bluuebunny/crossref_metadata_2025 huggingface dataset:
Provokable bilateral vertebral artery compression diagnosed with transcranial Doppler.
Authors: Brautaset N J
Published: June 2011

Head and neck movements may cause vascular compression that produces a syndrome of vertebrobasilar insufficiency. Vertebrobasilar circulation was examined noninvasively in two patients who were able to provoke these symptoms repeatedly on demand.

Blood flow velocities in the basilar artery (case 1) and both posterior cerebral arteries (both cases) were measured continuously by transcranial Doppler sonography while the patients voluntarily performed the offending maneuvers and reproduced their symptoms. The provocative maneuvers evoked an immediate and precipitous drop in blood flow velocity, producing symptoms within seconds. Upon relief, the blood flow velocities showed a transient overshoot before returning to baseline values.

These observations indicate that the symptoms of vertebrobasilar insufficiency were due to real reductions in blood flow and demonstrate the usefulness of transcranial Doppler sonography to diagnose bilateral extracranial vertebral artery compression.
Prevalence and significance of hyperdense middle cerebral artery in acute stroke.
Authors: Leys D , Pruvo J P , Godefroy O , Rondepierre P , Leclerc X
Published: June 2011

Early noncontrast computed tomographic scans may visualize a hyperdense middle cerebral artery before the infarct becomes visible. This sign disappears within a few days, corresponds to the clot itself, and might be associated with a poor prognosis. The aim of the study was to determine its prevalence, diagnostic value, relationship to demographic data, ability to separate embolic from nonembolic causes, short-term prognostic value, evolution over time, and relationship to arterial occlusion on angiography.

We performed this study using computed tomographic scans performed within 12 hours after onset in 272 consecutive unselected patients with a first acute cerebrovascular event.

Seventy-three subjects had the hyperdense middle cerebral artery sign, leading to a prevalence of 26.8% in the whole group and 41.2% in patients with a middle cerebral artery infarct. Specificity was 100%, but sensitivity was only 30%. This sign was not dependent on cerebrovascular risk factors, but was more likely to occur in cortical and in large, deep, middle cerebral artery infarcts (p less than 0.01). It provided only a 3.5% gain in predicting death, and one fifth of patients with the sign recovered within 2 weeks; this sign was not an independent variable of poor outcome on multiple linear regression. It spontaneously disappeared within a few days and was always related to an occlusion of the middle cerebral artery in patients who underwent early angiography.

The hyperdense middle cerebral artery sign is useful in the diagnosis of middle cerebral artery occlusion but does not always predict a poor prognosis.
Degeneration of the ipsilateral substantia nigra following cerebral infarction in the striatum.
Authors: Nakane M , Teraoka A , Asato R , Tamura A
Published: June 2011

In rats, degeneration of the ipsilateral substantia nigra occurs a few weeks after occlusion of the middle cerebral artery. The aim of this study was to clarify whether similar change is observed in stroke patients.

Eighteen patients with striatal infarction and six patients with cortical infarction in the territory of the middle cerebral artery were examined by means of sequential magnetic resonance imaging.

In all patients with striatal infarction, T2-weighted images revealed a high-signal-intensity spot in the ipsilateral substantia nigra. Changes in the ipsilateral substantial nigra appeared at day 14 after stroke on average and then became less intense and smaller a few months after the stroke. By contrast, we observed no nigral changes in any patient with cortical infarction.

The degenerative change in the ipsilateral substantia nigra initially found in the rat model similarly occurred in patients with striatal infarction. This remote change in the substantia nigra may represent magnetic resonance imaging detection of neuropathologic changes in this region through the striatonigral pathway.
Proton magnetic resonance spectroscopy of cerebral lactate and other metabolites in stroke patients.
Authors: Graham G D , Blamire A M , Howseman A M , Rothman D L , Fayad P B , Brass L M , Petroff O A , Shulman R G , Prichard J W
Published: June 2011

Proton magnetic resonance spectroscopy can measure in vivo brain lactate and other metabolites noninvasively. We measured the biochemical changes accompanying stroke in 16 human subjects with cortical or deep cerebral infarcts within the first 3 weeks after symptom onset, and performed follow-up studies on six.

One-dimensional proton spectroscopic imaging encompassing the infarct region was performed with a 2.1-T whole-body magnet using the stimulated echo pulse sequence and an echo time of 270 msec.

All but one of the cortical stroke patients had increased lactate within or near the infarct. Persistently elevated cerebral lactate was documented in five of six cases studied serially as long as 251 days after infarction. N-acetylaspartate levels were decreased in most cortical strokes. Elevated lactate, accompanied by minimal reduction in N-acetylaspartate, was recorded in two of four patients in the first week following a small subcortical infarct.

Long-term elevation of lactate commonly occurs after stroke. This lactate may arise from ongoing ischemia or infiltrating leukocytes, or it may be a residual of the lactate formed during the initial insult. The ability to observe stroke-elevated lactate pools at any time after lesion onset provides an approach to distinguishing among these possibilities in the future.
Predictive value of repeated systolic blood pressure measurements for stroke risk. The Zutphen Study.
Authors: Keli S , Bloemberg B , Kromhout D
Published: June 2011

The strength of the association between blood pressure and stroke incidence is dependent on the number of blood pressure measurements. Different summary variables of repeated blood pressure measurements taken during 10 years were evaluated in relation to the long-term risk of stroke in the Zutphen Study.

During the period 1960-1970 repeated blood pressure measures were taken yearly in 603 men aged 50-69 years in 1970 in the town of Zutphen, The Netherlands. The individual average systolic blood pressure between 1960 and 1970, the predicted systolic blood pressure for 1970 (based on regression of blood pressure readings on time), and the single observed systolic blood pressure in 1970 were used as systolic blood pressure estimates. Their strength in predicting the 15-year stroke incidence was assessed using Cox proportional hazards models. Adjustment was made for the confounding effects of age, cigarette smoking, and serum total cholesterol.

The average systolic blood pressure between 1960 and 1970 was the strongest predictor of 15-year stroke incidence. The strength of the association was underestimated by 55% when a casual systolic blood pressure measurement was used instead of 11 yearly measurements.

It can be concluded that a casual blood pressure measurement leads to a substantial underestimation of the long-term stroke risk of an individual.
Blood flow and metabolism during and after repeated partial brain ischemia in neonatal piglets.
Authors: Laptook A R , Corbett R J , Ruley J , Olivares E
Published: June 2011

Our investigation sought to determine whether neonatal brain ischemic vascular and metabolic effects were altered by repeated episodes of ischemia.

We studied twelve piglets using in vivo magnetic resonance spectroscopy to obtain multiple, simultaneous measurements of cerebral blood flow and phosphorylated metabolites from the same tissue volume. The relationship between cerebral blood flow and energy metabolism was examined over a range of reduced cerebral blood flow (90-10% of control). Three episodes of partial ischemia were studied, each lasting 10 minutes and separated by 45 minutes.

During each interval of ischemia, plots of the percent reduction in cerebral blood flow versus the percent change in phosphorylated metabolites (phosphocreatine, inorganic phosphorus) or unit change in intracellular pH did not differ in slope and intercept. The relationship between beta-ATP and cerebral blood flow during repeated ischemia revealed similar slopes, but a lower intercept during the third interval of ischemia (p = 0.029). After ischemia, cerebral blood flow was reduced as a function of the severity of the preceding ischemia. After each interval of ischemia, phosphocreatine and intracellular pH were unchanged from preischemic values. Inorganic phosphorus remained elevated after ischemia (117 +/- 16 and 118 +/- 11% of control, p less than 0.005, following the first and second intervals of ischemia), and beta-ATP was restored to progressively lower values (92 +/- 10 and 83 +/- 11% of control, p less than 0.025). Calculated free ADP decreased after ischemia and correlated with the postischemic level of beta-ATP (r = 0.63, p = 0.001).

These results demonstrate that the relationship between cerebral blood flow and metabolism was reasonably preserved during repeated partial ischemia. However, following ischemia, alterations occurred in both cerebral blood flow and metabolism. These alterations may reflect a relative inhibition of ATP production by metabolic regulators such as ADP on either glycolysis or oxidative phosphorylation or both.
Neuroprotective effects of SKF 10,047 in cultured rat cerebellar neurons and in gerbil global brain ischemia.
Authors: Lysko P G , Gagnon R C , Yue T L , Gu J L , Feuerstein G
Published: June 2011

Excitatory amino acids and their receptors are involved in mediating ischemic neuronal damage. The sigma-agonists are believed to interact with the N-methyl-D-aspartate receptor. Therefore, we studied the neuroprotective, hypothermic, and motor deficit effects of the sigma-agonist SKF 10,047 and the N-methyl-D-aspartate antagonist MK-801.

Neuroprotective effects were compared using an in vitro ischemia model of cultured rat cerebellar granule cells and the gerbil model of global brain ischemia induced by 5 minutes of bilateral carotid artery occlusion followed by 7 days of reperfusion.

In vitro, (+)MK-801 protected against 100 microM glutamate with a 50% protective concentration of 30 nM, followed by (-)MK-801 (150 nM), cyclazocine (0.5 microM), (+)SKF 10,047 (3.3 microM), pentazocine (5 microM), and (-)SKF 10,047 (10 microM). In vivo, (+)SKF 10,047 pretreatment (60 mg/kg) or multiple postischemic treatments provided neuroprotection comparable with MK-801 pretreatment (10 mg/kg). When ischemic animals were administered the multiple dosing regimen of (+)SKF 10,047, no hypothermic effect was noted in the temporalis muscle over 4 hours' postischemia. Motor deficits monitored by a swing grid test showed that 50% recovery from (+)SKF 10,047 was 5.5 times faster than recovery from MK-801.

These results are the first to report a hypothermia-free, in vivo neuroprotective effect of (+)SKF 10,047, a prototypical drug of the sigma-agonist class.
Significance of low perfusion with increased oxygen extraction fraction in a case of internal carotid artery stenosis.
Authors: Yamauchi H , Fukuyama H , Fujimoto N , Nabatame H , Kimura J
Published: June 2011

Decreased cerebral blood flow with an increased oxygen extraction fraction, the so-called misery perfusion syndrome, suggests a vulnerability to reduction in cerebral perfusion pressure and a tendency to develop cerebral infarction. It is uncertain, however, whether the infarct would occur in the brain region specifically exhibiting this condition.

We report the case of a patient with right intracranial internal carotid artery stenosis who presented with mild left hemiparesis resulting from a right frontal watershed infarct. Positron emission tomography 2 months after the stroke showed decreased cerebral blood flow with an increased oxygen extraction fraction in noninfarcted areas of the affected hemisphere. Maximal changes were detected in the watershed area between the middle cerebral artery and the posterior cerebral artery. Three months later, while on antiplatelet therapy, he suffered a new infarct in the right temporo-occipital watershed area that had shown the highest oxygen extraction fraction value on the first positron emission tomographic study. One month after the recurrence of stroke, a second study showed that low perfusion with increased oxygen extraction fraction persisted in the affected hemisphere to a lesser degree than in the first study.

This observation suggests that the area of low perfusion exhibiting the highest oxygen extraction fraction has the highest risk for infarction. Increased oxygen extraction fraction may be an important factor in the development of hemodynamic infarction.
Early clinical differentiation of cerebral infarction from severe atherosclerotic stenosis and cardioembolism.
Authors: Timsit S G , Sacco R L , Mohr J P , Foulkes M A , Tatemichi T K , Wolf P A , Price T R , Hier D B
Published: June 2011

Hyperacute cerebral infarction trials require early differentiation of infarction subtype. Our aim was to determine clinical factors predictive of infarction subtype from data collected in the early hours of admission.

Using the 1,273 patients enrolled in the Stroke Data Bank, stroke risk factors and demographic, clinical, and radiological features were compared between the 246 cardioembolic and 113 large-vessel atherosclerotic cerebral infarcts.

Stroke Data Bank definitions ensured more transient ischemic attacks in atherosclerotic infarcts and more cardiac disease in cardioembolic infarcts, but the diagnosis was distinguished further using a logistic regression model. Fractional arm weakness (shoulder different from hand) (odds ratio 3.1, 95% confidence interval [CI] 1.6-5.8), hypertension (odds ratio 2.8, CI 1.4-5.3), diabetes (odds ratio 2.5, CI 1.2-5.1) and male gender (odds ratio = 2.2, CI 1.2-4.1) occurred more frequently in patients with atherosclerotic than cardioembolic infarcts. Reduced consciousness (odds ratio = 3.2, CI 1.4-7.3) was more frequent in cardioembolism. For a male patient with hypertension, diabetes, and fractional arm weakness, the estimated odds of an atherosclerotic infarction were 47-fold that of a cardioembolic infarction. Patients with atherosclerotic infarcts were more likely to have a fractional arm weakness regardless of infarct size, whereas, for those with cardioembolic infarctions, fractional weakness was more frequent in infarcts less than 20 cc in volume.

Clinical features that are observed at stroke onset can help distinguish cerebral infarction subtypes and may allow for early stratification in therapeutic trials.
Correlations between cerebral arterial velocities, blood flow, and delayed ischemia after subarachnoid hemorrhage.
Authors: Davis S M , Andrews J T , Lichtenstein M , Rossiter S C , Kaye A H , Hopper J
Published: June 2011

Elevated middle cerebral erythrocyte velocities and tissue hypoperfusion have been correlated with delayed ischemia after subarachnoid hemorrhage, but few studies have compared serial arterial velocities with cerebral blood flow and neurological deficits.

Serial measurements of middle cerebral velocities, using transcranial Doppler ultrasonography, were performed in 34 patients after subarachnoid hemorrhage and correlated with cerebral blood flow, measured in 20 of the 34 using single-photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime and neurological evidence of delayed ischemia.

In 16 patients without delayed ischemia, eight had evidence of vasospasm (greater than 120 cm/sec), but only one of seven had hypoperfusion, suggesting that vasospasm might be more common than hypoperfusion in this group (p = 0.1). In 10 patients with delayed ischemia and a lateralizing deficit, both asymmetrical middle cerebral vasospasm (eight of nine with vasospasm) and hypoperfusion (six of six studied) were concordant with the clinically ischemic hemisphere (p less than 0.05). Vasospasm occurred with nonlateralized delayed ischemia in seven of eight patients and with hypoperfusion in five of six, affecting the anterior cerebral territory in three.

Concordant vasospasm and hypoperfusion were most often present in patients with delayed ischemia and lateralizing neurological deficits. Discordant results reflect inherent limitations and the different levels of the circulation monitored by the two techniques.
Penumbral tissues salvaged by reperfusion following middle cerebral artery occlusion in rats.
Authors: Memezawa H , Smith M L , Siesjö B K
Published: June 2011

The rat is now extensively used for studies on focal cerebral ischemia, and several novel pharmacological principles have been worked out in rat models of middle cerebral artery occlusion. The objective of the present study was to assess how ischemic tissue can be salvaged by reperfusion in a model of transient focal ischemia that gives infarction of both the caudoputamen and the neocortex.

The middle cerebral artery of anesthetized rats was occluded for 15, 30, 60, 90, 120, or 180 minutes by an intraluminal filament, and recirculation was instituted for 7 days to allow assessment of the density and localization of ischemic brain damage using histopathologic techniques. Local cerebral blood flow was measured in separate animals to verify that removal of the filament was followed by adequate recirculation.

Following 15 minutes of middle cerebral artery occlusion seven of eight rats showed selective neuronal necrosis in the caudoputamen, while the neocortex was normal. After 30 minutes of occlusion, seven of eight animals had infarcts localized to the lateral caudoputamen, and four of eight had selective neuronal necrosis in the neocortex. Prolongation of the ischemia to 60 minutes induced cortical infarction in all eight rats. The infarct size increased progressively with increasing occlusion time, up to 120-180 minutes, when the infarcts were as extensive as those observed following 24 hours of permanent middle cerebral artery occlusion.

The results demonstrate a time window for salvage of penumbral tissues by reperfusion that is shorter than that suggested on the basis of previous data in other species. The results probably reflect a lower collateral blood flow in the rat than in other species. This should be taken into account when the effect of pharmacological agents is studied in rats.
Estimation of cerebrovascular reactivity using transcranial Doppler, including the use of breath-holding as the vasodilatory stimulus.
Authors: Markus H S , Harrison M J
Published: June 2011

A proportion of individuals with carotid artery stenosis show a reduced cerebrovascular reserve as measured by a reduced cerebral arterial vasodilatory response to carbon dioxide. Two methods of quantifying this vasodilatory response, using transcranial Doppler ultrasonography, have been in general use: the total range of vasodilation between hypocapnia, induced by hyperventilation, and hypercapnia induced by breathing carbon dioxide, and the response to breathing a fixed concentration of 5% carbon dioxide. We studied whether it is possible to use the rise in carbon dioxide occurring during breath-holding as the vasodilatory stimulus.

Using transcranial Doppler, cerebral reactivity to carbon dioxide was measured in 23 subjects undergoing intravenous digital subtraction angiography of their carotid arteries for symptoms of cerebrovascular disease. A breath-holding method was compared with the two previous methods, which required administration of carbon dioxide.

All three methods gave results that correlated highly significantly with the degree of carotid stenosis, although the correlation was highest when the full vasodilatory range was measured. This method was adopted as the gold standard, and the other methods were compared with it. The breath-holding method correlated at least as well (rho = 0.67) as the 5% CO2 method (rho = 0.64). It identified a similar group of low reactors to our gold standard method, whereas the 5% CO2 method gave some discrepant results.

The breath-holding method offers potential as a convenient, well-tolerated screening method of assessing carbon dioxide reactivity not requiring the administration of carbon dioxide, although further validation against more established methods of measuring cerebrovascular reserve is first required.
Amount of smoking independently predicts carotid artery atherosclerosis severity.
Authors: Dempsey R J , Moore R W
Published: June 2011

Cigarette smoking is correlated with extracranial carotid artery plaque thickness. Our aim in the present study was to determine whether the level of prior cigarette use is a significant predictor of carotid artery plaque thickness when age, history of hypertension, and history of diabetes are controlled.

We studied a continuous sample of 790 patients with a history of smoking referred for diagnostic ultrasound imaging of the carotid arteries. Subjects (mean age 61 years) had an average of 51 pack-years of cigarette use. History of hypertension was present in 44% and history of diabetes in 18%.

Right and left maximum carotid artery plaque thicknesses were averaged for each patient; the average of this value for all 790 subjects was 1.9 mm. In bivariate analysis, age (p less than 0.0001), pack-years (p less than 0.0001), history of hypertension (p = 0.0003), and history of diabetes (p = 0.037) were each positively associated with carotid artery plaque thickness. In multiple regression analysis, age (p less than 0.0001), pack-years (p = 0.0005), and history of hypertension (p = 0.0044) were statistically significant independent predictors of carotid artery plaque thickness, but history of diabetes (p = 0.2451) was not.

In smokers, the level of cigarette use is associated with an acceleration of carotid artery atherosclerosis development. This effect is independent of age, hypertension, and diabetes. These results support smoking abatement as an important element to stroke prevention in clinical practice.
Induction of transient neurological dysfunction in baboons by platelet microemboli.
Authors: Kessler C , Kelly A B , Suggs W D , Weissman J D , Epstein C M , Hanson S R , Harker L A
Published: June 2011

To investigate experimental mechanisms of reversible cerebral dysfunction, we produced transient focal cerebral ischemia in five baboons by unilateral perfusion of internal carotid territories with platelet microemboli generated endogenously.

Platelet microemboli were formed by incorporating segments of Dacron vascular graft for 1 hour as unilateral carotid arterio-arterial shunts. Platelet embolization was assessed by ultrasonography and isotopic imaging; cerebral function was evaluated by measurements of somatosensory evoked potentials and clinical motor performance.

Platelet microemboli, detected by transcranial Doppler ultrasonography, accumulated rapidly in the shunted carotid hemispheric territory. Indium-111-labeled platelets reached a maximum value of 3.2 +/- 0.8 x 10(9) platelets in the dependent hemisphere of five animals after 20 minutes of carotid blood flow through the grafts when measured in real time by continuous scintillation camera imaging. The retained 111In-platelet microemboli cleared from the cerebral vasculature within 1 hour after removing the grafts. Corresponding blood markers of in vivo thrombus formation, beta-thromboglobulin, platelet factor 4, and fibrinopeptide A, increased eightfold to 20-fold after incorporating graft segments and normalized within 1 hour after removing the grafts. Coincidently, focal neurological function was temporarily impaired, as shown by the ipsilateral loss of somatosensory evoked potentials 5 minutes after initiating platelet microembolization, with restoration 1 hour after removing the grafts in five baboons, and contralateral hemiparesis in two recovered baboons, with complete resolution by 24 hours.

Endogenously generated platelet microemboli accumulate transiently in the dependent cerebral circulation and produce corresponding focal neurological dysfunction that resolves within hours after microembolization.
Inhibition of polymorphonuclear leukocyte adherence suppresses no-reflow after focal cerebral ischemia in baboons.
Authors: Mori E , del Zoppo G J , Chambers J D , Copeland B R , Arfors K E
Published: June 2011

While polymorphonuclear leukocytes may contribute to the "no-reflow" phenomenon after focal cardiac and skeletal muscle ischemia/reperfusion, their contribution to acute focal cerebral ischemia is unresolved. We have examined the role of polymorphonuclear leukocytes in microvascular perfusion defects after focal cerebral ischemia/reperfusion in a baboon model of reversible middle cerebral artery occlusion with the anti-CD18 monoclonal antibody IB4, which inhibits neutrophil adherence to endothelium.

Microvascular patency in the basal ganglia after 3-hour middle cerebral artery occlusion and 1-hour reperfusion (by india ink tracer perfusion) was quantified by computerized video imaging. Animals were randomized to receive intravenous IB4 infusion 15 minutes before reperfusion (n = 7) or to receive no treatment (n = 6). Binding of IB4 to baboon leukocytes was maximal within 5 minutes of infusion.

In the untreated group, a significant reduction in patency was observed in microvessels less than 30 microns diameter: mean percent reflow was 51% in the capillary diameter class (4.0-7.5 microns) and 39% in the precapillary arteriole and postcapillary venule diameter class (7.5-30 microns). Infusion of IB4 before middle cerebral artery reperfusion increased reflow in microvessels of all size classes, most significantly in those 7.5-30 microns (p = 0.049) and 30-50 microns (p = 0.034) in diameter.

These results suggest that CD18-mediated polymorphonuclear leukocyte-endothelium adherence contributes to no-reflow predominantly in noncapillary microvessels and at least partially to that in capillaries.
Combination therapy with nimodipine and dizocilpine in a rat model of transient forebrain ischemia.
Authors: Rod M R , Auer R N
Published: June 2011

We explored the effectiveness of dual blockade of calcium channels in preventing ischemic necrosis in a rat model of transient forebrain ischemia.

To assess all the major brain regions, the entire brain was subserially sectioned and examined histologically 1 week after ischemia in 44 male Wistar rats. Brain temperature was monitored and controlled to avoid hypothermia or intergroup temperature differences at the time drugs were administered. All regimens were begun 20 minutes after ischemia. Treated animals received either the L-type calcium channel blocker nimodipine (0.25 microgram/min x 24-hour i.v. infusion), the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine; 5 mg/kg i.v.), or both regimens in combination.

In the neocortex (p less than 0.05) and striatum (p less than 0.05), only double-treated animals showed a statistically significant reduction in neuronal necrosis. Dual therapy eliminated neuronal necrosis in the caudate nucleus entirely. In the septal (densely ischemic) hippocampus, protection was weak and inconsistent (0.012 less than p less than 0.788), but in the temporal (incompletely ischemic) hippocampus, the dual-treated group showed the most significant reduction (p less than 0.006).

We conclude that the combination of nimodipine and MK-801, if begun 20 minutes after ischemia, may offer a neuroprotective effect against neuronal necrosis in transient forebrain ischemia and that protection is maximal in the major extrahippocampal brain regions.
Quantal bioassay and stroke.
Authors: Zivin J A , Waud D R
Published: June 2011

Experimental investigation of stroke, in particular the evaluation of therapeutic maneuvers, is difficult because even well-controlled experiments show considerable variability. Optimal use of resources requires efficient statistical analysis.

A body of experience in pharmacology that is directly applicable to stroke studies is reviewed. The general approach, though well known to pharmacologists, is less familiar to neurologists. This paper attempts to give a survey so that neurologists encountering studies using this general class of analysis will better be able to put the technique into context. The general nature of a quantal bioassay is described, the underlying conceptual models are discussed, and specific examples are given.

The pharmacologist's approach to the analysis of quantal bioassays can easily be adapted to the quantification of results in studies of stroke.
Histopathological analysis of the mechanisms of intracranial hemorrhage complicating infective endocarditis.
Authors: Masuda J , Yutani C , Waki R , Ogata J , Kuriyama Y , Yamaguchi T
Published: June 2011

We conducted the present study to elucidate the pathological mechanisms leading to intracranial hemorrhage complicating infective endocarditis.

Neurological, neuroradiological, and histopathological analyses were performed in 16 patients (one surgical and 15 autopsy cases), 12 men and four women 26-68 years of age, who had demonstrated central nervous system complications during the course of infective endocarditis.

Intracranial hemorrhage was found in all cases; parenchymal hematomas were found in 12 cases, hemorrhagic infarcts in four cases, and primary subarachnoid hemorrhages in two cases. Chronological analysis of neurological examination and computed tomographic scan of the brain confirmed that antecedent cerebral ischemic events had occurred in five of 12 patients showing parenchymal hematomas at autopsy. Hemorrhagic infarct, indicated by petechial or diffuse hemorrhages within the infarct, was seen in another four patients, so that hemorrhagic transformation of the ischemic infarct was confirmed in nine patients. Although mycotic aneurysms were found in five patients, only three of these were ruptured; the other two were occluded with septic emboli. Pyogenic arteritis without aneurysm was found to be distributed in the small cortical arterial branches located in the spaces of cortical sulci, with rupture occurring in five patients.

These results suggest that hemorrhagic transformation of the ischemic infarct due to septic emboli is the most frequent mechanism leading to intracerebral hemorrhage encountered in patients dying of infective endocarditis and that rupture of pyogenic arteritis may be responsible for such hemorrhage in many cases, with ruptures of mycotic aneurysms as an alternative mechanism.
Cerebroprotective effect of a non-N-methyl-D-aspartate antagonist, GYKI 52466, after focal ischemia in the rat.
Authors: Smith S E , Meldrum B S
Published: June 2011

Cerebroprotection after the administration of N-methyl-D-aspartate antagonists has been well documented. The present study sought to determine whether a cerebroprotective effect could be achieved with the administration of a non-N-methyl-D-aspartate antagonist, GYKI 52466 (1-(4-aminophenyl)-4-methyl-7,8-methylene-dioxy-5H-2,3-benzodiazep ine hydrochloride; molecular weight, 330) after middle cerebral artery occlusion in the rat.

Neurological deficit and infarct volume 24 hours after permanent left middle cerebral artery occlusion in Fischer rats (n = 7-13 per group per dose) were studied. Cerebral infarcts was visualized by the lack of reduction of 2,3,5-triphenyltetrazolium chloride.

GYKI 52466 (10 mg.kg-1 i.p. at 0, 2, 4 hours) after middle cerebral artery occlusion had no effect on infarct volume. GYKI 52466 (10 mg.kg-1 i.v. for 5 minutes followed by 15 mg.kg-1.hr-1 i.v. for 2 hours immediately after middle cerebral artery occlusion reduced cortical infarct volume by 68% (from 69 mm3 in vehicle-treated to 22 mm3 in GYKI 52466-treated animals; p less than 0.05). A 1-hour delay before initiation of drug infusion resulted in a 48% reduction in cortical infarct volume (from 60 mm3 vehicle-treated rats to 31 mm3 in GYKI 52466-treated rats; p less than 0.05). A 2-hour delay before initiation of drug infusion had no effect on cortical infarct volume. Neurological deficits (with blinded assessment after 24 hours) were improved after immediate treatment and after delayed treatment (1 or 2 hours).

The cerebroprotective effect of GYKI 52466 in the rat suggests a possible therapeutic role for non-N-methyl-D-aspartate antagonists given shortly after the onset of stroke.
Small infarctions of cochlear, retinal, and encephalic tissue in young women.
Authors: Schwitter J , Agosti R , Ott P , Kalman A , Waespe W
Published: June 2011

Recently, a rare syndrome that involves uniformly the brain, inner ear, and retina in previously healthy young women has been described. Brain biopsies and ophthalmologic examinations disclosed small infarcts as a pathoanatomical substrate of the disease. In previous reports, an autoimmune disorder or a coagulopathy have been suggested as possible etiologies.

Both patients (aged 22 and 20 years) had brain involvement with neurological and neuropsychological deficits. Multifocal small hyperintensities were shown in magnetic resonance imaging of the brain. Findings of cerebrospinal fluid examination and electroencephalography were pathological in case 1 and of cerebral angiography in case 2. Both patients had a neurosensory hearing loss and multiple retinal branch arteriolar occlusions. Both women were on fenfluramine before onset of the disease. In case 1, attacks recurred during a follow-up of 34 months. At onset of the disease the 5-hydroxyindoleacetic acid and homovanillic acid levels of the cerebrospinal fluid were reduced; 13 months later the 5-hydroxyindoleacetic acid level was still reduced and the homovanillic acid level was low-normal. In case 2, with the longest follow-up of 13 years, the disease was active during only the initial 2 1/4 years. During this period a combination of oral anticoagulant and antiplatelet agents was ineffective.

Our findings could not support current etiologic hypotheses. Whether changes in 5-hydroxyindoleacetic acid and homovanillic acid levels in the cerebrospinal fluid and/or fenfluramine intake play a role in the pathogenesis of the disease remains to be elucidated.
Treatment of cerebellar infarction by decompressive suboccipital craniectomy.
Authors: Chen H J , Lee T C , Wei C P
Published: June 2011

We present an anecdotal series of 11 patients without past history of stroke with progressive neurological deterioration while on medical therapy for large cerebellar infarctions. Clinical signs of brain stem compression developed in these patients. Computerized tomography of the head confirmed mass effect from brain edema. It was the clinical judgment of the neurologists and neurosurgeons that each of these 11 patients would expire without surgical intervention.

All 11 patients (seven men, four women; mean age, 54 years) were treated with suboccipital craniectomy for decompression and temporary ventriculostomy for cerebrospinal fluid pressure monitoring and drainage.

Seven patients demonstrated neurological improvement on the first postoperative day. Two patients returned to their previous jobs 3 months after surgery. The Barthel Index indicated that six individuals were functioning with minimal assistance within a follow-up period of 16-60 months. The remaining three were functionally dependent. No mortality was noted in this series.

These results suggest that decompressive suboccipital craniectomy may be an effective, lifesaving procedure for malignant cerebellar edema after a large infarction.
Treatment of acute cerebral hemorrhage with intravenous glycerol. A double-blind, placebo-controlled, randomized trial.
Authors: Yu Y L , Kumana C R , Lauder I J , Cheung Y K , Chan F L , Kou M , Chang C M , Cheung R T , Fong K Y
Published: June 2011

Hitherto, treatment of acute cerebral hemorrhage with intravenous glycerol has not been evaluated in rigorous clinical studies with sufficient patient numbers.

We undertook a double-blind, stratified and randomized, placebo-controlled clinical trial. Only patients with a first stroke admitted to the hospital within 24 hours after onset of symptoms were recruited, provided computed tomography confirmed hemorrhage and informed consent was obtained. After stratification into alert, semicoma, and coma subgroups using the Glasgow Coma Scale, 107 patients received active treatment (500 ml of 10% glycerol in saline by intravenous infusion over 4 hours on 6 consecutive days) and 109 were given corresponding saline treatment. Using a variety of objective scoring systems, patients were followed up for up to 6 months.

At follow-up, all measures of outcome in the treated and control groups were very similar. At 6 months, respective mortality rates were 37 of 107 and 33 of 109. Corresponding mean +/- SD improvements in Scandinavian Stroke Study Group scores were 8.35 +/- 16.9 versus 11.55 +/- 15.6 (long-term) and 0.64 +/- 7.3 versus 2.40 +/- 6.9 (prognostic), and improvements in the Barthel Index ratings were 10.72 +/- 24.7 versus 13.95 +/- 23.3, respectively. Glasgow Coma Scale score improvements in the survivors were 0.81 +/- 1.5 and 1.16 +/- 1.7 in the treated and control groups, respectively. Hemolysis (generally subclinical) was the only adverse effect of glycerol noted.

In the absence of any clinically or statistically significant difference in outcome between the treated and control groups, this trial provides no justification for glycerol therapy following acute cerebral hemorrhage.
Reproducibility of noninvasive ultrasonic measurement of carotid atherosclerosis. The Asymptomatic Carotid Artery Plaque Study.
Authors: Riley W A , Barnes R W , Applegate W B , Dempsey R , Hartwell T , Davis V G , Bond M G , Furberg C D
Published: June 2011

To determine the effect of a lipid-lowering agent and/or a low-dose antithrombotic agent on the progression of early-stage carotid atherosclerosis, noninvasive B-mode ultrasound was used to measure intimal-medial thickness in asymptomatic individuals with moderately elevated lipids as part of the ongoing multicenter Asymptomatic Carotid Artery Plaque Study.

Uniform ultrasonic scanning and reading protocols were implemented to obtain maximum intimal-medial thickness measurements in 12 standard segments in patients having a small to moderate wall thickness (1.5-3.5 mm) in at least one of the carotid arteries. Paired B-mode image recordings on 858 patients, performed 1 month apart and read at a core laboratory (each pair by the same reader), determined both within-sonographer (W, n = 405) and between-sonographer (B, n = 453) reproducibility.

The primary end point (mean +/- SD), defined in each individual as the mean value of the 12 maximum intimal-medial thickness measurements, was 1.31 +/- 0.21 mm (W) and 1.32 +/- 0.22 (B) at the time of the second examination. The mean difference in the primary end point (exam 2-exam 1) was -0.01 +/- 0.13 mm (W) and 0.00 +/- 0.15 mm (B). The Pearson correlation coefficients were 0.79 (W) and 0.75 (B). In 90% of the patients, the absolute difference in the primary end point was less than 0.22 mm (W) and less than 0.24 mm (B). Variability of the secondary end point, defined as the single largest intimal-medial thickness measurement in a patient, was between three and four times larger than the variability for the primary end point. Differences in sonographer performance between clinical centers were very small.

The results demonstrate that standardized noninvasive ultrasonic techniques yield highly reproducible measures of carotid intimal-medial thickness, which can serve as a measure of carotid atherosclerosis in clinical trials that monitor small rates of lesion progression.
Measurement of motor recovery after stroke. Outcome assessment and sample size requirements.
Authors: Duncan P W , Goldstein L B , Matchar D , Divine G W , Feussner J
Published: June 2011

The purpose of this study was to analyze recovery of motor function in a cohort of patients presenting with an acute occlusion in the carotid distribution. Analysis of recovery patterns is important for estimating patient care needs, establishing therapeutic plans, and estimating sample sizes for clinical intervention trials.

We prospectively measured the motor deficits of 104 stroke patients over a 6-month period to identify earliest measures that would predict subsequent motor recovery. Motor function was measured with the Fugl-Meyer Assessment. Fifty-four patients were randomly assigned to a training set for model development; 50 patients were assigned to a test set for model validation. In a second analysis, patients were stratified on basis of time and stroke severity. The sample size required to detect a 50% improvement in residual motor function was calculated for each level of impairment and at three points in time.

At baseline the initial Fugl-Meyer motor scores accounted for only half the variance in 6-month motor function (r2 = 0.53, p less than 0.001). After 5 days, both the 5-day motor and sensory scores explained 74% of the variance (p less than 0.001). After 30 days, the 30-day motor score explained 86% of the variance (p less than 0.001). Application of these best models to the test set confirmed the results obtained with the training set. Sample-size calculations revealed that as severity and time since stroke increased, sample sizes required to detect a 50% improvement in residual motor deficits decreased.

Most of the variability in motor recovery can be explained by 30 days after stroke. These findings have important implications for clinical practice and research.
Endothelium-derived nitric oxide synthase inhibition. Effects on cerebral blood flow, pial artery diameter, and vascular morphology in rats.
Authors: Prado R , Watson B D , Kuluz J , Dietrich W D
Published: June 2011

We determined the effects of inhibiting the production of cerebral endothelium-derived nitric oxide on pial artery diameter, cortical blood flow, and vascular morphology.

An inhibitor of endothelium-derived nitric oxide synthesis, NG-nitro-L-arginine methyl ester hydrochloride (L-NAME), or an equivalent volume of 0.9% saline was infused into rats intra-arterially in a retrograde fashion via the right external carotid artery at a rate of 3 mg/kg/min to a total dose of 190 mg/kg or intravenously at 1 mg/kg/min to a total dose of 15 mg/kg. Large pial arteries were continuously visualized through an operating microscope, and cortical cerebral blood flow was monitored by laser-Doppler flowmetry. To localize areas of morphological interest, the protein tracer horseradish peroxidase was injected 15 minutes before termination of the L-NAME infusion and the rats were perfusion-fixed 15 minutes later for light and electron microscopic analysis.

Infusion of L-NAME significantly raised arterial blood pressure at both doses (for 190 mg/kg, from 103.2 +/- 3.4 to 135 +/- 3.4 mm Hg; for 15 mg/kg, from 125 +/- 2.8 to 144.4 +/- 4.0 mm Hg). Pial arteries constricted within 10 minutes after the start of the intracarotid infusion to 40% of the preinfusion diameter, while cortical cerebral blood flow decreased to an average of 72.5% of that at baseline. Morphological abnormalities in the experimental rats included microvascular stasis and focal areas of blood-brain barrier disruption to protein. Ultrastructural examination of cortical leaky sites revealed constricted arterioles with many endothelial pinocytotic vesicles and microvilli.

These observations suggest that inhibition of endothelium-derived nitric oxide synthesis affects the relation between cerebral arterial diameter and cerebral blood flow and can lead to subtle cerebral vascular pathological changes consistent with focal brain ischemia.
Early changes in rabbit cerebral artery reactivity after subarachnoid hemorrhage.
Authors: Debdi M , Seylaz J , Sercombe R
Published: June 2011

Subarachnoid hemorrhage frequently leads to long-term cerebral artery narrowing called vasospasm. Very early changes in cerebral arteries have not been studied extensively and may be critical for the later pathological developments. We therefore determined what changes in the reactivity of cerebral arteries could be observed after 10 minutes' or 24 hours' contact with subarachnoid blood.

Ten minutes or 24 hours after the injection of blood or physiological solution (sham hemorrhage) into the cisterna magna of anesthetized rabbits or no injection (control rabbits), segments of the middle cerebral, basilar, and vertebral arteries were removed for conventional in vitro tension measurements. Concentration-response curves to four endogenous constrictors likely to be released after hemorrhage were obtained, and the maximum relaxation to acetylcholine was determined.

There were no significant differences between the sham hemorrhage and control groups. Compared with control rabbits, treated animals showed increased reactivity to uridine triphosphate in the basilar and vertebral arteries at 10 minutes but not at 24 hours, whereas reactivity was increased in the middle cerebral artery only at 24 hours. Reactivity to serotonin was greatly increased in all arteries at both latencies (up to 2.7 times). Reactivity to noradrenaline was unchanged in the basilar and vertebral arteries at 10 minutes; reactivity in both the basilar and middle cerebral arteries was increased at 24 hours, which is compatible with denervation supersensitivity. There were only minor changes in the reactivity to histamine, and only at 10 minutes. Relaxation to acetylcholine was increased for the middle cerebral artery at 10 minutes but otherwise was not significantly changed.

Reactivity to uridine triphosphate, serotonin, and noradrenaline greatly increases by 10 minutes to 24 hours after subarachnoid hemorrhage, and this increase is not owing to the mechanical effects of intracranial hypertension, nor is it related to impaired endothelium-dependent relaxation. It is suggested that these and other spasmogens cause excessive muscular calcium loading with a very rapid onset after subarachnoid hemorrhage.
Fatal basilar vasculopathy complicating bacterial meningitis.
Authors: Perry J R , Bilbao J M , Gray T
Published: June 2011

Bacterial meningitis complicated by thrombosis, vasculitis, and aneurysm formation affecting both small and distal branches of cerebral vessels has been well described. Involvement of major cerebral vessels is rare and has only been documented late in the course of disease.

We describe the clinical and pathological findings in a young man who presented with pontine infarction as an early manifestation of bacterial meningitis. Streptococcus milleri, an unusual organism in this setting, was cultured. Despite improvement with antibiotic therapy, the patient experienced fatal subarachnoid hemorrhage. A ruptured inflammatory aneurysm of the basilar artery, evidence of residual meningitis and vasculitis, and basilar thrombosis associated with pontine infarction were found.

Bacterial meningitis, which may be associated with severe vasculopathy of the basilar artery and lead to cerebral infarction, aneurysm formation, and subarachnoid hemorrhage, should be considered in the differential diagnosis of these conditions. The role of S. milleri in meningitis and its vascular complications merits further study.