Hervella Pablo, Alonso-Alonso Maria Luz, Sampedro-Viana Ana, Rodríguez-Yáñez Manuel, López-Dequidt Iria, Pumar José M, Ouro Alberto, Romaus-Sanjurjo Daniel, Campos Francisco, Sobrino Tomás, Castillo José, Leira Yago, Iglesias-Rey Ramón
Neuroimaging and Biotechnology Laboratory, Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain.
Stroke Unit, Department of Neurology, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Ther Adv Neurol Disord. 2024 May 31;17:17562864241243274. doi: 10.1177/17562864241243274. eCollection 2024.
Cerebral small vessel disease is the most common cause of lacunar strokes (LS). Understanding LS pathogenesis is vital for predicting disease severity, prognosis, and developing therapies.
To research molecular profiles that differentiate LS in deep brain structures from those in subcortical white matter.
Prospective case-control study involving 120 patients with imaging-confirmed LS and a 120 control group.
We examined the relationship between Alzheimer's disease biomarkers [amyloid beta (Aβ, Aβ)], serum inflammatory marker (interleukin-6, IL-6), and endothelial dysfunction markers [soluble tumor necrosis factor-like weak inducer of apoptosis, and pentraxin-3 (sTWEAK, PTX3)] with respect to LS occurring in deep brain structures and subcortical white matter. In addition, we investigated links between LS, leukoaraiosis presence (white matter hyperintensities, WMHs), and functional outcomes at 3 months. Poor outcome was defined as a modified Rankin scale >2 at 3 months.
Significant differences were observed in levels of IL-6, PTX3, and sTWEAK between patients with deep lacunar infarcts and those with recent small subcortical infarcts (20.8 15.6 pg/mL, < 0.001; 7221.3 4624.4 pg/mL, < 0.0001; 2528.5 1660.5 pg/mL, = 0.001). Patients with poor outcomes at 3 months displayed notably higher concentrations of these biomarkers compared to those with good outcomes. By contrast, Aβ and Aβ were significantly lower in patients with deep LS ( < 0.0001). Aβ levels were significantly higher in patients with LS in subcortical white matter who had poor outcomes. WMH severity only showed a significant association with deep LS and correlated with sTWEAK ( < 0.0001).
The pathophysiological mechanisms of lacunar infarcts in deep brain structures seem different from those in the subcortical white matter. As a result, specific therapeutic and preventive strategies should be explored.
脑小血管病是腔隙性卒中（LS）最常见的病因。了解LS的发病机制对于预测疾病严重程度、预后以及开发治疗方法至关重要。
研究区分深部脑结构中LS与皮质下白质中LS的分子特征。
前瞻性病例对照研究，纳入120例经影像学确诊的LS患者和120例对照组。
我们研究了阿尔茨海默病生物标志物[淀粉样β蛋白（Aβ，Aβ）]、血清炎症标志物（白细胞介素-6，IL-6）和内皮功能障碍标志物[可溶性肿瘤坏死因子样凋亡弱诱导剂和五聚素-3（sTWEAK，PTX3）]与深部脑结构和皮质下白质中发生的LS之间的关系。此外，我们调查了LS、脑白质疏松症（白质高信号，WMHs）的存在与3个月时功能结局之间的联系。不良结局定义为3个月时改良Rankin量表评分>2分。
深部腔隙性梗死患者与近期皮质下小梗死患者之间，IL-6、PTX3和sTWEAK水平存在显著差异（20.8±15.6 pg/mL，P<0.001；7221.3±4624.4 pg/mL，P<0.0001；2528.5±1660.5 pg/mL，P=0.001）。3个月时预后不良的患者与预后良好的患者相比，这些生物标志物的浓度明显更高。相比之下，深部LS患者的Aβ和Aβ明显较低（P<0.0001）。皮质下白质中LS且预后不良的患者Aβ水平明显更高。WMH严重程度仅与深部LS显著相关，且与sTWEAK相关（P<0.0001）。
深部脑结构中腔隙性梗死的病理生理机制似乎与皮质下白质中的不同。因此，应探索特定的治疗和预防策略。
