Critical study Migraine and risk of subarachnoid haemorrhage: a population-based case-control study Kristie N Carter 1 MSC HONS MSC HONS, Neil Anderson 2 MB CHB FRACP MB CHB FRACP, Konrad Jamrozik 3 FAFPHM DPHIL FAFPHM DPHIL, Graeme Hankey 4 FRCP FRACP MD FRCP FRACP MD, Craig S Anderson 1 PHD FRACP FAFPHM PHD FRACP FAFPHM, for the Australasian Co-operative Research on Subarachnoid Haemorrhage Study (ACROSS) Group 1 The George Institute for International Health, University of Sydney, Sydney, Australia, 2 Department of Neurology, Auckland Hospital, Auckland, New Zealand, 3 School of Population Health, University of Queensland, Queensland, Australia, 4 Stroke Unit, Royal Perth Hospital, Perth, Western Australia, Australia Summary Objective. Evidence exists for an association between migraine and ischaemic stroke, but there is uncertainty about whether migraine is a risk factor for subarachnoid haemorrhage (SAH). Methods. A multi-centre, population-based, case-control study using cases of first-ever SAH during 1995–98 and matched controls in four study centres in Australia and New Zealand. Self- or proxy-reported history, frequency and characteristics of headaches, classified according to 1988 International Headache Society diagnostic criteria. Results. 206 of 432 (48%) cases and 236 of 473 (50%) controls had a history of headaches. The frequency and characteristics of headaches were similar between the two groups. No association was found in logistic regression analyses for history or frequency of headaches, or migraine headaches. Conclusions. No evidence was found for an association between recurrent headaches and SAH. Such information is important for counselling patients and families about the significance of past and ongoing headaches in relation to this illness. ª 2005 Elsevier Ltd. All rights reserved. Keywords: subarachnoid haemorrhage, case control, migraine, risk factors, headache INTRODUCTION Migraine is an inherited episodic disorder of the central nervous system that is not only common and, when severe, disabling, 1 but accumulating evidence indicates that it is also a risk factor for stroke. 2–9 Although the association appears strongest for ischaemic stroke in younger adults, 4,5,7 migraine might also be re- lated to subarachnoid haemorrhage (SAH), the most serious form of stroke in people of working age. 8 The low incidence of SAH means that large series of cases are difficult to accrue, 8,9 and pre- cise information on the association of migraine and SAH is corre- spondingly limited. The evidence to date, though, suggests that such an association may exist, particularly in people with a family history of migraine, in the presence of other vascular risk factors, such as smoking, 2,5 or in women who use low-dose oral contra- ceptives. 10 These risk estimates, however, are complicated by wide confidence intervals, often including unity, due to small numbers. Some aspect of the pathophysiological mechanisms involved in the cranial vasodilatation of migraine, or an effect of the medica- tions used by people with chronic headaches on the integrity of the walls of cerebral blood vessels, might provide both causal and non-causal interpretations of an association between migraine and SAH. Confirmation of such an association is important not only in providing information about the potential mechanisms for the formation and/or rupture of intracerebral aneurysms, but it is also of value in clinical practice for guiding the diagnosis and management of patients with headaches and survivors of SAH. Herein, we report an evaluation of whether a history of headaches, including migraine, was associated with an increased risk of SAH in the Australasian Cooperative Research on Sub- arachnoid Haemorrhage Study (ACROSS). 9 METHODS Cases As described in detail elsewhere, 9 ACROSS was a population- based, case-control study of SAH undertaken in four cities (Ade- laide, Hobart, and Perth, Australia; and Auckland, New Zealand), with a total study population (aged P15 years) of approximately 2.8 million, during 1995–98. Multiple overlapping sources were used to identify all new hospitalised and non-hospitalised (both fatal and non-fatal) cases of primary SAH. SAH was defined according to standard criteria, 11 as an abrupt onset of severe head- ache and/or loss of consciousness, with or without focal neurolog- ical signs; and where computerised tomography (CT), autopsy, or lumbar puncture revealed focal or generalised blood within the subarachnoid space. We included cases with proven rupture of an intracerebral aneurysm, as well as those where the cause of the SAH could not be identified either by angiography or at necropsy. Controls During the same study period, controls with no history of SAH were randomly selected from electoral rolls of the same areas from which the cases arose, and frequency matched to cases by sex and age (10-year strata) on the basis of projected rates. Enrol- ment to vote is compulsory in Australia and New Zealand. A post- al invitation to participate in a study investigating the role of health and lifestyle factors in the aetiology of SAH was followed up with a telephone call or visit to the home. Replacements were sought when potential control subjects could not be contacted after several attempts, or refused to participate. On the assumption that proxy interviews would be required for approximately 40% of Journal of Clinical Neuroscience (2005) 12(5), 534–537 0967-5868/$ - see front matter ª 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2004.09.009 Received 10 August 2004 Accepted 2 September 2004 Correspondence to: Kristie Carter, The George Institute for International Health, PO Box M201, Missenden Rd, Camperdown, NSW 2050, Australia. Tel.: +(61 2) 99934579; Fax: +(61 2) 99934502; E-mail: kcarter@thegeorgeinstitute.org 534