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1.  Coil Embolization for Intracranial Aneurysms 
Executive Summary
To determine the effectiveness and cost-effectiveness of coil embolization compared with surgical clipping to treat intracranial aneurysms.
The Technology
Endovascular coil embolization is a percutaneous approach to treat an intracranial aneurysm from within the blood vessel without the need of a craniotomy. In this procedure, a microcatheter is inserted into the femoral artery near the groin and navigated to the site of the aneurysm. Small helical platinum coils are deployed through the microcatheter to fill the aneurysm, and prevent it from further expansion and rupture. Health Canada has approved numerous types of coils and coil delivery systems to treat intracranial aneurysms. The most favoured are controlled detachable coils. Coil embolization may be used with other adjunct endovascular devices such as stents and balloons.
Intracranial Aneurysms
Intracranial aneurysms are the dilation or ballooning of part of a blood vessel in the brain. Intracranial aneurysms range in size from small (<12 mm in diameter) to large (12–25 mm), and to giant (>25 mm). There are 3 main types of aneurysms. Fusiform aneurysms involve the entire circumference of the artery; saccular aneurysms have outpouchings; and dissecting aneurysms have tears in the arterial wall. Berry aneurysms are saccular aneurysms with well-defined necks.
Intracranial aneurysms may occur in any blood vessel of the brain; however, they are most commonly found at the branch points of large arteries that form the circle of Willis at the base of the brain. In 85% to 95% of patients, they are found in the anterior circulation. Aneurysms in the posterior circulation are less frequent, and are more difficult to treat surgically due to inaccessibility.
Most intracranial aneurysms are small and asymptomatic. Large aneurysms may have a mass effect, causing compression on the brain and cranial nerves and neurological deficits. When an intracranial aneurysm ruptures and bleeds, resulting in a subarachnoid hemorrhage (SAH), the mortality rate can be 40% to 50%, with severe morbidity of 10% to 20%. The reported overall risk of rupture is 1.9% per year and is higher for women, cigarette smokers, and cocaine users, and in aneurysms that are symptomatic, greater than 10 mm in diameter, or located in the posterior circulation. If left untreated, there is a considerable risk of repeat hemorrhage in a ruptured aneurysm that results in increased mortality.
In Ontario, intracranial aneurysms occur in about 1% to 4% of the population, and the annual incidence of SAH is about 10 cases per 100,000 people. In 2004-2005, about 660 intracranial aneurysm repairs were performed in Ontario.
Treatment of Intracranial Aneurysms
Treatment of an unruptured aneurysm attempts to prevent the aneurysm from rupturing. The treatment of a ruptured intracranial aneurysm aims to prevent further hemorrhage. There are 3 approaches to treating an intracranial aneurysm.
Small, asymptomatic aneurysms less than 10 mm in diameter may be monitored without any intervention other than treatment for underlying risk factors such as hypertension.
Open surgical clipping, involves craniotomy, brain retraction, and placement of a silver clip across the neck of the aneurysm while a patient is under general anesthesia. This procedure is associated with surgical risks and neurological deficits.
Endovascular coil embolization, introduced in the 1990s, is the health technology under review.
Literature Review
The Medical Advisory Secretariat searched the International Health Technology Assessment (INAHTA) Database and the Cochrane Database of Systematic Reviews to identify relevant systematic reviews. OVID Medline, Medline In-Process and Other Non-Indexed Citations, and Embase were searched for English-language journal articles that reported primary data on the effectiveness or cost-effectiveness of treatments for intracranial aneurysms, obtained in a clinical setting or analyses of primary data maintained in registers or institutional databases. Internet searches of Medscape and manufacturers’ databases were conducted to identify product information and recent reports on trials that were unpublished but that were presented at international conferences. Four systematic reviews, 3 reports on 2 randomized controlled trials comparing coil embolization with surgical clipping of ruptured aneurysms, 30 observational studies, and 3 economic analysis reports were included in this review.
Safety and Effectiveness
Coil embolization appears to be a safe procedure. Complications associated with coil embolization ranged from 8.6% to 18.6% with a median of about 10.6%. Observational studies showed that coil embolization is associated with lower complication rates than surgical clipping (permanent complication 3-7% versus 10.9%; overall 23% versus 46% respectively, p=0.009). Common complications of coil embolization are thrombo-embolic events (2.5%–14.5%), perforation of aneurysm (2.3%–4.7%), parent artery obstruction (2%–3%), collapsed coils (8%), coil malposition (14.6%), and coil migration (0.5%–3%).
Randomized controlled trials showed that for ruptured intracranial aneurysms with SAH, suitable for both coil embolization and surgical clipping (mostly saccular aneurysms <10 mm in diameter located in the anterior circulation) in people with good clinical condition:Coil embolization resulted in a statistically significant 23.9% relative risk reduction and 7% absolute risk reduction in the composite rate of death and dependency compared to surgical clipping (modified Rankin score 3–6) at 1-year.
The advantage of coil embolization over surgical clipping varies widely with aneurysm location, but endovascular treatment seems beneficial for all sites.
There were less deaths in the first 7 years following coil embolization compared to surgical clipping (10.8% vs 13.7%). This survival benefit seemed to be consistent over time, and was statistically significant (log-rank p= 0.03).
Coil embolization is associated with less frequent MRI-detected superficial brain deficits and ischemic lesions at 1-year.
The 1- year rebleeding rate was 2.4% after coil embolization and 1% for surgical clipping. Confirmed rebleeding from the repaired aneurysm after the first year and up to year eight was low and not significantly different between coil embolization and surgical clipping (7 patients for coil embolization vs 2 patients for surgical clipping, log-rank p=0.22).
Observational studies showed that patients with SAH and good clinical grade had better 6-month outcomes and lower risk of symptomatic cerebral vasospasm after coil embolization compared to surgical clipping.
For unruptured intracranial aneurysms, there were no randomized controlled trials that compared coil embolization to surgical clipping. Large observational studies showed that:
The risk of rupture in unruptured aneurysms less than 10 mm in diameter is about 0.05% per year for patients with no pervious history of SAH from another aneurysm. The risk of rupture increases with history of SAH and as the diameter of the aneurysm reaches 10 mm or more.
Coil embolization reduced the composite rate of in hospital deaths and discharge to long-term or short-term care facilities compared to surgical clipping (Odds Ratio 2.2, 95% CI 1.6–3.1, p<0.001). The improvement in discharge disposition was highest in people older than 65 years.
In-hospital mortality rate following treatment of intracranial aneurysm ranged from 0.5% to 1.7% for coil embolization and from 2.1% to 3.5% for surgical clipping. The overall 1-year mortality rate was 3.1% for coil embolization and 2.3% for surgical clipping. One-year morbidity rate was 6.4% for coil embolization and 9.8% for surgical clipping. It is not clear whether these differences were statistically significant.
Coil embolization is associated with shorter hospital stay compared to surgical clipping.
For both ruptured and unruptured aneurysms, the outcome of coil embolization does not appear to be dependent on age, whereas surgical clipping has been shown to yield worse outcome for patients older than 64 years.
Angiographic Efficiency and Recurrences
The main drawback of coil embolization is its low angiographic efficiency. The percentage of complete aneurysm occlusion after coil embolization (27%–79%, median 55%) remains lower than that achieved with surgical clipping (82%–100%). However, about 90% of coiled aneurysms achieve near total occlusion or better. Incompletely coiled aneurysms have been shown to have higher aneurysm recurrence rates ranging from 7% to 39% for coil embolization compared to 2.9% for surgical clipping. Recurrence is defined as refilling of the neck, sac, or dome of a successfully treated aneurysm as shown on an angiogram. The long-term clinical significance of incomplete occlusion following coil embolization is unknown, but in one case series, 20% of patients had major recurrences, and 50% of these required further treatment.
Long-Term Outcomes
A large international randomized trial reported that the survival benefit from coil embolization was sustained for at least 7 years. The rebleeding rate between year 2 and year 8 following coil embolization was low and not significantly different from that of surgical clipping. However, high quality long-term angiographic evidence is lacking. Accordingly, there is uncertainty about long-term occlusion status, coil durability, and recurrence rates. While surgical clipping is associated with higher immediate procedural risks, its long-term effectiveness has been established.
Indications and Contraindications
Coil embolization offers treatment for people at increased risk for craniotomy, such as those over 65 years of age, with poor clinical status, or with comorbid conditions. The technology also makes it possible to treat surgical high-risk aneurysms.
Not all aneurysms are suitable for coil embolization. Suitability depends on the size, anatomy, and location of the aneurysm. Aneurysms more than 10 mm in diameter or with an aneurysm neck greater than or equal to 4 mm are less likely to achieve total occlusion. They are also more prone to aneurysm recurrences and to complications such as coil compaction or parent vessel occlusion. Aneurysms with a dome to neck ratio of less than 1 have been shown to have lower obliteration rates and poorer outcome following coil embolization. Furthermore, aneurysms in the middle cerebral artery bifurcation are less suitable for coil embolization. For some aneurysms, treatment may require the use of both coil embolization and surgical clipping or adjunctive technologies, such as stents and balloons, to obtain optimal results.
Information from 3 countries indicates that coil embolization is a rapidly diffusing technology. For example, it accounted for about 40% of aneurysm treatments in the United Kingdom.
In Ontario, coil embolization is an insured health service, with the same fee code and fee schedule as open surgical repair requiring craniotomy. Other costs associated with coil embolization are covered under hospitals’ global budgets. Utilization data showed that in 2004-2005, coil embolization accounted for about 38% (251 cases) of all intracranial aneurysm repairs in the province. With the 2005 publication of the positive long-term survival data from the International Subarachnoid Aneursym Trial, the pressure for diffusion will likely increase.
Economic Analysis
Recent economic studies show that treatment of unruptured intracranial aneurysms smaller than 10 mm in diameter in people with no previous history of SAH, either by coil embolization or surgical clipping, would not be effective or cost-effective. However, in patients with aneurysms that are greater than or equal to 10 mm or symptomatic, or in patients with a history of SAH, treatment appears to be cost-effective.
In Ontario, the average device cost of coil embolization per case was estimated to be about $7,500 higher than surgical clipping. Assuming that the total number of intracranial aneurysm repairs in Ontario increases to 750 in the fiscal year of 2007, and assuming that up to 60% (450 cases) of these will be repaired by coil embolization, the difference in device costs for the 450 cases (including a 15% recurrence rate) would be approximately $3.8 million. This figure does not include capital costs (e.g. $3 million for an angiosuite), additional human resources required, or costs of follow-up. The increase in expenditures associated with coil embolization may be offset partially, by shorter operating room times and hospitalization stays for endovascular repair of unruptured aneurysms; however, the impact of these cost savings is probably not likely to be greater than 25% of the total outlay since the majority of cases involve ruptured aneurysms. Furthermore, the recent growth in aneurysm repair has predominantly been in the area of coil embolization presumably for patients for whom surgical clipping would not be advised; therefore, no offset of surgical clipping costs could be applied in such cases. For ruptured aneurysms, downstream cost savings from endovascular repair are likely to be minimal even though the savings for individual cases may be substantial due to lower perioperative complications for endovascular aneurysm repair.
The two Guidance documents issued by the National Institute of Clinical Excellence (UK) in 2005 support the use of coil embolization for both unruptured and ruptured (SAH) intracranial aneurysms, provided that procedures are in place for informed consent, audit, and clinical governance, and that the procedure is performed in specialist units with expertise in the endovascular treatment of intracranial aneurysms.
For people in good clinical condition following subarachnoid hemorrhage from an acute ruptured intracranial aneurysm suitable for either surgical clipping or endovascular repair, coil embolization results in improved independent survival in the first year and improved survival for up to seven years compared to surgical clipping. The rebleeding rate is low and not significantly different between the two procedures after the first year. However, there is uncertainty regarding the long-term occlusion status, durability of the stent graft, and long-term complications.
For people with unruptured aneurysms, level 4 evidence suggests that coil embolization may be associated with comparable or less mortality and morbidity, shorter hospital stay, and less need for discharge to short-term rehabilitation facilities. The greatest benefit was observed in people over 65 years of age. In these patients, the decision regarding treatment needs to be based on the assessment of the risk of rupture against the risk of the procedure, as well as the morphology of the aneurysm.
In people who require treatment for intracranial aneurysm, but for whom surgical clipping is too risky or not feasible, coil embolization provides survival benefits over surgical clipping, even though the outcomes may not be as favourable as in people in good clinical condition and with small aneurysms. The procedure may be considered under the following circumstances provided that the aneurysm is suitable for coil embolization:
Patients in poor/unstable clinical or neurological state
Patients at high risk for surgical repair (e.g. people>age 65 or with comorbidity), or
Aneurysm(s) with poor accessibility or visibility for surgical treatment due to their location (e.g. ophthalmic or basilar tip aneurysms)
Compared to small aneurysms with a narrow neck in the anterior circulation, large aneurysms (> 10 mm in diameter), aneurysms with a wide neck (>4mm in diameter), and aneurysms in the posterior circulation have lower occlusion rates and higher rate of hemorrhage when treated with coil embolization.
The extent of aneurysm obliteration after coil embolization remains lower than that achieved with surgical clipping. Aneurysm recurrences after successful coiling may require repeat treatment with endovascular or surgical procedures. Experts caution that long-term angiographic outcomes of coil embolization are unknown at this time. Informed consent for and long-term follow-up after coil embolization are recommended.
The decision to treat an intracranial aneurysm with surgical clipping or coil embolization needs to be made jointly by the neurosurgeon and neuro-intervention specialist, based on the clinical status of the patient, the size and morphology of the aneurysm, and the preference of the patient.
The performance of endovascular coil embolization should take place in centres with expertise in both neurosurgery and endovascular neuro-interventions, with adequate treatment volumes to maintain good outcomes. Distribution of the technology should also take into account that patients with SAH should be treated as soon as possible with minimal disruption.
PMCID: PMC3379525  PMID: 23074479
2.  Combined Endovascular and Microsurgical Procedures as Complementary Approaches in the Treatment of a Single Intracranial Aneurysm 
Both endovascular coil embolization and microsurgical clipping are now firmly established as treatment options for the management of cerebral aneurysms. Moreover, they are sometimes used as complementary approaches each other. This study retrospectively analyzed our experience with endovascular and microsurgical procedures as complementary approaches in treating a single aneurysm.
Nineteen patients with intracranial aneurysm were managed with both endovascular and microsurgical treatments. All of the aneurysms were located in the anterior circulation. Eighteen patients presented with SAH, and 14 aneurysms had diameters of less than 10 mm, and five had diameters of 10-25 mm.
Thirteen of the 19 patients were initially treated with endovascular coil embolization, followed by microsurgical management. Of the 13 patients, 9 patients had intraprocedural complications during coil embolization (intraprocedural rupture, coil protrusion, coil migration), rebleeding with regrowth of aneurysm in two patients, residual sac in one patient, and coil compaction in one patient. Six patients who had undergone microsurgical clipping were followed by coil embolization because of a residual aneurysm sac in four patients, and regrowth in two patients.
In intracranial aneurysms involving procedural endovascular complications or incomplete coil embolization and failed microsurgical clipping, because of anatomical and/or technical difficulties, the combined and complementary therapy with endovascular coiling and microsurgical clipping are valuable in providing the best outcome.
PMCID: PMC2588162  PMID: 19096540
Cerebral aneurysm; Clipping; Coil embolization; Complementary therapy
3.  Aneurysm Clipping after Partial Endovascular Embolization for Ruptured Cerebral Aneurysms 
Interventional Neuroradiology  2001;6(Suppl 1):49-58.
The aim of this study was to investigate the advantages and disadvantages of a two-stage treatment for ruptured cerebral aneurysms; partial embolization in acute stage followed by clipping in chronic stage of subarachnoid hemorrhage.
Between April 1997 and August 1999, twenty ruptured cerebral aneurysms were initially treated endovasculary using Guglielmi detachable coils in our institution. Among them, complete embolization could not be achieved in 6 lesions. For these lesions, subsequent clipping was added. The radiological and operative findings, and outcomes of these cases were retrospectively reviewed.
In 1 case, rerupture occurred during the endovascular procedure. Rerupture was not observed in any cases in the postembolization period. In 2 cases, complications related to the clipping but not the endovascular procedure occurred. These complications included impaired visual acuity for unverified reasons, and memory disturbance due to sacrifice of a perforator arising from the anterior communicating artery. In 3 cases, coil extraction was needed during the clipping, because the loops of the coil extended into the residual neck. Complications related to coil extraction were not observed in these 3 cases.
Acute partial embolization of ruptured aneurysm appears to be effective for the prevention of subsequent rerupture during the subacute period, in which treatment for vasospasm should be performed, and the clipping procedure. However, in the case of relatively large aneurysms, small arteries or other normal structures behind the aneurysm cannot be observed directly during surgery, because of the immovability of the embolized aneurysm. Further; complete clip closure is impossible when loops of coil herniate into the neck. In such situations, coil extraction with or without resection of the aneurysm might be necessary, and care must be taken not to damage parent artery and surrounding vessels.
PMCID: PMC3685935  PMID: 20667221
ruptured cerebral aneurysm, partial embolization, clipping, electrolytically detachable coil
4.  Rate of Recanalization and Safety of Endovascular Embolization of Intracranial Saccular Aneurysms Framed with GDC 360 Coils 
Interventional Neuroradiology  2009;14(4):397-401.
Coil compaction and recanalization of cerebral aneurysms treated with coil embolization continue to be of great concern, especially in patients that presented with subarachnoid hemorrhage. The incidence of recanalization reported by previous studies ranges from 12 to 40 percent in experienced centers. We reviewed the incidence of recanalization requiring retreatment in patients treated with GDC 360 framing coils.
A retrospective review of every patient who underwent coil embolization with GDC 360 coils for saccular aneurysms at our institution from December 2004 to March 2008 was performed. We studied the patients’ demographics, clinical presentation, aneurysm size and configuration, type of coils used to embolize the aneurysm, the percentage of coils that were GDC 360 in any given aneurysm, the need for remodeling techniques like stent and/or balloon for embolization, immediate complications, cases in which we were unable to frame with the GDC 360 coil, and rate of recanalization on follow-up.
A total of 110 patients (33 men, 77 women) and 114 aneurysms were treated with GDC 360 coils. Ninety-eight aneurysms were framed with the GDC 360 coils. There were two patients in whom the initial GDC 360 coil intended for framing had to be pulled out and exchanged for another type of coil. There were five procedure related complications (4.4%). Four patients required intra-arterial abciximab due to thrombus formation. One patient that presented with a grade III subarachnoid hemorrhage had aneur-ysm rupture while the coil was being advanced. A total of 50 patients (15 men and 35 women) underwent follow-up femoral cerebral angio-grams at least six months after coiling (mean follow-up was 15 months). Forty-four of the patients with follow-up had the GDC 360 coil used as a framing coil. Three patients (6%) required retreatment due to recanalization. Every patient with recanalization requiring treatment had aneurysms of the anterior communicating complex that presented with subarachnoid hemorrhage.
The rate of recanalization of cerebral aneur-ysms embolized with GDC 360 framing coils was lower in our case series compared to the existing literature reports. Patients with aneurysms of the anterior communicating artery were at increased incidence of recanalization in our patient cohort.
PMCID: PMC3313807  PMID: 20557739
cerebral aneurysm, coil, GDC 360
5.  Rupture of Aneurysms during and after Embolization with Guglielmi Detachable Coils 
Interventional Neuroradiology  2002;7(Suppl 1):83-87.
Between March, 1997 and June, 2000, 104 aneurysms, including 75 ruptured and 29 unruptured aneurysms, were treated with Guglielmi detachable coils by 120 embolizations in our institution. Intraprocedual perforation occurred in four cases, representing 3.3% of the embolizations. Subsequently, two cases deteriorated, and the other two cases recovered completely without any deficit. Aneurysmal perforations mostly occurred in acutely ruptured aneurysms, small aneurysms less than 4 mm, anterior communicating artery aneurysms, or first coil delivery. Rebleedings in the acute period of subarachnoid hemorrhage occurred in four cases of partial occlusion due to aneurysmal morphology, such as a wide neck or an irregular shape. Rebleedings in the chronic period occurred in two cases, one of which rebled two months after partial occlusion, and the other of which rebled 27 months after nearly total occlusion. No subarachnoid hemorrhages documented from previously unruptured aneurysms occurred after embolizations. Insufficient embolization for ruptured aneurysms cannot prevent rebleeding, and partially occluded aneurysms and recurring aneurysms in the follow-up period require immediate re-treatment.
PMCID: PMC3627253  PMID: 20663383
aneurysm, Guglielmi detachable coil, perforation, rebleeding
6.  Endovascular Coil Embolization After Clipping: Endovascular Treatment of Incompletely Clipped or Recurred Cerebral Aneurysms 
The presence of a cerebral aneurysm remnant after surgical clipping is associated with a risk of regrowth or rupture. For these recurred aneurysms, coil embolization can be considered as a treatment option. We retrospectively reviewed cases of ruptured or regrown aneurysms after clipping treated by endovascular coil embolization.
Materials and Methods
We conducted a retrospective review of patients with ruptured or recurred aneurysm after clipping, who underwent coil embolization between January 1995 and December 2013. We evaluated clinical information and the outcomes of these cases.
Eight patients were treated by endovascular coil embolization after surgical clipping. Six aneurysms were located in the anterior communicating artery, one in the posterior communicating artery, and one in the middle cerebral artery bifurcation. All patients were initially treated by surgical clipping because of a ruptured aneurysm. Aneurysm recurrence at the initial clipping site was detected in all cases. The median interval from initial to second presentation was 42 months. In four patients, aneurysms were detected before rupture and the four remaining patients presented with recurrent subarachnoid hemorrhage. All patients were treated by coil embolization and showed successful occlusion of aneurysms without complications.
Endovascular coil embolization can be a safe and successful treatment option for recurred aneurysms after clipping.
PMCID: PMC4205253  PMID: 25340029
Intracranial aneurysm; Recurrence; Coil embolization; Clipping
7.  Endovascular Treatment of ACom Intracranial Aneurysms 
Interventional Neuroradiology  2010;16(1):7-16.
The immediate and long-term outcomes, complications, recurrences and the need for retreatment were analyzed in a series of 280 consecutive patients with anterior communicating artery aneurysms treated with the endovascular technique. From October 1992 to October 2001 280 patients with 282 anterior communicating artery aneurysms were addressed to our center. For the analysis, the population was divided into two major groups: group 1, comprising 239 (85%) patients with ruptured aneurysms and group 2 comprising of 42 (15%) patients with unruptured aneurysms. In group 1, 185 (77.4%) patients had a good initial pre-treatment Hunt and Hess grade of I-III. Aneurysm size was divided into three categories according to the larger diameter: less than 4 mm, between 4 and 10 mm and larger than 10 mm. The sizes of aneurysms in groups 1 and 2 were identical but a less favorable neck to depth ratio of 0.5 was more frequent in group 2.
Endovascular treatment was finally performed in 234 patients in group 1 and 34 patients in group 2. Complete obliteration was more frequently obtained in group 2 unlike a residual neck or opacification of the sac that were more frequently seen in group 1. No peri-treatment complications were recorded in group 2. In group 1 the peri-treatment mortality and overall peri-treatment morbidity were 5.1% and 8.1% respectively. Eight patients (3.4%) in group 1 presented early post treatment rebleeding with a mortality of 88%. The mean time to follow-up was 3.09 years. In group 1, 51 (21.7%) recurrences occurred of which 14 were minor and 37 major. In group 2, eight (23.5%) recurrences occurred, five minor and three major. Two patients (0.8%) presented late rebleeding in group 1.
Twenty-seven second endovascular retreatments were performed, 24 (10.2%) in group 1 and three (8.8%) in group 2, seven third endovascular retreatments and two surgical clippings in group 1 only. There was no additional morbidity related to retreatments.
Endovascular treatment is an effective method for the treatment of anterior communicating artery aneurysms allowing late rebleeding prevention. Peri-treatment rebleeding warrants caution in anticoagulation management. This is a single center experience and the follow-up period is limited. Patients should be followed-up in the long-term as recurrences may occur and warrant additional treatment.
PMCID: PMC3277962  PMID: 20377974
brain, cerebral, anterior communicating, aneurysm
8.  Risk of recurrent subarachnoid haemorrhage, death, or dependence and standardised mortality ratios after clipping or coiling of an intracranial aneurysm in the International Subarachnoid Aneurysm Trial (ISAT): long-term follow-up 
Lancet Neurology  2009;8(5):427-433.
Our aim was to assess the long-term risks of death, disability, and rebleeding in patients randomly assigned to clipping or endovascular coiling after rupture of an intracranial aneurysm in the follow-up of the International Subarachnoid Aneurysm Trial (ISAT).
2143 patients with ruptured intracranial aneurysms were enrolled between 1994 and 2002 at 43 neurosurgical centres and randomly assigned to clipping or coiling. Clinical outcomes at 1 year have been previously reported. All UK and some non-UK centres continued long-term follow-up of 2004 patients enrolled in the original cohort. Annual follow-up has been done for a minimum of 6 years and a maximum of 14 years (mean follow-up 9 years). All deaths and rebleeding events were recorded. Analysis of rebleeding was by allocation and by treatment received. ISAT is registered, number ISRCTN49866681.
24 rebleeds had occurred more than 1 year after treatment. Of these, 13 were from the treated aneurysm (ten in the coiling group and three in the clipping group; log rank p=0·06 by intention-to-treat analysis). There were 8447 person-years of follow-up in the coiling group and 8177 person-years of follow-up in the clipping group. Four rebleeds occurred from a pre-existing aneurysm and six from new aneurysms. At 5 years, 11% (112 of 1046) of the patients in the endovascular group and 14% (144 of 1041) of the patients in the neurosurgical group had died (log-rank p=0·03). The risk of death at 5 years was significantly lower in the coiling group than in the clipping group (relative risk 0·77, 95% CI 0·61–0·98; p=0·03), but the proportion of survivors at 5 years who were independent did not differ between the two groups: endovascular 83% (626 of 755) and neurosurgical 82% (584 of 713). The standardised mortality rate, conditional on survival at 1 year, was increased for patients treated for ruptured aneurysms compared with the general population (1·57, 95% CI 1·32–1·82; p<0·0001).
There was an increased risk of recurrent bleeding from a coiled aneurysm compared with a clipped aneurysm, but the risks were small. The risk of death at 5 years was significantly lower in the coiled group than it was in the clipped group. The standardised mortality rate for patients treated for ruptured aneurysms was increased compared with the general population.
UK Medical Research Council.
PMCID: PMC2669592  PMID: 19329361
9.  Endovascular Repair of Abdominal Aortic Aneurysm 
The Medical Advisory Secretariat conducted a systematic review of the evidence on the effectiveness and cost-effectiveness of endovascular repair of abdominal aortic aneurysm in comparison to open surgical repair. An abdominal aortic aneurysm [AAA] is the enlargement and weakening of the aorta (major blood artery) that may rupture and result in stroke and death. Endovascular abdominal aortic aneurysm repair [EVAR] is a procedure for repairing abdominal aortic aneurysms from within the blood vessel without open surgery. In this procedure, an aneurysm is excluded from blood circulation by an endograft (a device) delivered to the site of the aneurysm via a catheter inserted into an artery in the groin. The Medical Advisory Secretariat conducted a review of the evidence on the effectiveness and cost-effectiveness of this technology. The review included 44 eligible articles out of 489 citations identified through a systematic literature search. Most of the research evidence is based on non-randomized comparative studies and case series. In the short-term, EVAR appears to be safe and comparable to open surgical repair in terms of survival. It is associated with less severe hemodynamic changes, less blood transfusion and shorter stay in the intensive care and hospital. However, there is concern about a high incidence of endoleak, requiring secondary interventions, and in some cases, conversion to open surgical repair. Current evidence does not support the use of EVAR in all patients. EVAR might benefit individuals who are not fit for surgical repair of abdominal aortic aneurysm and whose risk of rupture of the aneurysm outweighs the risk of death from EVAR. The long-term effectiveness and cost-effectiveness of EVAR cannot be determined at this time. Further evaluation of this technology is required.
The objective of this health technology policy assessment was to determine the effectiveness and cost-effectiveness of endovascular repair of abdominal aortic aneurysms (EVAR) in comparison to open surgical repair (OSR).
Clinical Need
An abdominal aortic aneurysm (AAA) is a localized, abnormal dilatation of the aorta greater than 3 cm or 50% of the aortic diameter at the diaphragm. (1) A true AAA involves all 3 layers of the vessel wall. If left untreated, the continuing extension and thinning of the vessel wall may eventually result in rupture of the AAA. The risk of death from ruptured AAA is 80% to 90%. (61) Heller et al. (44) analyzed information from a national hospital database in the United States. They found no significant change in the incidence rate of elective AAA repair or ruptured AAA presented to the nation’s hospitals. The investigators concluded that technologic and treatment advances over the past 19 years have not affected the outcomes of patients with AAAs, and the ability to identify and to treat patients with AAAs has not improved.
Classification of Abdominal Aortic Aneurysms
At least 90% of the AAAs are affected by atherosclerosis, and most of these aneurysms are below the level of the renal arteries.(1)
An abdominal aortic aneurysm may be symptomatic or asymptomatic. An AAA may be classified according to their sizes:(7)
Small aneurysms: less than 5 cm in diameter.
Medium aneurysms: 5-7cm.
Large aneurysms: more than 7 cm in diameter.
Small aneurysms account for approximately 50% of all clinically recognized aneurysms.(7)
Aortic aneurysms may be classified according to their gross appearance as follows (1):
Fusiform aneurysms affect the entire circumference of a vessel, resulting in a diffusely dilated lesion
Saccular aneurysms involve only a portion of the circumference, resulting in an outpouching (protrusion) in the vessel wall.
Prevalence of Abdominal Aortic Aneurysms
In community surveys, the prevalence of AAA is reported to be between 1% and 5.4%. (61) The prevalence is related to age and vascular risk factors. It is more common in men and in those with a positive family history.
In Canada, Abdominal aortic aneurysms are the 10th leading cause of death in men 65 years of age or older. (60) Naylor (60) reported that the rate of AAA repair in Ontario has increased from 38 per 100,000 population in 1981/1982 to 54 per 100,000 population in 1991/1992. For the period of 1989/90 to 1991/92, the rate of AAA repair in Ontarians age 45 years and over was 53 per 100,000. (60) In the United States, about 200,000 new cases are diagnosed each year, and 50,000 to 60,000 surgical AAA repairs are performed. (2) Ruptured AAAs are responsible for about 15,000 deaths in the United States annually. One in 10 men older than 80 years has some aneurysmal change in his aorta. (2)
Symptoms of Abdominal Aortic Aneurysms
AAAs usually do not produce symptoms. However, as they expand, they may become painful. Compression or erosion of adjacent tissue by aneurysms also may cause symptoms. The formation of mural thrombi, a type of blood clots, within the aneurysm may predispose people to peripheral embolization, where blood vessels become blocked. Occasionally, an aneurysm may leak into the vessel wall and the periadventitial area, causing pain and local tenderness. More often, acute rupture occurs without any prior warning, causing acute pain and hypotension. This complication is always life-threatening and requires an emergency operation.
Diagnosis of Abdominal Aortic Aneurysms
An AAA is usually detected on routine examination as a palpable, pulsatile, and non-tender mass. (1)
Abdominal radiography may show the calcified outline of the aneurysms; however, about 25% of aneurysms are not calcified and cannot be visualized by plain x-ray. (1) An abdominal ultrasound provides more accurate detection, can delineate the traverse and longitudinal dimensions of the aneurysm, and is useful for serial documentation of aneurysm size. Computed tomography and magnetic resonance have also been used for follow-up of aortic aneurysms. These technologies, particularly contrast-enhanced computer tomography, provide higher resolution than ultrasound.
Abdominal aortography remains the gold standard to evaluate patients with aneurysms for surgery. This technique helps document the extent of the aneurysms, especially their upper and lower limits. It also helps show the extent of associated athereosclerotic vascular disease. However, the procedure carries a small risk of complications, such as bleeding, allergic reactions, and atheroembolism. (1)
Prognosis of Abdominal Aortic Aneurysms
The risk of rupture of an untreated AAA is a continuous function of aneurysm size as represented by the maximal diameter of the AAA. The annual rupture rate is near zero for aneurysms less than 4 cm in diameter. The risk is about 1% per year for aneurysms 4 to 4.9 cm, 11% per year for aneurysms 5 to 5.9 cm, and 25% per year or more for aneurysms greater than 6 cm. (7)
The 1-year mortality rate of patients with AAAs who do not undergo surgical treatment is about 25% if the aneurysms are 4 to 6 cm in diameter. This increases to 50% for aneurysms exceeding 6 cm. Other major causes of mortality for people with AAAs include coronary heart disease and stroke.
Treatment of Abdominal Aortic Aneurysms
Treatment of an aneurysm is indicated under any one of the following conditions:
The AAA is greater than 6 cm in diameter.
The patient is symptomatic.
The AAA is rapidly expanding irrespective of the absolute diameter.
Open surgical repair of AAA is still the gold standard. It is a major operation involving the excision of dilated area and placement of a sutured woven graft. The surgery may be performed under emergent situation following the rupture of an AAA, or it may be performed electively.
Elective OSR is generally considered appropriate for healthy patients with aneurysms 5 to 6 cm in diameter. (7) Coronary artery disease is the major underlying illness contributing to morbidity and mortality in OSR. Other medical comorbidities, such as chronic renal failure, chronic lung disease, and liver cirrhosis with portal hypertension, may double or triple the usual risk of OSR.
Serial noninvasive follow-up of small aneurysms (less than 5 cm) is an alternative to immediate surgery.
Endovascular repair of AAA is the third treatment option and is the topic of this review.
PMCID: PMC3387737  PMID: 23074438
10.  The Efficacy of Coil Embolization at the Dissection Site of Ruptured Dissecting Vertebral Aneurysms 
Interventional Neuroradiology  2002;7(Suppl 1):73-82.
Proximal occlusion of the parent artery has been widely used for treatment of vertebral dissecting ruptured aneurysms., but this does not always completely prevent re-rupture. In this series; the efficacy of occlusion at the dissection site using detachable coils was compared with proximal balloon occlusion.
Over a five year period, 25 patients suffering from subarachnoid hemorrhage with dissecting vertebral aneurysms were treated by endovascular surgery. The first three of these 25 patients were treated with proximal balloon occlusion of the parent artery. The remainder underwent platinum coil occlusion at the affected site as early as possible after the diagnosis.
In two of the three cases treated with proximal balloon occlusion, clipping or coating surgery were added because of progressive dissection. In all 22 cases of coil embolization, the intervention was successfully performed without complication. In one case with a dissection involving bilateral vertebral arteries, minor rebleeding from a contralateral dissection occurred after embolization. In the other 21 cases, rebleeding was not apparent (clinical follow-up: mean 24 months). Radiological findings showed complete occlusion of the dissection site and patency of the non affected artery (follow-up: mean ten months).
We conclude that detachable platinum coil embolization at the dissection site is more effective than proximal occlusion for treatment of ruptured vertebral dissecting aneurysms because of immediate cessation of blood flow to the dissection site. However, in cases with bilateral dissections or hypoplastic contralateral vertebral arteries, preceding bypass surgery or stent treatment to preserve the affected vertebral artery may be needed.
PMCID: PMC3627252  PMID: 20663382
Coil embolization, dissection, vertebral aneurysms
11.  Endovascular Treatment of Ruptured Anterior Communicating Artery Aneurysms 
Interventional Neuroradiology  2006;12(Suppl 1):61-66.
The aim of this paper is to provide a review of our experience in using the endovascular treatment of ruptured anterior communicating artery (ACoA) aneurysms. Between March 1997 and May 2004, 211 ruptured aneurysms were treated with Guglielmi detachable coil (GDC) system in Mito Medical Center, 73 were located at the ACoA. Two cases were incomplete embolization, and performed microsurgical clipping. In the initial embolization for the 71 aneurysms, complete occlusion was achieved in 44 aneurysms, neck remnant in 11 aneurysms and body filling in 16 aneurysms. Intra-operative complication was occurred in six cases (8.2%).
Aneurysm perforation was occurred in three cases (4.1%), thromboembolic complication was occurred in three cases (4.1%). Acute rebleeding were observed in two cases (2.7%). Endovascular treatment is an effective technique for treating ACoA aneurysms, and 3D-rotational angiography is important diagnostic tool for evaluating the ACoA complex.
PMCID: PMC3387970  PMID: 20569604
anterior communicating artery aneurysm, Guglielmi Detachable Coil, subarachnoid haemorrhage
12.  Endovascular Treatment of Berry Intracranial Aneurysms Using a New Detachable Coil System 
Interventional Neuroradiology  2001;7(2):93-102.
We aimed to assess and to demonstrate the efficiency of a new mechanical system in the endovascular treatment of berry intracranial aneurysms.
From September 1999 to October 2000, 38 patients with 40 aneurysms experienced selective embolization using Detach Coils (DCS® - Cook). They were 12 men and 26 women, aged 26 to 77 years, mean age 53.4. The clinical status of patients was graded by Hunt and Hess scale: Stage 0:8 - stage 1:3 - Stage II: 11 - Stage III: 11 - Stage TV: 2 - Stage V: 3. The localization of aneurysms was as follows: internal carotid artery: 11; sylvian artery: 10; anterior communicating artery: 5; anterior cerebral artery Al-A2: 5; intra-cavernous carotid artery: 1; basilar trunk: 5; PICA: 2; posterior cerebral artery: 1. The size of the aneurysms ranged from 2 to 40 mm. For embolization of aneurysms, we utilized 242 coils (mean number 6.05). The shape and size of coils varied as follows: longest J 6.25 - shortest 14-3 - longest S 10-20 - shortest S 2-2.
The mean time of procedure was 43 minutes (max 180 minutes - min 7 minutes). We did not have any technical complications during the procedure and no immediate rebleeding occurred. Initial follow-up of the patients showed angiographic full occlusion.
Detach Coils appear to be a very precise, reliable and rapid system, with high stability during coil detachment (in very small or very giant aneurysms) in the embolization of intracranial aneurysms, with an interesting aspect concerning the low cost of this new mechanical device.
PMCID: PMC3621540  PMID: 20663333
aneurysm, subarachnoid hemorrhagen, endovascular treatment
13.  Endovascular Surgery for Ruptured Aneurysms with Vasospasm 
Interventional Neuroradiology  2007;13(Suppl 1):48-52.
With the existence of vasospasm, it is recommended that direct clipping surgery for a ruptured aneurysm be delayed until its disappearance, but this may be associated with aneurysmal re-rupture resulting in a poor outcome for the patients. Indications for endovascular coil embolization in such cases are discussed.
Since November in 2003, we have applied endovascular coil embolization in 11 consecutive patients with ruptured aneurysms and apparent vasospasm of the parent artery from two to 17 days (average: eight days) after initial subarachnoid hemorrhage. Three patients had aneurysmal re-rupture before treatment, but the other eight had only experienced the one episode of subarachnoid hemorrhage. With one exception, all endovascular procedures could be successfully performed, resulting in complete occlusion of aneurysms and remarkable dilatation of inserted spastic vessels without technical complications or aneurysmal re-rupture.
For the one case of failure because of a tortuous artery, direct clipping surgery was performed after disappearance of vasospasm. Cerebral infarction occurred in four, but only one correlated with the distribution of catheterization, and neurological deficits had completely disappeared three months after the onset. This preliminary report concerning a small number of patients suggests that endovascular coil embolization is not contra-indicated for aneurysms with vasospasm requiring catheterization. A large study for confirmation is now warranted.
PMCID: PMC3345466  PMID: 20566076
endovascular surgery, vasospasm, aneurysm
14.  Endovascular Surgery as the First-Choice Treatment for Ruptured Cerebral Aneurysms: How Far Has It Come? 
Interventional Neuroradiology  2008;10(Suppl 2):41-47.
One hundred and seventy patients with ruptured cerebral aneurysms were treated by coil embolization from September 1997 to December 2002. After January 2000, coil embolization was selected as the first-choice treatment for ruptured aneurysms. During this period, the authors investigated the number of aborted cases, the number of complications, and how many patients could be treated by coil embolization according to the locations of ruptured cerebral aneurysms. One hundred and ninety-five sessions were performed on 170 patients, and 13 sessions (6.7%) were aborted mainly because of the difficulty of the approach and the wide necks of the aneurysms. In four patients, although procedural perforation and haemorrhage occurred, the outcome was good or excellent. Eight poorgrade patients experienced haemorrhage after coil embolization and seven patients died. The volume embolization ratios of small and large aneurysms were 27% and 21%, and the recanalization of small and large aneurysms occurred in 9% and 38% of patients, respectively. From January 2000 to December 2002, 119 (66%) of 180 ruptured cerebral aneurysms were treated by coil embolization. According to the location of aneurysms, 89% vertebrobasilar, 87% anterior cerebral, 65% internal carotid and 24% middle cerebral artery aneurysms could be treated by coil embolization. Because the tight packing of large aneurysms was difficult, the recanalization rate of large aneurysms was high. However, the results of small aneurysms were satisfactory. Almost 90% of vertebrobasilar and anterior cerebral artery aneurysms could be treated by coil embolization.
PMCID: PMC3522220  PMID: 20587248
subarachnoid haemorrhage, cerebral aneurysm, endovascular surgery
15.  Detachable Coil Embolization for Saccular Posterior Inferior Cerebellar Artery Aneurysms 
Surgical treatment of posterior inferior cerebellar artery (PICA) aneurysms is challenging due to limited surgical accessibility. Endovascular approach has a benefit of avoiding direct injury to the brainstem or lower cranial nerves. Therefore, it has recently been considered an alternative or primary modality for PICA aneurysms. We retrospectively assessed outcomes following detachable coil embolization of saccular PICA aneurysms.
From February 1997 to December 2007, we performed endovascular procedures to treat 15 patients with 15 PICA aneurysms. Fourteen patients with 14 PICA aneurysms morphology of which was saccular were reviewed retrospectively. Twelve patients had ruptured aneurysms. The aneurysms arose from the PICA origin site (n = 12), the PICA lateral medullary segment (n = 1), or the PICA tonsilomedullary segment (n = 1).
Complete aneurysm occlusion was achieved in 10 patients, residual neck in 3, and residual sac in one. Radiological follow-up was performed in 7 patients with mean duration of 34.7 months (range, 1-97 months) and showed stable or complete occlusion in 6 patients. There were no rebleeding or retreatment after endovascular treatment. Thromboembolism was the only procedure-related complication (n = 4 ; 28.6%). Asymptomatic PICA infarction occurred in two patients and symptomatic PICA infarction in two elderly patients with poor clinical grade. Of these procedural PICA infarction cases, 1 symptomatic PICA infarction patient developed ventriculitis and septic shock leading to death. The clinical outcome was good in 10 patients (71.4%).
In the present study, detachable coil embolization has shown as an efficient modality for PICA saccular aneurysms challenging indications of microsurgery. However, thromboembolic complications should be considered, especially in poor clinical elderly patients with ruptured aneurysms.
PMCID: PMC2764020  PMID: 19844622
Posterior inferior cerebellar artery; Endovascular; Microsurgery; Thromboembolism
16.  Leo Stent for Endovascular Treatment of Broad-Necked and Fusiform Intracranial Aneurysms 
Interventional Neuroradiology  2007;13(3):255-269.
The advent of intracranial stents has widened the indications for endovascular treatment of broad-necked and fusiform aneurysms. Leo stent is a self-expandable, nitinol, braided stent dedicated to intracranial vessels. The aim of this study is to present our experience in endovascular treatment of broad-necked and fusiform intracranial aneurysms using self-expanding, nitinol Leo stents.
Between February 2004 and November 2006, 25 broad-necked and three fusiform aneurysms in 28 patients were treated using Leo stents in our centre. There were 18 patients who experienced acute subarachnoid haemorrhage due to aneurysm rupture, two patients who experienced SAH at least 12 months ago and in eight patients aneurysms were found incidentally. Aneurysms were located as follows: internal carotid artery15, basilar artery5, basilar tip3, posterior inferior cerebral artery2, M1/M2 segment1, A2 segment1 and vertebral artery1.
There were no difficulties with stent deployment and delivery. All patients after acute SAH (n=18) underwent stent implantation and coil embolization in one procedure. The remaining patients underwent coil embolization in a staged procedure. Immediate aneurysm occlusion of more than 95% was achieved in all patients who underwent stent placement and coil embolization in one procedure. There were three thromboembolic complications encountered in patients in an acute setting of SAH, preloaded only on acetylsalicylic acid. Use of abciximab led to patency within the stent and parent vessel. However, one of these patients presented rebleeding from the aneurysm during administration of abciximab and died.
Application of Leo stents in cases of broadnecked and fusiform intracranial aneurysms is safe and effective with a low complication rate.
PMCID: PMC3345341  PMID: 20566117
endovascular, intracranial aneurysm, Leo, stent, fusiform
17.  Clinical and Radiogical Outcomes of Endovascular Detachable Coil Embolization in Paraclinoid Aneurysms : A 10-Year Experience 
Direct surgical clipping of paraclinoid aneurysms poses technical challenges to even very experienced neurosurgeons, making endovascular treatment an alternative treatment modality in many centers. We have therefore retrospectively evaluated the safety and efficacy of endovascular detachable coil embolization of paraclinoid aneurysms.
From June 1997 to June 2007, 65 patients underwent endovascular detachable coiling for 67 paraclinoid aneurysms (of which 9 were ruptured and 58 were unruptured) in our institute. Their medical records, radiological images and readings, and operation records were reviewed retrospectively.
After the initial embolization procedure, complete occlusion was achieved in 29 (43.3%) of the aneurysms treated by endovascular detachable coiling. Six aneurysms required retreatment, with two each requiring one, two, or three additional endovascular procedures. Fifty-five (82.1%) aneurysms were measured by three-dimensional time of flight (TOF) magnetic resonance images (MRI) or transfemoral cerebral angiography (TFCA) at a mean follow-up of 29.7 months (range from 4 to 94 months), with 39 aneurysms (70.9%) showing complete occlusion. Thromboembolic events (3.8%) were the most frequent complication. Rupture did not occur during or after any of the procedures. According to the Glasgow Outcome Scale (GOS), 98.4% of the patients treated by coil embolization had a score of 4 or 5.
Our results indicate that endovascular detachable coiling is a safe and effective treatment modality in paraclinoid aneurysms.
PMCID: PMC2640819  PMID: 19242564
Paraclinoid; Aneurysms; Endovascular
18.  Retreatment of Cerebral Aneurysms after Guglielmi Detachable Coil Embolization 
Interventional Neuroradiology  2008;10(Suppl 1):167-171.
Of 175 patients with 181 aneurysms initially treated with Guglielmi Detachable Coils (GDC), 25 were retreated. All retreatments except one were performed on previously ruptured aneurysms. Thirteen aneurysms were retreated because of recurrence, and 12 aneurysms were retreated to complete initial insufficient embolization. Sixteen patients underwent re-embolization and 9 patients were operated upon surgically. No complications related to the retreatment were experienced. We consider that repeat embolization should be attempted before considering surgical treatment in case that additional therapy is required. However, it is difficult to retreat aneurysms having wide necks. In regard to surgical clipping, aneurysms without a coil in the neck are easier to treat with primary clipping, whereas aneurysms with a coil mass in the neck are difficult to surgical clip. We have never used temporary clipping and coil extraction if the distance between the coil and the parent artery was wider than 2 mm. Emerging new embolic agents or devices and technical improvement might decrease the need for retreatment and increase long-term efficacy after endovascular treatment.
PMCID: PMC3490167  PMID: 20587295
Cerebral aneurysm, Guglielmi detachable coil, embolization, retreatment
19.  Endovascular Treatment of Recurrent Coiled Aneurysms: Assessment of Complications and Rebleeding during a Decade in a Single Center 
Interventional Neuroradiology  2012;18(1):14-19.
Recurrence is the main drawback of aneurysmal coiling. Additional coiling must sometimes be considered in patients with reopened aneurysms and expose the patient to the risk of a new procedure. Our purpose was to assess the procedural complications of additional endovascular treatments in patients with previously coiled but recurrent aneurysms treated by two neurointerventionalists during a decade in a single center.
Between 1999 and 2009, 637 intracranial aneurysms were coiled and had a clinical and angiographic follow-up at our institution. Following the first embolization, 44 aneurysms were retreated with coils and 11 were retreated a second time. Retreatment was decided when a recurrence showed at angiographic follow-up. Early retreatments, performed in the first month after an incomplete or failed initial coiling, were excluded.
We retrospectively analysed the procedural complications, rebleeding, clinical and angiographic outcomes of the retreatments. No death or bleeding occurred in these 55 additional procedures. We had three periprocedural thromboembolic complications and the procedural permanent morbidity was 1.8%. Clinical and angiographic follow-ups ranged from six months to nine years (mean: 37 months, median: 36 months). Thirty-seven of the 44 retreated aneurysms (84%) showed a stable occlusion at follow-up. Seven showed a recurrence but were not retreated due to the stability of the packing. No rebleeding was observed during the follow-up period. Our results show that endovascular treatment of recurrent aneurysms is associated with a low procedural risk.
PMCID: PMC3312084  PMID: 22440596
detachable coils, endovascular treatment, intracranial aneurysms, outcome
20.  Bare, Bio-Active and Hydrogel-Coated Coils for Endovascular Treatment of Experimentally Induced Aneurysms 
Interventional Neuroradiology  2010;16(2):139-150.
Endovascular treatments of cerebral aneurysms with bare platinum coils have a higher rate of recurrence compared to surgical clipping. This may be related to failed vessel wall reconstruction since histological and scanning electron microscopy results following embolization failed to demonstrate neoendothelialization over the aneurysm neck. The present study tried to elucidate whether the use of modified coils resulted in a better rate of reconstructing the vessel wall over the aneurysm neck in experimental aneurysms.
Aneurysms were created in 20 rabbits by intraluminal elastase incubation of the common carotid artery. Five animals each were assigned to the following groups: untreated, bare platinum coils, bioactive coils with polyglycolic/polylactic acid coating, and hydrogel-coated platinum coils. After 12 months, angiography, histology and scanning electron microscopy was performed.
No neoendothelial layer was visualized in the bioactive and bare coil groups with a tendency to an increased layering of fibroblasts along the bioactive coils at the aneurysm fundus. However, at the aneurysm neck perfused clefts were present and although a thin fibrinous layer was present over some coils, no bridging neointimal or neoendothial layer was noted over different coils. Following loose Hydrogel coiling, a complete obliteration of the aneurysm was present with neoendothelialization present over different coil loops.
The study demonstrates that with surface coil modifications complete and stable aneurysm obliteration may become possible. A smooth and dense surface over the aneurysm neck may be necessary for endothelial cells to bridge the aneurysm neck and to lead to vessel wall reconstruction.
PMCID: PMC3277983  PMID: 20642888
aneurysm, coiling, surface modification, Hydrogel-coated coils, bioactive coils
21.  Coil Embolization for Ruptured Cerebral Aneurysms of 2×3 mm Diameter 
Interventional Neuroradiology  2006;12(Suppl 1):97-100.
Small ruptured cerebral aneurysms, such as those of 2×3 mm diameter, are considered to be difficult to embolize by detachable coils because of the risk of procedural perforation of the aneurysms. We have treated these small aneurysms and report the techniques and pitfalls of these embolizations. Twenty-four patients with ruptured cerebral aneurysms of 2×3 mm diameter were intended for treatment by coil embolization. Before coil embolization, three-dimensional digital subtraction angiography was performed, and the simulation of the volume embolization ratio (VER) was performed in all patients, except for the first basilar artery aneurysm patient. The tip of the microcatheter was steam-shaped several times and was placed on the neck of the aneurysm. A balloon neck remodeling technique was used for two aneurysms. GDC 10 softs and soft SRs were used for the first ten aneurysms, and Ultrasofts were used for the last eleven aneurysms. Out of twenty-four aneurysm embolizations, we aborted the procedure in three cases, because of a failure in catheterization; we performed clipping surgery for these cases. For the first case of a basilar tip aneurysm, the aneurysm was perforated, due to the use of too long a coil and the insertion of the tip of the microcatheter into the aneurysmal dome. Minor infarction occurred in one patient.
The mean VER was 33.9%, and two aneurysms recanalized, and out of these one needed a second embolization. Six months postoperatively, 81% of patients had made in a good recovery or had a moderate disability. We recommend the following techniques to embolize aneurysms of 2×3 mm diameter: the tip of the microcatheter should be stabilized on the aneurysmal neck by steam shaping of the micro-catheter, GDC 10 soft and Ultrasoft should be selected for use, and the simulation of the VER should be performed before embolization to select coils of a suitable length.
PMCID: PMC3387975  PMID: 20569610
subarachnoid haemorrhage, cerebral aneurysm, endovascular surgery
22.  Coil Retrieval Following Embolization of Cerebral Aneurysms 
Interventional Neuroradiology  2004;9(Suppl 1):149-155.
Failed coil embolization of cerebral aneurysms may be occasionally followed by direct surgical treatment. We had 5 patients who underwent coil retrieval and surgical clipping after coil embolization because of periprocedural complications. The patients, ranging in age from 40 to 71, had wide-neck aneurysms located at the anterior communicating artery (AcomA) in 3 patients, the middle cerebral artery (MCA) in 1, and the internal carotidophthalmic artery (IC-Ophthalmic) in 1. They were embolized with Guglielmi detachable coils (GDCs), which had to be retrieved within 8 days because of coil protrusion and migration in 3 patients, aneurysm rupture in 1, and increased mass effect due to coil compaction in 1. Coils were successfully removed with aneurysmotomy or arteriotomy under temporary trapping, aneurysms were then clipped or trapped. Three patients had a good outcome, but one suffered permanent visual disturbance and the other had a motor deficit. Our study revealed that a small AcomA aneurysm had a high risk of complication in a case of complex anatomy of the AcomA-Al-A2 complex with its difficult access. In addition, insufficient packing of the inflow zone in a large and symptomatic aneurysm may cause coil compaction and regrow with increasing mass effect.
The indication and treatment strategy for these aneurysms should be carefully determined.
PMCID: PMC3553471  PMID: 20591245
coil embolization, coil retrieval, cerebral aneurysm
23.  Subarachnoid haemorrhage (spontaneous aneurysmal) 
Clinical Evidence  2009;2009:1213.
Subarachnoid haemorrhage (SAH) may arise spontaneously or as a result of trauma. Spontaneous SAH accounts for about 5% of all strokes. Ruptured aneurysms are the cause of 85% of spontaneous SAH. The most characteristic clinical feature is sudden-onset severe headache. Other features include vomiting, photophobia, and focal neurological deficit or seizures, or both. As the headache may have insidious onset in some cases, or may even be absent, a high degree of suspicion is required to diagnose SAH with less typical presentations.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of surgical treatments for people with confirmed aneurysmal subarachnoid haemorrhage? What are the effects of medical treatments to prevent delayed cerebral ischaemia in people with confirmed aneurysmal subarachnoid haemorrhage? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 6 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: endovascular coiling; surgical clipping; timing of surgery; and oral and intravenous nimodipine.
Key Points
Subarachnoid haemorrhage (SAH) may arise spontaneously or as a result of trauma. Spontaneous SAH accounts for about 5% of all strokes. Ruptured aneurysms are the cause of 85% of spontaneous SAH. This review deals with only spontaneous aneurysmal SAH. Without treatment, mortality rates of about 50% at 1 month after spontaneous aneurysmal SAH have been reported.
Treatment is aimed at prevention of re-bleeding from the same aneurysm. This can be performed by surgical clipping or by endovascular coiling. In people suitable for either procedure, endovascular coiling has lower rates of poor functional outcome compared with surgical clipping, but it is also associated with increased rate of recurrent haemorrhage from the treated aneurysm and a higher rate of re-treatment for the same aneurysm. Most evidence is in small (<11 mm) aneurysms of the anterior circulation. Therefore, the conclusions cannot be applied to all aneurysms (particularly large and giant aneurysms, and aneurysms with broad necks).Factors that should be considered when deciding on the method of treatment include the morphology of the aneurysm, the age and clinical condition of the person, and the presence or absence of a space-occupying intracranial haematoma.
We do not know the optimal timeframe for carrying out surgical clipping or endovascular coiling after aneurysmal SAH. However, early surgery will prevent re-bleeding from the aneurysm, and is preferred in most people.
Oral nimodipine reduces poor outcome (death or dependence), secondary ischaemia, and CT/MRI evidence of infarction after aneurysmal SAH.
We found no evidence on the effects of intravenous nimodipine alone.
PMCID: PMC2907802  PMID: 21726472
24.  Stent-assisted coil emboilization of ruptured intracranial aneurysms: A retrospective multicenter review 
The purpose of this study is to retrospectively review our experience with stent-assisted embolization of patients with an acutely ruptured cerebral aneurysm.
Medical records and imaging were reviewed for 36 patients who underwent stent-assisted embolization of a ruptured cerebral aneurysm.
Seventeen patients (47%) received a preprocedural loading dose of clopidogrel and five patients (14%) received an intraprocedural dose of clopidogrel. The remaining 14 patients (36%) were treated with antiplatelet therapy following the procedure. Six (17%) stent related intraprocedural thromboembolic complications were encountered; four of these resolved (one partial, three complete) following treatment with abciximab and/or heparin during the procedure. Five of the six thromboembolic events occurred in patients who were not pretreated with clopidogrel (P = 0.043). Two patients in this series (6%) had a permanent thrombotic complication resulting in mild hemiparesis in one patient, and hemianopsia in the second. No procedure related hemorrhagic complications occurred in any patient. One patient had a spontaneous parenchymal hemorrhage contralateral to the treated aneurysm discovered 10 days after treatment. Twenty-eight patients (78%) had a Glasgow Outcome Score of 4 or better at discharge. Seven of 21 patients (33%) with angiographic follow-up required further treatment of the coiled aneurysm.
Stent-assisted coil embolization is an option for treatment of ruptured wide neck ruptured aneurysms and for salvage treatment during unassisted embolization of ruptured aneurysms but complications and retreatment rates are higher than for routine clipping or coiling of cerebral aneurysms. Pretreatment with clopidogrel appears effective in reducing thrombotic complications without significant increasing risk of hemorrhagic complications.
PMCID: PMC3424670  PMID: 22937484
Cerebral aneurysm; coil; embolization; stent; stroke subarachnoid hemorrhage
25.  Thromboembolic Events Associated with Coil Protrusion into Parent Arteries after GDC Treatment 
Interventional Neuroradiology  2006;12(Suppl 1):105-111.
Aneurysm embolization using Guglielmi detachable coils(GDC) is gaining acceptance as a viable alternative to surgery in the treatment of cerebral aneurysms. During GDC treatment of cerebral aneurysms, thromboembolic events are the most frequent complications. As risk factors of thromboembolic events, large aneurysms, wide-necked aneurysms, use of the balloon-assisted technique and protruding coils into the parent arteries are previously reported. From March, 1997 till August, 2004, 270 consecutive patients were treated with GDC embolization at our institute. Fourteen (5.2%) patients with 14 aneurysms of these 270 patients presented with protruding coils into the parent vessels.
Twelve aneurysms of these 14 aneurysms were small (diameter <10 mm), and two were large (diameter 15 mm). Nine aneurysms had small necks (neck diameter <4 mm), and five had wide necks (neck diameter >4 mm). The fundus-to-neck ratio ranged from 1.04 to 2.78, with an average of 1.53.
In this series, ten patients (71%) were treated with balloon-remodelling technique because every patient had either a wide-necked aneurysm or complicated morphologic factors. These 14 aneurysms were divided into two groups according to the mode of coil protrusion, loop type and tail type protrusion. The first coil was protruded in five (36%) cases of 14 patients, four of these five cases presented with the loop type protrusion. The last coil was protruded in seven cases (50%), Five of these seven cases presented with the tail type protrusion. Diffusion-weighted imaging abnormalities were found for seven (50%) of 14 patients within 24 hours of the coiling procedures. Three (21%) of 14 patients showed small lesions (<5 mm) in the subcortical white matter at the border zone or perforating regions. In four (29%) patients, large territorial infarctions (> 5 mm) were detected. Symptomatic complications occurred in four (29%) patients, and all of these four patients presented the loop type protrusion. One patient who had small infarctions experienced minimal deficits (slight motor weakness, quadrantic hemianopsia) after six days postprocedure and fully recovered by discharge after stronger systemic heparinization (24000U, for three days), aspirin (100 mg/day) and Ticlopidine (100 mg/day). Three patients who had large territorial infarctions experienced moderate deficits.
Two patients were treated with stronger systemic heparinization and one with Argatroban (60 mg/day, for two days), and following aspirin (100 mg/day) and Ticlopidine (100 mg/day). Finally, two patiens were discharged with permanent minimal deficits (hypoesthesia only) and one with moderate hemiparesis. The infarctions related to the GDC procedures were more common sequelae in wide-necked aneurysms and coil protrusions, especially loop type protrusion. Although permanent neurological deficits were rare, the high rate of thromboembolic events associated with coil protrusion suggest that more aggressive medical treatment should be considered.
PMCID: PMC3387935  PMID: 20569612
coil protrusion, thromboembolic events, DW imaging

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