Role of apoptosis in intracranial aneurysm rupture

2004 ◽  
Vol 101 (6) ◽  
pp. 1018-1025 ◽  
Author(s):  
Luigi Pentimalli ◽  
Andrea Modesti ◽  
Andrea Vignati ◽  
Enrico Marchese ◽  
Alessio Albanese ◽  
...  

Object. Mechanisms involved in the rupture of intracranial aneurysms remain unclear, and the literature on apoptosis in these lesions is extremely limited. The hypothesis that apoptosis may reduce aneurysm wall resistance, thus contributing to its rupture, warrants investigation. The authors in this study focused on the comparative evaluation of apoptosis in ruptured and unruptured intracranial aneurysms. Peripheral arteries in patients harboring the aneurysms and in a group of controls were also analyzed. Methods. Between September 1999 and February 2002, specimens from 27 intracranial aneurysms were studied. In 13 of these patients apoptosis was also evaluated in specimens of the middle meningeal artery (MMA) and the superficial temporal artery (STA). The terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling technique was used to study apoptosis via optical microscopy; electron microscopy evaluation was performed as well. Apoptotic cell levels were related to patient age and sex, aneurysm volume and shape, and surgical timing. Significant differences in apoptosis were observed when comparing ruptured and unruptured aneurysms. High levels of apoptosis were found in 88% of ruptured aneurysms and in only 10% of unruptured lesions (p < 0.001). Elevated apoptosis levels were also detected in all MMA and STA specimens obtained in patients harboring ruptured aneurysms, whereas absent or very low apoptosis levels were observed in MMA and STA specimens from patients with unruptured aneurysms. A significant correlation between aneurysm shape and apoptosis was found. Conclusions. In this series, aneurysm rupture appeared to be more related to elevated apoptosis levels than to the volume of the aneurysm sac. Data in this study could open the field to investigations clarifying the causes of aneurysm enlargement and rupture.

2000 ◽  
Vol 93 (3) ◽  
pp. 379-387 ◽  
Author(s):  
Seppo Juvela ◽  
Matti Porras ◽  
Kristiina Poussa

Object. The authors conducted a study to investigate the long-term natural history of unruptured intracranial aneurysms and the predictive risk factors determining subsequent rupture in a patient population in which surgical selection of cases was not performed.Methods. One hundred forty-two patients with 181 unruptured aneurysms were followed from the 1950s until death or the occurrence of subarachnoid hemorrhage or until the years 1997 to 1998. The annual and cumulative incidence of aneurysm rupture as well as several potential risk factors predictive of rupture were studied using life-table analyses and Cox's proportional hazards regression models including time-dependent covariates.The median follow-up time was 19.7 years (range 0.8–38.9 years). During 2575 person-years of follow up, there were 33 first-time episodes of hemorrhage from previously unruptured aneurysms, for an average annual incidence of 1.3%. In 17 patients, hemorrhage led to death. The cumulative rate of bleeding was 10.5% at 10 years, 23% at 20 years, and 30.3% at 30 years after diagnosis. The diameter of the unruptured aneurysm (relative risk [RR] 1.11 per mm in diameter, 95% confidence interval [CI] 1–1.23, p = 0.05) and patient age at diagnosis inversely (RR 0.97 per year, 95% CI 0.93–1, p = 0.05) were significant independent predictors for a subsequent aneurysm rupture after adjustment for sex, hypertension, and aneurysm group. Active smoking status at the time of diagnosis was a significant risk factor for aneurysm rupture (RR 1.46, 95% CI 1.04–2.06, p = 0.033) after adjustment for size of the aneurysm, patient age, sex, presence of hypertension, and aneurysm group. Active smoking status as a time-dependent covariate was an even more significant risk factor for aneurysm rupture (adjusted RR 3.04, 95% CI 1.21–7.66, p = 0.02).Conclusions. Cigarette smoking, size of the unruptured intracranial aneurysm, and age, inversely, are important factors determining risk for subsequent aneurysm rupture. The authors conclude that such unruptured aneurysms should be surgically treated regardless of their size and of a patient's smoking status, especially in young and middle-aged adults, if this is technically possible and if the patient's concurrent diseases are not contraindications. Cessation of smoking may also be a good alternative to surgery in older patients with small-sized aneurysms.


1994 ◽  
Vol 80 (3) ◽  
pp. 440-446 ◽  
Author(s):  
Robert A. Solomon ◽  
Matthew E. Fink ◽  
John Pile-Spellman

✓ The surgical management of patients with unruptured intracranial aneurysms continues to be controversial. The criteria for withholding treatment or choosing between endovascular embolization and conventional microsurgery are not well delineated. The present study analyzes the morbidity and mortality that can be expected with modern surgical management of unruptured aneurysms, and therefore serves as a point of reference for clinical decision-making in this group of patients. A total of 202 consecutive operations for attempted clipping of unruptured intracranial aneurysms are reported. Subarachnoid hemorrhage from another aneurysm was the most common presentation (55 cases). Thirty-seven patients presented with headache, 36 with mass effect from the aneurysm, and 19 with embolic events; 11 aneurysms were associated with an arteriovenous malformation, 10 caused seizures, and 34 were incidental findings. Excellent or good outcome was achieved in 100% of patients with aneurysms less than 10 mm in diameter, 95% with aneurysms 11 to 25 mm, and 79% with aneurysms greater than 25 mm. Except for giant basilar aneurysms, size (and not location) of the aneurysm was the key predictor of risk for surgical morbidity. These data may be useful when discussing with patients the risk:benefit ratio of choosing between conservative management, endovascular embolization, and microsurgical clipping.


2019 ◽  
Vol 26 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Jens J Froelich ◽  
Nicholas Cheung ◽  
Johan AB de Lange ◽  
Jessica Monkhorst ◽  
Michael W Carr ◽  
...  

Objective Incomplete aneurysm occlusions and re-treatment rates of 52 and 10–30%, respectively, have been reported following endovascular treatment of intracranial aneurysms, raising clinical concerns regarding procedural efficacy. We compare residual, recurrence and re-treatment rates subject to different endovascular techniques in both ruptured and unruptured intracranial aneurysms at a comprehensive state-wide tertiary neurovascular centre in Australia. Methods Medical records, procedural and follow-up imaging studies of all patients who underwent endovascular treatment for intracranial aneurysms between July 2010 and July 2017 were reviewed retrospectively. Residuals, recurrences and re-treatment rates were assessed regarding initial aneurysm rupture status and applied endovascular technique: primary coiling, balloon- and stent-assisted coiling and flow diversion. Results Among 233 aneurysms, residual, recurrence and re-treatment rates were 27, 11.2 and 9.4%, respectively. Compared with unruptured aneurysms, similar residual and recurrence (p > .05), but higher re-treatment rates (4.5% vs. 19%; p < .001) were found for ruptured aneurysms. Residual, recurrence and re-treatment rates were: 13.3, 16 and 12% for primary coiling; 12, 12 and 10.7% for balloon-assisted coiling; 14.9, 7.5 and 4.5% for stent-assisted coiling; 91.9, 0 and 5.4% for flow diversion. Stent-assistance and flow-diversion were associated with lower recurrence and re-treatment rates, when compared with primary- and balloon-assisted coiling (p < .05). Conclusions Residuals and recurrences after endovascular treatment of intracranial aneurysms are less common than previously reported. Stent assistance and flow diversion seem associated with reduced recurrence- and re-treatment rates, when compared with primary- and balloon-assisted coiling. Restrained use of stents in ruptured aneurysms may be a contributing factor for higher recurrence/retreatment rates compared to unruptured aneurysms.


1996 ◽  
Vol 84 (1) ◽  
pp. 49-54 ◽  
Author(s):  
Rohit K. Khanna ◽  
Ghaus M. Malik ◽  
Nuzhat Qureshi

✓ Surgical treatment of unruptured aneurysms is gaining increased support owing to the recently defined poor long-term natural history of these aneurysms. The benefit of treatment ultimately depends on the relative risk of subsequent aneurysm rupture in untreated patients versus the risk of surgery. To identify those patients at a higher risk from surgery, the authors reviewed the management of 172 patients with unruptured intracranial aneurysms treated at their institution. The size of the aneurysms ranged from 3 to 45 mm (mean 13.7 mm). Twenty-two patients (12.8%) had aneurysms in the posterior circulation, and 32 (18.6%) of these were giant aneurysms. Major morbidity occurred in 12 patients (6.9%) and five patients (2.9%) died. Multivariate logistic analysis of several risk factors revealed that aneurysm size and location had an independent correlation with surgical outcome and that patient age approached statistical significance. Patients presenting with ischemic cerebrovascular disease, in particular, did not have a higher risk of a poor outcome. A simple classification for predicting patients at high risk from surgical morbidity and mortality is proposed. Preoperative grading is based on the size and location of the aneurysm and patient's age. The lowest grade is given to young patients with small anterior circulation aneurysms, and the highest grade includes elderly patients with complex giant posterior circulation aneurysms. A retrospective analysis of this classification demonstrated a strong correlation with postoperative outcome. The incidence of poor outcome progressively increased with a higher grade, ranging from 0% in Grade 0 to 66.6% in Grade VI. An analysis of this classification on 50 consecutive surgically treated patients with unruptured aneurysms not included in the analysis also validated the predictive value of this system. Along with predicting outcome, this classification should provide a standardized format for comparison of results from different clinical centers as well as different therapeutic techniques (surgical vs. endovascular) without omission of significant risk factors found to influence outcome.


2001 ◽  
Vol 94 (3) ◽  
pp. 417-421 ◽  
Author(s):  
Douglas Chyatte ◽  
Rebecca Porterfield

Object. Repair of unruptured aneurysms is a reasonable course of action if their expected natural history is worse than the predicted risks of treatment. The purpose of this study was to examine the presenting symptoms of unruptured aneurysms and to test the hypothesis that unruptured intracranial aneurysms can be repaired without significant functional worsening. A second hypothesis was also examined—that is, that the experience of the surgeon, the aneurysm size, and the patient age can be used to predict functional outcome. Methods. Consecutive patients who underwent repair of an unruptured intracranial aneurysm at a single institution between 1980 and 1998 were studied. Clinical and radiographic data were collected in all patients. Their modified Rankin Scale (mRS) score was determined before treatment (baseline), at 6 weeks, and at 6 months. The primary endpoint for analysis was the mRS score. Four hundred forty-nine aneurysms were repaired in 366 patients by 10 surgeons. The mean size of the primary lesion repaired was 14.6 + 10.4 mm and 27% were judged to be symptomatic. Aneurysm treatment involved either microsurgical clipping (78%), wrapping (4%), trapping with or without bypass (5%), hunterian ligation with or without bypass (9%), or other methods (4%). The mRS scores at 6 weeks were worse than at baseline (p < 0.0001), but there was no significant difference between the baseline and 6-month mRS score. At 6 months, 94% of patients showed no significant functional worsening as a result of treatment. The number of aneurysms treated by a specific surgeon was a strong predictor of better functional outcome (r = 0.99, p = 0.05). Increasing patient age (r = 0.16, p = 0.003) and increasing aneurysm size (r = 0.15, p = 0.004) were predictors of worsened functional outcome. Conclusions. Many unruptured aneurysms produce symptoms. Unruptured intracranial aneurysms can be treated without significant permanent functional worsening. The surgeon's experience, aneurysm size, and patient age are predictors of functional outcome.


2002 ◽  
Vol 96 (1) ◽  
pp. 3-42 ◽  
Author(s):  
Bryce Weir

Object. In this article, pathological, radiological, and clinical information regarding unruptured intracranial aneurysms is reviewed. Methods. Treatment decisions require that surgeons and interventionists take into account information obtained in pathological, radiological, and clinical studies of unruptured aneurysms. The author has performed a detailed review of the literature and has compared, contrasted, and summarized his findings. Unruptured aneurysms may be classified as truly incidental, part of a multiple aneurysm constellation, or symptomatic by virtue of their mass, irritative, or embolic effects. Unruptured aneurysms with clinical pathological profiles resembling those of ruptured lesions should be considered for treatment at a smaller size than unruptured lesions with profiles typical of intact aneurysms, as has been determined at autopsy in patients who have died of other causes. The track record of the surgeon or interventionist and the institution in which treatment is to be performed should be considered while debating treatment options. In cases in which treatment is not performed immediately, ongoing periodic radiological assessment may be wise. Radiological investigations to detect unruptured aneurysms in asymptomatic patients should be restricted to high-prevalence groups such as adults with a strong family history of aneurysms or patients with autosomal dominant polycystic kidney disease. All patients with intact lesions should be strongly advised to discontinue cigarette smoking if they are addicted. Conclusions. The current state of knowledge about unruptured aneurysms does not support the use of the largest diameter of the lesion as the sole criterion on which to base treatment decisions, although it is of undoubted importance.


2002 ◽  
Vol 96 (1) ◽  
pp. 57 ◽  
Author(s):  
Seppo Juvela ◽  
Matti Porras ◽  
Kristiina Poussa

Object. The authors conducted a study to investigate the long-term natural history of unruptured intracranial aneurysms and the predictive risk factors determining subsequent rupture in a patient population in which surgical selection of cases was not performed. Methods. One hundred forty-two patients with 181 unruptured aneurysms were followed from the 1950s until death or the occurrence of subarachnoid hemorrhage or until the years 1997 to 1998. The annual and cumulative incidence of aneurysm rupture as well as several potential risk factors predictive of rupture were studied using life-table analyses and Cox's proportional hazards regression models including time-dependent covariates. The median follow-up time was 19.7 years (range 0.8–38.9 years). During 2575 person-years of follow up, there were 33 first-time episodes of hemorrhage from previously unruptured aneurysms, for an average annual incidence of 1.3%. In 17 patients, hemorrhage led to death. The cumulative rate of bleeding was 10.5% at 10 years, 23% at 20 years, and 30.3% at 30 years after diagnosis. The diameter of the unruptured aneurysm (relative risk [RR] 1.11 per mm in diameter, 95% confidence interval [CI] 1–1.23, p = 0.05) and patient age at diagnosis inversely (RR 0.97 per year, 95% CI 0.93–1, p = 0.05) were significant independent predictors for a subsequent aneurysm rupture after adjustment for sex, hypertension, and aneurysm group. Active smoking status at the time of diagnosis was a significant risk factor for aneurysm rupture (RR 1.46, 95% CI 1.04–2.06, p = 0.033) after adjustment for size of the aneurysm, patient age, sex, presence of hypertension, and aneurysm group. Active smoking status as a time-dependent covariate was an even more significant risk factor for aneurysm rupture (adjusted RR 3.04, 95% CI 1.21–7.66, p = 0.02). Conclusions. Cigarette smoking, size of the unruptured intracranial aneurysm, and age, inversely, are important factors determining risk for subsequent aneurysm rupture. The authors conclude that such unruptured aneurysms should be surgically treated regardless of their size and of a patient's smoking status, especially in young and middle-aged adults, if this is technically possible and if the patient's concurrent diseases are not contraindications. Cessation of smoking may also be a good alternative to surgery in older patients with small-sized aneurysms.


1971 ◽  
Vol 34 (5) ◽  
pp. 706-708 ◽  
Author(s):  
Martin L. Lazar ◽  
Clark C. Watts ◽  
Bassett Kilgore ◽  
Kemp Clark

✓ Angiography during the operative procedure is desirable, but is often difficult because of the problem of maintaining a needle or cannula in an artery for long periods of time. Cannulation of the superficial temporal artery avoids this technical problem. The artery is easily found, cannulation is simple, and obliteration of the artery is of no consequence. Cerebral angiography then provides a means for prompt evaluation of the surgical procedure at any time during the actual operation.


2013 ◽  
Vol 19 (1) ◽  
pp. 43-48 ◽  
Author(s):  
K. Wang ◽  
Y. Sun ◽  
A-M. Li

Despite experience and technological improvements, stent-assisted coiling for intracranial aneurysms still has inherent risks. We evaluated peri-procedural morbidity and mortality associated with stent-assisted coiling for intracranial aneurysms. Patients with cerebral aneurysms that were broad-based (>4 mm) or had unfavorable dome/neck ratios (<1.5) were enrolled in this study between February and November 2011 at our center. Aneurysms were treated with the self-expanding neurovascular stents with adjunctive coil embolization. Seventy-two consecutive patients (27 men and 45 women; 22–78 years of age; mean age, 52.8 years) underwent 13 procedures for 13 ruptured aneurysms and 64 procedures for 73 unruptured aneurysms. Nine [11.7%, 95% CI(4.5%–18.9%)] procedure-related complications occurred: one and eight with initial embolization of ruptured and unruptured aneurysms, respectively. Complications included six acute in-stent thromboses, one spontaneous stent migration, one post-procedural aneurysm rupture, and one perforator occlusion. Three complications had no neurologic consequences. Two caused transient neurologic morbidity, two persistent neurologic morbidity, and two death. Procedure-related neurologic morbidity and mortality rates, respectively, were as follows: overall, 5.2% (95%CI, 0.2%–10.2%) and 2.6% (95%CI, 0%–6.2%); ruptured aneurysms, 7.7% (95%CI, 0%–36%) and 0% (95%CI, 0%–25%); unruptured aneurysms, 4.7% (95%CI, 0%–9.9%) and 3.1% (95%CI, 0%–7.3%). Combined procedure-related morbidity and mortality rates for ruptured and unruptured aneurysms were 7.7% (95%CI, 1.7%–13.7%) and 7.8% (95%CI, 1.8%–13.8%), respectively. Stent-assisted coiling is an attractive option for intracranial aneurysms. However, stent-assisted coiling for unruptured aneurysms is controversial for its comparable risk to natural history.


2019 ◽  
Vol 131 (4) ◽  
pp. 1262-1268 ◽  
Author(s):  
Shunsuke Omodaka ◽  
Hidenori Endo ◽  
Kuniyasu Niizuma ◽  
Miki Fujimura ◽  
Takashi Inoue ◽  
...  

OBJECTIVERecent MR vessel wall imaging studies have indicated intracranial aneurysms in the active state could show circumferential enhancement along the aneurysm wall (CEAW). While ruptured aneurysms frequently show CEAW, CEAW in unruptured aneurysms at the evolving state (i.e., growing or symptomatic) has not been studied in detail. The authors quantitatively assessed the degree of CEAW in evolving unruptured aneurysms by comparing it separately to that in stable unruptured and ruptured aneurysms.METHODSA quantitative analysis of CEAW was performed in 26 consecutive evolving aneurysms using MR vessel wall imaging. Three-dimensional T1-weighted fast spin echo sequences were obtained before and after contrast media injection, and the contrast ratio of the aneurysm wall against the pituitary stalk (CRstalk) was calculated as the indicator of CEAW. Aneurysm characteristics of evolving aneurysms were compared with those of 69 stable unruptured and 67 ruptured aneurysms.RESULTSThe CRstalk values in evolving aneurysms were significantly higher than those in stable aneurysms (0.54 vs 0.34, p < 0.0001), and lower than those in ruptured aneurysms (0.54 vs 0.83, p < 0.0002). In multivariable analysis, CRstalk remained significant when comparing evolving with stable aneurysms (odds ratio [OR] 12.23, 95% confidence interval [CI] 3.53–42.41), and with ruptured aneurysms (OR 0.083, 95% CI 0.022–0.310).CONCLUSIONSThe CEAW in evolving aneurysms was higher than those in stable aneurysms, and lower than those in ruptured aneurysms. The degree of CEAW may indicate the process leading to rupture of intracranial aneurysms, which can be useful additional information to determine an indication for surgical treatment of unruptured aneurysms.


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