Natural History of Unruptured Intracranial Aneurysms
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. We followed 142 patients with 181 unruptured aneurysms 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 the 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 a previously unruptured aneurysm, giving an average annual incidence of 1.3%. In seventeen of these cases, hemorrhages led to the patients' deaths. The cumulative rate of bleeding was 10.5% at 10 years, 23.0% 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] 1.00-1.23, p = 0.05) and patient age at diagnosis inversely (RR 0.97 per year, 95% CI 0.93-1.00, 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 the size of the aneurysm, 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 = 0.020).
Despite recent improvements in surgical and medical management of aneurysmal SAH, the overall mortality rate in this disease is high (approximately 40-50%). The high mortality and morbidity rates are attributed mainly to brain damage caused by a severe initial hemorrhage, early rebleeding, and delayed cerebral ischemia.
Incidental aneurysms, as well as unruptured aneurysms in patients with multiple aneurysms, have been surgically treated at the time of discovery, at quite a low risk. Such preventive surgical intervention can eliminate the high rates of mortality and morbidity associated with a severe initial episode of bleeding or early rebleeding.
During the last two decades, detection of unruptured intracranial aneurysms has increased because of new and improving diagnostic technology (digital subtraction angiography, magnetic resonance angiography, and three-dimensional computerized tomography angiography), in addition to a more active treatment policy for patients with ruptured intracranial aneurysms; that is, older patients and in those poorer condition are now treated more often than in the past.
However, the natural history of unruptured intracranial aneurysms is poorly known, as are the risk factors associated with the rupture of unruptured aneurysms, because of the paucity of studies in which there are sufficient numbers of patients and follow-up years. In addition, most studies are more or less biased by surgical selection of patients with unruptured aneurysms, because surgical intervention has also increased since the 1970s in most neurosurgical centers, except in older patients with severe diseases and difficult aneurysms in whom conservative treatment is undertaken; it is this older population that forms the basis for the follow-up studies found in the literature. The findings reported in such cohorts cannot represent the natural history of a disease unless it is proven that a similar risk for rupture existed for the surgically treated and excluded patients. Current knowledge of the natural history of unruptured aneurysms is based on only a few studies, with risk as well as risk factors being even more controversial now than previously because of the differing results published in these studies. Thus, the decision of how to treat patients with unruptured intracranial aneurysms varies.
Before 1979, unruptured aneurysms were not surgically treated in our clinic, which was the only neurosurgical center in Finland until the late 1960s. Preliminary results of our long-term cohort study in patients in whom unruptured aneurysms were diagnosed before 1979 have previously been published. In the present study we report the final results, including a greater number of follow-up years and analysis of more potential risk factors for rupture.
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. We followed 142 patients with 181 unruptured aneurysms 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 the 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 a previously unruptured aneurysm, giving an average annual incidence of 1.3%. In seventeen of these cases, hemorrhages led to the patients' deaths. The cumulative rate of bleeding was 10.5% at 10 years, 23.0% 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] 1.00-1.23, p = 0.05) and patient age at diagnosis inversely (RR 0.97 per year, 95% CI 0.93-1.00, 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 the size of the aneurysm, 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 = 0.020).
Despite recent improvements in surgical and medical management of aneurysmal SAH, the overall mortality rate in this disease is high (approximately 40-50%). The high mortality and morbidity rates are attributed mainly to brain damage caused by a severe initial hemorrhage, early rebleeding, and delayed cerebral ischemia.
Incidental aneurysms, as well as unruptured aneurysms in patients with multiple aneurysms, have been surgically treated at the time of discovery, at quite a low risk. Such preventive surgical intervention can eliminate the high rates of mortality and morbidity associated with a severe initial episode of bleeding or early rebleeding.
During the last two decades, detection of unruptured intracranial aneurysms has increased because of new and improving diagnostic technology (digital subtraction angiography, magnetic resonance angiography, and three-dimensional computerized tomography angiography), in addition to a more active treatment policy for patients with ruptured intracranial aneurysms; that is, older patients and in those poorer condition are now treated more often than in the past.
However, the natural history of unruptured intracranial aneurysms is poorly known, as are the risk factors associated with the rupture of unruptured aneurysms, because of the paucity of studies in which there are sufficient numbers of patients and follow-up years. In addition, most studies are more or less biased by surgical selection of patients with unruptured aneurysms, because surgical intervention has also increased since the 1970s in most neurosurgical centers, except in older patients with severe diseases and difficult aneurysms in whom conservative treatment is undertaken; it is this older population that forms the basis for the follow-up studies found in the literature. The findings reported in such cohorts cannot represent the natural history of a disease unless it is proven that a similar risk for rupture existed for the surgically treated and excluded patients. Current knowledge of the natural history of unruptured aneurysms is based on only a few studies, with risk as well as risk factors being even more controversial now than previously because of the differing results published in these studies. Thus, the decision of how to treat patients with unruptured intracranial aneurysms varies.
Before 1979, unruptured aneurysms were not surgically treated in our clinic, which was the only neurosurgical center in Finland until the late 1960s. Preliminary results of our long-term cohort study in patients in whom unruptured aneurysms were diagnosed before 1979 have previously been published. In the present study we report the final results, including a greater number of follow-up years and analysis of more potential risk factors for rupture.