肝细胞生长因子在烟雾病发病机制中的作用

目的 探讨肝细胞生长因子（hepatocyte growth factor,HGF）在烟雾病发病机制中的作用.方法 采用酶联免疫吸附法检测30例烟雾病患者组、60例健康对照组、8例非烟雾病脑缺血对照组的血清HGF浓度;以2例非烟雾病患者的颞浅动脉分支作为对照,应用免疫组织化学的方法研究12例烟雾病患者的6例颞浅动脉分支和6例脑膜中动脉分支的HGF及其受体c-Met的表达情况.结果 烟雾病组和非烟雾病脑缺血对照组的血清HGF浓度分别为1154.3±348.9pg/ml和955.6±277.5pg/ml,均明显高于健康对照组（701.3±134.3pg/ml）,统计概率分别为P＜0.001和P＜0.05;烟雾病组与非烟雾病脑缺血对照组之间的差异虽尚无显著性（P＞0.05）,但前者比后者仍有升高趋势.免疫组化研究显示HGF及c-Met在烟雾病组颞浅动脉分支和脑膜中动脉分支的管壁平滑肌细胞和内皮细胞的表达均强于对照组.结论 烟雾病患者的血清HGF浓度比健康对照组明显升高,HGF及其受体c-Met在烟雾病颞浅动脉分支、脑膜中动脉分支的管壁表达增多,提示HGF在烟雾病的发病机制中可能具有重要作用.     

烟雾病颈内、外动脉造影和超微病理学研究——Ⅰ.烟雾病颞浅动脉与脑膜中动脉的电镜与光镜观察

用光镜和电镜观察了13例烟雾病人中的12例颞浅A和6例脑膜中A,其主要病变是:内膜平滑肌细胞增生,内膜增厚,中膜和内膜肌细胞破坏,浓缩的细胞器散在于肌细胞间和内弹力板内外侧间质,内弹力板断裂。这些变化与烟雾病颈内动脉末端的病变相同,与炎性血管病、动脉粥样硬化不同,是烟雾病固有的病变。烟雾病不仅是脑血管病,颈外A系统亦可受累。     

烟雾病血管的病理研究

烟雾病（Moyamoya Disease，MMD）是一种少见的狭窄、闭塞性脑血管疾病，基本病理改变主要为颅内狭窄段动脉的内膜呈纤维细胞性增厚，内弹力膜增生分层，中膜平滑肌层变薄。经典的病变部位为颈内动脉（Interal Carotid Artery，ICA）末端以及其主要分枝的起始段，例如大脑前动脉（anterior cerebral artery，ACA），大脑中动脉（Middle Cerebral Artery，MCA）。随着相关病理学的进展，更多MMD血管病理改变被发现，例如脑血管系统之外的肺动脉、肾动脉也存在特征性病理改变。MCA被证实存在明显的细胞凋亡。这些病理改变的研究，有助于最终探明烟雾病的病因。     

小儿moyamoya病颞浅动脉组织学和超微结构与免疫组化研究

报告了５例小儿ｍｏｙａｍｏｙａ病（ＭＤ）颞浅动脉（ＳＴＡ）的组织学和超微结构病理，它们的变化是中膜平滑肌细胞变性、破坏，内弹力板变薄、断裂和内膜平滑肌细胞增生。这些变化与成人ＭＤ脑动脉和ＳＴＡ的病变一致。小儿ＭＤ的ＳＴＡ中能看到大量较早期和较轻的病变，如中膜平滑肌细胞空泡变性、质膜破坏、或仅见于内弹力板两侧的肌细胞坏死；内弹力板破坏轻；内膜增生轻，没有管腔狭窄，与成人不同。本文对ＭＤ动脉病变的发展过程和病因问题提出了看法。     

颞浅动脉植入联合脑膜反转手术治疗烟雾病

目的 分析颞浅动脉植入联合脑膜反转治疗烟雾病的临床效果.方法 对16例经数字减影血管造影(DSA)证实的烟雾病患者,均采用颞浅动脉植入联合脑膜反转手术的方法治疗.结果 16例患者随访6-18个月,未再发生脑缺血或脑出血,所有病例都没有新脑梗塞出现,临床症状均好转,复查见颅底血管网增加,血液供应有明显改善,伴侧支血管形成.结论 颞浅动脉植入联合脑膜反转是治疗烟雾病的一种选择.     

综合术式治疗成年烟雾病的临床作用

目的探讨综合术式(即颞浅动脉-大脑中动脉分支吻合术结合脑-硬脑膜-肌肉血管融合术)在治疗成年烟雾病中的效果。方法 37例成年烟雾病中,出血首发者9例,缺血首发者28例,均接收综合术式的治疗,其中18例接收双侧手术,12例接收同侧两支吻合。结果经该手术治疗后,手术侧血流均有立即改善,缺血症状迅速缓解,随访效果好。手术并发症1例,在吻合区附近出现小梗塞灶。结论本手术方式是将颞浅动脉用作与大脑中动脉分支直接吻合的血管供体,同时又将硬脑膜(脑膜中动脉)、颞肌(颞深动脉)用作血管融合术的血管供体,故综合术式是治疗成年烟雾病患者有效而合理的选择方法。     

烟雾病颈内外动脉造影和超微病理学研究——Ⅱ、烟雾病颈内外动脉造影和组织病理学观察

观察了13例病人的脑血管造影,发现烟雾病的动脉狭窄不仅发生在颈内 A 和椎-基底 A,也可发生在颈内 A 颈段和颈外 A 的颅内、外 A。血管造影观察与病理组织变化结合,发现颞浅 A 和脑膜中 A 常表现一段或一支狭窄,另一段或一支扩张,未见狭窄的节段也有内膜增生。说明烟雾病的病变广泛存在,颞浅 A、脑膜中 A 的血管造影改变应予重视。代偿扩张和侧枝 A 又发生狭窄,提示病变是反复发生的。     

颞浅动脉-大脑中动脉分支吻合结合脑-硬脑膜-肌肉血管融合术治疗成人烟雾病

目的：探讨颞浅动脉‐大脑中动脉分支吻合结合脑‐硬脑膜‐肌肉血管融合术治疗成人烟雾病的效果。方法11例成人烟雾病患者,为双侧病变,缺血型2例,出血型9例,均采用颞浅动脉‐大脑中动脉分支吻合结合脑‐硬脑膜‐肌肉血管融合术进行手术治疗。11例患者均为双侧手术,3例行同侧颞浅动脉两个分支吻合。术后均采用CTA、DSA等检查,吻合口血管通畅情况,术后行C T灌注评估脑血流改善情况。结果11例患者采用此方式进行手术,25个吻合血管,其中24个吻合口通畅,1例因并发症未复查,术后复查CT灌注,显示吻合口血流量及血容量明显优于术前。缺血患者术后症状改善明显,无T IA发作;随访9例,无再次出血。并发症：1例患者在第1次手术后3个月恢复良好,行对侧手术,术后3 h患者突发意识状态下降,发现颅内出血,考虑过度灌注综合征预后差。结论颞浅动脉‐大脑中动脉分支吻合结合脑‐硬脑膜‐肌肉血管融合术治疗成人烟雾病,效果显著,但手术难度较大,风险较高。     

猕猴大脑中动脉超微结构的年龄变化定性定量分析

用透射电镜对猕猴大脑中动脉的增龄改变进行了研究。定性结果:内皮细胞器不丰富,内弹力膜逐渐增厚。内弹力膜窗孔、肌内皮连接及内膜平滑肌也逐渐增多。中膜平滑肌形态变得不规则,并出现不同程度的坏死。细胞间隙增宽、间质增多。幼年组和老年组中膜平滑肌细胞内合成与分泌性细胞器丰富。定量结果:内膜和中膜的厚度随增龄而增加,但中膜平滑肌占中膜面积的百分比随增龄而下降。本结果为脑血管病的研究提供了资料。     

脑硬脑膜颞浅动脉血管融通术治疗缺血型烟雾病的疗效观察

目的观察脑硬脑膜颞浅动脉血管融通术治疗缺血性烟雾病的临床效果。方法选取我院收治的50例缺血性烟雾病患者为研究对象,均采用脑硬脑膜颞浅动脉血管通融术治疗,比较治疗前后患者血流动力学变化,评估治疗效果。结果术后患者颈内动脉、颈外动脉分支血流量分别降低至(18.23±0.06)10-4 m3/s、(11.48±2.11)10-4 m3/s,与术前比较差异有统计学意义(P0.05);术后,患者颈内动脉血管压力值降低至(8274.95±151.21)Pa,与术前比较差异有统计学意义(P0.05);而其术后颈外动脉分支供血血管压力值为(8327.16±4.12)Pa,与术前比较差异无统计学意义(P0.05)。结论在缺血型烟雾病患者的临床治疗中,采用脑硬脑膜颞浅动脉血管融通术治疗方案,可重建患者脑血流,改善脑组织供血,提高患者脑组织血供,保护脑组织功能,整体手术疗效好。     

Ultrastructural studies of cerebral arteries and collateral vessels in moyamoya disease

Moyamoya disease was originally defined as a characteristic syndrome of recurrent headaches, occlusion of the distal internal carotid arteries and the foggy (moyamoya) clusters of collateral vessels at the base of the brain as demonstrated by cerebral angiography. The etiology is unknown and pathobiology is poorly understood. We examined the intracranial arteries in 3 patients to demonstrate characteristic changes and to obtain a better understanding of the basis mechanisms of the disease. Controls were obtained from 3 normotensive patients who died as a result of cancer. Occluded internal carotid arteries were characterized by severe thickening of the intima with a dense luminal array of smooth muscle cells, a deeper less cellular zone, pronounced tortuosity of the internal elastica and thinning of the media. Collateral vessels were arterial in structure and were affected by similar proliferative changes in the intima, thinning of the media, and contorted internal elastica. Stainable lipids were not part of the typical components. Severe contortion of the internal elastica, medial damage and intimal proliferation may result from recurrent and sustained spasticity of the cerebral arteries. The distal lenticulostriate arteries showed severe medial damage similar to what is termed as a moth-eaten change in hypertensive patients dying of massive cerebral hemorrhage.     

Systemic vascular changes in spontaneous occlusion of the circle of Willis.

BACKGROUND AND PURPOSE: We examined the presence of systemic etiologic factors causing vascular changes in so-called "spontaneous occlusion of the circle of Willis" (cerebrovascular moyamoya disease) to determine whether extracranial, as well as intracranial, vessels are involved in this disease. METHODS: Histopathologic examination and morphometric analysis of the extracranial vessels were performed in 13 patients with this disease. RESULTS: The histopathologic findings of the extracranial vessels were as follows: 1) advanced intimal fibrous thickening similar to that of the intracranial vessels; and 2) characteristic intimal fibrous nodular thickening, which may indicate organization of mural thrombi, at the proximal portions of the pulmonary arteries in three of 13 patients. Morphometric analysis revealed significant intimal thickening of the pulmonary arteries (p less than 0.05), renal arteries (p less than 0.05), and pancreatic arteries (p less than 0.01) in patients with this disease as compared with age- and sex-matched control patients. CONCLUSIONS: On the basis of these findings, it is highly likely that this disease has systemic etiologic factors, as well as focal etiologic factors, that work to create vascular change in both the intracranial and extracranial vessels.     

Pathological and immunohistochemical findings of an autopsy case of adult moyamoya disease

Moyamoya disease is vaso‐occlusive disease involving the arteries of the circle of Willis that is accompanied by a compensatory recruitment of a vascular network. The pathological and immunohistochemical findings of an autopsy case of hemorrhagic moyamoya disease in a 69‐year‐old woman are described in the present report. The autopsy findings of the brain revealed cerebral and intraventricular hemorrhage with edema. The left anterior cerebral artery, bilateral middle cerebral arteries and left posterior cerebral artery were marked narrowing, and the other arteries revealed mild narrowing. Microscopically, the arteries of the circle of Willis showed narrowed lumen, fibrocellular intimal thickening, marked tortuousness of internal elastic lamina and attenuation of media. The thickened intima was composed of smooth muscle cells. The vessels with dilated or irregular‐shaped lumen suggested abnormal vascular networks demonstrated by angiography. In this case, no correlation between the abnormal vascular network and expression of VEGF or VEGF receptor was disclosed. It was hypothesized that abnormal vascular networks might be composed of collateral vessels in relation to various pathological changes of the arteries, such as occlusion and stenosis, and intracranial hemorrhage in patients with moyamoya disease might occur as a result of rupture of arteries including abnormal vascular networks.     

Binswanger’s encephalopathy: serial sections and morphometry of the cerebral arteries

To identify arterial changes that are characteristic of Binswanger’s encephalopathy (BE), we analyzed cerebral subarachnoid and medullary arteries of seven BE autopsy specimens by reconstruction of stained serial sections. We also noted the frequency of intimal fibrosis with or without atheroma of the subarachnoid arteries, and determined the medial thickness of the subarachnoid and medullary arteries. The results for the BE specimens were compared with those of six hypertensive brain hemorrhage (HH) specimens and six normotensive (NT) specimens from patients without cerebral abnormalities. In medullary arteries of BE in comparison with HH, we observed nonspecific but significantly more widespread intimal fibrosis with or without atheroma, as well as segmental loss of the medial smooth muscle cells (SMCs), which was sometimes associated with intimal plasma exudation or microaneurysm. A few medullary arteries in BE were completely occluded by fibrous connective tissue. Intimal fibrosis of the subarachnoid arteries was significantly more widespread in BE than in HH and NT. The media of the subarachnoid and medullary arteries was significantly thicker in BE and HH than in NT, and tended to be thicker in BE than in HH. In NT specimens the medullay arteries tended to be thinner in medial thickness than the subarachnoid arteries. These findings suggest that dysfunction of blood flow regulation due to increased arterial stiffness caused by hypertension-induced intimal fibrosis and loss of medial SMCs is an essential mechanism resulting in diffuse myelin loss of the cerebral white matter in BE, whereas luminal stenosis or occlusion and adventitial fibrosis are secondary. Moreover, selective and severe involvement of the cerebral medullary arteries compared with the subarachnoid arteries may be explained by the following two factors, (1) that many medullary arteries have normally dilated sigments, and (2) that their media is thinner compared with that of the subarachnoid arteries of the corresponding diameter. Received: 15 November 1999 / Revised, accepted: 28 December 1999     

An autopsy case of Fabry disease with neuropathological investigation of the pathogenesis of associated dementia

The pathogenesis of dementia associated with Fabry disease was examined neuropathologically in an autopsy case. The patient was a 47‐year‐old computer programmer who developed renal failure at the age of 36, necessitating peritoneal dialysis, and thereafter suffered in succession episodic pulmonary congestion, bradyacusia, heart failure, and dementia, before dying of acute myocardial infarction. MRI of the brain demonstrated leuko‐araiosis. The CNS parenchyma showed widespread segmental hydropic swelling of axons in the bilateral cerebral and cerebellar deep white matter in addition to neuronal ballooning due to glycolipid storage in a few restricted nuclei and multiple tiny lacunae. Hydropic axonal swelling was also sparsely distributed in the pyramidal tract, pedunculus cerebellaris superior and brachium colliculi inferioris, but wallerian degeneration of these tracts was absent. Additional features included angiopathy of the subarachnoidal arteries due to Fabry disease, such as medial thickening resulting from glycolipid deposition in smooth muscle cells (SMCs) and adventitial fibrosis with lymphocytic infiltration, together with widespread subtotal or total replacement of medial SMCs by fibrosis, associated with prominent intimal fibrous thickening and undulation of the internal elastic membrane of medium‐sized (1000–100 μm diameter) arteries. The findings in this case suggest that axonopathic leukoencephalopathy due to multisegmental hydropic swelling of axons in the bilateral cerebral deep white matter is responsible for the dementia associated with Fabry disease, and may be caused by ischemia resulting from widespread narrowing and stiffening of medium‐sized subarachnoidal arteries and progressive heart failure.     

Cerebral arterial pathology of CADASIL and CARASIL (Maeda syndrome)

Two familial cerebro‐vascular diseases characterized by different cerebral arterial pathologies and presenting in non‐hypertensive young and middle‐aged adults are described. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by the deposition of smudged periodic acid–Schiff (PAS)‐positive granules known as granular osmiophilic materials (GOM) in the media of small arteries and arterioles. The medial smooth muscle cells are completely lost, and intense adventitial fibrosis is present. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), or Maeda syndrome, is characterized by intense arteriolosclerosis without GOM deposition. Fibrous intimal proliferation, hyaline degeneration of the media, thickening and splitting of the internal elastic lamina, and concentric narrowing of the lumen are characteristic features. In PAS preparation, small arteries are occasionally stained homogeneously due to exudative changes, but never exhibit granular appearance in CARASIL (Maeda syndrome). Each of the small arterial changes is intense in the cerebral medullary and leptomeningeal arteries, leading to multifocal, confluent, or diffuse ischemic changes in the cerebrum. The authors suggest that CARASIL be referred to as ‘Maeda syndrome’ or ‘CARASIL (Maeda syndrome)’ to avoid confusion with CADASIL.     

Giant cell arteritis in a 19-year-old woman associated with vertebral artery aneurysm and subarachnoid hemorrhage

Giant cell arteritis (GCA) is a disease chiefly found in elderly patients. Intracranial vessels are rarely involved in GCA. Here we report the case of a 19-year-old woman with GCA in the basilar and vertebral arteries. Two weeks after the first symptoms, she developed an aneurysmatical dilatation of the right vertebral artery which ruptured leading to subarachnoid hemorrhage. Although the ruptured right vertebral artery was clipped neurosurgically, she died two days later. Autopsy revealed GCA with focal medial necrosis and intimal thickening of the vertebral arteries and the basilar artery. No other arteries were affected. In the involved vessels, the media exhibited C1q immunoreactivity. At the intimal site of the internal elastic lamina there were increased levels of elastase. Other arterial diseases showing the pattern of GCA were excluded. This case demonstrates that GCA is not necessarily restricted to elderly people. Moreover, this case shows that a GCA-induced aneurysm is a very rare reason for subarachnoid hemorrhage even in young adults.