Natural History of Ruptured but Untreated Intracranial Aneurysms
Background and Purpose—Knowledge on a natural history of untreated ruptured intracranial aneurysms is based on a small historical cohort from 1960s. We calculated mortality rates for patients with untreated ruptured intracranial aneurysms using a more recent and relatively large hospital cohort.
Methods—Patients admitted to the study hospital between 1968 and 2007 with saccular but untreated ruptured intracranial aneurysms were identified from the hospital aneurysm registry of 6850 patients. The study cohort included only patients who were followed up until death and for whom the date of symptom onset and the date of hospital admission were available.
Results—For 510 patients identified, the median survival time from symptom onset to death was 20 days. The 1-year mortality rate was 65%, but varied substantially by admission delays and clinical status on admission, being lowest (13%) for patients admitted later than a month after symptom onset and highest (89%) for poor-grade patients. The 1-year mortality rate was 75% for good-grade patients admitted within a week.
Conclusions—Mortality rates for patients with untreated ruptured intracranial aneurysms are even worse than presented in the historical study. When discussing with subarachnoid hemorrhage patients and their relatives about treatment options, the presented natural history figures are of use.
In 2013, the European Stroke Organization guideline for the management of ruptured intracranial aneurysms (RIAs) stated1 that the most reliable knowledge of the risk of death from untreated RIAs comes from a Finnish study published in 1967.2 For 116 hospitalized patients (admitted with significant delays and a vast majority were in good grade on admission) with untreated RIAs, the study reported a 1-year mortality rate of ≈63%.2 In addition to treatment policies, current everyday discussions with patients and their proxies about the risk/benefit ratio of treatments are essentially based on these historical data.2
New prospective follow-up studies on patients with untreated RIAs are impractical to conduct, especially because treatments of RIAs are established, widely accepted, and strongly recommended.1,3 Our aim was to revise the 50-year-old data2 and define mortality rates for patients with untreated saccular RIAs.
The study design was approved by the local ethics committee (Dnro 469/EO/04).
The Aneurysm Registry includes 6850 patients admitted between 1968 and 2007 to the Department of Neurosurgery, Helsinki University Hospital. Throughout a 40-year long period between January 1968 and December 2007, 510 patients (50% women) without previous treatments of IAs, without a history of aneurysmal subarachnoid hemorrhage (SAH), with data on the time of symptom onset, and with the data on the time of death were identified from the registry. The cohort was also divided into chronological admission quartiles (Table 1).
The time from the onset of symptoms to admission to the Department of Neurosurgery, Helsinki University Hospital, was defined as an admission delay.
Diagnosis and Location of RIAs
The diagnosis of SAH was based on lumbar punctures and computed tomography scans. RIAs were diagnosed by conventional catheter angiographies or computed tomography/magnetic resonance angiographies, which were also used to categorize the RIA location. For admitted patients who died before diagnostic angiographies, diagnose and RIA location were confirmed at autopsy.
After reviewing medical records, treatment decisions were recorded on the Aneurysm Registry.
Survival time was defined as the interval from onset of symptoms (leading to hospitalization) to death. Furthermore, 1-year, 5-year, and 10-year mortality rates were calculated. All patients were followed up until death.
The total follow-up time from admission to death was 3544 years. The mean and median follow-up times were 7 years and 10 days, respectively (range, 0 days to 45 years). The mean age on admission was 48 years (Table 1), and only 3 patients were <18 years. The mean and median age on admission varied by admission quartiles (Table 1), and 79% of the patients were admitted by January 1990 and 91% by January 2000.
One patient was admitted to another hospital in 1976 because of SAH, but was admitted to the Helsinki University Hospital for angiography and treatment not until 1986. When excluding this patient, the mean time from the onset of symptoms to the admission was 11 days (Table 1). The mean delay in the symptom-onset-to-admission time decreased from the first admission quartile to the fourth (Table 1).
Diagnosis of RIAs
Catheter angiography was used in diagnostics in 345 (68%) patients. Only 29 (6%) of the patients had a 4-vessel catheter angiography. A postmortem autopsy confirmed the clinical diagnosis in 119 (23%) of the cases. Thirty-eight (7%) patients underwent a computed tomography/magnetic resonance angiography. RIAs were detected in a contrast-enhanced computed tomography in 6 (1%) cases. For 2 patients, the definite procedure in detecting the RIA was somewhat ill-defined, despite the fact that the RIA and its location were described in medical notes.
Three most common locations were the (1) middle cerebral artery (34%), (2) anterior communicating artery (33%), and (3) posterior communicating artery (10%). In 41 (8%) patients, RIAs were located in the posterior circulation.
Most common reasons for conservative treatment were (1) poor grade (according to clinical criteria at the time) on admission (40%), (2) anticipated operative challenges (19%), and (3) death before the planned treatment (16%). Sixteen (3%) patients refused treatment, 9 (2%) patients were considered too old for treatment (median, 75 years; range, 60–83 years), and 3 (1%) patients had so small RIAs that treatment was considered impractical.
Mortality rates are presented in Tables 1 and 2 and in the Figure. Patients with delayed admissions were less often in poor grade (Table 2). Of 510 patients, 205 (40%) were in poor grade on admission. Of these 205 patients with the median survival time of 4 days, 163 (80%) died in a month and 182 (89%) within a year from the onset of symptoms. For the 305 patients in other than poor grade on admission (considered as good-grade patients), 1-month and 1-year mortality rates were 42% and 49%, respectively. Of these 305 patients, 127 were admitted within a week, and the 1-year mortality rate was 75% for these patients. For 180 (35%) 1-year survivors, the median and mean overall survival time was 19 years (range, 1–45 years).
During a lifelong follow-up of 510 untreated SAH patients, the 1-year mortality rate was 65%, 5-year mortality 69%, and 10-year mortality 76%. Hospital-admitted poor-grade patients with untreated RIAs had 1-year mortality rates of ≈90%. The 1-year mortality rate was 75% for good-grade patients admitted within a week. In theory, today’s patients, who are admitted within a week after SAH and who are not in poor condition on admission, have an ≈25% possibility to survive a year if treated conservatively.
Of those patients, who were admitted later than a month after the symptom onset, only 11% died during the following year. A natural selection of RIA patients with a low rate of rebleeding could contribute to the low mortality rate in patients with delayed admissions. Admissions after the symptom onset are still delayed in many countries, Morocco as an example.4 In such countries, these results may affect treatment strategies of, for example, elderly SAH patients with significant admission delays. One-year survivors had a lifelong annual mortality rate of 5.4% (results not shown) and a first 5-year (after surviving a year) annual mortality rate of 4.0%. In comparison, 1-year survivors of treated SAH have an annual mortality rate of 3.5%.5 Although these 2 mortality rates are not directly comparable, the figures suggest that the early survival benefit of 1-year survivors of untreated SAH patients may last for years.
The study has several shortcomings. The definition of poor grade has probably changed over the years, and poor grade in 2000s indicated most likely worse clinical condition than poor grade in 1960s. In addition, given that half of the cohort consisted of patients admitted between 1968 and 1978, the data are still mostly from the time period before modern neurosurgical practices. Therefore, the study cohort unlikely represents today’s SAH patients. Moreover, the study did not include sudden SAH deaths away from the study hospital. As ≈25% of SAH patients die suddenly5,6 and many of these away from hospitals, the overall mortality rates are even higher. Finally, the study has a referral bias. During the historical era, only good-grade SAH patients and patients who recovered to good grade were candidates for treatment. Since 1978 (the third quartile), the median admission delay to the study hospital was <1 day because most of the patients were considered candidates for treatment or for organ donation. We tried to diminish admission-related confounding by calculating the mortality rates for 4 time periods (admission quartiles).
In conclusion, 1-year mortality rates of patients with untreated RIAs are worse than reported in 1960s.2 In a 40-year long period, the treatment philosophy of patients with RIAs seems to have changed dramatically in a large academic SAH treatment center. When discussing with SAH patients and their relatives about treatment options, these updated and relatively detailed natural history figures are of use.
- Received June 24, 2016.
- Revision received December 30, 2016.
- Accepted January 19, 2017.
- © 2017 American Heart Association, Inc.
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