Generic placeholder image

Current Neurovascular Research


ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

Research Article

The Positional Relationship between Lacunae and White Matter Hyperintensity in Patients with Cerebral Small Vessel Disease

Author(s): Lu An, Wenxin Yuan, Yunchao Wang, Shanshan Li, Ce Zong, Yuan Gao, Yusheng Li, Limei Wang, Ya Peng Li, Yan Ji* and Yuming Xu*

Volume 20, Issue 3, 2023

Published on: 28 August, 2023

Page: [399 - 409] Pages: 11

DOI: 10.2174/1567202620666230721124707

Price: $65


Background: Lacunae and white matter hyperintensity (WMH) are two crucial imaging biomarkers of cerebral small vessel disease (CSVD). Multiple studies have revealed a close relationship between WMH and lacunae and found that a double penumbra existed at the edge of WMH that affects lacunae formation. The study aimed to explore the spatial distribution characteristics and possible influencing factors of lacuna in relation to white matter hyperintensity in patients with CSVD.

Methods: A total of 480 CSVD patients with WMH and with or without lacunae were included. Data about blood biochemical indicators, cerebrovascular CT angiography, 24-hour ambulatory blood pressure and ambulatory electrocardiogram, brain magnetic resonance imaging, and transcranial Doppler ultrasound were gathered from all subjects. They were categorised into four groups based on the spatial interaction between lacunae and WMH. Univariate analyses and multiple logistic regression analyses were used to compare the differences in traditional vascular risk factors, heart rate and blood pressure indicators, arterial pulsatility index (PI) values, and arterial stenosis among different groups.

Results: The average age of 480 patients was (58.63 ± 11.91) years, with 347 males (72.3%). Univariate analysis indicated that age, fasting blood glucose, triglycerides, total cholesterol, highdensity lipoprotein, 24-hour and daytime and night systolic and diastolic blood pressure, nocturnal heart rate, heart rate variability, PI values of ipsilateral and contralateral MCA (middle cerebral artery) and ICA (Internal carotid artery) of the lacunae, Fazekas score of PWMH (periventricular white matter hyperintensities), the proportion of MCA or ICA with stenosis rate over 50% on the ipsilateral side of the lacunae were significantly different between different groups (p < 0.05). High fasting blood glucose (OR=1.632, 95% CI= (1.128, 2.361), p =0.009), (OR=1.789, 95%CI= (1.270, 2.520), p = 0.001), (OR=1.806, 95% CI= (1.292, 2.524), p =0.001) was identified as a risk factor for lacunae formation by logistic regression analysis.

Conclusion: High fasting blood glucose can be considered a risk factor for lacunae formation in patients with WMH. The more severe the PWMH and the higher the nocturnal heart rate, the more likely the lacunae, as well as PWMH, overlap completely. Ipsilateral arteriosclerosis and stenosis are independent risk factors for no contact between lacunae and PWMH.

Keywords: Lacunae, white matter hyperintensity, cerebral small vessel disease, positional relationship, risk factors, neuroimaging.

Wardlaw JM, Smith C, Dichgans M. Small vessel disease: Mechanisms and clinical implications. Lancet Neurol 2019; 18(7): 684-96.
[] [PMID: 31097385]
Nam KW, Kwon HM, Lim JS, Han MK, Nam H, Lee YS. The presence and severity of cerebral small vessel disease increases the frequency of stroke in a cohort of patients with large artery occlusive disease. PLoS One 2017; 12(10): e0184944.
[] [PMID: 28991905]
Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cognitive impairment and dementia: A statement for healthcare professionals from the american heart association/american stroke association. Stroke 2011; 42(9): 2672-713.
[] [PMID: 21778438]
Wardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 2013; 12(8): 822-38.
[] [PMID: 23867200]
van den Brink H, Doubal FN, Duering M. Advanced MRI in cerebral small vessel disease. Int J Stroke 2023; 18(1): 28-35.
[] [PMID: 35311609]
Promjunyakul N, Lahna DL, Kaye JA, et al. Comparison of cerebral blood flow and structural penumbras in relation to white matter hyperintensities: A multi-modal magnetic resonance imaging study. J Cereb Blood Flow Metab 2016; 36(9): 1528-36.
[] [PMID: 27270266]
Promjunyakul N, Lahna D, Kaye JA, et al. Characterizing the white matter hyperintensity penumbra with cerebral blood flow measures. Neuroimage Clin 2015; 8: 224-9.
[] [PMID: 26106546]
Duering M, Csanadi E, Gesierich B, et al. Incident lacunes preferentially localize to the edge of white matter hyperintensities: Insights into the pathophysiology of cerebral small vessel disease. Brain 2013; 136(9): 2717-26.
[] [PMID: 23864274]
Zhang X, Ding L, Yang L, et al. Relationship between white matter hyperintensities penumbra and cavity formation. Med Sci Monit 2016; 22: 41-9.
[] [PMID: 26729408]
Ghaznawi R, Geerlings MI, Jaarsma-Coes MG, et al. The association between lacunes and white matter hyperintensity features on MRI: The SMART-MR study. J Cereb Blood Flow Metab 2019; 39(12): 2486-96.
[] [PMID: 30204039]
Yi F, Cai M, Jacob MA, et al. Spatial relation between white matter hyperintensities and incident lacunes of presumed vascular origin: A 14-Year Follow-Up Study. Stroke 2022; 53(12): 3688-95.
[] [PMID: 36189679]
Samuels OB, Joseph GJ, Lynn MJ, Smith HA, Chimowitz MI. A standardized method for measuring intracranial arterial stenosis. AJNR Am J Neuroradiol 2000; 21(4): 643-6.
[PMID: 10782772]
Zeng W, Chen Y, Zhu Z, et al. Severity of white matter hyperintensities: Lesion patterns, cognition, and microstructural changes. J Cereb Blood Flow Metab 2020; 40(12): 2454-63.
[] [PMID: 31865841]
Tully PJ, Yano Y, Launer LJ, et al. Association between blood pressure variability and cerebral small‐vessel disease: A systematic review and meta‐analysis. J Am Heart Assoc 2020; 9(1): e013841.
[] [PMID: 31870233]
Maillard P, Fletcher E, Harvey D, et al. White matter hyperintensity penumbra. Stroke 2011; 42(7): 1917-22.
[] [PMID: 21636811]
Reijmer YD, Freeze WM, Leemans A, Biessels GJ. Utrecht Vascular Cognitive Impairment Study Group. The effect of lacunar infarcts on white matter tract integrity. Stroke 2013; 44(7): 2019-21.
[] [PMID: 23686971]
Nam KW, Kwon HM, Jeong HY, Park JH, Kwon H, Jeong SM. High triglyceride-glucose index is associated with subclinical cerebral small vessel disease in a healthy population: a cross-sectional study. Cardiovasc Diabetol 2020; 19(1): 53.
[] [PMID: 32375783]
Rudilosso S, Mena L, Esteller D, et al. Higher cerebral small vessel disease burden in patients with white matter recent small subcortical infarcts. J Stroke Cerebrovasc Dis 2021; 30(7): 105824.
[] [PMID: 33906070]
Zhang X, Ding L, Yuan J, Qin W, Hu W. Spatial relationship between acute lacunar infarction and white matter hyperintensities. Eur Neurol 2015; 74(5-6): 259-66.
[] [PMID: 26645081]
Aries MJH, Elting JW, De Keyser J, Kremer BPH, Vroomen PCAJ. Cerebral autoregulation in stroke: A review of transcranial Doppler studies. Stroke 2010; 41(11): 2697-704.
[] [PMID: 20930158]
Han SW, Lee SS, Kim SH, et al. Effect of cilostazol in acute lacunar infarction based on pulsatility index of transcranial Doppler (ECLIPse): A multicenter, randomized, double-blind, placebo-controlled trial. Eur Neurol 2013; 69(1): 33-40.
[] [PMID: 23128968]
Agha M, Alboudi A. Arterial pulsatility as an index of cerebral microangiopathy in diabetes type 2[J]. East Mediterr Health J 2014; S198-203.
Webb AJS, Simoni M, Mazzucco S, Kuker W, Schulz U, Rothwell PM. Increased cerebral arterial pulsatility in patients with leukoaraiosis: Arterial stiffness enhances transmission of aortic pulsatility. Stroke 2012; 43(10): 2631-6.
[] [PMID: 22923446]
Shan E, Ewang Y, Exu A, et al. Chinese Ischemic Stroke Subclassification. In: CISS. 2011. Available from:
Gao S, Wang Y, Xu A, et al. Chinese ischemic stroke subclassification. Front Neurol 2011; 2: 6.
Fisher CM. Lacunar strokes and infarcts: A review. Rev Neurol 1982; 32(8): 871-6.
[] [PMID: 7048128]
Kim JY, Bushnell CD, Park JH, et al. Central aortic pressure and pulsatility index in acute ischemic stroke. J Neuroimaging 2015; 25(3): 438-42.
[] [PMID: 25060557]
Yong SW, Bang OY, Lee PH, Li WY. Internal and cortical border-zone infarction: Clinical and diffusion-weighted imaging features. Stroke 2006; 37(3): 841-6.
[] [PMID: 16424374]
Kim JS, Yoon Y. Single subcortical infarction associated with parental arterial disease: Important yet neglected sub-type of atherothrombotic stroke. Int J Stroke 2013; 8(3): 197-203.
[] [PMID: 22568537]
Nah HW, Kang DW, Kwon SU, Kim JS. Diversity of single small subcortical infarctions according to infarct location and parent artery disease: Analysis of indicators for small vessel disease and atherosclerosis. Stroke 2010; 41(12): 2822-7.
[] [PMID: 20966406]
Shu MJ, Zhai FF, Zhang DD, et al. Metabolic syndrome, intracranial arterial stenosis and cerebral small vessel disease in community-dwelling populations. Stroke Vasc Neurol 2021; 6(4): 589-94.
[] [PMID: 33903177]
Liu S, Hu WX, Zu QQ, et al. A novel embolic stroke model resembling lacunar infarction following proximal middle cerebral artery occlusion in beagle dogs. J Neurosci Methods 2012; 209(1): 90-6.
[] [PMID: 22722089]
Yu L, Li Y, Wang Y, et al. association of nocturnal heart rate with white matter hyperintensity burden in cerebral small vessel disease patients. Curr Neurovasc Res 2021; 18(5): 565-71.
[] [PMID: 34970952]
Yamaguchi Y, Wada M, Sato H, et al. Impact of nocturnal heart rate variability on cerebral small-vessel disease progression: A longitudinal study in community-dwelling elderly japanese. Hypertens Res 2015; 38(8): 564-9.
Del Brutto OH, Mera RM, Costa AF, Castillo PR. Effect of heart rate variability on the association between the apnea-hypopnea index and cerebral small vessel disease. Stroke 2019; 50(9): 2486-91.
[] [PMID: 31345136]
Yu L, Yang L, Li Y, et al. Hyperhomocysteinemia can predict the severity of white matter hyperintensities in elderly lacunar infarction patients. Int J Neurosci 2020; 130(3): 231-6.
[] [PMID: 31744348]
Longstreth WT Jr, Arnold AM, Beauchamp NJ Jr, et al. Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: The cardiovascular health study. Stroke 2005; 36(1): 56-61.
[] [PMID: 15569873]
Ren J, Grundy SM, Liu J, et al. Long-term coronary heart disease risk associated with very-low-density lipoprotein cholesterol in chinese: the results of a 15-year chinese multi-provincial cohort study (CMCS). Atherosclerosis 2010; 211(1): 327-32.
[] [PMID: 20223457]
Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45(7): 2160-236.
Jensen M, Thomalla G. Causes and secondary prevention of acute ischemic stroke in adults. Hämostaseologie 2020; 40(01): 022-30.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy