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Aging and disease    2018, Vol. 9 Issue (6) : 999-1009     DOI: 10.14336/AD.2018.0108
Orginal Article |
Relationship between White Matter Hyperintensities and Hematoma Volume in Patients with Intracerebral Hematoma
Chen Xuemei1,3,4, Jin Yuexinzi1, Chen Jian1, Chen Xin1, Cao Xiang2,3,4, Yu Linjie2, Xu Yun1,2,3,4,*
1Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China
2Department of Neurology, Affiliated Drum Tower Hospital, and Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing 210008, China.
3Jiangsu Province Stroke Center for Diagnosis and Therapy, Nanjing 210008, China
4Nanjing Neuropsychiatry Clinic Medical Center, Nanjing 210008, China
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Abstract  

The relationship of white-matter hyperintensity (WMH) to intracerebral hemorrhage (ICH) remains unclear. In this retrospective study, we investigated whether the severity and progression of WMH could be related to the hematoma volume and absorption in ICH. 2338 WMH patients with ICH aged≥40 years receiving brain computed tomography (CT) imaging within 12 hours of ICH symptom onset were screened, and 227 patients were included in the final study. The severity and progression of WMH were assessed using the software programs MRICRON and ITK-SNAP on brain magnetic resonance imaging (MRI) and the hematoma volumes and absorption with ITK-SNAP software on CT. We assessed the association of WMH severity with ICH volume in 227 patients at baseline. Totally 183 of 227 patients underwent repeated CT within 14 days of ICH onset. The relationship of WMH severity to ICH absorption was analyzed in 183 patients. Additionally, among all 227 patients, 37 subjected to another MRI before ICH onset were divided into two groups according to WMH progression: non-progression and progression groups. The link between WMH progression and hematoma volume was examined. The ICH volume was significantly larger in patients with the highest WMH scores than in those with the lowest WMH scores. Larger WMH volume was independently associated with larger ICH volume (odds ratio 1.00; 95% CI, 1.00 to 1.00; P = 0.049). There was a trend towards WMH progression being related to ICH volume (P =0.049). Contrastingly, the WMH volume was not linked with hematoma absorption (P = 0.79). In conclusion, we found that greater severity and progression of WMH were associated with larger ICH volume. Our findings suggest that WMH might provide important prognostic information about patients with ICH and may have implications for treatment stratification.

Keywords intracerebral hemorrhage      white matter hyperintensities      hematoma      leukoaraiosis      quantitative analysis     
Corresponding Authors: Xu Yun   
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These authors contributed equally to this work

Issue Date: 27 October 2017
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Chen Xuemei
Jin Yuexinzi
Chen Jian
Chen Xin
Cao Xiang
Yu Linjie
Xu Yun
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Chen Xuemei,Jin Yuexinzi,Chen Jian, et al. Relationship between White Matter Hyperintensities and Hematoma Volume in Patients with Intracerebral Hematoma[J]. Aging and disease, 2018, 9(6): 999-1009.
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http://www.aginganddisease.org/EN/10.14336/AD.2018.0108     OR     http://www.aginganddisease.org/EN/Y2018/V9/I6/999
Figure 1.  Diagrammatic sketch of the screening process.
Figure 2.  Quantitative steps of ICH volume. (A) Original CT image. (B) The high-density area. (C) A sketch of the high-density area. D) Calculation of ICH volume.
Fazekas Score
P Value
123

0-2 (n=79)3-4 (n=127)5-6 (n=21)
Age, y, mean±SD63.32±13.3364.73±12.29*72.10±10.66#0.02
Men, n (%)6292180.52
Past medical history, n (%)
  Hypertension5294160.24
  Coronary artery disease102270.09
  Diabetes mellitus142940.56
  Hyperlipidemia1600.19
Smoking, n (%)222030.17
Alcohol, n (%)161220.13
Medications, n (%)
 Use of antiplatelet agents31910.11
  Use of anticoagulation0420.25
  Use of statin1700.10
NIHSS, mean±SD4.84±5.504.43±4.27*8.67±7.02#<0.01
Clinical variables, mean±SD
  SBP, mm Hg149.76±25.09152.65±21.15151.76±16.580.66
  DBP, mm Hg87.32±13.5987.94±16.3482.90±12.380.38
  FBG, mM6.27±2.545.83±1.847.03±3.430.06
  RBG, mM7.18±2.557.10±2.596.66±1.630.72
  PBG, mM8.84±3.308.09±2.978.43±2.460.28
  HbAIc, %5.99±1.125.95±1.035.79±0.670.77
  HCY, μM14.00±4.1717.35±9.8314.41±6.100.09
  TC, mM4.38±1.194.28±0.973.69±0.88#0.03
  TG, mM1.57±1.051.36±0.821.74±1.340.12
  LDL, mM2.39±0.912.26±0.691.90±0.69#0.04
  HDL, mM1.01±0.321.07±0.390.99±0.450.46
  ApoA I, g/L1.02±0.251.12±0.521.01±0.310.25
  BUN, mM6.14±4.946.55±6.786.38±4.140.89
  Cr, μM66.8±23.5380.8±76.9865.06±17.350.20
  UA, μM297.56±129.91281.57±120.35255.81±92.680.39
  Partial thromboplastin time, sec32.12±32.0528.82±5.4227.15±7.790.42
  International Normalized Ratio1.26±1.591.27±2.241.09±0.140.91
  Fibrinogen, g/L3.7±2.363.3±1.184.15±3.720.16
  D-dimer, mg/L2.07±3.481.27±1.331.54±2.550.11
Radiologic data
  ICH volume, mL, mean±SD13.01±13.3412.23±13.1621.16±31.21#<0.01
  ICH position, n (%)0.41
Lobar ICH254611
Basal ganglia region ICH44678
Brain stem ICH110
Intraventricular ICH201
  Multiple ICH461
  Cerebellar ICH470
Table 1  Baseline characteristics classified according to trichotomized Fazekas Score.
Hemorrhage Volume
P Value
0-50% (n=114)51-100% (n=113)
Age, y, mean±SD64.97±12.7364.87±12.730.95
Men, n (%)70640.47
Past medical history, n (%)
 Hypertension82800.85
 Coronary artery disease12190.17
 Diabetes mellitus23200.63
 Hyperlipidemia330.99
Smoking, n (%)21170.50
Alcohol, n (%)14100.40
Medications, n (%)
 Use of antiplatelet agents1180.49
 Use of anticoagulation130.31
 Use of statin430.51
NIHSS, mean±SD3.92±4.006.01±5.91<0.01*
Clinical variables, mean±SD
 SBP, mm Hg151.47±24.65151.65±19.530.95
 DBP, mm Hg86.68±15.8887.87±14.620.56
 FBG, mM5.91±2.156.27±2.440.24
 RBG, mM7.30±2.726.86±2.230.22
 PBG, mM8.54±3.068.23±3.060.49
 HbAIc, %6.03±1.125.87±0.930.32
 HCY, μM15.81±9.3815.93±6.410.93
 TC, mM4.21±1.074.29±1.040.56
 TG, mM1.47±0.911.46±1.020.87
 LDL, mM2.25±0.7512.28±0.810.83
 HDL, mM1.06±0.311.02±0.420.39
 ApoA I, g/L1.12±0.521.02±0.310.08
 BUN, mM6.03±6.136.75±5.790.37
 Cr, μM72.04±33.0276.92±78.090.54
 UA, μM285.7±108.19283.72±148.160.91
 Partial thromboplastin time, sec28.44±7.0431.22±26.890.30
 International Normalized Ratio1.40±2.691.09±0.340.23
 Fibrinogen, g/l3.56±2.563.49±1.200.79
 D-dimer, mg/l1.06±1.192.12±3.19<0.01*
Radiologic data
 WMH volume, mm3, mean±SD13345.29±10768.4316510.27±9888.570.02*
 ICH position, n (%)0.01*
Lobar ICH2953
Basal ganglia region ICH7148
Brain stem ICH20
Intraventricular ICH12
 Multiple ICH56
 Cerebellar ICH64
Table 2  Univariate Risk Factors for Hemorrhage Volume.
Figure 3.  Quantitative steps of WMH volume. (A) Original FLAIR image. (B) The high signal area. C) A sketch of the effective WMH area. (D) Extraction of the effective WMH area.
Odds Ratio95% CIP Value
NIHSS1.081.01-1.150.03*
D-Dimer1.230.99-1.530.06
WMH volume1.001.00-1.000.049*
ApoA I0.490.20-1.800.37
ICH position1.441.09-1.910.01*
Table 3  Multivariate logistic regression analysis of risk factors for ICH volume.
WMH progress
No (n=17)Yes (n=20)P Value
Age, y, mean±SD59.24±19.4357.90±15.600.82
Men, n (%)12140.97
Past medical history, n (%)
Hypertension7120.25
Coronary artery disease010.26
Diabetes mellitus330.83
Hyperlipidemia100.21
Smoking, n (%)140.19
Alcohol, n (%)150.10
Medications, n (%)
Use of antiplatelet agents010.26
Use of anticoagulation00-
Use of statin100.21
Clinical variables, mean±SD
SBP, mm Hg136.65±21.92145.20±19.170.21
DBP, mm Hg77.35±12.6183.75±10.560.10
FBG, mM5.61±1.755.48±1.720.82
RBG, mM7.32±4.116.99±2.700.80
PBG, mM8.43±4.097.90±2.030.67
HbAIc, %6.07±0.676.02±1.290.93
TC, mM4.02±1.293.79±0.690.57
TG, mM1.13±0.441.37±0.830.38
LDL, mM2.15±0.951.98±0.520.58
HDL, mM1.00±0.280.93±0.270.57
ApoA I, g/L1.06±0.250.98±0.270.41
BUN, mM6.54±3.415.56±1.500.34
Cr, μM87.17±31.2369.29±25.030.12
UA, μM319.00±112.34297.71±118.940.65
Partial thromboplastin time, sec32.21±5.1932.73±11.950.89
International Normalized Ratio1.10±0.071.14±0.280.65
Fibrinogen, g/L2.85±1.103.36±1.110.26
D-dimer, mg/L1.39±1.211.20±1.010.70
Radiologic data
ICH volume, ml, mean±SD7.12±9.1913.59±10.250.049*
Table 4  Analysis of relationship of hematoma volume and WMH progression.
Hemorrhage Absorption Proportion
P Value
0-50% (n=48)51-100% (n=63)
Age, y, mean ±SD64.35±12.6565.47±12.420.56
Men, n (%)48630.11
Past medical history, n (%)
Hypertension48910.03*
Coronary artery disease10120.64
Diabetes mellitus11240.34
Hyperlipidemia030.28
Smoking, n (%)11210.56
Alcohol, n (%)8100.80
Medications, n (%)
Use of antiplatelet agents4120.29
Use of anticoagulation130.49
Use of statin140.65
NIHSS, mean±SD5.44±6.004.58±4.500.28
Clinical variables, mean±SD
SBP, mm Hg149.73±26.85153.32±19.690.30
DBP, mm Hg87.75±15.7687.88±14.990.95
FBG, mM5.94±2.265.88±1.890.84
RBG, mM6.95±2.457.31±2.650.40
PBG, mM7.72±2.548.79±3.340.04*
HbAIc, %5.87±0.926.06±1.150.33
HCY, μM14.74±7.5417.45±8.940.14
TC, mM4.25±1.064.28±0.990.82
TG, mM1.38±1.001.39±0.780.97
LDL, mM2.24±0.832.31±0.710.54
HDL, mM1.04±0.381.07±0.390.69
ApoA I, g/L1.04±0.291.11±0.530.32
BUN, mM5.74±2.736.40±7.070.45
Cr, μM66.81±27.1079.78±80.870.19
UA, μM276.62±94.89272.38±123.870.81
Partial thromboplastin time, sec29.33±5.5727.99±5.490.12
International Normalized Ratio1.06±0.201.29±2.410.42
Fibrinogen, g/l3.49±1.143.57±1.870.78
D-dimer, mg/l1.91±2.991.41±2.300.26
Radiologic data
WMH volume, mm3, mean±SD15344.49±10501.5414939.61.82±9674.110.79
Fazakse score, mean±SD2.06±1.122.09±0.970.83
ICH volume, mL, mean±SD16045.12±14055.4511720.40±12750.350.03*
ICH position, n (%)0.16
Lobar ICH2634
Basal ganglia region ICH3765
Brain stem ICH11
Intraventricular ICH----
Multiple ICH17
Cerebellar ICH63
Table 5  Univariate analysis of hematoma absorption proportion.
Odds Ratio95% CIP Value
Hypertension0.560.24-1.330.19
ICH volume1.001.00-1.000.02*
PBG1.120.99-1.280.08
Table 6  Multivariate Logistic Regression Analysis of Risk Factors for Hematoma Absorption Proportion.
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