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(Stroke. 1999;30:1099-1102.)
© 1999 American Heart Association, Inc.
Original Contributions |
Familial Subarachnoid Hemorrhage
Outcome Study
From the Departments of Neurosurgery (A.R.) and Anesthesiology and Intensive Care (M.N.), University Hospital of Kuopio (R.P.), Kuopio, Finland, and the Department of Neurosurgery, University Hospital of Helsinki (J.H.), Helsinki, Finland.
Correspondence to Antti Ronkainen, Department of Neurosurgery, Kuopio University Hospital, PO Box 1777, FIN-70210, Kuopio, Finland. E-mail antti.ronkainen{at}kuh.fi
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Background and Purpose—The aim of our study was to compare outcome and its determinants in familial subarachnoid hemorrhage and in sporadic subarachnoid hemorrhage in a large and well-documented patient population.
Methods—Patients with aneurysmal subarachnoid hemorrhage (SAH) treated at the Department of Neurosurgery, Kuopio University Hospital, from 1977 to 1995 were included. Patients with polycystic kidney disease were excluded. The Glasgow Outcome Scale (GOS) score at 12 months was studied.
Results—There were 120 patients (97 first-, 15 second-, and 8 third-degree family connections) in 96 different families with familial SAH and 1237 patients with sporadic SAH. Age, gender, and admission grade on the Hunt and Hess scale did not differ between these 2 groups. In both groups >80% of patients were in relatively good condition at admission. The outcome was good (GOS score of 1 to 2) in 87 patients (73%) with familial SAH and in 874 patients (71%) with sporadic SAH. Analysis of 20 variables, including presence of coexisting diseases, aneurysm site and size, amount of blood shown on CT scan, intraventricular bleeding, preoperative intracerebral hematoma and hydrocephalus, as well as postoperative bleeding and vasospasm, revealed no significant differences between study groups. The degree of family connection (first-, second-, and third-degree) did not have any statistically important effect on outcome in the familial group in the Finnish study population. In multivariate analysis the knowledge of familial SAH was not an independent prognostic factor.
Conclusions—Admission status, postoperative course, and outcome were similar in the familial and sporadic SAH groups in this Finnish population, in contrast to previous results. Familial SAH may not be a significant risk factor for poor outcome.
Key Words: cerebral aneurysm • family • Finland • outcome • subarachnoid hemorrhage
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Despite modern microsurgical techniques and rapidly developing endovascular treatments, we still lose nearly half of aneurysmal subarachnoid hemorrhage (SAH) patients because of primary bleeding or subsequent complications.1 2 3 Preventive treatment of unruptured intracranial aneurysms (IAs) is the only definite way to prevent the devastating rupture of IAs and to improve the outcome of SAH patients. The mortality rate of 2% after surgical repair of unruptured IAs is distinctly lower than the 15% to 20% mortality associated with ruptured IAs.4 5 6 At least 10% of aneurysmal SAH patients have a positive family history of SAH, with at least 2 first-degree family members with IAs.5 7 Within familial SAH families, the risk for harboring IAs among asymptomatic family members is at least 4 times higher than in sporadic SAH families.8 These results support the need for screening familial SAH family members.
Despite the fact that familial SAH is well documented, very little is known about differences between the clinical courses of familial and sporadic SAH. Bromberg et al9 in the Netherlands reported a prospective outcome study comparing familial cases with sporadic cases. Their results suggest that the outcome of familial SAH is more unfavorable than the outcome of sporadic SAH. A truly worst outcome among familial SAH patients would confirm the need for aggressive screening of incidental IAs among asymptomatic family members. We studied the outcome in familial and sporadic SAH patients in a large and well-documented patient population from East Finland.10 We compared the long-term outcome between familial and sporadic SAH, and tried to determine whether there are any differences between these patient groups with respect to preoperative conditions or postoperative course.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The study population consisted of 1580 patients with proven IAs who were treated at Kuopio University Hospital during the 18-year period from 1977 to the end of 1995. The Department of Neurosurgery at Kuopio University Hospital is the only neurosurgical unit in East Finland, with a catchment area of nearly 900 000 inhabitants. All patients with SAH from this geographical region are transferred to Kuopio for treatment. For this report we included only those patients who had aneurysmal SAH. The study population was divided into 2 groups: familial SAH patients and sporadic SAH patients. The inclusion criterion for the familial SAH group was the presence of 2 or more family members (up to first cousins) with a proven aneurysmal SAH. All patients with known autosomal dominantly inherited adult polycystic kidney disease or any other genetic diseases associated with aneurysmal SAH were excluded from the present study. In every case, aneurysmal SAH was confirmed by clinical records, angiography findings, autopsy findings, or death certificates. Cases lacking such confirmation were excluded from the familial SAH group. Likewise, all sporadic aneurysm patients or their near relatives were questioned by a neurosurgeon or a trained nurse regarding possible SAH cases among their relations. All such cases were investigated as mentioned above, to ensure the exclusion of any familial SAH patients from the sporadic SAH group. If the family history of possible SAH was negative, no attempt was made to study all first-, second-, and third-degree relatives for false-negative cases. The familial SAH group has been previously described and documented.10 11
Variables describing preoperative status, severity of the SAH,
characteristics of the aneurysm, and the
perioperative and postoperative courses were registered
(Table 1
). The selection of
studied variables was based on our earlier outcome studies for SAH
patients.12 The preoperative grade was classified
according to Hunt and Hess.13 The outcome was assessed at
1 year after admission at an outpatient visit by use of the Glasgow
Outcome Scale (GOS).14 Outcome was divided into 2
categories: a GOS score of 1 to 2 (good recovery or moderate
disability) was classified as a good outcome and a GOS score of 3 to 5
(severe disability, vegetative state, or death) as a poor outcome.
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The results are presented as mean±SD unless otherwise
indicated. Differences between groups were analyzed by the
Student unpaired t test or the Mann-Whitney U
test for continuous variables and the 
2
test for categorized variables. The Spearman rank order correlation
was used to examine the correlation between preoperative grade and
outcome. Logistic regression analysis was carried out to study
the independent contributions of the prognostic factors to the outcome.
The statistical computer program SPSS for Windows (SPSS Inc) was used
for the statistical calculations.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The final study population consisted of a total of 1357 patients with aneurysmal SAH. There were 120 patients (97 first-, 15 second-, and 8 third-degree family connections) in 96 families with familial SAH and 1237 patients with sporadic SAH. Baseline characteristics of these 2 groups are presented in Table 2
. The groups were similar with
respect to age, gender, and admission grade (Table 2). There
were no differences in 1-year outcome (Table 2) between the
groups. In both groups advanced age, hypertension, a large amount of
blood revealed by CT, as well as postoperative
intracerebral hemorrhage or
intraventricular hematoma at admission and
hypodense areas in the CT were associated with poor outcome (Table 3). In studying the independent
contribution of prognostic factors to the outcome, familial background
was found to be insignificant. More important variables than
familial background were age, preoperative grade, and postoperative
hypodense areas on the CT scan (Table 4).
The degree of familial connection (first-, second-, and third-degree)
did not have any statistically important effect on the outcome in the
familial group.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The main finding of the present study is that the outcome of familial SAH patients does not differ from that of sporadic SAH patients
Our results confirm the importance to outcome of increased age at onset, preoperative grade, and postoperative hypodense areas on CT, facts that are well known from previous outcome studies.3 12 15 Our finding of no differences in outcome between the study groups is also similar to what we have seen in clinical practice. We have not made any changes in the management of familial SAH cases compared with sporadic cases at our department.
Bromberg et al9 prospectively studied the outcome at discharge among 29 familial SAH and 125 sporadic SAH patients and found that 52% of familial patients had poor outcome compared with 35% of the sporadic group. The authors were very careful with their inclusion criteria for the familial SAH study group, including only confirmed familial cases. The age- and sex-adjusted OR for poor outcome in the familial group was 2.5, with a very wide 95% CI (1.0 to 6.0).
The reason for the difference between our results and those of Bromberg et al9 could be the time at which outcome was defined. In our opinion, the outcome at discharge does not accurately reflect final patient outcome, because the major portion of neurological recovery occurs during the year after onset. Also, a 1-year follow-up time has been widely used in the literature to estimate the final outcome of various treatments. The small size of the study groups of Bromberg et al might also have influenced the results, as suggested by the wide 95% CIs in their statistical calculations. The degree of family connection (first-, second-. and third-degree relatives) did not have any effects on our study results. This may be explained by 2 reasons. First, in the present study, most of the familial SAH cases had first-degree family connections; second, there were no major differences in the distribution of outcomes among first-, second-, and third-degree relatives. The influence of different study protocols (prospective in the Bromberg study and retrospective in the present study) is, in our opinion, insignificant in the comparison of outcome.
However, differences in the study populations may have influenced the results. It is well known that in Finland the incidence of aneurysmal SAH is the highest in the world, that in Finnish IA and SAH studies males are more often affected, and that in Finland the typical location for IA is the middle cerebral artery instead of the internal carotid artery.16 17 18 19 20 Genealogically, Finland is a very homogeneous population, with very little gene exchange over the past centuries.21 Also, possible differences in treatment or postoperative care may have influenced outcome results.
In conclusion, our study in the Finnish population could not confirm previous study results suggesting that the outcome of familial SAH patients was more unfavorable than that of sporadic cases. Our results may reflect the possibility that in both familial and sporadic cases the basic pathological reason for the formation of intracranial aneurysms could be the same. We fully agree with earlier studies that underline the need to screen asymptomatic family members for incidental intracranial aneurysms in familial cases, because that is the only way to prevent devastating bleeding. The ultimate breakthrough in treating intracranial aneurysms would be the identification of the genetic defect(s) responsible for the formation of intracranial aneurysms.
Received September 18, 1998; revision received January 26, 1999; accepted February 2, 1999.
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References |
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