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1.  Results of Surgical and Nonsurgical Treatment of Aneurysms in a Developing Country 
Stroke Research and Treatment  2011;2011:560831.
Background. The impact of invasive methods of treatment on results in developing countries may differ from that in developed countries. Methods. This is a prospective clinical study of consecutive patients with Subarachnoid Haemorrhage (SAH) admitted to the Ghaem Hospital, Mashhad during the period from 2005 to 2009. The initial diagnosis and investigations were carried out by neurologists. The patients were divided into two groups. One received surgical treatment whilst the other group was managed medically. The decision as to the choice of the method of treatment was made by the neurosurgeons. The initial medical treatment was standardised for all the patients. The rate of complications and mortality was compared in both medical and surgical groups. Results. 120 SAH patients (52% females) with a mean age of 50.6 ± 7 years were evaluated. The angiography revealed the presence of an aneurysm in 62 patients. 63.5% of the patients received medical treatment and 37.5% underwent aneurysmal surgery. Difference of rebleeding rate in the two therapeutic groups was not significant; X2 = .014, P = .91. The effect of rebleeding on mortality was not significant; X2 = 2.54, P = .14. Within 62 SAH patients with cerebral aneurysm, the mortality rate in both therapeutic groups was also not significantly different; X2 = .16, P = .77. Conclusion. There is no significant difference in the mortality rate between the “surgical” and non-“surgical” groups of Iranian patients with SAH. This could be due to delay in performance of surgery in Iranian neurovascular centers.
PMCID: PMC3137994  PMID: 21776362
2.  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
3.  Timing of surgery for supratentorial aneurysmal subarachnoid haemorrhage: report of a prospective study 
Objectives: The debate on the timing of aneurysm surgery after subarachnoid haemorrhage (SAH) pivots on the balance of the temporal risk for fatal rebleeding versus the risk of surgical morbidity when operating early on an acutely injured brain. By following a strict management protocol for SAH, the hypothesis has been tested that in the modern arena of treatment for aneurysmal SAH the timing of surgery to secure supratentorial aneurysms does not affect surgical outcome.
Methods: Over a 6 year period, patients admitted with a diagnosis of SAH to a regional neurosurgical unit have been prospectively studied. All have been on a management protocol in which early transfer and resuscitation has been followed regardless of age and clinical condition. Angiographic investigation and surgery have been pursued in those who have been able to at least flex to pain. A total of 1168 patients (60.7% female, mean age 54.3) with proved SAH were received on median day 1 (86.4% arrived within 3 days) of the ictus. Of these, 784 (67.1%) showed aneurysms on angiography and were prepared for surgery. Those who received surgery for a supratentorial aneurysm within 21 days of the ictus were included in the final analysis (n=550). Patients with an initial negative angiogram, with posterior circulation aneurysms, or aneurysms treated by endovascular means, with aneurysms requiring emergency surgery for space occupying haematomas, with aneurysms which re-bled before surgery, and those who received very late surgery (after 21 days from ictus) were excluded. Surgical outcomes at hospital discharge and after 6 months were assessed using the Glasgow outcome score (GOS). Discharge destination and duration of stay in a neurosurgical ward were also documented. The influence of the timing of surgery (early group day 1–3 postictus, intermediate group day 4–10, or late group day 11–21) was analysed prospectively.
Results: 60.2% of cases fell into the early surgery group, 32.4% into the intermediate group, and 7.5% into the late operated group. Late surgery was due to delays in diagnosis, transfer, and logistic factors, but not clinical decision. The demographic characteristics, site of aneurysm, and clinical condition of the patients at the time of initial medical assessment were balanced in the three surgical timing groups. There was no significant difference in GOS between the surgical timing groups at 6 months (favourable GOS score 4 and 5: 83.2%, 80.5%, and 83.8% respectively; p=0.47, Kruskal-Wallis test). Outcome was favourable in 84% of patients under 65 years, and 70% in those over 65. The discharge destinations (home, referring hospital, nursing home, rehabilitation centre) showed no significant difference between surgical timing groups. There was no significant difference in mean time to discharge after admission to this hospital from the referring hospital (16.2, 16.2, and 14.6 days for early, intermediate, and late groups respectively; p=0.789, Analysis of variance (ANOVA)). As a result, there was reduction in the mean duration of total hospital inpatient stay in favour of the earliest operated patients (mean time 18.1, 22.0, and 28.3 days respectively; p=0.001. ANOVA showed that besides age, the only determinant of surgical outcome and duration of stay was presenting clinical grade (p<0.0005).
Conclusion: The current management of patients presenting with SAH from anterior circulation aneurysms allows early surgery to be followed safely regardless of age. The only independent variables affecting outcome are age and clinical grade at presentation. The timing of surgery did not significantly affect surgical outcome, promoting a policy for early surgery that avoids the known risks of rebleeding and reduces inpatient stay.
PMCID: PMC1737846  PMID: 11909907
4.  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
5.  Combinatorial administration of insulin and vitamin C alleviates the cerebral vasospasm after experimental subarachnoid hemorrhage in rabbit 
BMC Neuroscience  2011;12:77.
Cerebral vasospasm (CVS) is a common serious complication after the spontaneous subarachnoid hemorrhage (SAH). Despite recent advances in medical and surgical treatments, the 30-day mortality rate of SAH remains high, and there is lack of especially effective clinical treatment to alleviate and improve CVS. The present study has investigated the therapeutic effect of insulin and vitamin C on CVS after SAH.
Five days after SAH, there is obvious basilar artery spasm in SAH group, whose average vascular cross-sectional area (233,099 ± 16,750 μm2) is significantly smaller than that in control group (462,128 ± 74,756 μm2), which is also significantly different from those in SAH + insulin group (221,114 ± 43,457 μm2) and SAH + vitamin C group (237,820 ± 21,703 μm2). SAH + insulin + vitamin C group shows no evident vasospasm and maintains a vascular cross-sectional area of 425,530 ± 45,503 μm2, which is significantly different from that in SAH group. Insulin receptor α (InRα) expression is significantly downregulated in the vascular endothelial cells of SAH, SAH + insulin, and SAH + vitamin C groups (P < 0.01) but remains unchanged in vascular endothelial cells of SAH + insulin + vitamin C group (P > 0.05). Five days after SAH, serum and cerebrospinal fluid NO levels in SAH, SAH + insulin, and SAH + vitamin C groups decrease significantly (P < 0.01) compared to that in control group, whereas the reduction is not evident in SAH + insulin + vitamin C group (P > 0.05).
Combinatorial treatment with insulin and vitamin C has effectively relieved the CVS after SAH in rabbit, possibly through increasing the InRα expression and NO level, whereas treatment with insulin or vitamin C alone fails to do so.
PMCID: PMC3160961  PMID: 21801458
6.  An audit of aneurysmal subarachnoid haemorrhage: earlier resuscitation and surgery reduces inpatient stay and deaths from rebleeding. 
OBJECTIVE--To audit the outcome in patients with subarachnoid haemorrhage (SAH) after a change in management strategy. METHODS--A retrospective analysis of patients with aneurysmal subarachnoid haemorrhage over a 20 month period (phase 1) was followed by a prospective analysis of patients presenting during the next 20 months (phase 2) in which a protocol driven management regime of immediate intravenous fluid resuscitation and earlier surgery was pursued. Patients in this phase were grouped into those receiving early (within four days of subarachnoid haemorrhage) and late (after four days of subarachnoid haemorrhage) surgery. In phase 1, 75 out of a total of 92 patients underwent surgery on (median) day 12. From phase 2, 109 patients out of a total of 129 underwent surgery on (median) day 4, 58 of which had their surgery within 4 days of the subarachnoid haemorrhage. Patients in each phase/group were well matched for demographic features, site of aneurysm, and severity of subarachnoid haemorrhage. RESULTS--The surgical morbidity and mortality were no different in the two phases (P < 0.92; chi2 test). The management outcomes in the two phases of the study were also no different (P < 0.52). However, there was a significant reduction in the rebleed rate in patients undergoing surgery within four days of the subarachnoid haemorrhage in phase 2 (P < 0.0001) with an associated trend towards reduced incidence of postoperative ischaemia (P = 0.06) and mortality (P = 0.11). Operating earlier in phase 2 of the trial resulted in a lower total hospital inpatient stay of 15.8 (95% CI 13.1-18.5) days for survivors compared with 25.7 (95% CI 21.6-29.8) days in the late group (P < 0.00001; t test). CONCLUSIONS--surgical morbidity and mortality seemed independent of the timing of aneurysm surgery. Early surgery within four days was associated with a highly significant reduction in rebleed rate, and in the duration of total hospital inpatient stay.
PMCID: PMC1073854  PMID: 8609508
7.  Decompressive Surgery in Patients with Poor-grade Aneurysmal Subarachnoid Hemorrhage: Clipping with Simultaneous Decompression Versus Coil Embolization Followed by Decompression 
In addition to obliterating the aneurysm using clipping or coiling, decompressive surgery for control of rising intracranial pressure (ICP) is thought to be crucial to prevention of adverse outcomes in patients with poor grade aneurysmal subarachnoid hemorrhage (aSAH). We evaluated the clinical characteristics of patients with poor-grade aSAH, and compared outcomes of aneurysmal clipping with simultaneous decompressive surgery to those of coil embolization followed by decompression.
Materials and Methods
In 591 patients with aSAH, 70 patients with H-H grade IV and V underwent decompressive surgery including craniectomy, lobectomy, and hematoma removal. We divided the patients into two groups according to clipping vs. coil embolization (clip group vs. coil group), and analyzed outcomes and mortality.
Aneurysmal clipping was performed in 40 patients and coil embolization was performed in 30 patients. No significant differences in demographics were observed between the two groups. Middle cerebral artery and posterior circulation aneurysms were more frequent in the clip group. Among 70 patients, mortality occurred in 29 patients (41.4%) and 61 patients (87.1%) had a poor score on the Glasgow outcome scale (scores I-III). No significant difference in mortality was observed between the two groups, but a favorable outcome was more frequent in the coil group (p < 0.05).
In this study, despite aggressive surgical and endovascular management for elevated ICP, there were high rates of adverse outcomes and mortality in poor-grade aSAH. Despite poor outcomes overall, early coil embolization followed by decompression surgery could lead to more favorable outcomes in patients with poor-grade aSAH.
PMCID: PMC4205252  PMID: 25340028
Subarachnoid hemorrhage; Intracranial aneurysm; Decompressive craniectomy; Endovascular; Microsurgery; Intracranial hypertension
8.  Benefits of early aneurysm surgery: Southern Iran experience 
Journal of Injury and Violence Research  2012;4(3 Suppl 1): Paper No. 29.
Neurovascular surgery has been practiced in Shiraz, the main referral center of the Southern Iran, for over 30 years. However, because of the development of a subspecialization specialty of neurovascular surgery in Shiraz Department of Neurosurgery the trend has increasingly accelerated in recent years. The present study focuses on the description of techniques we are currently used for early clipping of ruptured intracranial aneurysms in the anterior circulation. Improvements in outcome, mortality and rebleeding rates are also addressed.
Our previous and conventional strategy for management of aneurysmal subarachnoid hemorrhage (SAH) earlier than 2010 was delayed surgery using the pterional approach with an old neuroanesthetic protocol for most of patients. Since 2010, we have shifted to an early surgery program using the lateral supraorbital approach and advanced neuroanesthesia (the Helsinki protocol) for nearly all patients. The outcome data and preliminary results are presented here.
Mortality rate, which was about 40% in conventional approach, is now reported to be about 14%, regardless of the significant increase in the number of high grade patients. Furthermore, in the conventional method, acute phase of rebleeding occurred in 10.5% of patients, while in this new protocol the incidence is 1-2%, which occurs most frequently in patients with a delayed refer more than 72 hours for surgery.
The establishment of the early-surgery approach for ruptured anterior circulation aneurysms through the lateral supraorbital approach along with specific anesthetic protocol has resulted in significant improvement of morbidity, mortality and rebleeding rates in our department.
Neurovascular surgery, Early-surgery approach, Aneurysmal subarachnoid hemorrhage
PMCID: PMC3571555
9.  Subarachnoid Hemorrhage with Negative Baseline Digital Subtraction Angiography: Is Repeat Digital Subtraction Angiography Necessary? 
Patients with negative initial digital subtraction angiography (DSA) are at significant risk for re-bleeding, which can lead to severe disability and death. The purpose of this study was to evaluate the necessity of repeat DSA in subgroups of patients with subarachnoid hemorrhage (SAH) with negative initial DSA.
A total of 904 spontaneous SAH patients were admitted to our department between May 2005 and May 2012. Twenty eight patients were selected for inclusion in this study because repeated DSA performed due to the etiology of the SAH could not be demonstrated on the initial DSA. According to the SAH pattern on initial computed tomography scans, patients were divided into perimesencephalic nonaneurysmal SAH (PN-SAH) and non PN-SAH (NPN-SAH) groups. Repeat DSA was performed in all patients, and two of these patients underwent a third DSA.
Of the 904 patients, 28 patients (3.1%) had no vascular abnormality on initial DSA. Sixteen PN-SAH patients underwent a repeat DSA; however, no aneurysms were found. In contrast, 12 patients with NPN-SAH underwent repeat DSA, with detection of two cerebral aneurysms. Overall, the false-negative rate of the initial DSA was 7.1% (2/28 patients). No significant differences in false-negative results on initial DSA were observed between the PN-SAH and NPN-SAH groups.
In the line with the results of the current study, we should be highly suspicious of patients with a nonaneurysmal SAH, especially those with a NPN-SAH pattern. In order to reduce the morbidity and mortality resulting from a misdiagnosis, repeat DSA is necessary, and exclusion of an aneurysm is important.
PMCID: PMC3491216  PMID: 23210049
Subarachnoid hemorrhage; Digital subtraction angiography; Aneurysm
10.  Modern Approach to SAH in Intensive Care Unit (ICU) 
Interventional Neuroradiology  2008;14(Suppl 1):13-16.
SAH is still a severe pathology carrying a high risk of death or severe neurological morbidity. New diagnostic, monitoring and therapeutic methods are available for the detection and treatment of vasospasm. This includes transcranial Doppler, CT or MRI perfusion scan, protein S100B dosage, cerebral blood flow monitoring at the bedside. Medical treatment of vasospasm relies on increased blood pressure and dobutamine.
Emergency balloon angioplasty or arterial vasodilator infusion is mandatory in case of vasospam-induced ischemic deficit.
Despite several medical advances in the treatment of subarachnoid haemorrhage (SAH) due to aneurysm rupture, particularly interventional neuroradiology, it remains a potentially devastating illness with a high mortality rate. The most important determinant of outcome is neurologic state on arrival in the hospital, assessed with the World Federation of Neurological Surgeons (WFNS) scale (table 1)1. Delayed cerebral ischemia due to cerebral vasospasm and medical complications due to SAH have both a major impact on outcome.
The cooperative aneurysm study, including 457 patients with SAH, showed that the proportion of deaths from medical complications (23%) was comparable with the proportion of deaths attributed to the direct effects of the initial hemorrhage (19%), rebleeding (22%), and vasospasm (23%) after aneurysmal rupture (2). Thus, the aim of ICU management is to prevent or to limit the consequences of vasospasm and to treat medical complications that can have an adverse effect on the brain. Table 1Classification of the World Federation of Neurological Surgeons (WFNS)GradeGlasgow Coma ScoreMotor deficitGOS 1-3 at 6 months (%)*I  15     absent13II 13-14absent20III13-14present42IV7-12  present or absent51V 3-6   present or absent68GOS: Glasgow Outcome Score (1-3 : dead, persistent vegetative state or severe disability)
PMCID: PMC3328047  PMID: 20557769
subarachnoid haemorrhage, vasospasm, intensive care unit
11.  Intracranial aneurysms: optimized diagnostic tools call for thorough interdisciplinary treatment strategies 
Objective: Intracranial aneurysms (IAs) require deliberately selected treatment strategies as they are incrementally found prior to rupture and deleterious subarachnoid haemorrhage (SAH). Multiple and recurrent aneurysms necessitate both neurointerventionalists and neurosurgeons to optimize aneurysmal occlusion in an interdisciplinary effort. The present study was conducted to condense essential strategies from a single neurovascular centre with regard to the lessons learned.
Method: Medical charts of 321 consecutive patients treated for IAs at our centre from September 2008 until December 2010 were retrospectively analysed for clinical presentation of the aneurysms, multiplicity and treatment pathways. In addition, a selective Medline search was performed.
Results: A total of 321 patients with 492 aneurysms underwent occlusion of their symptomatic aneurysm: 132 (41.1%) individuals were treated surgically, 189 (58.2%) interventionally; 138 patients presented with a SAH, of these 44.2% were clipped and 55.8% were coiled. Aneurysms of the middle cerebral artery were primarily occluded surgically (88), whereas most of the aneurysms of the internal carotid artery and anterior communicating artery (114) were treated endovascularly. Multiple aneurysms (range 2–5 aneurysms/individual) were diagnosed in 98 patients (30.2%). During the study period 12 patients with recurrent aneurysms were allocated to another treatment modality (previously clip to coil and vice versa).
Conclusions: Our data show that successful interdisciplinary occlusion of IAs is based on both neurosurgical and neurointerventional therapy. In particular, multiple and recurrent aneurysms require tailored individual approaches to aneurysmal occlusion. This is achieved by a consequent interdisciplinary pondering of the optimal strategy to occlude IAs in order to prevent SAH.
PMCID: PMC3187677  PMID: 22010040
intracranial aneurysms; clipping; coiling; interdisciplinary treatment
12.  Depression and post-traumatic stress disorder after aneurysmal subarachnoid haemorrhage in relation to lifetime psychiatric morbidity 
British Journal of Neurosurgery  2011;25(6):693-700.
Little is known about the roles that lifetime psychiatric disorders play in psychiatric and vocational outcomes of aneurysmal subarachnoid haemorrhage (SAH).
Materials and methods
Eighty-three SAH patients without apparent cognitive dysfunction were assessed using the Structured Clinical Interview for DSM-IV axis I disorders (SCID-I) after their SAH. Diagnoses were assessed for three time periods, ‘lifetime before SAH', ‘12 months before SAH’ and ‘7 months after SAH'.
Forty-five percentage of patients with SAH reported at least one lifetime psychiatric disorder. After SAH, symptoms of depression and/or post-traumatic stress disorder (PTSD) were seen in 41%, more often in those with a psychiatric history prior to SAH (p = 0.001). In logistic regressions, depression after SAH was associated with a lifetime history of major depression, or of anxiety or substance use disorder, as well as with lifetime psychiatric comorbidity. Subsyndromal or full PTSD was predicted by a lifetime history of major depression. After the SAH, 18 patients (22%) had received psychotropic medication and/or psychological treatment, 13 of whom had a disorder. Those with a lifetime history of major depression or treatment with antidepressants before SAH had lower return to work rates than others (p = 0.019 and p = 0.031, respectively). This was also true for those with symptoms of depression and/or PTSD, or with antidepressant treatment after SAH 0 = 0.001 and p = 0.031, respectively).
Depression and PTSD are present in a substantial proportion of patients 7 months after SAH. Those with a history of psychiatric morbidity, any time before the SAH, are more at risk and also constitute a risk group for difficulties in returning to work.
PMCID: PMC3233275  PMID: 21591856
Subarachnoid haemorrhage; mental disorders; depression; stress disorders; post-traumatic
13.  Intraoperative microvascular Doppler ultrasonography in cerebral aneurysm surgery 
OBJECTIVES—Outcome of surgical treatment of cerebral aneurysms may be severely compromised by local cerebral ischaemia or infarction resulting from the inadvertent occlusion of an adjacent vessel by the aneurysm clip, or by incomplete aneurysm closure. It is therefore mandatory to optimise clip placement in situ to reduce the complication rate. The present study was performed to investigate the reliability of intraoperative microvascular Doppler ultrasonography (MDU) in cerebral aneurysm surgery, and to assess the impact of this method on the surgical procedure itself.
METHODS—Seventy five patients (19 men, 56 women, mean age 54.8 years, range 22-84 years) with 90 saccular cerebral aneurysms were evaluated. Blood flow velocities in the aneurysmal sac and in the adjacent vessels were determined by MDU before and after aneurysm clipping. The findings of MDU were analysed and compared with those of visual inspection of the surgical site and of postoperative angiography. Analysis was also made of the cases in which the clip was repositioned due to MDU findings.
RESULTS—A relevant stenosis of an adjacent vessel induced by clip positioning that had escaped detection by visual inspection was identified by Doppler ultrasonography in 17 out of 90 (18.9%) aneurysms. In addition, Doppler ultrasound demonstrated a primarily unoccluded aneurysm in 11 out of 90 (12.2%) patients. The aneurysm clip was repositioned on the basis of the MDU findings in 26 out of 90 (28.8%) cases. In middle cerebral artery (MCA) aneurysms, the MDU results were relevant to the surgical procedure in 17out of 44 (38.6%) cases. Whereas with aneurysms of the anterior cerebral artery significant findings occurred in only five of 32cases (15.6%; p<0.05). The clip was repositioned on the basis of the MDU results in 18 out of 50 (36%) aneurysms in patients with subarachnoid haemorrhage (SAH) grade I-V compared with only eight out of 40 (20%) aneurysms in patients without SAH (p<0.05).
CONCLUSIONS—MDU should be used routinely in cerebral aneurysm surgery, especially in cases of MCA aneurysms and after SAH. Present data show that a postoperative angiography becomes superfluous whenever there is good visualisation of the "working site" and MDU findings are clear.

PMCID: PMC1760608  PMID: 10601397
14.  Predisposing Factors Related to Shunt-Dependent Chronic Hydrocephalus after Aneurysmal Subarachnoid Hemorrhage 
Hydrocephalus is a common sequelae of aneurysmal subarachnoid hemorrhage (SAH) and patients who develop hydrocephalus after SAH typically have a worse prognosis than those who do not. This study was designed to identify factors predictive of shunt-dependent chronic hydrocephalus among patients with aneurysmal SAH, and patients who require permanent cerebrospinal fluid diversion.
Seven-hundred-and-thirty-four patients with aneurysmal SAH who were treated surgically between 1990 and 2006 were retrospectively studied. Three stages of hydrocephalus have been categorized in this paper, i.e., acute (0-3 days after SAH), subacute (4-13 days after SAH), chronic (≥14 days after SAH). Criteria indicating the occurrence of hydrocephalus were the presence of significantly enlarged temporal horns or ratio of frontal horn to maximal biparietal diameter more than 30% in computerized tomography.
Overall, 66 of the 734 patients (8.9%) underwent shunting procedures for the treatment of chronic hydrocephalus. Statistically significant associations among the following factors and shunt-dependent chronic hydrocephalus were observed. (1) Increased age (p < 0.05), (2) poor Hunt and Hess grade at admission (p < 0.05), (3) intraventricular hemorrhage (p < 0.05), (4) Fisher grade III, IV at admission (p < 0.05), (5) radiological hydrocephalus at admission (p < 0.05), and (6) post surgery meningitis (p < 0.05) did affect development of chronic hydrocephalus. However the presence of intracerebral hemorrhage, multiple aneurysms, vasospasm, and gender did not influence on the development of shunt-dependent chronic hydrocephalus. In addition, the location of the ruptured aneurysms in posterior cerebral circulation did not correlate with the development of shunt-dependent chronic hydrocephalus.
Hydrocephalus after aneurysmal SAH seems to have a multifactorial etiology. Understanding predisposing factors related to the shunt-dependent chronic hydrocephalus may help to guide neurosurgeons for better treatment outcomes.
PMCID: PMC2588257  PMID: 19096639
Subarachnoid hemorrhage; Ventriculoperitoneal shunt; Chronic hydrocephalus; Related factor
15.  Progesterone Attenuates Experimental Subarachnoid Hemorrhage-Induced Vasospasm by Upregulation of Endothelial Nitric Oxide Synthase via Akt Signaling Pathway 
BioMed Research International  2014;2014:207616.
Cerebral vasospasm is the leading cause of mortality and morbidity in patients after aneurysmal subarachnoid hemorrhage (SAH). However, the mechanism and adequate treatment of vasospasm are still elusive. In the present study, we evaluate the effect and possible mechanism of progesterone on SAH-induced vasospasm in a two-hemorrhage rodent model of SAH. Progesterone (8 mg/kg) was subcutaneously injected in ovariectomized female Sprague-Dawley rats one hour after SAH induction. The degree of vasospasm was determined by averaging the cross-sectional areas of basilar artery 7 days after first SAH. Expressions of endothelial nitric oxide synthase (eNOS) and phosphorylated Akt (phospho-Akt) in basilar arteries were evaluated. Prior to perfusion fixation, there were no significant differences among the control and treated groups in physiological parameters recorded. Progesterone treatment significantly (P < 0.01) attenuated SAH-induced vasospasm. The SAH-induced suppression of eNOS protein and phospho-Akt were relieved by progesterone treatment. This result further confirmed that progesterone is effective in preventing SAH-induced vasospasm. The beneficial effect of progesterone might be in part related to upregulation of expression of eNOS via Akt signaling pathway after SAH. Progesterone holds therapeutic promise in the treatment of cerebral vasospasm following SAH.
PMCID: PMC4052693  PMID: 24949428
16.  Hyponatremia after aneurysmal subarachnoid hemorrhage: Implications and outcomes 
Hyponatremia is the most common electrolyte abnormality seen in patients with aneurysmal SAH. Clinically significant hyponatremia (Serum Sodium <131 mEq/L) which needs treatment, has been redefined recently and there is a paucity of outcome studies based on this. This study aims to identify the mean Serum Sodium (S.Na+) level and its duration among inpatients with SAH and to identify the relationship between hyponatremia and the outcome status of patients undergoing surgery for SAH.
Materials and Methods:
This outcome study is undertaken in the department of neurosurgery, The Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala. Medical records of all patients with SAH from 1st January to 31st July 2010 were reviewed. Preoperative status was assessed using World Federation of Neurosurgical Societies (WFNS) grading system. Discharge status was calculated using the Glasgow outcome score scale.
Fifty nine patients were included in the study and 53 (89.8%) of them have undergone surgical treatment. Hyponatremia was observed in 22 of 59 patients (37%). The mean Sodium level of hyponatremic patients was 126.97 mEq/L for a median duration of two days. Glasgow outcome score was good in 89.8% of patients. We lost two patients, one of whom had hyponatremia and vasospasm.
Hyponatremia is significantly associated with poor outcome in patients with SAH. Anticipate hyponatremia in patients with aneurysmal subarachnoid hemorrhage, timely detect and appropriately treat it to improve outcome. It is more common in patients who are more than 50 years old and whose aneurysm is in the anterior communicating artery. Our comprehensive monitoring ensured early detection and efficient surgical and nursing management reduced morbidity and mortality.
PMCID: PMC3579037  PMID: 23546343
Aneurysmal subarachnoid hemorrhage; hyponatremia; neurosurgical; outcome
17.  Aneurysmal Rebleeding : Factors Associated with Clinical Outcome in the Rebleeding Patients 
Aneurysmal rebleeding is a major cause of death and disability. The aim of this study is to investigate the incidence of rebleeding, and the factors related with patient's outcome.
During a period of 12 years, from September 1995 to August 2007, 492 consecutive patients with aneurysmal subarachnoid hemorrhage (SAH) underwent surgery at our institution. We reviewed the patient's clinical records, radiologic findings, and possible factors inducing rebleeding. Also, we statistically analyzed various factors between favorable outcome group (FG) and unfavorable outcome group (UG) in the rebleeding patients.
Rebleeding occurred in 38 (7.7%) of 492 patients. Male gender, location of aneurysm (anterior communicating artery) were statistically significant between rebleeding group and non-rebleeding group (p = 0.01 and p = 0.04, respectively). Rebleeding occurred in 26 patients (74.3%) within 2 hours from initial attack. There were no statistically significant factors between FG and UG. However, time interval between initial SAH to rebleeding was shorter in the UG compared to FG (FG = 28.71 hrs, UG = 2.9 hrs).
Rebleeding occurs more frequently in the earlier period after initial SAH. Thus, careful management in the earlier period after SAH and early obliteration of aneurysm will be necessary.
PMCID: PMC2836446  PMID: 20224710
Aneurysm; Outcome; Rebleeding; Subarachnoid hemorrhage
18.  Endovascular Repair of Descending Thoracic Aortic Aneurysm 
Executive Summary
To conduct an assessment on endovascular repair of descending thoracic aortic aneurysm (TAA).
Clinical Need
Aneurysm is the most common condition of the thoracic aorta requiring surgery. Aortic aneurysm is defined as a localized dilatation of the aorta. Most aneurysms of the thoracic aorta are asymptomatic and incidentally discovered. However, TAA tends to enlarge progressively and compress surrounding structures causing symptoms such as chest or back pain, dysphagia (difficulty swallowing), dyspnea (shortness of breath), cough, stridor (a harsh, high-pitched breath sound), and hoarseness. Significant aortic regurgitation causes symptoms of congestive heart failure. Embolization of the thrombus to the distal arterial circulation may occur and cause related symptoms. The aneurysm may eventually rupture and create a life-threatening condition.
The overall incidence rate of TAA is about 10 per 100,000 person-years. The descending aorta is involved in about 30% to 40% of these cases.
The prognosis of large untreated TAAs is poor, with a 3-year survival rate as low as 25%. Intervention is strongly recommended for any symptomatic TAA or any TAA that exceeds twice the diameter of a normal aorta or is 6 cm or larger. Open surgical treatment of TAA involves left thoracotomy and aortic graft replacement. Surgical treatment has been found to improve survival when compared with medical therapy. However, despite dramatic advances in surgical techniques for performing such complex operations, operative mortality from centres of excellence are between 8% and 20% for elective cases, and up to 50% in patients requiring emergency operations. In addition, survivors of open surgical repair of TAAs may suffer from severe complications. Postoperative or postprocedural complications of descending TAA repair include paraplegia, myocardial infarction, stroke, respiratory failure, renal failure, and intestinal ischemia.
The Technology
Endovascular aortic aneurysm repair (EVAR) using a stent graft, a procedure called endovascular stent-graft (ESG) placement, is a new alternative to the traditional surgical approach. It is less invasive, and initial results from several studies suggest that it may reduce mortality and morbidity associated with the repair of descending TAAs.
The goal in endovascular repair is to exclude the aneurysm from the systemic circulation and prevent it from rupturing, which is life-threatening. The endovascular placement of a stent graft eliminates the systemic pressure acting on the weakened wall of the aneurysm that may lead to the rupture. However, ESG placement has some specific complications, including endovascular leak (endoleak), graft migration, stent fracture, and mechanical damage to the access artery and aortic wall.
The Talent stent graft (manufactured by Medtronic Inc., Minneapolis, MN) is licensed in Canada for the treatment of patients with TAA (Class 4; licence 36552). The design of this device has evolved since its clinical introduction. The current version has a more flexible delivery catheter than did the original system. The prosthesis is composed of nitinol stents between thin layers of polyester graft material. Each stent is secured with oversewn sutures to prevent migration.
Review Strategy
To compare the effectiveness and cost-effectiveness of ESG placement in the treatment of TAAs with a conventional surgical approach
To summarize the safety profile and effectiveness of ESG placement in the treatment of descending TAAs
Measures of Effectiveness
Primary Outcome
Mortality rates (30-day and longer term)
Secondary Outcomes
Technical success rate of introducing a stent graft and exclusion of the aneurysm sac from systemic circulation
Rate of reintervention (through surgical or endovascular approach)
Measures of Safety
Complications were categorized into 2 classes:
Those specific to the ESG procedure, including rates of aneurysm rupture, endoleak, graft migration, stent fracture, and kinking; and
Those due to the intervention, either surgical or endovascular. These include paraplegia, stroke, cardiovascular events, respiratory failure, real insufficiency, and intestinal ischemia.
Inclusion Criteria
Studies comparing the clinical outcomes of ESG treatment with surgical approaches
Studies reporting on the safety and effectiveness of the ESG procedure for the treatment of descending TAAs
Exclusion Criteria
Studies investigating the clinical effectiveness of ESG placement for other conditions such as aortic dissection, aortic ulcer, and traumatic injuries of the thoracic aorta
Studies investigating the aneurysms of the ascending and the arch of the aorta
Studies using custom-made grafts
Literature Search
The Medical Advisory Secretariat searched The International Network of Agencies for Health Technology Assessment and the Cochrane Database of Systematic Reviews for health technology assessments. It also searched MEDLINE, EMBASE, Medline In-Process & Other Non-Indexed Citations, and Cochrane CENTRAL from January 1, 2000 to July 11, 2005 for studies on ESG procedures. The search was limited to English-language articles and human studies.
One health technology assessment from the United Kingdom was identified. This systematic review included all pathologies of the thoracic aorta; therefore, it did not match the inclusion criteria. The search yielded 435 citations; of these, 9 studies met inclusion criteria.
Summary of Findings
The results of a comparative study found that in-hospital mortality was not significantly different between ESG placement and surgery patients (2 [4.8%] for ESG vs. 6 [11.3%] for surgery).
Pooled data from case series with a mean follow-up ranging from 12 to 38 months showed a 30-day mortality and late mortality rate of 3.9% and 5.5%, respectively. These rates are lower than are those reported in the literature for surgical repair of TAA.
Case series showed that the most common cause of early death in patients undergoing endovascular repair is aortic rupture, and the most common causes of late death are cardiac events and aortoesophageal or aortobronchial fistula.
Technical Success Rate
Technical success rates reported by case series are 55% to 100% (100% and 94.4% in 2 studies with all elective cases, 89% in a study with 5% emergent cases, and 55% in a study with 42% emergent cases).
Surgical Reintervention
In the comparative study, 3 (7.1%) patients in the ESG group and 14 (26.5%) patients in the surgery group required surgical reintervention. In the ESG group, the reasons for surgical intervention were postoperative bleeding at the access site, paraplegia, and type 1 endoleak. In the surgical group, the reasons for surgery were duodenal perforation, persistent thoracic duct leakage, false aneurysm, and 11 cases of postoperative bleeding.
Pooled data from case series show that 9 (2.6%) patients required surgical intervention. The reasons for surgical intervention were endoleak (3 cases), aneurysm enlargement and suspected infection (1 case), aortic dissection (1 case), pseudoaneurysm of common femoral artery (1 case), evacuation of hematoma (1 case), graft migration (1 case), and injury to the access site (1 case).
Endovascular Revision
In the comparative study, 3 (7.1%) patients required endovascular revision due to persistent endoleak.
Pooled data from case series show that 19 (5.3%) patients required endovascular revision due to persistent endoleak.
Graft Migration
Two case series reported graft migration. In one study, 3 proximal and 4 component migrations were noted at 2-year follow-up (total of 5%). Another study reported 1 (3.7%) case of graft migration. Overall, the incidence of graft migration was 2.6%.
Aortic Rupture
In the comparative study, aortic rupture due to bare stent occurred in 1 case (2%). The pooled incidence of aortic rupture or dissection reported by case series was 1.4%.
Postprocedural Complications
In the comparative study, there were no statistically significant differences between the ESG and surgery groups in postprocedural complications, except for pneumonia. The rate of pneumonia was 9% for those who received an ESG and 28% for those who had surgery (P = .02). There were no cases of paraplegia in either group. The rate of other complications for ESG and surgery including stroke, cardiac, respiratory, and intestinal ischemia were all 5.1% for ESG placement and 10% for surgery. The rate for mild renal failure was 16% in the ESG group and 30% in the surgery group. The rate for severe renal failure was 11% for ESG placement and 10% for surgery.
Pooled data from case series show the following postprocedural complication rates in the ESG placement group: paraplegia (2.2%), stroke (3.9%), cardiac (2.9%), respiratory (8.7%), renal failure (2.8%), and intestinal ischemia (1%).
Time-Related Outcomes
The results of the comparative study show statistically significant differences between the ESG and surgery group for mean operative time (ESG, 2.7 hours; surgery, 5 hours), mean duration of intensive care unit stay (ESG, 11 days; surgery, 14 days), and mean length of hospital stay (ESG, 10 days; surgery, 30 days).
The mean duration of intensive care unit stay and hospital stay derived from case series is 1.6 and 7.8 days, respectively.
Ontario-Based Economic Analysis
In Ontario, the annual treatment figures for fiscal year 2004 include 17 cases of descending TAA repair procedures (source: Provincial Health Planning Database). Fourteen of these have been identified as “not ruptured” with a mean hospital length of stay of 9.23 days, and 3 cases have been identified as “ruptured,” with a mean hospital length of stay of 28 days. However, because one Canadian Classification of Health Interventions code was used for both procedures, it is not possible to determine how many were repaired with an EVAR procedure or with an open surgical procedure.
Hospitalization Costs
The current fiscal year forecast of in-hospital direct treatment costs for all in-province procedures of repair of descending TAAs is about $560,000 (Cdn). The forecast in-hospital total cost per year for in-province procedures is about $720,000 (Cdn). These costs include the device cost when the procedure is EVAR (source: Ontario Case Costing Initiative).
Professional (Ontario Health Insurance Plan) Costs
Professional costs per treated patient were calculated and include 2 preoperative thoracic surgery or EVAR consultations.
The professional costs of an EVAR include the fees paid to the surgeons, anesthetist, and surgical assistant (source: fee service codes). The procedure was calculated to take about 150 minutes.
The professional costs of an open surgical repair include the fees of the surgeon, anesthetist, and surgical assistant. Open surgical repair was estimated to take about 300 minutes.
Services provided by professionals in intensive care units were also taken into consideration, as were the costs of 2 postoperative consultations that the patients receive on average once they are discharged from the hospital. Therefore, total Ontario Health Insurance Plan costs per treated patient treated with EVAR are on average $2,956 (ruptured or not ruptured), as opposed to $5,824 for open surgical repair and $6,157 for open surgical repair when the aneurysm is ruptured.
Endovascular stent graft placement is a less invasive procedure for repair of TAA than is open surgical repair.
There is no high-quality evidence with long-term follow-up data to support the use of EVAR as the first choice of treatment for patients with TAA that are suitable candidates for surgical intervention.
However, short- and medium-term outcomes of ESG placement reported by several studies are satisfactory and comparable to surgical intervention; therefore, for patients at high risk of surgery, it is a practical option to consider. Short- and medium-term results show that the benefit of ESG placement over the surgical approach is a lower 30-day mortality and paraplegia rate; and shorter operative time, ICU stay, and hospital stay.
PMCID: PMC3382300  PMID: 23074469
19.  Insurance Status Is Associated with Treatment Allocation and Outcomes after Subarachnoid Hemorrhage 
PLoS ONE  2014;9(8):e105124.
Subarachnoid hemorrhage (SAH) is a particularly devastating type of stroke which is responsible for one third of all stroke-related years of potential life lost before age 65. Surgical treatment has been shown to decrease both morbidity and mortality after subarachnoid hemorrhage. We hypothesized that payer status other than private insurance is associated with lower allocation to surgical treatment for patients with SAH and worse outcomes.
We examined the association between insurance type and surgical treatment allocation and outcomes for patients with SAH while adjusting for a wide range of patient and hospital factors. We analyzed the Nationwide Inpatient Sample hospital discharge database using survey procedures to produce weighted estimates representative of the United States population.
We studied 21047 discharges, representing a weighted estimate of 102595 patients age 18 and above with a discharge diagnosis of SAH between 2003 and 2008.
Multivariable logistic and generalized linear regression analyses were used to assess for any associations between insurance status and surgery allocation and outcomes.
Main Results
Despite the benefits of surgery 66% of SAH patients did not undergo surgical treatment to prevent rebleeding. Mortality was more than twice as likely for patients with no surgical treatment compared to those who received surgery. Medicare patients were significantly less likely to receive surgical treatment.
Nearly two thirds of patients with SAH don't receive operative care, and Medicare patients were significantly less likely to receive surgical treatment than other patients. Bias against the elderly and those with chronic illness and disability may play a part in these findings. A system of regionalized care for patients presenting with SAH may reduce disparities and improve appropriate allocation to surgical care and deserves prospective study.
PMCID: PMC4139299  PMID: 25141303
20.  Emergent Clipping without Prophylactic Decompressive Craniectomy in Patients with a Large Aneurysmal Intracerebral Hematoma 
Many vascular neurosurgeons tend to remove bone flap in patients with large aneurysmal intracerebral hematomas (ICH). However, relatively little work has been done regarding the effectiveness of prophylactic decompressive craniectomy in a patient with a large aneurysmal ICH.
Large ICH was defined as hematoma when its volume exceeded 25 mL, ipsilateral to aneurysms. The patients were divided into two groups; aneurysmal subarachnoid hemorrhage (SAH) associated with large ICH, January, 1994 - December, 1999 (Group A, 41 patients), aneurysmal SAH associated with large ICH, January, 2000 - May, 2005 (Group B, 27 patients). Demographic and clinical variables including age, sex, hypertension, vasospasm, rebleeding, Hunt-Hess grade, aneurysm location, aneurysm size, and outcome were compared between two groups, and also compared between craniotomy and craniectomy patients in Group A.
In Group A, 21 of 41 patients underwent prophylactic decompressive craniectomy. In Group B, only two patients underwent craniectomy. Surgical outcome in Group A (good 23, poor 18) was statistically not different from Group B (good 15, poor 12). Surgical outcomes between craniectomy (good 12, poor 9) and craniotomy cases (good 11, poor 9) in Group A were also comparable.
We recommend that a craniotomy can be carried out safely without prophylactic craniectomy in patients with a large aneurysmal ICH if intracranial pressure is controllable with hematoma evacuation.
PMCID: PMC2615137  PMID: 19137078
Clipping; Craniectomy; Aneurysm; Intracerebral hematoma
21.  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
22.  Effect of rebleeding on the course and incidence of vasospasm after subarachnoid hemorrhage 
Neurology  2012;78(1):31-37.
Rebleeding of an aneurysm is a leading cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Whereas numerous studies have demonstrated the risk factors associated with rebleeding, few data on complications of rebleeding, including its effect on the development of delayed cerebral ischemia (DCI), are available.
A nested case-control study was performed on patients with rebleeding and control subjects matched for modified Fisher scale, Hunt-Hess grade, age, and sex previously entered into a prospective database. Rebleeding was defined as new hemorrhage apparent on repeat CT with or without new symptoms. Incidence and time course of DCI and hospital complications were compared. A secondary analysis of DCI and hospital complications was also performed on subjects surviving to postbleed day 7.
We identified 120 patients with rebleeding and 359 control subjects from 1996 to 2011. The rebleeding rate was 8.6%. In both the primary and secondary analyses, there was no difference in the incidence of DCI or its time course (29% vs 27%, p = 0.6; 7 ± 5 vs 7 ± 6 days, p = 0.9 for primary analysis; 39% vs 31%, p = 0.1, 7 ± 5 vs 7 ± 6 days, p = 0.6 for the secondary analysis). In a multivariate logistic regression model, rebleeding was associated with the complications of hyponatremia, respiratory failure, and hydrocephalus. Patients with rebleeding had higher rates of mortality, brain death, and poor outcomes.
Rebleeding after SAH is associated with multiple medical and neurologic complications, resulting in higher morbidity and mortality, but is not associated with change of incidence or timing of DCI.
PMCID: PMC3466499  PMID: 22170890
23.  A Multicenter prospective study of poor-grade aneurysmal subarachnoid hemorrhage (AMPAS): observational registry study 
BMC Neurology  2014;14:86.
Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with very high mortality and morbidity. Our limited knowledge on predictors of long-term outcome in poor-grade patients with aSAH definitively managed comes from retrospective and prospective studies of small case series of patients in single center. The purpose of the AMPAS is to determine the long-term outcomes in poor-grade patients with different managements within different time after aSAH, and identify the independent predictors of the outcome that help guide the decision on definitive management.
The AMPAS study is a prospective, multicenter, observational registry of consecutive hospitalized patients with poor grade aSAH (WFNS grade IV and V). The aim is to enroll at least 226 poor-grade patients in 11 high-volume medical centers (eg, >150 aSAH cases per year) affiliated to different universities in China. This study will describe poor grade patients and aneurysm characteristics, treatment strategies (modality and time of definitive management), hospitalization complications and outcomes evolve over time. The definitive management is ruptured aneurysm treatment. Outcomes at 3, 6, 12 months after the management were measured using the Glasgow Outcome Scale and the Modified Rankin Scale.
The AMPAS is the first prospective, multicenter, observational registry of poor grade aSAH with any management. This study will contribute to a better understanding of significant predictors of outcome in poor grade patients and help guide future treatment of the worst patients after aSAH.
Trial registration
Chinese Clinical Trial Registry: ChiCTR-TNRC-10001041.
PMCID: PMC3997185  PMID: 24742248
Aneurysmal subarachnoid hemorrhage; Poor-grade; Definitive management; Outcome; Predicators
24.  Carotid ligation: what happens in the long term? 
The authors reviewed a consecutive series of 115 patients who underwent common carotid ligation during the period 1954-1984. Average follow-up was 10 years. Seventy-three (63%) patients presented following a subarachnoid haemorrhage (SAH) and 42 (36%) presented with the mass effect of an unruptured aneurysm. Thirty-nine (34%) patients were lost to follow-up of whom 27 had had a previous SAH. Forty-six (63%) of the 73 patients traced had suffered a SAH and amongst this group, 11 patients (24%) died from a proven or suspected recurrent haemorrhage within 10 years of ligation. The fatal recurrent haemorrhage rate was, therefore, 2.4%/year. Thirty (71%) of the 42 patients who presented with unruptured aneurysms were traced. Seven of these (23%) died: two following haemorrhage, 1 year and 16 years after carotid ligation and three patients died as a direct consequence of carotid ligation. Check angiographic studies were available for 55 patients following carotid ligation, a mean of 8.4 years after the procedure. Thirteen were conventional angiograms and 42 were intravenous angiograms obtained using the digital subtraction technique. Seventy-six per cent of the aneurysms visualised on the initial studies were either smaller or had apparently disappeared. Only four new aneurysms were detected and in two of these instances, the initial angiographic studies had been incomplete. The authors conclude that the annual rate of fatal recurrent haemorrhage from an intracranial aneurysm following common carotid ligation is of a similar magnitude to that of the natural history of conservatively managed ruptured intracranial aneurysms. Moreover, carotid ligation apparently does not prevent haemorrhage from a previously unruptured aneurysm and the procedure appears to carry a significant morbidity and mortality, even in patients with an unruptured aneurysm.
PMCID: PMC1028950  PMID: 3746325
25.  Correlation between plasma total nitric oxide levels and cerebral vasospasm and clinical outcome in patients with aneurysmal subarachnoid hemorrhage in Indian population 
Cerebral vasospasm remains a major cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Reduced bioavailability of nitric oxide has been associated with the development of cerebral vasospasm after aSAH. Such data is not available in Indian population.
The objective of the study was to measure the plasma total nitric oxide (nitrite and nitrate-NOx) level in aSAH patients and healthy controls treated at a tertiary hospital in India and to investigate a possible association between plasma total nitric oxide level and cerebral vasospasm and clinical outcome following treatment in patients with aSAH.
Settings and Design:
A case-control study of aSAH patients was conducted. Plasma total NOx levels were estimated in aSAH patients with and without vasospasm and compared the results with NOx levels in healthy individuals.
Materials and Methods:
aSAH in patients was diagnosed on the basis of clinical and neuro-imaging findings. Plasma total NOx levels in different subject groups were determined by Griess assay.
Plasma total NOx level was found to be significantly decreased in patients with aSAH when compared to controls. Plasma total NOx level in the poor-grade SAH group was lower than that in the good-grade SAH group. Plasma total NOx level further reduced in patients with angiographic (P < 0.05) and clinical vasospasm.
Reduced plasma NOx level is seen in aSAH patients as compared to normal individuals. In aSAH patients reduced levels are associated with increased incidence of cerebral vasospasm and poor outcome. Plasma total NOx level could be used as a candidate biomarker for predicting vasospasm and outcome for this pathology.
PMCID: PMC4271376  PMID: 25540533
Aneurysmal subarachnoid hemorrhage; cerebral vasospasm; nitric oxide; poor outcome

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