Cortical microinfarcts on 7T MRI in patients with spontaneous intracerebral hemorrhage

In patients with spontaneous intracerebral hemorrhage (ICH) coexisting abnormalities on brain imaging can provide clues on the etiology of the underlying small vessel disease. We examined cortical cerebral microinfarcts as a novel marker of coexistent vascular damage in ICH. Twelve patients with spontaneous ICH and 15 controls underwent 7Tesla magnetic resonance imaging (MRI). Microinfarcts were present in 9 of 12 patients with spontaneous ICH, and in 5 of 15 controls. This explorative study shows, for the first time, that microinfarcts appear to be a very common vascular comorbidity in spontaneous ICH. Future larger studies should further assess the etiological significance of these lesions.     

A clinico-pathological study of heart and brain lesions in vascular dementia

All vascular dementia (VaD) cases, neuropathologically verified in a longitudinal prospective dementia project, were classified according to the vascular brain lesion type and related to the dementia type and cardiovascular pathology. From 1976 to 1995, there were 175 VaD cases, 49 of which were pure, without Alzheimer pathology and only one type of cerebrovascular lesion. Furthermore, it was found that 6 cases suffered hypoxic hypoperfusive disease, while 7 were found to have large vessel disease and 36 small vessel disease. In addition to Alzheimer pathology, more than one type of vascular brain pathology was found in the remaining 126 cases. In these cases, diagnosed in accordance with the predominant type of VaD, hypoxic-hypoperfusive lesions were found in 55, large vessel lesions in 50 and small vessel lesions in 110 cases. It should be stressed that 87% of all cases with hypoxic hypoperfusive lesions also had Alzheimer pathology. Cardiovascular and aortic pathologies were more prevalent in small vessel dementia than in the other VaD groups. Clinically diagnosed arterial hypertension was significantly associated with small vessel dementia, but not with hypoxic-hypoperfusive dementia. Cardiovascular symptoms varied considerably in frequency between different dementia groups. VaD is a heterogeneous group regarding lesions caused by different pathophysiological mechanisms and with different combinations of brain pathologies. It is therefore necessary to identify the various types of vascular brain lesions for a correlation with clinical symptoms and for diagnostic purposes in the search for risk factors and therapeutic strategies.     

脑出血急性期合并脑梗死的危险因素分析

目的 探讨脑出血急性期合并脑梗死的危险因素。方法 按照发病后2周内弥散加权成像(diffusion weighted image,DWI)上是否有新的脑梗死灶将125例原发性脑出血患者分为2组,比较临床资料的差异。结果 21例DWI阳性者脑叶出血发生率、颅内大动脉狭窄发生率、平均血肿体积显著高于38例DWI阴性者(P<0.05)。Logistic回归分析显示入院第1 d平均动脉压降低幅度(OR=7.384,P<0.001)、脑叶出血(OR=3.124,P=0.021)及颅内大动脉狭窄(OR=5.044,P=0.027)与脑出血急性期合并新发脑梗死灶呈正相关。结论 平均动脉压降低幅度、脑叶出血、颅内大动脉狭窄可增加脑出血急性期合并急性脑梗死的风险。     

Glioblastoma presenting as spontaneous intracranial haemorrhage: Case report and review of the literature

Glioblastoma (GB) classically presents with symptoms of raised intracranial pressure and gradual progressive neurological deficits. An acute presentation, with intracerebral haemorrhage (ICH) and rapid clinical deterioration, occurs infrequently. Contemporary imaging modalities do not reliably reflect underlying mass lesions in parenchymal brain haemorrhage at first presentation. We report a delayed diagnosis of GB in a 21-year-old patient presenting with spontaneous ICH and a negative initial neurovascular workup. A comprehensive literature review was performed to investigate the incidence of malignant aetiology for spontaneous ICH in young adults, and to underscore the importance of early utilisation of diagnostic magnetic resonance imaging (MRI) in such cases.     

破裂动静脉畸形脑出血量相关因素分析

目的筛选与脑动静脉畸形(brain arteriovenous malformation,BAVM)破裂后出血量相关的因素,为治疗策略制定提供参考。方法回顾性分析2014年1月至2016年6月就诊于中南大学湘雅医院神经外科的破裂BAVM患者,采用改良Rankin量表评价出血后的预后,应用线性回归筛选与出血量相关的因素。结果入组106例患者,26例病变位于后颅窝,57例位于脑室周围。后颅窝、非后颅窝BAVM平均出血量分别为8.81±5.12ml及15.00±10.00ml,脑室周围、非脑室周围BAVM平均出血量分别为15.28±8.78ml及10.00±14.00ml,多因素线性回归提示后颅窝(P=0.002)、脑室周围(P=0.04)病变与出血量相关联,卡方检验提示后颅窝(P=0.041)及脑室周围(P=0.042)病变出血后预后更差。结论脑室周围BAVM破裂出血量较多,后颅窝病变破裂出血量较少,两者出血后预后均更差,可用于指导未破裂患者治疗的选择。     

Vaskuläre Demenz

The term vascular dementia refers to dementia syndromes which are caused by hypoxic-ischaemic brain lesions. Lesions found in vascular dementia such as complete and incomplete infarctions, selective necroses, and others are nonspecific. The characteristics and severity of the clinical syndrome are determined by the size and topography of the ischaemic lesions. Among others, age and pre-existing brain atrophy are risk factors for the development of dementia based on vascular lesions. There is a high comorbidity of Alzheimer's disease and vascular dementia. It can be presumed that ischaemic lesions and Alzheimer-like pathological changes exert additive effects in the manifestation of the clinical dementia syndrome. The diagnostic process follows three steps: 1. presence of a dementia syndrome, 2. presence of cerebrovascular disease, 3. evidence for a relationship between 1 and 2. Present diagnostic criteria, such as "International Classification of Diseases" (ICD-10), "National Institute of Neurological Disorders," "Stroke-Associated Internationale pour la Reserche et l'Enseignement en Neurosciences" (NINDS-AIREN), and "Alzheimer's Disease Diagnostic and Treatment Centers" (ADDTC) describe differing constellations and show little congruence. Estimates of the prevalence depend highly on the set of criteria used. Hence, they differ considerably.     

Role of functional brain imaging in the evaluation of vascular dementia

There are various types of underlying damage to tissue and vessels in vascular dementia, including (1) single or multiple infarcts that involve association and limbic cortices, (2) small subcortical infarcts disrupting cortico-subcortical circuits, and (3) white matter lesions. The clinical picture of vascular dementia varies, and the role of functional brain imaging of cerebral blood flow and metabolism would be expected to be different among subtypes of vascular dementia. The role and value of functional brain imaging is limited for cortical infarcts; it is very valuable in assessing the impact on cortical function for small subcortical infarcts; and it is probably useful for evaluating white matter lesions, but this needs to be determined in further studies. At least in research of vascular dementia, functional brain imaging criteria should be included for proper patient selection. Careful studies using functional imaging tools in a well-characterized patient population will be needed.     

Vascular-ischemic dementia: an update

Both the clinical criteria and morphologic substrates of dementia resulting from cerebrovascular disease and its relation to Alzheimer disease and other age-related brain changes are controversial. In clinical and autopsy studies in the Western world the prevalence of vascular-ischemic dementia (VID) is around 7-10%, while vascular cognitive impairment without dementia is much more frequent and the risk of poststroke dementia is increased in patients with prestroke cognitive decline. In contrast to previous suggestions that VID was largely the result of large hemispheral infarcts, according to recent studies, it is most commonly associated with widespread small ischemic or vascular lesions (microinfarcts, lacunes) throughout the CNS with predominant subcortical lesions in the basal ganglia and white matter or in strategically important brain regions (thalamus, hippocampus). The lesion pattern of rare "pure" VID, which is related to arteriolosclerotic and hypertensive microangiopathy, differs from that in mixed type dementia (Alzheimer disease and cerebrovascular lesions) that more often shows larger hemispheral infarcts. Another form of VID that is not infrequent in very old subjects is hippocampal sclerosis, a selective damage to the hippocampus that is often accompanied by multiple other cerebrovascular lesions. Both, mild Alzheimer type pathology and small vessel disease-associated subcortical vascular pathology appear to be common and may interact in causing cognitive decline, but the impact of cerebrovascular lesions on cognitive impairment and dementia needs to be further elucidated.     

血管性痴呆和血管性认知障碍的临床研究进展

血管性认知障碍和痴呆是认知障碍和痴呆领域以及脑血管病领域研究方面的交叉点。本文综述了血管性痴呆和认知障碍的定义、诊断标准和药物治疗进展。在诊断方面重点介绍了血管性痴呆各个亚型的临床特点。在治疗方面重点介绍了血管性痴呆和认知障碍的胆碱能递质代谢障碍以及胆碱酯酶抑制剂治疗的进展。     

Carotid Plaques and Multiple Brain Infarctions

Cerebral ischemic lesions sometimes are clinically characterized by major cognitive impairment such as vascular dementia. Among the quantifiable factors able to cause focal and/or diffuse ischemic lesions, carotid atherothrombotic plaques represent possible "foci" of embolism that lead to cortical and/or subcortical infarcts. The aim of the present study was to investigate the qualitative and quantitative aspects of carotid plaques in a group of patients affected by vascular dementia and a group of patients affected by multiple brain infarctions, in order to verify whether significant differences can be detected. These data point out the importance of plaque composition and morphology in the pathogenesis of brain infarction leading to dementia.     

Brain hypoperfusion: a critical factor in vascular dementia

Subcortical ischemic vascular dementia is a relatively common form of dementia. Anatomical changes of ageing in the brain arteries predispose the elderly to the effects of hypotension. Depending on their circulatory pattern, particular regions of the brain are susceptible to ischemic hypoperfusive lesions. These regions include the periventricular white matter, basal ganglia, and hippocampus. Interruption of prefrontal-basal ganglia circuits important for cognition and memory may result from these lesions. Hypotension and hypoperfusion explain the high risk for the development of cognitive impairment and vascular dementia in older patients affected by orthostatic hypotension, congestive heart failure, as well as in those undergoing surgical procedures such as hip and knee replacement and coronary artery bypass graft (CABG). Recognition of the susceptibility of elderly subjects to cerebral lesions induced by hypoperfusion should result in appropriate preventive measures and better treatment.     

脑出血大鼠脑红蛋白表达与脑含水量变化

目的：观察脑出血大鼠脑组织内脑红蛋白（Ngb）的表达,探讨其与脑出血后脑水肿之间的关系。方法：将大鼠随机分为3组：正常对照组,假手术组和脑出血组。脑出血组和假手术组动物在模型建立后1、6、24、48、72h5个时间点各随机分为5个亚组。采用立体定向技术将自体血注入大鼠尾状核建立脑出血模型（假手术组注入生理盐水）,用干湿重法测定脑出血后脑含水量的变化,用Western blot检测脑出血后不同时间脑组织内Ngb的表达。结果：与假手术组或正常对照组比较,脑出血组1h时血肿周围脑组织内Ngb表达开始增高（P〈0.05）,24h时脑含水量开始升高（P〈0.05）,二者均在48h时达到高峰并持续至72h（P〈0.01）。结论：脑出血后脑组织内Ngb表达上调。脑出血后Ngb表达水平的变化与脑水肿的发生、发展在时间上不完全同步。     

脑出血大鼠血肿周围脑组织白细胞和凋亡细胞变化及其与脑组织含水量的关系

目的 探讨脑出血大鼠血肿周围脑组织白细胞和凋亡细胞变化及其与脑组织含水量的关系.方法 48只大鼠采用自体不凝血注入法制备脑出血模型,随机分为8组:假手术组、脑出血6h组、脑出血12h组、脑出血24h组、脑出血48 h组、脑出血72 h组、脑出血1周组和脑出血2周组.分别在相应时间点断头取脑,进行脑组织含水量测定和HE染...     

Diagnosis and management of vascular cognitive impairment and dementia

Vascular dementias (VaDs) are the second most common cause of dementia. Cerebrovascular disease (CVD) and stroke relates to high risk of cognitive impairment, but also relate to Alzheimer's disease (AD): Vascular cognitive impairment (VCI) and dementias extend beyond the traditional multi-infarct dementia. Pathophysiology of VaD incorporates interactions between vascular etiologies (CVD and vascular risk-factors), changes in the brain (infarcts, white matter lesions, atrophy), host factors (age, education) and cognition. Variation in defining the cognitive syndrome, in vascular etiologies, and allowable brain changes in current criteria have resulted in variable estimates of prevalence, of groups of subjects, and of the types and distribution of putative causal brain lesions. Should new criteria be developed? Ideally in constructing new criteria the diagnostic elements should be tested with prospective studies with clinical-pathological correlation: replace dogma with data. Meanwhile focus on more homogenous subtypes of VaD, and on imaging criteria could be a solution. Subcortical ischemic vascular disease and dementia (SIVD) incorporate small vessel disease as the chief vascular etiology, lacunar infarct and ischaemic white matter lesions as primary type of brain lesions, subcortical location as the primary location of lesions, and subcortical syndrome as the primary clinical manifestation. It incorporates two clinical entities "Binswanger's disease" and "the lacunar state". AD with VaD (mixed dementia) has been underestimated as a prevalent cause in the older population. In addition to simple co-existence, VaD and AD have closer interaction: several vascular risk factors and vascular brain changes relate to clinical manifestation of AD, and they share also common pathogenetic mechanisms. Vascular cognitive impairment (VCI) is a category aiming to replace the "Alzhemerized" dementia concept in the setting of CVD, and substitute it with a spectrum that includes subtle cognitive deficits of vascular origin, post-stroke dementia, and the complex group of the vascular dementias. As far there is no standard treatment for VaDs, and still little is known on the primary prevention (brain at risk for CVD) and secondary prevention (CVD brain at risk for VCI/VaD). There is no standard symptomatic treatment for VaD. Recently symptomatic cholinergic treatment has shown promise in AD with VaD, as well as probable VaD. Future focus should be directed to the distinct etiological and pathological factors: the vascular and the AD burden of the brain.     

Unexpectedly low prevalence of intracerebral hemorrhages in sporadic cerebral amyloid angiopathy

In a retrospective study of a consecutive autopsy series of 2060 elderly subjects (mean age 78.5 ± 6.8 SD years), sporadic cerebral amyloid angiopathy (CAA) of various degrees was detected in 73.2% and in 98.5% of autopsy-confirmed cases of typical (plaque and tangle) Alzheimer disease (AD). Spontaneous (non-traumatic) intracerebral hemorrhages (ICH) (excluding microbleeds) were seen in 5.6% of the total cohort and in 7.2% of definite AD cases; CAA was found in 49% of brains without and in 48.7% with ICH which was not significantly different. The latter groups showed a significantly higher frequency of severe degrees of CAA than those without ICH (80.4 vs 30.9%, p < 0.001). Patients with CAA were older than those without CAA, showing a higher frequency of clinical dementia and pathologically confirmed AD, but signs of hypertension (history and/or autopsy) were seen in 41 and 33.6% of these cases, respectively, compared to 70–75% in patients with non-CAA related ICHs. CAA-related ICH much more frequently involved cerebral lobes or hemispheres, while non-CAA related lesions were more often located in basal ganglia and brainstem. The data of a lower prevalence of CAA in cases without than with ICH, but a similar prevalence of ICH with and without CAA do not support the concept that CAA represents the most evident risk factor for ICH in the aged. While severe degrees of CAA were indeed associated with ICH, the general prevalence of large ICH in this autopsy cohort was much higher in cases without CAA, probably due to other risk factors including hypertension, which was documented in around 40% of cases with CAA-related ICH. APOE ε3/4 and ε4/4 were significantly more frequent in AD (n = 163) than in age-matched controls (n = 47) and were associated with more severe degrees of CAA, but no general genotyping in ICHs with and without CAA was performed. Hence, the role of APOE in the pathogenesis of ICH with and without CAA needs further elucidation.     

Vascular cognitive deterioration and stroke

Vascular cognitive impairment, the recent modification of the terminology related to vascular burden of the brain, reflects the all-encompassing effects of vascular disease or lesions on cognition. It incorporates the complex interactions between vascular aetiologies, risk factors and cellular changes within the brain and cognition. The concept covers the frequent poststroke cognitive impairment and dementia, as well as cerebrovascular disease (CVD) as the second most common factor related to dementia. CVD as well as vascular risk factors including arterial hypertension, history of high cholesterol, diabetes or forms of heart disease are independently associated with an increased risk of cognitive impairment and dementia. Traditional vascular risk factors and stroke are also independent factors for the clinical presentation of Alzheimer's disease (AD). In addition to these vascular factors, CVD/strokes, infarcts and white-matter lesions may trigger and modify the progression of AD as the most common cause of neurodegenerative dementia. The main subtypes of previously defined vascular dementia (VaD) include the cortical VaD or multi-infarct dementia also referred as poststroke VaD, subcortical ischaemic vascular disease and dementia or small-vessel dementia and strategic-infarct dementia. Whilst CVD is preventable and treatable, it is clearly a major factor in the prevalence of cognitive impairment in the elderly worldwide.     

中风后癫痫59例分析

对641例中风患者追踪观察1～3年,结果59例出现癫痫发作,中风后癫痫发生率为9.20％;脑出血与脑梗塞癫痫发生率间比较无已著差异(P>0.05);皮层损害者癫痫发生率显著高于皮层下损害者(P<0.01);脑出血继发癫痫发作多属早期发作(8/11),而脑梗塞多属迟发性癫痫发作(40/48)(P<0.01);早期癫痫发作需长期服抗癫痫药控制者显著低于迟发性癫痫发作(P<0.01)。提示:病损波及皮层是重要的致痫因素;早期发作与迟发性癫痫发作的发病机理不同,故表现出治疗与转归不同;迟发性癫痫尤其病灶波及皮层者长期规则服抗癫痫药是必要的。     

大鼠脑出血早期应用他莫西芬的治疗作用

目的:本研究探讨大鼠实验性脑出血（ICH）早期应用不同剂量他莫西芬（Tam）对脑损伤的保护作用。方法:雄性SD大鼠56只,予右侧基底节注射100μL自体动脉血制作ICH模型,并分为3大组。①24h脑水含量及病理观察组（各亚组均n=6）:大鼠在ICH后2 h分别接受不同剂量Tam(Tam 2.5 mg·kg^-1组、Tam 5 mg·kg^-1组)和4%DMSO生理盐水（24 h对照组）腹腔注射,24 h后处死进行脑水含量及病理观察。②72 h脑水含量观察组（各亚组均n=6）:大鼠在ICH后2h和24h分别接受不同剂量Tam(72h Tam2.5mg·kg^-1+2.5mg·kg^-1组、72hTam2.5mg.kg^-1+5mg·kg^-1组、72h Tam 5mg.kg^-1+5mg·kg^-1组)和4%DMSO生理盐水（72 h对照组）腹腔注射,于术后72 h处死测量脑水含量。③28 d影像学及病理学观察组:大鼠在ICH后2和24h分别2次给予tam(28d Tam 5mg.kg^-1+5mg,kg^-1组)（n=6）,4%DMSO生理盐水（28 d对照组）（n=8）腹腔注射,分别在术后1、7、14和28d随访MRI和行为学变化,并在第28天处死进行组织学检查。结果:Tam5 mg·kg^-1能明显减轻ICH后3 d时脑水肿（P<0.05）,改善术后行为学评分（P<0.05）,并能明显减轻ICH术后28 d同侧尾状核的脑萎缩（P<0.01）,但MRI提示2例大鼠出现幕上脑室异常扩大。结论:Tam作为选择性雌激素受体调节剂,在ICH后有明显的神经保护作用,但发生了脑积水的不良反应,需要进一步的研究。     

Subcortical ischemic vascular disease and dementia

Subcortical ischemic vascular disease and dementia (SIVD) incorporate small vessel disease as the chief vascular etiology, lacunar infarct and ischemic white-matter lesions (WMLs) as primary type of brain lesions, subcortical location as the primary location of lesions, and subcortical syndrome as the primary clinical manifestation. It incorporates two clinical entities: Binswanger's syndrome and the lacunar state. Patients with SIVD present with extensive white-matter lesions and multiple lacunae on neuroimaging. SIVD is expected to be a more homogenous subtype of vascular cognitive impairment and dementia. Recently modified NINDS-AIREN research criteria for SIVD have been proposed. Further empirical research is needed to refine the syndrome and stages and validate the brain imaging criteria, as well as to detail the natural history and outcomes of SIVD.     

Lack of Aquaporin 9 Reduces Brain Angiogenesis and Exaggerates Neuronal Loss in the Hippocampus Following Intracranial Hemorrhage in Mice

Intracranial hemorrhage (ICH) is a common subtype of stroke with high morbidity and mortality. However, few clinical therapies that can reduce ICH-induced brain injury and promote the recovery outcome in ICH patients are available to improve the recovery from ICH. Given that aquaporin 9 (AQP9) plays a critical role in brain edema after ischemic stroke and traumatic brain injury and is involved in the regulation of angiogenesis, we examined the role of AQP9 in preventing neuronal loss and in neovascularization in the dorsal hippocampus (DH) after ICH. We found that intra-DH collagenase-induced ICH increased AQP9 protein levels in the hippocampus, which was associated with behavioral deficits in wild-type mice. However, ICH robustly enhanced behavioral deficits in the AQP9-null mice, as compared with the wild-type mice. Furthermore, neovascularization and proliferation of brain microvascular endothelial cells following ICH were severely impaired in the AQP9-null mice, as compared with the wild-type mice. Finally, hippocampal neuronal loss following ICH became severer in the AQP9-null mice, relative to the wild-type mice. Taken together, our findings indicated that AQP9 in the brain may play a compensatory role in response to ICH, promote brain angiogenesis, and prevent subsequent neuronal death, thus preventing the deterioration of neurological outcome of ICH.