Showing papers on "Cerebral infarction published in 1995"
TL;DR: Patients with asymptomaticCarotid artery stenosis of 60% or greater reduction in diameter and whose general health makes them good candidates for elective surgery will have a reduced 5-year risk of ipsilateral stroke if carotid endarterectomy performed with less than 3% perioperative morbidity and mortality is added to aggressive management of modifiable risk factors.
Abstract: Objective —To determine whether the addition of carotid endarterectomy to aggressive medical management can reduce the incidence of cerebral infarction in patients with asymptomatic carotid artery stenosis Design —Prospective, randomized, multicenter trial Setting —Thirty-nine clinical sites across the United States and Canada Patients —Between December 1987 and December 1993, a total of 1662 patients with asymptomatic carotid artery stenosis of 60% or greater reduction in diameter were randomized; follow-up data are available on 1659 At baseline, recognized risk factors for stroke were similar between the two treatment groups Intervention —Daily aspirin administration and medical risk factor management for all patients; carotid endarterectomy for patients randomized to receive surgery Main Outcome Measures —Initially, transient ischemic attack or cerebral infarction occurring in the distribution of the study artery and any transient ischemic attack, stroke, or death occurring in the perioperative period In March 1993, the primary outcome measures were changed to cerebral infarction occurring in the distribution of the study artery or any stroke or death occurring in the perioperative period Results —After a median follow-up of 27 years, with 4657 patient-years of observation, the aggregate risk over 5 years for ipsilateral stroke and any perioperative stroke or death was estimated to be 51% for surgical patients and 110% for patients treated medically (aggregate risk reduction of 53% [95% confidence interval, 22% to 72%]) Conclusion —Patients with asymptomatic carotid artery stenosis of 60% or greater reduction in diameter and whose general health makes them good candidates for elective surgery will have a reduced 5-year risk of ipsilateral stroke if carotid endarterectomy performed with less than 3% perioperative morbidity and mortality is added to aggressive management of modifiable risk factors ( JAMA 1995;273:1421-1428)
2,714 citations
TL;DR: The histological effects of an intracranial arterial occlusion in the adult rat can be predicted on day 1 by the neurological score described in this report, and significant improvement can be obtained in these animals by reestablishing arterial flow 60 minutes or sooner after the ictus.
Abstract: Background and Purpose Occluding a large intracranial artery in rats produces a brain lesion that grows in terms of an increase in both surface area and number of necrotic neurons. The present study investigated whether reperfusing the ischemic territory 30 to 60 minutes after the arterial occlusion would have a beneficial effect on either the clinical or the histological outcome of the lesion. Methods One hundred four adult rats (including appropriate controls) were used; 97 had a middle cerebral artery occluded by inserting a nylon monofilament via the right external carotid artery. The arterial occlusion was transient in two groups and permanent in another; survival times were comparable for all groups. Control animals were subjected to a sham operation during which the artery was occluded for less than 1 minute. The outcome was evaluated by measuring the extent of the neurological deficit and the severity of the histological injury. Results Mean neurological score and mean number of necrotic neurons i...
1,274 citations
TL;DR: The greater prevalence of diabetes and hypercholesterolemia among blacks and Hispanics from northern Manhattan accounted for much of the increased frequency of intracranial atherosclerotic stroke.
Abstract: Background and Purpose The aim of this investigation was to determine the importance of race as a determinant of intracranial atherosclerotic stroke in a community-based stroke sample. Methods Residents from northern Manhattan over age 39 years hospitalized for acute ischemic stroke (n=438, black 35%, Hispanic 46%, white 19%) were prospectively evaluated. Index ischemic strokes were classified as atherosclerotic (17%), lacunar (30%), cardioembolic (21%), cryptogenic (31%), and other (1%). Atherosclerotic infarcts were subdivided into extracranial (9%) and intracranial (8%) atherosclerosis. Results The proportion of extracranial atherosclerotic stroke was similar among the three race-ethnic groups, while intracranial atherosclerosis was more frequent in blacks and Hispanics. The unadjusted odds ratio for nonwhites (blacks and Hispanics combined) was 0.8 (confidence interval [CI], 0.4 to 1.8) for extracranial and 7.8 (CI, 1.04 to 57.7) for intracranial atherosclerosis. Patients with intracranial disease wer...
874 citations
TL;DR: In carotid artery dissections, completed stroke usually occurs in the first few days after the onset of the first symptoms, whether local or ischemic, but it can occur as much as 1 month later.
Abstract: Background and Purpose Cerebral infarction is the most frequent and severe manifestation of extracranial internal carotid artery dissection. However, few data exist on the precise time course of symptoms preceding the onset of stroke.
Methods We studied 80 consecutive patients (29 retrospectively, 51 prospectively) with angiographically diagnosed extracranial internal carotid artery dissection and, during a 6-month follow-up, recorded the time elapsed between the onset of the first symptoms and the onset of any ischemic event (transient ischemic attack or stroke). We compared patients with and without ischemic events, with and without completed stroke, and, among patients who had local signs at onset, those with and without subsequent ischemic events.
Results Cerebral or retinal infarction occurred in 42 patients. It was inaugural in 9 patients. In the 33 others, the time interval between the first symptoms (local signs and/or transient ischemic attacks) and the onset of stroke ranged from a few minutes to 31 days; it was ≤7 days in 82% of the patients. No significant difference in the baseline characteristics of the patients or in the angiographic pattern of dissection was found based on the presence or absence of ischemic signs or of completed stroke.
Conclusions In carotid artery dissections, completed stroke usually occurs in the first few days after the onset of the first symptoms, whether local or ischemic, but it can occur as much as 1 month later. This suggests that any potential preventive treatment should be initiated as early as possible after the onset of the first symptoms but might also be worth initiating even 1 month later.
333 citations
TL;DR: In this paper, the authors analyzed the incidence, timing, and outcomes of stroke in an international trial and found that 1.4% of the patients had a stroke (93% anatomic documentation) and the risk ranged from 1.19% with streptokinase/subcutaneous heparin therapy to 1.64% with combination thrombolytic therapy.
Abstract: Background Stroke is the most feared complication of thrombolysis for acute myocardial infarction because of the resulting mortality and disability. We analyzed the incidence, timing, and outcomes of stroke in an international trial. Methods and Results Patients were randomly assigned to one of four thrombolytic strategies. Neurological events were confirmed clinically and anatomically and were adjudicated by a blinded committee. Stroke survivors, categorized by residual deficit and disability, assessed their quality of life with a time trade-off technique. Multivariable regression identified patient characteristics associated with intracranial hemorrhage. Overall, 1.4% of the patients had a stroke (93% anatomic documentation). The risk ranged from 1.19% with streptokinase/subcutaneous heparin therapy to 1.64% with combination thrombolytic therapy (P=.007). Primary intracranial hemorrhage rates ranged from 0.46% with streptokinase/subcutaneous heparin to 0.88% with combination therapy (P<.001). Of all str...
320 citations
TL;DR: The data suggest that cardiac operations can be done safely 4 weeks after cerebral infarction, and if the delay is more than 2 weeks, the exacerbation rate will be around 10%, and the risk of progression of cerebral damage is still significant 15 days and even 4 weeks afterwards.
287 citations
TL;DR: Whether ICP elevation is a common cause of deterioration from LHIE by measuring the initial ICP and cerebral perfusion pressure in 19 patients deteriorating to stupor within 3 hours of deterioration is sought, after ruling out metabolic aberrations, medication side effects, infection, and seizures.
Abstract: Neurologic deterioration from large hemispheric infarction with edema (LHIE) often leads to the use of therapies directed at decreasing intracranial pressure (ICP). Many of these ICP therapies can potentially accentuate tissue shifts from unilateral mass lesions and lead to rebound ICP elevations. We sought to determine whether ICP elevation is a common cause of deterioration from LHIE by measuring the initial ICP and cerebral perfusion pressure (CPP) in 19 patients deteriorating to stupor from LHIE within 3 hours of deterioration, after ruling out metabolic aberrations, medication side effects, infection, and seizures and prior to commencement of any ICP-lowering therapies. We evaluated 19 patients aged 23 to 77 years--14 with complete middle cerebral artery and five with complete internal carotid artery territory infarctions. Stupor began 59 +/- 37 hours after the stroke onset. ICP monitoring (12 ipsilateral Camino, five contralateral ventriculostomy, and two ipsilateral epidural) demonstrated elevation of ICP (> 15 mm Hg) in only five patients (26.3%), with group mean initial ICP = 13.4 +/- 10 mm Hg. Similarly, the initial CPP was diminished (< 55 mm Hg) in only two patients (10.5%), with group mean initial CPP = 74.9 +/- 14 mm Hg. Globally elevated ICP is not a common cause of initial neurologic deterioration from LHIE mass effect.
285 citations
TL;DR: A U-shaped relation was observed between temperature and mortality from coronary artery disease and cerebral infarction and these results imply a pathophysiological difference between thromboembolic and haemorrhagic cardiovascular diseases.
265 citations
TL;DR: Age, history of hypertension, active angina, and elevated mean systolic blood pressure were associated with silent infarction at entry, while Active angina at baseline was the only significant independent predictor for the later development of symptomatic stroke.
Abstract: Background Cerebral infarction in patients with atrial fibrillation may vary from being clinically silent to catastrophic. The prevalence of silent cerebral infarction and its effect as a risk factor for symptomatic stroke are important considerations for the evaluation of patients with atrial fibrillation. Methods and Results This Veterans Affairs cooperative study was a double-blind controlled trial designed primarily to determine the efficacy of warfarin for the prevention of stroke in neurologically normal patients with nonrheumatic atrial fibrillation. It also was designed to evaluate patients with silent cerebral infarction. Computed tomography scans of the head were performed at entry, at the time of any subsequent stroke, and at termination of follow-up on all patients who completed the study without a neurological event. Of 516 evaluable scans performed at entry, 76 (14.7%) had evidence of one or more silent cerebral infarcts. Age (P=.011), a history of hypertension (P=.003), active angina (P=.01...
249 citations
TL;DR: The loss of cerebral reactivity in patients with symptoms who had greater than or equal to 70% carotid stenosis or occlusion is an important predictor of impending cerebral infarction.
242 citations
TL;DR: Severe AA is associated with an increased frequency of cerebral infarction in patients with AD, and appears to be largely due to an interaction between severe AA and hypertension that may produce multiplicative injuries on the vasculature.
Abstract: Objective: To determine if severe cerebral amyloid angiopathy (AA) in patients with Alzheimer's disease (AD) is associated with an increased prevalence of cerebral infarction diagnosed at autopsy. Amyloid angiopathy is increasingly recognized as a cause of ischemic infarcts, as well as cerebral hemorrhages. However, the relationship of AA to cerebral infarction in patients with AD is uncertain. Design: Retrospective clinicopathological study of autopsy-confirmed cases of AD. Patients: One hundred forty-five deceased patients with AD confirmed at autopsy. Main Outcome Measures: Semiquantitative scores of AA severity were done in four brain regions: midfrontal, inferior parietal, superior temporal, and hippocampal. The finding of cerebral infarction at autopsy was modeled as a function of AA severity, hypertension, age at death, AD severity, and sex in X 2 and multiple logistic regression analyses. Results: Severe AA was significantly associated with cerebral infarction at autopsy in patients with AD (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.4 to 8.9). None of the other independent variables in the multiple logistic regression analysis were significant predictors. While hypertension was equally common in the severe and mild AA subgroups, the combination of both severe AA and hypertension interacted to increase the risk of infarction (OR, 14.2; 95% CI, 3.2 to 63.4) beyond that observed with hypertension (OR, 1.1; 95% CI, 0.4 to 3.2) or severe AA (OR, 1.3; 95% CI, 0.3 to 5.3) alone. Conclusions: Severe AA is associated with an increased frequency of cerebral infarction in patients with AD. This appears to be largely due to an interaction between severe AA and hypertension that may produce multiplicative injuries on the vasculature. Further study with regard as to how AA may cause ischemia and its role in the neuropathologic and clinical progression of AD is needed.
TL;DR: An MR tissue signature model based on experimentally derived relationships of the apparent diffusion coefficient of water (ADCw) and T2 to ischemic brain tissue histopathology can now be tested for its potential to predict reversible and identify irreversible cellular damage in human isChemic brain regions.
Abstract: Background and Purpose We sought to identify MRI measures that have high probability in a short acquisition time to predict, at early time points after onset of ischemia, the eventual development of cerebral infarction in clinical patients who suffer occlusion of a cerebral artery.
Methods We developed an MR tissue signature model based on experimentally derived relationships of the apparent diffusion coefficient of water (ADCw) and T2 to ischemic brain tissue histopathology. In eight stroke patients we measured ADCw and T2 intensity using diffusion-weighted echo-planar imaging (DW-EPI). Tissue signature regions were defined, and theme maps of the ischemic focus at subacute time points after stroke onset were generated.
Results Five MR signatures were identified in human stroke foci: two that may predict either cell recovery or progression to necrosis, one that may mark the transition to cell necrosis, and two that may be markers of established cell necrosis.
Conclusions An MR tissue signature model of ischemic histopathology using ADCw and T2 can now be tested for its potential to predict reversible and identify irreversible cellular damage in human ischemic brain regions.
TL;DR: The results demonstrate that familiarity with the initial symptoms, especially headache, and performance of an ultrasonographic study without delay are the cornerstones of an early diagnosis of cerebral embolism.
Abstract: First symptoms and initial clinical, ultrasonographic and neuroradiological findings ascertained a mean of 5.6 days (SD = 5.6 days), 7.7 days (7.0), and 11.2 days (8.0) after symptom onset were analysed in 44 patients who suffered a spontaneous internal carotid artery dissection (ICD) verified by magnetic resonance imaging, angiography, or both. Common symptoms signalling dissection were unilateral headache in 68%, transient ischaemic attack in 20%, and cerebral infarction in 9%. Severe pain preceded cerebral ischaemia by more than 3 days in 60% of those patients who eventually suffered a stroke. However, only 2 were admitted because of pain alone and 33 for evolving neurological deficits. During the first month, ipsilateral severe headache occurred in 89%, neck pain in 36%, ipsilateral cerebral ischaemia in 82%, ocular ischaemia in 16%, oculosympathetic palsy in 48%, and cranial nerve palsy in 5%. Recent "trivial" head or neck trauma was elicited in 41%. Doppler and duplex sonography confirmed the clinical suspicion of ICD in 91.5% and in 96% of those with a significant stenosis or occlusion. MRI demonstrated a thickened vessel wall in all 33 imaged carotid dissections and a mural haematoma in 30. None of the 32 patients who received anticoagulant treatment subsequently deteriorated. Monitoring anticoagulant treatment with ultrasonographic follow-up studies demonstrated recanalization in 70% and persistent occlusion in 30%. The results demonstrate that familiarity with the initial symptoms, especially headache, and performance of an ultrasonographic study without delay are the cornerstones of an early diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: The type of stroke per se has no influence on stroke prognosis in general; the extent of the injury is decisive; the poorer prognosis is due to the increase in frequency of intracerebral hemorrhage with increasing stroke severity.
Abstract: The purpose of this study was to compare stroke severity, risk factors, and prognosis in patients with intracerebral hemorrhage versus infarction. We prospectively studied 1,000 unselected patients with acute stroke of a verified type in the Copenhagen Stoke Study. Neurological deficits and functional disabilities were evaluated weekly from the time of acute admission throughout the rehabilitation period. Eighty-eight (9%) had intracerebral hemorrhage. The relative frequency of intracerebral hemorrhage rose exponentially with increasing stroke severity. In multivariate analyses, stroke type had no influence on mortality, neurological outcome, functional outcome, or the time course of recovery. Initial stroke severity was the all-important prognostic factor. The relative importance of hypertension and blood pressure on admission was not greater for intracerebral hemorrhage than for infarction. No preponderance was found between type of stroke and sex, age, and smoking. Diabetes, ischemic heart disease, and elevated serum total cholesterol level all favored cerebral infarction as opposed to intracerebral hemorrhage. We conclude that the type of stroke per se has no influence on stroke prognosis in general; the extent of the injury is decisive. The poorer prognosis in patients with intracerebral hemorrhage is due to the increase in frequency of intracerebral hemorrhage with increasing stroke severity. The likelihood of cerebral infarction occurring as opposed to intracerebral hemorrhage seems increased fivefold in stroke patients with diabetes. Hypertension and blood pressure on admission were not predictors of stroke type.
TL;DR: In long‐term follow‐up, intravascular balloon occlusion was a relatively safe, effective treatment for eliminating ICA aneurysms that posed low risk for early or delayed ischemia or infarction.
Abstract: Long-term evaluation of patients with aneurysms of the internal carotid artery (ICA) treated by intravascular balloon occlusion has not been reported. From 1977 to 1992, 58 patients (age 14 to 81 years) with ICA aneurysms were treated at our institution by this technique. The aneurysms included 40 intracavernous carotid, 5 petrous carotid, 3 cervical carotid, and 10 ophthalmic segment aneurysms. Presenting symptoms were caused by mass effect in 45 patients, transient ischemia or cerebral infarction as a result of emboli in 6, subarachnoid hemorrhage in 4, and epistaxis in 3. Preoperative temporary balloon occlusion of the ICA combined with cerebral blood flow monitoring and induced hypotension were used to determine tolerance for occlusion. Two patients not tolerating test occlusion required an extracranial-intracranial bypass procedure, and another patient underwent extracranial-intracranial bypass prior to test occlusion because of contralateral ICA stenosis. In 55 patients, aneurysms were excluded from the circulation by either occluding the proximal ICA or trapping the aneurysm neck. In three patients, the aneurysm was directly obliterated with intravascular balloons with preservation of the parent ICA. Three patients died during treatment, one from subarachnoid hemorrhage and two from cerebral infarction. Mean follow-up was 76 months (range, 6 months to 15 years). Six patients who developed transient ischemia caused by emboli responded to volume expansion and anticoagulation treatment. Two patients developed a delayed infarction, and one patient developed aneurysm enlargement that required surgical clipping and obliteration. (ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: This study indicates that computer analysis of carotid plaque can identify high-riskCarotid plaques and the potential of such analysis in the identification of asymptomatic high- risk patients should be explored in further studies.
TL;DR: Basic fibroblast growth factor was infused intravenously for 3 h, beginning at 30 min after permanent middle cerebral artery occlusion by intraluminal suture in mature Sprague–Dawley rats and showed that labeled bFGF crossed the damaged blood–brain barrier to enter the ischemic hemisphere.
Abstract: Basic fibroblast growth factor (bFGF) is a polypeptide that supports the survival of brain cells (including neurons, glia, and endothelia) and protects neurons against a number of toxins and insults in vitro. This factor is also a potent dilator of cerebral pial arterioles in vivo. In previous studies, we found that intraventricularly administered bFGF reduced infarct volume in a model of focal cerebral ischemia in rats. In the current study, bFGF (45 μg/kg/h) in vehicle, or vehicle alone, was infused intravenously for 3 h, beginning at 30 min after permanent middle cerebral artery occlusion by intraluminal suture in mature Sprague–Dawley rats. After 24 h, neurological deficit (as assessed by a 0- to 5-point scale, with 5 = most severe) was 2.6 ± 1.0 in vehicle-treated and 1.5 ± 1.3 in bFGF-treated rats (mean ± SD; TV = 12 vs. 11; p = 0.009). Infarct volume was 297 ± 65 mm3 in vehicle- and 143 ± 135 mm3 in bFGF-treated animals (p = 0.002). During infusion, there was a modest decrease in mean arterial bloo...
TL;DR: The results suggest that decompressive craniectomy for cerebral ischemia not only reduces mortality but also significantly improves outcome and reduces infarction size, probably because of increased perfusion pressure through leptomeningeal collaterals.
Abstract: Background and Purpose Acute ischemia in the territory of the carotid artery can lead to massive cerebral edema with raised intracranial pressure and progression to coma and death due to uncal, cingulate, or tonsillar herniation. Thus far, only anecdotal experience with supratentorial ischemia treated by decompressive craniectomy has been reported, and there are no published experimental data dealing with this kind of therapy in acute supratentorial stroke. In this study, we present our results on the effect of decompressive craniectomy in an endovascular model of cerebral infarction in rats. Methods Focal cerebral ischemia was induced in 50 rats using an endovascular occlusion technique of the middle cerebral artery. Decompressive craniectomy was performed in 30 animals: in 15 animals after 1 hour and in the remaining 15 animals 24 hours after vessel occlusion. Twenty animals were not treated by decompressive craniectomy (control group). Results Mortality in the nontreated group was 35%, whereas none of ...
TL;DR: Among hypertensive individuals, heavy alcohol consumption leads to a significant increase in the risk of cerebral hemorrhage, suggesting a synergistic effect of alcohol and hypertension, while light alcohol consumption significantly reduces therisk of cerebral infarction.
Abstract: Background and Purpose The relationship between alcohol intake and stroke has been inconsistent in previous studies. We examined the separate and combined effects of drinking habits and hypertension on stroke incidence in a prospective survey of a general Japanese population. Methods A total of 1621 stroke-free Hisayama residents aged 40 years or older were classified by their alcohol intake into nondrinkers, light drinkers (<34 g of ethanol per day), and heavy drinkers (≥34 g of ethanol per day) and followed up prospectively for 26 years from 1961. Results During the follow-up period, cerebral infarction developed in 244 subjects and cerebral hemorrhage in 60. For men, the incidence of cerebral hemorrhage increased significantly with rising alcohol consumption. In contrast, the incidence of cerebral infarction was slightly lower in light drinkers than in nondrinkers, while it increased significantly in heavy drinkers compared with light drinkers. Female drinkers had a lower incidence of cerebral infarcti...
TL;DR: A distinct syndrome of cerebral ischemia should be recognized for its younger age at onset, predominance of women, high risk of recurrent thrombo‐occlusive events, and the possible use of the IgG anticardiolipin antibody titer for prognosis.
Abstract: We prospectively studied 81 consecutively identified patients with antiphospholipid antibodies (aPLs) who developed focal cerebral ischemia over a 7-year period. The mean age of this cohort was approximately a decade younger than the average atherothromboembolic stroke victim and women were more commonly involved than men. The frequency of conventional stroke risk factors was lowest in the group of stroke patients with the highest levels of IgG cardiolipin immunoreactivity. Other serological abnormalities associated with aPL (false-positive Veneral Disease Research Laboratory test, thrombocytopenia, prolonged activated partial thromboplastin time [aPTT]) were more common in the group with over 100 GPL units (high positive). Patients with the highest IgG anticardiolipin titers had the shortest times to subsequent thrombo-occlusive events. The most common recurrent event was cerebral infarction, often occurring within the first year of follow-up during a mean prospective follow-up of 3 years. Over one-half of the cohort had at least one recurrent thrombo-occlusive event during follow-up. This distinct syndrome of cerebral ischemia should be recognized for its younger age at onset, predominance of women, high risk of recurrent thrombo-occlusive events, and the possible use of the IgG anticardiolipin antibody titer for prognosis.
TL;DR: Diastolic blood pressure and atrial fibrillation appear to be strong predictors of silent cerebral infarction in the Japanese general population.
Abstract: Background and Purpose The purpose of this study was to assess the prevalence and characteristics of silent cerebral infarction in a population-based consecutive autopsy series of residents of Hisayama, Kyushu, Japan.
Methods Autopsy records, cerebral pathological findings, and clinical charts of 966 Hisayama residents recorded during the 26 years from 1961 to 1987 were examined (autopsy rate, 82.4%). The subjects were divided into three groups: those with both clinically apparent strokes and pathologically verified cerebral infarcts (stroke group), those having pathological evidence of cerebral infarction in the brain but without clinical stroke episodes (silent infarction group), and those with neither infarction nor stroke episode (noninfarction group). Risk factors and brain pathology in the three groups were compared.
Results Silent cerebral infarction was found in 12.9% of the 966 subjects who had undergone autopsy, and its frequency increased with age. The subjects with silent infarcts were older, had higher systolic or diastolic blood pressure, and had atrial fibrillation more frequently than subjects in the noninfarction group. There were no significant differences in the locations of infarcts between the stroke and silent infarction groups, although infarcts tended to be located in the deeper area of the brain in the latter. The number and size of infarcts were smaller in the silent infarction group than in the stroke group.
Conclusions Diastolic blood pressure and atrial fibrillation appear to be strong predictors of silent cerebral infarction in the Japanese general population. Stroke becomes clinically apparent as infarct volume increases.
TL;DR: It is indicated that EAAs are tremendously increased in brain tissue after occlusive stroke, and Administration of EAA antagonists to patients with ischemic stroke may therefore be beneficial.
Abstract: Background Animal stroke models demonstrate excitatory amino acid (EAA) release in ischemic tissue, as measured by microdialysis. Currently glutamate antagonist drugs are being developed to protect brain tissue after ischemic events. However, the role of EAAs in human occlusive stroke is not well known. We therefore measured glutamate and aspartate release in a patient after occlusive stroke. Case Description We describe a case of occlusive stroke in a 50-year-old man. A partial temporal lobectomy was done to remove infarcted tissue and to prevent brain stem compression as well as uncal herniation. A microdialysis probe was placed into the cortex to measure EAAs. Massively increased levels of glutamate and aspartate were detected in the extracellular fluid in this patient (>300 times normal levels 6 days after infarction). Conclusions These findings indicate that EAAs are tremendously increased in brain tissue after occlusive stroke. The time course of the release of EAAs is much longer than animal studie...
TL;DR: A significant neuroprotective effect of rNIF with continuous treatment for 48 hours following 2 hours of MCAO is demonstrated, correlated with a reduced number of neutrophils within the ischemic tissue.
Abstract: We tested the neuroprotective potential of neutrophil inhibitory factor (rNIF), a novel 41-kd recombinant glycoprotein derived from a hookworm, in a model of focal cerebral ischemia in the rat. Male Wistar rats were assigned to treatment with rNIF and vehicle. Middle cerebral artery occlusion (MCAO) for 2 hours was induced by insertion of an intraluminal suture. Infusion of the drug was initiated at the onset of reperfusion. Infarct volume was determined 48 hours after reperfusion. Neutrophils were measured within the ischemic tissue by myeloperoxidase (MPO) staining. Treatment with rNIF resulted in a 48% reduction in cerebral infarction compared with control animals (p < 0.01). Neutrophil accumulation in the ischemic brains of rNIF-treated rats was reduced significantly (p < 0.01) compared with control animals. The number of neutrophils within the infarcted tissue correlated positively with the size of the area of infarction (p < 0.001, r = 0.6) within representative cerebral coronal sections. We demonstrated a significant neuroprotective effect of rNIF with continuous treatment for 48 hours following 2 hours of MCAO. The neuroprotective effect was correlated with a reduced number of neutrophils within the ischemic tissue. These results demonstrate potential therapeutic properties of rNIF in the management of stroke.
TL;DR: The demonstration of the continuing loss of cerebral metabolites within an infarct region suggests that further cell loss occurs up to 10 days after infarction, which may represent continued ischemic damage after middle cerebral arteryInfarction.
Abstract: Background and Purpose Proton MR spectroscopy is a noninvasive method of monitoring in vivo metabolite concentration changes over time. The aim of this work was to study the ischemic penumbra in humans by measuring the metabolic changes that occur after a middle cerebral artery territory infarction.
Methods Diagnostic MRI and short–echo time MR spectroscopy were performed on a 1.5-T system. Localized proton MR spectroscopy was performed within the area of cerebral infarction and in a homologous area of the contralateral hemisphere. The residual water resonance in the spectra was removed with the use of the Hankel Lanczos singular value decomposition method, after which peak area estimates were obtained by means of the variable projection time domain fitting analysis. The unsuppressed water signal was used as an internal concentration standard. Ten patients with acute middle cerebral artery infarction were studied within 28 hours of stroke onset and followed up for a period of up to 3 months.
Results Significant changes were seen in the initial spectra from the infarct compared with the contralateral spectra. Lactate, a marker of anaerobic metabolism, was present within the infarct but not detected in the contralateral hemisphere. N -Acetyl aspartate, a neuronal marker, and total creatine were significantly reduced. The initial choline signal, arising from choline-containing compounds within the cell and cell membrane, remained unchanged in the infarct core compared with the contralateral hemisphere. Further reductions in N -acetyl aspartate and total creatine concentrations occurred within the first week. A fall in the lactate concentration was seen within the infarct core during the first 7 to 10 days. Similar reductions in the choline concentration were observed during this period.
Conclusions The demonstration of the continuing loss of cerebral metabolites within an infarct region suggests that further cell loss occurs up to 10 days after infarction. The continuing loss of neurons may represent continued ischemic damage after middle cerebral artery infarction.
TL;DR: The high risk associated with hypertension but absent risk with heart disease supports the ``lacunar hypothesis'' of a unique pathophysiologic mechanism for lacunar stroke.
Abstract: Background and purpose: Lacunar infarction is an important stroke subgroup with unique clinical and pathologic features, but its relative risks for associated risk factors have been rarely documented. To address this matter, we studied 203 consecutive patients with first-ever stroke due to lacunar infarction admitted to four general hospitals during the period 1985 to 1992. Methods: We obtained information concerning risk factor exposure status among the patients by interview using a structured questionnaire and by comparison with age- and sex-matched neighborhood controls. Odds ratios were estimated with adjustment for confounding variables by using multivariate logistic regression. Results: Significantly increasing the risk of lacunar stroke were hypertension (with an odds ratio of 8.9 [95% confidence intervals 4.2, 18.8]), current smoking (6.6 [2.9, 14.8]), and diabetes (2.3 [1.0, 5.5]), whereas frequent physical exercise was associated with a significantly decreased risk (0.3 [0.1, 0.7]). There was no risk of lacunar stroke associated with heart disease (odds ratio 1.0 [0.5, 1.9]). Conclusions: Patients with hypertension or diabetes, and those who currently smoke, are at a higher risk of lacunar stroke, whereas those who undertake regular physical exercise may be at lower risk. The high risk associated with hypertension but absent risk with heart disease supports the ``lacunar hypothesis99 of a unique pathophysiologic mechanism for lacunar stroke. NEUROLOGY 1995;45: 1483-1487
TL;DR: A model of occlusive stroke in the aging rat brain has been developed and used to establish the effects of age on cerebral infarction and to evaluate the scope for protecting the aging brain during ischemia, and NMDA receptor antagonism was neuroprotective in the Aging brain.
Abstract: Background and Purpose Experimental stroke research has for the most part incorporated the use of young animals despite the importance of aging in cerebrovascular disease in humans. We hypothesized that age-related reductions in the density and function of cortical N -methyl-d-aspartate (NMDA) receptors might limit neuroprotective potential in the elderly. In this study, a model of occlusive stroke in the aging rat brain has been developed and used to establish the effects of age on cerebral infarction and to evaluate the scope for protecting the aging brain during ischemia.
Methods Focal cerebral ischemia was produced by thermocoagulation of the left middle cerebral artery in adult (11 to 17 months) and aged (28 to 36 months) male Wistar rats. Infarcts were assessed histologically with volumetric analysis of infarct size, hemodynamically by serial cerebral blood flow measurement using the hydrogen clearance technique, and by analysis of specific gravity as an index of brain edema. Neuroprotective potential was assessed using the competitive NMDA receptor antagonist 3-(2-carboxy piperazin-4-yl)propyl-1-phosphonate (d-CPPene).
Results Aging was associated with a significant increase in infarct size, with a mean infarct volume of 40.5±2.6% of the hemisphere volume in aged rats compared with 30.9±0.7% in adult rats ( P <.01). d-CPPene reduced the mean infarct volume to 33±1.8% and 20.7±3.2% in aged and adult rats, respectively ( P <.05). Cerebral blood flow fell markedly after infarction, but thereafter d-CPPene–pretreated rats maintained higher cerebral blood flow than untreated animals throughout the duration of the experiment (22.8±3.2 and 30.1±5.5 mL · 100 g−1 · min−1 in treated aged and adult rats, respectively, compared with 11.3±2.7 and 16.5±3.2 mL · 100 g−1 · min−1 in untreated aged and adult groups, 90 minutes after infarction [ P <.05]). Pretreatment also reduced cortical edema; mean cortical specific gravity 4 hours after infarction was 1.0381±0.0013 in untreated aged rats and 1.0391±0.0014 in untreated adults compared with 1.0458±0.0031 in treated aged rats and 1.0442±0.0014 in treated adult rats ( P <.05).
Conclusions Under similar experimental conditions, there was an age-related increase in cerebral infarct size. However, NMDA receptor antagonism was neuroprotective in the aging brain and resulted in a significant reduction in cerebral ischemic damage, less cortical edema, and preservation of cerebral blood flow.
TL;DR: Results indicate that much of the increased risk for cerebral infarction experienced by blacks can be explained by their higher prevalence of stroke risk factors, especially diabetes, hypertension, and lower educational attainment.
Abstract: Objective: To determine whether blacks in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study remained at increased risk for cerebral infarction after adjusting for stroke risk factors and sociodemographic factors. Methods: A cohort study involving 8203 whites and 1362 blacks who participated in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. During the 13-year follow-up, 538 and 122 cerebral infarctions occurred in whites and blacks, respectively. Results: The black-white risk for cerebral infarction varied by age (P=.007 for race-age interaction). Compared with whites of the same age, blacks aged 35 to 44 years were at significantly increased risk for cerebral infarction (relative risk, 2.62; 95% confidence interval, 1.23 to 5.57), while older blacks, those older than 64 years, were not at increased risk (relative risk, 1.14; 95% confidence interval, 0.90 to 1.46). The relative risk for cerebral infarction decreased to 2.07 (95% confidence interval, 0.97 to 4.42) in younger blacks and 0.82 (95% confidence interval, 0.29 to 2.33) in older blacks after adjustment for age, sex, education, history of heart disease, diabetes, systolic blood pressure, treatment for hypertension, Quetelet index, and serum hemoglobin and magnesium levels. Conclusions: These results indicate that much of the increased risk for cerebral infarction experienced by blacks can be explained by their higher prevalence of stroke risk factors, especially diabetes, hypertension, and lower educational attainment. Younger blacks, however, may still be at increased risk after adjusting for stroke risk factors. (Arch Intern Med. 1995;155:1319-1324)
TL;DR: The high frequency of hypertension, hypertensive intracerebral hemorrhage, and lacunar infarction among young black patients with stroke suggests accelerated hypertensive arteriolar damage, possibly due to poor control of hypertension.
Abstract: Background and Purpose Stroke subtypes and prognosis differ among older black patients compared with whites; however, few data are available regarding stroke among young black patients. Methods To determine the risk factors for stroke, stroke subtype, and prognosis among young black patients, we retrospectively reviewed the medical records of all 15- to 44-year-old patients admitted with stroke to a university-affiliated public hospital from January 1990 through June 1994. Results Of the 248 eligible patients admitted with stroke, 219 were blacks. Hypertension was more frequently associated with stroke in young black than in non-black patients (55% versus 24%, P=.003). Cocaine abuse was frequent among both black and non-black patients (27% versus 38%, P=NS). Hypertensive intracerebral hemorrhage (64%) was the most common subtype of intracerebral hemorrhage (n=67), and lacunar infarction (21%) was the most common subtype of cerebral infarction (n=112) in young black patients. Outcome in black patients with...
TL;DR: Insulin is shown to ameliorate damage in models of global brain ischemia and reduce total damage (atrophy plus cortical and striatal necrosis), expressed as the percentage of the normal hemisphere, from a control of untreated animals.
Abstract: ✓ Insulin has recently been shown to ameliorate damage in models of global brain ischemia. To determine whether insulin is also neuroprotective in focal ischemia, 20 rats were given 2 to 3 IU/kg insulin and 10 did not receive treatment prior to normothermic transient middle cerebral artery occlusion for 2 hours at a blood pressure of 60 mm Hg. To further elucidate whether infarction volume is influenced by variations in blood glucose levels within the physiological range, blood glucose was raised in 10 of the insulin-treated animals to levels comparable with the untreated controls. At 1-week survival, damage was assessed using quantitative neuropathological examination of 25 coronal planes. It was found that preischemic insulin lowered the mean intraischemic blood glucose level from 8.4 ± 0.2 mM (µ ± standard error of the mean) in the control group to 3.4 ± 0.2 mM and reduced total damage (atrophy plus cortical and striatal necrosis), expressed as the percentage of the normal hemisphere, from a control of...
TL;DR: The results demonstrate that measurement of the size of middle cerebral artery infarction with MRI is a useful tool in assessing prognosis and will have a valuable role in assessing new therapeutic agents.
Abstract: Background and Purpose An accurate measure of the severity of ischemic insult and the resulting prognosis is needed to assess the effectiveness of new treatments for acute stroke. We studied the reproducibility and accuracy of measurements of infarct volume with MRI and correlated the measurements with outcome. Methods Infarct volume was measured on T2-weighted images with the Analyze image analysis software. This technique was found to be highly accurate and reproducible. Results Measurements of infarct volume were found to be highly accurate and reproducible. Twenty-one patients (mean age, 66.5 years; range, 28 to 90 years) with cortical middle cerebral artery territory infarcts in whom adequate data could be obtained were studied within 72 hours from onset (mean delay to MRI, 27.5 hours; range, 5 to 72 hours). The Scandinavian Stroke Scale was used to calculate a prognostic score, and clinical outcome was assessed at 3 months. Infarct volume was found to significantly predict outcome. Mean infarct volu...