Difference in Rupture Risk Between Familial and Sporadic Intracranial Aneurysms: An Individual Patient Data Meta-analysis

Charlotte C M Zuurbier; Liselore A Mensing; Marieke J H Wermer; Seppo Juvela; Antti E Lindgren; Timo Koivisto; Juha E Jääskeläinen; Tomosato Yamazaki; Rob Molenberg; J Marc C van Dijk; Maarten Uyttenboogaart; Marlien Aalbers; Akio Morita; Shinjiro Tominari; Hajime Arai; Kazuhiko Nozaki; Yuichi Murayama; Toshihiro Ishibashi; Hiroyuki Takao; Gabriel J E Rinkel; Jacoba P Greving; Ynte M Ruigrok

doi:10.1212/WNL.0000000000012885

Difference in Rupture Risk Between Familial and Sporadic Intracranial Aneurysms: An Individual Patient Data Meta-analysis

Neurology. 2021 Nov 30;97(22):e2195-e2203. doi: 10.1212/WNL.0000000000012885. Epub 2021 Oct 20.

Authors

Charlotte C M Zuurbier¹, Liselore A Mensing¹, Marieke J H Wermer¹, Seppo Juvela¹, Antti E Lindgren¹, Timo Koivisto¹, Juha E Jääskeläinen¹, Tomosato Yamazaki¹, Rob Molenberg¹, J Marc C van Dijk¹, Maarten Uyttenboogaart¹, Marlien Aalbers¹, Akio Morita¹, Shinjiro Tominari¹, Hajime Arai¹, Kazuhiko Nozaki¹, Yuichi Murayama¹, Toshihiro Ishibashi¹, Hiroyuki Takao¹, Gabriel J E Rinkel¹, Jacoba P Greving¹, Ynte M Ruigrok²

Affiliations

¹ From the Department of Neurology and Neurosurgery, UMC Utrecht Brain Center (C.C.M.Z., L.A.M., G.J.E.R., Y.M.R.), and Julius Centre for Health Sciences and Primary Care (J.P.G.), University Medical Center Utrecht; Department of Neurology (M.J.H.W.), Leiden University Medical Center, the Netherlands; Department of Clinical Neurosciences (S.J.), University of Helsinki; Neurosurgery of NeuroCenter (A.E.L., T.K., J.E.J.), University of Eastern Finland, Kuopio, Finland; Department of Neurosurgery (T.Y.), National Hospital Organization, Mito Medical Center, Japan; Departments of Neurosurgery (R.M., J.M.C.v.D., M.U., M.A.), University Medical Center Groningen, the Netherlands; University of Tokyo-Nippon Medical School (A.M.); Department of Health Informatics, School of Public Health (S.T.), Kyoto University; Department of Neurosurgery (H.A.), Juntendo University Medical School, Tokyo; Department of Neurosurgery (K.N.), Shiga University of Medical Science; and Department of Endovascular Neurosurgery (Y.M., T.I., H.T.), Tokyo Jikei University School of Medicine, Japan.
² From the Department of Neurology and Neurosurgery, UMC Utrecht Brain Center (C.C.M.Z., L.A.M., G.J.E.R., Y.M.R.), and Julius Centre for Health Sciences and Primary Care (J.P.G.), University Medical Center Utrecht; Department of Neurology (M.J.H.W.), Leiden University Medical Center, the Netherlands; Department of Clinical Neurosciences (S.J.), University of Helsinki; Neurosurgery of NeuroCenter (A.E.L., T.K., J.E.J.), University of Eastern Finland, Kuopio, Finland; Department of Neurosurgery (T.Y.), National Hospital Organization, Mito Medical Center, Japan; Departments of Neurosurgery (R.M., J.M.C.v.D., M.U., M.A.), University Medical Center Groningen, the Netherlands; University of Tokyo-Nippon Medical School (A.M.); Department of Health Informatics, School of Public Health (S.T.), Kyoto University; Department of Neurosurgery (H.A.), Juntendo University Medical School, Tokyo; Department of Neurosurgery (K.N.), Shiga University of Medical Science; and Department of Endovascular Neurosurgery (Y.M., T.I., H.T.), Tokyo Jikei University School of Medicine, Japan. ij.m.ruigrok@umcutrecht.nl.

PMID: 34670818
DOI: 10.1212/WNL.0000000000012885

Abstract

Background and objectives: We combined individual patient data (IPD) from prospective cohorts of patients with unruptured intracranial aneurysms (UIAs) to assess to what extent patients with familial UIA have a higher rupture risk than those with sporadic UIA.

Methods: For this IPD meta-analysis, we performed an Embase and PubMed search for studies published up to December 1, 2020. We included studies that (1) had a prospective study design; (2) included 50 or more patients with UIA; (3) studied the natural course of UIA and risk factors for aneurysm rupture including family history for aneurysmal subarachnoid haemorrhage and UIA; and (4) had aneurysm rupture as an outcome. Cohorts with available IPD were included. All studies included patients with newly diagnosed UIA visiting one of the study centers. The primary outcome was aneurysmal rupture. Patients with polycystic kidney disease and moyamoya disease were excluded. We compared rupture rates of familial vs sporadic UIA using a Cox proportional hazard regression model adjusted for PHASES score and smoking. We performed 2 analyses: (1) only studies defining first-degree relatives as parents, children, and siblings and (2) all studies, including those in which first-degree relatives are defined as only parents and children, but not siblings.

Results: We pooled IPD from 8 cohorts with a low and moderate risk of bias. First-degree relatives were defined as parents, siblings, and children in 6 cohorts (29% Dutch, 55% Finnish, 15% Japanese), totaling 2,297 patients (17% familial, 399 patients) with 3,089 UIAs and 7,301 person-years follow-up. Rupture occurred in 10 familial cases (rupture rate: 0.89%/person-year; 95% confidence interval [CI] 0.45-1.59) and 41 sporadic cases (0.66%/person-year; 95% CI 0.48-0.89); adjusted hazard ratio (HR) for familial cases 2.56 (95% CI 1.18-5.56). After adding the 2 cohorts excluding siblings as first-degree relatives, resulting in 9,511 patients, the adjusted HR was 1.44 (95% CI 0.86-2.40).

Discussion: The risk of rupture of UIA is 2.5 times higher, with a range from a 1.2 to 5 times higher risk, in familial than in sporadic UIA. When assessing the risk of rupture in UIA, family history should be taken into account.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Aneurysm, Ruptured* / epidemiology
Child
Humans
Intracranial Aneurysm* / diagnosis
Intracranial Aneurysm* / epidemiology
Intracranial Aneurysm* / genetics
Prospective Studies
Risk Factors
Subarachnoid Hemorrhage* / epidemiology
Subarachnoid Hemorrhage* / genetics