A pilot study of urokinase therapy in cerebral infarction.

Thirty-one patients with acute cerebral infarction were treated with the thrombolytic agent urokinase for either a single or a double infusion period, each of ten hours. The effects of urokinase therapy administered at dosage rates of 1,200, 1,500 or 1,700 CTA urokinase units per pound of body weight per hour were followed by serial blood coagulation and other biochemical studies. In the dosage used, urokinase produced a prompt sustained increase, 20-fold to 40-fold, of plasma thrombolytic activity with relatively minor disturbance of the blood coagulation system. Nevertheless, hemorrhagic complications occurred in several patients and distinctly favorable therapeutic effects were not observed.     

A model of embolic cerebral ischemia in the rat

Experimental studies of embolic cerebral ischemia using the rat are limited by variability in the location, size, and frequency of lesions produced. A technique is described herein which improves the reliability of an established model. Eight male Sprague-Dawley rats underwent injection of the cervical internal carotid artery with 0.1 ml of 1-h-old fragmented autologous blood clot through an external carotid artery cannula. The pterygopalatine artery was ligated prior to embolization. At killing 2 h after embolization, clot was observed in the proximal middle cerebral and posterior cerebral arteries in all animals. Areas of reduced blood flow at 2 h postembolization were assessed by digital image processing of iodo-[¹⁴C]antipyrine autoradiographic images. No-flow and low-flow areas were measured for each of approximately 25 serial brain sections with a computerized bit-pad. Volumes were calculated and lesions localized by anatomical reconstructions. No animal sustained a hemorrhagic lesion. One animal sustained only a very small area of ischemia in the internal capsule. Of the remaining seven, all had large regions of ischemia in the middle cerebral distribution involving cortex and basal ganglia. Posterior cerebral involvement was observed in six of the seven animals as well. The contralateral hemisphere was unaffected. Volume values could be calculated for primary vascular distributions. Most variability occurred in the pattern of posterior cerebral involvement. The technique described produces a relatively consistent region of ischemia in the middle and posterior cerebral artery distributions in the rat and is a useful model for the study of cerebral ischemia.     

Anticoagulant therapy in recurrent cerebral embolism: a retrospective study in non-valvular atrial fibrillation

Summary For the prevention of recurrent embolic stroke, 23 elderly patients with non-valvular atrial fibrillation (NVAF) were treated with oral anticoagulants (warfarin) during a mean period of 3.8 years. Only one patient suffered recurrent embolism, and another had acute myocardial infarction. There was no cerebral haemorrhage during the treatment. In an untreated control group (from an autopsy series), recurrent embolic strokes occurred in 18 of 70 NVAF patients (26%) during a mean period of 1.3 years. Long-term anticoagulant therapy appears to be effective in the prevention of recurrent embolic stroke in elderly patients with NVAF.     

Electroconvulsive therapy and cerebral computed tomography. A prospective study

Cerebral computed tomography (CT) was performed before and after right-sided electroconvulsive therapy (ECT) in 40 patients aged 26-87 years with major affective disorders. Nine patients with a concomitant definite or possible non-acute organic brain disorder were included. Several patients had long seizure durations, maximum 6.5 min, caused by hyperventilation-induced hypocapnia. Twenty-nine patients received at least 16 treatments (maximum 46). No CT changes occurred following ECT. A questionable dilatation of the left temporal horn in a 69-year-old hypertensive man who recovered completely without side effects after 3 ECT sessions was probably unrelated to the ECT. Provided sufficient oxygenation, even relatively long ECT series and seizures lasting several minutes do not cause any brain damage visible on CT.     

Hemorrhagic cerebral infarct and ulcerative colitis. A case report

We report the occurrence of a cerebral ischemic infarct in a young normotensive woman suffering from ulcerative colitis. One week later, clinical neurological deterioration corresponded with hemorrhagic transformation of the previously ischemic region and white matter edema. Extensive laboratory investigation excluded other possible causes for stroke mechanism and rather supported a cerebral vasculitic process, while significant improvement both on neurological and bowel function was observed under prednisone therapy. This report provides some additional support to the possible association between ulcerative colitis and cerebrovascular complications.     

Hydroxyethyl starch 200/0.5 reduces infarct volume after embolic stroke in rats.

BACKGROUND AND PURPOSE: We evaluated isovolumic hemodilution with hydroxyethyl starch 200/0.5 in a rat model of focal cerebral ischemia. This compound avoids the unfavorable viscosity and erythrocyte aggregation abnormalities of low molecular weight dextran during administration over a period of several days. METHODS: Sprague-Dawley rats, anesthetized with 0.5-1% halothane and 70% N2O, were subjected to silicon cylinder (treated and control groups) or sham (sham group) embolization of the cerebral circulation. Thirty minutes after embolization, the treated group (n = 5) was infused with 11 ml/kg of 10% hydroxyethyl starch 200/0.5, and the control (n = 5) and sham (n = 4) groups were infused with saline for 1 hour. In the treated group, 7.1 ml/kg of blood was withdrawn. After 24 hours, the animals were reanesthetized, and cerebral blood flow was determined with [14C]iodoantipyrine. Alternative brain slices were either incubated with 2,3,5-triphenyltetrazolium chloride for infarct volume determination or frozen for ischemic volume and cerebral blood flow determination using autoradiography. RESULTS: The hematocrit in the treated group was reduced from (mean +/- SEM) 46 +/- 1% to 35 +/- 2% at 1.5 hours (p < 0.01). Cortical blood flow was within the normal range of 115-185 ml/min/100 g, except for the ischemic cortex in the embolized groups, treated and control. The ischemic and infarct volume of the treated group was reduced by 74% (p < 0.05) and 89% (p < 0.05), respectively, from the control group. The treated and sham ischemic and infarct volumes were not statistically different. CONCLUSIONS: These data suggest that hydroxyethyl starch 200/0.5 could be an effective treatment for ischemic stroke when administered early, because it reduces infarct and ischemic volumes from control values to levels indistinguishable from those of the sham group.     

脑微出血相关危险因素回顾性研究

目的探讨与脑血管疾病相关的危险因素中哪些与脑微出血(CMBs)的相关。方法回顾性分析2016年1月至2017年1月在甘肃省人民医院行颅脑MRI磁敏感加权(SWI)检查的患者641例,其中确诊为CMBs的患者100例(CMBs组),正常153例(正常组)。依据SWI对CMBs患者进行病灶计数,分析CMBs患者各危险因素与CMBs的关系。结果 CMBs组与正常组独立样本检验结果表明,肌酐(CREA)、同型半胱氨酸(Hcy)、胱抑素C(cys C)、超氧化物歧化酶(SOD)、纤维蛋白原(FIB)以及年龄和高血压差异均有统计学意义(P0.05)。采用Spearman相关分析显示CMBs严重程度与年龄(r=0.687,P=0.000)及高血压的严重程度相关(r=0.087,P=0.389)。多因素Logistic回归分析显示,发生CMBs与年龄(OR=0.930,P=0.000)、高血压病史(OR=0.126,P=0.000)、平均动脉压(MAP)(OR=0.937,P=0.000)、收缩压(SP)(OR=0.954,P=0.005)和舒张压(DP)(OR=1.049,P=0.048)相关。结论 CMBs的发生与年龄、高血压病史、收缩压、舒张压和平均动脉压水平相关。     

Primary cerebral malignant non-Hodgkin's lymphomas: A retrospective clinical study

Summary In this retrospective study a series of 54 patients (seen from 1982 to 1989) with sporadic primary cerebral malignant lymphomas (PCML), which were uniformly classified with the support of immunocytochemical data, is presented. The analysis shows that on CT PCML are shown as cirumscribed, homogeneous, contrast-enhanced multifocal (70%) or solitary (30%) mass lesions within the subcortical white matter; they were found mainly close to the ventricular system or the subarachnoid space. To prove the histological diagnosis and for the purposes of differential diagnosis, low-risk CT-stereotactic biopsy is necessary and is the method of choice. Immunomorphological techniques are valuable adjuncts to confirm the histological diagnosis of PCML. In the series presented these tumours have been predominantly classified as high-grade blastic B-cell lymphomas. For this reason, this type should be regarded as the prevalent variant of malignant brain lymphomas. The evaluation of possible prognostic factors suggests that age at admission and morphological features of regression are relevant determinants of survival time. A correlation between neuroradiological evidence of a decrease in tumour size, morphological signs of regression and glucocorticoid administration has been found. Thus, patients suspected of having PCML require rapid diagnosis prior to corticosteroid administration. PCML have been shown to be radioresponsive, but not curable. Because of the lack of uniformity in management of this rare brain neoplasm, the different treatment protocols are not comparable, and hence the optimum therapy has not been satisfactorily determined. Therefore, a rational diagnostic strategy is proposed as a basis for prospective randomized long-term follow-up studies in order to evaluate different treatment modalities and to obtain more insight into the biological behaviour of primary cerebral malignant lymphomas.     

An improved photochemical model of embolic cerebral infarction in rats.

To provide further evidence that the multiple cerebral infarcts found in rats following photochemical damage to the carotid artery are caused by emboli and to eliminate the systemic hypotension and heating of the blood reported with the previous photochemical embolic stroke model (rose bengal and a green laser), I have modified the photochemical technique. Brain pathology was studied in 18 Wistar rats following carotid artery irradiation with a red laser (632 nm) at powers ranging from 100 to 800 mW/cm2 for 10 or 20 minutes following the injection of the photosensitizing dye Photofrin II. Multiple cerebral arterioles were occluded by platelet aggregates containing frequent erythrocytes and leukocytes, identical to the thrombotic material in the carotid artery but different from the platelet aggregates seen in the carotid artery and the brain in the rose bengal model. Eighty infarcts were distributed randomly throughout the brain ipsilateral to the nonocclusive carotid thrombus. Significant heating (0.5 degree C or more) of the blood occurred only with laser powers higher (1,600 mW/cm2) or laser irradiations longer (25 minutes) than those used in the improved model of embolic stroke. This model mimics one mechanism of stroke in humans and provides a means to study systematically the morphological evolution of small cerebral infarcts.     

不同时间窗大鼠脑血栓溶解治疗后梗死体积和脑电图的研究

目的：研究不同时间窗脑血栓溶解治疗后脑电变化与梗死体积的关系。方法：应用肾血管性高血压大鼠,用光化学法制成一侧大脑中动脉闭塞模型,在血栓形成后不同时间应用尿激酶静脉溶栓,观察脑电图变化与梗死体积的大小。结果：缺血２小时之内实行溶栓治疗,可缩小梗死性。ＭＣＡＯ３０分钟后溶栓复流后,ＥＥＧ有改善,一小时后慢波减少,２４小时ＥＥＧ可恢复到基本正常。     

Reduction of infarct volume and mortality by thrombolysis in a rat embolic stroke model.

BACKGROUND AND PURPOSE: Thrombolytic therapy with recombinant tissue plasminogen activator was tested in a rat embolic stroke model. METHODS: The rat carotid territory was embolized with arterial-like microthrombi formed under pressure. Hemispheric cerebral blood flow before and after embolization was measured by the intraarterial Xenon-133 injection method. Fifteen minutes after embolization, 24 rats were treated with 3 mg/kg or 10 mg/kg tissue plasminogen activator, and 27 were treated with saline. Carotid angiography displayed the rate of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed and evaluated neuropathologically and infarct volume was measured. RESULTS: Cerebral blood flow was reduced 70-86% after embolization. The comparison of pretreatment and posttreatment angiography showed significant (p = 0.0005) reperfusion in the treated rats. Thrombolytic therapy significantly reduced the infarct volume from 55.1% to 24.4% of embolized hemisphere volume (p = 0.007) and increased the survival rate from 0.48 to 0.96 (p = 0.0004). Fifty-three percent of the embolized rats recanalized completely after thrombolytic treatment and developed almost no infarction (median volume 2.8%), and all survived. No hemorrhagic complications were observed. CONCLUSIONS: Early thrombolytic therapy induced recanalization and reduced mortality and infarct volume after embolic stroke in this model.     

Results of electroconvulsive therapy in restrictive indications. A retrospective study of 15 years]

In Tübingen ECT is restricted to severely ill patients who do not respond to other somatic therapies; especially to patients with endogenous depression and pernicious catatonia. Between 1976 and 1990, 45 patients were treated with ECT, of whom 22 suffered from endogenous depression and 10 from pernicious catatonia. Thirteen patients with other diagnoses (schizophrenic and schizoaffective psychoses, borderline schizophrenia and obsessive-compulsive disorder) were treated with ECT for severe depressive states after failure of psychopharmacological therapy. A positive therapeutic response to ECT was observed in 46% of patients with endogenous depression and in all 10 with pernicious catatonia. In the patients with schizophrenia and schizoaffective psychosis, borderline schizophrenia and obsessive-compulsive disorder, an amelioration of the depressive or anxiety syndrome was observed only in individual cases. Side effects of ECT were transit syndromes (20%), reversible amnestic syndromes (20%) and cardiac arrhythmias (6%). According to our results, ECT is highly effective in therapy-resistant endogenous depression and pernicious catatonia, and therefore remains a necessary part of psychiatric therapy.     

Patency of cerebral microvessels after focal embolic stroke in the rat.

In patients with thrombotic stroke, the occluded artery often reopens over time. This results through a natural dissolution of the occluding material, and fragments of the material may move downstream to obstruct distal arteries. The current study was undertaken to investigate the patency of brain microvessels at varying time intervals after injection of a preformed clot into the right internal carotid artery of rats. Cerebral microvessels in brain sections were visualized using immunohistochemistry for fibronectin (detecting existing microvessels) and Evans blue (visualizing perfused microvessels). The percentage of patent microvessels was calculated as the number of Evans blue-positive microvessels divided by the number of fibronectin-positive microvessels. In normal control animals, results showed that 98% +/- 3% (mean +/- SD) of microvessels in the cortex and 94% +/- 14% in the striatum were patent. In the ischemic animals, immediately after clot injection, microvessels in the cortex and striatum were occluded, mainly in the territory irrigated by the middle cerebral artery. One hour after clot injection, microvessels had reopened in most of the cortex but remained occluded in some portions of the striatum, possibly as a result of downstream movement of fragments formed from the original clot. By 3 hours after clot injection, microvessels in the cortex were patent in all animals, whereas in the striatum microvessels were patent in 50% of the animals. In the other 50%, small striatal perfusion deficits persisted. At 24 hours after clot injection, microvessels were patent in both the cortex and striatum of all animals except one. These findings suggest that intracerebral clots dissolve spontaneously in a relatively short period of time, but that fragments formed from the clot may obstruct more distal blood vessels. It is likely that clot fragments lodge in arteries with lower blood flow and poor collateral perfusion, where they continue to cause ischemia for a longer duration. These results may in part explain the resistance of the striatum to neuroprotective strategies used for the treatment of focal cerebral ischemia.     

A model for quantitative evaluation of embolic stroke therapy

We developed a small animal embolic stroke model for pharmacological screening trials. Microspheres are injected into the carotid circulations and group embolus dose-response relationships are calculated. Emboli quantity is related to neurologic injury, and small changes in neurologic function are detectable. Rabbits tolerated twice as many microspheres when cyproheptadine-treated after embolization. This demonstrated both the sensitivity of the model and the value of serotonin antagonists in reducing neurological injury.     

Sural nerve biopsy in the diagnosis of progressive cerebral degenerative disorders of childhood. A retrospective study

A retrospective study of sural nerve biopsies in 105 children with progressive cerebral degeneration is presented. The indications for the procedure are discussed in relation to current views. The conclusion is that the biopsy is still useful only in occasional patients with associated peripheral neuropathy. In patients without neuropathy there is no current indication for the biopsy at all.     

ACTH versus vigabatrin therapy in infantile spasms: a retrospective study.

ACTH is the standard treatment for infantile spasms (IS) in North America. Recent reports showed that vigabatrin is a valuable treatment for IS, but comparative studies with ACTH are limited. In this study, we compare the effectiveness of ACTH versus vigabatrin on IS. Our results support that vigabatrin is as effective as and better tolerated than ACTH. Because of their similar efficacy, we believe that vigabatrin should be the first intention drug for the treatment of IS.     

Increased cerebral infarct volumes in polyglobulic mice overexpressing erythropoietin.

There is increasing evidence that erythropoietin (Epo) has a protective function in cerebral ischemia. When used for treatment, high Epo plasma levels associated with increases in blood viscosity, however, may counteract beneficial effects of Epo in brain ischemia. The authors generated two transgenic mouse lines that overexpress human Epo preferentially, but not exclusively, in neuronal cells. In mouse line tg21, a fourfold increase of Epo protein level was found in brain only, whereas line tg6 showed a dramatic increase of cerebral and systemic transgene expression resulting in hematocrit levels of 80%. Cerebral blood flow (CBF), as determined by bolus tracking magnetic resonance imaging, was not altered in the tg6 line. The time-to-peak interval for the tracer, however, increased approximately threefold in polyglobulic tg6 mice. Immunohistochemical analysis revealed an increase in dilated vessels in tg6 mice, providing an explanation for unaltered CBF in polyglobulic animals. Permanent occlusion of the middle cerebral artery (pMCAO) led to similar perfusion deficits in wild-type, tg6, and tg21 mice. Compared with wild-type controls, infarct volumes were not significantly smaller (22%) in tg21 animals 24 hours after pMCAO, but were 49% enlarged (P < 0.05) in polyglobulic tg6 mice. In the latter animals, elevated numbers of Mac-1 immunoreactive cells in infarcted tissue suggested that leukocyte infiltration contributed to enlarged infarct volume. The current results indicate that moderately increased brain levels of Epo in tg21 transgenic mice were not sufficient to provide significant tissue protection after pMCAO. The results with tg6 mice indicate that systemic chronic treatment with Epo associated with elevated hematocrit might deteriorate outcome after stroke either because of the elevated hematocrit or other chronic effects.