Ischemic Brain Infarction Research Articles

Mild to moderate atheromatous disease of the thoracic aorta and new ischemic brain lesions after conventional coronary artery bypass graft surgery.

The presence of new ischemic brain infarcts, detected by diffusion-weighted magnetic resonance imaging (DW-MRI), have been reported in considerable number of patients after cardiac surgery. We sought to determine the role of proximal thoracic aortic atheroma in predicting embolic events and new ischemic brain lesions in patients undergoing conventional coronary revascularization surgery. Transesophageal echocardiography and epiaortic scanning was performed to assess the severity of aortic atherosclerosis in the ascending aorta and the aortic arch. Patients were allocated to either low-risk group, (intimal thickness < or =2mm), or high-risk group (intimal thickness >2mm). Transcranial Doppler was used to monitor the middle cerebral artery. DW-MRI was performed 3-7 days after surgery. The NEECHAM Confusion Scale was used for assessment and monitoring patient consciousness level. Patients in the high-risk group were considerably older; 71+/-6 (n=38) versus 67+/-6 (n=72) years, P=0.004 and were more likely to have impaired left ventricular function. Confusion was present in 6 (16%) patients in the high-risk group and 5 (7%) patients in the low-risk group. Patients in the high-risk group had a three-fold increase in median embolic count, 223.5 versus 70.0, P=0.0003. DW-MRI detected brain lesions were only present in patients from high-risk group, 61.5 versus 0%, P<0.0001. There was significant correlation between the NEECHAM scores and embolic count in the high-risk group; r=0.63, P<0.001. The findings of this investigation suggest that mild to moderate atheromatous disease of the ascending aorta and the aortic arch (intimal thickness >2mm) is a major contributor to ischemic brain injury after cardiac surgery.

Prophylactic creatine administration mediates neuroprotection in cerebral ischemia in mice.

Creatine mediates remarkable neuroprotection in experimental models of amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and traumatic brain injury. Because caspase-mediated pathways are shared functional mechanistic components in these diseases, as well as in ischemia, we evaluated the effect of creatine supplementation on an experimental stroke model. Oral creatine administration resulted in a remarkable reduction in ischemic brain infarction and neuroprotection after cerebral ischemia in mice. Postischemic caspase-3 activation and cytochrome c release were significantly reduced in creatine-treated mice. Creatine administration buffered ischemia-mediated cerebral ATP depletion. These data provide the first direct correlation between the preservation of bioenergetic cellular status and the inhibition of activation of caspase cell-death pathways in vivo. An alternative explanation to our findings is that creatine is neuroprotective through other mechanisms that are independent of mitochondrial cell-death pathways, and therefore postischemic ATP preservation is the result of tissue sparing. Given its safety record, creatine might be considered as a novel therapeutic agent for inhibition of ischemic brain injury in humans. Prophylactic creatine supplementation, similar to what is recommended for an agent such as aspirin, may be considered for patients in high stroke-risk categories.

Alcohol Misuse: A Risk Factor for Putaminal Damage by Ischemic Brain Infarct?

The relationship between alcohol consumption and the risk of ischemic stroke has been widely studied, whereas the effect of alcohol use on stroke features is not well established. This study compared the clinical and stroke features of ischemic stroke in two groups of patients with ischemic stroke: those with a history of alcohol misuse and those with a history of more social drinking. DSM-IV criteria were used to diagnose alcohol use disorder (dependency or abuse) in 275 of 486 consecutive patients aged 55–85 years, 3–4 months after ischemic stroke. Magnetic resonance imaging of the head was performed 3 months after stroke. Alcohol use disorder was diagnosed in 37/275 (13.5%) of ischemic stroke patients. These patients had more frequently (70.3 vs. 34.5%; OR 4.5; 95% CI 2.2–9.1; p < 0.000) an infarct affecting the putamen compared with patients who indulged in more social drinking. Another predisposed area was the superior anterior cerebral artery area. The stroke due to large- artery atherosclerosis was more common in patients with alcohol use disorder. The misuse of alcohol seemed to be associated with cerebral infarct localization in the putamen and superior anterior cerebral artery area. Prospective studies are needed to verify our preliminary finding.

Response

Response

Administration of Nonionic Iodinated Contrast Medium Does Not Influence the Outcome of Patients with Ischemic Brain Infarction

Some reports indicate that exposure to iodinated contrast medium (CM) could worsen the outcome of patients with brain infarction. In this prospective study, we compared the outcome of 77 patients receiving and 128 not receiving nonionic iodinated CM. Stroke severity was assessed by the Scandinavian Prognostic Stroke Score, and outcome by the Rankin Scale. All radiological studies using intravenous or intra-arterial CM were registered. Two nonionic iodinated CM (iopamidol and iohexol) were used. Exposure to CM did not influence case fatality, ability to live at home, ability to walk, disability and stroke severity. Initial stroke severity and arterial hypertension were independent determinants of poor neurological recovery or death. Large infarct, age, male gender, and baseline stroke severity were independent determinants of major disability or death. CM enhancement on CT did not show any harmful effect on stroke severity or outcome. As a conclusion, intravascular administration of nonionic iodinated CM did not influence stroke severity or outcome of our patients.

Proximal and distal hyperattenuating middle cerebral artery signs at CT: different prognostic implications.

To determine whether a proximal (M1-segment) or distal (M2- and/or M3-segment) hyperattenuating middle cerebral artery (MCA) sign in patients with ischemic infarction in the territory of the MCA indicates a worse short-term prognosis than that in patients without a hyperattenuating MCA sign. We retrospectively reviewed the records of 352 patients who were diagnosed with ischemic brain infarction in the territory of the MCA. Of these patients, 186 patients met our final criteria and were included in this study. Nonenhanced computed tomography (CT) was performed for the entire brain, with a 5-mm section thickness in all patients, within 24 hours after symptom onset. The presence and location of a hyperattenuating MCA sign was correlated with neurologic deficit at discharge from the hospital (ie, short-term prognosis) by using the chi(2) test to detect differences between patient groups. Patients with a hyperattenuating MCA sign at CT have a worse short-term prognosis than do patients without a hyperattenuating MCA sign (P <.05). Patients with a proximal hyperattenuating MCA sign have a significantly (P <.01) worse short-term prognosis than do patients with a distal hyperattenuating MCA sign. A proximal hyperattenuating MCA sign is a reliable predictor of poor short-term prognosis in patients who experience acute stroke.

Neuroprotective effect of cilostazol against focal cerebral ischemia via antiapoptotic action in rats.

This study examined the protective effects of cilostazol on cerebral infarcts produced by subjecting rats to 2-h occlusion of the left middle cerebral artery followed by 24-h reperfusion. The ischemic cerebral infarct consistently involved the cortex and striatum. The infarct size was significantly reduced, when rats received 10 mg/kg cilostazol intravenously 5 min or 1 h after the completion of 2-h ischemia. Cyclic AMP level was significantly elevated in the cortex of 4- and 12-h reperfusion (P < 0.01) following treatment with cilostazol (10 mg/kg, 5 min after 2-h ischemia) accompanied by decreased tumor necrosis factor-alpha level. Samples from the regions corresponding to the penumbra showed markedly reduced Bcl-2 protein level and, in contrast, high levels of Bax protein and cytochrome c release. Cilostazol decreased Bax protein and cytochrome c release and increased the levels of Bcl-2 protein. Cilostazol (10(-7)-10(-5) M) potently and concentration dependently scavenged hydroxyl and peroxyl radicals. In conclusion, cilostazol treatment decreases ischemic brain infarction in association with inhibition of apoptotic and oxidative cell death.

Early stroke: a dynamic process.

In the acutely infarcted brain, cytokines are released into cerebrospinal fluid and blood. Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, among others, may play a role in the acute increases in plasma adrenocorticotropic hormone, cortisol, epinephrine, norepinephrine, and vasopressin.1–6 Increases in cytokines and hormones may in turn induce changes in other variables. When recorded on admission in acute stroke patients, many variables have been found to be associated with poor outcome in acute stroke. Body temperature7 is one such variable, blood glucose another,8–18 and C-reactive protein (CRP)19–22 and white blood cell count (WBC)20,23 serum cortisol and ferritin24 are further examples. Elevated plasma and cerebrospinal fluid levels of glutamate, glycine,25 ferritin,26 and IL-627 were also associated with deteriorating stroke. It seems plausible that these variables generally are unaffected at stroke onset and then increase in the early hours after onset, depending on the severity of the stroke. We found this to be the case with temperature,28 which in a large series of patients was normal when measured within 2 hours of stroke onset, but which rose at 4 to 6 hours after stroke onset in patients with severe neurological deficits. At 8 to 10 hours after stroke onset, elevated temperature was associated with poor outcome. This association arose several hours after onset of severe stroke. Thus, the initial severity of the stroke …

Association of immune responses and ischemic brain infarction in rat.

Inflammation plays an important role in the pathogenesis of neurodegenerative diseases including ischemia. Occlusion of common carotid artery and middle cerebral artery has been used to produce focal ischemic lesions in the rat. Here, we examined the associations between immune reactions and postischemic brain infarction. Ischemia/reperfusion time-dependently caused brain infarction. The kinetics of inflammatory reactions in rat brain including inflammatory cell infiltration, edema formation, cytokines/chemokines and adhesion molecules production and matrix metalloproteinase activation were relevant to the progression of ischemic infarction. Differential induction profile after ischemia suggests that this activation might contribute to secondary brain damage in ischemic tissues. On the other hand, another possibility of this response is to trigger processes that mediate the neural regeneration after ischemic injury.

Masking of Vertebral Artery Dissection by Severe Trauma to the Cervical Spine

A prospective case study was performed. To illustrate the association of cervical trauma with vertebral artery dissection, and to propose a diagnostic and therapeutic algorithm for suspected traumatic vertebral artery dissection. Vertebral artery dissection is a recognized but underdiagnosed complication of trauma to the cervical spine. Symptoms of spinal cord injury, however, may obscure those of vertebral artery dissection, presumably causing gross underdiagnosis of this complication. All patients with vertebral artery dissection admitted to the authors' facility between 1992 and 1997 were screened for cervical trauma. This article presents four patients with severe trauma to the cervical spine, defined as luxation, subluxation, or fracture, in whom symptoms of vertebral artery dissection developed after a delay ranging from several hours to weeks. The traumatic vertebral artery dissection typically was located at the site of vertebral injury or cranial to it. One patient with fracture of the odontoid process survived symptom free without ischemic brain infarctions. Another patient survived with traumatic quadriplegia in addition to large cerebellar and posterior cerebral artery infarctions. Two patients died as a result of fulminant vertebrobasilar infarctions, both with only moderate impairment from the primary spinal cord injury. Early signs of vertebral artery dissection include head and neck pain, often localized to the site of intimal disruption, which may be disguised by the signs of the spinal injury. Early Doppler ultrasound and duplex sonography as a noninvasive screening method should be performed for patients with severe trauma to the cervical spine. In cases of vertebral artery dissection, immediate anticoagulation should be initiated. Traumatologists should be aware of this complication in evaluating patients with severe trauma of the cervical spine, and also for a variety of forensic reasons.

Diffusion-Weighted MR Imaging in Animal Model with Acute Ischemic Brain Infarction: Evaluation of Reversible Brain Injury

Purpose: To determine whether the analysis of abnormally high signal intensities in ischemic tissue, as revealed by diffusion-weighted MR imaging (DWI) can be used to evaluate reversible brain lesions in a cat model of acute ischemia. Materials and Methods: Ten cats were divided into two groups of five (Group I and Group II), and in all animals the middle cerebral artery was temporarily occluded. Group I underwent T2-DWI 30 minutes after occlusion, and Group II 120 minutes after occlusion. In both groups, DWI was performed one hour and 24 hours after reperfusion (at one hour, non-T2-weighted; at 24 hours, T2-weighted). Both occlusion and reperfusion were monitored by brain perfusion SPECT. All animals were sacrificed 24 hours later and their brain tissue was stained with TTC. Signal intensity ratios (SIR, signifying average signal intensity within the region of interest divided by that in the contralateral, nonischemic, homologous region) of the two groups, as seen on DWI were compared. The percentage of hemispheric lesions occurring in the two groups was also compared.Results: SIR after occlusion of the middle cerebral artery was 1.29 in Group I and 1.59 in Group II. Twenty-four hours after reperfusion, SIR in Group I was higher than in Group II (p

Abstracts of literature

Abstracts of literature

Aphasia, Depression, and Non-Verbal Cognitive Impairment in Ischaemic Stroke

Aphasia, depression, and cognitive dysfunction are common consequences of stroke, but knowledge of their interrelationship is limited. This 1-year prospective study was designed to evaluate prevalence and course of post-stroke aphasia and to study its psychiatric, neurological, and cognitive correlates. We studied a series of 106 consecutive patients (46 women and 60 men, mean age 65.8 years) with first-ever ischaemic brain infarction. The patients were clinically examined, and presence and type of aphasia were evaluated during the 1st week after stroke and 3 and 12 months later. Psychiatric and neuropsychological evaluations were performed 3 and 12 months after stroke. Aphasia was diagnosed in 34% of the patients during the acute phase, and two thirds of them remained so 12 months later. Seventy percent of the aphasic patients fulfilled the DSM-III-R criteria of depression 3 months and 62% 12 months after stroke. The prevalence of major depression increased from 11 to 33% during the 12-month follow-up period. The non-verbal neuropsychological test performance in the aphasic patients was significantly inferior to that of the patients with dominant hemisphere lesion without aphasia. One third of the patients with ischaemic stroke suffer from communicative disorders which seem to increase the risk of depression and non-verbal cognitive deficits. Although the prevalence of depression in aphasic patients decreases in the long term, the proportion of patients suffering from major depression seems to increase. We emphasize the importance of the multidimensional evaluation of aphasic stroke patients.

How complex interactions of ischemic brain infarcts, white matter lesions, and atrophy relate to poststroke dementia.

Cerebrovascular disease is a major factor related to cognitive impairment. However, behavioral correlates of ischemic brain lesions are insufficiently characterized. To examine magnetic resonance imaging correlates of dementia in a large, well-defined series of patients with ischemic stroke. Detailed medical, neurological, and neuropsychological examinations were conducted 3 months after ischemic stroke for 337 of 486 consecutive patients aged 55 to 85 years. Infarcts (type, site, side, number, and volume), extent of white matter lesions (WMLs), and degree of atrophy were categorized according to magnetic resonance images of the head. The definition for dementia of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) was used. Dementia was diagnosed in 107 (31.8%) of the patients and stroke-related dementia in 87 (25.8%). Volumes, numbers, distinct sites of infarcts, extent of WMLs, and degree of atrophy were different for the demented and nondemented subjects. Particularly, volumes of infarcts in any (right- or left-sided) superior middle cerebral artery territory (27.3 vs 13.7 cm(3), P =. 002) and left thalamocortical connection (14.8 vs 4.0 cm(3), P =. 002) differentiated the 2 groups. Logistic regression analysis showed that the correlates of any dementia included the combination of infarct features (volume of infarcts in any superior middle cerebral artery: odds ratio [OR], 1.11; frequency of left-sided infarcts: OR, 1.21), extent of WMLs (OR, 1.3), medial temporal lobe atrophy (OR, 2.1), and host factors (education; OR, 0.91). In the patients with stroke-related dementia, the main correlate was volume of infarcts in the left anterior corona radiata (OR, 1.68). Correlates of poststroke dementia do not include merely 1 feature but a combination of infarct features, extent of WMLs, medial temporal lobe atrophy, and host features.

脳梗塞急性期医療の実態 厚生省健康科学総合研究事業脳梗塞急性期医療の実態に関する研究

To investigate present status of ischemic stroke patients in Japan, a nation-wide, hospital-based survey was performed during a period from April 1997 to March 1998. Questionnaires were sent by mail to 4, 957 institutes selected on the basis of hospital lists published by the Ministry of Health and Welfare and of active members of Japan Stroke Society, Japanese Society of Neurology, Japanese Society of Emergency Medicine, and members of rank-A Neurosurgical training hospital.2, 048 valid responses were obtained from 1, 787 institutes (Responses were sent from 2 or more departents of the same institute).Results are summarized as follows :1) Ischemic brain infarction was found to be over 70% of all strokes. 2) Less than 30% of patients visited hospital within 6 hours of onset. 3) 43.6% of the institutes replied that they used thrombolytic agents at least in one patient (Thrombolytic agents were used, by calculation, in 8.3% of all patients), but true thrombolytic therapy (sufficient dose for thrombolysis) were performed in less than 17% of the institutes. 4) Intraarterial thrombolysis was carried out in 26% of the institutes, which made 2.7% of the all patients, by rough calculation. 5) The drug most frequently used for acute ischemic stroke in Japan was ozagrel sodium. 6) Only 3% of the institutes were equipped with stroke (care) unit (SCU). In 73% of the institutes, stroke patients were treated in general wards. 7) A mean hospital stay exceeded 28 days in 75% of the institutes (41 days in average). 8) An estimated mortality during admission was about 9%.

Hypoglossal motoneurons are postsynaptically inhibited during carbachol-induced rapid eye movement sleep

The obstructive sleep apnea syndrome is characterized by the occurrence of cyclic snoring and frequent apneic episodes during sleep, with consequent hypoxia and hypercapnia. 12 Obstructive sleep apnea syndrome is associated with excess daytime sleepiness, depression, and an increased incidence of ischemic cardiopathy, cardiac arrythmias, systemic hypertension and brain infarction. 12,13,28,29 Hypoglossal motoneurons, which innervate extrinsic and intrinsic muscles of the tongue, play a key role in maintaining the patency of the upper airway and in the pathophysiology of obstructive sleep apnea syndrome. 14,16,23 Based on data obtained by using extracellular recording techniques, 19 there is a consensus that hypoglossal motoneurons cease to discharge during rapid eye movement sleep, 17,24,32 because they are disfacilitated. 19–21 Since other somatic motoneurons are known to be postsynaptically inhibited during rapid eye movement sleep, 6,25,27,30 we sought to determine, by the use of intracellular recording techniques during cholinergically induced rapid eye movement sleep, 2,21,22,26,34 whether postsynaptic inhibitory mechanisms act on hypoglossal motoneurons. We found that, during this state, a powerful glycinergic premotor inhibitory system acts to suppress hypoglossal motoneurons. This finding opens new avenues for the treatment of obstructive sleep apnea syndrome, and provides a foundation to explore the neural and pharmacological control of respiration-related motoneurons during rapid eye movement sleep.

Aterosclerosis y circulación cerebral

Atherosclerosis affects the vascular system in a diffuse way and its is clearly implicated in some of the most prevalent diseases in western countries such as cerebrovascular and cardiovascular diseases. Knowing more about the underlying pathogenic mechanisms may contribute to a better understanding of this entities and the development of therapies for both its treatment and prevention. We review herein the concepts included in the term atherosclerosis, the growth of the atheromatous plaque and its complications and the cellular mechanisms which intervene in its development. We analyze how it influences brain hemodynamics and its implication in cerebrovascular ischemic disease paying attention to the dissimilarities with other vascular territories and the clinical syndromes which derive from its development on different vascular structures. Under the concept of ischemic cerebrovascular disease we can find a group of heterogeneous clinical syndromes, usually associated to different etiopathogenic mechanisms: cardioembolic, atherothrombotic or hemodynamic. Although their risk factors may be common, these processes are clearly different form each other. Therefore including ischemic brain infarctions all together without attending to their etiology may produce important methodological biases when interpreting the results in clinical trials or other studies, and may also be a suitable explanation for differences between authors.

Inhibition of Neutrophil Migration by a Protein Kinase Inhibitor for the Treatment of Ischemic Brain Infarction

This study investigated the therapeutic potential of agents that inhibited neutrophil infiltration in cerebral ischemic infarction. The migration of neutrophils elicited by N-formyl-methionyl-leucyl-phenylalanine, tumor necrosis factor, C5a or platelet-activating factor was potently inhibited by fasudil, an inhibitor of protein kinases including rho kinase, protein kinase C and myosin light chain kinase, and hydroxy fasudil, a metabolite of fasudil, in vitro. In a microembolism model in rats, myeloperoxidase-quantified neutrophil accumulation in the ischemic brain was observed 24 hr after embolization. Intravenous administration of fasudil prevented the accumulation of neutrophils. In rats given fasudil, myeloperoxidase activity in the ipsilateral hemisphere (0.04±0.01 unit/g wet tissue) was significantly lower than that in ischemic rats (0.11±0.02 unit/g wet tissue). Fasudil also significantly reduced the size of the infarct area and improved neurological functions. These results suggest that neutrophil infiltration into the ischemic brain is involved in the pathogenesis of ischemic injury and that inhibiting neutrophil infiltration may provide an effective therapeutic intervention to reduce ischemic injury.

Kinking and stenosis of the carotid artery associated with homolateral ischaemic brain infarction in a patient treated with cyclosporin A

We present a 3-year-old patient with stenotic kinking of the left internal carotid artery (ICA) who developed an ischaemic infarction of the left brain hemisphere followed by severe neurological sequelae after a prolonged generalized seizure. At time of the seizure the boy was in biological remission of a nephrotic syndrome and received prednisolone and cyclosporin A (CsA) treatment. The haemodynamic consequences of inborn kinking of the ICA is discussed controversely in the literature. The presented case shows that stenotic kinking of the ICA may significantly impair the blood flow towards the homolateral hemisphere and therefore may result in an ischaemic infarction. The influence of CsA on seizure activity is discussed. This case provides clinical and radiological evidence supporting an association between stenotic kinking of the carotid artery and homolateral hemispheric brain infarction.

Long-Term Compliance with Continuous Positive Airway Pressure in Patients with Obstructive Sleep Apnea Syndrome

A ten-year retrospective analysis of the clinical features and survival of 60 Saudi children with systemic lupus erythematosus (SLE) was made. All the patients fulfilled the 1982 American College of Rheumatologyâs revised criteria for SLE and had had the disease at or before the age of 16 years. The female to male ratio was 5:1, the mean age of onset was 12.1 years (range 1.6-16 years), and the mean duration of follow-up was 4.7 years (range 2.2-11). Thirty-eight patients (63%) were diagnosed correctly before referral to KFSH&RC or KKUH. The mode of presentation was as follows: 55 patients had musculoskeletal involvement (91.6%), 49 patients had skin involvement (81.6%), 40 patients had hematological abnormalities (66.6%), 39 patients had renal disease (65%), 10 patients had pulmonary involvement (16%), 23 patients had cardiovascular disease (38%) and 18 patients had central nervous system involvement. During the study period four patients died (6.6%)âtwo of renal failure, one from meningitis and one from severe sepsis. This is the largest collection of childhood systemic lupus erythematosus from the Middle East and it shows that SLE is more common in Saudis than was hitherto believed, and that it has a high rate of organ involvement.