Vascular comorbidities have a deleterious impact on multiple sclerosis clinical outcomes but it is unclear whether this is mediated by an excess of extracranial vascular disease (i.e. atherosclerosis) and/or of cerebral small vessel disease or worse multiple sclerosis pathology. To address these questions, a study using a unique post-mortem cohort wherein whole body autopsy reports and brain tissue were available for interrogation was established. Whole body autopsy reports were used to develop a global score of systemic vascular disease that included aorta and coronary artery atheroma, cardiac hypertensive disease, myocardial infarction and ischaemic stroke. The score was applied to 85 multiple sclerosis cases (46 females, age range 39 to 84 years, median 62.0 years) and 68 control cases. Post-mortem brain material from a subset of the multiple sclerosis (n = 42; age range 39–84 years, median 61.5 years) and control (n = 39) cases was selected for detailed neuropathological study. For each case, formalin-fixed paraffin-embedded tissue from the frontal and occipital white matter, basal ganglia and pons was used to obtain a global cerebral small vessel disease score that captured the presence and/or severity of arteriolosclerosis, periarteriolar space dilatation, haemosiderin leakage, microinfarcts, and microbleeds. The extent of multiple sclerosis-related pathology (focal demyelination and inflammation) was characterized in the multiple sclerosis cases. Regression models were used to investigate the influence of disease status on systemic vascular disease and cerebral small vessel disease scores and, in the multiple sclerosis group, the relationship between multiple sclerosis-related pathology and both vascular scores. We show that: (i) systemic cardiovascular burden, and specifically atherosclerosis, is lower and cerebral small vessel disease is higher in multiple sclerosis cases that die at younger ages compared with control subjects; (ii) the association between systemic vascular disease and cerebral small vessel disease is stronger in patients with multiple sclerosis compared with control subjects; and (iii) periarteriolar changes, including periarteriolar space dilatation, haemosiderin deposition and inflammation, are key features of multiple sclerosis pathology outside the classic demyelinating lesion. Our data argue against a common primary trigger for atherosclerosis and multiple sclerosis but suggest that an excess burden of cerebral small vessel disease in multiple sclerosis may explain the link between vascular comorbidity and accelerated irreversibility disability.

中文翻译：

---

血管疾病和多发性硬化症：验尸研究，探讨它们之间的关系。

血管合并症对多发性硬化症的临床结局具有有害影响，但尚不清楚这是否由过量的颅外血管疾病（即动脉粥样硬化）和/或脑小血管疾病或多发性硬化症病理恶化所介导。为了解决这些问题，建立了一项使用独特的验尸队列的研究，其中可以使用全身尸检报告和脑组织进行讯问。全身尸检报告被用于制定全身性血管疾病的总体评分，包括主动脉和冠状动脉粥样硬化，心脏高血压疾病，心肌梗塞和缺血性中风。该分数适用于85例多发性硬化症病例（46例女性，年龄范围39至84岁，中位数62.0岁）和68例对照病例。n  =  42；年龄范围39-84岁，中位数61.5岁）和控制者（n  = 39）选择病例进行详细的神经病理学研究。对于每种情况，均使用额叶和枕叶白质，基底神经节和脑桥的福尔马林固定石蜡包埋组织来获得总体脑小血管疾病评分，该评分反映了动脉粥样硬化的存在和/或严重程度，小动脉周围空间扩张，血红素渗漏，微梗塞和微出血。在多发性硬化症病例中表征了多发性硬化症相关病理学的程度（局灶性脱髓鞘和炎症）。回归模型用于研究疾病状况对全身血管疾病和脑小血管疾病评分的影响，以及在多发性硬化症组中，多发性硬化相关病理与两个血管分数之间的关系。我们证明：（i）与对照组相比，在较年轻时死亡的多发性硬化症病例中，全身性心血管疾病的负担，特别是动脉粥样硬化的发生率较低，而脑小血管疾病的发生率较高；（ii）多发性硬化症患者的系统性血管疾病与脑小血管疾病之间的关联性比对照组更强；（iii）小动脉周围的改变，包括小动脉周围空间的扩张，血铁蛋白的沉积和炎症，是典型的脱髓鞘病变以外的多发性硬化症病理的关键特征。