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Aging and disease    2018, Vol. 9 Issue (3) : 444-452     DOI: 10.14336/AD.2017.0808
Orginal Article |
Progression of White Matter Hyperintensities Contributes to Lacunar Infarction
Xu Xin1,2,3, Gao Yuanyuan1,2,3, Liu Renyuan1,2,3, Qian Lai1,2,3, Chen Yan1,2,3, Wang Xiaoying4, Xu Yun1,2,3,*
1Department of Neurology, Affiliated Drum Tower Hospital, and Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing 210008, China.
2Jiangsu Province Stroke Center for Diagnosis and Therapy, Nanjing 210008, China.
3Nanjing Neuropsychiatry Clinic Medical Center, Nanjing 210008, China.
4Departments of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
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Both white matter hyperintensities (WMHs) and lacunar infarctions (LIs) are magnetic resonance imaging (MRI) markers of cerebral small vessel disease (SVD). However, the association between WMH and LI remains unclear. In this study, we asked whether WMH progression is related to LI occurrence using retrospective data. Overall, 8475 WMH patients with at least two MRI images were screened, and 187 patients were included in the final study; 76 patients had WMH with LI (WL), and 111 patients had WMH without LI (WOL). The 187 patients were divided into three groups according to WMH progression: Group 1 (no progression), Group 2 (0-53.64% WMH progression) and Group 3 (≥53.64% WMH progression). We found that both WMH volumes and Fazekas scores were higher in WL patients compared with those in WOL patients according to the 1st and 2nd MRI images (P<0.001), whereas WMH progression was not significantly different between these two groups (P>0.05). Importantly, we found that the occurrence rates for LI were increased in Groups 2 and 3 compared with those in Group 1. Multiple logistic regression analysis demonstrated that the risk of LI occurrence was significantly increased in Group 2 versus that in Group 1 (odds ratio, 3.36; 95% CI, 1.48 to 7.67; P=0.004) after adjusting for the baseline patient characteristics and the interval between the two MRI scans. Additionally, with a stratification time of less than 24 months, the risk of LI occurrence was higher in Group 2 versus that in Group 1, after adjusting for baseline confounding factors (odds ratio, 3.68; 95% CI, 1.51 to 8.99; P=0.004). In conclusion, we found that WMH progression was significantly associated with LI occurrence, particularly within the first two years, and that this progression could serve as an independent indicator of LI development.

Keywords progression of white matter hyperintensities      lacunar infarction      incidence      quantitative analysis     
Corresponding Authors: Xu Yun   
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SZ and JZ denote equal first authorship contribution.

Issue Date: 05 June 2018
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Xu Xin
Gao Yuanyuan
Liu Renyuan
Qian Lai
Chen Yan
Wang Xiaoying
Xu Yun
Cite this article:   
Xu Xin,Gao Yuanyuan,Liu Renyuan, et al. Progression of White Matter Hyperintensities Contributes to Lacunar Infarction[J]. Aging and disease, 2018, 9(3): 444-452.
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Figure 1.  Diagrammatic sketch of the screening process.
Figure 2.  Quantitative steps of WMH volume. (A) Original FLAIR image. (B) The high signal area. (C) A sketch of the effective WMH area. (D) Extract of the effective WMH area.
WL (n=76)WOL (n=111)P Value
Age, mean ± SD72.45±10.9368.37±10.810.013 *
Men, n (%)52 (68.42)61 (54.95)0.064
Smoking, n (%)12 (15.79)13 (11.71)0.421
Alcohol, n (%)4 (5.26)7 (6.31)0.766
SBP, mean ± SD139.33±19.19131.47±14.910.002 **
DBP, mean ± SD76.36±12.4473.77±11.590.147
FPG, median (IQR)5.27 (4.69-6.74)5.21 (4.60-6.39)0.391
RBG, median (IQR)7.05 (5.60-9.00)7.20 (6.00-8.90)0.577
PBG, median (IQR)10.40 (7.65-12.85)8.00 (7.00-11.00)0.005 **
HbA1c, median (IQR)6.00 (5.60-6.70)6.00 (5.50-6.70)0.993
TC, median (IQR)3.81 (3.14-4.67)4.12 (3.58-4.90)0.027 *
TG, median (IQR)1.33 (0.86-1.89)1.34 (0.95-1.96)0.414
LDL, median (IQR)1.96 (1.35-2.57)2.21 (1.74-2.72)0.121
HDL, median (IQR)1.02 (0.89-1.15)1.05 (0.86-1.25)0.337
ApoA I, median (IQR)1.06 (0.95-1.27)1.15 (1.04-1.38)0.009 **
BUN, median (IQR)5.40 (4.40-6.96)5.20 (4.30-6.30)0.347
Cr, median (IQR)70.50 (61.50-89.50)66.00 (56.00-78.00)0.044 *
UA, median (IQR)315.5 (243.5-380)315 (268-384)0.412
CRP, median (IQR)4.1 (3.0-10.3)3.7 (2.5-4.8)0.004 **
Hypertension, n (%)37 (48.68)34 (30.63)0.013 *
Diabetes mellitus, n (%)44 (57.89)48 (43.24)0.049 *
Dyslipidaemia, n (%)46 (60.53)60 (54.05)0.380
Interval time, n (%)19 (11-29)15.5 (10-27)0.2931
Table 1  Baseline characteristics.
Group by WMH ProgressionUnivariate Analysis
Multivariate Analysis
OR (95%CI)P ValueOR (95% CI)#P Value
Group 1(≤0)1.001.000
Group 2 (0, 53.64%)3.29 (1.51-7.15)0.0033.36 (1.48-7.67)0.004
Group 3 (≥53.64%)2.21 (1.02-4.81)0.0462.14 (0.93-4.92)0.073
Table 2  Relationship between WMH Progression and LI.
Group by WMH Progression≤24 months
>24 months
OR(95%CI)P ValueOR(95%CI)P Value
Group 1(≤0)1.001.000
Group 2 (0, 53.64%)3.68 (1.51-8.99)0.0042.40 (0.48-11.93)0.285
Group 3 (≥53.64%)2.39 (0.94-6.05)0.0661.83 (0.40-8.49)0.438
Table 3  WMH Progression stratified by time between the two times for MRI.
Figure 3.  WMH volume and Fazekas scale scores for the 1st and 2nd MRI scans for WL and WOL. (A) Comparison of WMH volumes between two groups for two MRI scans. (B) Comparison of WMH progression between two groups. (C) Comparison of Fazekas scale score between two groups for two MRI scans. (D) Comparison of Fazekas scale score changes between two groups. ΔFazekas scale score = the total Fazekas scale score at 2nd MRI scan - the total Fazekas scale score at 1st MRI scan. *** Significant difference (P<0.001).
Figure 4.  Prevalence of LI in patients stratified by WMH progression.
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