下载掌阅APP，畅读海量书库
立即打开
皮层下小血管疾病（subcortical small-vessel disease, SSVD）是一种从临床表现、影像学和神经病理学角度都具有明显特征的疾病。SSVD被认为是最普遍的缺血性脑疾病，发病率随年龄增长而增加。其主要的血管危险因素包括高血压、糖尿病、高脂血症、高同型半胱氨酸和阻塞性睡眠呼吸暂停。缺血性白质病变是SSVD的标志，其他病理改变包括小动脉硬化、血管周围间隙扩张、静脉胶原沉积、CAA、微出血、微梗死、腔隙和大面积梗死等。SSVD的发病机制尚不完全清楚，但包括金属蛋白酶、血管内皮生长因子、血管紧张素Ⅱ、西罗莫司通路的哺乳动物靶点在内的内皮变化和血脑屏障改变，以及代谢和遗传性变化，但迄今很少有明确结论性的研究。SSVD的临床诊断包括早期执行功能障碍，表现为使用复杂信息、制定策略和自我控制能力受损。与AD相比，SSVD患者表现出较少的情景记忆缺陷。脑成像技术在SSVD的诊断方面有了长足的进步。除了皮质微梗死外，MRI能很好地显示所有其他病变。从SSVD中分离AD的诊断性生物标志物包括脑脊液Aβ42的减少和Aβ42/Aβ40比值的降低。然而，需要更好地反应脑血管功能指标，除控制血管危险因素外，SSVD的治疗仍不令人满意。目前迫切需要找到减缓和阻止这种普遍存在但还未被发现的疾病进展的治疗靶标 [20] 。
[1]HARTMANN D A, HYACINTH H I, LIAO F F, et al. Does pathology of small venules contribute to cerebral microinfarcts and dementia? [J]. Neurochem, 2018, 144 (5): 517-526.
[2]SONDERGAARD C B, NIELSEN J E, HANSEN C K, et al. Hereditary cerebral small vessel disease and stroke [J]. Clin Neurol Neurosurg, 2017, 155: 45-57.
[3]PASI M, CHARIDIMOU A, BOULOUIS G, et al. Cerebral small vessel disease in patients with spontaneous cerebellar hemorrhage [J]. J Neurol, 2019, 266 (3): 625-630.
[4]DINSDALE H B. Spontaneous hemorrhage in the posterior fossa: a study of primary cerebellar and pontine hemorrhages with observations on their pathogenesis [J]. Arch Neurol, 1964, 10: 200-217.
[5] PASI M, MARINI S, MOROTTI A, et al. Cerebellar hematoma location: implications for the underlying microangiopathy[J]. Strok, 2018, 49: 207-210.
[6] ITOH Y, YAMADA M, HAYAKAWA M, et al. Cerebral amyloid angiopathy: a significant cause of cerebellar as well as lobar cerebral hemorrhage in the elderly [J]. J Neurol Sci, 1993, 116: 135-141.
[7]PASI M, CHARIDIMOU A, BOULOUIS G, et al. Mixed-location cerebral hemorrhage/microbleeds: underlying microangiopathy and recurrence risk [J]. Neurology, 2018, 90: 119-126.
[8]BLEVINS B L, VINTERS H V, LOVE S, et al. Brain arteriolosclerosis [J]. Acta Neuropathol, 2021, 141 (1): 1-24.
[9]SKROBOT O A, ATTEMS J, ESII M, et al. Vascular cognitive impairment neuropathology guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment [J]. Brain, 2016, 139: 2957-2969.
[10]ARVANITAKIS Z, CAPUANO A W, LEURGANS S E, et al. The relationship of cerebral vessel pathology to brain microinfarcts [J]. Brain Pathol, 2017, 27 (1): 77-85.
[11]HARDY J A, HIGGINS G A. Alzheimer’s disease: the amyloid cascade hypothesis [J]. Science, 1992, 256 (5054): 184-185.
[12]REISS A B, ARAIN H A, STECKER M M, et al. Amyloid toxicity in Alzheimer’s disease [J]. Rev Neurosci, 29 (6): 613-627.
[13]CHARIDIMOU A, BOULOUIS G, GUROL M E, et al. Emerging concepts in sporadic cerebral amyloid angiopathy [J].Brain, 2017, 140 (7): 1829-1850.
[14]OLAFSSON I, THORSTEINSSON L, JENSSON O. The molecular pathology of hereditary cystatin C amyloid angiopathy causing brain hemorrhage [J]. Brain Pathol, 1996, 6 (2): 121-126.
[15]VISWANATHAN A, GREENBERG S M. Cerebral amyloid angiopathy in the elderly [J]. Ann Neurol, 2011, 70 (6): 871-880.
[16]KRINGS T, MANDELL D M, KIEHL T R, et al. Intracranial aneurysms: from vessel wall pathology to therapeutic approach [J]. Nat Rev Neurol, 2011, 7 (10): 547-559.
[17]WANG Y T, EMETO T I, LEE J, et al. Mouse models of intracranial aneurysm [J]. Brain Pathol, 2015, 25 (3): 237-247.
[18]SHIMIZU K, KUSHAMAE M, MIZUTANI T, et al. Intracranial aneurysm as a macrophage-mediated inflammatory disease [J]. Neurol Med Chir (Tokyo), 2019, 59 (4): 126-132.
[19]GABEREL T, ROCHEY A, PALMA C D, et al. Ruptured intracranial aneurysm in patients with osteogenesis imperfecta:2 familial cases and a systematic review of the literature [J]. Neurochirurgie, 2016, 62 (6): 317-320.
[20]WALLIN A, ROMAN G C, ESIRI M, et al. Update on vascular cognitive impairment associated with subcortical small-Vessel disease [J]. J Alzheimers Dis, 2018, 62 (3): 1417-1441.
（许森林）