Skip to main content

Advertisement

SpringerLink
Log in

Vasospasm-related complications after subarachnoid hemorrhage: the role of patients’ age and sex

  • Original Article - Vascular Neurosurgery - Aneurysm
  • Published:
Acta Neurochirurgica Aims and scope Submit manuscript

Abstract

Background

Outcome of aneurysmal subarachnoid hemorrhage (SAH) depends strongly on occurrence of symptomatic vasospasm (SV) leading to delayed cerebral ischemia (DCI). Various demographic, radiographic, and clinical predictors of SV have been reported so far, partially with conflicting results. The aim of this study was to analyze the role of patients’ age and sex on SV/DCI risk, especially to identify age and sex-specific risk groups.

Methods

All patients admitted with acute SAH during a 14-year-period ending in 2016 were eligible for this study. The study endpoints were the following: SV requiring spasmolysis, occurrence of DCI in follow-up computed tomography scans and unfavorable outcome at 6 months (modified Rankin scale > 2).

Results

Nine hundred ninety-four patients were included in this study. The majority was female (666; 67%). SV, DCI, and unfavorable outcomes were observed in 21.5, 21.8, and 43.6% of the patients, respectively. Younger age (p < 0.001; OR = 1.03 per year decrease) and female sex (p = 0.025; OR = 1.510) were confirmed as independent predictors of SV. Regarding the sex differences, there were three age groups for SV/DCI risk ≤ 54, 55–74, and ≥ 75 years. Male patients showed earlier decrease in SV risk (at ≥ 55 vs. ≥ 75 years in females). Therefore, SAH females aged between 55 and 74 years were at the highest risk for DCI and unfavorable outcome, as compared to younger/older females (p = 0.001, OR = 1.77/p = 0.001, OR = 1.80). In contrast, their male counterparts did not show these risk alterations (p = 0.445/p = 0.822).

Conclusion

After acute SAH, female and male patients seem to show different age patterns for the risk of SV and DCI. Females aged between 55 and 74 years are at particular risk of vasospasm-related SAH complications, possibly due to onset of menopause.

Clinical trial registration number

DRKS, Unique identifier: DRKS00008749

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

CI 95%:

Confidence interval 95%

CT:

Computed tomography

DCI:

Delayed cerebral ischemia

ICH:

Intracerebral hemorrhage

IVH:

Intraventricular hemorrhage

mRS:

Modified Rankin scale

OR:

Odds ratio

SAH:

Subarachnoid hemorrhage

SD:

Standard deviation

SV:

Symptomatic vasospasm

TCD:

Transcranial Doppler ultrasound

WFNS:

World Federation of Neurosurgical Societies

References

  1. Algra AM, Klijn CJ, Helmerhorst FM, Algra A, Rinkel GJ (2012) Female risk factors for subarachnoid hemorrhage: a systematic review. Neurology 79:1230–1236. https://doi.org/10.1212/WNL.0b013e31826aace6

    Article  PubMed  Google Scholar 

  2. Anderson RC, Kan P, Klimo P, Brockmeyer DL, Walker ML, Kestle JR (2004) Complications of intracranial pressure monitoring in children with head trauma. J Neurosurg 101:53–58. https://doi.org/10.3171/ped.2004.101.2.0053

    Article  PubMed  Google Scholar 

  3. Calleja-Agius J, Brincat M (2012) The effect of menopause on the skin and other connective tissues. Gynecol Endocrinol 28:273–277. https://doi.org/10.3109/09513590.2011.613970

    Article  PubMed  CAS  Google Scholar 

  4. Charpentier C, Audibert G, Guillemin F, Civit T, Ducrocq X, Bracard S, Hepner H, Picard L, Laxenaire MC (1999) Multivariate analysis of predictors of cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage. Stroke 30:1402–1408

    Article  PubMed  CAS  Google Scholar 

  5. Claassen J, Bernardini GL, Kreiter K, Bates J, Du YE, Copeland D, Connolly ES, Mayer SA (2001) Effect of cisternal and ventricular blood on risk of delayed cerebral ischemia after subarachnoid hemorrhage: the Fisher scale revisited. Stroke 32:2012–2020

    Article  PubMed  CAS  Google Scholar 

  6. Claus JJ, Breteler MM, Hasan D, Krenning EP, Bots ML, Grobbee DE, Van Swieten JC, Van Harskamp F, Hofman A (1998) Regional cerebral blood flow and cerebrovascular risk factors in the elderly population. Neurobiol Aging 19:57–64

    Article  PubMed  CAS  Google Scholar 

  7. de Moraes-Ruehsen M, Jones GS (1967) Premature ovarian failure. Fertil Steril 18:440–461

    Article  PubMed  Google Scholar 

  8. Ding C, Toll V, Ouyang B, Chen M (2013) Younger age of menopause in women with cerebral aneurysms. J Neurointerv Surg 5:327–331. https://doi.org/10.1136/neurintsurg-2012-010364

    Article  PubMed  Google Scholar 

  9. Dratva J, Gomez Real F, Schindler C, Ackermann-Liebrich U, Gerbase MW, Probst-Hensch NM, Svanes C, Omenaas ER, Neukirch F, Wjst M, Morabia A, Jarvis D, Leynaert B, Zemp E (2009) Is age at menopause increasing across Europe? Results on age at menopause and determinants from two population-based studies. Menopause 16:385–394. https://doi.org/10.1097/gme.0b013e31818aefef

    Article  PubMed  Google Scholar 

  10. Dumont AS, Crowley RW, Monteith SJ, Ilodigwe D, Kassell NF, Mayer S, Ruefenacht D, Weidauer S, Pasqualin A, Macdonald RL (2010) Endovascular treatment or neurosurgical clipping of ruptured intracranial aneurysms: effect on angiographic vasospasm, delayed ischemic neurological deficit, cerebral infarction, and clinical outcome. Stroke 41:2519–2524. https://doi.org/10.1161/strokeaha.110.579383

    Article  PubMed  Google Scholar 

  11. Fisher CM, Kistler JP, Davis JM (1980) Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 6:1–9

    Article  PubMed  CAS  Google Scholar 

  12. Foreman B (2016) The pathophysiology of delayed cerebral ischemia. J Clin Neurophysiol 33:174–182. https://doi.org/10.1097/wnp.0000000000000273

    Article  PubMed  Google Scholar 

  13. Frontera JA, Fernandez A, Schmidt JM, Claassen J, Wartenberg KE, Badjatia N, Connolly ES, Mayer SA (2009) Defining vasospasm after subarachnoid hemorrhage: what is the most clinically relevant definition? Stroke 40:1963–1968. https://doi.org/10.1161/strokeaha.108.544700

    Article  PubMed  Google Scholar 

  14. Germans MR, Jaja BNR, de Oliviera Manoel AL, Cohen AH, Macdonald RL (2017) Sex differences in delayed cerebral ischemia after subarachnoid hemorrhage. J Neurosurg:1–7. https://doi.org/10.3171/2017.3.jns162808

  15. Gross BA, Rosalind Lai PM, Frerichs KU, Du R (2014) Treatment modality and vasospasm after aneurysmal subarachnoid hemorrhage. World Neurosurg 82:e725–e730. https://doi.org/10.1016/j.wneu.2013.08.017

    Article  PubMed  Google Scholar 

  16. Hirashima Y, Kurimoto M, Hori E, Origasa H, Endo S (2005) Lower incidence of symptomatic vasospasm after subarachnoid hemorrhage owing to ruptured vertebrobasilar aneurysms. Neurosurgery 57:1110–1116 discussion 1110-1116

    Article  PubMed  Google Scholar 

  17. Inagawa T (2016) Risk factors for cerebral vasospasm following aneurysmal subarachnoid hemorrhage: a review of the literature. World neurosurgery 85:56–76. https://doi.org/10.1016/j.wneu.2015.08.052

    Article  PubMed  Google Scholar 

  18. Jabbarli R, Glasker S, Weber J, Taschner C, Olschewski M, Van Velthoven V (2013) Predictors of severity of cerebral vasospasm caused by aneurysmal subarachnoid hemorrhage. J Stroke Cerebrovasc Dis 22:1332–1339. https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.01.006

    Article  PubMed  Google Scholar 

  19. Jamous MA, Nagahiro S, Kitazato KT, Satomi J, Satoh K (2005) Role of estrogen deficiency in the formation and progression of cerebral aneurysms. Part I: experimental study of the effect of oophorectomy in rats. J Neurosurg 103:1046–1051. https://doi.org/10.3171/jns.2005.103.6.1046

    Article  PubMed  CAS  Google Scholar 

  20. Jiang C, Zuo F, Wang Y, Lu H, Yang Q, Wang J (2016) Progesterone changes VEGF and BDNF expression and promotes neurogenesis after ischemic stroke. Mol Neurobiol. https://doi.org/10.1007/s12035-015-9651-y

  21. Jiang C, Zuo F, Wang Y, Wan J, Yang Z, Lu H, Chen W, Zang W, Yang Q, Wang J (2016) Progesterone exerts neuroprotective effects and improves long-term neurologic outcome after intracerebral hemorrhage in middle-aged mice. Neurobiol Aging 42:13–24. https://doi.org/10.1016/j.neurobiolaging.2016.02.029

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Kongable GL, Lanzino G, Germanson TP, Truskowski LL, Alves WM, Torner JC, Kassell NF (1996) Gender-related differences in aneurysmal subarachnoid hemorrhage. J Neurosurg 84:43–48. https://doi.org/10.3171/jns.1996.84.1.0043

    Article  PubMed  CAS  Google Scholar 

  23. Lawton MT, Vates GE (2017) Subarachnoid hemorrhage. N Engl J Med 377:257–266. https://doi.org/10.1056/NEJMcp1605827

    Article  PubMed  Google Scholar 

  24. Lin CL, Dumont AS, Wu SC, Wang CJ, Howng SL, Huang YF, Wong WY, Kassell NF, Jeng AY, Kwan AL (2006) 17beta-estradiol inhibits endothelin-1 production and attenuates cerebral vasospasm after experimental subarachnoid hemorrhage. Exp Biol Med 231:1054–1057

    CAS  Google Scholar 

  25. Lin CL, Shih HC, Dumont AS, Kassell NF, Lieu AS, Su YF, Hwong SL, Hsu C (2006) The effect of 17beta-estradiol in attenuating experimental subarachnoid hemorrhage-induced cerebral vasospasm. J Neurosurg 104:298–304. https://doi.org/10.3171/jns.2006.104.2.298

    Article  PubMed  CAS  Google Scholar 

  26. Macdonald RL, Wallace MC, Coyne TJ (1994) The effect of surgery on the severity of vasospasm. J Neurosurg 80:433–439. https://doi.org/10.3171/jns.1994.80.3.0433

    Article  PubMed  CAS  Google Scholar 

  27. Macdonald RL, Rosengart A, Huo D, Karrison T (2003) Factors associated with the development of vasospasm after planned surgical treatment of aneurysmal subarachnoid hemorrhage. J Neurosurg 99:644–652. https://doi.org/10.3171/jns.2003.99.4.0644

    Article  PubMed  Google Scholar 

  28. Magge SN, Chen HI, Ramakrishna R, Cen L, Chen Z, Elliott JP, Winn HR, Le Roux PD (2010) Association of a younger age with an increased risk of angiographic and symptomatic vasospasms following subarachnoid hemorrhage. J Neurosurg 112:1208–1215. https://doi.org/10.3171/2009.9.jns081670

    Article  PubMed  Google Scholar 

  29. McGirt MJ, Mavropoulos JC, McGirt LY, Alexander MJ, Friedman AH, Laskowitz DT, Lynch JR (2003) Leukocytosis as an independent risk factor for cerebral vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg 98:1222–1226. https://doi.org/10.3171/jns.2003.98.6.1222

    Article  PubMed  Google Scholar 

  30. McGirt MJ, Blessing R, Alexander MJ, Nimjee SM, Woodworth GF, Friedman AH, Graffagnino C, Laskowitz DT, Lynch JR (2006) Risk of cerebral vasopasm after subarachnoid hemorrhage reduced by statin therapy: a multivariate analysis of an institutional experience. J Neurosurg 105:671–674. https://doi.org/10.3171/jns.2006.105.5.671

    Article  PubMed  CAS  Google Scholar 

  31. Meyer JS, Terayama Y, Takashima S (1993) Cerebral circulation in the elderly. Cerebrovasc Brain Metab Rev 5:122–146

    PubMed  CAS  Google Scholar 

  32. Moss EL, Taneja S, Munir F, Kent C, Robinson L, Potdar N, Sarhanis P, McDermott H (2016) Iatrogenic menopause after treatment for cervical cancer. Clin Oncol (R Coll Radiol) 28:766–775. https://doi.org/10.1016/j.clon.2016.08.016

    Article  CAS  Google Scholar 

  33. Nabulsi AA, Folsom AR, White A, Patsch W, Heiss G, Wu KK, Szklo M (1993) Association of hormone-replacement therapy with various cardiovascular risk factors in postmenopausal women. The Atherosclerosis Risk in Communities Study Investigators. N Engl J Med 328:1069–1075. https://doi.org/10.1056/nejm199304153281501

    Article  PubMed  CAS  Google Scholar 

  34. Parazzini F (2007) Determinants of age at menopause in women attending menopause clinics in Italy. Maturitas 56:280–287. https://doi.org/10.1016/j.maturitas.2006.09.003

    Article  PubMed  Google Scholar 

  35. Phipps AI, Ichikawa L, Bowles EJ, Carney PA, Kerlikowske K, Miglioretti DL, Buist DS (2010) Defining menopausal status in epidemiologic studies: a comparison of multiple approaches and their effects on breast cancer rates. Maturitas 67:60–66. https://doi.org/10.1016/j.maturitas.2010.04.015

    Article  PubMed  PubMed Central  Google Scholar 

  36. Qureshi AI, Malik AA, Saeed O, Defillo A, Sherr GT, Suri MF (2016) Hormone replacement therapy and the risk of subarachnoid hemorrhage in postmenopausal women. J Neurosurg 124:45–50. https://doi.org/10.3171/2014.12.jns142329

    Article  PubMed  CAS  Google Scholar 

  37. Rabb CH, Tang G, Chin LS, Giannotta SL (1994) A statistical analysis of factors related to symptomatic cerebral vasospasm. Acta Neurochir 127:27–31

    Article  PubMed  CAS  Google Scholar 

  38. Rosenlrn J, Eskesen V, Schmidt K (1993) Clinical features and outcome in females and males with ruptured intracranial saccular aneurysms. Br J Neurosurg 7:287–290

    Article  PubMed  CAS  Google Scholar 

  39. Ryttlefors M, Enblad P, Ronne-Engstrom E, Persson L, Ilodigwe D, Macdonald RL (2010) Patient age and vasospasm after subarachnoid hemorrhage. Neurosurgery 67:911–917. https://doi.org/10.1227/NEU.0b013e3181ed11ab

    Article  PubMed  Google Scholar 

  40. Schumacher M, Sitruk-Ware R, De Nicola AF (2008) Progesterone and progestins: neuroprotection and myelin repair. Curr Opin Pharmacol 8:740–746. https://doi.org/10.1016/j.coph.2008.10.002

    Article  PubMed  CAS  Google Scholar 

  41. Shih HC, Lin CL, Lee TY, Lee WS, Hsu C (2006) 17beta-estradiol inhibits subarachnoid hemorrhage-induced inducible nitric oxide synthase gene expression by interfering with the nuclear factor kappa B transactivation. Stroke 37:3025–3031. https://doi.org/10.1161/01.STR.0000249008.18669.5a

    Article  PubMed  CAS  Google Scholar 

  42. Sobrino A, Mata M, Laguna-Fernandez A, Novella S, Oviedo PJ, Garcia-Perez MA, Tarin JJ, Cano A, Hermenegildo C (2009) Estradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells. PLoS One 4:e8242. https://doi.org/10.1371/journal.pone.0008242

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Stepaniak U, Szafraniec K, Kubinova R, Malyutina S, Peasey A, Pikhart H, Pajak A, Bobak M (2013) Age at natural menopause in three central and eastern European urban populations: the HAPIEE study. Maturitas 75:87–93. https://doi.org/10.1016/j.maturitas.2013.02.008

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Tabuchi S (2015) Relationship between postmenopausal estrogen deficiency and aneurysmal subarachnoid hemorrhage. Behav Neurol 2015:720141. https://doi.org/10.1155/2015/720141

    Article  PubMed  PubMed Central  Google Scholar 

  45. Tada Y, Makino H, Furukawa H, Shimada K, Wada K, Liang EI, Murakami S, Kudo M, Kung DK, Hasan DM, Kitazato KT, Nagahiro S, Lawton MT, Hashimoto T (2014) Roles of estrogen in the formation of intracranial aneurysms in ovariectomized female mice. Neurosurgery 75:690–695; discussion 695. https://doi.org/10.1227/neu.0000000000000528

    Article  PubMed  PubMed Central  Google Scholar 

  46. Tada Y, Wada K, Shimada K, Makino H, Liang EI, Murakami S, Kudo M, Shikata F, Pena Silva RA, Kitazato KT, Hasan DM, Kanematsu Y, Nagahiro S, Hashimoto T (2014) Estrogen protects against intracranial aneurysm rupture in ovariectomized mice. Hypertension 63:1339–1344. https://doi.org/10.1161/hypertensionaha.114.03300

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Teasdale GM, Drake CG, Hunt W, Kassell N, Sano K, Pertuiset B, De Villiers JC (1988) A universal subarachnoid hemorrhage scale: report of a committee of the World Federation of Neurosurgical Societies. J Neurol Neurosurg Psychiatry 51:1457

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Teunissen LL, Rinkel GJ, Algra A, van Gijn J (1996) Risk factors for subarachnoid hemorrhage: a systematic review. Stroke 27:544–549

    Article  PubMed  CAS  Google Scholar 

  49. van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J (1988) Interobserver agreement for the assessment of handicap in stroke patients. Stroke 19:604–607

    Article  PubMed  Google Scholar 

  50. Vergouwen MD, Vermeulen M, van Gijn J, Rinkel GJ, Wijdicks EF, Muizelaar JP, Mendelow AD, Juvela S, Yonas H, Terbrugge KG, Macdonald RL, Diringer MN, Broderick JP, Dreier JP, Roos YB (2010) Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke 41:2391–2395. https://doi.org/10.1161/strokeaha.110.589275

    Article  PubMed  Google Scholar 

  51. Yousef K, Crago E, Kuo CW, Horowitz M, Hravnak M (2010) Predictors of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: a cardiac focus. Neurocrit Care 13:366–372. https://doi.org/10.1007/s12028-010-9408-4

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, University Hospital, University of Duisburg-Essen, 45147, Essen, Germany

    Marvin Darkwah Oppong, Oliver Gembruch, Daniela Pierscianek, Mehdi Chihi, Philipp Dammann, Oliver Müller, Ulrich Sure & Ramazan Jabbarli

  2. Department of Gynecology and Obstetrics, University Hospital, University of Duisburg-Essen, Essen, Germany

    Antonella Iannaccone & Angela Köninger

  3. Institute for Diagnostic and Interventional Radiology, University Hospital, University of Duisburg-Essen, Essen, Germany

    Michael Forsting

Authors
  1. Marvin Darkwah Oppong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonella Iannaccone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Oliver Gembruch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniela Pierscianek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mehdi Chihi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Philipp Dammann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Angela Köninger
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Oliver Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michael Forsting
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ulrich Sure
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ramazan Jabbarli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marvin Darkwah Oppong.

Ethics declarations

Conflict of Interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

Additional information

Comments

A large retrospective study evaluating the effect of sex and age on the prediction, and occurrence of symptomatic vasospasm, and clinical outcome. The novel finding is that female age 55–75 are at higher risks of symptomatic vasospasm and poor outcome, possibly due to postmenopausal hormonal effect, lack of estrogen and decrease in NO production thus decreasing the vasodilator effect on blood vessels. There are many speculation based on a retrospective study with several limitations as outlined by the authors. If they could regroup the hormonal data on this subgroup of patients, it could significantly enhance the value of this study. Perhaps for the future analyses.

Amir Dehdashti

NY, USA

Appendix

Appendix

Table 3 Age-dependent risk for DCI divided by sex groups
Full size table
Fig. 4
figure 4

Sex-dependent risk for unfavorable outcome in the three different age groups (≤ 55, 55–74, and ≥ 74 years) in percent. And comparison with the same sex younger/older counterparts

Full size image

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Darkwah Oppong, M., Iannaccone, A., Gembruch, O. et al. Vasospasm-related complications after subarachnoid hemorrhage: the role of patients’ age and sex. Acta Neurochir 160, 1393–1400 (2018). https://doi.org/10.1007/s00701-018-3549-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00701-018-3549-1

Keywords

Search

Navigation