Abstract
Rupture of an intracranial aneurysm is the most common cause of subarachnoid haemorrhage (SAH), which is a life-threatening acute cerebrovascular event that typically affects working-age people. The exact prevalence of unruptured intracranial aneurysms (UIAs) is unknown, but at least one in 20 to 30 adults is likely to carry an asymptomatic UIA. Approximately one quarter of these UIAs rupture in a lifetime. Complex methodological challenges in conducting studies of epidemiology and risk factors for UIAs and SAH might have led to conclusions being drawn on the basis of epidemiological data of variable quality. We believe that, as a result, misconceptions about UIAs and SAH may have arisen. In this Perspectives article, we discuss three possible misconceptions about the epidemiology of UIAs and SAH, and suggest how the quality of future research could be improved.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Korja, M. et al. Cause-specific mortality of 1-year survivors of subarachnoid hemorrhage. Neurology 80, 481–486 (2013).
Thompson, B. G. et al. Guidelines for the management of patients with unruptured intracranial aneurysms: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 46, 2368–2400 (2015).
Korja, M., Lehto, H. & Juvela, S. Lifelong rupture risk of intracranial aneurysms depends on risk factors: a prospective Finnish cohort study. Stroke 45, 1958–1963 (2014).
Brown, R. D. Jr & Broderick, J. P. Unruptured intracranial aneurysms: epidemiology, natural history, management options, and familial screening. Lancet Neurol. 13, 393–404 (2014).
Greving, J. P. 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. 13, 59–66 (2014).
UCAS Japan Investigators et al. The natural course of unruptured cerebral aneurysms in a Japanese cohort. N. Engl. J. Med. 366, 2474–2482 (2012).
Wiebers, D. O. et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 362, 103–110 (2003).
Sonobe, M., Yamazaki, T., Yonekura, M. & Kikuchi, H. Small unruptured intracranial aneurysm verification study: SUAVe study, Japan. Stroke 41, 1969–1977 (2010).
Ishibashi, T. et al. Unruptured intracranial aneurysms: incidence of rupture and risk factors. Stroke 40, 313–316 (2009).
Wermer, M. J. et al. Yield of short-term follow-up CT/MR angiography for small aneurysms detected at screening. Stroke 37, 414–418 (2006).
Zhao, L. et al. An analysis of 1256 cases of sporadic ruptured cerebral aneurysm in a single Chinese institution. PLoS ONE 9, e85668 (2014).
Molyneux, A. J. et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet 366, 809–817 (2005).
Molyneux, A. et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet 360, 1267–1274 (2002).
Forget, T. R. Jr et al. A review of size and location of ruptured intracranial aneurysms. Neurosurgery 49, 1322–1325 (2001).
Joo, S. W. et al. What is the significance of a large number of ruptured aneurysms smaller than 7 mm in diameter? J. Korean Neurosurg. Soc. 45, 85–89 (2009).
Jagadeesan, B. D. et al. Size and anatomic location of ruptured intracranial aneurysms in patients with single and multiple aneurysms: a retrospective study from a single center. J. Neurointerv. Surg. 6, 169–174 (2014).
Muller, T. B. et al. Unruptured intracranial aneurysms in the Norwegian Nord-Trøndelag Health Study (HUNT): risk of rupture calculated from data in a population-based cohort study. Neurosurgery 73, 256–261 (2013).
Korja, M. et al. Risk factors and their combined effects on the incidence rate of subarachnoid hemorrhage — a population-based cohort study. PLoS ONE 8, e73760 (2013).
Knekt, P. et al. Risk factors for subarachnoid hemorrhage in a longitudinal population study. J. Clin. Epidemiol. 44, 933–939 (1991).
Sandvei, M. S., Romundstad, P. R., Muller, T. B., Vatten, L. & Vik, A. Risk factors for aneurysmal subarachnoid hemorrhage in a prospective population study: the HUNT study in Norway. Stroke 40, 1958–1962 (2009).
Linn, F. H., Rinkel, G. J., Algra, A. & van Gijn, J. Incidence of subarachnoid hemorrhage: role of region, year, and rate of computed tomography: a meta-analysis. Stroke 27, 625–629 (1996).
de Rooij, N. K., Linn, F. H., van der Plas, J. A., Algra, A. & Rinkel, G. J. Incidence of subarachnoid haemorrhage: a systematic review with emphasis on region, age, gender and time trends. J. Neurol. Neurosurg. Psychiatry 78, 1365–1372 (2007).
van Gijn, J., Kerr, R. S. & Rinkel, G. J. Subarachnoid haemorrhage. Lancet 369, 306–318 (2007).
Numminen, H., Kotila, M., Waltimo, O., Aho, K. & Kaste, M. Declining incidence and mortality rates of stroke in Finland from 1972 to 1991. Results of three population-based stroke registers. Stroke 27, 1487–1491 (1996).
Lunetta, P., Lounamaa, A. & Sihvonen, S. Surveillance of injury-related deaths: medicolegal autopsy rates and trends in Finland. Inj. Prev. 13, 282–284 (2007).
Penttila, A., Lahti, R. A. & Lunetta, P. Autopsies as a guarantee of legal protection and quality of patient care [Finnish]. Duodecim 115, 1524–1530 (1999).
Sandvei, M. S. et al. Incidence and mortality of aneurysmal subarachnoid hemorrhage in two Norwegian cohorts, 1984–2007. Neurology 77, 1833–1839 (2011).
Koffijberg, H. et al. Subarachnoid haemorrhage in Sweden 1987–2002: regional incidence and case fatality rates. J. Neurol. Neurosurg. Psychiatry 79, 294–299 (2008).
Engberg, A. W. & Teasdale, T. W. Epidemiology of non-traumatic brain injury of sudden onset in Denmark 1994–2002. Ugeskrift Laeger 169, 204–208 (2007).
Rinkel, G. J. Intracranial aneurysm screening: indications and advice for practice. Lancet Neurol. 4, 122–128 (2005).
Ronkainen, A. et al. Familial intracranial aneurysms. Lancet 349, 380–384 (1997).
Ronkainen, A. et al. Risk of harboring an unruptured intracranial aneurysm. Stroke 29, 359–362 (1998).
Bor, A. S. et al. Risk of subarachnoid haemorrhage according to number of affected relatives: a population based case-control study. Brain 131, 2662–2665 (2008).
Korja, M. et al. Genetic epidemiology of spontaneous subarachnoid hemorrhage: Nordic Twin Study. Stroke 41, 2458–2462 (2010).
van't Hof, F. N. et al. Genetic risk load according to the site of intracranial aneurysms. Neurology 83, 34–39 (2014).
Yasuno, K. et al. Genome-wide association study of intracranial aneurysm identifies three new risk loci. Nat. Genet. 42, 420–425 (2010).
Vlak, M. H., Algra, A., Brandenburg, R. & Rinkel, G. J. Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis. Lancet Neurol. 10, 626–636 (2011).
Vernooij, M. W. et al. Incidental findings on brain MRI in the general population. N. Engl. J. Med. 357, 1821–1828 (2007).
Green, G., Macintyre, S., West, P. & Ecob, R. Like parent like child? Associations between drinking and smoking behaviour of parents and their children. Br. J. Addict. 86, 745–758 (1991).
Murray, M., Kiryluk, S. & Swan, A. V. Relation between parents' and children's smoking behaviour and attitudes. J. Epidemiol. Commun. Health 39, 169–174 (1985).
Barman, S. K., Pulkkinen, L., Kaprio, J. & Rose, R. J. Inattentiveness, parental smoking and adolescent smoking initiation. Addiction 99, 1049–1061 (2004).
Chiu, S. Y., Chen, L. S., Yen, A. M. & Chen, H. H. Population-based proband-oriented pedigree information system: application to hypertension with population-based screening data (KCIS No. 25). J. Am. Med. Inform. Assoc. 19, 102–110 (2012).
Fuentes, R. M., Notkola, I. L., Shemeikka, S., Tuomilehto, J. & Nissinen, A. Familial aggregation of blood pressure: a population-based family study in eastern Finland. J. Hum. Hypertens. 14, 441–445 (2000).
Miller, T. D., White, P. M., Davenport, R. J. & Al- Shahi Salman, R. Screening patients with a family history of subarachnoid haemorrhage for intracranial aneurysms: screening uptake, patient characteristics and outcome. J. Neurol. Neurosurg. Psychiatry 83, 86–88 (2012).
Brown, R. D. Jr et al. Screening for brain aneurysm in the Familial Intracranial Aneurysm study: frequency and predictors of lesion detection. J. Neurosurg. 108, 1132–1138 (2008).
Ekblad, M., Gissler, M., Korkeila, J. & Lehtonen, L. Trends and risk groups for smoking during pregnancy in Finland and other Nordic countries. Eur. J. Publ. Health 24, 544–551 (2014).
Jaakkola, N., Ruotsalainen, R. & Jaakkola, J. J. What are the determinants of children's exposure to environmental tobacco smoke at home? Scand. J. Soc. Med. 22, 107–112 (1994).
Vartiainen, E. et al. Thirty-five-year trends in cardiovascular risk factors in Finland. Int. J. Epidemiol. 39, 504–518 (2010).
Pierce, J. P., Messer, K., White, M. M., Cowling, D. W. & Thomas, D. P. Prevalence of heavy smoking in California and the United States, 1965–2007. JAMA 305, 1106–1112 (2011).
West, H. W. et al. Exposure to parental smoking in childhood is associated with increased risk of carotid atherosclerotic plaque in adulthood: the cardiovascular risk in young Finns study. Circulation 131, 1239–1246 (2015).
Gaal, E. I. et al. Intracranial aneurysm risk locus 5q23.2 is associated with elevated systolic blood pressure. PLoS Genet. 8, e1002563 (2012).
Oxman, A. D. et al. Agreement among reviewers of review articles. J. Clin. Epidemiol. 44, 91–98 (1991).
Klimo, P. Jr., Thompson, C. J., Ragel, B. T. & Boop, F. A. Methodology and reporting of meta-analyses in the neurosurgical literature. J. Neurosurg. 120, 796–810 (2014).
Etminan, N. et al. Multidisciplinary consensus on assessment of unruptured intracranial aneurysms: proposal of an international research group. Stroke 45, 1523–1530 (2014).
Bor, A. S., Koffijberg, H., Wermer, M. J. & Rinkel, G. J. Optimal screening strategy for familial intracranial aneurysms: a cost-effectiveness analysis. Neurology 74, 1671–1679 (2010).
Bor, A. S., Rinkel, G. J., van Norden, J. & Wermer, M. J. Long-term, serial screening for intracranial aneurysms in individuals with a family history of aneurysmal subarachnoid haemorrhage: a cohort study. Lancet Neurol. 13, 385–392 (2014).
Backes, D. et al. Difference in aneurysm characteristics between ruptured and unruptured aneurysms in patients with multiple intracranial aneurysms. Stroke 45, 1299–1303 (2014).
Miura, Y. et al. Low wall shear stress is independently associated with the rupture status of middle cerebral artery aneurysms. Stroke 44, 519–521 (2013).
Kirchoff-Torres, K. F. & Labovitz, D. L. Letter by Kirchoff-Torres and Labovitz regarding article, “Lifelong rupture risk of intracranial aneurysms depends on risk factors: a prospective Finnish cohort study”. Stroke 45, e210 (2014).
Korja, M., Juvela, S. & Hernesniemi, J. Unruptured cerebral aneurysms in a Japanese cohort. N. Engl. J. Med. 367, 1268; author reply 1269 (2012).
Tolonen, H. et al. The validation of the Finnish Hospital Discharge Register and Causes of Death Register data on stroke diagnoses. Eur. J. Cardiovasc. Prev. Rehabil. 14, 380–385 (2007).
Leppala, J. M., Virtamo, J. & Heinonen, O. P. Validation of stroke diagnosis in the National Hospital Discharge Register and the Register of Causes of Death in Finland. Eur. J. Epidemiol. 15, 155–160 (1999).
Korja, M., Hernesniemi, J., Lawton, M. T., Spetzler, R. F. & Morgan, M. K. Is cerebrovascular neurosurgery sacrificed on the altar of RCTs? Lancet 384, 27–28 (2014).
Korja, M. ISAT: end of the debate on coiling versus clipping? Lancet 385, 2250–2251 (2015).
Acknowledgements
M.K. has received personal grants from the Sigrid Jusélius, Biomedicum Helsinki, Orion-Farmos Research, and Instrumentarium Research Foundations, as well as from the Finnish Medical Association. J.K. is supported by the Academy of Finland (grants 265240, 263278). The study sponsors did not have any role in the writing of the manuscript, or in the decision to submit the manuscript for publication.
Author information
Authors and Affiliations
Contributions
M.K. researched data for the article and wrote the article. J.K. reviewed/edited the manuscript before submission. Both authors provided substantial contribution to discussion of content.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
PowerPoint slides
Rights and permissions
About this article
Cite this article
Korja, M., Kaprio, J. Controversies in epidemiology of intracranial aneurysms and SAH. Nat Rev Neurol 12, 50–55 (2016). https://doi.org/10.1038/nrneurol.2015.228
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrneurol.2015.228
This article is cited by
-
MicroRNA-513b-5p targets COL1A1 and COL1A2 associated with the formation and rupture of intracranial aneurysm
Scientific Reports (2021)
-
Activation of Galanin Receptor 1 with M617 Attenuates Neuronal Apoptosis via ERK/GSK-3β/TIP60 Pathway After Subarachnoid Hemorrhage in Rats
Neurotherapeutics (2021)
-
Injectable inclusion complex composed of α-cyclodextrin and hydrophobically modified poly(vinyl alcohol) as a cerebral aneurysm embolization material
Polymer Journal (2020)
-
Prediction of Intracranial Aneurysm Risk using Machine Learning
Scientific Reports (2020)
-
Incidence and case fatality of aneurysmal subarachnoid hemorrhage admitted to hospital between 2008 and 2014 in Norway
Acta Neurochirurgica (2020)