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PubMed1986

[MR of ischemic brain diseases. A comparison with CT, PET (18-fluorodeoxyglucose) and angiographic results].

The results of MRI and CT in 55 patients with brain infarcts were compared; in 26 of these cases an additional PET examination was obtained in order to study the regional glucose utilisation. MRI was superior to CT, demonstrating 11% more of the infarcts, particularly during the first 24 hours, in small lesions confined to the grey or subcortical white matter and in infratentorial ischemic lesion. On the other hand, only CT was able to show fresh hemorrhage, although MRI was the method of choice to demonstrate old blood collections. To characterise the follow up of an infarct, CT and MRI were similar, except the marginal contrast enhancement sometimes demonstrated by CT studies between the 2nd and 4th week after stroke event. PET was inferior to show details because of its poorer spatial resolution, but anyhow had a high sensitivity and provided additional informations concerning secondary inactivations of brain areas not directly damaged. Additionally PET was able to demonstrate areas of anaerobic glycolysis and lesions of diminished glucose utilisation in TIAs. Small areas of gliosis in the white matter of the cerebral hemispheres were frequently found in patients with cerebro-vascular diseases; they were best shown by MRI, but do not correlate with the extent of vascular stenoses or occlusions, shown by angiography.

Adolescent↗
PubMed1983

Childhood Köhlmeier-Degos disease with atypical skin lesions.

We report clinical and pathologic findings in a 16-year-old boy whose disease began in infancy with maculopapular skin lesions, followed by cyclic nodular cutaneous eruptions, intermittent enlargement of liver and spleen, episodic abdominal pain, and sporadic unexplained fever. Subsequently, various ophthalmologic disturbances, along with a multitude of neurologic signs and symptoms, dominated the clinical picture. The CNS bore the brunt of pathologic changes, characterized by widespread leptomeningeal fibrosis, ventricular enlargement, and multiple brain infarcts. Striking intimal thickening led to narrowing or occlusion of almost all the medium-sized and small extraparenchymal arteries.

Arterial Occlusive Diseases↗
PubMedDate not supplied

[Treatment of hypertension in acute neurological diseases].

Continuous brain blood supply in healthy individuals is warranted by brain autoregulation, the borders of which are not completely strict and can be changed as a part of dynamic physiological control. In acute neurological diseases like hypertensive encephalopathy, brain infarction, intracerebral hemorrhage and subarachnoid hemorrhage, a great attention should be paid to cerebral perfusion pressure preservation (which represents a difference between mean arterial pressure and intracranial pressure) when blood pressure is regulated. To preserve neurological function it is necessary to know anatomic and pathophysiological qualities of brain circulation and to approach the treatment of hypertension. In case of ishemic stroke hypertension should be reduced gradually, through several days, having in mind the distance of ischemic penumbra. The ideal antihypertensive for the reduction of hypertension in acute neurological diseases should have the following characteristics precise value and time control of blood pressure, not to have a rebound-phemonenon, not to cause the effect of exceeding with initially severe hypotension, not to have impact on heart muscle and not to worsen intracranial pressure. In everyday clinical work with these patients one should act according to the instructions for management of patients with stroke prepared by the Croatian Society for Neurovascular Disorders of the Croatian Medical Association and the Croatian Society for the Prevention of Stroke.

Acute Disease↗
PubMed1995

[Clinical significance of selective cerebral perfusion with cold blood on the brain protection].

In 42 patients with thoracic aortic disease, a selective cerebral perfusion with 16 degrees C cold blood was applied for the brain protection during the repair of the thoracic aorta. The surgical repair consisted of the replacement of the ascending aorta (9 cases), the ascending aorta and aortic arch (12 cases), the aortic arch (18 cases), and the aortic arch and descending aorta (3 cases). Twenty-two patients of them (52%) required emergency surgery and four patients died due to postoperative complications including visceral organ ischemia (2 cases) and multiple organ failure (2 cases). The mortality rate of this group was 18.2% (4/22 cases). In elective surgical classes, one patient died due to intraoperative coronary embolism. The mortality rate of this group was 5.0% (1/20 cases). No postoperative obvious brain defect was observed except one old patient (85-year-old female) with ruptured aortic arch who already had the brain infarction preoperatively. She died due to multiple organ failure with unconsciousness. Other patients including the patients with long cerebral perfusion (> 180 min) recovered well and returned to normal daily life. The selective cerebral perfusion with cold blood was easy to prepare and demonstrated the superb efficacy of brain protection in the patient.

Adult↗
PubMed2006

[Acute disorders of cerebral circulation: prognostic factors in essential hypertension].

AIM: To study subclinical signs of cerebrovascular pathology as prognostic factors of development of acute disorders of cerebral circulation (ADCC) in essential hypertension (EH). MATERIAL AND METHODS: A prospective (10-13 years) cohort trial of prognostic significance of subclinical forms of cerebral pathology in EH in relation to ADCC development covered 111 men aged 45-55 years who had undergone a unified neurological and cardiological examination in 1992-1993. RESULTS: Such factors as disordered circulation along major arteries of the head (a relative risk 3.1 [1.2; 10.3]), thick intima-media complex of the common carotid artery (a relative risk: 5.2 [2.1; 14.3]), the presence of asymptomatic lacunar brain infarctions (a relative risk: 6.6 [2.3; 13.5]) were revealed to be of unfavourable prognostic significance in respect to development of ADCC in EH. CONCLUSION: Some subclinical risk factors may have prognostic value in relation to development of ADCC in EH.

Acute Disease↗
PubMed1988

Experimental thromboembolic stroke studied by positron emission tomography: immediate versus delayed reperfusion by fibrinolysis.

Acute obstruction of the middle cerebral artery (MCA) was obtained by injecting a single autologous blood clot into the internal carotid artery of dogs. The technique induced very reproducible unilateral ischemic lesions in the MCA territory; hemorrhagic transformation of the lesions was often seen. The hemodynamic and metabolic effects of blood clot embolism were studied in 35 dogs with positron emission tomography (PET) and the 15O steady-state technique, and compared with a control group of seven intact animals. In the acute phase, the involved brain tissue still had a nearly normal oxygen consumption (-11%) despite the lowered tissue perfusion (-20%) caused by the vascular obstruction. The lowered oxygen availability was compensated by an increased oxygen extraction ratio (+11%). Twenty-four hours after the insult, the hemodynamic situation had barely changed, and the ischemic event had evolved into a brain infarct in which oxygen consumption was clearly lowered (-25%) and accompanied by a significant lowering (-22%) of the oxygen extraction ratio compared with the acute situation. Therapeutic thrombolysis by local administration of streptokinase (500,000 IU), starting 30 min after the insult, was not able to salvage any brain tissue or to ameliorate tissue perfusion despite angiographically confirmed clot lysis. However, when fibrinolytic therapy was started within the first 5 min after the insult, hemispheric blood flow was normalized, and most of the threatened brain tissue was salvaged, as was indicated by its normalized oxygen consumption and oxygen extraction ratio. Early fibrinolysis was accompanied by definite clinical improvement and substantial reduction in the severity of the morphological lesions that were never hemorrhagic.

Animals↗
PubMed2006

The Khorasan Stroke Registry: results of a five-year hospital-based study.

The hospital-based stroke registry is useful for understanding the diverse clinical characteristics of stroke related to geographical, racial or environmental differences. The Khorasan Stroke Registry (KSR) was established for the evaluation of incidence, clinical manifestations, risk factors, topography and etiology of ischemic stroke in Southern Khorasan, Iran, during 2001-2005. Consecutive stroke patients underwent a standard battery of diagnostic investigations by a stroke neurologist. The topography and etiology of brain infarction were determined by the Practical Iranian Criteria classification. The incidence of ischemic stroke in the Persian population is 43.17 cases per 100,000 people per year. A total of 1,392 ischemic stroke patients (738 females, 654 males) were evaluated in the KSR. The etiologies included atherosclerosis (53.6%), followed by uncertain causes (19.9%), cardioembolism (11.8%) and miscellaneous etiologies (2.9%). Of our patients, 11.7% had both atherosclerosis and cardioembolic mechanisms. Rheumatic valvular disease was present in 44.8% of cardioembolic stroke patients and caused 4.31 preventable stroke cases per 100,000 Persian people per year. Hypertension and history of ischemic cerebrovascular events were the most frequent risk factors, 53.1 and 22.3%, respectively. The in-hospital mortality of our ischemic stroke patients was 7.3%. A total of 336 patients with intracerebral hemorrhage (189 females, 147 males) were evaluated in the KSR. The incidence of intracerebral hemorrhage in the Persian population is 10.43 cases per 100,000 people per year. The high frequency of atherosclerotic etiology in the KSR is due to its classification criteria, which do not separate small vessel territory infarcts as a different etiologic subtype. Rheumatic valvular disease is an important cause of stroke in the Persian population.

Aged↗
PubMed1993

Cerebral perfusion and neuropsychological consequences of chronic cocaine use.

Research indicates that cocaine significantly constricts the cerebral vasculature and can lead to ischemic brain infarction. Long-term effects of intermittent or casual cocaine use in patients without symptoms of stroke or transient ischemic attack were investigated. Single-photon emission computed tomography with xenon-133 and [99mTc]hexamethylpropyleneamine oxime, magnetic resonance imaging, and selected neuropsychological measures were used to study cerebral perfusion, brain morphology, and cognitive functioning. Patients were drug free for at least 6 months before evaluation. All showed regions of significant cerebral hypoperfusion in the frontal, periventricular, and/or temporal-parietal areas. Deficits in attention, concentration, new learning, visual and verbal memory, word production, and visuomotor integration were observed. This study indicates that long-term cocaine use may produce sustained brain perfusion deficits and persistent neuropsychological compromise in some subgroups of cocaine-abusing patients.

Adult↗
PubMed2001

Phenotype of a homozygous CADASIL patient in comparison to 9 age-matched heterozygous patients with the same R133C Notch3 mutation.

BACKGROUND AND PURPOSE: CADASIL is an autosomal dominant arteriopathy, characterized by multiple brain infarcts, cognitive decline, and finally dementia, which is caused by mutations in Notch3 gene encoding a Notch3 receptor protein. We describe the clinical, neuropsychological, imaging, genetic, and skin biopsy findings in a CADASIL patient homozygous for the C475T mutation resulting in R133C amino acid substitution, in comparison to 9 age-matched heterozygous patients with the same mutation. METHODS: The patients were examined clinically and neuropsychologically and with MRI and positron emission tomography for assessment of cerebral blood flow. The gene defect was analyzed by sequencing the products of polymerase chain reaction of exons 3 and 4 of the Notch3 gene. Dermal arteries were analyzed electron microscopically. RESULTS: The homozygous patient had his first-ever stroke at age 28 years. This is markedly earlier than the average, but the patient's heterozygous son had his first transient ischemic attack-like episode at the same age and another heterozygous patient had his first-ever stroke when only 2 years older. He was neuropsychologically more severely deteriorated than all but 1 of the heterozygous patients. These 2 patients had the most severe (confluent grade D) white matter MRI changes. Positron emission tomography showed markedly reduced cerebral blood flow. Skin biopsy revealed profuse deposits of granular osmiophilic material. The progression of disease in the homozygous case was, however, slower than in the most severely affected heterozygous patient. CONCLUSIONS: Our homozygous patient's phenotype is within the clinical spectrum of CADASIL, although at its severe end. Thus, CADASIL may follow the classic definition of a dominant disease, according to which the heterozygous and homozygous patients are clinically indistinguishable.

Adult↗
PubMed2004

Robust unsupervised segmentation of infarct lesion from diffusion tensor MR images using multiscale statistical classification and partial volume voxel reclassification.

Manual region tracing method for segmentation of infarction lesions in images from diffusion tensor magnetic resonance imaging (DT-MRI) is usually used in clinical works, but it is time consuming. A new unsupervised method has been developed, which is a multistage procedure, involving image preprocessing, calculation of tensor field and measurement of diffusion anisotropy, segmentation of infarction volume based on adaptive multiscale statistical classification (MSSC), and partial volume voxel reclassification (PVVR). The method accounts for random noise, intensity overlapping, partial volume effect (PVE), and intensity shading artifacts, which always appear in DT-MR images. The proposed method was applied to 20 patients with clinically diagnosed brain infarction by DT-MRI scans. The accuracy and reproducibility in terms of identifying the infarction lesion have been confirmed by clinical experts. This automatic segmentation method is promising not only in detecting the location and the size of infarction lesion in stroke patient but also in quantitatively analyzing diffusion anisotropy of lesion to guide clinical diagnoses and therapy.

Algorithms↗
PubMed1978

Non-invasive regional study of chronic cerebrovascular disorders using the oxygen-15 inhalation technique.

The regional cerebral metabolism-to-perfusion imbalance has been studied in the three main categories of cerebrovascular disorders in a chronic phase of the disease, using the non-invasive oxygen-15 inhalation technique. In patients presenting with a history of transient ischaemic attacks, regional defects in cerebral perfusion were greater than for the corresponding oxygen uptakes. Areas of relative ischaemia within which there was an enforced increase in the oxygen extraction ratio were highlighted. The reverse pattern was observed frequently in patients with brain infarcts arising from strokes, so indicating areas of relative luxury perfusion as is inferred from the reduction in the oxygen extraction ratio. In the multi-infarct dementia group of patients, there were parallel focal reductions in both flow and metabolism. The oxygen-15 inhalation technique is shown to be a unique tool in investigating cerebrovascular disorders because of its non-invasiveness and its ability to define regional metabolism-to-perfusion imbalance within the brain.

Adult↗
PubMed1994

Stroke associated with methamphetamine inhalation.

Seven patients (all men, mean age 32 years, range 17-47) with stroke following methamphetamine inhalation were collected during the last 2 years. Like oral or intravenous abusers, our patients had more hemorrhagic (n = 5) than ischemic strokes (n = 2). Cases of intracerebral hemorrhage (ICH) were lobar (n = 3), caudate (n = 1) or putaminal (n = 1), whereas the infarctions were both in the middle cerebral artery region. Each stroke event occurred within 3 days after drug use. Three patients had hypertension on admission. Though young in age, most patients had multiple stroke risk factors. In 3 patients with ICH, we also found small, low attenuated lesions on the brain computed tomography, however, without clinical correlations. Except for arteriovenous malformation in 1 patient, all angiograms failed to show vasculopathy or vasospasm. Contrary to what one might surmise from previously published reports, methamphetamine inhalation is at least as likely to produce ICH as it is to produce brain infarction.

Administration, Inhalation↗
PubMed1991

Effect of oxiracetam on cerebrovascular impairment in rats.

The effect of oxiracetam (CGP 21690E, CAS 62613-82-5) on cerebrovascular impairment was investigated in rats. 1. After injection of tranylcypromine (a MAO inhibitor), spontaneously hypertensive rats (SHR) which had been previously infused with norepinephrine (NE) for 14 days displayed stroke-related behaviour including kangaroo-like posture, seizures and death. Administration of oxiracetam at doses of 400 and 800 mg/kg/d p.o. for 14 days before tranylcypromine injection inhibited the stroke-related behaviour. 2. Bilateral common carotid and vertebral artery occlusion induced electroencephalogram (EEG) flattening, the EEG recovering gradually after re-perfusion of cerebral blood flow. Oxiracetam administered after the re-perfusion at a dose of 100 mg/kg, i.v. accelerated the recovery. This facilitatory effect was not seen when either piracetam (50 and 100 mg/kg i.v.) or idebenone (50 and 100 mg/kg i.v.) were administered. 3. Occlusion of middle cerebral artery produced cerebral infarction and disturbed the circadian rhythm of spontaneous motor activity with an relative increase of activity in the light period. Treatment with oxiracetam (400 mg/kg/d p.o.) for 14 days after the occlusion showed a tendency to an improvement in the disturbed circadian rhythm but did not influence the size of brain infarction. From these results, oxiracetam is thought to have a protective effect in cerebrovascular impairment.

Animals↗
PubMed1998

Usual and unusual methods for detection of lipid peroxides as indicators of tissue injury in cerebral ischemia: what is appropriate and useful?

1. Free radical-dependent lipid peroxidation processes have long been thought to contribute to brain damage following stroke or cerebral ischemia/reperfusion. 2. The preponderance of evidence for this belief has been derived indirectly, through diminution of tissue injury indices (e.g., brain infarct volume) facilitated by application of free radical scavenger substances. 3. Direct, unequivocal evidence for lipid peroxidation in terms of classical assays (detection of conjugated diene absorbance or thiobarbituric acid-reactive substances) is considerably less common, and its validity can be questioned. 4. Correlations of treatment-induced diminishment of brain injury indices with reductions in lipid peroxidation level are rarer still. 5. Reasons underlying the disparity between the belief that lipid peroxidation contributes to ischemic brain injury and direct evidence for this contribution (at least acutely) are proposed, along with evidence that new methods are being developed which should provide the basis for obtaining a definitive answer.

Animals↗
PubMed1997

[The effect of FK 506, an immunosuppressant, on cerebral infarction volume in focal cerebral ischemia in rats].

The effect of FK 506, an immunosuppressant which is widely used in the transplantation of liver, kidney and bone marrow, on cerebral infarction volume in transient focal ischemia was investigated. Focal cerebral ischemia was produced by 2 h occlusion of the left middle cerebral artery in rats. FK 506 (0.3 mg/kg body weight) and vehicle were administered intravenously immediately after induction of cerebral ischemia. After 24 h reperfusion the rats were sacrificed and brain infarct volume and edema volume were determined. The FK 506 treatment group showed a significantly reduced infarct volume in the cerebral cortex when it was compared with the vehicle treatment group, but infarct volume was not significantly reduced in the striatum which was the ischemic core in this focal ischemia model. However, FK 506 did not reduce the edema volume significantly. These results suggest that the reduction of infarct volume is a result of the neuroprotective effect of FK 506. This immunosuppressant may be useful in the treatment of cerebral infarction.

Animals↗
PubMed2004

Activation of proinflammatory caspases by cathepsin B in focal cerebral ischemia.

Cathepsins and caspases are two families of proteases that play pivotal roles in ischemic cell death. This study investigated the existence of a cross-talk between cathepsin B and proinflammatory caspases in stroke-induced cell death, as recently suggested by in vitro data. Cortical ischemic damage was induced in mice by distal and permanent occlusion of the middle cerebral artery. Cytoplasmic activation of cathepsin B was observed from the early stages of infarction, and displayed an activation pattern parallel to the activation pattern of caspase-1 and -11. Immunohistochemistry revealed the colocalization of cathepsin B with each caspase in cells of the infarct core. The apical position of cathepsin B in both caspase-activation cascades was confirmed by pretreatment of the animals with the cathepsin B inhibitor CA-074, which also potently protected cortical structures from ischemic damage, indicating involvement of the proteases in the lesion process. The results show that cathepsin B release is an early event following occlusion of cerebral arteries, which eventually triggers the activation of proinflammatory caspases in the absence of reperfusion. This new pathway may play a critical role in brain infarction by promoting inflammatory responses, and/or by amplifying the apoptotic process.

Animals↗
PubMed2004

Neuroprotective action of halogenated derivatives of L-phenylalanine.

BACKGROUND AND PURPOSE: The aromatic amino acid L-Phenylalanine (L-Phe) significantly and reversibly depresses excitatory glutamatergic synaptic transmission (GST) via a unique set of presynaptic and postsynaptic mechanisms. Therefore, we hypothesized that endogenous derivatives of L-Phe, which display potent antiglutamatergic activity, may safely and efficaciously protect the brain during conditions characterized by overactivation of glutamate receptors. METHODS: We tested this hypothesis in vitro with a combination of patch-clamp and lactate dehydrogenase (LDH) analyses in rat cultured neurons exposed to simulated ischemia, and in vivo using a rat model of experimental stroke caused by transient middle cerebral artery occlusion (MCAO). RESULTS: 3,5-diiodo-L-tyrosine (DIT) and 3,5-dibromo-L-tyrosine (DBrT), endogenous halogenated derivatives of L-Phe, attenuated GST by similar mechanisms as L-Phe, but with greater potency. For example, the IC50s for DIT and DBrT to depress the frequency of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor-mediated mEPSCs were 104.6+/-14.1 micromol/L and 127.5+/-13.3 micromol/L, respectively. Depression of GST by DIT and DBrT persisted during energy deprivation. Furthermore, DBrT significantly reduced LDH release in neuronal cultures exposed to oxygen glucose deprivation. In rats subjected to transient MCAO, DBrT decreased the brain infarct volume and neurological deficit score to 52.7+/-14.1% and 57.1+/-12.0% of control values, respectively. DBrT neither altered atrioventricular nodal and intraventricular conduction in isolated heart, nor heart rate and blood pressure in vivo. CONCLUSIONS: DBrT, an endogenous halogenated derivative of L-Phe, shows promise as a representative of a novel class of neuroprotective agents by exerting significant neuroprotection in both in vitro and in vivo models of brain ischemia.

Animals↗
PubMed1990

Encephalopathy in liver transplantation: neuropathology and CMV infection.

The clinical histories and pathological findings of 27 autopsied cases of orthotopic liver transplantation (OLT) were reviewed. Fatal OLT was complicated in 93% of cases by neurological dysfunction, usually manifested by encephalopathy, with or without seizures. The etiology of the encephalopathy was largely multifactorial (44%) or undetermined (20%). Subarachnoid hemorrhage, central pontine myelinolysis, meningitis, brain infarction, polyclonal B cell lymphoma and spinal cord necrosis were common neuropathological findings. These diagnoses were often masked by other systemic illnesses. The role of cytomegalovirus (CMV) in neurologic dysfunction was explored with in situ hybridization and immunohistochemical techniques. OLT cases showed a significantly higher (89%) frequency of CMV genomic material in brain tissue compared to age-matched non immunocompromised (NIC) patients (23%). All OLT cases with encephalopathy of undetermined cause demonstrated usually prominent hybridization to the CMV probe. CMV may be an important cause of encephalopathy in such patients.

Adolescent↗