*Olivier Naggara, Tim Darsaut, Denis Trystram, Lambros Tselikas, Jean Raymond [email protected]
Department of Neuroradiology, Paris-Descartes University, Centre Hospitalier Sainte-Anne, INSERM UMR894, 75014 Paris, France (ON, DT, LT); Division of Neurosurgery, Department of Surgery, University of Alberta Hospital, Mackenzie Health Sciences Centre, Edmonton, Alberta, Canada (TD); and International Consortium of Neuroendovascular Centres, Interventional Neuroradiology Research Unit, Department of Radiology, University of Montreal, CHUM Notre-Dame Hospital, Montreal, QC, Canada (JR) 1
Greving JP, Wermer MJ, Brown RD Jr, et al. Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies. Lancet Neurol 2014; 13: 59–66. Raymond J, Darsaut TE, Molyneux AJ. A trial on unruptured intracranial aneurysms (the TEAM trial): results, lessons from a failure and the necessity for clinical care trials. Trials 2011; 12: 64. Brinjikji W, Rabinstein AA, Nasr DM, Lanzino G, Kallmes DF, Cloft HJ. Better outcomes with treatment by coiling relative to clipping of unruptured intracranial aneurysms in the United States, 2001-2008. AJNR Am J Neuroradiol 2011; 32: 1071–75. International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured intracranial aneurysms—risk of rupture and risks of surgical intervention. N Eng J Med 1998; 339: 1725–33. Morita A, Kirino T, Hashi K, et al. The natural course of unruptured cerebral aneurysms in a Japanese cohort. N Engl J Med 2012; 366: 2474–82. Kotowski M, Naggara O, Darsaut TE, et al. Safety and occlusion rates of surgical treatment of unruptured intracranial aneurysms: a systematic review and meta-analysis of the literature from 1990 to 2011. J Neurol Neurosurg Psychiatry 2013; 84: 42–48. Naggara ON, Lecler A, Oppenheim C, Meder JF, Raymond J. Endovascular treatment of intracranial unruptured aneurysms: a systematic review of the literature on safety with emphasis on subgroup analyses. Radiology 2012; 263: 828–35. Naggara ON, White PM, Guilbert F, Roy D, Weill A, Raymond J. Endovascular treatment of intracranial unruptured aneurysms: systematic review and meta-analysis of the literature on safety and eﬃcacy. Radiology 2010; 256: 887–97.
Authors’ reply We thank Olivier Nagarra and colleagues for their interest in our pooled analysis of individual patient data on risk of rupture.1 Their comments focus on insufficient evidence from randomised clinical trials for prophylactic vascular interventions of unruptured 538
intracranial aneurysms. The Trial on Endovascular Aneurysm Management (TEAM) was such an enterprise that failed because of poor recruitment.2 We agree that treatment recommendations ideally should be assessed in properly designed randomised clinical trials. However, whether such a trial could be accomplished for unruptured intracranial aneurysms is unclear. Our study showed that in populations from North America and European countries other than Finland, most aneurysms have a very small (3% risk in 5 years), a trial of endovascular or surgical intervention would also be challenging because of the concern about risk of rupture, and many patients and providers would not agree to randomisation. Some have also argued that the intervention techniques used during a trial could already have become outdated by the trial’s conclusion, which precludes the results from being generalisable to future practice. How should we proceed in the assessment of the effectiveness of endovascular and surgical interventions for aneurysms with a high risk of rupture? First, we should have better risk predictions for complications of interventions. These predictions lag far behind the risk predictions of rupture. Second, once valid contemporary aneurysm site-specific and size-specific interventional treatment outcome data are available, we propose to use decision analytical techniques to determine which patients with unruptured intracranial aneurysms
would beneﬁt from an endovascular or surgical intervention.3 The PHASES score can then be used to quantify risks of rupture for these decision models. For now, although there are some limitations, the PHASES score can be used to better deﬁne the risk of rupture and to weigh these risks against the undetermined risks and effectiveness of endovascular or surgical interventions in terms of the prevention of future rupture. We declare that we have no competing interests.
*Jacoba P Greving, Marieke J H Wermer, Gabriël J E Rinkel, Ale Algra [email protected]
Julius Center for Health Sciences and Primary Care (JPG, AA), Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus (AA, GJER), University Medical Center Utrecht, Utrecht, Netherlands; and Department of Neurology, Leiden University Medical Center, Leiden, Netherlands (MJHW) 1
Greving JP, Wermer MJ, Brown RD Jr, et al. Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies. Lancet Neurol 2014; 13: 59–66. Raymond J, Darsaut TE, Molyneux AJ. A trial on unruptured intracranial aneurysms (the TEAM trial): results, lessons from a failure and the necessity for clinical care trials. Trials 2011; 12: 64. Greving JP, Rinkel GJ, Buskens E, Algra A. Cost-eﬀectiveness of preventive treatment of intracranial aneurysms: new data and uncertainties. Neurology 2009; 73: 258–65.
Developing biomarkers for cerebral amyloid angiopathy trials: do potential disease phenotypes hold promise? We read with great interest the Review by Steve Greenberg and colleagues1 about possible outcome markers in disease-modifying trials of cerebral amyloid angiopathy. Sporadic cerebral amyloid angiopathy is generally identified in elderly people and is characterised by the accumulation of amyloid β in cortical www.thelancet.com/neurology Vol 13 June 2014