Natural history of unruptured intracranial aneurysms: probability of and risk factors for aneurysm 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.

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.


2008 ◽  
Vol 108 (5) ◽  
pp. 1052-1060 ◽  
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.


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.


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.


2020 ◽  
pp. 159101992095953
Author(s):  
Dylan Noblett ◽  
Lotfi Hacein-Bey ◽  
Ben Waldau ◽  
Jordan Ziegler ◽  
Brian Dahlin ◽  
...  

Background Aneurysmal subarachnoid hemorrhage (SAH) is the most common cause of nontraumatic SAH. Current guidelines generally recommend observation for unruptured intracranial aneurysms smaller than 7 mm, for those are considered at low risk for spontaneous rupture according to available scoring systems. Objective We observed a tendency for SAH in small intracranial aneurysms in patients who are methamphetamine users. A retrospective, single center study to characterize the size and location of ruptured and unruptured intracranial aneurysms in methamphetamine users was performed. Materials and methods Clinical characteristics and patient data were collected via retrospective chart review of patients with intracranial aneurysms and a history of methamphetamine use with a specific focus on aneurysm size and location. Results A total of 62 patients were identified with at least one intracranial aneurysm and a history of methamphetamine use, yielding 73 intracranial aneurysms (n = 73). The mean largest diameter of unruptured aneurysms (n = 44) was 5.1 mm (median 4.5, SD 2.5 mm), smaller than for ruptured aneurysms (n = 29) with a mean diameter of 6.3 mm (median 5.5, SD 2.5 mm). Aneurysms measuring less than 7 mm presented with SAH in 36.5%. With regard to location, 28% (n = 42) of anterior circulation aneurysms less than 7 mm presented with rupture, in contrast to 70% (n = 10) of posterior circulation aneurysms which were found to be ruptured. Conclusions Methamphetamine use may be considered a significant risk factor for aneurysmal SAH at a smaller aneurysm size than for other patients. These patients may benefit from a lower threshold for intervention and/or aggressive imaging and clinical follow-up.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2487-2487 ◽  
Author(s):  
Francoise Bernaudin ◽  
Suzanne Verlhac ◽  
Annie Kamdem ◽  
Cécile Arnaud ◽  
Lena Coïc ◽  
...  

Abstract Background Silent infarcts are associated with impaired cognitive functioning and have been shown to be predictors of stroke (Miller ST J Pediatr 2001). Until now, reported risk factors for silent infarcts were low pain event rate, history of seizures, high leukocyte count and Sen bS haplotype (Kinney TR Pediatrics 1999). Here, we seek to define the prevalence and risk factors of silent infarcts in the Créteil SCA pediatric cohort comprising patients assessed at least yearly by transcranial doppler (TCD) since 1992, and by MRI/MRA. Methods This study retrospectively analyzed data from the Créteil cohort stroke-free SS/Sb0 children (280; 134 F, 146 M), according to institutional review board. Time-averaged mean of maximum velocities higher than 200 cm/sec were considered as abnormal, resulting in initiation of a transfusion program (TP). A switch to hydroxyurea was proposed to patients with normalized velocities (&lt; 170 cm/sec) and normal MRA on TP, although TP was re-initiated in case of abnormal velocities recurrence. Patients with “conditional” velocities (170–199 cm/sec) were assessed by TCD 4 times yearly. Alpha genes and beta-globin haplotypes were determined. Baseline biological parameters (G6PD activity; WBC, PMN, Reticulocytes, Platelets counts; Hemoglobin, Hematocrit, HbF, LDH levels; MCV; SpO2) were obtained a minimum of 3 months away from a transfusion, one month from a painful episode, after 12 months of age, before the first TCD, and always before therapy intensification. Results. Patients were followed for a total of 2139 patient-years. Alpha-Thal was present in 114/254 patients (45%) and 27/241 (11.2%) had G6PD deficiency. Beta genotype, available in 240 patients, was BaBa in 102 (42.5%), BeBe in 54 (22.5%), SeSe in 19 (7.9%) and “other” in 65 (27.1%); TCD was abnormal in 52 of 280 patients (18.6%). MRA showed stenoses in 30 of 226 evaluated patients (13.3%) while MRI demonstrated presence of silent infarcts in 81/280 patients (28.9%). Abnormal TCD (p&lt;0.001), G6PD deficiency (p=0.008), high LDH (p=0.03), and low Hb (p=0.026) were significant risk factors for stenoses by univariate analysis while multivariate analysis retained only abnormal TCD as a significant risk factor for stenoses ([OR= 10.6, 95% CI (4.6–24.4)]; p&lt;0.001). Univariate logistic regression analysis showed that the risk of silent infarcts was not related to alpha-Thal, beta genotype, abnormal TCD, WBC, PMN, platelets, reticulocyte counts, MCV, LDH level, HbF %, pain or ACS rates but was significantly associated with stenoses detected by MRA (p&lt;0.001), gender (male; p=0.04), G6PD deficiency (p=0.05), low Hb (p=0.016) and Hct (p=0.012). Multivariate logistic regression analysis showed that gender ([OR= 2.1, 95% CI (1.03–4.27)]; p=0.042), low Hb ([OR= 1.4, 95% CI (1.0–1.1)]; p=0.05) and stenoses ([OR= 4.8, 95% CI (1.88–12.28)]; p=0.001) were all significant independent risk factors for silent infarcts. The presence of stenoses was the only significant risk factor for silent infarcts in patients with a history of abnormal TCD ([OR= 5.9, 95% CI (1.6–21.7)]; p=0.008). Conclusion We recently showed that G6PD deficiency, absence of alpha-Thal, and hemolysis are independent significant risk factors for abnormal TCD in stroke-free SCA patients (Bernaudin et al, Blood, 2008, in press). Here, we report that an abnormal TCD is the most significant risk factor for stenoses and, expanding previous studies, we demonstrate that stenoses, low Hb and gender are significant independent risk factors for silent infarcts.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19056-e19056
Author(s):  
K. Hotta ◽  
K. Kiura ◽  
N. Takigawa ◽  
H. Yoshioka ◽  
S. Harita ◽  
...  

e19056 Background: Erlotinib was approved in Dec 2007 in Japan, and incidence and pattern of ILD during its therapy for Japanese pts with NSCLC has not still been determined, although we had previously reported the frequency of ILD through the gefitinib treatment [PASCO2004, #7063]. In this study, we intended to elucidate this issue in pts receiving erlotinib therapy. Methods: We reviewed the clinical records of 159 pts who had initiated erlotinib therapy last year (cohort A), and of 330 pts receiving gefitinib between 2000 and 2003 (cohort B) for comparing the incidence and pattern of ILD during the both TKI treatments. Toxicity data during the first months after the initiation of TKIs were obtained. Results: The demographics of 489 pts were as follows; M:63%, Ad:75%, and PS 0–1:69%. None of pts in the cohort B received erlotinib therapy before the gefitinib treatment, whereas 66 of the 159 cohort A pts (42%) were given gefitinib before the erlotinib therapy. In 23% and 28% of the pts in the cohorts A and B, erlotinib and gefitinb treatments were discontinued within 1 month after the initiation of TKI therapy, respectively. Two pts (1.3%) developed ILD in the cohort A during the first month of erlotinib treatment, while 8 ILD-events (2.4%) were observed in the gefitinib therapy (cohort B) during the same treatment period. Both 2 pts who developed ILD during the erlotinib therapy had not had a history of prior gefitinib treatment. The toxicity grades of ILD were as follows: grades 1 and 2 in 1 each (cohort A) and grades 3, 4 and 5 in 1, 1 and 6 pts, respectively (cohort B). Statistically significant factors affecting the occurrence of ILD by multivariate analysis were presence of prior pulmonary fibrosis (OR=37.3, p<0.01) and poor PS (OR=6.4, p=0.02), but type of TKIs was not a significant risk factor for ILD. Conclusions: In this setting, the type of TKIs did not affect the incidence of ILD although its incidence after the initiation of erlotinib was somewhat low as compared with that during gefitinib therapy. In addition, the grade of ILD was less severe in the cohort A. These might be partly due to a patient selection based on the recent awareness of Japanese physicians regarding the risk factors for ILD events who learned it through the gefitinib treatment. No significant financial relationships to disclose.


1997 ◽  
Vol 86 (2) ◽  
pp. 211-219 ◽  
Author(s):  
Jean Raymond ◽  
Daniel Roy ◽  
Michel Bojanowski ◽  
Robert Moumdjian ◽  
Georges L'Espérance

✓ The surgical treatment of basilar bifurcation aneurysms is difficult and the need for an alternative approach is frequently stated. To assess the efficacy and safety of endovascular treatment of aneurysms located at the basilar bifurcation, the authors prospectively studied angiographic results, clinical results, and complications in 31 patients treated with Guglielmi detachable coils (GDCs). Patients treated acutely after subarachnoid hemorrhage (SAH) were graded according to the Hunt and Hess classification and clinical outcome was determined at 1- and 6-month intervals according to the Glasgow Outcome Scale (GOS). There were 18 women and 13 men, ranging in age from 34 to 67 years (mean age 48 years). Twenty-three were treated acutely after SAH. Clinical Hunt and Hess grades at presentation were as follows: Grade I, six patients; Grade II, three; Grade III, 11; Grade IV, two; and Grade V, one. The GOS score for the group of patients treated acutely was: GOS I, 18 patients; GOS II, III, and IV, one patient each; and GOS V, two patients. There were seven technical complications in this group, most often asymptomatic, but one patient died after aneurysm rupture during treatment and one had residual diplopia at 4 months. Eight patients were treated for incidental basilar bifurcation aneurysms. One technical complication with no neurological deficit occurred in this group of patients with incidental aneurysms. Immediate angiographic results were considered to be satisfactory in 94% of patients, with complete obliteration in 42% and residual neck and dog ears in 52%. There was no bleeding episode after treatment during clinical follow-up periods ranging from 3 to 42 months (mean 15.5 months in 29 surviving patients). Angiographic results were available for 27 patients at 6 months and were as follows: 30% of the lesions were completely obliterated, 59% presented some residual neck, and 11% showed some opacification of the aneurysm sac. During the follow-up period of up to 42 months, a total of seven recurrences were noted, necessitating retreatment with GDCs in five patients. Endovascular treatment of basilar bifurcation aneurysms prevented rebleeding and could be performed without clinically significant complications in 94% of patients. Clinical results after SAH compared favorably with surgical series. Morphological results appear less satisfactory, and long-term angiographic follow-up review is mandatory to detect recurrences.


2000 ◽  
Vol 93 (6) ◽  
pp. 976-980 ◽  
Author(s):  
Eiichi Kobayashi ◽  
Naokatsu Saeki ◽  
Hiromichi Oishi ◽  
Shinji Hirai ◽  
Akira Yamaura

Object. The purpose of this study was to delineate the long-term natural history of hemorrhagic moyamoya disease (MMD).Methods. A retrospective review was conducted among 42 patients suffering from hemorrhagic MMD who had been treated conservatively without bypass surgery. The group included four patients who had undergone indirect bypass surgery after an episode of rebleeding. The follow-up period averaged 80.6 months. The clinical features of the first bleeding episode and repeated bleeding episodes were analyzed to determine the risk factors of rebleeding and poor outcome.Intraventricular hemorrhage with or without intracerebral hemorrhage was a dominant finding on computerized tomography scans during the first bleeding episode in 29 cases (69%). During the follow-up period, 14 patients experienced a second episode of bleeding, which occurred 10 years or longer after the original hemorrhage in five cases (35.7%). The annual rebleeding rate was 7.09%/person/year. The second bleeding episode was characterized by a change in which hemisphere bleeding occurred in three cases (21.4%) and by the type of bleeding in seven cases (50%). After rebleeding the rate of good recovery fell from 45.5% to 21.4% and the mortality rate rose from 6.8% to 28.6%. Rebleeding and patient age were statistically significant risk factors of poor outcome. All four patients in whom there was indirect revascularization after the second bleeding episode experienced a repeated bleeding episode within 8 years.Conclusions. The occurrence of rebleeding a long time after the first hemorrhagic episode was not uncommon. Furthermore, the change in which hemisphere and the type of bleeding that occurred after the first episode suggested the difficulty encountered in the prevention of repeated hemorrhage.


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.


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