Type and extent of hemispheric brain infarctions and clinical outcome in early and delayed middle cerebral artery recanalization.

We evaluated the influence of time of recanalization or degree of initial leptomeningeal collateral blood flow in cardioembolic or arterio-arterial middle cerebral artery (MCA) occlusion on infarct size and clinical outcome in a series of 34 consecutive acute stroke patients with main stem (N = 31) or major branch (N = 3) occlusions using CT, initial cerebral arteriography (N = 21), repetitive close-meshed transcranial Doppler ultrasonography, and a neurologic stroke scale. We treated 15 patients with tissue plasminogen activator intravenously within the first 6 hours. The type and size of infarction depended on the location of the occluding lesions within the MCA trunk. Proximal MCA occlusion always led to infarction involving the striatum and internal capsule. Sixty-five percent of patients showed recanalization of the occluded MCA within 1 week. Following MCA recanalization, hyperperfusion was present in 38 to 44% of cases. There was a marginally significant relation between size of infarction on CT and recanalization time within the first 24 hours. The more rapidly recanalization occurred, the smaller the size of the infarct. When recanalization time was greater than 8 hours, the lesions always extended to the cortex. An additional good leptomeningeal collateral blood flow significantly reduced the size of the infarct and improved clinical outcome after 17 days and after 10 months. Early recanalization of embolic MCA occlusions within up to 8 hours, in conjunction with good transcortical collateralization, has a favorable impact on infarct size and outcome and may constitute the therapeutic window of opportunity.     

Dynamics of regional distribution of ischemic lesions in middle cerebral artery trunk occlusion relates to collateral circulation

We describe the regional distribution of acute perfusion, diffusion, and final infarct lesions in middle cerebral artery (MCA) trunk occlusion. A total of 31 patients with acute ischemic stroke and MCA trunk occlusion were studied by multiparametric magnetic resonance imaging. Probabilistic maps of lesion distribution were generated. The probability of initial and final infarcts was highest in the central MCA region with decreasing probability toward the periphery where the probability of the tissue at risk of infarction to be saved was highest. The probability of brain regions being involved in acute diffusion lesions and evolving into or escaping from the final infarct relates to the anatomy of arterial blood supply.     

心房颤动引起心源性脑栓塞颅内梗死灶空间分布特点

目的：探讨心房颤动引起心源性脑栓塞颅内梗死灶空间分布特点。方法：回顾性分析66例由心房颤动引起心源性脑栓塞患者早期弥散加权成像（DWI）的特征。结果：66例患者中有1例患者DWI上未见病灶,65例患者DWI上可见本次责任病灶。多发梗死灶患者有21／65例,占32．31％;双侧前循环供血区同时梗死7／21例,占多发脑梗死灶患者的33．33％;45例单独前循环供血区梗死患者中,左侧前循环供血区梗死23／45例（51．11％）,右侧前循环供血区梗死15／45例（33．33％）,脑栓塞以左侧居多;前循环供血区中大脑中动脉（MCA）供血区发生栓塞的概率最大（35／45例,77．78％）,35例大脑MCA供血区梗死患者中,皮质下梗死[9／35例（25．71％）]和皮质-皮质下梗死[22／35例（62．86％）1的患者例数明显多于皮质区梗死[4／35例（11．43％）]患者。结论：心房颤动引起心源性脑栓塞的脑内病灶左侧脑多见,大脑中动脉更易发生,皮质下和皮质-皮质下梗死多于皮质区梗死。     

Modified permanent middle cerebral artery occlusion rat model aiming to reduce variability in infarct size

In animal cerebral infarct experiments, the most important aspect is to produce consistent infarct size and localization. In an attempt to improve the conventional middle cerebral artery (MCA) coagulation technique, we developed a new animal model using a microclip to reduce variability in infarct size. Male Sprague-Dawley rats were subjected to right MCA occlusion. The animals were divided into two groups; conventional MCA occlusion group (Group 1; n = 9) and modified clip occlusion group (Group 2; n = 9). In Group 2, the proximal portion of MCA was occluded by applying a small clip just proximal to the olfactory nerve, and the MCA from the clipped position to the position just proximal to the level of the inferior cerebral vein was electrocoagulated using a bipolar diathermy in the same manner as in Group 1. In other words, the only difference between these two groups was the manner of occlusion of the most proximal portion of the MCA. Rats were killed 24 hours after the stroke-inducing surgery, and infarct volume was determined by an image analysis program following staining with 2,3,5-triphenyltetrazolium chloride. The cortical infarct volumes were 51.0 +/- 13.8% in Group 1 and 46.3 +/- 6.2% in Group 2. The scattering of cortical infarct volume was significantly small in Group 2 (p=0.0176). The differences in scattering of striatal and total infarct volumes did not reach statistical significance. The present results demonstrated that the new MCA occlusion model using a clip significantly reduces the variability in cortical infarct volume, solving the problems of the model using coagulation alone. That permanent MCA occlusion model using a clip is an excellent method that produces more consistent and reproducible infarction.     

Traumatic middle cerebral artery occlusion: case report and review of pathogenesis.

Traumatic occlusion of the middle cerebral artery (MCA) is a rare cause of cerebral infarct. We describe a case of MCA occlusion following blunt head trauma. The literature reports some 65 cases of MCA occlusion following non-penetrating blunt trauma to the head. Arterial dissection, cerebral vasospasm and thrombosis have been some of the theories discussed in the pathogenesis of this condition. We review the pathogenesis based on anatomy of the M1 segment.     

人工合成E-选择素治疗大鼠局灶脑缺血再灌注损伤的探讨

目的：探讨新的药物治疗脑缺血再灌注损伤。方法：用人工合成 Ｅ－选择素 ２ｍｇ·ｋｇ－１或 １０ ｍｇ·ｋｇ－１溶解于生理盐水中,静脉注入自发性高血压大鼠永久左侧大脑中动脉／颈总动脉（ＭＣＡ／ＣＣＡ）闭塞或ＭＣＡ／ＣＣＡ闭塞２ｈ后ＣＣＡ再灌注模型中。２４ｈ后,脑梗死体积用计算机扫描计算。结果：在永久性ＭＣＡ／ＣＣＡ闭死组中脑梗死体积没有差别,在ＭＣＡ／ＣＣＡ闭死后ＣＣＡ再灌注组中脑梗死体积有意义地缩小（Ｐ＜０．０１）。结论：Ｅ－选择素能够有效地减少大鼠脑缺血再灌注损伤。     

Bilateral paramedian thalamic infarction with hypothalamic dysfunction

Unilateral thalamic lesions cause transient or permanent behavioral, sensory and oculomotor disturbances; bilateral lesions of thalamus result in more severe and longer lasting symptoms. We present an atypical case of bilateral paramedian thalamic infarct with concomitant hypothalamic dysfunction. The only risk factor of ischaemic stroke found in the patient was a short lasting episode of atrial fibrillation. Bilateral paramedian thalamic infarcts may result from occlusion of one paramedian thalamic artery, which arises from the posterior cerebral artery, either with separated or with a common trunk, thus supplying the thalamus bilaterally. Independently of anatomical variants of thalamus blood supply, the most probable cause of infarct in our patient was unilateral or bilateral occlusion of the posterior cerebral artery by cardioembolism, probably in the course of basilar artery occlusion. Hypothalamic dysfunction may accompany thalamic infarcts; thus hypothalamo-pituitary function should be routinely assessed in bithalamic infarcts.     

大鼠大脑中动脉缺血/再灌注模型中Caspase-3的表达

目的 研究Caspase-3在缺血性脑损伤中的作用，进一步探讨缺血性脑血管病的分子机制。方法 用Belayev改良的Longa线栓法制备大鼠局灶性大脑中动脉(MCA)缺血／再灌注模型，TTC染色观察梗死灶的形成，分别用原位杂交及免疫组化技术检测鼠脑中Caspase-3 mRNA与活性蛋白的表达。结果 缺血2小时再灌注24小时，TTC染色见明显的梗死灶形成，正常脑组织、假手术组及MCAO缺血对侧脑中有少量的Caspase-3 mRNA表达，但活性蛋白几无表达；再灌注24小时后，缺血侧脑中Caspase-3 mRNA表达明显增强，蛋白质活化增多，再灌注48小时进一步增加。结论 细胞凋亡机制参与了缺血后迟发性神经元死亡，Caspase-3在其中起重要作用。     

DWI prediction of symptomatic hemorrhagic transformation in acute MCA infarct

PURPOSE: Symptomatic hemorrhagic transformation is a severe complication of acute ischemic stroke which occurs at a higher frequency after thrombolysis. The present study was designed to analyze whether early DWI can be used for predicting the risk of hemorrhagic transformation with clinical worsening in MCA stroke patients. MATERIALS AND METHODS: Of 28 patients with a middle cerebral artery (MCA) infarct and proven MCA or carotid T occlusion on DWI and MR angiography performed within 14 hours after onset (mean 6.5 +/- 3.5 hours, median 5.2 hours), 4 developed hemorrhagic transformation with clinical worsening, while 24 did not. For the 2 groups, we compared admission NIHSS score, site of arterial occlusion, volume of DWI abnormalities, and several apparent diffusion coefficient (ADC) measurements: ADC(infarct) (mean ADC value of the whole infarct), ADC(core) (peak ADC decrease as calculated in a 57 mm(2) circular ROI, manually centered on the ischemic area with the lowest ADC value on the ADC maps), ADC(superficial) and ADC(deep). Discriminant function analysis was used to determine the most accurate predictors of symptomatic hemorrhagic transformation. RESULTS: The best predictor was the ADC(core) (F=5.34, p=2.9%, cut-off value=300 x 10(-6) mm(2)/s). This monovariate model allowed to correctly classify all 4 patients (ADC(core) 300 x 10(-6) mm(2)/s) with subsequent symptomatic hemorrhage, and 17 of the 24 patients without symptomatic hemmorrhage (ADC(core)>300 x 10(-6) mm(2)/s) (100% sensitivity, 71% specificity). CONCLUSION: Although preliminary, these results suggest that a simple measurement of minimum ADC values within an acute MCA stroke could be useful in targeting those patients with a high risk of severe hemorrhagic transformation.     

Ischemic brain edema following occlusion of the middle cerebral artery in the rat. I: The time courses of the brain water, sodium and potassium contents and blood-brain barrier permeability to 125I-albumin

The present study was undertaken to analyze the roles of brain cations and of the blood-brain barrier (BBB) to albumin in the development of ischemic brain edema. Using the rat middle cerebral artery (MCA) occlusion model, changes in the brain water, sodium, and potassium contents were followed for a period of seven days. The permeability of the BBB to proteins was also followed by 125I-albumin transfer from the blood into the brain. A significant edema developed as early as three hours after MCA occlusion. This progressed rapidly to reach a maximum on the third day, gradually regressing thereafter. The increase in the brain water contents showed a parallel time course to the increase in the sodium and decrease in the potassium contents. A significant increase in the BBB permeability to albumin occurred 72 hours after MCA occlusion. However, there was no correlation between the brain water content and BBB permeability to albumin in the hemispheres studied 72 hours after MCA occlusion. The correlation between the brain water and sodium contents was not clear during the first six hours, but became highly significant thereafter. The data suggest that an increase in the BBB permeability to sodium occurred 12-48 hours after MCA occlusion, which, together with an antecedent intracellular shift of sodium, resulted in a massive influx of water and sodium into the brain. The BBB permeability change to sodium, not to proteins, seems to play a predominant role in the pathogenesis underlying ischemic brain edema.     

Bilateral occlusion of the trunk of the middle cerebral artery. Results of an international randomized trial. The EC/IC Bypass Study Group

Bilateral occlusion of the middle cerebral artery (MCA) trunk theoretically should be a very severe condition, but its actual prognosis has never been studied. Nine of 1,377 patients (7 Asians, 1 Black, 1 Caucasian) from the Cooperative Study of Extracranial/Intracranial Arterial Anastomosis were found to have atherosclerotic bilateral occlusion of the middle cerebral artery (MCA) trunk before entering the trial. Three presented with a stroke followed by a contralateral stroke, two experienced a unilateral stroke, two had a unilateral stroke preceded by ipsilateral TIAs, one had a unilateral stroke preceded by TIAs on both sides and one experienced isolated unilateral TIAs. Retrograde filling to the distal MCA was universally present. During follow-up (mean: 45 months), only one (non-operated) patient had further cerebrovascular events, and ultimately a fatal stroke. One additional patient died of sepsis and one had a silent myocardial infarct. All survivors resumed their previous activities. This study shows that in bilateral MCA trunk occlusion, the long-term prognosis is reasonable in the patients who do not present with a devastating stroke.     

Outcome of acutely ischemic brain tissue in prolonged middle cerebral artery occlusion: a serial positron emission tomography investigation in the baboon.

Thrombolysis within 3 to 6 hours of symptom onset is recommended therapy for acute middle cerebral artery (MCA) stroke, but recent imaging studies in humans suggest that the penumbra may last much longer in some patients. It is therefore important to study the events that take place with occlusions that last longer than 6 hours. Based upon positron emission tomography (PET), the tissue with high oxygen extraction fraction (OEF) is at risk of infarction. In a previous sequential PET study in anesthetized baboons, we documented that when reperfusion was initiated at 6 hours after MCA occlusion, the region with the acutely highest OEF was not incorporated within the final magnetic resonance imaging (MRI)-defined infarct, suggesting reperfusion prevented such demise. In agreement with this hypothesis, we report here using the same sequential PET paradigm with final chronic-stage volume MRI that a 20-hour MCA occlusion resulted in, on average, 36% of the highest OEF area being recruited into the final infarct. We also found that the portion of the highest OEF area that went on to infarct had at the earliest time-point significantly lower cerebral blood flow and cerebral oxygen metabolism (mean reductions relative to unoccluded side, 56% and 32%, respectively) than the portion that did not (41% and 11%, respectively) and that some reperfusion occurred in the latter at second time-point, that is, before recanalization. Thus, apart from duration of occlusion, the fate of the at-risk tissue is predicated by the initial severity of the ischemia as well as by early secondary events such as partial spontaneous reperfusion.     

ME3277, a GPIIb/IIIa antagonist reduces cerebral infarction without enhancing intracranial hemorrhage in photothrombotic occlusion of rabbit middle cerebral artery.

GPIIb/IIIa antagonists are expected to have a beneficial effect on acute cerebral infarction, however, the occurrence of intracranial hemorrhage has not been as widely investigated. A rabbit focal thrombotic occlusion model of the middle cerebral artery was established by creating a photochemical reaction between green light and Rose Bengal. Hemorrhagic transformation was common in the area of cerebral infarction. Using this model, the effect of a GPIIb/IIIa antagonist, ME3277 (low dose, (L); 0.15 mg/kg + 0.125 mg/kg x h, middle dose, (M); 0.3 mg/kg + 0.25 mg/kg x h and high dose, (H); 0.6 mg/kg + 0.5 mg/kg x h), aspirin (20 mg/kg) and sodium ozagrel (thromboxane A2 synthase inhibitor, 1 mg/kg + 2 mg/ kg x h) were evaluated. Drugs were intravenously administrated 30 minutes after the photochemical reaction for 24 hours. Aspirin inhibited the ex vivo platelet aggregation induced by arachidonic acid and collagen but not by adenosine diphosphate (ADP), while sodium ozagrel only inhibited the arachidonic acid-induced aggregation. ME3277 dose-dependently inhibited the platelet aggregation induced by all the inducers (approximately 60% in L, 80% in M, and 90% in H). At 24 hours of middle cerebral artery (MCA) occlusion, infarct volume was significantly reduced by aspirin and each dose of ME3277. These agents improved neurologic deficits, with ME3277 being more potent than aspirin. Sodium ozagrel did not alter the infarct volume nor neurologic deficits. No drug was found to worsen hemorrhage volume despite increasing bleeding time (2-3 fold) in the skin. In this model, the occluded artery was spontaneously recanalized and re-thrombosed frequently. One mechanism by which antiplatelet agents reduced infarct volume was inhibition of rethrombosis of the MCA. These results suggest that treatment with a GPIIb/IIIa antagonist is a useful intervention for acute cerebral infarction prolonging dose bleeding time to 3 times the basal value.     

The cyclooxygenase-2 inhibitor NS-398 ameliorates ischemic brain injury in wild-type mice but not in mice with deletion of the inducible nitric oxide synthase gene.

The authors investigated the role of the prostaglandin-synthesizing enzyme cyclooxygenase-2 (COX-2) in the mechanisms of focal cerebral ischemia and its interaction with inducible nitric oxide synthase (iNOS). Focal cerebral ischemia was produced by permanent occlusion of the middle cerebral artery (MCA) in mice. Infarct volume was measured 96 hours later by computer-assisted planimetry in thionin-stained brain sections. The highly selective COX-2 inhibitor NS398 (20 mg/kg; intraperitoneally), administered twice a day starting 6 hours after MCA occlusion, reduced total infarct volume in C57BL/6 (-23%) and 129/SVeV mice (-21%), and ameliorated the motor deficits produced by MCA occlusion (P < .05). However, NS398 did not influence infarct volume in mice with deletion of the iNOS gene (P > .05). In contrast, the neuronal NOS inhibitor 7-NI (50 mg/kg; intraperitoneally), administered once 5 minutes after MCA occlusion, reduced neocortical infarct volume by 20% in iNOS -/- mice (P < .05). NS398 did not affect arterial pressure, resting CBF or the CBF reactivity to hypercapnia in anesthetized iNOS null mice (P > .05). The data suggest that COX-2 reaction products, in mouse as in rat, contribute to ischemic brain injury. However, the failure of NS398 to reduce infarct volume in iNOS null mice suggests that iNOS-derived NO is required for the deleterious effects of COX-2 to occur. Thus, COX-2 reaction products may be another mechanism by which iNOS-derived NO contributes to ischemic brain injury.     

症状性大脑中动脉不同部位闭塞的临床和影像特征

目的 分析单侧大脑中动脉闭塞(MCAO)的脑梗死患者的临床和影像学特征,并探讨不同部位MCAO的脑梗死发病机制及出血转化的相关因素.方法 选取MCAO急性脑梗死患者159例,根据闭塞部位分为近端MCAO组和远端MCAO组,比较两组临床和影像学特征,采用多因素Logistics回归分析不同部位MCAO出血转化的独立危险因...     

A case of cardiogenic cerebral embolism with successful recanalization: apparent diffusion coefficient analysis for prediction of reversible cerebral ischemia]

A 54-year-old woman complaining of left hemiplegia was transferred to our hospital. Computed tomography on admission demonstrated normal. Electrocardiogram showed atrial fibrillation. Cerebral blood flow (CBF) was decreased in both the cortex and the perforator territory of the right middle cerebral artery (MCA), whereas the apparent diffusion coefficient (ADC) in the cortex was normal. Digital subtraction angiography (DSA) revealed an occlusion of the right MCA (M 1 proximal) with collateral flow from the right anterior cerebral artery (ACA) to the territory of the right MCA. After intra-arterial injection of tissue-plasminogen activator (t-PA), DSA showed partial recanalization, and the symptoms of the patient improved considerably. Five days after that, the patient deteriorated again and showed disturbance of consciousness and left hemiplegia. In this episode, both CBF and ADC in the cortex of the right MCA were decreased. DSA revealed an occlusion of the right internal carotid artery (ICA) and collateral flow from the right ACA to the territory of the right MCA disappeared. After intra-arterial injection of t-PA, DSA showed partial recanalization with collateral flow from the right ACA, and the symptoms of the patient improved. DSA 5 weeks after onset showed complete recanalization of both the right MCA and the ICA. The patient was diagnosed as both mitral and aortic stenosis and regurgitation (MSR + ASR) and underwent an operation for both mitral and aortic value replacement. She was discharged with no neurological deficit 4 months after onset. ADC analysis is especially useful for the prediction of reversible ischemic damage and the prevention of hemorrhagic transformation and fatal edema in acute ischemic stroke.     

Isolation of speech area from focal brain ischemia

A patient with atrial fibrillation and internal carotid artery occlusion developed mixed transcortical aphasia. The CT scan showed two recent distinct infarcts in the dominant hemisphere, one in the precentral artery area (pial artery infarct) and one in the borderzone area between the posterior and middle cerebral arteries territories (watershed infarct). The perisylvian speech areas were spared, but probably disconnected from other areas by the infarcts. The syndrome of isolation of speech area may be caused by vascular conditions which are able to produce simultaneous pial artery and watershed infarcts, and is not necessarily related to more extensive processes of the brain.     

Statin Use is Independently Associated with Smaller Infarct Volume in Nonlacunar MCA Territory Stroke

BACKGROUND: Studies have shown an association between HMG-CoA reductase inhibitors (statins) and improved stroke outcomes, possibly secondary to neuroprotective properties. OBJECTIVE: To assess whether patients taking statins prior to ischemic stroke have smaller infarcts on magnetic resonance imaging (MRI), adjusting for other relevant clinical factors. DESIGN: We retrospectively reviewed the Cleveland Clinic Foundation (CCF) Neurology Inpatient Database from June 2002 through June 2004. Demographics, medications, stroke subtype, diffusion-weighted imaging (DWI) infarct volume, admission NIHSS, and hours to MRI were collected. Patients with a nonlacunar middle cerebral artery (MCA) territory infarct and MRI less than 48 hours from symptom onset were included (n= 143). A multivariable linear regression model was constructed to determine independent predictors of smaller infarct volume. RESULTS: A total of 143 patients were studied, including 38 patients taking statins at the time of their stroke. In univariate analysis, patients using statins were significantly more likely to have a history of hyperlipidemia, atrial fibrillation, and coronary artery disease and to be using coumadin, antiplatelet drugs, and angiotensin-converting enzyme inhibitors. Patients on statins had a tendency toward smaller infarcts in univariate analysis (median 25.4 cm(3) vs. 15.5 cm(3), P= 0.054). In multivariable linear regression analysis statin use, patient age, and TIA within the prior 4 weeks were independently associated with smaller DWI volumes; vessel occlusion on vascular imaging, and cardioembolic stroke subtype with larger infarct size. CONCLUSIONS: Statin use prior to the onset of nonlacunar MCA infarction was associated with a smaller infarct volume independent of other factors. Further studies utilizing both clinical and radiologic outcomes will be required to confirm these findings.     

Focal ischemic preconditioning induces rapid tolerance to middle cerebral artery occlusion in mice.

In a process called ischemic preconditioning, a brief, sublethal ischemic insult protects tissue from subsequent, more severe injury. There have been no reports of rapidly induced ischemic preconditioning. The authors sought to develop a model of cerebral ischemic preconditioning in the mouse that can be applied to transgenic and knockout animals. They found that brief middle cerebral artery (MCA) occlusion only minutes before a severe ischemic insult can induce protection from that insult. Here the investigators describe a mouse model of preconditioning using intraluminal MCA occlusion as both the conditioning and the test stimulus. One or three 5-minute episodes of ischemia given 30 minutes before MCA occlusion for 1 or 24 hours (permanent occlusion) confer significant protection as assessed by infarct volume measurements 24 hours later.     

Factors affecting haemorrhagic transformation in middle cerebral artery infarctions.

OBJECTIVE: Haemorrhagic transformation (HT) affects treatment and prognosis in patients with acute ischaemic stroke. The factors affecting haemorrhagic transformation in infarcts due to occlusion of middle cerebral artery (MCA) stem or branch were investigated. MATERIALS AND METHODS: Of 412 patients who were followed in our clinic between January 2001 and December 2001 with acute ischaemic stroke, 86 patients with occlusion in MCA stem or branch were enrolled in this study. These patients were divided into 2 groups, those with HT (n = 35) and without HT (n = 51). Age, sex, systemic arterial hypertension, diabetes mellitus, blood glucose level in the acute period, renal and liver function tests, systolic and diastolic arterial blood pressure in the acute period, previous cerebrovascular disease, leukoaraiosis, modified Rankin Disability Score (mRDS) and stroke subtype were evaluated. RESULTS: High blood glucose level in the acute period and presence of leukoaraiosis on cranial computerized (CCT) tomography were detected as risk factors in development of HT. HT was seen more frequently in MCA stem infarction than branch infarction. mRDS were worse in the group with HT. In multivariate analysis, there were independent relationships between mean blood glucose level on admission, mRDS, presence of diabetes mellitus, and MCA stem infarction and development of haemorrhagic transformation in patients with MCA territorial infarction.