Zupan Matija, Šabović Mišo, Zaletel Marjan, Popovič Katarina Šurlan, Žvan Bojana
Division of Vascular Neurology, Department of Neurology, University Medical Centre Ljubljana, 2 Zaloška Street, 1000, Ljubljana, Slovenia.
Division of Vascular Diseases, Department of Internal Medicine, University Medical Centre Ljubljana, 2 Zaloška Street, 1000, Ljubljana, Slovenia.
BMC Neurol. 2015 Sep 2;15:158. doi: 10.1186/s12883-015-0416-z.
In spite of high prevalence and clinical relevance of leukoaraiosis (LA), its pathophysiology is still incompletely understood. Theories of ischaemic genesis and a leaky blood-brain barrier are contradictory yet could share a common denominator-endothelial dysfunction (cerebral, systemic or both), which has not been studied thoroughly in LA.
Thirty patients with LA (58 years (SD 7)) and 30 gender- and age-matched controls without LA (55 years (SD 6)) were recruited. The vascular risk factors (VRF) were identical in both groups. Cerebral endothelial function was determined by cerebrovascular reactivity to L-arginine (CVR). Systemic endothelial function was determined by flow-mediated dilatation (FMD) of the brachial artery after hyperaemia. All participants underwent a brain MRI to search for radiological signs of LA that was classified according to the Fazekas score. Linear regression was used to explore the correlation between CVR and FMD in patients with LA. A 95 % confidence interval was used. For any statistical test used in the study, p ≤ 0.050 was regarded as statistically significant.
We found a marked and significant decrease in both CVR (9.6 % (SD 3.2) vs. 15.8 % (SD 6.1), p < 0.001) and FMD (4.8 % (SD 3.1) vs. 7.4 % (SD 3.8), p = 0.004) in LA patients compared to controls. Both CVR (7.4 % (SD 3.1) vs. 12.2 % (SD 2.6), p = 0.001) and FMD (3.0 % (SD 2.2) vs. 6.4 % (SD 3.1), p = 0.011) were significantly decreased in LA subgroup Fazekas 3 compared to subgroup Fazekas 1. CVR and FMD significantly positively correlated (b = 0.192, 95 % CI = 0.031-0.354, p = 0.02).
The results of our pilot study suggest that patients with LA have a significant impairment of both cerebral and systemic endothelial function that is larger than could be expected based on present VRF. Endothelial dysfunction increases in parallel with LA severity and correlates between cerebral and systemic arterial territory. Overall, our results suggest a so far unknown "intrinsic" generalised endothelial dysfunction in patients with LA that could be involved in LA pathophysiology. This interesting issue needs to be confirmed in larger samples since it could help better understand the mechanisms underlying LA.
尽管脑白质疏松症（LA）具有较高的患病率和临床相关性，但其病理生理学仍未完全明确。缺血性发病机制理论和血脑屏障渗漏理论相互矛盾，但可能存在一个共同因素——内皮功能障碍（脑、全身或两者皆有），而这在LA中尚未得到充分研究。
招募了30例LA患者（年龄58岁（标准差7岁））和30例年龄及性别匹配的无LA对照者（年龄55岁（标准差6岁））。两组的血管危险因素（VRF）相同。通过脑血管对L-精氨酸的反应性（CVR）测定脑内皮功能。通过充血后肱动脉的血流介导的扩张（FMD）测定全身内皮功能。所有参与者均接受脑部MRI检查，以寻找根据Fazekas评分分类的LA影像学征象。采用线性回归分析LA患者中CVR与FMD之间的相关性。使用95%置信区间。对于本研究中使用的任何统计检验，p≤0.050被视为具有统计学意义。
我们发现，与对照组相比，LA患者的CVR（9.6%（标准差3.2）对15.8%（标准差6.1），p<0.001）和FMD（4.8%（标准差3.1）对7.4%（标准差3.8），p=0.004）均显著降低。与Fazekas 1亚组相比，Fazekas 3亚组的LA患者CVR（7.4%（标准差3.1）对12.2%（标准差2.6），p=0.001）和FMD（3.0%（标准差2.2）对6.4%（标准差3.1），p=0.011）也均显著降低。CVR与FMD显著正相关（b=0.192，95%置信区间=0.031-0.354，p=0.02）。
我们的初步研究结果表明，LA患者的脑和全身内皮功能均有显著损害，且损害程度大于基于当前VRF所预期的程度。内皮功能障碍随LA严重程度平行增加，且在脑和全身动脉区域之间存在相关性。总体而言，我们的结果提示LA患者存在一种迄今未知的“内在”全身性内皮功能障碍，可能参与了LA的病理生理学过程。由于这有助于更好地理解LA的潜在机制，这个有趣的问题需要在更大样本中得到证实。
