Impact of white matter hypodensities on outcome after intracerebral hemorrhage



      White matter hypodensities (WMH), a surrogate of small vessel disease, associate with cognitive decline and stroke risk. The impact of WMH on functional outcome after intracerebral hemorrhage (ICH) has differed between studies. We aimed to examine factors associated with the severity of WMH in ICH, and whether there is an independent association between the extent of WMH and outcome.

      Materials and methods

      This was a prospective study of consented patients with non-traumatic primary ICH, admitted to the Helsinki University Hospital between May 2014 and December 2018. To evaluate the extent of the WMH, modified van Swieten score of the side contralateral to the ICH was obtained. Patients were grouped into 3 categories of the scores. We performed univariate and multivariable analyses to find out factors associated with the severity of WMH, and whether WMH associate with functional outcome and mortality up to 12 months, adjusted for the known major outcome predictors.


      In our cohort of 417 ICH patients, WMH severity associated with older age, female sex, admission National Institutes of Health Stroke Scale (NIHSS) points, and signs of previous ischemic stroke on CT. We found an independent association between WMH severity and poor functional outcome at 3 months (OR 1.72, 95% CI 1.27-2.33), and 1 year (OR 2.16, 95% CI 1.57-2.95), and mortality at 1 year (OR 1.91, 95% CI 1.29-2.85).


      In our ICH patients, vascular comorbidities and older age associated with the presence of WMH, which, in turn, strongly associated with poor functional outcome.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Stroke and Cerebrovascular Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • van Asch C.J.
        • Luitse M.J.
        • Rinkel G.J.
        • et al.
        Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis.
        Lancet Neurol. 2010; 9: 167-176
        • Hemphill J.C.
        • Bonovich D.C.
        • Besmertis L.
        • et al.
        The ICH score: a simple, reliable grading scale for intracerebral hemorrhage.
        Stroke. 2001; 32: 891-897
        • Georgakis M.K.
        • Duering M.
        • Wardlaw J.M.
        • et al.
        WMH and long-term outcomes in ischemic stroke: A systematic review and meta-analysis.
        Neurology. 2019; 92: e1298-e1308
        • Wardlaw J.M.
        • Smith E.E.
        • Biessels G.J.
        • et al.
        Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration.
        Lancet Neurol. 2013; 12: 822-838
        • Yu Z.
        • Zheng J.
        • Guo R.
        • et al.
        Prognostic significance of leukoaraiosis in intracerebral hemorrhage: A meta-analysis.
        J Neurol Sci. 2019; 397: 34-41
        • Pantoni L.
        Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges.
        Lancet Neurol. 2010; 9: 689-701
        • Hostettler I.C.
        • Schwarz G.
        • Ambler G.
        • et al.
        Cerebral small vessel disease and functional outcome prediction after intracerebral hemorrhage.
        Neurology. 2021; 96: e1954-e1965
        • Lee S.-H.
        • Kim B.J.
        • Ryu W.-S.
        • et al.
        White matter lesions and poor outcome after intracerebral hemorrhage.
        Neurology. 2010; 74: 1502-1510
        • Wardlaw J.M.
        • Smith C.
        • Dichgans M.
        Small vessel disease: mechanisms and clinical implications.
        Lancet Neurol. 2019; 18: 684-696
        • Ferguson K.J.
        • Cvoro V.
        • MacLullich A.M.J.
        • et al.
        Visual rating scales of white matter hyperintensities and atrophy: comparison of computed tomography and magnetic resonance imaging.
        J Stroke Cerebrovasc Dis. 2018; 27: 1815-1821
        • Kothari R.U.
        • Brott T.
        • Broderick J.P.
        • et al.
        The ABCs of measuring intracerebral hemorrhage volumes.
        Stroke. 1996; 27: 1304-1305
        • van Swieten J.C.
        • Hijdra A.
        • Koudstaal P.J.
        • et al.
        Grading white matter lesions on CT and MRI: a simple scale.
        J Neurol Neurosurg Psychiatry. 1990; 53: 1080-1083
        • Palumbo V.
        • Boulanger J.M.
        • Hill M.D.
        • et al.
        Leukoaraiosis and intracerebral hemorrhage after thrombolysis in acute stroke.
        Neurology. 2007; 68: 1020-1024
        • Leys D.
        • Englund E.
        • Del Ser T.
        • et al.
        White matter changes in stroke patients.
        Eur Neurol. 1999; 42: 67-75
        • Sykora M.
        • Herweh C.
        • Steiner T.
        The association between leukoaraiosis and poor outcome in intracerebral hemorrhage is not mediated by hematoma growth.
        J Stroke Cerebrovasc Dis. 2017; 26: 1328-1333
        • Purkayastha S.
        • Fadar O.
        • Mehregan A.
        • et al.
        Impaired cerebrovascular hemodynamics are associated with cerebral white matter damage.
        J Cereb Blood Flow Metabolism. 2014; 34: 228-234
        • Alqarni A.
        • Jiang J.
        • Crawford J.D.
        • et al.
        Sex differences in risk factors for white matter hyperintensities in non-demented older individuals.
        Neurobiol Aging. 2021; 98: 197-204
        • Fatemi F.
        • Kantarci K.
        • Graff-Radford J.
        • et al.
        Sex differences in cerebrovascular pathologies on FLAIR in cognitively unimpaired elderly.
        Neurology. 2018; 90: e466-e473
        • Lou M.
        • Al-Hazzani A.
        • Goddeau Jr, R.P.
        • et al.
        Relationship between white-matter hyperintensities and hematoma volume and growth in patients with intracerebral hemorrhage.
        Stroke. 2010; 41: 34-40
        • Chen X.
        • Jin Y.
        • Chen J.
        • et al.
        Relationship between white matter hyperintensities and hematoma volume in patients with intracerebral hematoma.
        Aging Dis. 2018; 9: 999-1009
        • Boulouis G.
        • van Etten E.S.
        • Charidimou A.
        • et al.
        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. 2016; 73: 1440-1447
        • Venema S.M.U.
        • Marini S.
        • Brouwers H.B.
        • et al.
        Associations of radiographic cerebral small vessel disease with acute intracerebral hemorrhage volume, hematoma expansion, and intraventricular hemorrhage.
        Neurocrit Care. 2020; 32: 383-391
        • Venema S.M.U.
        • Marini S.
        • Lena U.K.
        • et al.
        Impact of cerebral small vessel disease on functional recovery after intracerebral hemorrhage.
        Stroke. 2019; 50: 2722-2728
        • Sato S.
        • Delcourt C.
        • Heeley E.
        • et al.
        Significance of cerebral small-vessel disease in acute intracerebral hemorrhage.
        Stroke. 2016; 47: 701-707
        • Won Y.S.
        • Chung P.-W.
        • Kim Y.B.
        • et al.
        Leukoaraiosis predicts poor outcome after spontaneous supratentorial intracerebral hemorrhage.
        Eur Neurol. 2010; 64: 253-257
        • Caprio F.Z.
        • Maas M.B.
        • Rosenberg N.F.
        • et al.
        Leukoaraiosis on magnetic resonance imaging correlates with worse outcomes after spontaneous intracerebral hemorrhage.
        Stroke. 2013; 44: 642-646
        • Lioutas V.-A.
        • Wu B.
        • Norton C.
        • et al.
        Cerebral small vessel disease burden and functional and radiographic outcomes in intracerebral hemorrhage.
        J Neurol. 2018; 265: 2803-2814
        • Tveiten A.
        • Ljøstad U.
        • Mygland Å.
        • et al.
        Leukoaraiosis is associated with short- and long-term mortality in patients with intracerebral hemorrhage.
        J Stroke Cerebrovasc Dis. 2013; 22: 919-925
        • Gregório T.
        • Pipa S.
        • Cavaleiro P.
        • et al.
        Assessment and comparison of the four most extensively validated prognostic scales for intracerebral hemorrhage: systematic review with meta-analysis.
        Neurocrit Care. 2019; 30: 449-466
        • Wardlaw J.M.
        • Smith C.
        • Dichgans M.
        Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging.
        Lancet Neurol. 2013; 12: 483-497