The relationship between recurrent intracerebral hemorrhage (ICH) and total burden of cerebral small vessel disease (CSVD) is not completely investigated. We aimed to study whether recurrent intracerebral hemorrhage (ICH) had higher CSVD score than first-ever ICH. Lacunes, white matter hyperintensities (WMH), cerebral microbleeds (CMBs), enlarged perivascular spaces (EPVS), cortical superficial siderosis (cSS) and CSVD score were rated on brain magnetic resonance imaging (MRI) in primary ICH patients. Recurrent ICHs were confirmed by reviewing the medical records and MRI scans. Mixed hematomas were defined as follows: deep + lobar, deep + cerebellar, or deep + lobar + cerebellar. Of the 184 patients with primary ICH enrolled (mean age, 61.0 years; 75.5% men), recurrent ICH was present in 45 (24.5%) patients; 26.1% (48/184) had ≥2 hematomas, 93.8% (45/48) of which exhibited recurrent ICH. Mixed hematomas were identified in 8.7% (16/184) of patients and bilateral hematomas in 17.9% (33/184). All mixed hematomas and bilateral hematomas were from cases of recurrent ICH. Patients with mixed etiology-ICH were more likely to have recurrent ICH than patients with cerebral amyloid angiopathy (CAA) or hypertensive angiopathy (HA)-related ICH (36.8% vs17.8%, p=0.008). Multivariate ordinal regression analysis showed that the presence of recurrent ICH (p=0.001), ≥2 hematomas (p=0.002), mixed hematomas (p<0.00001), and bilateral hematomas (p=0.002) were separately significantly associated with a high CSVD score. Recurrent ICH occurs mostly among patients with mixed etiology-ICH and is associated with a higher CSVD burden than first-ever ICH, which needs to be verified by future larger studies.
Table 1 Clinical and neuroimaging characteristics of the study population.
Figure 1. Flow gram of patient selection.
All participants (n=184)
Recurrent ICH (n=45)
First-ever ICH (n=139)
0, n (%)
1, n (%)
2, n (%)
3, n (%)
4, n (%)
Table 2 Total CSVD score for patients with recurrent ICH and first-ever ICH.
Figure 2. Hematoma characteristics and CSVD score. A) the presence of recurrent ICH and CSVD score. B) The number of hematomas and CSVD score. C) the presence of mixed hematomas and CSVD score. D) the presence of bilateral hematomas and CSVD score.
Age- + sex-adjusted
OR (95% CI)
OR (95% CI)
OR (95% CI)
0.361 (0.195 to 0.668)
0.313 (0.167 to 0.587)
0.332 (0.174 to 0.632)
0.375 (0.206 to 0.685)
0.334 (0.181 to 0.616)
0.365 (0.195 to 0.683)
0.093 (0.034 to 0.258)
0.064 (0.022 to 0.187)
0.073 (0.024 to 0.216)
0.354 (0.178 to 0.705)
0.288 (0.142 to 0.582)
0.322 (0.156 to 0.664)
Table 3 Association between ICH and total burden of CSVD in ordinal regression analysis.
Pantoni L, Fierini F, Poggesi A (2014). Thrombolysis in acute stroke patients with cerebral small vessel disease. Cerebrovasc Dis, 37:5-13.
Pantoni L (2010). Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol, 9:689-701.
van der Flier WM, van Straaten EC, Barkhof F, Verdelho A, Madureira S, Pantoni L, et al. (2005). Small vessel disease and general cognitive function in nondisabled elderly: the LADIS study. Stroke, 36:2116-2120.
Herrmann LL, Le Masurier M, Ebmeier KP (2008). White matter hyperintensities in late life depression: a systematic review. J Neurol Neurosurg Psychiatry, 79:619-624.
Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, et al. (2011). Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke, 42:2672-2713.
Wardlaw JM, Smith C, Dichgans M (2013). Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol, 12:483-497.
Roongpiboonsopit D, Charidimou A, William CM, Lauer A, Falcone GJ, Martinez-Ramirez S, et al. (2016). Cortical superficial siderosis predicts early recurrent lobar hemorrhage. Neurology, 87:1863-1870.
Klarenbeek P, van Oostenbrugge RJ, Rouhl RP, Knottnerus IL, Staals J (2013). Ambulatory blood pressure in patients with lacunar stroke: association with total MRI burden of cerebral small vessel disease. Stroke, 44:2995-2999.
Staals J, Makin SD, Doubal FN, Dennis MS, Wardlaw JM (2014). Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. Neurology, 83:1228-1234.
Huijts M, Duits A, van Oostenbrugge RJ, Kroon AA, de Leeuw PW, Staals J (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.
Song TJ, Kim J, Song D, Yoo J, Lee HS, Kim YJ, et al. (2017). Total Cerebral Small-Vessel Disease Score is Associated with Mortality during Follow-Up after Acute Ischemic Stroke. J Clin Neurol, 13:187-195.
Uiterwijk R, van Oostenbrugge RJ, Huijts M, De Leeuw PW, Kroon AA, Staals J (2016). Total Cerebral Small Vessel Disease MRI Score Is Associated with Cognitive Decline in Executive Function in Patients with Hypertension. Front Aging Neurosci, 8:301.
Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, et al. (2013). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol, 12:822-838.
Lau KK, Li L, Schulz U, Simoni M, Chan KH, Ho SL, et al. (2017). Total small vessel disease score and risk of recurrent stroke: Validation in 2 large cohorts. Neurology, 88:2260-2267.
Charidimou A, Imaizumi T, Moulin S, Biffi A, Samarasekera N, Yakushiji Y, et al. (2017). Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds: A meta-analysis. Neurology, 89:820-829.
Charidimou A, Werring DJ (2014). Cerebral microbleeds as a predictor of macrobleeds: what is the evidence? Int J Stroke, 9:457-459.
Linn J, Halpin A, Demaerel P, Ruhland J, Giese AD, Dichgans M, et al. (2010). Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology, 74:1346-1350.
Charidimou A, Boulouis G, Haley K, Auriel E, van Etten ES, Fotiadis P, et al. (2016). White matter hyperintensity patterns in cerebral amyloid angiopathy and hypertensive arteriopathy. Neurology, 86:505-511.
Pasi M, Boulouis G, Fotiadis P, Auriel E, Charidimou A, Haley K, et al. (2017). Distribution of lacunes in cerebral amyloid angiopathy and hypertensive small vessel disease. Neurology, 88:2162-2168.
Wu B, Yao X, Lei C, Liu M, Selim MH (2015). Enlarged perivascular spaces and small diffusion-weighted lesions in intracerebral hemorrhage. Neurology, 85:2045-2052.
Greenberg SM, Vernooij MW, Cordonnier C, Viswanathan A, Al-Shahi Salman R, Warach S, et al. (2009). Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol, 8:165-174.
Charidimou A, Boulouis G, Xiong L, Jessel MJ, Roongpiboonsopit D, Ayres A, et al. (2017). Cortical superficial siderosis and first-ever cerebral hemorrhage in cerebral amyloid angiopathy. Neurology, 88:1607-1614.
Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA (1987). MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol, 149:351-356.
Charidimou A, Meegahage R, Fox Z, Peeters A, Vandermeeren Y, Laloux P, et al. (2013). Enlarged perivascular spaces as a marker of underlying arteriopathy in intracerebral haemorrhage: a multicentre MRI cohort study. J Neurol Neurosurg Psychiatry, 84:624-629.
Imaizumi T, Inamura S, Nomura T (2014). The severities of white matter lesions possibly influence the recurrences of several stroke types. J Stroke Cerebrovasc Dis, 23:1897-1902.
Pasi M, Charidimou A, Boulouis G, Auriel E, Ayres A, Schwab KM, et al. (2018). Mixed-location cerebral hemorrhage/microbleeds: Underlying microangiopathy and recurrence risk. Neurology, 90:e119-e126.