Lubeluzole in acute ischemic stroke. A double-blind, placebo-controlled phase II trial. Lubeluzole International Study Group.

Background And Purpose: We aimed to assess the safety and efficacy of lubeluzole in patients with a clinical diagnosis of acute (< 6 hours) ischemic stroke in the carotid artery territory.

Methods: A randomized, double-blind, placebo-controlled multicenter trial was conducted in 232 patients. Because treatment was administered within 6 hours and a CT scan was not mandatory before the start of treatment, 39 patients with either an intracerebral hemorrhage or ischemic stroke in the vertebrobasilar circulation were excluded from the primary efficacy analysis as prespecified in the protocol.

[Aspirin dosage for prevention of cerebral infarct: arguments for low dosage].

Acetylsalicylic acid (ASS) is one of the best examined substances used in secondary prevention after TIA and stroke. Since different strategies and measurement variables were used in numerous randomised, double-blind, placebo-controlled studies (one end-variable, such as non-fatal stroke, myocardium infarction and vascular mortality, or combined end-variables, such as TIA, stroke and death), meta-analysis was necessary to prove that ASS resulted in about 22% reduction of secondary stroke. There is disagreement over the optimal dosage to prevent a stroke: earlier studies considered > or = 975 mg ASS per day, sometimes in combination with other substances, while more recently, lower dosages of about 300 mg per day or even as low as < or = 100 mg per day have been proposed.

Modification of low-frequency spontaneous oscillations in blood flow velocity in large- and small-artery disease.

During a 30-minute period, the blood flow velocity of both middle cerebral arteries (MCAs) was measured bilaterally in 27 patients with obstructive carotid disease (n = 18, large-artery disease) or subcortical vascular encephalopathy (n = 9, small-artery disease) and in control subjects of similar age and sex distribution (n = 14). To identify low-frequency spontaneous oscillations (LFSOs), MCA envelope curves were Fourier transformed with filter application to select low-frequency spectra (0.01-0.

Circulating selectin- and immunoglobulin-type adhesion molecules in acute ischemic stroke.

Background And Purpose: Cellular adhesion molecules mediate adhesion between endothelial cells and leukocytes as a precondition for extravasation of leukocytes at sites of tissue injury. The pattern of release of circulating adhesion molecules has been characterized in patients with acute ischemic stroke.

Methods: Serum concentrations of soluble selectin-type adhesion molecules (solube endothelial leukocyte adhesion molecule-1 [sELAM-1], soluble lymph node homing receptor [sL-selectin]) and immunoglobulin-type adhesion molecules (soluble vascular cell adhesion molecule-1 [sVCAM-1], soluble intercellular adhesion molecule-1 [sICAM-1]) were serially determined (at hours 4, 8, and 10 and at days 1, 3, and 5) in 22 patients with acute ischemic stroke.

Magnetic resonance angiography of spontaneous vertebral artery dissection suspected on Doppler ultrasonography.

Spontaneous vertebral artery dissection (VAD) is a rare but well-known cause of cerebrovascular disease and is often difficult to diagnose even using conventional arteriography. While noninvasive tests such as Doppler ultrasonography and magnetic resonance imaging (MRI) have failed to provide reliable criteria for the diagnosis of VAD, the diagnostic value of magnetic resonance angiography (MRA) has not yet been undetermined. To establish the reliability of a combined noninvasive approach, 11 patients were prospectively examined for VAD by means of colour-coded duplex studies, MRI and three-dimensional time-of-flight MRA prior to conventional angiography.

Epileptic seizures in subcortical vascular encephalopathy.

Cerebrovascular disease is one of the most common causes of epilepsy in the elderly. Most of the studies published relate to cortical infarction, subarachnoid, and intracranial hemorrhage, whereas the incidence of epilepsy from subcortical ischemia, i.e.

Variability of vascular territory in stroke. Pitfalls and failure of stroke pattern interpretation.

Background And Purpose: We investigated the efficacy and feasibility of determining infarction mechanisms and underlying embolic or hemodynamic pathologies from topographical patterns of ischemic damage seen on computed tomography or magnetic resonance imaging.

Methods: Infarction patterns from 22 patients with ipsilateral severe, hemodynamically relevant carotid stenosis (n = 6) or occlusions (n = 16) were superimposed, using two matching algorithms, onto maps showing the variability of the cerebral vascular territories as determined from recent cadaver studies. These images were used to classify the infarctions as border-zone or territorial for the two conditions of minimal and maximal middle cerebral artery distribution.

Vascular dementia: a changing concept.

The traditional concept of vascular dementia implied the thickening of arteries of the brain as a source of diffuse reduction of cerebral blood flow leading to neuronal death, cerebral atrophy, and finally dementia. Although this concept has been recently revived, with the increasing use of brain imaging technologies, new concepts of vascular dementia came into view. Present classification tends to separate various pathomechanisms (large- and small-vessel disease), to define different brain territories involved (strategic infarctions, cortico-subcortical and subcortical lacunes, borderzone/junctional zone infarctions, and white matter lesions) and most recently even genetics dispositions to vascular dementia of nonatherosclerotic etiology (CADASIL).

New and future developments in cerebrovascular ultrasound, magnetic resonance angiography, and related techniques.

Four-dimensional (4D) analysis of atherosclerotic plaque and wall motion, the application of 4D ultrasound to the study of atherogenesis, and the incorporation of ultrasound data into flow models for simulation of cerebrovascular hemodynamics are new frontiers in diagnostic ultrasound that use computer vision and optical flow techniques to exploit the full potential of real-time imaging and Doppler studies. New approaches to improve blood vessel delineation with ultrasound include application of contrast agents, harmonic imaging, and red blood cell density imaging. An assessment of the potential clinical utility of these new developments in cerebrovascular ultrasound requires an analysis of comparable trends in magnetic resonance (MR) technology, eg, rapid advances in the fields of MR angiography, dynamic contrast-enhanced MR, and MR diffusion imaging.

Cerebrovascular regulation and vasoneuronal coupling.

Maintenance of cerebral perfusion pressure is a prerequisite for the prevention of cerebral ischemia. Physiological fluctuations in systemic perfusion pressure are compensated by cerebrovascular autoregulation. Cerebral hypoperfusion could result from (1) systemic hemodynamic failure (eg, distal to severe arterial stenosis), overcharging the vasoregulatory capacity; (2) dysfunction and exhaustion of cerebrovascular autoregulation; or (3) both.

[Prognosis and therapy of carotid stenoses--a review of results of current studies].

Carotid stenoses as either a source of artery-to-artery emboli or a hemodynamic process of reduced brain perfusion can lead to transient ischemic attacks and brain infarcts. Although the prognosis of both symptomatic and asymptomatic patients correlates with the degree of the lumen narrowing and the progression of the atherosclerotic vessel process, the risk of a new cerebral ischemia is 5 to 15 times greater in symptomatic patients than in those whose vessel process has remained silent. Correspondingly, multicenter studies have shown that surgical treatment of high degree carotid stenosis under certain conditions as secondary prevention is warranted while until now no indication for carotid endarterectomy in the asymptomatic stage can be verified.

Compensatory carotid artery dilatation in early atherosclerosis.

Background: From pathological studies of coronary arteries, it has been recognized that progressive plaque development may be compensated for by an increase of the arterial diameter. However, the dynamics of this process have not been investigated, and it is not known whether compensatory dilatation is a general pathomechanism in human arteries.

Methods And Results: Using a high-resolution duplex scanner and subsequent three-dimensional plaque reconstruction, we prospectively studied the effect of carotid plaque development on the vascular geometry in 32 patients at 6- to 12-month intervals.

Pattern of activation of the hypothalamic-pituitary-adrenal axis in acute stroke. Relation to acute confusional state, extent of brain damage, and clinical outcome.

Background And Purpose: The aim of this study was to characterize the response of the hypothalamic-pituitary-adrenal system in the first hours of ischemic stroke and to relate its extent to the occurrence of acute confusional state, volume of brain damage, and clinical outcome.

Methods: The secretion of corticotropin (adrenocorticotropic hormone [ACTH]) and cortisol was studied in 23 patients by determinations at hours 4, 6, 8, 10, and 14 and days 1, 3, 5, and 7 after onset of symptoms. Acute confusional state (DSM-III-R criteria), extent of lesion (volumetry of computed tomographic scans), and neurological and functional outcome (Scandinavian Stroke Scale, Barthel Index scores) were assessed.

Are gait disturbances and white matter degeneration early indicators of vascular dementia?

The objective of this study was to correlate clinical and brain imaging findings with walking inabilities in patients with possible vascular dementia. For 24 patients with suspected initial vascular dementia according to DSM-III-R, structured neurological, neuropsychological and neuroimaging (magnetic resonance tomography) examinations were evaluated alongside computerized gait analysis. All patients revealed an increased variability of gait lines of various degrees: mild (11%), moderate (32%) and severe (57%).

Noninvasive monitoring of internal carotid artery dissection.

Background And Purpose: Internal carotid artery dissection has increasingly been reported as a cause of transient ischemic attack or stroke. However, scarce data exist on the natural history of the arterial lesions and the temporal profile of recanalization.

Methods: We followed 48 patients with 50 angiographically confirmed internal carotid artery dissections by sequential duplex Doppler studies in 2- to 4-day intervals during the first weeks after the onset of symptoms and after 4 weeks in 1- to 2-month intervals for up to 2 years.

Proinflammatory cytokines in serum of patients with acute cerebral ischemia: kinetics of secretion and relation to the extent of brain damage and outcome of disease.

The release of the proinflammatory cytokines IL-1 beta, IL-6, TNF-alpha and soluble TNF-receptors p55 and p75 in peripheral blood was serially determined in 19 patients with acute cerebral ischemia. Only patients admitted within 4 h following onset of symptoms were studied. In contrast to serum levels of IL-1 beta, TNF-alpha and TNF-receptors, which did not exhibit a significant response, IL-6 showed a significant increase of serum levels already within the first hours following onset of disease and reached a plateau at 10 h until day 3 and returned to baseline by day 7.

Pathophysiologic assessment of data from a stroke data bank.

Stroke data banks have been instrumental in helping us to clarify stroke etiology and in the investigation of clinical-topographic correlations. For these purposes they have relied upon results from noninvasive vascular and cardiac methods, including extra- and transcranial Doppler sonography and echocardiography, as well as from procedures such as cranial computed tomography and magnetic resonance imaging. Conventional database concepts have also been used to assess pathophysiologic aspects of stroke.

Magnetic resonance angiography in vertebrobasilar ischemia.

Background And Purpose: Magnetic resonance angiography is a new, noninvasive technique whose diagnostic value in vertebrobasilar artery disease has not yet been determined.

Methods: Forty-one patients with acute cerebellar and/or brain-stem ischemia were examined by routine magnetic resonance imaging, extracranial and transcranial Doppler ultrasound, and selective intra-arterial arteriography. Results were correlated with magnetic resonance angiography.