超声助溶治疗急性大脑中动脉闭塞性脑梗死的临床研究

目的 探讨经颅多普勒超声联合rt-PA静脉溶栓治疗急性大脑中动脉闭塞性脑梗死的有效性及安全性,同时探索超声助溶的合适时间。方法 急性大脑中动脉闭塞性脑梗死患者73例,所有患者均行rt-PA静脉溶栓治疗,并按照超声助溶的时间随机分为3组,2 h超声助溶组24例、1.5 h超声助溶组25例和对照组24例。采用脑缺血溶栓血流分级判断血管再通情况,用美国国立卫生研究院卒中量表评分评估患者神经功能缺损程度,以溶栓后有无症状性颅内出血来评定其安全性,溶栓后3个月用改良Rankin量表及Barthel指数评分评定远期预后。结果 2 h助溶组与1.5 h助溶组治疗后2 h血管再通率以及治疗后3个月BI值显著高于对照组(P<0.05),而2助溶组之间血管再通率无明显差异(P>0.05); 2 h助溶组与1.5 h助溶组治疗24 h后NIHSS评分、治疗后3个月mRS评分显著低于对照组(P<0.05),而2助溶组之间无明显差异(P>0.05); 3组患者治疗后24 h均未出现症状性颅内出血。结论 超声助溶治疗急性大脑中动脉闭塞性脑梗死安全、有效、远期预后良好,而针对于助溶时间选择上建议将时间缩短至1.5 h。     

Allopurinol and dimethylthiourea reduce brain infarction following middle cerebral artery occlusion in rats

Free radicals have been shown to play an important role in ischemia-reperfusion injury in several organ systems; however, the role of free radicals in central nervous system ischemia has been less well studied. Many potential free radical-generating systems exist. The primary products of these reactions, superoxide and hydrogen peroxide, may combine to produce hydroxyl radicals. Of the many potential sources of free radical generation, the enzyme xanthine oxidase has been shown to be important in ischemia in noncerebral tissue. We investigated the effect of the hydroxyl radical scavenger dimethylthiourea and the xanthine oxidase inhibitor allopurinol on infarct volume in a model of continuous partial ischemia. Male Sprague-Dawley rats were treated with dimethylthiourea or allopurinol before middle cerebral artery occlusion. Infarct volume was measured by triphenyltetrazolium chloride staining of brains removed 3 or 24 hours after occlusion. Stroke volume was reduced by 30% after dimethylthiourea treatment and by 32-35% after allopurinol treatment. At 24 hours after stroke, cortical tissue was more effectively protected than caudate tissue with both agents. Pretreatment with dimethylthiourea and allopurinol also significantly reduced cerebral edema formation and improved blood-brain barrier function as measured by fluorescein uptake. Our results imply that hydroxyl radicals are important in tissue injury secondary to partial cerebral ischemia and that xanthine oxidase may be the primary source of these radicals.     

Outcome following occlusion of the middle cerebral artery

Outcome was studied prospectively in 28 consecutive patients with occlusion of the middle cerebral artery (MCA). They comprise a subgroup of 101 consecutive patients with TIA or stroke less than or equal to 75 years of age, admitted within 72 h after the stroke. Cerebral angiography and CT-scan were performed within 1-2 days of admission. CT-scan was repeated 6 months later. Functional status on admission, 3 and 6 months after the stroke was evaluated using the Rankin disability scale (score 1-2: independent of others care, score 3-5: dependent on others care). The degree of hemiparesis was measured using the Medical Research Council's score. Thirteen had infarcts with a diameter less than or equal to 3 cm (mean 2.5 +/- 0.9 cm); 15 had infarcts greater than 3 cm (mean 6.3 +/- 1.4 cm); 10 had trunk occlusions; 18 had branch occlusions. MCA occlusions with large infarcts and severe hemiparesis on admission carried a poor outcome. Eleven (85%) of 13 patients with the case in only 1 (7%) of the 15 with infarcts greater than 3 cm, the remaining 14 (93%) had either died (40%) or were dependent (53%) (p less than 0.00005). Eleven (85%) of 13 patients with mild hemiparesis on admission were independent, while 13 (87%) of 15 with moderate or severe hemiparesis on admission had either died (40%) or were dependent on others' care (47%) 6 months after the stroke (p less than 0.0004). Type of occlusion (branch trunk) was a poor predictor of outcome.     

急性脑梗死患者脑动脉狭窄或闭塞后梗死灶体积的影响因素

目的：探讨急性脑梗死患者脑动脉狭窄或者闭塞后梗死灶体积的影响因素。方法选取2015年1～12月收入我院神经内科的急性脑梗死患者80例为研究对象,采用 mRS 评分判断患者的临床转归情况,采用 ROC 曲线预测患者临床转归梗死灶体积的最佳切点,采用 Logistic 多因素回归模型分析影响梗死灶体积的因素。结果梗死灶体积≤29．23 ml 时,其临床转归的效果较好,且灵敏度及特异度较高,ROC 曲线下面积为0．997。梗死灶体积≤29．23 ml 组和梗死灶体积＞29．23 ml 组患者,在年龄、NIHSS 评分、白细胞数、血清白蛋白、hs － CRP 、GHbA1c 水平及脑白质疏松程度方面比较,差异有统计学意义（P ＜0．05）。 Logistic 多因素分析显示,血清白蛋白是脑动脉狭窄或者闭塞后梗死灶体积＞29．23 ml 的保护因素（P ＜0．05）,GHbA1c 和脑白质疏松程度是危险因素（P ＜0．05）。结论血清白蛋白、GHbA1c 水平和脑白质疏松程度是急性脑梗死患者脑动脉狭窄或者闭塞后梗死灶体积的影响因素。     

Proximal posterior cerebral artery occlusion simulating middle cerebral artery occlusion

We describe 12 cases of acute stroke in which clinical features of proximal posterior cerebral artery occlusion simulated the clinical syndrome of middle cerebral artery occlusion. The majority of patients developed contralateral hemiparesis, homonymous hemianopia, hemispatial neglect, and sensory loss or sensory inattention. All 8 patients with dominant hemisphere lesions were aphasic. Accurate diagnosis in each case was achieved only after a head CT, showing occipital lobe, thalamic, and inferomesial temporal lobe infarction. "Cortical" signs are probably explained by thalamic involvement. Recognition of this syndrome has implications for management and prognosis.     

Parasympathetic denervation of rat pial vessels significantly increases infarction volume following middle cerebral artery occlusion

Studies were undertaken in Long Evans rats to examine the hypothesis that chronic unilateral sectioning of vasodilating nerve fibers (parasympathetic and/or sensory) innervating the circle of Willis increases infarction volume following unilateral branch occlusion of the middle cerebral artery (MCA) combined with temporary (45 min) bilateral common carotid occlusion. Infarct size was measured 24 h after surgical occlusion from seven coronal slices. Infarction volume (mean +/- SD) in sham animals (group A) and surgically naive animals (group B) measured 153 +/- 43 and 131 +/- 38 mm3, respectively. After lesions of both sensory (nasociliary nerve) and parasympathetic efferents at the ethmoidal foramen (group C, combined lesion) or selective lesions of parasympathetic efferents (group D), infarction volume increased [214 +/- 47 mm3 (p less than 0.01) and 209 +/- 46 mm3 (p less than 0.05), respectively]. No increases were detected after cutting the nasociliary nerve alone (group E) or occluding the external ethmoidal artery (group F) [145 +/- 39 mm3 (p greater than 0.05) and 124 +/- 63 mm3 (p greater than 0.05), respectively]. The infarct was predominantly located within cortical gray matter and became enlarged on its superior and inferior aspects after parasympathectomy. Large infarcts were noted whether animals breathed spontaneously (all of the above) or were artificially respired or whether animals were anesthetized with xylazine and ketamine or chloral hydrate. Taken together, these studies suggest a previously unrecognized protective role for autonomic parasympathetic fibers in the pathophysiology of focal cerebral ischemia that is not shared by sensory fibers. The importance of autonomic vasodilating fibers to blood flow in ischemic brain merits further study.     

Physostigmine induced reversal of ischemia following acute middle cerebral artery occlusion in the rat

Cerebral cortical ischemia was induced in anesthetized rats by occlusion of the middle cerebral artery (MCA). Cerebral blood flow (CBF) was measured with the H2 clearance technique in the center and periphery of the ischemic territory. A decrease of CBF to about 50% of pre-occlusion values was observed in both areas. Administration of Physostigmine, a cholinesterase inhibitor, at a dose of 0.15 mg/Kg by intravenous route, induced an increase of CBF in the ischemic cortex. This change in CBF reached 120% of pre-occlusion level in the periphery and 80% of pre-occlusion value in the center of the area of distribution of the occluded artery. Although Physostigmine induced an increase in arterial blood pressure, the cerebral hyperemia observed both in normal and ischemic cortex could still be demonstrated after blockade of the pressor effect by bleeding or Phentolamine administration.     

Posterior cerebral artery infarction from middle cerebral artery infarction

BACKGROUND: While it is known that posterior cerebral artery (PCA) infarction may simulate middle cerebral artery (MCA) infarction, the frequency and localization of this occurrence are unknown. OBJECTIVE: To determine the frequency of PCA infarction mimicking MCA infarction and the territory of the PCA most commonly involved in this simulation. DESIGN: We studied 202 patients with isolated infarction in the PCA admitted to our stroke center to determine the frequency of PCA infarction simulating MCA infarction, the involved PCA territory, and the patterns of clinical presentation. RESULTS: We found 36 patients (17.8%) with PCA ischemic stroke who had clinical features suggesting MCA stroke. The PCA territory most commonly involved was the superficial PCA territory (66.7%), followed by the proximal PCA territory (16.7%) and both the proximal and the superficial PCA territories (16.7%). The principal stroke mechanism was cardioembolic (54.1%) in the superficial PCA territory, lacunar (46.2%) in the proximal PCA territory, and undetermined (40.2%) in both the proximal and the superficial territories. Among the 36 patients, the most common clinical associations were aphasia (13 patients), visuospatial neglect (13 patients), and severe hemiparesis (7 patients). CONCLUSIONS: Posterior cerebral artery infarction simulating MCA infarction is more common than previously thought. Early recognition of the different stroke subtypes in these 2 arteries may allow specific management.     

Regional flow-metabolism couple following middle cerebral artery occlusion in cats

The regional flow-metabolism couple was studied during the recovery period after 1 h of left middle cerebral artery (MCA) occlusion in cats. Local CBF (LCBF) was assessed at the end of ischemia as well as at the end of 4 h of recirculation by the microsphere technique. Local CMRgl (LCMRgl) was measured at the end of the recirculation period with [14C]2-deoxyglucose. Histology was evaluated by light microscopy from coronal brain blocks adjacent to those used for the determination of LCBF and LCMRgl. When LCBF in the central and peripheral MCA territories during the recovery period was between 40 and 115% of the value in sham occlusion studies, LCMRgl was greater than the control level found in the sham studies, and was accompanied by slight histological damage. This finding suggests that anaerobic glycolysis may persist after transient ischemia in spite of the recovery of LCBF to a level that is normally greater than the threshold for the activation of anaerobic glycolysis (less than 40% of the control). Persistent anaerobic glycolysis in the reperfusion period following an ischemic insult may be a sign of early tissue damage. Some of the regions in the peripheral MCA territory with LCBF between 40 and 110% of the levels during the recovery period in the sham studies showed a mild to moderate depression in LCMRgl so that the flow-metabolism ratio remained normal. These regions did not exhibit histological damage. This possible protective mechanism of the tissue in response to ischemia is discussed from the standpoint of the relationship between flow and metabolism.     

Changes in regional cerebral catecholamines following middle cerebral artery occlusion in the rat

Ischemic brain injury affects the content and metabolism of brain monomines. Our aim was to know the time course of changes in regional cerebral catecholamines during focal cerebral ischemia, and whether focal cerebral ischemia may affect the metabolism of catecholamines in distant area of the brain. Methods Fifty-five rats were subjected to occlusion of the middle cerebral artery (MCA) on the olfactory tract, under halothane anesthesia. Fourteen animals were sham-operated group. Animals were decapitated at 1/2, 1,2,3,6,12 and 24 hours post-occlusion (PO), respectively. The brains were removed, and the brain structures dissected out include bilateral corpus striatum, cerebral cortex (MCA territory) and cerebellar hemisphere. Catecholamines were extracted by alumina procedure, and determined by high-performance liquid chromatography with electrochemical detection. Results Dopamine (DA) contents, in ipsilateral corpus striatum and cerebral cortex to the ischemia, decreased at 1 hour PO, and reached, at 6 hours PO, to 40% of control value in corpus striatum and 30% in cerebral cortex, respectively. After 6 hours PO, DA remained low. Norepinephrine (NE) content in the ipsilateral corpus striatum gradually reduced and reached to 60% of control value at 24 hours PO. NE in the ipsilateral cerebral cortex decreased to 50% of control at 1 hour PO, and thereafter remained reduced. In the contralateral corpus striatum and cerebral cortex, either DA or NE showed no significant changes, except 1/2 hour PO. NE contents in bilateral cerebral cortex showed a transient increase at 1/2 hour PO. Cerebellar NE content, bilaterally, reduced slowly to 70% of control at 24 hours PO.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phenylephrine-induced hypertension reduces ischemia following middle cerebral artery occlusion in rats

We studied the influence of phenylephrine-induced hypertension on the area of ischemia during brief middle cerebral artery occlusion. Rats were anesthetized with 1.2 minimal alveolar concentration (MAC) isoflurane, and the middle cerebral artery was occluded via a subtemporal craniectomy. Immediately thereafter, in one group (n = 9) arterial blood pressure was increased 30-35 mm Hg above the preocclusion level by intravenous infusion of phenylephrine. In a second, control, group (n = 10) there was no manipulation of blood pressure. Local cerebral blood flow was determined autoradiographically 15 minutes after occlusion. The areas (expressed as a percentage of the total coronal cross-sectional area) in which local cerebral blood flow decreased to three ranges (0-6 ml/100 g/min [rapid neuronal death probable], 6-15 ml/100 g/min [delayed neuronal death probable], and 15-23 ml/100 g/min [electrophysiologic dysfunction with prolonged survival probable]) were measured. The areas in which local cerebral blood flow decreased to the two more severely ischemic ranges were smaller in the phenylephrine group than in the control group. For example, in the coronal section in the center of the middle cerebral artery distribution, local cerebral blood flow was 0-6 ml/100 g/min in 6.7 +/- 1.4% of the section in normotensive rats but was in that range in only 1.7 +/- 0.6% of the section during phenylephrine-induced hypertension (p less than 0.05). For the 6-15 ml/100 g/min range, the areas were 6.8 +/- 0.8% and 3.8 +/- 0.7%, respectively (p less than 0.05). For the 15-23 ml/100 g/min range, there were no differences between groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Examination of sensorimotor performance following middle cerebral artery occlusion in rats

Middle cerebral artery occlusion (MCAO) in rats is the most commonly used stroke model. Besides the infarct size, assessment of sensorimotor performance has become increasingly important in neuroprotective drug research. However, contradictions exist about procedures for testing functional outcome following MCAO. The aim of the present study was to evaluate a relatively simple set of neurological tests based on the most commonly used scoring systems, and to describe the functional recovery and correlation with the infarct size in rats sacrificed 2 or 14 days after permanent or transient MCAO. The smaller infarct size of rats with transient occlusion was reflected in the neurological scores only during the first 6h. By day 14, no recovery occurred in postural signs, lateral resistance and spontaneous activity, other signs showed different degrees of recovery. Correlation with the infarct size was found only on certain days in gait disturbance, placing reactions, daily body weight and spontaneous activity. According to our observations, the most commonly used sensorimotor tests provide a useful initial screening of functional deficits, but these tests most probably measure deficits caused by infarction of the core area. It is suggested that these tests should be completed by more refined tests when testing a neuroprotective drug which reduces the infarct size in penumbral areas.     

Persistent phosphorylation of synaptic proteins following middle cerebral artery occlusion.

Transient cerebral ischemia following 1 to 2 hours of middle cerebral artery occlusion (MCAO) in the rat leads to infarction, which can be diminished by synaptic transmission modulators, implying aberrant cell signaling in the pathogenetic process. The authors report here changes in the levels of tyrosine phosphorylated proteins (PTyr) and calcium calmodulin kinase II (CaMKII) phosphorylation of Thr 286, in synaptosomal, particulate, and cytosolic fractions of different cortical areas following 1 or 2 hours of MCAO, or 2 hours of MCAO followed by 2 hours of reperfusion. At the end of 2-hour MCAO, PTyr, and in particular the pp180, indicative of NR2A/B subunit, increased in the synaptosomal fraction in less ischemic areas while it decreased in more severe ischemic regions. During reperfusion, phosphorylation increased at least 2-fold in all reperfused areas. During 2 hours of MCAO, the phosphorylation of CaMKII increased 8- to 10-fold in the synaptosomal fraction in all ischemic brain regions. During reperfusion, the phospho-CaMKII levels remained elevated by approximately 300% compared with the contralateral hemisphere (control). There was no increase in phospho-CaMKII in the cytosolic fraction at any time during or following ischemia in any of the brain regions examined. The authors conclude that both tyrosine kinase coupled pathways, as well as CaMKII-mediated cellular processes associated with synaptic activity, are strongly activated during and particularly following MCAO. These results support the hypothesis that aberrant cell signaling may contribute to ischemic cell death and dysfunction, and that selective modulators of cell signaling may be targets for pharmacological intervention against ischemic brain damage.     

Obstructive sleep apnea intensifies stroke severity following middle cerebral artery occlusion

Study objectivesObstructive sleep apnea (OSA) is a sleep disorder caused by transient obstruction of the upper airway and results in intermittent hypoxia, sleep fragmentation, sympathetic nervous system activation, and arousal which can have an adverse effect on cardiovascular disease. It is theorized that OSA might intensify stroke injury. Our goal here was to develop a new model of experimental OSA and test its ability to aggravate behavioral and morphological outcomes following transient brain ischemia/reperfusion.MethodsWe used a 3D printed OSA device to expose C57BL6 mice to 3 h of OSA (obstructive apnea index of 20 events per hour) for three days. These mice were then subjected to ischemia/reperfusion using the middle cerebral artery occlusion model (MCAO) stroke and examined for overall survival, infarct size and neurological scoring.ResultsWe found that OSA transiently decreased respiration and reduced oxygen saturation with bradycardia and tachycardia typical of human responses during apneic events. Brain injury from MCAO was significantly increased by OSA as measured by infarct size and location as well as by intensification of neurological deficits; mortality following MCAO was also increased in OSA animals.ConclusionsOur findings suggest that our new model of OSA alters respiratory and cardiovascular physiological functions and is associated with enhanced ischemia/reperfusion mediated injury in our non-invasive, OSA intensified model of stroke.     

Hydrocephalus following decompressive craniectomy for malignant middle cerebral artery infarction

Objective

The aim of this study was to evaluate the incidence of hydrocephalus and understand the influence of hydrocephalus on the functional outcome of patients undergoing decompressive craniectomy for malignant middle cerebral artery (MCA) infarction.

Methods

We retrospectively analyzed data of consecutive patients who underwent decompressive craniectomy for malignant MCA infarction. Clinical and imaging data were reviewed to confirm the incidence of hydrocephalus and evaluate the impact of hydrocephalus on functional outcome. The functional outcomes of patients were estimated with the Glasgow outcome score at 1 year after stroke onset.

Results

Seventeen patients who received decompressive craniectomy for malignant MCA infarction from January 2003 to December 2006 were enrolled. Persistent hydrocephalus developed in 5 patients. The functional outcomes in these patients were uniformly poor regardless of cerebrospinal fluid diversion surgery. Our data revealed that functional outcome was related to patient age and the duration from infarction to craniectomy.

Conclusions

Persistent hydrocephalus is common in patients who receive decompressive craniectomy for malignant MCA infarction. However, the shunt procedure does not significantly improve the patient's clinical condition. The timing of operation in relation to the functional outcome may be critical.     

Prognosis in middle cerebral artery occlusion

The natural history of MCA occlusion has become increasingly important since the surgical option of EC/IC bypass surgery has been available. The clinical course of 24 patients with angiographically-demonstrated occlusion of the MCA artery was reviewed. Eight patients presented with a major disabling stroke and five of these died during the acute phase of this ischemic event. The remaining 19 patients were followed for a mean of 54.2 months. There were five deaths in follow-up and two of these were due to subsequent strokes. Fourteen patients manifested a benign course: one of these had a further minor stroke and four had TIAs. Altogether, 3 strokes occurred during the follow-up period (2 fatal, 1 minor) and all were in the territory of the artery known to be occluded. Of those patients who survived their presenting ischemic event, 12 (63%) remained completely functional in terms of activities of daily living. MCA occlusion does not necessarily carry a poor prognosis with medial therapy alone and the role of bypass surgery hopefully will be clarified by the ongoing clinically randomized trial.     

Musical hallucinosis following infarction of the right middle cerebral artery

A 44-year-old woman demonstrated a musical hallucinosis four months after a massive infarction in the territory of the right middle cerebral artery. This musical hallucinosis consisting of familiar tunes, was continuous and perceived by both ears. Magnetic Resonance Imaging, middle and late auditory evoked potentials suggested that right Heschl's gyrus and associative areas were imparied. Audiometry demonstrated a low right transmission deafness. The hallucinosis was persistent for seven months and stopped just after hemorrhage of the right ear. This case gives the opportunity to review the different mechanisms responsible for musical hallucinosis.