Date Published: April 8, 2019
Publisher: Public Library of Science
Author(s): Emma M. H. Slot, Gabriel J. E. Rinkel, Ale Algra, Ynte M. Ruigrok, Stephan Meckel.
Patient and aneurysm characteristics have been reported to differ between patients with familial and non-familial intracranial aneurysms (IAs), although results are inconsistent. We systematically reviewed and meta-analyzed the literature to identify and quantify patient- and aneurysm characteristics associated with familial IAs.
We searched PubMed and EMBASE for case-control and cohort studies comparing patient- and aneurysm characteristics between familial and non-familial IAs. Two observers independently assessed study eligibility and appraised quality with the Newcastle Ottawa Scale. With univariable weighted linear regression analysis we calculated β-coefficients with corresponding 95% confidence intervals (CIs) for ruptured and unruptured IAs combined and for ruptured IAs only. Heterogeneity was assessed with Higgins I2.
A total of 15 articles were included in the meta-analysis in which 16,346 patients were analyzed with a total of 14,225 IAs. For ruptured and unruptured IAs combined, multiple IAs were more prevalent in familial (28.5%) than in non-familial IAs (20.4%; β = 0.10, 95% CI, 0.04 to 0.16; I2 0%). For ruptured IAs only, in familial patients IAs were more prevalent on the middle cerebral artery (41.1% versus 29.5%; β = 0.12, 95% CI, 0.01 to 0.24; I2 12%) and ruptured at a younger age (46.5 years versus 50.8 years; β = -5.00, 95% CI, -9.31 to -0.69; I2 98%) than in non-familial patients. No significant differences were found for the proportion of women, size of the aneurysm at time of rupture, smoking or hypertension.
These results suggest that characteristics of familial and non-familial IAs show considerable overlap, yet differ on specific aspects. However, results for age at rupture showed considerable heterogeneity. These findings should be taken into consideration for future etiological research into IAs.
Family history is the strongest risk factor for aneurysmal subarachnoid hemorrhage (aSAH) caused by a ruptured intracranial aneurysm (IA) and 10% of aSAH patients have a positive family history for aSAH [1,2]. Differences in clinical characteristics have been described for patients with familial IAs compared to those with non-familial IAs, although the reported results are inconsistent, for example for proportion of women [3–10], age at SAH onset [3,4, 9, 11–13], site [4–7, 9–12], size [11, 13, 14] and multiplicity of aneurysms [3, 5, 7, 9–14] and outcome after SAH [15–17]. A clear understanding of etiological differences between familial and non-familial IA is essential for clinical practice of IA patients and in future etiologic research on IA.
The database search yielded 2,092 articles of which 15 articles were eligible for our meta-analysis (Fig 1). The vast majority of manuscripts was excluded based on screening of title or abstract because they did not compare patient or aneurysm characteristics between familial and non-familial patients. Five articles were excluded because they were written in languages than those defined in our inclusion criteria. Two of these could be excluded based on their English written abstract. We intended to analyze the characteristics condition on admission and outcome at or after discharge in our meta-analysis. However, since the studies reporting on these characteristics used different outcome measures, which were also measured at different time points [15–17] we had to exclude these characteristics from further analysis (Fig 1). We identified a single study showing a higher risk of rupture of familial IAs compared to non-familial IAs . Therefore, we were not able to include the characteristic risk of rupture in the meta-analysis either. We included 15 articles in the meta-analysis. For patient characteristics 16,346 patients were analyzed of whom 2,359 were familial IA patients. For aneurysm characteristics 14,225 IAs of which 2,275 were familial ones. Table 1 provides an overview of the study characteristics and included patient-populations. The different definitions of familial IAs used and the different ways of how the familial IAs were diagnosed in the included studies are reported in S1 Table. Eight out of the 15 included studies were considered as high quality studies (S2 Table) [2,3, 7, 9, 10, 13, 14, 20].
In familial patients IAs are more often located at the MCA and more often multiple. These findings were consistent across the studies. Familial aneurysms also seem to rupture at younger age than non-familial aneurysms, but these data showed high heterogeneity between the included studies and should therefore be interpreted carefully. No relevant differences between familial IA and non-familial IA patients were found for the characteristics sex, smoking, hypertension, size at time of rupture.
The results of this meta-analysis suggest that characteristics of familial and non-familial IAs show considerable overlap, yet differ on specific aspects. This should be taken into consideration for future etiological research into IAs. Further studies into differences in the risk of rupture and outcome between familial and non-familial IA are necessary to be able to draw more robust conclusions regarding the clinical implications of a positive family history in IA.