J Cerebrovasc Endovasc Neurosurg.  2018 Jun;20(2):112-119. 10.7461/jcen.2018.20.2.112.

The Prevalence and Characterization of Cerebral Microbleeds in Young People Having Intracerebral Hemorrhage

• Lee YM
• Koo HW
• Kang HK
• Kim JW
• Han SR
• Yoon SW
• Choi CY
• Sohn MJ
• Lee CH

• KMID: 2422605
• DOI: http://doi.org/10.7461/jcen.2018.20.2.112

Abstract

OBJECTIVE
Cerebral microbleeds (CMBs) are known as the neuroimaging markers of risk in stroke and dementia. Many studies on CMBs in elderly patients with hemorrhagic or ischemic stroke have been reported; however, reports on CMBs in young populations with intracerebral hemorrhage (ICH) are lacking.
MATERIALS AND METHODS
A total of 272 patients aged 18-54 years presented to our hospital with ICH between December 2009 and August 2017. Among these, CMB presence, count, and topography with respect to ICH were evaluated on magnetic resonance imaging (MRI) gradient echo images (GREs). We also evaluated the prevalence and risk factors of CMBs.
RESULTS
Among 272 patients, only 66 underwent GRE T2-weighted MRI. CMBs were detected in 40 patients (61%), with 29 (73%) being of the multifocal type. Among the 219 CMBs, 150 (68.5%) were of the deep type and 69 (31.5%) of the lobar type. CMB prevalence was higher in men. In multivariate logistic regression analysis, history of hypertension (adjusted odds ratio [aOR], 4.048; 95% confidence interval [CI], 1.14-14.32; p = 0.030), and male sex (aOR, 4.233; 95% CI, 1.09-16.48; p = 0.037) were independently associated with CMBs.
CONCLUSION
In young patients who presented with spontaneous ICH, CMBs were highly prevalent in 61% of patients and strongly associated with history of hypertension and male sex.

Keyword

Cerebral microbleeds; Intracranial hemorrhage; Risk factors; Young adult

MeSH Terms

Aged
Cerebral Hemorrhage*
Dementia
Humans
Hypertension
Intracranial Hemorrhages
Logistic Models
Magnetic Resonance Imaging
Male
Neuroimaging
Odds Ratio
Prevalence*
Risk Factors
Stroke
Young Adult

Reference

1. Al-Shahi Salman R, Berg MJ, Morrison L, Awad IA. Angioma Alliance Scientific Advisory B. Hemorrhage from cavernous malformations of the brain: definition and reporting standards. Angioma Alliance Scientific Advisory Board. Stroke. 2008; 12. 39(12):3222–3230. PMID: 18974380.

2. Charidimou A, Boulouis G, Haley K, Auriel E, van Etten ES, Fotiadis P, et al. White matter hyperintensity patterns in cerebral amyloid angiopathy and hypertensive arteriopathy. Neurology. 2016; 2. 86(6):505–511. PMID: 26747886.

3. Charidimou A, Jäger RH, Fox Z, Peeters A, Vandermeeren Y, Laloux P, et al. Prevalence and mechanisms of cortical superficial siderosis in cerebral amyloid angiopathy. Neurology. 2013; 8. 81(7):626–632. PMID: 23864315.

4. Charidimou A, Jaunmuktane Z, Baron JC, Burnell M, Varlet P, Peeters A, et al. White matter perivascular spaces: an MRI marker in pathology-proven cerebral amyloid angiopathy? Neurology. 2014; 1. 82(1):57–62. PMID: 24285616.

5. Charidimou A, Krishnan A, Werring DJ, Rolf Jäger H. Cerebral microbleeds: a guide to detection and clinical relevance in different disease settings. Neuroradiology. 2013; 6. 55(6):655–674. PMID: 23708941.

6. Charidimou A, Meegahage R, Fox Z, Peeters A, Vandermeeren Y, Laloux P, et al. Enlarged perivascular spaces as a marker of underlying arteriopathy in intracerebral haemorrhage: a multicentre MRI cohort study. J Neurol Neurosurg Psychiatry. 2013; 6. 84(6):624–629. PMID: 23412074.

7. Charidimou A, Shakeshaft C, Werring DJ. Cerebral microbleeds on magnetic resonance imaging and anticoagulant-associated intracerebral hemorrhage risk. Front Neurol. 2012; 9. 3:133. PMID: 23015806.

8. Chen ST, Chiang CY, Hsu CY, Lee TH, Tang LM. Recurrent hypertensive intracerebral hemorrhage. Acta Neurol Scand. 1995; 2. 91(2):128–132. PMID: 7785422.

9. Cordonnier C, Al-Shahi Salman R, Wardlaw J. Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain. 2007; 8. 130(Pt 8):1988–2003. PMID: 17322562.

10. Del Brutto VJ, Zambrano M, Mera RM, Del Brutto OH. Population-based study of cerebral microbleeds in stroke-free older adults living in rural ecuador: the atahualpa project. Stroke. 2015; 7. 46(7):1984–1986. PMID: 26022640.

11. Douglas MA, Haerer AF. Long-term prognosis of hypertensive intracerebral hemorrhage. Stroke. 1982; Jul-Aug. 13(4):488–491. PMID: 7101349.

12. Dumas A, Dierksen GA, Gurol ME, Halpin A, Martinez-Ramirez S, Schwab K, et al. Functional magnetic resonance imaging detection of vascular reactivity in cerebral amyloid angiopathy. Ann Neurol. 2012; 7. 72(1):76–81. PMID: 22829269.

13. Fanou EM, Coutinho JM, Shannon P, Kiehl TR, Levi MM, Wilcox ME, et al. Critical illness-associated cerebral microbleeds. Stroke. 2017; 4. 48(4):1085–1087. PMID: 28235962.

14. Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol. 1987; 8. 149(2):351–356. PMID: 3496763.

15. Fazekas F, Kleinert R, Roob G, Kleinert G, Kapeller P, Schmidt R, et al. Histopathologic analysis of foci of signal loss on gradient-echo T2^*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds. AJNR Am J Neuroradiol. 1999; 4. 20(4):637–642. PMID: 10319975.

16. Fieschi C, Carolei A, Fiorelli M, Argentino C, Bozzao L, Fazio C, et al. Changing prognosis of primary intracerebral hemorrhage: results of a clinical and computed tomographic follow-up study of 104 patients. Stroke. 1988; 2. 19(2):192–195. PMID: 3344534.

17. Greenberg SM, Finklestein SP, Schaefer PW. Petechial hemorrhages accompanying lobar hemorrhage: detection by gradient-echo MRI. Neurology. 1996; 6. 46(6):1751–1754. PMID: 8649586.

18. Greenberg SM, Vernooij MW, Cordonnier C, Viswanathan A, Al-Shahi Salman R, Warach S, et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol. 2009; 2. 8(2):165–174. PMID: 19161908.

19. Gregoire SM, Chaudhary UJ, Brown MM, Yousry TA, Kallis C, Jäger HR, et al. The Microbleed Anatomical Rating Scale (MARS): reliability of a tool to map brain microbleeds. Neurology. 2009; 11. 73(21):1759–1766. PMID: 19933977.

20. Gurol ME, Irizarry MC, Smith EE, Raju S, Diaz-Arrastia R, Bottiglieri T, et al. Plasma beta-amyloid and white matter lesions in AD, MCI, and cerebral amyloid angiopathy. Neurology. 2006; 1. 66(1):23–29. PMID: 16401840.

21. Gurol ME, Viswanathan A, Gidicsin C, Hedden T, Martinez-Ramirez S, Dumas A, et al. Cerebral amyloid angiopathy burden associated with leukoaraiosis: a positron emission tomography/magnetic resonance imaging study. Ann Neurol. 2013; 4. 73(4):529–536. PMID: 23424091.

22. Hill MD, Silver FL, Austin PC, Tu JV. Rate of stroke recurrence in patients with primary intracerebral hemorrhage. Stroke. 2000; 1. 31(1):123–127. PMID: 10625726.

23. Jeerakathil T, Wolf PA, Beiser A, Hald JK, Au R, Kase CS, et al. Cerebral microbleeds: prevalence and associations with cardiovascular risk factors in the Framingham Study. Stroke. 2004; 8. 35(8):1831–1835. PMID: 15155954.

24. Kato H, Izumiyama M, Izumiyama K, Takahashi A, Itoyama Y. Silent cerebral microbleeds on T2^*-weighted MRI: correlation with stroke subtype, stroke recurrence, and leukoaraiosis. Stroke. 2002; 6. 33(6):1536–1540. PMID: 12052987.

25. Kinoshita T, Okudera T, Tamura H, Ogawa T, Hatazawa J. Assessment of lacunar hemorrhage associated with hypertensive stroke by echo-planar gradient-echo T2^*-weighted MRI. Stroke. 2000; 7. 31(7):1646–1650. PMID: 10884467.

26. Knudsen KA, Rosand J, Karluk D, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology. 2001; 2. 56(4):537–539. PMID: 11222803.

27. Koennecke HC. Cerebral microbleeds on MRI: prevalence, associations, and potential clinical implications. Neurology. 2006; 1. 66(2):165–171. PMID: 16434647.

28. Koo HW, Jo KI, Yeon JY, Kim JS, Hong SC. Clinical features of high-degree centrum semiovale-perivascular spaces in cerebral amyloid angiopathy. J Neurol Sci. 2016; 8. 367:89–94. PMID: 27423569.

29. Lee KS, Bae HG, Yun IG. Recurrent intracerebral hemorrhage due to hypertension. Neurosurgery. 1990; 4. 26(4):586–590. PMID: 2330079.

30. Lee SH, Kwon SJ, Kim KS, Yoon BW, Roh JK. Cerebral microbleeds in patients with hypertensive stroke. Topographical distribution in the supratentorial area. J Neurol. 2004; 10. 251(10):1183–1189. PMID: 15503095.

31. Martinez-Ramirez S, Pontes-Neto OM, Dumas AP, Auriel E, Halpin A, Quimby M, et al. Topography of dilated perivascular spaces in subjects from a memory clinic cohort. Neurology. 2013; 4. 80(17):1551–1556. PMID: 23553482.

32. Neau JP, Ingrand P, Couderq C, Rosier MP, Bailbe M, Dumas P, et al. Recurrent intracerebral hemorrhage. Neurology. 1997; 7. 49(1):106–113. PMID: 9222177.

33. Ohtani S, Shimizu K, Asari M, Maseda C, Oka K, Yamada H, et al. Brain stem hemorrhage due to cerebral amyloid angiopathy: the autopsy of a patient with Alzheimer's disease at a young age. Leg Med (Tokyo). 2014; 3. 16(2):98–101. PMID: 24491518.

34. Pantoni L, Basile AM, Pracucci G, Asplund K, Bogousslavsky J, Chabriat H, et al. Impact of age-related cerebral white matter changes on the transition to disability - the LADIS study: rationale, design and methodology. Neuroepidemiology. 2005; 24(1-2):51–62. PMID: 15459510.

35. Poels MM, Vernooij MW, Ikram MA, Hofman A, Krestin GP, van der Lugt A, et al. Prevalence and risk factors of cerebral microbleeds: an update of the Rotterdam scan study. Stroke. 2010; 10. 41(10 Suppl):S103–S106. PMID: 20876479.

36. Romero JR, Preis SR, Beiser A, DeCarli C, Viswanathan A, Martinez-Ramirez S, et al. Risk factors, stroke prevention treatments, and prevalence of cerebral microbleeds in the Framingham Heart Study. Stroke. 2014; 5. 45(5):1492–1494. PMID: 24713533.

37. Shoamanesh A, Catanese L, Romero JR, Lau H, Babikian VL, Benavente OR, et al. High prevalence of cerebral microbleeds in inner city young stroke patients. J Stroke Cerebrovasc Dis. 2016; 4. 25(4):733–738. PMID: 26775270.

38. Vernooij MW, van der Lugt A, Ikram MA, Wielopolski PA, Niessen WJ, Hofman A, et al. Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study. Neurology. 2008; 4. 70(14):1208–1214. PMID: 18378884.

39. Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013; 8. 12(8):822–838. PMID: 23867200.

40. Wong KS, Chan YL, Liu JY, Gao S, Lam WW. Asymptomatic microbleeds as a risk factor for aspirin-associated intracerebral hemorrhages. Neurology. 2003; 2. 60(3):511–513. PMID: 12578941.

41. Wong MP, Ng TH, Chan KH. Cerebral amyloid angiopathy and spontaneous intracerebral haemorrhage. Report of a sporadic case in a young Chinese. Clin Neurol Neurosurg. 1991; 93(2):133–136. PMID: 1652394.

42. Yakushiji Y. Cerebral microbleeds: detection, associations and clinical implications. Front Neurol Neurosci. 2015; 37:78–92. PMID: 26587900.