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Surgical Outcome of Patients with Very Small Intracranial Aneurysms: A Single-Center Experience from Southern Iran
Accepted Manuscript Surgical Outcome of Patients with Very Small Intracranial Aneurysms; A Single Center Experience from Southern Iran Abdolkarim Rahmanian, MD, Fariborz Ghaffarpasand, MD, Nima Derakhshan, MD PII:
S1878-8750(16)31234-7
DOI:
10.1016/j.wneu.2016.11.086
Reference:
WNEU 4896
To appear in:
World Neurosurgery
Received Date: 12 September 2016 Revised Date:
14 November 2016
Accepted Date: 15 November 2016
Please cite this article as: Rahmanian A, Ghaffarpasand F, Derakhshan N, Surgical Outcome of Patients with Very Small Intracranial Aneurysms; A Single Center Experience from Southern Iran, World Neurosurgery (2016), doi: 10.1016/j.wneu.2016.11.086. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Title:
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Surgical Outcome of Patients with Very Small Intracranial Aneurysms; A Single Center Experience from Southern Iran
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Authors: 1. Abdolkarim Rahmanian, MD – Associate Professor of Neurosurgery – Department of Neurosurgery – Shiraz University of Medical Sciences, Shiraz, Iran.
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2. Fariborz Ghaffarpasand, MD – Resident of Neurosurgery – Department of neurosurgery – Shiraz University of Medical Sciences, Shiraz, Iran. 3. Nima Derakhshan, MD – Resident of Neurosurgery – Department of neurosurgery – Shiraz University of Medical Sciences, Shiraz, Iran.
Running title: Surgical outcome very small intracranial aneurysms in Iran
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Conflict of Interest: No conflict of interest
Keywords: Very Small Intracranial Aneurysms (VSIAs); Surgical Clipping; Double-Clip Technique; Outcome; Iran
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Word Count: 3164
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Corresponding Author: Fariborz Ghaffarpasand, MD Resident of Neurosurgery, Shiraz University of Medical Sciences Neurosurgery Office, Namazi Hospital, Namazi Square, Shiraz, Iran. Postal Code: 71973–11351 Tel/Fax: +98–713–6474259 Cellphone: +98–917–3095214 Email: [email protected]; [email protected]
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ABSTRACT OBJECTIVES: To report the surgical outcome of very small intracranial aneurysms (VSIAs; ≤3mm) in a large referral neurovascular center in Southern Iran.
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METHODS: This cross-sectional study was conducted in Southern Iran during a6-year period between 2010 and 2016. We included all the patients with VSIAs (≤3mm) who underwent surgery in our center. All the patients were operated by a single neurosurgeon.
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Pre- and postoperative CT angiography, intraoperative imaging with indo-cyanine green video angiography was performed in all the cases. The short- and long-term outcome was
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determined by Glasgow Coma Scale (GOS) and Modified Rankin Scale (MRS). RESULTS: Total number of 62 VSIAs in 52 patients was operated during the study period. There was no remnant and the complete occlusion rate was 100%. None of the patients experienced rebleeding. The 6-month mortality rate was 0% in unruptured VSIA, 3.8% in
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ruptured VSIA and 5.7% in ruptured intracranial aneurysms other than VSIAs. Most of the patients had favorable outcome (84.6%).Unfavorable outcome was associated with increased age (p=0.027), higher rates of hypertension (p=0.022) and ischemic heart disease
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(p=0.023), lower GCS on admission (p<0.001), higher Hunt and Hess grade (p<0.001),
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higher rate of preoperative VP-shunt insertion (p=0.040) and subarachnoid hemorrhage (p=0.015).
CONCLUSION: Surgical clipping of ruptured and unruptured VSIAs is a safe and effective modality of treatment associated with low mortality and morbidity. Age, comorbidities (hypertension, ischemic heart disease), on admission GCS, Hunt and Hess grade, preoperative VP-Shunt insertion and subarachnoid hemorrhage are important predictors of outcome in patients with VSIAs undergoing surgery.
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Introduction Very small intracranial aneurysms (VSIAs) are defined as intracranial aneurysms with a diameter smaller or equal to 3 mm.1,2 The prevalence of VSIAs has not been identified
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exactly, but has been reported to be low.3 Management of VSIAs is always a dilemma to neurovascular surgeons because the natural course and risk of bleeding in unruptured VSIAs is not fully understood yet.4,5 Currently it has been shown that even VSIAs carry a
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subsequent risk of subarachnoid hemorrhage.6-8 Most of the authors believe that surgery is the main option for treatment of ruptured VSIAs because coiling of these very small
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aneurysms is technically demanding and is associated with higher complication rates compared with larger aneurysms.6 Endovascular treatment is technically challenging, considering the difficulty in placing coil into the small out pouching and has a steep learning curve for interventional radiologists and neurovascular surgeons.6,9 The
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endovascular management of unruptured VSIAs has also been associated with higher complication rates compared to larger aneurysms.10 The surgical outcome of VSIAs (both
rate.1,11,12
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ruptured and unruptured) has been reported to be excellent with a low morbidity
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Surgical management of VSIAs requires special considerations in order to minimize the complication and morbidity rates. These aneurysms should be clipped with mini-clips, which have a smaller closing force than the standard aneurysm clips.11,13 Surgeon’s experience and operating room experience is among the most important factors determining the outcome in surgical management of patients with VSIAs.1,2,11,12 Although several studies have addressed the surgical outcome of VSIAs, data from Iran is scarce. In the current study we are going to present the surgical outcome of patients with VSIAs in
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large neurovascular referral center in Southern Iran14 with huge number of operation per year.
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Materials and Methods Study population
This cross-sectional study was conducted in a 6-year period from September 2010 to
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March 2016 in Namazi hospital, a tertiary healthcare center affiliated with Shiraz University of Medical Sciences. This center is the referral center for neurovascular diseases
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in Southern Iran with high load of patients and operations (both open and endovascular) which is well-equipped.14 We included all the patients with VSIAs (≤3mm) who underwent operation in our center during the study period. We included both ruptured (those presenting with subarachnoid hemorrhage) and unruptured (those being detected in
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neurovascular imagines or associated with other larger intracranial aneurysms) VSIAs. Those who underwent endovascular coiling were not considered in the current study. The study protocol was approved by the institutional review board (IRB) and medical ethics
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committee of Shiraz University of Medical Sciences. As this was a retrospective review of
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the medical charts, no informed written consents were required. Study Protocol and Surgical Technique All the medical charts of the eligible patients were retrieved and reviewed for demographic, clinical, radiological and outcome data. We recorded age, gender, presentation, number of total aneurysms, number of VSIAs, location of aneurysms and patients’ clinical information (on admission GCS, co-morbidities). We reviewed the initial CT-scans and CT-angiography of the patients and determined the total number and location
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of the intracranial aneurysms (Fig. 1 A, B). We also determined the Fisher 15 and Hunt and Hess 16 grade in all the patients. All the data were recorded into a data gathering form. We also reviewed the outpatient documents of the patients to record the outcome measures.
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The VSIAs were all diagnosed in CT-angiography performed by a spiral 16-slice multidetector CT-scan machine (BrightSpeed® Series, General Electric Corporation, Boston, USA) using maximum intensity projection (MIP) images and 3D-reconstruction
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which have been shown to have acceptable diagnostic accuracy in detecting VSIAs.17,18 All the patients underwent open surgical occlusion of the VSIAs by the senior author (A.R.) in
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Namazi hospital. We used lateral supraorbital or interhemispheric approach for operation based on the aneurysm location and direction. In lateral supraorbital approach, after dissection of the arachnoid, we exposed the optic nerve and internal carotid artery and exposed the VSIA. Then an appropriate temporary clip was applied. The aneurysm was
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then clipped using direct clipping technique or double-clip technique11 (Fig. 1 C, D, E). In some patients, as clipping was not applicable (wide neck or blister-like aneurysms), we used wrapping technique.19 In this technique we cauterized the aneurysm with blunt
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bipolar and minimal current and then performed wrapping with catanoid. This technique
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provides fibrosis of the aneurysm wall.20,21 The patency of the main artery was checked intraoperatively by intraoperative indocyanine green (ICG) angiography (Pentero 800 microscope, Carl Zeiss AG., Oberkochen, Germany) and Doppler sonography. Postoperative CT-angiography was performed in all the patients in order to determine the residual aneurysm (Fig. 1F). In our center, the aneurysm surgery is performed in the next elective operating day (a semi-emergency setting). Those patients with subarachnoid hemorrhage who have severe hydrocephalus undergo emergency VP-shunt insertion. We do not usually
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use external drainage systems as their rates of infection are considerably high (10-15%) and are associated with significant morbidity.22 All the patients were followed for at least 6 months and the functional recovery was
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evaluated using Glasgow Outcome Scale (GOS) and Modified Rankin Scale (MRS).23 We also recorded the intraoperative variables (duration, bleeding and number of applied clips). Unfavorable outcome was defined as GOS of 1 (dead), 2 (Persistent Vegetative State) and 3
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(severe disability) while favorable outcome was defined as GOS of 4 (moderate disability) and 5 (good recovery).
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Statistical analysis
All the statistical analysis was performed by statistical package for social sciences (SPSS Inc., Chicago, Illinois, USA) version 18.0. Data are presented as mean ± SD and proportions as appropriate. in order to determine the determinants of outcome in patients with VSIAs
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undergoing surgery, we compared the variables between those with favorable and unfavorable outcome. For comparing the parametric data with normal distribution, we used independent t-test. Mann-Whitney U-test was used to compare the parametric
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variables without normal distribution. Chi-square test was used to compare the
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proportions. In order to eliminate the role of confounders we ran a multivariate logistic regression model at the end of the analysis. A 2-sided p-value of less than 0.05 was considered statistically significant.
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Results Overall we included 52 patients with VSIAs who underwent operation in our center during the study period. The mean age of the patients was 53.7 ± 10.8 (ranging from 28 to 75)
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years and there were 31 (59.6%) women and 21 (40.1%) men among the patients. These 52 patients had total number of 94 intracranial aneurysms from which 62 (65.9%) were VSIAs. Twenty-seven (51.9%) patients had more than one intracranial aneurysms and 8
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(15.3%) had more than one VSIAs. Nineteen (36.5%) patients had ruptured VSIA while 18 (34.6%) had ruptured intracranial aneurysm other than VSIA. Fifteen (28.8%) patients
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presented with unruptured VSIA and any other intracranial aneurysm. Hypertension was the most common co-morbidity (48.1%). The baseline characteristics of the patients are summarized in Table 1.
Middle cerebral artery was the most common location of VSIAs (50.0%) followed by
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anterior communicating artery (19.3%) (Table 2). Preoperative hydrocephalus was detected in 29 (55.7%) patients of whom 6 (12.5%) required VP-shunt insertion prior to surgery. In those undergoing surgery with double-clip or direct clipping technique there
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was no remnant and the complete occlusion rate was 100%. None of the patients
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experienced rebleeding. The intraoperative characteristics of the patients are summarized in Table 2. Most of the patients had favorable outcome (84.6%) determined by good recovery in 73.1% according to 6-month GOS and no significant disability in 51.9% according to 6-month MRS. The 6-month mortality rate was 0% in unruptured VSIA group while it was 2 (3.8%) in ruptured VSIA group and 3 (5.7%) in those with ruptured intracranial aneurysm other than VSIA. All the patients with unruptured VSIA had good recovery and none had permanent neurological deficit. In those with ruptured VSIA, 1
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(5.3%) patient was persistent vegetative state at 6-moths and 1 (5.3%) had sever disability. There were 2 (11.1%) persistent vegetative state and 1 (5.5%) had severe disability in those with ruptured aneurysm other than VSIAs. One (5.5%) of the patients with A-com
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VSIA developed left visual loss after the operation due to manipulation of optic nerve. All the other complications were related to subarachnoid hemorrhage and only the previously mentioned one was associated with surgery. Table 3 summarizes the outcome measures of
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the patients.
We determined the outcome measure predictors in patients with VSIAs undergoing surgery
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in our institute. We found that unfavorable outcome was associated with increased age (p=0.027). Those with unfavorable outcome had significantly higher rates of hypertension [p=0.022; OR: 1.337 (CI95%: 1.036-1.727)] and ischemic heart disease [p=0.023; OR: 1.633 (CI95%: 0.903-2.951)]. On admission GCS was significantly lower in those with unfavorable
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outcome (p<0.001). The Hunt and Hess grade was significantly higher in those with unfavorable outcome (p<0.001). Subarachnoid hemorrhage was found to be among the predictors of outcome in patients with VSIAs [p=0.015; OR: 2.188 (CI95%: 1.563-
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2.892)].The rate of preoperative VP-shunt insertion was significantly higher among those
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with unfavorable outcome [p=0.040; OR: 1.783 (CI95%: 0.796-3.993)]. Other parameters such as number of aneurysms, Fisher grade, and intraoperative characteristics were comparable between those with favorable and unfavorable outcomes (Table 4). The multivariate logistic regression model revealed that age, on admission GCS, Hunt and Hess grade, preoperative VP-shunt insertion, hypertension, ischemic heart disease rate and subarachnoid hemorrhage remained significant after eliminating the cofounders (Table 5).
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Discussion VSIAs are a dilemma to neurovascular surgeons as their management remains controversial.1,4,10 Although some trials believes that neurosurgical clipping is superior to
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endovascular coiling in patients with ruptured VSIAs,2,8,11,24 however, recent evidence suggest that these two are equal and in some parameters, endovascular coiling is superior to surgical clipping.25-28 Recently, flow-diversion stents (Pipeline Embolization Device and
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SILK stent) have been shown to be associated with higher success rate and lower complications for treatment of intracranial aneurysms as well as VSIAs.29-31 In the current
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study we reported the outcome of surgical management of 52 patients with 62 VSIAs in our referral center in Southern Iran. Although endovascular coiling is performed in our center, the experience is still in its infancy and most of the patients are managed surgically. The other limiting factor for endovascular approaches in our center is the expenditure which is
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not covered by the insurance companies. Although for example flow-diversion is available, but only limited patients can afford them. Compared to endovascular management of aneurysmal subarachnoid hemorrhage, surgical clipping is much cheaper and feasible. We
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found that most of the patients had minimal disability after 6-month. The mortality rate
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was 0% among unruptured VSIA and was 3.8% among those with ruptured VSIA. Those with ruptured intracranial aneurysms other than VSIAs had 5.7% mortality rate. We also determined the outcome predictors of VSIAs undergoing surgical clipping in our center. We found that age, co-morbidities (hypertension and ischemic heart disease), on admission GCS, Hunt and Hess grade, preoperative VP shunt insertion and subarachnoid hemorrhage were the important outcome determinants in these group of patients. To the best of our
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knowledge, this is the first study reporting the surgical outcome of patients with VSIAs from Iran. We included both ruptured and unruptured VSIAs. Currently there is no consensus
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regarding interventional or watchful management of patients with unruptured VSIAs.1,4,32 Recently, Aishima et al.32 determined the overall risks and long-term impact of unruptured aneurysms on lifetime quality of life through a mathematical approach. They found that the
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age-specific ratios of death of subarachnoid hemorrhage in the individuals harboring unruptured aneurysm, if dying at 60 years old, were 25% in males and 43% in females.
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These ratios decreased rapidly with higher age. The majority (more than 90%) of patients with small aneurysms were expected to die of diseases other than subarachnoid hemorrhage. In the baseline analysis (60-year-old individuals), lifetime lost to small aneurysms could be estimated as 3.8% for males and 4.2% for females, but somewhat
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larger impact could be identified in the young and/or female individuals than in the elderly and/or male individuals. These result clearly demonstrate that life time risk of rupture in patients with VSIAs is low.32 On the other hand, Krisht et al.12 demonstrated that the 10-
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year cumulative bleeding-related mortality and severe morbidity of small intracranial
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aneurysm is not less than 7.5% which was higher than surgical clipping with an 0.8% rate of mortality and 3.4% permanent morbidity. This suggests that surgical clipping has the potential of a superior outcome to the natural history of patients who have an estimated life expectancy of no less than 10 years.12 In addition, Bruneau et al.1 demonstrated that surgical management of unruptured VSIAs is associated with 98.2% complete occlusion rate, 0% mortality, and a 2.7% persistent neurological complication rate emphasizing on
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safety and efficacy of surgery in VSIAs. The outcome of VSIAs in different studies is summarized in Table 6. In the current study we demonstrated that the total occlusion rate was 100% and none of
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the patients had remnant aneurysms and none experienced rebleeding. The mortality rate was 0% in unruptured VSIA group and was 3.8% in ruptures VSIA group. The rate of permanent neurological deficit was 0% in unruptured and 10.6% in ruptured VSIA group.
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In Bruneau et al.1 series the mortality rate was 0% and the rate of total occlusion was 98.2% and only 2.7% experience persistent neurological complications which is
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comparable to our study. Kiran et al.11 also reported a surgery associated mortality and morbidity of 0% in 39 patients with 40 VSIAs undergoing surgical clipping utilizing doubleclip technique. In another recent study Grasso and Perra2 reported the outcome of 53 patients with ruptured VSIAs undergoing surgical clipping. Ischemia related to surgery was
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observed in 15% of the cases and hemorrhage in 13.2%. No mortality related to clipping was observed. Overall, major and minor neurological deficit related to clipping were 5.2% and 2.2%, respectively. At the time of discharge, 84.9% of the patients attained a favorable
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outcome (moderate, mild, or no disability). Only 8 patients (15.1%) had poor clinical
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outcome which is comparable with our study.2 Krisht et al.12 reported the surgical outcome of 25 patients with unruptured VSIAs. Surgical-related mortality was 0.82%. Surgical related permanent morbidity was 3.44% and transient surgical-related mild morbidities was 7.7%. Immediate postsurgical good outcome (Glasgow Outcome Score = 4-5) was 87.93% and 95.68% in 3 months. Residual aneurysms were seen in none of the postoperative angiograms.12 These statistics are comparable to those reported in the current study. The different statistics presented in the current study could be because
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these studies included patients with unruptured VSIAs in which the surgery was performed in an elective setting. Most of our patients presented with ruptured VSIAs or ruptured other intracranial aneurysms with high Hunt and Hess grade which affected the outcome
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negatively. The definition of small intracranial aneurysm also differs between these studies as Krisht et al.12 define it as diameter less than 7mm while Kiran et al.11 and Bruneau et al.1 define it as diameter less than 3mm. In our study we assumed the maximum diameter to be
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3mm.
We used surgical wrapping technique is those blister-like aneurysm and those VSIAs which
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were wide neck and hard to clip. Recently, Germano et al.19 demonstrated that microsurgical muscle-wrapping of ruptured intracranial aneurysm is safe method and is associated with a low rate of acute and delayed postoperative complications and rebleeding, and could be a valid alternative for unclippable and non-amenable to
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endovascular procedure ruptured aneurysms.19 In the same way, Safavi-Abbasi et al.21 that microsurgical wrapping of ruptured and unruptured intracranial aneurysm with Gore-Tex is associated with acceptable recurrence and rehemorrhage rates without granulation
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tissue formation and reaction.21
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In the current study we demonstrated that age, on admission GCS, Hunt and Hess grade, comorbidities and subarachnoid hemorrhage were significantly associated with outcome of patients with VSIAs. Although we eliminated the role of confounders by performing a multivariate logistic regression analysis, the role of co-linear variables should be considered. For example VP-shunting was associated with higher Hunt and Hess grading and thus more unfavorable outcome. It has been previously demonstrated that age is a significant predictor of outcome in patients with ruptured intracranial aneurysms.33 In
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addition, Matsukawa et al.34 demonstrated that age was not associated with poor outcome in patients with unruptured intracranial aneurysms undergoing surgery. On the other hand, Mahaney et al.5 demonstrated that surgery poses a significant risk of morbidity and
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death in patients older than 65 years of age. Risk of endovascular treatment did not appear to increase with age.5 It has been reported that patients with ruptured intracranial aneurysms <5 mm are associated with a higher rate of presentation with poor Hunt and
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Hess grades than ruptured intracranial aneurysms larger than 5 mm. Moreover, in the clinical setting, approximately, half of the ruptured intracranial aneurysms <5 mm and
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65% of ruptured intracranial aneurysms larger than 5 mm are clinically presented with a good Hunt and Hess SAH grade.35 This is in line with our study that most of the patients presented with poor Hunt and Hess as well as fisher grades of subarachnoid hemorrhage and Hunt and Hess grade directly was associated with outcome in our series. Park et al.36
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demonstrated that the interval between presentation and operation was a significant predictor of outcome while we did not fund this correlation. Other predictors of the outcome in patients with ruptured intracranial aneurysms has been reported to be the size
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and location of the aneurysm8,37 and the cumulative experience of the neurosurgeon.38 We
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did not found any association between the location of VSIAs and the outcome in our series. The size was not determined in our study as all the patients had VSIAs (less than 3mm in diameter). The cumulative experience of the neurosurgeon and the staff has a direct effect on the outcome of the patients.38 The experience of our center in neurovascular surgery has increased during the previous decade with high load of patients and updated equipment and expertise.14 We hope that the mortality and morbidity rates decrease in near future by increasing the experience in our center.
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We note some limitations to our study. First, we included both unruptured and ruptured VSIAs or other intracranial aneurysms and reported the outcome in this mixes population. The aim of the current study was to report the surgical outcome in patients with VSIAs.
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Thus we included all the patients to increase the sample size population and determine the outcome measures. Second, this was retrospective study utilizing the data from our registry. Thus we could not perform data analysis in some prospective variables. Currently
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we are settling down our online neurovascular registry to solve these problems. To the best of our knowledge, this is the first study from Iran reporting the surgical outcome of
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patients with VSIAs undergoing clipping.
In conclusion, surgical clipping of ruptured and unruptured VSIAs is a safe and effective modality of treatment associated with low mortality and morbidity. Age, co-morbidities (hypertension, ischemic heart disease), on admission GCS, Hunt and Hess grade,
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preoperative VP-Shunt insertion and subarachnoid hemorrhage are important predictors of outcome in patients with VSIAs undergoing surgery.
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Acknowledgment
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We would like to acknowledge all the patients and their families whose information was used in this study.
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Embolization Device in 100 small intracranial aneurysms. J Neurosurg 2015;122:1498-502. 30.
Giacomini L, Piske RL, Baccin CE, et al. Neurovascular reconstruction with flow
diverter stents for the treatment of 87 intracranial aneurysms: Clinical results. Interv Neuroradiol 2015;21:292-9.
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31.
Ji W, Kang H, Liu A, et al. Stent-assisted coiling of very small wide-necked
intracranial aneurysms: Complications, anatomical results and clinical outcomes. Neurol Neurochir Pol 2016;50:410-7. Aishima K, Shimizu T, Aihara M, et al. Lifetime Effects of Small Unruptured
Intracranial Aneurysms. World Neurosurgery 2016;95:434-40. 33.
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32.
Brinjikji W, Lanzino G, Rabinstein AA, et al. Age-related trends in the treatment and
2001-2009. AJNR Am J Neuroradiol 2013;34:1022-7.
Matsukawa H, Kamiyama H, Tsuboi T, et al. Is age a risk factor for poor outcome of
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34.
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outcomes of ruptured cerebral aneurysms: a study of the nationwide inpatient sample
surgical treatment of unruptured intracranial aneurysms? World Neurosurg 2016. 35.
Dolati P, Pittman D, Morrish WF, et al. The Frequency of Subarachnoid Hemorrhage
2015;7:e279. 36.
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from Very Small Cerebral Aneurysms (< 5 mm): A Population-Based Study. Cureus
Park J, Woo H, Kang DH, et al. Formal protocol for emergency treatment of ruptured
intracranial aneurysms to reduce in-hospital rebleeding and improve clinical outcomes. J
Orz Y, AlYamany M. The impact of size and location on rupture of intracranial
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37.
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Neurosurg 2015;122:383-91.
aneurysms. Asian J Neurosurg 2015;10:26-31. 38.
Le Reste PJ, Henaux PL, Riffaud L, et al. Influence of cumulative surgical experience
on the outcome of poor-grade patients with ruptured intracranial aneurysm. Acta Neurochir (Wien) 2015;157:1-7.
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Tables
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Table 1 Baseline characteristics of 52patients with very small intracranial aneurysms undergoing surgery in our center from 2010 to 2016. Variable Value Age (years) 53.7 ± 10.8 Gender Men (%) 21 (40.1%) Women (%) 31 (59.6%) Presentation Ruptures VISA (%) 19 (36.5%) Ruptured larger aneurysm (%) 18 (34.6%) Unruptured VISA (%) 15 (28.8%) GCS on admission 13.38 ± 2.98 Hunt and Hess grade 1 (%) 17 (32.7%) 2 (%) 11 (21.2%) 3 (%) 1 (1.9%) 4 (%) 5 (9.6%) 5 (%) 3 (5.8%) Fisher grade 1 (%) 4 (7.7%) 2 (%) 6 (11.5%) 3 (%) 24 (46.2%) 4 (%) 3 (5.8%) Co-morbidities Hypertension (%) 25 (48.1%) Smoking (%) 12 (23.1%) Ischemic heart disease (%) 9 (17.3%) Diabetes mellitus (%) 6 (11.5%) Opium addiction (%) 5 (9.6%) Total number of intracranial aneurysms 1 (%) 25 (48.1%) 2 (%) 16 (30.8%) 3 (%) 9 (17.3%) 5 (%) 2 (3.8%) Total number of VSIAs 1 (%) 44 (84.6%) 2 (%) 6 (11.5%) 3 (%) 2 (3.8%) GCS: Glasgow Coma Scale (GCS); VISA: Very Small Intracranial Aneurysm
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Table 2Pre-, intra- and postoperative characteristicsof 94intracranial aneurysms and 62 VSIAs in 52 patients undergoing surgery in our center from 2010 to 2016. Location Frequency Location of intracranial aneurysms MCA (%) 49 (52.1%) A-Com (%) 19 (20.2%) ACA (%) 11 (11.7%) P-Com (%) 7 (7.6%) Internal Carotid (%) 4 (4.2%) Ophthalmic (%) 4 (4.2%) Location of VSIAs MCA (%) 31 (50.0%) A-Com (%) 12 (19.3%) ACA (%) 10 (16.1%) P-Com (%) 5 (8.1%) Ophthalmic (%) 3 (4.8%) Internal Carotid (%) 1 (1.7%) Intraoperative variables Intraoperative rupture (%) 14 (26.9%) Preoperative VP-Shunt insertion (%) 6 (12.5%) Intraoperative bleeding (mL) 180.38 ± 137.88 Operation duration (min) 66.3 ± 41.3 Surgery Approach Lateral supraorbital (%) 48 (92.3%) Interhemispheric (%) 4 (7.7%) Surgery technique Helper clip technique (%) 26 (50.0%) Direct clipping (%) 19 (36.5%) Catanoid wrapping (%) 7 (13.5%) Prognosis Favorable (%) 44 (84.6%) Unfavorable (%) 8 (15.4%) ACA: Anterior Cerebral Artery; A-Com: Anterior Communicating Artery; MCA: Middle Cerebral Artery;P-Com: Posterior Communicating Artery; VSIA: Very Small Intracranial Aneurysm
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Table 3 The outcome of52 patients with very small intracranial aneurysms undergoing surgery in our center determined by Glasgow outcome scale and modified ranking scale. Unruptured VISA (n=15)
13 (68.4%) 2 (10.5%) 1 (5.3%) 1 (5.3%) 2 (10.5%)
15 (100%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
4 (21.1%) 9 (47.4%) 1 (5.3%) 1 (5.3%) 1 (5.3%) 1 (5.3%) 2 (10.5%)
5 (33.3%) 9 (60.0%) 1 (6.7%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
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6-month GOS Good Recovery (%) 10 (55.6%) Moderate disability (%) 2 (11.1%) Severe disability (%) 1 (5.5%) Persistent vegetative state (%) 2 (11.1%) Death (%) 3 (16.7%) 6-month MRS No Symptoms (%) 1 (5.5%) No significant disability (%) 9 (50.0%) Slight disability (%) 2 (11.1%) Moderate disability (%) 0 (0.0%) Moderately severe disability (%) 0 (0.0%) Severe disability (%) 3 (16.7%) Dead (%) 3 (16.7%) GOS: Glasgow Outcome Scale; MRS: Modified Rankin Scale
Ruptured VISA (n=19)
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Ruptured aneurysm (n=18)
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Table 4 Intraoperative and outcome of 52 patients with very small intracranial aneurysms undergoing surgery in our center from 2010 to 2016. Favorable (n=44) Unfavorable (n=8) p-value Age (years) 52.3 ± 10.5 61.5 ± 9.8 0.027 Gender Men (%) 20 (45.5%) 1 (12.5%) 0.122 Women (%) 24 (54.5%) 7 (87.5%) Co-morbidities Hypertension (%) 18 (40.9%) 7 (87.5%) 0.022 Ischemic heart disease (%) 5 (11.4%) 4 (50.0%) 0.023 Smoking (%) 12 (27.3%) 0 (0.0%) 0.174 Diabetes mellitus (%) 4 (9.1%) 2 (25.0%) 0.227 Opium addiction (%) 5 (11.4%) 0 (0.0%) 0.418 GCS on admission 14.11 ± 2.16 9.37 ± 3.77 <0.001 Subarachnoid hemorrhage (%) 29 (65.9%) 8 (100%) 0.015 Hunt and Hess grade 1.68 ± 1.07 3.50 ± 1.31 <0.001 Fisher grade 2.58 ± 0.82 3.12 ± 0.35 0.082 Number of aneurysms 1.82 ± 1.04 1.75 ± 0.71 0.860 Number of VSIAs 1.23 ± 0.52 1.03 ± 0.43 0.228 Intraoperative bleeding (mL) 175.6 ± 131.7 206.2 ± 176.2 0.569 Operation duration (min) 63.2 ± 38.6 83.7 ± 53.3 0.198 Preoperative VP-Shunt (%) 3 (6.8%) 3 (37.5%) 0.040 Intraoperative rupture (%) 11 (25.0%) 3 (37.5%) 0.666 Location VSIAs MCA (%) 21 (47.7%) 4 (50.0%) A-Com (%) 8 (16.6%) 2 (25.0%) P-Com (%) 5 (11.3%) 0 (0.0%) 0.088 ACA (%) 3 (6.25%) 1 (12.5%) Distal ACA (%) 3 (6.25%) 1 (12.5%) Ophthalmic (%) 3 (6.25%) 0 (0.0%) Internal Carotid (%) 1 (5.56%) 0 (0.0%)
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Table 5 Multivariate analysis for association with unfavorable outcome (GOS of 1-3). OR
95% CI
Age
0.002
2.726
1.426-3.264
On admission GCS
<0.001
5.785
3.466-7.021
Hypertension
0.022
1.337
Ischemic heart disease
0.023
1.633
Subarachnoid hemorrhage
0.015
2.188
Hunt and Hess grade
0.001
4.012
Confidence
interval;
GCS:
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Ventriculoperitoneal
Glasgow
1.036-1.727 0.903-2.951
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Preoperative VP-shunt insertion 0.040 CI:
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p-value
1.783
Coma
Scale;
1.563-2.892 2.233-5.902 0.796-3.993
OR:
Odds
Ratio,
VP:
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Table 6 The series of very small intracranial aneurysms (VSIAs) published in the literature. Condition
Procedure
Morbidity
Occlusion rate
Mortality
Our series
62
Rupture/Unruptured
Surgery
9.61%
86.5%
9.61%
Bruneau et al.1
228
Unruptured
Surgery
2.7%
98.2%
0.0%
Kiran et al.11
40
Rupture/Unruptured
Surgery
12.8%
97.4%
0.0%
Krisht et al.12
25
Unruptured
Surgery
3.44%
100%
0.82%
Li et al.9
85
Ruptured
Surgery
7.10%
94.3%
2.35%
Li et al.9
97
Ruptured
Endovascular
1.03%
64.9%
1.03%
Im et al.10
435
Unruptured
Endovascular
0.27%
76.8%
0.0%
van Rooij et al.13
196
Rupture/Unruptured
Endovascular
2.1%
94.9%
1.1%
Chalouhi et al. 29
100
Rupture/Unruptured
Endovascular
3%
72%
0.0%
Ji et al.31
112
Rupture/Unruptured
Endovascular
3.2%
96.3%
0.0%
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No. of VISAs
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B
C
D
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E
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A
F
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Fig 1. A 55-year-old man with family history of intracranial aneurysm surgery in mother, brother and sister underwent screening with brain CT angiography which revealed an unruptured intracranial aneurysm in left middle cerebral artery bifurcation measuring 2.5mm (A, B). intraoperative image demonstrating the aneurysm before (C) and after applying a temporary clip (D). the aneurysm was successfully clipped directly with a 4mm mini clip (E) without any remnant. The postoperative brain CT-scan revealed no hematoma or hydrocephalus (F). The patient was discharged with good health in 4th postoperative day and had good recovery in 6-month follow up.
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Surgical clipping of ruptured and unruptured VSIAs is a safe and effective modality of treatment associated with low mortality and morbidity. Age, comorbidities (hypertension, ischemic heart disease), on admission GCS,
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subarachnoid hemorrhage, Hunt and Hess grade, preoperative VP-Shunt insertion are important predictors of outcome in patients with VSIAs undergoing
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surgery.
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•
ACCEPTED MANUSCRIPT Abbreviations GCS: Glasgow Coma Scale GOS: Glasgow Outcome Scale ICG: Indocyanine green
MRS: Modified Rankin Scale VP: Ventriculoperitoneal
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VSIA: Very Small Intracranial Aneurysm
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IRB: Institutional Review Board
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Disclosure of conflict of interest
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None of the authors have any conflict of interest to be declared regarding the manuscript.
S1878-8750(16)31234-7
DOI:
10.1016/j.wneu.2016.11.086
Reference:
WNEU 4896
To appear in:
World Neurosurgery
Received Date: 12 September 2016 Revised Date:
14 November 2016
Accepted Date: 15 November 2016
Please cite this article as: Rahmanian A, Ghaffarpasand F, Derakhshan N, Surgical Outcome of Patients with Very Small Intracranial Aneurysms; A Single Center Experience from Southern Iran, World Neurosurgery (2016), doi: 10.1016/j.wneu.2016.11.086. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Title:
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Surgical Outcome of Patients with Very Small Intracranial Aneurysms; A Single Center Experience from Southern Iran
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Authors: 1. Abdolkarim Rahmanian, MD – Associate Professor of Neurosurgery – Department of Neurosurgery – Shiraz University of Medical Sciences, Shiraz, Iran.
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2. Fariborz Ghaffarpasand, MD – Resident of Neurosurgery – Department of neurosurgery – Shiraz University of Medical Sciences, Shiraz, Iran. 3. Nima Derakhshan, MD – Resident of Neurosurgery – Department of neurosurgery – Shiraz University of Medical Sciences, Shiraz, Iran.
Running title: Surgical outcome very small intracranial aneurysms in Iran
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Conflict of Interest: No conflict of interest
Keywords: Very Small Intracranial Aneurysms (VSIAs); Surgical Clipping; Double-Clip Technique; Outcome; Iran
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Word Count: 3164
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Corresponding Author: Fariborz Ghaffarpasand, MD Resident of Neurosurgery, Shiraz University of Medical Sciences Neurosurgery Office, Namazi Hospital, Namazi Square, Shiraz, Iran. Postal Code: 71973–11351 Tel/Fax: +98–713–6474259 Cellphone: +98–917–3095214 Email: [email protected]; [email protected]
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ABSTRACT OBJECTIVES: To report the surgical outcome of very small intracranial aneurysms (VSIAs; ≤3mm) in a large referral neurovascular center in Southern Iran.
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METHODS: This cross-sectional study was conducted in Southern Iran during a6-year period between 2010 and 2016. We included all the patients with VSIAs (≤3mm) who underwent surgery in our center. All the patients were operated by a single neurosurgeon.
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Pre- and postoperative CT angiography, intraoperative imaging with indo-cyanine green video angiography was performed in all the cases. The short- and long-term outcome was
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determined by Glasgow Coma Scale (GOS) and Modified Rankin Scale (MRS). RESULTS: Total number of 62 VSIAs in 52 patients was operated during the study period. There was no remnant and the complete occlusion rate was 100%. None of the patients experienced rebleeding. The 6-month mortality rate was 0% in unruptured VSIA, 3.8% in
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ruptured VSIA and 5.7% in ruptured intracranial aneurysms other than VSIAs. Most of the patients had favorable outcome (84.6%).Unfavorable outcome was associated with increased age (p=0.027), higher rates of hypertension (p=0.022) and ischemic heart disease
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(p=0.023), lower GCS on admission (p<0.001), higher Hunt and Hess grade (p<0.001),
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higher rate of preoperative VP-shunt insertion (p=0.040) and subarachnoid hemorrhage (p=0.015).
CONCLUSION: Surgical clipping of ruptured and unruptured VSIAs is a safe and effective modality of treatment associated with low mortality and morbidity. Age, comorbidities (hypertension, ischemic heart disease), on admission GCS, Hunt and Hess grade, preoperative VP-Shunt insertion and subarachnoid hemorrhage are important predictors of outcome in patients with VSIAs undergoing surgery.
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Introduction Very small intracranial aneurysms (VSIAs) are defined as intracranial aneurysms with a diameter smaller or equal to 3 mm.1,2 The prevalence of VSIAs has not been identified
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exactly, but has been reported to be low.3 Management of VSIAs is always a dilemma to neurovascular surgeons because the natural course and risk of bleeding in unruptured VSIAs is not fully understood yet.4,5 Currently it has been shown that even VSIAs carry a
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subsequent risk of subarachnoid hemorrhage.6-8 Most of the authors believe that surgery is the main option for treatment of ruptured VSIAs because coiling of these very small
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aneurysms is technically demanding and is associated with higher complication rates compared with larger aneurysms.6 Endovascular treatment is technically challenging, considering the difficulty in placing coil into the small out pouching and has a steep learning curve for interventional radiologists and neurovascular surgeons.6,9 The
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endovascular management of unruptured VSIAs has also been associated with higher complication rates compared to larger aneurysms.10 The surgical outcome of VSIAs (both
rate.1,11,12
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ruptured and unruptured) has been reported to be excellent with a low morbidity
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Surgical management of VSIAs requires special considerations in order to minimize the complication and morbidity rates. These aneurysms should be clipped with mini-clips, which have a smaller closing force than the standard aneurysm clips.11,13 Surgeon’s experience and operating room experience is among the most important factors determining the outcome in surgical management of patients with VSIAs.1,2,11,12 Although several studies have addressed the surgical outcome of VSIAs, data from Iran is scarce. In the current study we are going to present the surgical outcome of patients with VSIAs in
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large neurovascular referral center in Southern Iran14 with huge number of operation per year.
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Materials and Methods Study population
This cross-sectional study was conducted in a 6-year period from September 2010 to
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March 2016 in Namazi hospital, a tertiary healthcare center affiliated with Shiraz University of Medical Sciences. This center is the referral center for neurovascular diseases
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in Southern Iran with high load of patients and operations (both open and endovascular) which is well-equipped.14 We included all the patients with VSIAs (≤3mm) who underwent operation in our center during the study period. We included both ruptured (those presenting with subarachnoid hemorrhage) and unruptured (those being detected in
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neurovascular imagines or associated with other larger intracranial aneurysms) VSIAs. Those who underwent endovascular coiling were not considered in the current study. The study protocol was approved by the institutional review board (IRB) and medical ethics
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committee of Shiraz University of Medical Sciences. As this was a retrospective review of
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the medical charts, no informed written consents were required. Study Protocol and Surgical Technique All the medical charts of the eligible patients were retrieved and reviewed for demographic, clinical, radiological and outcome data. We recorded age, gender, presentation, number of total aneurysms, number of VSIAs, location of aneurysms and patients’ clinical information (on admission GCS, co-morbidities). We reviewed the initial CT-scans and CT-angiography of the patients and determined the total number and location
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of the intracranial aneurysms (Fig. 1 A, B). We also determined the Fisher 15 and Hunt and Hess 16 grade in all the patients. All the data were recorded into a data gathering form. We also reviewed the outpatient documents of the patients to record the outcome measures.
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The VSIAs were all diagnosed in CT-angiography performed by a spiral 16-slice multidetector CT-scan machine (BrightSpeed® Series, General Electric Corporation, Boston, USA) using maximum intensity projection (MIP) images and 3D-reconstruction
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which have been shown to have acceptable diagnostic accuracy in detecting VSIAs.17,18 All the patients underwent open surgical occlusion of the VSIAs by the senior author (A.R.) in
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Namazi hospital. We used lateral supraorbital or interhemispheric approach for operation based on the aneurysm location and direction. In lateral supraorbital approach, after dissection of the arachnoid, we exposed the optic nerve and internal carotid artery and exposed the VSIA. Then an appropriate temporary clip was applied. The aneurysm was
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then clipped using direct clipping technique or double-clip technique11 (Fig. 1 C, D, E). In some patients, as clipping was not applicable (wide neck or blister-like aneurysms), we used wrapping technique.19 In this technique we cauterized the aneurysm with blunt
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bipolar and minimal current and then performed wrapping with catanoid. This technique
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provides fibrosis of the aneurysm wall.20,21 The patency of the main artery was checked intraoperatively by intraoperative indocyanine green (ICG) angiography (Pentero 800 microscope, Carl Zeiss AG., Oberkochen, Germany) and Doppler sonography. Postoperative CT-angiography was performed in all the patients in order to determine the residual aneurysm (Fig. 1F). In our center, the aneurysm surgery is performed in the next elective operating day (a semi-emergency setting). Those patients with subarachnoid hemorrhage who have severe hydrocephalus undergo emergency VP-shunt insertion. We do not usually
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use external drainage systems as their rates of infection are considerably high (10-15%) and are associated with significant morbidity.22 All the patients were followed for at least 6 months and the functional recovery was
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evaluated using Glasgow Outcome Scale (GOS) and Modified Rankin Scale (MRS).23 We also recorded the intraoperative variables (duration, bleeding and number of applied clips). Unfavorable outcome was defined as GOS of 1 (dead), 2 (Persistent Vegetative State) and 3
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(severe disability) while favorable outcome was defined as GOS of 4 (moderate disability) and 5 (good recovery).
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Statistical analysis
All the statistical analysis was performed by statistical package for social sciences (SPSS Inc., Chicago, Illinois, USA) version 18.0. Data are presented as mean ± SD and proportions as appropriate. in order to determine the determinants of outcome in patients with VSIAs
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undergoing surgery, we compared the variables between those with favorable and unfavorable outcome. For comparing the parametric data with normal distribution, we used independent t-test. Mann-Whitney U-test was used to compare the parametric
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variables without normal distribution. Chi-square test was used to compare the
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proportions. In order to eliminate the role of confounders we ran a multivariate logistic regression model at the end of the analysis. A 2-sided p-value of less than 0.05 was considered statistically significant.
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Results Overall we included 52 patients with VSIAs who underwent operation in our center during the study period. The mean age of the patients was 53.7 ± 10.8 (ranging from 28 to 75)
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years and there were 31 (59.6%) women and 21 (40.1%) men among the patients. These 52 patients had total number of 94 intracranial aneurysms from which 62 (65.9%) were VSIAs. Twenty-seven (51.9%) patients had more than one intracranial aneurysms and 8
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(15.3%) had more than one VSIAs. Nineteen (36.5%) patients had ruptured VSIA while 18 (34.6%) had ruptured intracranial aneurysm other than VSIA. Fifteen (28.8%) patients
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presented with unruptured VSIA and any other intracranial aneurysm. Hypertension was the most common co-morbidity (48.1%). The baseline characteristics of the patients are summarized in Table 1.
Middle cerebral artery was the most common location of VSIAs (50.0%) followed by
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anterior communicating artery (19.3%) (Table 2). Preoperative hydrocephalus was detected in 29 (55.7%) patients of whom 6 (12.5%) required VP-shunt insertion prior to surgery. In those undergoing surgery with double-clip or direct clipping technique there
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was no remnant and the complete occlusion rate was 100%. None of the patients
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experienced rebleeding. The intraoperative characteristics of the patients are summarized in Table 2. Most of the patients had favorable outcome (84.6%) determined by good recovery in 73.1% according to 6-month GOS and no significant disability in 51.9% according to 6-month MRS. The 6-month mortality rate was 0% in unruptured VSIA group while it was 2 (3.8%) in ruptured VSIA group and 3 (5.7%) in those with ruptured intracranial aneurysm other than VSIA. All the patients with unruptured VSIA had good recovery and none had permanent neurological deficit. In those with ruptured VSIA, 1
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(5.3%) patient was persistent vegetative state at 6-moths and 1 (5.3%) had sever disability. There were 2 (11.1%) persistent vegetative state and 1 (5.5%) had severe disability in those with ruptured aneurysm other than VSIAs. One (5.5%) of the patients with A-com
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VSIA developed left visual loss after the operation due to manipulation of optic nerve. All the other complications were related to subarachnoid hemorrhage and only the previously mentioned one was associated with surgery. Table 3 summarizes the outcome measures of
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the patients.
We determined the outcome measure predictors in patients with VSIAs undergoing surgery
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in our institute. We found that unfavorable outcome was associated with increased age (p=0.027). Those with unfavorable outcome had significantly higher rates of hypertension [p=0.022; OR: 1.337 (CI95%: 1.036-1.727)] and ischemic heart disease [p=0.023; OR: 1.633 (CI95%: 0.903-2.951)]. On admission GCS was significantly lower in those with unfavorable
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outcome (p<0.001). The Hunt and Hess grade was significantly higher in those with unfavorable outcome (p<0.001). Subarachnoid hemorrhage was found to be among the predictors of outcome in patients with VSIAs [p=0.015; OR: 2.188 (CI95%: 1.563-
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2.892)].The rate of preoperative VP-shunt insertion was significantly higher among those
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with unfavorable outcome [p=0.040; OR: 1.783 (CI95%: 0.796-3.993)]. Other parameters such as number of aneurysms, Fisher grade, and intraoperative characteristics were comparable between those with favorable and unfavorable outcomes (Table 4). The multivariate logistic regression model revealed that age, on admission GCS, Hunt and Hess grade, preoperative VP-shunt insertion, hypertension, ischemic heart disease rate and subarachnoid hemorrhage remained significant after eliminating the cofounders (Table 5).
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Discussion VSIAs are a dilemma to neurovascular surgeons as their management remains controversial.1,4,10 Although some trials believes that neurosurgical clipping is superior to
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endovascular coiling in patients with ruptured VSIAs,2,8,11,24 however, recent evidence suggest that these two are equal and in some parameters, endovascular coiling is superior to surgical clipping.25-28 Recently, flow-diversion stents (Pipeline Embolization Device and
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SILK stent) have been shown to be associated with higher success rate and lower complications for treatment of intracranial aneurysms as well as VSIAs.29-31 In the current
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study we reported the outcome of surgical management of 52 patients with 62 VSIAs in our referral center in Southern Iran. Although endovascular coiling is performed in our center, the experience is still in its infancy and most of the patients are managed surgically. The other limiting factor for endovascular approaches in our center is the expenditure which is
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not covered by the insurance companies. Although for example flow-diversion is available, but only limited patients can afford them. Compared to endovascular management of aneurysmal subarachnoid hemorrhage, surgical clipping is much cheaper and feasible. We
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found that most of the patients had minimal disability after 6-month. The mortality rate
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was 0% among unruptured VSIA and was 3.8% among those with ruptured VSIA. Those with ruptured intracranial aneurysms other than VSIAs had 5.7% mortality rate. We also determined the outcome predictors of VSIAs undergoing surgical clipping in our center. We found that age, co-morbidities (hypertension and ischemic heart disease), on admission GCS, Hunt and Hess grade, preoperative VP shunt insertion and subarachnoid hemorrhage were the important outcome determinants in these group of patients. To the best of our
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knowledge, this is the first study reporting the surgical outcome of patients with VSIAs from Iran. We included both ruptured and unruptured VSIAs. Currently there is no consensus
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regarding interventional or watchful management of patients with unruptured VSIAs.1,4,32 Recently, Aishima et al.32 determined the overall risks and long-term impact of unruptured aneurysms on lifetime quality of life through a mathematical approach. They found that the
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age-specific ratios of death of subarachnoid hemorrhage in the individuals harboring unruptured aneurysm, if dying at 60 years old, were 25% in males and 43% in females.
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These ratios decreased rapidly with higher age. The majority (more than 90%) of patients with small aneurysms were expected to die of diseases other than subarachnoid hemorrhage. In the baseline analysis (60-year-old individuals), lifetime lost to small aneurysms could be estimated as 3.8% for males and 4.2% for females, but somewhat
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larger impact could be identified in the young and/or female individuals than in the elderly and/or male individuals. These result clearly demonstrate that life time risk of rupture in patients with VSIAs is low.32 On the other hand, Krisht et al.12 demonstrated that the 10-
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year cumulative bleeding-related mortality and severe morbidity of small intracranial
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aneurysm is not less than 7.5% which was higher than surgical clipping with an 0.8% rate of mortality and 3.4% permanent morbidity. This suggests that surgical clipping has the potential of a superior outcome to the natural history of patients who have an estimated life expectancy of no less than 10 years.12 In addition, Bruneau et al.1 demonstrated that surgical management of unruptured VSIAs is associated with 98.2% complete occlusion rate, 0% mortality, and a 2.7% persistent neurological complication rate emphasizing on
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safety and efficacy of surgery in VSIAs. The outcome of VSIAs in different studies is summarized in Table 6. In the current study we demonstrated that the total occlusion rate was 100% and none of
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the patients had remnant aneurysms and none experienced rebleeding. The mortality rate was 0% in unruptured VSIA group and was 3.8% in ruptures VSIA group. The rate of permanent neurological deficit was 0% in unruptured and 10.6% in ruptured VSIA group.
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In Bruneau et al.1 series the mortality rate was 0% and the rate of total occlusion was 98.2% and only 2.7% experience persistent neurological complications which is
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comparable to our study. Kiran et al.11 also reported a surgery associated mortality and morbidity of 0% in 39 patients with 40 VSIAs undergoing surgical clipping utilizing doubleclip technique. In another recent study Grasso and Perra2 reported the outcome of 53 patients with ruptured VSIAs undergoing surgical clipping. Ischemia related to surgery was
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observed in 15% of the cases and hemorrhage in 13.2%. No mortality related to clipping was observed. Overall, major and minor neurological deficit related to clipping were 5.2% and 2.2%, respectively. At the time of discharge, 84.9% of the patients attained a favorable
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outcome (moderate, mild, or no disability). Only 8 patients (15.1%) had poor clinical
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outcome which is comparable with our study.2 Krisht et al.12 reported the surgical outcome of 25 patients with unruptured VSIAs. Surgical-related mortality was 0.82%. Surgical related permanent morbidity was 3.44% and transient surgical-related mild morbidities was 7.7%. Immediate postsurgical good outcome (Glasgow Outcome Score = 4-5) was 87.93% and 95.68% in 3 months. Residual aneurysms were seen in none of the postoperative angiograms.12 These statistics are comparable to those reported in the current study. The different statistics presented in the current study could be because
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these studies included patients with unruptured VSIAs in which the surgery was performed in an elective setting. Most of our patients presented with ruptured VSIAs or ruptured other intracranial aneurysms with high Hunt and Hess grade which affected the outcome
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negatively. The definition of small intracranial aneurysm also differs between these studies as Krisht et al.12 define it as diameter less than 7mm while Kiran et al.11 and Bruneau et al.1 define it as diameter less than 3mm. In our study we assumed the maximum diameter to be
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3mm.
We used surgical wrapping technique is those blister-like aneurysm and those VSIAs which
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were wide neck and hard to clip. Recently, Germano et al.19 demonstrated that microsurgical muscle-wrapping of ruptured intracranial aneurysm is safe method and is associated with a low rate of acute and delayed postoperative complications and rebleeding, and could be a valid alternative for unclippable and non-amenable to
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endovascular procedure ruptured aneurysms.19 In the same way, Safavi-Abbasi et al.21 that microsurgical wrapping of ruptured and unruptured intracranial aneurysm with Gore-Tex is associated with acceptable recurrence and rehemorrhage rates without granulation
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tissue formation and reaction.21
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In the current study we demonstrated that age, on admission GCS, Hunt and Hess grade, comorbidities and subarachnoid hemorrhage were significantly associated with outcome of patients with VSIAs. Although we eliminated the role of confounders by performing a multivariate logistic regression analysis, the role of co-linear variables should be considered. For example VP-shunting was associated with higher Hunt and Hess grading and thus more unfavorable outcome. It has been previously demonstrated that age is a significant predictor of outcome in patients with ruptured intracranial aneurysms.33 In
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addition, Matsukawa et al.34 demonstrated that age was not associated with poor outcome in patients with unruptured intracranial aneurysms undergoing surgery. On the other hand, Mahaney et al.5 demonstrated that surgery poses a significant risk of morbidity and
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death in patients older than 65 years of age. Risk of endovascular treatment did not appear to increase with age.5 It has been reported that patients with ruptured intracranial aneurysms <5 mm are associated with a higher rate of presentation with poor Hunt and
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Hess grades than ruptured intracranial aneurysms larger than 5 mm. Moreover, in the clinical setting, approximately, half of the ruptured intracranial aneurysms <5 mm and
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65% of ruptured intracranial aneurysms larger than 5 mm are clinically presented with a good Hunt and Hess SAH grade.35 This is in line with our study that most of the patients presented with poor Hunt and Hess as well as fisher grades of subarachnoid hemorrhage and Hunt and Hess grade directly was associated with outcome in our series. Park et al.36
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demonstrated that the interval between presentation and operation was a significant predictor of outcome while we did not fund this correlation. Other predictors of the outcome in patients with ruptured intracranial aneurysms has been reported to be the size
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and location of the aneurysm8,37 and the cumulative experience of the neurosurgeon.38 We
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did not found any association between the location of VSIAs and the outcome in our series. The size was not determined in our study as all the patients had VSIAs (less than 3mm in diameter). The cumulative experience of the neurosurgeon and the staff has a direct effect on the outcome of the patients.38 The experience of our center in neurovascular surgery has increased during the previous decade with high load of patients and updated equipment and expertise.14 We hope that the mortality and morbidity rates decrease in near future by increasing the experience in our center.
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We note some limitations to our study. First, we included both unruptured and ruptured VSIAs or other intracranial aneurysms and reported the outcome in this mixes population. The aim of the current study was to report the surgical outcome in patients with VSIAs.
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Thus we included all the patients to increase the sample size population and determine the outcome measures. Second, this was retrospective study utilizing the data from our registry. Thus we could not perform data analysis in some prospective variables. Currently
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we are settling down our online neurovascular registry to solve these problems. To the best of our knowledge, this is the first study from Iran reporting the surgical outcome of
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patients with VSIAs undergoing clipping.
In conclusion, surgical clipping of ruptured and unruptured VSIAs is a safe and effective modality of treatment associated with low mortality and morbidity. Age, co-morbidities (hypertension, ischemic heart disease), on admission GCS, Hunt and Hess grade,
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preoperative VP-Shunt insertion and subarachnoid hemorrhage are important predictors of outcome in patients with VSIAs undergoing surgery.
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Acknowledgment
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We would like to acknowledge all the patients and their families whose information was used in this study.
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Tables
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Table 1 Baseline characteristics of 52patients with very small intracranial aneurysms undergoing surgery in our center from 2010 to 2016. Variable Value Age (years) 53.7 ± 10.8 Gender Men (%) 21 (40.1%) Women (%) 31 (59.6%) Presentation Ruptures VISA (%) 19 (36.5%) Ruptured larger aneurysm (%) 18 (34.6%) Unruptured VISA (%) 15 (28.8%) GCS on admission 13.38 ± 2.98 Hunt and Hess grade 1 (%) 17 (32.7%) 2 (%) 11 (21.2%) 3 (%) 1 (1.9%) 4 (%) 5 (9.6%) 5 (%) 3 (5.8%) Fisher grade 1 (%) 4 (7.7%) 2 (%) 6 (11.5%) 3 (%) 24 (46.2%) 4 (%) 3 (5.8%) Co-morbidities Hypertension (%) 25 (48.1%) Smoking (%) 12 (23.1%) Ischemic heart disease (%) 9 (17.3%) Diabetes mellitus (%) 6 (11.5%) Opium addiction (%) 5 (9.6%) Total number of intracranial aneurysms 1 (%) 25 (48.1%) 2 (%) 16 (30.8%) 3 (%) 9 (17.3%) 5 (%) 2 (3.8%) Total number of VSIAs 1 (%) 44 (84.6%) 2 (%) 6 (11.5%) 3 (%) 2 (3.8%) GCS: Glasgow Coma Scale (GCS); VISA: Very Small Intracranial Aneurysm
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Table 2Pre-, intra- and postoperative characteristicsof 94intracranial aneurysms and 62 VSIAs in 52 patients undergoing surgery in our center from 2010 to 2016. Location Frequency Location of intracranial aneurysms MCA (%) 49 (52.1%) A-Com (%) 19 (20.2%) ACA (%) 11 (11.7%) P-Com (%) 7 (7.6%) Internal Carotid (%) 4 (4.2%) Ophthalmic (%) 4 (4.2%) Location of VSIAs MCA (%) 31 (50.0%) A-Com (%) 12 (19.3%) ACA (%) 10 (16.1%) P-Com (%) 5 (8.1%) Ophthalmic (%) 3 (4.8%) Internal Carotid (%) 1 (1.7%) Intraoperative variables Intraoperative rupture (%) 14 (26.9%) Preoperative VP-Shunt insertion (%) 6 (12.5%) Intraoperative bleeding (mL) 180.38 ± 137.88 Operation duration (min) 66.3 ± 41.3 Surgery Approach Lateral supraorbital (%) 48 (92.3%) Interhemispheric (%) 4 (7.7%) Surgery technique Helper clip technique (%) 26 (50.0%) Direct clipping (%) 19 (36.5%) Catanoid wrapping (%) 7 (13.5%) Prognosis Favorable (%) 44 (84.6%) Unfavorable (%) 8 (15.4%) ACA: Anterior Cerebral Artery; A-Com: Anterior Communicating Artery; MCA: Middle Cerebral Artery;P-Com: Posterior Communicating Artery; VSIA: Very Small Intracranial Aneurysm
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Table 3 The outcome of52 patients with very small intracranial aneurysms undergoing surgery in our center determined by Glasgow outcome scale and modified ranking scale. Unruptured VISA (n=15)
13 (68.4%) 2 (10.5%) 1 (5.3%) 1 (5.3%) 2 (10.5%)
15 (100%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
4 (21.1%) 9 (47.4%) 1 (5.3%) 1 (5.3%) 1 (5.3%) 1 (5.3%) 2 (10.5%)
5 (33.3%) 9 (60.0%) 1 (6.7%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
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6-month GOS Good Recovery (%) 10 (55.6%) Moderate disability (%) 2 (11.1%) Severe disability (%) 1 (5.5%) Persistent vegetative state (%) 2 (11.1%) Death (%) 3 (16.7%) 6-month MRS No Symptoms (%) 1 (5.5%) No significant disability (%) 9 (50.0%) Slight disability (%) 2 (11.1%) Moderate disability (%) 0 (0.0%) Moderately severe disability (%) 0 (0.0%) Severe disability (%) 3 (16.7%) Dead (%) 3 (16.7%) GOS: Glasgow Outcome Scale; MRS: Modified Rankin Scale
Ruptured VISA (n=19)
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Ruptured aneurysm (n=18)
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Table 4 Intraoperative and outcome of 52 patients with very small intracranial aneurysms undergoing surgery in our center from 2010 to 2016. Favorable (n=44) Unfavorable (n=8) p-value Age (years) 52.3 ± 10.5 61.5 ± 9.8 0.027 Gender Men (%) 20 (45.5%) 1 (12.5%) 0.122 Women (%) 24 (54.5%) 7 (87.5%) Co-morbidities Hypertension (%) 18 (40.9%) 7 (87.5%) 0.022 Ischemic heart disease (%) 5 (11.4%) 4 (50.0%) 0.023 Smoking (%) 12 (27.3%) 0 (0.0%) 0.174 Diabetes mellitus (%) 4 (9.1%) 2 (25.0%) 0.227 Opium addiction (%) 5 (11.4%) 0 (0.0%) 0.418 GCS on admission 14.11 ± 2.16 9.37 ± 3.77 <0.001 Subarachnoid hemorrhage (%) 29 (65.9%) 8 (100%) 0.015 Hunt and Hess grade 1.68 ± 1.07 3.50 ± 1.31 <0.001 Fisher grade 2.58 ± 0.82 3.12 ± 0.35 0.082 Number of aneurysms 1.82 ± 1.04 1.75 ± 0.71 0.860 Number of VSIAs 1.23 ± 0.52 1.03 ± 0.43 0.228 Intraoperative bleeding (mL) 175.6 ± 131.7 206.2 ± 176.2 0.569 Operation duration (min) 63.2 ± 38.6 83.7 ± 53.3 0.198 Preoperative VP-Shunt (%) 3 (6.8%) 3 (37.5%) 0.040 Intraoperative rupture (%) 11 (25.0%) 3 (37.5%) 0.666 Location VSIAs MCA (%) 21 (47.7%) 4 (50.0%) A-Com (%) 8 (16.6%) 2 (25.0%) P-Com (%) 5 (11.3%) 0 (0.0%) 0.088 ACA (%) 3 (6.25%) 1 (12.5%) Distal ACA (%) 3 (6.25%) 1 (12.5%) Ophthalmic (%) 3 (6.25%) 0 (0.0%) Internal Carotid (%) 1 (5.56%) 0 (0.0%)
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Table 5 Multivariate analysis for association with unfavorable outcome (GOS of 1-3). OR
95% CI
Age
0.002
2.726
1.426-3.264
On admission GCS
<0.001
5.785
3.466-7.021
Hypertension
0.022
1.337
Ischemic heart disease
0.023
1.633
Subarachnoid hemorrhage
0.015
2.188
Hunt and Hess grade
0.001
4.012
Confidence
interval;
GCS:
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Ventriculoperitoneal
Glasgow
1.036-1.727 0.903-2.951
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Preoperative VP-shunt insertion 0.040 CI:
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p-value
1.783
Coma
Scale;
1.563-2.892 2.233-5.902 0.796-3.993
OR:
Odds
Ratio,
VP:
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Table 6 The series of very small intracranial aneurysms (VSIAs) published in the literature. Condition
Procedure
Morbidity
Occlusion rate
Mortality
Our series
62
Rupture/Unruptured
Surgery
9.61%
86.5%
9.61%
Bruneau et al.1
228
Unruptured
Surgery
2.7%
98.2%
0.0%
Kiran et al.11
40
Rupture/Unruptured
Surgery
12.8%
97.4%
0.0%
Krisht et al.12
25
Unruptured
Surgery
3.44%
100%
0.82%
Li et al.9
85
Ruptured
Surgery
7.10%
94.3%
2.35%
Li et al.9
97
Ruptured
Endovascular
1.03%
64.9%
1.03%
Im et al.10
435
Unruptured
Endovascular
0.27%
76.8%
0.0%
van Rooij et al.13
196
Rupture/Unruptured
Endovascular
2.1%
94.9%
1.1%
Chalouhi et al. 29
100
Rupture/Unruptured
Endovascular
3%
72%
0.0%
Ji et al.31
112
Rupture/Unruptured
Endovascular
3.2%
96.3%
0.0%
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No. of VISAs
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B
C
D
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E
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A
F
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Fig 1. A 55-year-old man with family history of intracranial aneurysm surgery in mother, brother and sister underwent screening with brain CT angiography which revealed an unruptured intracranial aneurysm in left middle cerebral artery bifurcation measuring 2.5mm (A, B). intraoperative image demonstrating the aneurysm before (C) and after applying a temporary clip (D). the aneurysm was successfully clipped directly with a 4mm mini clip (E) without any remnant. The postoperative brain CT-scan revealed no hematoma or hydrocephalus (F). The patient was discharged with good health in 4th postoperative day and had good recovery in 6-month follow up.
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Surgical clipping of ruptured and unruptured VSIAs is a safe and effective modality of treatment associated with low mortality and morbidity. Age, comorbidities (hypertension, ischemic heart disease), on admission GCS,
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subarachnoid hemorrhage, Hunt and Hess grade, preoperative VP-Shunt insertion are important predictors of outcome in patients with VSIAs undergoing
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surgery.
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•
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MRS: Modified Rankin Scale VP: Ventriculoperitoneal
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VSIA: Very Small Intracranial Aneurysm
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IRB: Institutional Review Board
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Disclosure of conflict of interest
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None of the authors have any conflict of interest to be declared regarding the manuscript.