability. Many studies report only on a few patients, and most studies report on the results of a single radiologist or a single center. The shortcomings of the included studies call for prospective, observational studies with sound methodology and a sufficient number of patients.

Nevertheless, decisions on treatment of intracavernous aneurysms must be made, and patients need to be informed. The data presented here are presently the best available evidence. The results of our review indicate that both balloon occlusion of the parent vessel and endosaccular coiling are reasonably safe and result in occlusion of the aneurysm in the majority of patients.

Embolization with coils did not result in permanent complications, but 20% of all aneurysms were only partially occluded. We found that nongiant aneurysms were more often occluded by coils by >90% than giant aneurysms, which often have wider neck sizes than nongiant aneurysms, with increased risk of coils herniating back into the patent vessel.⁴⁰ Also in a previously study, aneurysm size was a predictor for successful obliteration of the lumen, not as an independent predictor of success but more likely through its direct correlation with neck size.⁴¹

Embolization with coils is a newly developed treatment. During the period of data collection for the current review, many endovascular therapists probably still were on the steep part of the learning curve with regard to embolization with coils. With increasing experience, the clinical and radiological results are expected to improve. As yet, data on long-term follow-up are scarce and are therefore not included in this review.

Diplopia, if present before treatment, improved in nearly all patients after treatment by coiling and in 81% of patients after treatment by means of balloon occlusion. Almost all patients treated by balloon occlusion of the parent vessel had giant aneurysms.

Balloon occlusion of the parent vessel resulted in complete thrombosis in 99% of aneurysms.

The percentage of permanent, predominantly ischemic complications was 5%, in keeping with a study on stroke risk after abrupt internal carotid artery sacrifice, which reported an infarction rate ranging from 4% to 10% after balloon test occlusion with clinical tolerance as sole criterion,^40,42 as was performed in the majority of patients included in this review.

Recently, a test occlusion protocol consisting of clinical observation and synchronous venous filling on angiography has proved to be reliable in predicting acute and delayed cerebral ischemia after parent artery occlusion.⁴³ With the use of this protocol, the percentage of ischemic complications can be expected to decrease.

Publication bias may have influenced our results. Studies with good results are more likely to be submitted and accepted for publication than studies with poor results. To minimize publication bias, we included studies in all languages from all journals.

Direct clipping of intracavernous carotid aneurysms is difficult because of the surrounding structures. There is no thorough overview of results of surgical treatment of intracavernous carotid aneurysms, but in a series of 115 surgically treated patients, 3 died after surgery, 2 (with traumatic aneurysms) of associated brain injury and 1 of pulmonary embolism. Oculomotor palsy was present in the immediate postoperative period in 104 patients. However, 6 months after surgery, only 7 patients had residual palsy. Four patients had persistent residual contralateral hemiparesis.⁴⁴ Because endovascular treatment is less invasive, takes less time for treatment and recovery, and has low complication rates, it has increasingly replaced surgical treatment.

When considering treatment of patients with a cavernous sinus aneurysm, the risk of permanent complications must be weighed against the natural history of these aneurysms. Because of the methodological weaknesses of many studies included in this review and the scarcity of data on the natural course of intracavernous aneurysms, a general advice for treatment is still premature.

	Acknowledgments

 
This study was supported in part by an Established Clinical Investigator Grant from the Netherlands Heart foundation to Dr Rinkel (grant D98.014). We thank Dr W.J.J. van Rooij and Professor J. van Gijn for comments on a previous version of the manuscript. On request, the authors can provide the complete list of papers excluded for the current review.

Received June 21, 2001; revision received October 15, 2001; accepted October 16, 2001.

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