www.thelancet.com/neurology Published online November 27, 2013 http://dx.doi.org/10.1016/S1474-4422(13)70263-1 1 Articles Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies Jacoba P Greving, Marieke J H Wermer, Robert D Brown Jr, Akio Morita, Seppo Juvela, Masahiro Yonekura, Toshihiro Ishibashi, James C Torner, Takeo Nakayama, Gabriël J E Rinkel, Ale Algra Summary Background The decision of whether to treat incidental intracranial saccular aneurysms is complicated by limitations in current knowledge of their natural history. We combined individual patient data from prospective cohort studies to determine predictors of aneurysm rupture and to construct a risk prediction chart to estimate 5-year aneurysm rupture risk by risk factor status. Methods We did a systematic review and pooled analysis of individual patient data from 8382 participants in six prospective cohort studies with subarachnoid haemorrhage as outcome. We analysed cumulative rupture rates with Kaplan-Meier curves and assessed predictors with Cox proportional-hazard regression analysis. Findings Rupture occurred in 230 patients during 29 166 person-years of follow-up. The mean observed 1-year risk of aneurysm rupture was 1·4% (95% CI 1·1–1·6) and the 5-year risk was 3·4% (2·9–4·0). Predictors were age, hypertension, history of subarachnoid haemorrhage, aneurysm size, aneurysm location, and geographical region. In study populations from North America and European countries other than Finland, the estimated 5-year absolute risk of aneurysm rupture ranged from 0·25% in individuals younger than 70 years without vascular risk factors with a small-sized (<7 mm) internal carotid artery aneurysm, to more than 15% in patients aged 70 years or older with hypertension, a history of subarachnoid haemorrhage, and a giant-sized (>20 mm) posterior circulation aneurysm. By comparison with populations from North America and European countries other than Finland, Finnish people had a 3·6-times increased risk of aneurysm rupture and Japanese people a 2·8-times increased risk. Interpretation The PHASES score is an easily applicable aid for prediction of the risk of rupture of incidental intracranial aneurysms. Funding Netherlands Organisation for Health Research and Development. Introduction Intracranial aneurysms occur in around 3% of the population, 1 which means around 15 million inhabitants of the European Union have an unruptured intracranial aneurysm. Owing to the rising availability of brain imaging, the number of incidentally discovered aneurysms is increasing. 2 Rupture of intracranial aneurysms results in aneurysmal subarachnoid haemorrhage, a subset of stroke that has high case fatality and morbidity, and occurs at a relatively young age compared with other types of stroke. 3–5 In patients with unruptured aneurysms, the decision whether to treat is often not straightforward. Preventive treatment of intracranial aneurysms carries a risk of combined treatment-related fatality and morbidity of up to 5%. 6 Neurosurgical treatment has a higher risk of complications than does endovascular treatment, 7 but the risk of rupture after endovascular treatment is slightly higher than after surgery, with annual rupture rates of 0·2% according to a large systematic review. 6 The risks of treatment have to be balanced carefully against the risk of rupture. 8 However, prediction of the risk of rupture is difficult. Many prognostic factors for aneurysm rupture have been proposed. 9 Risk factors for subarachnoid haemorrhage include aneurysm size and aneurysm site, with higher risks for larger aneurysms and aneurysms in the posterior circulation. 10–14 Multiple aneurysms, 12 female sex, 9 young age, 11,12 history of subarachnoid haemor- rhage, 13 and cigarette smoking 11 have been suggested as risk factors in some studies, but not in others. Moreover, estimation of absolute risk of aneurysm rupture in a patient based on combination of risk factors is complex and a clinical risk score for aneurysm rupture does not exist. Ideally, one would be able to calculate the risk of aneurysm rupture on the basis of readily available data for patient and aneurysm characteristics. We undertook a pooled analysis of individual patient data from prospective cohort studies in which data were reported for the natural history of unruptured aneurysms and risk factors predicting rupture. The aim was to establish predictors of aneurysm rupture in patients with unruptured intracranial aneurysms and to provide a risk prediction chart that allows physicians to easily determine the 5-year risk of aneurysm rupture on the basis of a set of routinely assessed patient and aneurysm characteristics. Published Online November 27, 2013 http://dx.doi.org/10.1016/ S1474-4422(13)70263-1 See Online/Comment http://dx.doi.org/10.1016/ S1474-4422(13)70272-2 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands (J P Greving PhD, Prof A Algra MD); Department of Neurology, Leiden University Medical Center, Leiden, Netherlands (M J H Wermer MD); Department of Neurology, Mayo Clinic, Rochester, MN, USA (Prof R D Brown Jr MD); UCAS Japan Coordinating Office, University of Tokyo, Tokyo, Japan (Prof A Morita MD); Department of Neurological Surgery, Nippon Medical School, Tokyo, Japan (Prof A Morita); Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland (S Juvela MD); Department of Neurosurgery, National Nagasaki Medical Center, Nagasaki, Japan (M Yonekura MD); Division of Endovascular Neurosurgery, Tokyo Jikei University School of Medicine, Tokyo, Japan (T Ishibashi MD); Department of Epidemiology, University of Iowa, Iowa City, IA, USA (Prof J C Torner PhD); Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan (Prof T Nakayama MD); and Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands (Prof G J E Rinkel MD, Prof A Algra) Correspondence to: Dr Jacoba P Greving, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, Netherlands j.p.greving@umcutrecht.nl