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
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.
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.
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
1
2
3
0-2 (n=79)
3-4 (n=127)
5-6 (n=21)
Age, y, mean±SD
63.32±13.33
64.73±12.29*
72.10±10.66#
0.02
Men, n (%)
62
92
18
0.52
Past medical history, n (%)
Hypertension
52
94
16
0.24
Coronary artery disease
10
22
7
0.09
Diabetes mellitus
14
29
4
0.56
Hyperlipidemia
1
6
0
0.19
Smoking, n (%)
22
20
3
0.17
Alcohol, n (%)
16
12
2
0.13
Medications, n (%)
Use of antiplatelet agents
3
19
1
0.11
Use of anticoagulation
0
4
2
0.25
Use of statin
1
7
0
0.10
NIHSS, mean±SD
4.84±5.50
4.43±4.27*
8.67±7.02#
<0.01
Clinical variables, mean±SD
SBP, mm Hg
149.76±25.09
152.65±21.15
151.76±16.58
0.66
DBP, mm Hg
87.32±13.59
87.94±16.34
82.90±12.38
0.38
FBG, mM
6.27±2.54
5.83±1.84
7.03±3.43
0.06
RBG, mM
7.18±2.55
7.10±2.59
6.66±1.63
0.72
PBG, mM
8.84±3.30
8.09±2.97
8.43±2.46
0.28
HbAIc, %
5.99±1.12
5.95±1.03
5.79±0.67
0.77
HCY, μM
14.00±4.17
17.35±9.83
14.41±6.10
0.09
TC, mM
4.38±1.19
4.28±0.97
3.69±0.88#
0.03
TG, mM
1.57±1.05
1.36±0.82
1.74±1.34
0.12
LDL, mM
2.39±0.91
2.26±0.69
1.90±0.69#
0.04
HDL, mM
1.01±0.32
1.07±0.39
0.99±0.45
0.46
ApoA I, g/L
1.02±0.25
1.12±0.52
1.01±0.31
0.25
BUN, mM
6.14±4.94
6.55±6.78
6.38±4.14
0.89
Cr, μM
66.8±23.53
80.8±76.98
65.06±17.35
0.20
UA, μM
297.56±129.91
281.57±120.35
255.81±92.68
0.39
Partial thromboplastin time, sec
32.12±32.05
28.82±5.42
27.15±7.79
0.42
International Normalized Ratio
1.26±1.59
1.27±2.24
1.09±0.14
0.91
Fibrinogen, g/L
3.7±2.36
3.3±1.18
4.15±3.72
0.16
D-dimer, mg/L
2.07±3.48
1.27±1.33
1.54±2.55
0.11
Radiologic data
ICH volume, mL, mean±SD
13.01±13.34
12.23±13.16
21.16±31.21#
<0.01
ICH position, n (%)
0.41
Lobar ICH
25
46
11
Basal ganglia region ICH
44
67
8
Brain stem ICH
1
1
0
Intraventricular ICH
2
0
1
Multiple ICH
4
6
1
Cerebellar ICH
4
7
0
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±SD
64.97±12.73
64.87±12.73
0.95
Men, n (%)
70
64
0.47
Past medical history, n (%)
Hypertension
82
80
0.85
Coronary artery disease
12
19
0.17
Diabetes mellitus
23
20
0.63
Hyperlipidemia
3
3
0.99
Smoking, n (%)
21
17
0.50
Alcohol, n (%)
14
10
0.40
Medications, n (%)
Use of antiplatelet agents
11
8
0.49
Use of anticoagulation
1
3
0.31
Use of statin
4
3
0.51
NIHSS, mean±SD
3.92±4.00
6.01±5.91
<0.01*
Clinical variables, mean±SD
SBP, mm Hg
151.47±24.65
151.65±19.53
0.95
DBP, mm Hg
86.68±15.88
87.87±14.62
0.56
FBG, mM
5.91±2.15
6.27±2.44
0.24
RBG, mM
7.30±2.72
6.86±2.23
0.22
PBG, mM
8.54±3.06
8.23±3.06
0.49
HbAIc, %
6.03±1.12
5.87±0.93
0.32
HCY, μM
15.81±9.38
15.93±6.41
0.93
TC, mM
4.21±1.07
4.29±1.04
0.56
TG, mM
1.47±0.91
1.46±1.02
0.87
LDL, mM
2.25±0.751
2.28±0.81
0.83
HDL, mM
1.06±0.31
1.02±0.42
0.39
ApoA I, g/L
1.12±0.52
1.02±0.31
0.08
BUN, mM
6.03±6.13
6.75±5.79
0.37
Cr, μM
72.04±33.02
76.92±78.09
0.54
UA, μM
285.7±108.19
283.72±148.16
0.91
Partial thromboplastin time, sec
28.44±7.04
31.22±26.89
0.30
International Normalized Ratio
1.40±2.69
1.09±0.34
0.23
Fibrinogen, g/l
3.56±2.56
3.49±1.20
0.79
D-dimer, mg/l
1.06±1.19
2.12±3.19
<0.01*
Radiologic data
WMH volume, mm3, mean±SD
13345.29±10768.43
16510.27±9888.57
0.02*
ICH position, n (%)
0.01*
Lobar ICH
29
53
Basal ganglia region ICH
71
48
Brain stem ICH
2
0
Intraventricular ICH
1
2
Multiple ICH
5
6
Cerebellar ICH
6
4
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 Ratio
95% CI
P Value
NIHSS
1.08
1.01-1.15
0.03*
D-Dimer
1.23
0.99-1.53
0.06
WMH volume
1.00
1.00-1.00
0.049*
ApoA I
0.49
0.20-1.80
0.37
ICH position
1.44
1.09-1.91
0.01*
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±SD
59.24±19.43
57.90±15.60
0.82
Men, n (%)
12
14
0.97
Past medical history, n (%)
Hypertension
7
12
0.25
Coronary artery disease
0
1
0.26
Diabetes mellitus
3
3
0.83
Hyperlipidemia
1
0
0.21
Smoking, n (%)
1
4
0.19
Alcohol, n (%)
1
5
0.10
Medications, n (%)
Use of antiplatelet agents
0
1
0.26
Use of anticoagulation
0
0
-
Use of statin
1
0
0.21
Clinical variables, mean±SD
SBP, mm Hg
136.65±21.92
145.20±19.17
0.21
DBP, mm Hg
77.35±12.61
83.75±10.56
0.10
FBG, mM
5.61±1.75
5.48±1.72
0.82
RBG, mM
7.32±4.11
6.99±2.70
0.80
PBG, mM
8.43±4.09
7.90±2.03
0.67
HbAIc, %
6.07±0.67
6.02±1.29
0.93
TC, mM
4.02±1.29
3.79±0.69
0.57
TG, mM
1.13±0.44
1.37±0.83
0.38
LDL, mM
2.15±0.95
1.98±0.52
0.58
HDL, mM
1.00±0.28
0.93±0.27
0.57
ApoA I, g/L
1.06±0.25
0.98±0.27
0.41
BUN, mM
6.54±3.41
5.56±1.50
0.34
Cr, μM
87.17±31.23
69.29±25.03
0.12
UA, μM
319.00±112.34
297.71±118.94
0.65
Partial thromboplastin time, sec
32.21±5.19
32.73±11.95
0.89
International Normalized Ratio
1.10±0.07
1.14±0.28
0.65
Fibrinogen, g/L
2.85±1.10
3.36±1.11
0.26
D-dimer, mg/L
1.39±1.21
1.20±1.01
0.70
Radiologic data
ICH volume, ml, mean±SD
7.12±9.19
13.59±10.25
0.049*
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 ±SD
64.35±12.65
65.47±12.42
0.56
Men, n (%)
48
63
0.11
Past medical history, n (%)
Hypertension
48
91
0.03*
Coronary artery disease
10
12
0.64
Diabetes mellitus
11
24
0.34
Hyperlipidemia
0
3
0.28
Smoking, n (%)
11
21
0.56
Alcohol, n (%)
8
10
0.80
Medications, n (%)
Use of antiplatelet agents
4
12
0.29
Use of anticoagulation
1
3
0.49
Use of statin
1
4
0.65
NIHSS, mean±SD
5.44±6.00
4.58±4.50
0.28
Clinical variables, mean±SD
SBP, mm Hg
149.73±26.85
153.32±19.69
0.30
DBP, mm Hg
87.75±15.76
87.88±14.99
0.95
FBG, mM
5.94±2.26
5.88±1.89
0.84
RBG, mM
6.95±2.45
7.31±2.65
0.40
PBG, mM
7.72±2.54
8.79±3.34
0.04*
HbAIc, %
5.87±0.92
6.06±1.15
0.33
HCY, μM
14.74±7.54
17.45±8.94
0.14
TC, mM
4.25±1.06
4.28±0.99
0.82
TG, mM
1.38±1.00
1.39±0.78
0.97
LDL, mM
2.24±0.83
2.31±0.71
0.54
HDL, mM
1.04±0.38
1.07±0.39
0.69
ApoA I, g/L
1.04±0.29
1.11±0.53
0.32
BUN, mM
5.74±2.73
6.40±7.07
0.45
Cr, μM
66.81±27.10
79.78±80.87
0.19
UA, μM
276.62±94.89
272.38±123.87
0.81
Partial thromboplastin time, sec
29.33±5.57
27.99±5.49
0.12
International Normalized Ratio
1.06±0.20
1.29±2.41
0.42
Fibrinogen, g/l
3.49±1.14
3.57±1.87
0.78
D-dimer, mg/l
1.91±2.99
1.41±2.30
0.26
Radiologic data
WMH volume, mm3, mean±SD
15344.49±10501.54
14939.61.82±9674.11
0.79
Fazakse score, mean±SD
2.06±1.12
2.09±0.97
0.83
ICH volume, mL, mean±SD
16045.12±14055.45
11720.40±12750.35
0.03*
ICH position, n (%)
0.16
Lobar ICH
26
34
Basal ganglia region ICH
37
65
Brain stem ICH
1
1
Intraventricular ICH
--
--
Multiple ICH
1
7
Cerebellar ICH
6
3
Table 5 Univariate analysis of hematoma absorption proportion.
Odds Ratio
95% CI
P Value
Hypertension
0.56
0.24-1.33
0.19
ICH volume
1.00
1.00-1.00
0.02*
PBG
1.12
0.99-1.28
0.08
Table 6 Multivariate Logistic Regression Analysis of Risk Factors for Hematoma Absorption Proportion.
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