Familial intracranial aneurysms

Summary

Background

We set out to determine the prevalence of incidental intracranial aneurysms in first-degree relatives aged 30 years or more of people with intracranial aneurysms, and to see if polycystic kidney disease contributes to the aggregation of familial intracranial aneurysms.

Methods

91 families with two or more affected members had previously been identified from a 14 year series of 1150 intracranial aneurysm patients treated at the University Hospital of Kuopio, Finland. Magnetic resonance angiography was used as a preliminary screening method, followed by conventional four-vessel angiography to verify suspected aneurysms. Participants were also screened for polycystic kidneys by ultrasonography.

Findings

Incidental aneurysms were detected in 40 individuals: 38 of 438 individuals from 85 families without polycystic kidney disease or other diagnosed heritable disorders, and two of 22 individuals from six families known to have polycystic kidney disease. The crude and age-adjusted prevalence of incidental intracranial aneurysms among screened first-degree relatives was 8·7 (SE 1·3)% (95% CI 6·2–11·7) and 9·1 (1·4)% (6·2–11·7), respectively, for the familial group and the crude prevalence for the polycystic kidney group was 9·1 (6·1)% (1·1–29·2).

Interpretation

Our results demonstrate a high prevalence of incidental intracranial aneurysms among first-degree relatives aged 30 years or older of patients with the condition and indicate that the risk of having an aneurysm is about four times higher for a close relative than for someone from the general population. Also, polycystic kidney disease families are a small fraction of the familial intracranial aneurysm families.

Introduction

About one-quarter of cerebrovascular deaths are due to subarachnoid haemorrhage (SAH).¹ SAH is a devastating disease, since about half the patients die due to primary bleeding or to subsequent complications, and many of the survivors will need extended rehabilitaton to continue an independent life. This poor outcome has changed little during the past two or three decades, even though the treatment of SAH has become a daily routine in neurosurgical centres.² The economic impact of SAH is severe because it most often affects patients in their 40s and 50s during their most productive years.³ As many as 80–90% of SAHs are caused by ruptured intracranial aneurysms (IAs).4, 5, 6 Up to 60% of individuals who experience aneurysmal SAH will die before hospital admission.⁶ After hospital admission, about one-third will die, about one-sixth will recover with a severe disabilty, about one-sixth will have some disability, and about onethird will have excellent outcome.⁶ Increasing experience in treating ruptured IAs, either with advanced microsurgical or with endovascular techniques, has resulted in improved outcomes for elective surgery of unruptured IAs.7, 8 The per case mortality for treatment of unruptured IAs involving elective surgery is below 2%, whereas the per case mortality for treatment of ruptured aneurysms that involves emergency surgery may exceed 30% with mortality due to surgery rarely exceeding 30%.7, 9 In addition, the techniques of endovascular surgery such as selective occlusion of aneurysms with detachable balloons and metallic coils have the promise of reducing surgical complications and mortality even further.⁸ Given the strikingly different outcomes, it is evident that treating IAs before rupture would save lives.

Screening the population at large for the presence of IAs is not feasible, but identification of groups with increased risk may make screening feasible. Familial aggregation of IAs has been observed and IAs are often associated with the autosomal dominant form of polycystic kidney disease (PCKD).¹⁰ 6–20% of IA cases may be familial with two or more confirmed IA cases in the same family in the absence of any signs of other hereditary disorders.11, 12, 13, 14 Younger age of onset, presence of IAs among twins, and the fact that in siblings the age of onset is closer than expected by chance support the hypothesis that familial intracranial aneurysms (FIA), in the absence of other predisposing heritable disorders, are a distinct disease entity.15, 16

The risk of at least two individuals in a family being diagnosed with IA is unknown, primarily due to the lack of suitable methods for large-scale screening studies. Conventional angiography has been reported to be associated with an overall 4% risk of complications, about 1% risk of permanent neurological deficit, and less than 0·1% risk of mortality.¹⁷ Modern digital subtraction angiography (DSA) of the cranium is associated with a 1% transient and 0·5% permanent risk of neurological complication.¹⁸ Although the complication rates are low, the procedure is invasive and the risks are still, considerable for screening symptom-free, apparently healthy individuals. Development of magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) has made possible safe, accurate, and non-invasive detection of IAs.¹⁹ Recent results on FIA families have indicated that many symptom-free family members have IAs.20, 21

We set out to estimate the prevalence of IAs among symptom-free relatives of FIA families, and the fraction of PCKD families among those with familial aggregation of IAs.