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Cerebral small vessel disease burden and functional and radiographic outcomes in intracerebral hemorrhage

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Abstract

Objective

To examine the effect of individual cerebral small vessel disease (CSVD) markers and cumulative CSVD burden on functional independence, ambulation and hematoma expansion in spontaneous intracerebral hemorrhage (ICH).

Methods

Retrospective analysis of prospectively collected data from an observational study of consecutive patients with spontaneous ICH, brain MRI within 1 month from ictus, premorbid modified Rankin Scale (mRS) score ≤ 2, available imaging data and 90-day functional status in a tertiary academic center. Functional outcomes included 90-day functional independence (mRS ≤ 2) and independent ambulation; radiographic outcome was hematoma expansion (> 12.5 ml absolute or > 33% relative increase in ICH volume). We identified the presence and burden of individual CSVD markers (cerebral microbleeds (CMBs), enlarged perivascular spaces, lacunes, white matter hyperintensities) and composite CSVD burden score and explored their association with outcomes of interest in multivariable models adjusting for well-established confounders.

Results

111 patients were included, 65% lobar ICH, with a median volume 20.8 ml. 43 (38.7%) achieved functional independence and 71 (64%) independent ambulation. In multivariable adjusted models, there was higher total CSVD burden (OR 0.61, 95% CI 0.37–0.96, p = 0.03) and CMBs presence (OR 0.32, 95% CI 0.1–0.88, p = 0.04) remained independently inversely associated with functional independence. Individual CSVD markers or total CSVD score had no significant relation with ambulation and ICH expansion. Larger ICH volume and deep ICH location were the major determinants of lack of independent ambulation.

Conclusions

Our findings suggest that in ICH patients without previous functional dependence, total CSVD burden and particularly presence of CMBs significantly affect functional recovery. The latter is a novel finding and merits further exploration.

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Abbreviations

ICH:

Intracerebral hemorrhage

IVH:

Intraventricular hemorrhage

CSVD:

Cerebral small vessel disease

WMH:

White matter hyperintensities

EPVS:

Enlarged perivascular spaces

CMB:

Cerebral microbleeds

References

  1. Fisher CM (1965) Lacunes: small, deep cerebral infarcts. Neurology 15:774–784

    Article  CAS  Google Scholar 

  2. Wardlaw JM et al (2013) Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 12(8):822–838

    Article  Google Scholar 

  3. Charidimou A et al (2015) Cortical superficial siderosis: detection and clinical significance in cerebral amyloid angiopathy and related conditions. Brain 138(Pt 8):2126–2139

    Article  Google Scholar 

  4. van Veluw SJ et al (2017) Detection, risk factors, and functional consequences of cerebral microinfarcts. Lancet Neurol 16(9):730–740

    Article  Google Scholar 

  5. Martinez-Ramirez S, Greenberg SM, Viswanathan A (2014) Cerebral microbleeds: overview and implications in cognitive impairment. Alzheimers Res Ther 6(3):33

    Article  Google Scholar 

  6. Staals J et al (2015) Total MRI load of cerebral small vessel disease and cognitive ability in older people. Neurobiol Aging 36(10):2806–2811

    Article  Google Scholar 

  7. Valenti R et al (2017) Total small vessel disease burden and brain network efficiency in cerebral amyloid angiopathy. J Neurol Sci 382:10–12

    Article  Google Scholar 

  8. Charidimou A et al (2016) Total magnetic resonance imaging burden of small vessel disease in cerebral amyloid angiopathy: an imaging-pathologic study of concept validation. JAMA Neurol 73(8):994–1001

    Article  Google Scholar 

  9. Staals J et al (2014) Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. Neurology 83(14):1228–1234

    Article  Google Scholar 

  10. Huijts M et al (2013) Accumulation of MRI markers of cerebral small vessel disease is associated with decreased cognitive function. A study in first-ever lacunar stroke and hypertensive patients. Front Aging Neurosci 5:72

    Article  Google Scholar 

  11. Song TJ et al (2017) Total cerebral small-vessel disease score is associated with mortality during follow-up after acute ischemic stroke. J Clin Neurol 13(2):187–195

    Article  Google Scholar 

  12. van Etten ES et al (2014) Incidence of symptomatic hemorrhage in patients with lobar microbleeds. Stroke 45(8):2280–2285

    Article  Google Scholar 

  13. Charidimou A et al (2018) Clinical significance of cerebral microbleeds on MRI: a comprehensive meta-analysis of risk of intracerebral hemorrhage, ischemic stroke, mortality, and dementia in cohort studies (v1). Int J Stroke 13:454–468

    Article  Google Scholar 

  14. Charidimou A et al (2017) Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds: a meta-analysis. Neurology 89(8):820–829

    Article  Google Scholar 

  15. Lou M et al (2010) Relationship between white-matter hyperintensities and hematoma volume and growth in patients with intracerebral hemorrhage. Stroke 41(1):34–40

    Article  Google Scholar 

  16. Boulouis G et al (2016) Association of key magnetic resonance imaging markers of cerebral small vessel disease with hematoma volume and expansion in patients with lobar and deep intracerebral hemorrhage. JAMA Neurol 73(12):1440–1447

    Article  Google Scholar 

  17. He G et al (2012) Perivascular and perineural extension of formed and soluble blood elements in an intracerebral hemorrhage rat model. Brain Res 1451:10–18

    Article  CAS  Google Scholar 

  18. Yin J et al (2013) Intracerebral hematoma extends via perivascular spaces and perineurium. Tohoku J Exp Med 230(3):133–139

    Article  CAS  Google Scholar 

  19. Brouwers HB et al (2014) Predicting hematoma expansion after primary intracerebral hemorrhage. JAMA Neurol 71(2):158–164

    Article  Google Scholar 

  20. Yao X et al (2015) The HEP score: a nomogram-derived hematoma expansion prediction scale. Neurocrit Care 23(2):179–187

    Article  Google Scholar 

  21. Anderson CS et al (2013) Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med 368(25):2355–2365

    Article  CAS  Google Scholar 

  22. Tsivgoulis G et al (2016) Risk of symptomatic intracerebral hemorrhage after intravenous thrombolysis in patients with acute ischemic stroke and high cerebral microbleed burden: a meta-analysis. JAMA Neurol 73(6):675–683

    Article  Google Scholar 

  23. Wu B et al (2015) Enlarged perivascular spaces and small diffusion-weighted lesions in intracerebral hemorrhage. Neurology 85(23):2045–2052

    Article  Google Scholar 

  24. Broderick JP et al (1993) Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke 24(7):987–993

    Article  CAS  Google Scholar 

  25. Hemphill JC III et al (2015) Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 46(7):2032–2060

    Article  Google Scholar 

  26. Hemphill JC III et al (2001) The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke 32(4):891–897

    Article  Google Scholar 

  27. Klarenbeek P et al (2013) Ambulatory blood pressure in patients with lacunar stroke: association with total MRI burden of cerebral small vessel disease. Stroke 44(11):2995–2999

    Article  Google Scholar 

  28. Kongbunkiat K et al (2017) Leukoaraiosis, intracerebral hemorrhage, and functional outcome after acute stroke thrombolysis. Neurology 88(7):638–645

    Article  Google Scholar 

  29. Ding J et al (2017) Large perivascular spaces visible on magnetic resonance imaging, cerebral small vessel disease progression, and risk of dementia: the age, gene/environment susceptibility-reykjavik study. JAMA Neurol 74(9):1105–1112

    Article  Google Scholar 

  30. Svard D et al (2017) The effect of white matter hyperintensities on statistical analysis of diffusion tensor imaging in cognitively healthy elderly and prodromal Alzheimer’s disease. PLoS One 12(9):e0185239

    Article  Google Scholar 

  31. Gregoire SM et al (2013) Strictly lobar microbleeds are associated with executive impairment in patients with ischemic stroke or transient ischemic attack. Stroke 44(5):1267–1272

    Article  Google Scholar 

  32. Tsai HH et al (2017) Correlation of cerebral microbleed distribution to amyloid burden in patients with primary intracerebral hemorrhage. Sci Rep 7:44715

    Article  CAS  Google Scholar 

  33. Akoudad S et al (2016) Association of cerebral microbleeds with cognitive decline and dementia. JAMA Neurol 73(8):934–943

    Article  Google Scholar 

  34. Pasi M et al (2018) Mixed-location cerebral hemorrhage/microbleeds: underlying microangiopathy and recurrence risk. Neurology 90(2):e119–e126

    Article  Google Scholar 

  35. Herweh C et al (2013) Cerebral atrophy is an independent risk factor for unfavorable outcome after spontaneous supratentorial intracerebral hemorrhage. Stroke 44(4):968–971

    Article  Google Scholar 

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Acknowledgements

Dr. Lioutas had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Statistical analysis was performed by Dr. Lioutas (Beth Israel Deaconess Medical Center, Harvard Medical School).

Funding

None.

Author information

Authors and Affiliations

  1. Division of Cerebrovascular Diseases, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA

    Vasileios-Arsenios Lioutas, Casey Norton & Magdy Selim

  2. Department of Neurology, West China Hospital, Sichuan University, Chengdu, China

    Bo Wu

  3. Department of Neurology, Lahey Clinic, Burlington, MA, USA

    Johanna Helenius

  4. Department of Radiology, Hartford Hospital, Hartford, CT, USA

    Janhavi Modak

Authors
  1. Vasileios-Arsenios Lioutas
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  2. Bo Wu
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  3. Casey Norton
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  4. Johanna Helenius
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  5. Janhavi Modak
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  6. Magdy Selim
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Contributions

V-AL: design and conceptualization of the study, data collection, analysis and interpretation of the data, drafting of original manuscript. BW: data collection, revision of the manuscript for intellectual content. CN: data collection, revision of the manuscript for intellectual content. JH: data collection, revision of the manuscript for intellectual content. JM: revision of the manuscript for intellectual content. MS: analysis and interpretation of the data, revision of the manuscript for intellectual content.

Corresponding author

Correspondence to Vasileios-Arsenios Lioutas.

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Conflicts of interest

None of the authors reports any disclosures.

Ethical standard

The study was approved by the Institutional Review Board of Beth Israel Deaconess Medical Center without need for informed consent.

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Lioutas, VA., Wu, B., Norton, C. et al. Cerebral small vessel disease burden and functional and radiographic outcomes in intracerebral hemorrhage. J Neurol 265, 2803–2814 (2018). https://doi.org/10.1007/s00415-018-9059-5

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  • DOI: https://doi.org/10.1007/s00415-018-9059-5

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