bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute bilateral cerebellar infarction in the territory of the medial branches of posterior inferior cerebellar arteries.
Authors: Tada Y , Mizutani T , Nishimura T , Tamura M , Mori N
Published: June 2011

We describe the first clinicoradiological report of acute bilateral cerebellar infarction confined to the territory of the medial branches of the posterior inferior cerebellar arteries.

A 65-year-old man with atrial fibrillation and hypertension had sudden onset of vertigo, followed by brief loss of consciousness. Three days later a cranial computed tomographic scan showed acute hydrocephalus and low-density areas in the cerebellar vermis on both sides. On transfer the patient showed mild dysarthria, dysequilibrium with retropulsion, symmetrical bilateral horizontal gaze-evoked nystagmus on lateral gaze, and marked gait ataxia without brain stem signs, followed by marked vertigo that was induced by motion. Cranial magnetic resonance imaging revealed abnormalities consistent with fairly symmetrical bilateral cerebellar hemorrhagic infarction that was confined to the territory of the medial branches of the posterior inferior cerebellar arteries, in addition to minimal high-intensity areas in the pons on T2-weighted images. The patient improved with conservative therapy, including intravenous administration of glycerol.

We speculate that our patient likely had initial transient occlusion of the right vertebral artery at the origin of the right posterior inferior cerebellar artery, which probably gave rise to the bilateral medial branches of posterior inferior cerebellar arteries. This caused infarction in the territory of the medial branches on both sides without remaining brain stem signs. Such an unusual pattern of cerebellar infarction accompanied by acute hydrocephalus posed a diagnostic challenge at the time of transfer to our care, and correct diagnosis was facilitated by cranial magnetic resonance imaging.
Nitric oxide and the cerebral circulation.
Authors: Faraci F M , Brian J E
Published: June 2011

Nitric oxide (NO) is a potent vasodilator that was initially described as the mediator of endothelium-dependent relaxation (endothelium-derived relaxing factor, EDRF). It is now known that NO is produced by a variety of other cell types.

Endothelium produces NO (EDRF) under basal conditions and in response to a variety of vasoactive stimuli in large cerebral arteries and the cerebral microcirculation. Endothelium-dependent relaxation is impaired in the presence of several pathophysiological conditions. This impairment may contribute to cerebral ischemia or stroke. Activation of glutamate receptors appears to be a major stimulus for production of NO by neurons. Neuronally derived NO may mediate local increases in cerebral blood flow during increases in cerebral metabolism. NO synthase-containing neurons also innervate large cerebral arteries and cerebral arterioles on the brain surface. Activation of parasympathetic fibers that innervate cerebral vessels produces NO-dependent increases in cerebral blood flow. Increases in cerebral blood flow during hypercapnia also appear to be dependent on production of NO. Astrocytes may release some NO constitutively, but astrocytes and microglia can release relatively large quantities of NO after induction of NO synthase in response to endotoxin or some cytokines. Expression of inducible NO synthase, perhaps in response to local production of cytokines, may exert cytotoxic effects in brain during or after ischemia.

Because endothelium, neurons, and glia can all produce NO in response to some stimuli, the influence of NO on the cerebral circulation appears to be very important. Under normal conditions, constitutively produced NO influences basal cerebral vascular tone and mediates vascular responses to a diverse group of stimuli. The inducible form of NO synthase produces much greater amounts of NO that may be an important mediator of cytotoxicity in brain.
Elevated serum cholesterol is a risk factor for both coronary heart disease and thromboembolic stroke in Hawaiian Japanese men. Implications of shared risk.
Authors: Benfante R , Yano K , Hwang L J , Curb J D , Kagan A , Ross W
Published: June 2011

The relation between total serum cholesterol level and thromboembolic or nonhemorrhagic stroke is controversial. The Honolulu Heart Program cohort of Japanese-American men provides data which show that elevated serum cholesterol is an independent predictor of thromboembolic stroke as well as coronary heart disease (CHD). The data are presented to suggest that the association of elevated cholesterol with stroke is sometimes underestimated or underreported partly because of competing or shared risk with CHD, the other major atherosclerotic end point.

The data are based on 6352 men (aged 51 to 74 years) at baseline examination (1971 to 1974) who were free of clinical CHD and stroke and were followed an average of 15 years for new cases of both end points. Relative risks of serum cholesterol for CHD and thromboembolic stroke were calculated, controlling for other major cardiovascular covariates.

There was a continuous and progressive increase in both CHD and thromboembolic stroke rates with increasing levels of serum cholesterol. The relative risk between the highest and lowest quartiles of serum cholesterol was 1.7 (95% confidence interval, 1.4 to 2.0) for CHD and 1.4 (95% confidence interval, 1.1 to 1.9) for thromboembolic stroke. There was a decline in the difference in relative risks between CHD and thromboembolic stroke in older men (aged 60 years and older) compared with younger men (aged younger than 60 years).

These data provide additional evidence that elevated serum cholesterol should be considered a primary risk factor for thromboembolic stroke, presumably through its effect on both coronary and cerebrovascular atherosclerosis. It is suggested that this association is sometimes underestimated or underreported partly because of shared or competing risk with CHD, the clinical manifestation of atherosclerosis that generally occurs earlier in life and with greater frequency than thromboembolic stroke.
Comparison of carbon dioxide responsiveness of cerebellar blood flow between affected and unaffected sides with crossed cerebellar diaschisis.
Authors: Ishii K , Kanno I , Uemura K , Hatazawa J , Okudera T , Inugami A , Ogawa T , Fujita H , Shimosegawa E
Published: June 2011

Concerning vasoreactivity of cerebellar blood flow (CeBF) in patients affected with crossed cerebellar diaschisis (CCD), several controversies have been reported. One is reduced asymmetry of CeBF after acetazolamide administration in 99mTc hexamethylpropyleneamine oxime single-photon emission-computed tomography, and the other is persistent asymmetry with alternation in PaCO2 using the 133Xe clearance method. The purpose of this study is to examine whether CeBF vasoreactivity in the side affected with CCD is the same as that in the unaffected side.

We analyzed CeBF during hypocapnia, normocapnia, and hypercapnia performed in 27 patients with cerebrovascular disease (age range, 38 to 73 years; mean age, 62.0 +/- 8.5 years) affected by CCD. CeBF was measured using H2(15)O and positron emission tomography.

The CeBF ratio of CCD-affected side to CCD-unaffected side was consistent during the perturbation of PaCO2. This ratio was 0.82 +/- 0.08 for PaCO2 elevation and 0.83 +/- 0.07 for PaCO2 lowering. Both were not significantly different from unity.

The percent change of CeBF per millimeter of mercury PaCO2 change was uniform across affected and unaffected sides with CCD. These findings are consistent with our recent findings observed in activated cerebral tissue during photic stimulation.
p53-immunoreactive protein and p53 mRNA expression after transient middle cerebral artery occlusion in rats.
Authors: Li Y , Chopp M , Zhang Z G , Zaloga C , Niewenhuis L , Gautam S
Published: June 2011

We investigated the temporal distribution of the p53-immunoreactive protein in conjunction with cellular damage and the expression of the p53 mRNA after focal cerebral ischemia in rats.

Male Wistar rats (n = 66; controls, n = 7) were subjected to 2 hours of middle cerebral artery occlusion and were killed at various times of reperfusion (0.5 to 168 hours) for p53 immunohistochemistry and Northern blot analysis.

A cellular expression of mutant p53-immunoreactive protein was found localized to anatomic sites exhibiting severe neuronal damage. A maximal induction of mutant p53-immunoreactive protein was found at 12 hours after reperfusion and subsequently declined. No wild-type p53 protein expression was detected after ischemia. A time-dependent expression of p53 mRNA was observed in both hemispheres. The peak level of p53 mRNA occurred at 24 hours after reperfusion.

Our data indicate that the expressions of p53-immunoreactive protein and p53 mRNA are upregulated after transient focal cerebral ischemic insult in rats. The concomitant appearance of p53 and cell damage in ischemic brain suggests that p53 expression may impact cell biological response to an ischemic insult.
Chronic cerebral hypoperfusion and impaired neuronal function in rats.
Authors: Sekhon L H , Morgan M K , Spence I , Weber N C
Published: June 2011

Studies in acute cerebral ischemia have shown that reductions in cerebral blood flow of up to 50% do not lead to infarction or alterations in neuronal electric activity. Little is known about the effects of chronic reductions in cerebral blood flow. The purpose of this study was to evaluate neuronal electrophysiological function in brain that had been subjected to a chronic reduction of cerebral blood flow of less than 50%. Based on existing knowledge of thresholds of cerebral ischemia, neuronal electrophysiological function should be unaffected by hypoperfusion of this magnitude.

An arteriovenous fistula model in the rat was used to induce chronic cerebral hypoperfusion with reductions of cerebral blood flow of 25% to 50% as measured previously by 14C-labeled autoradiography. Using in vitro electrophysiological brain slice techniques, long-term potentiation in hippocampal CA1 neurons was examined extracellularly after 6 months of chronic noninfarctional cerebral hypoperfusion. Brains were also examined histologically at this time for evidence of cerebral infarction.

There was no evidence of cerebral infarction. Long-term potentiation was produced in 9 of 12 control animals and only 2 of 8 hypoperfused animals. This difference was significant (P < .05) and demonstrated that long-term potentiation was impaired in animals with chronic hypoperfusion.

Noninfarctional reductions in cerebral blood flow of up to 50% do impair neuronal function in chronic cerebral ischemia, a result quite distinct from that seen in acute ischemia. The threshold for neuronal dysfunction in chronic cerebral hypoperfusion is lower than that found in acute cerebral ischemia, suggesting that duration as well as severity of ischemic insult determines cellular viability. Chronic hypoperfusion may lead to a noninfarctional state with impaired neuronal function, a category of chronic cerebral ischemia not previously identified.
Cortical hypoperfusion after global forebrain ischemia in rats is not caused by microvascular leukocyte plugging.
Authors: Dirnagl U , Niwa K , Sixt G , Villringer A
Published: June 2011

We tested the hypothesis that cerebral hypoperfusion after experimental global cerebral ischemia is caused by plugging of the microcirculation with activated leukocytes using in vivo microscopic observation of the behavior of leukocytes in the cortical microcirculation during the transition from postischemic hyperperfusion to hypoperfusion.

Anesthetized and ventilated rats (n = 24) were equipped with a closed cranial window. Physiological variables and cortical regional cerebral blood flow (laser-Doppler flowmetry) were measured continuously. Leukocytes were labeled intravitally with rhodamine 6G and visualized in the microcirculation of the brain surface and outer layers of the cortex with confocal laser scanning microscopy from preischemia to 4 hours after reperfusion that followed 10 minutes of global cerebral ischemia (rCBF < 10% of control).

In controls (n = 8), there were no signs of leukocyte activation over the 4-hour observation period. In ischemic rats (n = 16), during the transition from hyperperfusion to hypoperfusion there was no change in the behavior of leukocytes. Most notably, no capillary pluggers were seen. In the postischemic period only a slight increase of the number of leukocytes rolling along or sticking to the venular endothelium was seen, and very few capillaries were plugged by leukocytes. Extravasation of leukocytes into the brain tissue was observed in 8 rats beginning 2 hours after ischemia with a variable degree between animals.

Because there was only mild activation of leukocyte-endothelium interaction within the first hours of reperfusion after 10 minutes of global forebrain ischemia, because no leukocytes plugged superficial cortical capillaries during the transition from hyperperfusion to hypoperfusion, and because the regional cerebral blood flow transition was very rapid, we speculate that leukocyte plugging is not responsible for the early cortical hypoperfusion seen after brief global ischemia in rats.
Tryptophan hydroxylase activity in rat brain base arteries related to innervation originating from the dorsal raphe nucleus.
Authors: Moreno M J , López de Pablo A L , Marco E J
Published: June 2011

Tryptophan hydroxylase activity was assayed in cell-free extracts of rat brain base arteries as marker of a serotonergic innervation.

Estimation of the enzymatic activity was made in untreated male Sprague-Dawley rats (n = 53) and in those who underwent destruction of the dorsal and median raphe nuclei (n = 10).

Tryptophan hydroxylase activity was measured in rat cerebral arteries. The time-dependent 5-hydroxytryptophan production was undetectable in the absence of tryptophan or 6-methyltetrahydropterine and in the presence of 6-fluorotryptophan, and it was significantly reduced in the presence of p-chlorophenylalanine. Destruction of the dorsal raphe nucleus but not the median raphe nucleus brought about a significant reduction in enzyme activity.

These results suggest that rat cerebral arteries receive a serotonergic innervation arising from the dorsal raphe nucleus.
Pathoanatomic correlation between poststroke pathological crying and damage to brain areas involved in serotonergic neurotransmission.
Authors: Andersen G , Ingeman-Nielsen M , Vestergaard K , Riis J O
Published: June 2011

The aim of the study was to correlate the severity of poststroke pathological crying with lesion size and location.

Twelve selected stroke patients were ranked in terms of overall clinical severity of the syndrome of pathological crying, and the size and location of the stroke lesion(s) were determined by magnetic resonance imaging.

The patients with the clinically most severe pathological crying had relatively large bilateral pontine lesions without lesions in the hemispheres. The intermediate group had bilateral central hemispheric lesions, and the clinically least affected patients had mainly unilateral large subcortical lesions.

Poststroke pathological crying may be attributable to stroke-induced partial destruction of the serotonergic raphe nuclei in the brain stem or their ascending projections to the hemispheres.
Oral contraception and stroke. Evidence from the Royal College of General Practitioners' Oral Contraception Study.
Authors: Hannaford P C , Croft P R , Kay C R
Published: June 2011

A nested case-control analysis of data collected during the prospective Royal College of General Practitioners' Oral Contraception Study was performed to examine the relation between use of oral contraception and risk of stroke.

The 253 women who had a first-ever stroke (International Classification of Diseases, eighth revision, codes 4300 to 4389) or amaurosis fugax (code 3791) between 1968 and 1990 (case subjects) were compared with 759 women who did not have this diagnosis (control subjects).

Smoking, social class, and history of hypertension were found to be important risk factors for stroke. Women who had ever used oral contraceptives had an increased risk of all stroke (odds ratio, 1.5; 95% confidence interval, 1.1 to 2.0, adjusted for smoking and social class) and of a fatal event (adjusted odds ratio, 2.3; 95% confidence interval, 1.2 to 4.4). A significant doubling of all stroke risk was observed among current users, an effect that was apparent in both smokers and nonsmokers. Former users had a small nonsignificant elevation in risk of all stroke but a stronger risk of a fatal event. The effects in former users appeared to be restricted to women who smoked.

Current users of oral contraceptives appeared to be at increased risk of stroke. There is some evidence that former users may also have a persisting effect, although further research is needed to confirm these observations.
The effect of velocity on the appearance of embolic signals studied in transcranial Doppler models.
Authors: Droste D W , Markus H S , Nassiri D , Brown M M
Published: June 2011

Transcranial Doppler ultrasound can be used to detect circulating cerebral emboli. Recent studies have demonstrated that embolus size is significantly related to both the relative intensity increase and duration of an embolic signal. This may allow information about embolus size to be obtained by analysis of Doppler embolic signals. However, theoretically duration will be inversely related to velocity, and therefore velocity may need to be accounted for if information on embolus size is to be derived from the duration of Doppler embolic signals.

The relation between velocity and both relative intensity increase and duration of embolic signal was investigated in an in vitro flow model, a sheep carotid artery model, and in patients with prosthetic heart valves. The same standard transcranial Doppler ultrasound machine was used for all studies. Embolic signals resulting from 99 glass microspheres (size, 210 to 250 microns) were studied in the in vitro model, as were those from 64 glass microspheres (size, 105 to 150 microns) in the sheep model. Embolic signals recorded from the six middle cerebral arteries of three patients with prosthetic cardiac valves were also studied.

There was a significant (P < .001) inverse relation between velocity and duration of high-intensity signal (in vitro model, r = -.82; sheep model, r = -.43); the exact relations were described using best-fit equations. Correlation coefficients for this relation in patients varied between -.30 and -.55. There was also an unexpected significant positive relation between velocity and intensity in the sheep model (r = .44, P < .001) but not in the in vitro model (P > .05). This relation was also seen in some, but not all, patients.

When the duration of embolic signals is used to provide information about the relative size of an embolus, the velocity of the embolic signal should be taken into account. A relation between velocity and relative intensity increase was found in the sheep model and in some patient recordings. It is suggested this relation may result from greater power being supplied to emboli traveling at higher velocities in the center of the vessel; this may occur under certain recording conditions.
Effective treatment of poststroke depression with the selective serotonin reuptake inhibitor citalopram.
Authors: Andersen G , Vestergaard K , Lauritzen L
Published: June 2011

The aim of the study was to investigate the efficacy and safety of the selective serotonin reuptake inhibitor citalopram in treating poststroke depression, since available treatments are usually poorly tolerated.

A 6-week double-blind, placebo-controlled trial was undertaken. Diagnosis and outcome were determined using the Hamilton Depression Scale, and unwanted effects were measured using the UKU side effect rating scale. Sixty-six consecutive depressed patients from an unselected population of 285 stroke patients aged 25 to 80 years entered the trial 2 to 52 weeks after stroke. They were assigned to equally sized treatment and placebo groups. The initial level of depression was comparable in the two groups (mean baseline Hamilton Depression scores, 19.4 and 18.9, respectively). Demographic parameters were also comparable in the two groups.

Significantly greater improvement was seen in patients treated with citalopram (10 to 40 mg/d) for 3 and 6 weeks, both when including all patients (intention-to-treat analysis, P < .05) and excluding patients who dropped out during the first 3 weeks (efficacy analysis, P < .005). Half of the 28 patients who entered the trial 2 to 6 weeks after stroke recovered within 1 month, independent of the treatment given. This indicates a high degree of spontaneous recovery in the early phase after stroke. In contrast, recovery was infrequent in placebo group patients who became depressed 7 weeks or more after stroke. No serious side effects related to the treatment were detected; those present were mild and usually transient.

This trial demonstrates that the selective serotonin reuptake inhibitor citalopram offers an advantageous new treatment of poststroke depression that is both safe and effective.
Trends in stroke incidence and mortality in Hawaiian Japanese men.
Authors: Kagan A , Popper J , Reed D M , MacLean C J , Grove J S
Published: June 2011

Vital statistics show a sharp decline in stroke mortality since the late 1960s. It is not clear whether this has been associated with a decline in stroke incidence.

Since 1966 the Honolulu Heart Program has monitored the incidence and mortality of coronary heart disease and stroke in a target population of 11,136 men of Japanese ancestry living on Oahu. Trends were analyzed from January 1, 1969, through December 31, 1988.

Of 7893 men aged 45 to 68 years and free of stroke at entry examination, 530 developed first episodes of stroke in the period 1969 to 1988 (389 cases of thromboembolic stroke, 124 cases of hemorrhagic stroke, and 17 cases of stroke of unknown type). Age-adjusted annual stroke incidence declined from 5.1 per 1000 person-years in 1969 to 1972 to 2.4 in 1985 to 1988. The incidences of thromboembolic stroke, hemorrhagic stroke, and total stroke decreased 3.5%, 4.2%, and 4.4% per year, respectively. The 1-month case-fatality rates for thromboembolic stroke decreased moderately; those for hemorrhagic stroke fell dramatically.

These findings suggest that the decline in stroke mortality in the past two or three decades results from a decline in both incidence rates and early case-fatality rates in thromboembolic and hemorrhagic stroke and stroke of unknown type. The decreases may be related to changes in risk factors, such as the decline in blood pressure and the decrease in cigarette smoking, as well as improvements in diagnosis and treatment.
Magnetic resonance imaging assessment of evolving focal cerebral ischemia. Comparison with histopathology in rats.
Authors: Knight R A , Dereski M O , Helpern J A , Ordidge R J , Chopp M
Published: June 2011

This study was performed to document the progression of ischemic brain damage after middle cerebral artery occlusion in the rat using magnetic resonance imaging and histopathologic methods.

Cerebral ischemia was induced through permanent tandem occlusion of ipsilateral middle cerebral and common carotid arteries. The evolution of magnetic resonance imaging and histopathologic parameter changes was studied, both short term (1.5 to 8 hours) and long term (24 to 168 hours), in five specific brain regions within the middle cerebral artery territory.

Significant changes in proton nuclear magnetic resonance spin-lattice and spin-spin relaxation times and the "apparent" diffusion coefficient of water could be detected within hours after the onset of permanent focal cerebral ischemia, whereas significant alterations in proton spin-density ratios were not apparent until approximately 48 hours. Histological changes were evident within 12 hours, with a significant loss of neurons seen in the most severely damaged regions at 7 days. Diffusion-weighted imaging was the most sensitive technique for visualizing acute ischemic alterations. The water diffusion coefficient was the only magnetic resonance imaging parameter studied to indicate significant alterations within the first 4 hours after arterial occlusion in all five brain regions.

The degree of change for a particular magnetic resonance imaging parameter appeared to be related to the location and extent of neuronal injury, with the most dramatic changes occurring within the areas displaying the most severe histological damage. These results indicate that complete specification of all brain regions affected by ischemic brain injury may require a combination of imaging strategies applied over a period of days and suggest the possibility of using magnetic resonance imaging to distinguish between permanent and reversible cell damage.
Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage.
Authors: Broderick J P , Brott T G , Duldner J E , Tomsick T , Leach A
Published: June 2011

The goal of this study was to determine the causes of mortality and morbidity after subarachnoid hemorrhage.

We identified all first-ever spontaneous subarachnoid hemorrhages that occurred in the nearly 1.3 million population of greater Cincinnati during 1988.

Thirty-day mortality for subarachnoid hemorrhage was 45% (36 of 80 cases). Of the 36 deaths, 22 (61%) died within 2 days of onset; 21 of these deaths were due to the initial hemorrhage, and one death was due to rebleeding documented by computer tomography. Nine of the remaining 14 deaths after day 2 were caused by the initial hemorrhage (2 cases) or rebleeding (7 cases). Volume of subarachnoid hemorrhage was a powerful predictor of 30-day morality (P = .0001). Only 3 of the 29 patients with a volume of subarachnoid hemorrhage of 15 cm3 or less died before 30 days. Two of these 3 patients died from documented rebleeding; the third had 87 cm3 of additional intraventricular hemorrhage. Delayed arterial vasospasm contributed to only 2 of all 36 deaths.

Most deaths after subarachnoid hemorrhage occur very rapidly and are due to the initial hemorrhage. Rebleeding is the most important preventable cause of death in hospitalized patients. In a large representative metropolitan population, delayed arterial vasospasm plays a very minor role in mortality caused by subarachnoid hemorrhage.
Interconversion of stroke scales. Implications for therapeutic trials.
Authors: Muir K W , Grosset D G , Lees K R
Published: June 2011

Stroke scales are intended to measure stroke severity for the purpose of clinical trials. Scores have been used to determine trial entry, to compare patient groups within or between trials, or as a secondary end point. The use of scores as an end point in meta-analysis has not been validated, but such analyses have nevertheless been performed when equivocal results have been obtained using the main outcome measure. The different scale designs suggest that conversion of scores may not be possible. We sought to determine whether scores on different scales could be interconverted.

A single observer scored 433 consecutive admissions to an acute stroke unit on the Canadian Neurological Scale, the middle cerebral artery Neurological Score (or Orgogozo scale), and the National Institutes of Health stroke scale. Data were separated into training and test sets, and linear regression was used to model conversion between scales. Prediction errors were calculated. Strokes were subdivided according to the Oxfordshire Community Stroke Project classification, and coefficients of determination were calculated for different subtypes.

Conversion between Canadian and middle cerebral artery Neurological scales was satisfactory (R2 = 94.7%), and prediction errors were acceptable (absolute prediction error, 5.0 +/- 5). Conversion from the National Institutes of Health scale was worse (R2 = 87.5% to Canadian and 89.0% to Neurological Score), and prediction errors were significantly greater (Neurological Score error, 8.7 +/- 7; Canadian Neurological Scale error, 8.5 +/- 7.3; P < .005 for both). Coefficients of determination for interconversion were significantly worse for dysphasic patients with total anterior circulation strokes than for other stroke types (P < .01). Reweighting the motor component of the National Institutes of Health scale improved coefficients of determination and reduced prediction errors, but prediction error for conversion to the Canadian scale remained significantly greater than other conversions (P = .001).

The Canadian Neurological Scale and the middle cerebral artery Neurological Score may reliably be converted. The National Institutes of Health scale cannot be used to predict these scores reliably, even with reweighting of the motor score. Interconversion is poorest for patients with dysphasia and total anterior circulation strokes. These results suggest that there will be more general difficulty in interconverting scales that use different test items and weighting. Meta-analysis using sequential changes in averaged scores from various stroke scales is not valid.
Leukocyte aggregation in patients with a previous cerebral ischemic event.
Authors: Silvestrini M , Pietroiusti A , Magrini A , Matteis M , Carta S , Bernardi G , Galante A
Published: June 2011

The role of leukocyte aggregation in ischemic stroke is controversial. In this study we investigated this hemorheologic alteration in patients at risk for stroke.

Leukocyte aggregation was evaluated with the leukergy test in 61 patients with a recent cerebral ischemic event and in 61 control subjects.

In patients leukocyte aggregation was significantly higher than in control subjects (3.8 +/- 3.4% versus 2.5 +/- 2.2%; P = .01). In control subjects, the presence of vascular risk factors was associated with values of aggregation similar to those observed in patients.

These findings suggest an association between altered leukocyte aggregation and cerebrovascular disease. Further investigations are needed to evaluate whether this hemorheologic alteration can be considered a marker of increased risk for stroke.
The protective effect of L-threo-3,4-dihydroxyphenylserine on ischemic hippocampal neuronal death in gerbils.
Authors: Lee T H , Abe K , Aoki M , Nakamura M , Kogure K , Itoyama Y
Published: June 2011

L-Threo-3,4-dihydroxyphenylserine (DOPS) is reported to increase the nerve growth factor (NGF) synthesis in cultured mouse L-M fibroblast and astroglial cells, and this effect is not blocked by treatment with decarboxylase inhibitor. NGF is suggested to play an important role in neuronal survival and regeneration under pathological conditions. We evaluated the possible protective effect of DOPS against hippocampal CA1 cell death after transient forebrain ischemia in gerbils.

Male mongolian gerbils were treated with DOPS (30, 100, or 300 mg/kg IP) plus benserazide (10 mg/kg IP) (n = 28) or vehicle (n = 7) before 3.5 minutes of forebrain ischemia. For histopathologic study, the animals were decapitated 7 days after recirculation, and neuronal density of the hippocampal CA1 area was counted after cresyl violet staining. For immunohistochemical study, another group of gerbils (n = 34) was recovered for 1, 3, and 8 hours and 1, 2, and 7 days, when they were decapitated. The brain sections were stained against NGF, NGF receptor, and HSP70 using the avidin-biotin-peroxidase method.

Preservation of the hippocampal CA1 cells was found in the brains treated with 300 mg/kg DOPS plus benserazide (neuronal density, 125 +/- 24 cells per millimeter) compared with the vehicle-treated ones (49 +/- 11 cells per millimeter) (P < .01). The immunoreactive NGF was greatly reduced from 3 hours after recirculation in the vehicle group, but it was much less reduced in the 300-mg/kg-DOPS-plus-benserazide group as compared with the vehicle group. The immunoreactivity for NGF receptor was gradually induced from 1 hour after recirculation with the peak at 1 day in the vehicle group, but it was only slightly induced at 8 hours in the 300-mg/kg-DOPS-plus-benserazide group. HSP70 immunoreactivity was also induced from 3 hours with the peak at 1 day in the vehicle group. However, in the 300-mg/kg-DOPS-plus-benserazide group, the induction of HSP70 was found from 8 hours and was much less intensive.

Treatment with DOPS is protective to the ischemic hippocampal CA1 cells, and the NGF-receptor system may play a role in this protective effect of DOPS.
Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion.
Authors: Matsuo Y , Onodera H , Shiga Y , Nakamura M , Ninomiya M , Kihara T , Kogure K
Published: June 2011

Neutrophils have been implicated in the pathogenesis of ischemia-reperfusion injury. The aim of the present study was to evaluate the correlation between neutrophil infiltration into ischemic tissues and brain injury after transient focal ischemia.

We evaluated the effects of depletion of circulating neutrophils by administration of an antineutrophil monoclonal antibody (RP3) on brain edema formation, infarct size, and neutrophil infiltration (myeloperoxidase [MPO]-quantified) in rats with 1 hour of middle cerebral artery (MCA) occlusion.

In the cerebral cortex perfused by the anterior cerebral artery (ACA area), there was a significant increase in MPO activity only 24 hours (P < .05) after reperfusion. In the cerebral cortex perfused by the middle cerebral artery (MCA area) and caudate putamen, MPO activity was significantly increased at 12 (MCA area, P < .01; caudate putamen, P < .05), 24 (MCA area, P < .05; caudate putamen, P < .01), and 72 hours (MCA area, P < .01; caudate putamen, P < .05) and returned to near-normal level by 168 hours after reperfusion. Brain MPO activity after transient MCA occlusion correlated well with the appearance of neutrophils. Depletion of neutrophils by RP3 treatment completely inhibited the increase in MPO activity in the ischemic brain after 24 hours of reperfusion. In addition, treatment with RP3 significantly attenuated the postischemic increase in brain water content at 24 hours after reperfusion. RP3 also significantly reduced the size of infarct area.

These results indicate that the increase in brain MPO activity after transient focal ischemia virtually reflects the neutrophil infiltration and that neutrophil infiltration into the ischemic brain is implicated in postischemic brain injury.
Contralateral conjugate eye deviation in acute supratentorial lesions.
Authors: Tijssen C C
Published: June 2011

Conjugate eye deviation (CED) in patients with acute supratentorial lesions is generally directed ipsilateral to the lesioned hemisphere. Incidentally, CED occurs to the contralateral side. We report five new cases and review previously published reports to elucidate the lesion responsible for and the mechanism underlying this phenomenon.

In a prospective study of 133 consecutive patients with CED caused by an acute supratentorial lesion, 5 patients showed contralateral CED. This was caused by an intracerebral hemorrhage located thalamic (n = 2), frontoparietal (n = 1), and frontoparietotemporal (n = 1). In 1 patient the cause was a subdural hematoma, an association that has not been reported earlier. Four of the 5 patients died. All patients had clinical signs of rostral brain stem dysfunction and a shift of midline structures on computed tomographic scan or at autopsy.

Contralateral CED is always associated with hemorrhagic lesions, most commonly in the thalamus. The prognosis of patients with this sign is generally poor. Involvement of descending oculomotor pathways from the contralateral hemisphere at midbrain level is the most probable explanation for this phenomenon.
Early treatment of stroke with monosialoganglioside GM-1. Efficacy and safety results of the Early Stroke Trial.
Authors: Lenzi G L , Grigoletto F , Gent M , Roberts R S , Walker M D , Easton J D , Carolei A , Dorsey F C , Rocca W A , Bruno R
Published: June 2011

The Early Stroke Trial (EST) is a randomized, double-blind, placebo-controlled trial to assess the effect of monosialoganglioside GM-1 in improving recovery in patients who experienced an ischemic supratentorial stroke.

Sixteen clinical centers recruited 805 patients, of whom 792 were confirmed to be eligible. Treatment, consisting of a first dose of either 200 mg GM-1 or placebo, was initiated within 5 hours of the onset of stroke; a second dose of either 100 mg GM-1 or placebo was administered 12 hours later. Thereafter, patients received a daily injection of 100 mg GM-1 or placebo intravenously from day 2 through 10 and intramuscularly from day 11 through 21. Patients were followed up for a total of 4 months.

Survival was similar in the two treatment groups. Improvement in neurological status, as measured by the change in Canadian Neurological Scale score between baseline and 4-month assessments, was greater in the group receiving GM-1; the observed difference between treatment groups was 0.22 (P = .06). A post hoc analysis in the subgroup of patients treated within 4 hours showed a statistically significant difference, with Canadian Neurological Scale mean improvement of 0.41 (P = .016). GM-1 use was not associated with differences in frequency, nature, or severity of adverse experiences.

These findings suggest that GM-1 is safe in the dose and treatment schedule used and that its efficacy in ischemic stroke is greater when given soon after onset of stroke.
Clinical correlates of high-intensity transient signals detected on transcranial Doppler sonography in patients with cerebrovascular disease.
Authors: Babikian V L , Hyde C , Pochay V , Winter M R
Published: June 2011

High-intensity transient signals detected by transcranial Doppler sonography have been associated with particulate cerebral emboli. Their clinical correlates are poorly understood. This study was undertaken to assess their relation to cerebral ischemia and to determine whether the severity of cerebral arterial stenosis has an impact on their occurrence.

We studied 96 arteries in 75 consecutive patients with extracranial or intracranial arterial lesions or potential cardiac sources of cerebral embolism. Sixty patients had histories of cerebral or retinal transient ischemic attacks or infarcts, and 15 were asymptomatic. The diagnosis of ischemia was based on the clinical presentation and was supported by extensive laboratory testing. A transcranial Doppler sonography unit equipped with special software for emboli detection was used. Signals were selected based on criteria established a priori.

Signals were detected in the territories of 28.3% of symptomatic and 11.6% of asymptomatic arteries. The difference was significant (P = .045). When patients with suspected cardiac embolic sources were excluded, the difference between symptomatic (27.9%) and asymptomatic (2.9%) arteries remained significant (P = .003), and signals were more frequent distal to arteries with more than 50% area stenosis (23.5%) than arteries with stenoses equal to or less than 50% (3.7%) (P = .028). In patients with only extracranial internal carotid artery stenoses, the difference between these degrees of stenosis remained significant (P = .043).

We conclude that high-intensity transient signals are significantly more common in the territories of symptomatic arteries and distal to lesions causing more than 50% stenosis. These findings may have diagnostic and therapeutic applications.
Blood flow velocity and vasomotor reactivity in patients with arteriovenous malformations. A transcranial Doppler study.
Authors: Diehl R R , Henkes H , Nahser H C , Kühne D , Berlit P
Published: June 2011

A large percentage of patients with a cerebral arteriovenous malformation (AVM) show focal neurological signs or have a history of intracranial hemorrhage. The present study used transcranial Doppler sonography to assess the clinical significance of hemodynamic disturbances in the intracranial arteries of patients with an AVM.

Eighteen patients with untreated AVMs were examined clinically, angiographically, and with transcranial Doppler sonography (blood flow velocity measurement and vasomotor reactivity in all main intracranial arteries).

A pathological increase in blood flow velocity (57.6%) and a decrease in vasomotor reactivity (72.7%) were frequently found in AVM feeding arteries. Vasomotor reactivity was also reduced in several nonfeeding arteries both ipsilateral (53.3%) and contralateral (30.8%) to the AVM. AVM size was a poor predictor of pathological transcranial Doppler results. Vasomotor reactivity of arteries ipsilateral to an AVM in patients with a history of hemorrhage was significantly higher (2.10 +/- 1.66% per mm Hg; mean +/- SD) than in patients with no history of bleeding (1.12 +/- 1.48% per mm Hg; P < .05). In patients with focal neurological signs but no history of hemorrhage, the percentage of arteries ipsilateral (100%) and contralateral (63.6%) to an AVM showing a pathological vasomotor reactivity was significantly larger than in nonhemorrhagic patients without focal signs (66.7% and 22.2%, respectively; both P < .05).

Our results suggest two distinct relations between transcranial Doppler results and clinical findings: (1) Relatively normal vasomotor reactivity values in arteries ipsilateral to an AVM indicate a high-pressure AVM with an increased risk of hemorrhage. (2) A strongly pathological vasomotor reactivity in arteries ipsilateral and contralateral to an AVM indicates a low-pressure AVM with a higher prevalence of hemodynamically induced neurological signs.
Prognosis after transient ischemic attack and ischemic stroke in young adults.
Authors: Ferro J M , Crespo M
Published: June 2011

We undertook this study to describe the risk of stroke recurrence and functional and occupational status in the long-term follow-up of young adults with ischemic strokes and to identify possible predictors for stroke recurrence, disability, and working status.

A cohort of 215 patients aged < or = 45 years with ischemic cerebral events (43 transient ischemic attacks, 135 minor strokes, 37 major strokes), evaluated at our institution from May 1985 through March 1992, was followed for a mean of 43.1 months (SD, 39.7 months; range, 1 to 228 months). Information on death and recurrent cerebral vascular events, functional disability (Rankin Scale), retirement, and working status was obtained from direct observation, mail questionnaire, and telephone interviews.

Four patients (2%) with major strokes died acutely. Information on stroke recurrence and disability was available for 184 (87%) of the survivors and on retirement and working status for 140 (67%) of the patients. Two patients died from cancer. Seven transient ischemic attacks and eight strokes (two hemorrhagic) occurred during follow-up. Patients with strokes of unknown cause experienced no recurrent strokes, contrasting with two deaths and eight strokes in those whose stroke cause was identified (difference between proportions: 8%; 95% confidence interval, 3 to 13). Eighty-eight patients had a complete recovery, and only 21 were disabled (Rankin grades 4 or 5). Logistic regression analysis identified the severity of the initial stroke (Rankin grade > 3) as the only significant predictor of disability (odds ratio, 10.7; 95% confidence interval, 3.7 to 30.6). Of the survivors, 73% were working, and only 18% were retired. Disability at follow-up was the best (but nonsignificant) predictor of retirement (odds ratio, 1.6; 95% confidence interval, 0.8 to 3.4).

Ischemic stroke in young adults has a low acute mortality and few recurrences, more so if the cause is not identified. The majority of patients return to an active professional life. Severity of the initial stroke is the major predictor of independence. The relation between disability and return to work or retirement is less clear.
Definition of initial grading, specific events, and overall outcome in patients with aneurysmal subarachnoid hemorrhage. A survey.
Authors: van Gijn J , Bromberg J E , Lindsay K W , Hasan D , Vermeulen M
Published: June 2011

Scientific communication in medicine can be effective only if reports are based on unequivocal criteria for clinical conditions or specific diagnoses.

We reviewed all articles about subarachnoid hemorrhage published in nine neurosurgical or neurological journals from 1985 through 1992 and assessed the presence and the precision of definitions used for reporting the initial grade, the specific complications of rebleeding, delayed cerebral ischemia, and hydrocephalus, and the overall outcome. We identified 184 articles reporting direct observations in at least 10 patients on one or more of these conditions.

Of 161 articles reporting the initial condition, only 19% used an unequivocal grading system (World Federation of Neurological Surgeons Scale or Glasgow Coma Scale); this proportion did not increase after 1988, when the World Federation of Neurological Surgeons Scale was introduced. The specific outcome events of rebleeding, ischemia, and hydrocephalus (283 instances) were sufficiently defined in only 31% of instances, incompletely in 22%, and not at all in 47%. The proportions were similar when the results were analyzed according to the type of complication, the year of publication, or per study. The four exclusively neurosurgical journals featured suitable definitions for any of the three outcome events in 20% of 209 instances, whereas the five mainly neurological journals published fewer articles about subarachnoid hemorrhage (74 instances of outcome events) but more often with precise criteria (65%). Overall outcome was adequately reported in 63% of all articles, with an increase over the years (54% in 1985 through 1988, 71% in 1989 through 1992).

Reports about subarachnoid hemorrhage require closer scrutiny before publication to ascertain whether the conclusions about specific outcome events are based on unequivocal criteria.
The cold hemiplegic arm.
Authors: Wanklyn P , Ilsley D W , Greenstein D , Hampton I F , Roper T A , Kester R C , Mulley G P
Published: June 2011

Vasomotor changes occur in the arm after hemiplegic stroke. Previous studies have provided conflicting results, with most showing an increase in skin temperature of the hemiplegic arm. However, a number of patients complain of distressing coldness of the hemiplegic arm.

Eleven patients with symptomatic coldness and 10 patients with hemiplegia but no coldness were recruited. The severity of the symptom of coldness was compared by questionnaire with other common symptoms after stroke. A thermographic camera was used to record the finger skin temperature response to cold stress. Blood flow to both hands was also measured simultaneously by means of two plethysmographs. In all patients there were no symptoms in the unaffected arm, and this was used as a control.

The symptom of coldness rated highly compared with other symptoms. In the symptomatic group the finger temperature on the hemiplegic side was lower at rest (median difference at rest, 0.65 degrees C; P < .0001) and at all times after cold stress. In the asymptomatic group the fingers on the hemiplegic side were colder at rest and after initial cooling (median temperature difference, 0.2 degrees C) but at no other time. Hand blood flow on the hemiplegic side was also decreased in the symptomatic group by 35%. This was not seen in the asymptomatic group.

Coldness of the hand may be a severe and distressing symptom in some patients after hemiplegia. Symptomatic patients have lower finger skin temperatures at rest and after standard cold stress. These symptomatic patients also had reduced blood flow to the hemiplegic hand.