bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelium-dependent effects of substance P and calcitonin gene-related peptide on mouse pial arterioles.
Authors: Rosenblum W I , Shimizu T , Nelson G H
Published: June 2011

The effects of substance P (SP) and calcitonin gene-related peptide (CGRP) were tested on pial arterioles of mice. This was done because (1) perivascular peptidergic nerves may play an important role in modulation of cerebrovascular responses; (2) there are conflicting data concerning the mechanism of action of CGRP; (3) there are few or no studies directly testing the endothelium dependence of dilation by these peptides in the cerebral circulation; and (4) we wished to extend previous observations of mice by comparing peptidergic responses in the mouse with those published for other species.

The pial arterioles were monitored in vivo using video microscopy and image-shearing techniques for measuring diameter. Focal endothelial injury was produced with a laser-Evans blue technique. Responses to SP and CGRP were tested before and after endothelial injury. They were also tested before and during treatment with agents that interfere with responses mediated by endothelium-derived relaxing factor (EDRFACh). They were also tested before and during treatment with indomethacin.

Both CGRP and SP produced dilation that was blocked by endothelial injury and by agents interfering with responses mediated by EDRFACh. Indomethacin had no effect.

SP and CGRP produce endothelium-dependent dilations. These dilations are probably mediated by EDRFACh. With respect to SP, these results are similar to those reported for other vessels and species. With respect to CGRP, the finding of endothelium dependence has not been previously reported for cerebral vessels. However, very few species have been tested. Reports of other vascular beds in other species sometimes parallel and sometimes contradict our findings with CGRP.
Glucose affects the severity of hypoxic-ischemic brain injury in newborn pigs.
Authors: LeBlanc M H , Huang M , Vig V , Patel D , Smith E E
Published: June 2011

The administration of glucose has been shown to worsen brain injury in adult animals but has no effect on the severity of injury in newborn rats. We wished to see whether the results in newborn rats could be extended to another newborn animal.

In 44 0- to 3-day-old piglets, hypoxic-ischemic central nervous system damage was induced by ligation of both carotid arteries and reduction of their blood pressure to two-thirds normal for one-half hour. In the last 15 minutes of this half hour, oxygen concentration was reduced to 6%. The piglets were randomized to receive either 2 mL/kg 50% dextrose in water followed by 2 mL/kg per hour for 2.5 hours beginning before ischemia or enough insulin to reduce their resting blood sugar to approximately 2 mmol/L.

Neurological exam scores in the glucose-treated piglets at 1 day after injury were significantly worse than those in the insulin-treated group. Pathological examination scores were poorer in the glucose-treated group (13.6 +/- 1.9 [mean +/- SEM]) than in the insulin-treated group (24.7 +/- 1.4, P < .01).

Increasing serum glucose during hypoxic-ischemic injury to the newborn piglet's brain worsens brain injury.
Delayed therapy of experimental ischemia with competitive N-methyl-D-aspartate antagonists in rabbits.
Authors: Madden K P , Clark W M , Zivin J A
Published: June 2011

N-methyl-D-aspartate antagonists are effective in limiting ischemic damage to the brain and spinal cord if treatment is begun at time of ischemic injury. More clinically relevant delayed therapy has not been adequately investigated. We report the temporal profile of efficacy for two competitive N-methyl-D-aspartate antagonists in therapy of central nervous system ischemia.

CGS-19755 (30 mg/kg) or LY233053 (100 mg/kg) was administered 5, 30, or 60 minutes after reversible spinal cord ischemia in rabbits, induced by temporary occlusion of the infrarenal aorta. Duration of occlusion for individual animals was varied to provide a range of ischemia for each experimental group. The P50 represents the duration (in minutes) associated with a 50% probability of resultant permanent paraplegia. Neuroprotection is demonstrated if a drug prolongs the P50.

CGS-19755 significantly prolonged the P50 (t test, P = .003) when given 5 minutes after ischemia, but not if delayed by 30 or 60 minutes (P50: control, 24.1; 5 minutes, 31.4; 30 minutes, 30.1; 60 minutes, 26.6). LY233053 was efficacious at 5 (P = .0008) and 30 (P = .002) minutes, but not at 60 minutes (P50: control, 26.8; 5 minutes, 39.4; 30 minutes, 36.0; 60 minutes, 25.6).

These competitive N-methyl-D-aspartate antagonists are effective in limiting ischemic damage, but protection is lost if therapy is not initiated within 60 minutes of injury.
Ticlopidine improves the enhanced erythrocyte aggregability in patients with cerebral infarction.
Authors: Tanahashi N , Fukuuchi Y , Tomita M , Matsuoka S , Takeda H
Published: June 2011

We examined the effect of ticlopidine hydrochloride on the enhanced erythrocyte aggregability in 14 patients with cerebral infarction during the chronic phase (over 1 month after onset).

Ticlopidine (100 mg BID) was administered for 8 weeks. We measured the rate of erythrocyte aggregation (aggregability), using the whole-blood erythrocyte aggregometer that we developed, before and at 4 and 8 weeks after the initiation of ticlopidine administration. Concomitant measurements were made of such blood factors as the hematocrit, albumin-globulin ratio, and fibrinogen concentration. The erythrocyte aggregation rates before and at 4 and 8 weeks after were 0.147 +/- 0.017/s, 0.138 +/- 0.019/s, and 0.133 +/- 0.017/s, respectively. The erythrocyte aggregation rates at 4 and 8 weeks were significantly lower (P < .05 by Bonferroni's modified t test) than those before ticlopidine administration. At 4 and 8 weeks after the initiation of ticlopidine treatment, the hematocrit value and concentration of fibrinogen were also significantly (P < .05) reduced.

Our results suggest that ticlopidine can improve the enhanced erythrocyte aggregability in patients with cerebral infarction during the chronic phase.
Association between low bone density and stroke in elderly women. The study of osteoporotic fractures.
Authors: Browner W S , Pressman A R , Nevitt M C , Cauley J A , Cummings S R
Published: June 2011

To determine whether women with low bone mineral density are at increased risk of stroke, the present study was conducted.

We studied 4024 ambulatory women aged 65 years or older participating in the prospective Study of Osteoporotic Fractures. Bone mineral density was measured at baseline using single photon absorptiometry; strokes were ascertained using a computerized Medicare data base and death certificates.

During a mean of 1.98 years of follow-up, 83 women suffered first strokes (five fatal). Osteopenia was associated with an increased stroke risk: Each SD decrease in bone mineral density at the calcaneus (0.09 g/cm2) was associated with a 1.31-fold increase in stroke (95% confidence interval, 1.03-1.65), adjusted for age, follow-up time, and several potential confounders, including diabetes, systolic blood pressure, use of alcohol, cigarettes or postmenopausal estrogens, cognitive ability, grip strength, and functional ability. The observed relation between bone density and stroke was strongest for intracerebral hemorrhages and occlusions.

Most likely, low bone density does not cause stroke; some other process probably results in both osteopenia and cerebrovascular disease.
Transient ischemic attacks in younger and older patients. A comparative study of 798 patients in South Africa.
Authors: Giovannoni G , Fritz V U
Published: June 2011

The literature concerning transient ischemic attacks in young adults compared with strokes in young adults is scanty. This study evaluates the profile of transient ischemic attacks in young patients (aged 45 years or younger) compared with older patients (aged older than 45 years).

Between 1981 and 1991, 75 young patients (aged 45 years or younger) and 723 older patients (aged older than 45 years) were diagnosed as having a transient ischemic attack and included in the study. History of presenting transient ischemic attack, risk factors, clinical features, investigations, and etiology were compared on the basis of the above age groups.

In younger patients the presenting transient ischemic attack occurred less frequently in the vertebrobasilar territory (9% versus 21%, P = .03). Risk factor analysis revealed significant differences between the groups, with hypertension, previous smoking history, ischemic heart disease, and peripheral vascular disease being more common in the older group. Migraine and valvular heart disease were more common in the younger group. Approximately 60% of the patients in each group had multiple etiologies. The most common etiology was atheromatous cerebrovascular disease in both groups (74% versus 37% [P < .0001] in the older and younger groups, respectively). Other significant etiologic differences included fibromuscular dysplasia, mitral valve prolapse, and use of oral contraceptives occurring more frequently in the younger group, and ischemic heart disease occurring more frequently in the older group.

This study reveals the clinical and etiologic differences between younger and older patients with transient ischemic attack. The importance of multiple etiologies in both groups of patients has diagnostic and management implications.
Treatment of acute cortical infarct 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 , Fong K Y , Cheung R T , Chang C M
Published: June 2011

This clinical trial investigates the effectiveness of intravenous glycerol therapy in patients with acute cortical infarction in whom intracerebral hemorrhage was rigorously excluded.

Within 48 hours of symptoms from their first ischemic stroke, 113 hospital inpatients were randomized into the trial, provided that hemorrhage was excluded by computed tomography and informed consent was obtained. Patients were stratified into alert, semicoma, and coma groups using the Glasgow Coma Scale. Treatment was allocated according to a double-blind, randomized protocol; 56 patients received 500 mL of 10% glycerol in saline over 4 hours on 6 consecutive days, and 57 patients received corresponding placebo treatment with saline. Using a variety of objective scoring systems, patient follow-up was up to 6 months.

Corresponding measures of outcome in the glycerol and placebo groups were similar. At 6 months, respective mortality rates were 17 of 56 and 16 of 57, and mean +/- SD improvements in scores were 9.98 +/- 14.40 vs 10.51 +/- 12.68 (long-term), 1.12 +/- 7.20 vs 1.57 +/- 6.30 (prognostic), -1.94 +/- 5.53 vs -2.06 +/- 5.34 (Glasgow Coma Scale), and 21.72 +/- 23.40 vs 11.94 +/- 18.10 (Barthel Index rating in survivors). Hemolysis (generally subclinical) was the only adverse effect.

There was no clinically or statistically significant difference in outcome between the groups; a trend toward greater functional recovery among survivors was evident after treatment with glycerol.
Color Doppler imaging of orbital arteries for detection of carotid occlusive disease.
Authors: Hu H H , Sheng W Y , Yen M Y , Lai S T , Teng M M
Published: June 2011

Distal to a hemodynamically significant stenosis, the Doppler effect becomes dampened. Thus, measuring the flow profile in the ophthalmic artery and the central retinal artery with color Doppler imaging may provide hemodynamic information about the carotid circulation.

To validate the flow profile measurement with color Doppler imaging in the ophthalmic and central retinal arteries and to determine the sensitivity and specificity of this examination in the detection of hemodynamically significant carotid stenosis, we compared color Doppler imaging examinations with ocular pneumoplethysmography and ophthalmodynamometry examinations in 66 patients with atherothrombotic ischemic cerebrovascular disease. The degree of carotid stenosis in these patients was determined by a duplex scan with color Doppler imaging, and 57 patients underwent angiography to verify the stenosis.

The flow velocities (systolic peak velocity and end-diastolic velocity) and pulsatility indices (A/B ratio and resistance index) in the ophthalmic and central retinal arteries decreased as the degree of carotid stenosis increased. There is a statistically significant difference in the mean of systolic peak velocity and the mean of end-diastolic velocity of the ophthalmic and central retinal arteries among groups with various degrees of carotid stenosis (P < .02). Using the flow velocities of the ophthalmic and central retinal arteries to diagnose carotid stenosis (> or = 75% stenosis and occlusion), 8 cm/s for systolic peak velocity in the central retinal artery and 29 cm/s for systolic peak velocity plus flow direction reversal in the ophthalmic artery gave the maximum accuracy (sensitivities, 84% and 85.7% and specificities, 89.6% and 81.7%, respectively). The systolic peak velocity in the central retinal artery varied directly with the systolic pressure of the ophthalmic and central retinal arteries.

The flow velocity and pulsatility in orbital arteries examined by color Doppler imaging provide further hemodynamic information; this test can be used to complement current sonographic examination of carotid disease.
Threshold of calcium disturbances after focal cerebral ischemia in rats. Implications of the window of therapeutic opportunity.
Authors: DeGraba T J , Ostrow P T , Grotta J C
Published: June 2011

One explanation for inconclusive results with calcium channel blockers in human acute stroke trials may be incomplete information about the time course of calcium-mediated ischemic neuronal injury. This study explores the temporal relation between duration of focal ischemia and the functional activity of increased intracellular calcium as measured by calcium-calmodulin binding.

Calcium-calmodulin binding, determined by immunohistochemical assay of free calmodulin, was measured in 60 male spontaneously hypertensive rats after 2 minutes and after 1, 2, 4, and 24 hours of permanent tandem common carotid and middle cerebral artery occlusion, and after 1 and 2 hours of reversible middle cerebral artery occlusion followed by 1 and 22 hours of reperfusion, respectively. Light microscopic histological damage was measured after 1 hour of occlusion with 23 hours of reperfusion and after 24 hours of occlusion.

Significant loss of calmodulin staining in the core of the infarction was noted by 1 hour and became maximal after 4 hours of ischemia. No reversal of calmodulin staining loss was noted after reperfusion following 1 and 2 hours of ischemia. Cortical necrosis seen by light microscopy correlated well with the area of maximal calcium-calmodulin binding. The border zone area, represented by a mild loss of calmodulin staining surrounding the central core of maximal binding, gradually decreased in size and became incorporated into the central core after 4 hours of ischemia; it may represent an area of reversible ischemia.

Calcium-calmodulin binding correlates with duration of focal ischemia, and histological neuronal necrosis corresponds to the cortical areas displaying a significant loss of calmodulin staining. Inasmuch as loss of calmodulin staining represents a marker for calcium-mediated activity after ischemia, it suggests a window of opportunity within 4 hours after acute stroke for therapeutic intervention with calcium antagonists.
Effect of S-emopamil, nimodipine, and mild hypothermia on hippocampal glutamate concentrations after repeated cerebral ischemia in rabbits.
Authors: Matsumoto M , Scheller M S , Zornow M H , Strnat M A
Published: June 2011

We sought to determine the effects of two different calcium channel antagonists, S-emopamil and nimodipine, on hippocampal glutamate and glycine release and to compare their effects to those of mild hypothermia.

New Zealand White rabbits were subjected to two 7.5-minute episodes of global cerebral ischemia at a 1-hour interval produced by neck tourniquet inflation (20 psi) combined with hypotension during halothane anesthesia. Hippocampal extracellular concentrations of glutamate and glycine were monitored using in vivo microdialysis. Animals were randomized to receive either S-emopamil (1 mg.kg-1 bolus, 0.1 mg.kg-1.min-1 infusion), nimodipine (10 micrograms.kg-1 bolus, 1 microgram.kg-1.min-1 infusion), hypothermia (32 degrees C), or saline (control) before ischemia. Drug infusion and hypothermia were continued throughout the study periods.

In all four groups, both ischemic episodes resulted in significant elevations of hippocampal extracellular concentrations of glutamate and glycine (baseline vs peak, P < .01 in all groups). However, glutamate levels were significantly lower in the S-emopamil (P = .0001) and hypothermia (P = .0003) groups when compared with the control group after the onset of the first ischemic episode through 1 hour after the second ischemic episode. There was no significant difference between the four groups in the concentrations of glycine. There was no significant difference between the peak concentrations of glutamate or glycine after each ischemic period.

These results suggest that preischemic administration of S-emopamil, but not nimodipine, attenuates the increase in hippocampal extracellular concentrations of glutamate in the peri-ischemic period in this model, and that this effect is also observed when mild hypothermia is instituted before ischemia. Decreased concentrations of glutamate after ischemic episodes may be a possible mechanism for the observed neuroprotective properties of S-emopamil and mild hypothermia (32 degrees C).
Postischemic (1 hour) hypothermia significantly reduces ischemic cell damage in rats subjected to 2 hours of middle cerebral artery occlusion.
Authors: Zhang R L , Chopp M , Chen H , Garcia J H , Zhang Z G
Published: June 2011

We investigated the effect of hypothermia induced 1 hour after transient (2-hour) middle cerebral artery occlusion on the extent of ischemic cell damage in the rat.

Middle cerebral artery occlusion was induced extracranially by insertion of a nylon filament into the right internal carotid artery. Two groups of rats were investigated: (1) rats (n = 10) subjected to normothermic (37 degrees C) ischemia and normothermic reperfusion; and (2) rats (n = 10) subjected to normothermic ischemia and 1 hour of normothermic reperfusion followed by 3 hours of hypothermia (30 degrees C). All rats were killed 1 week after the experiment, and brain sections were stained with hematoxylin and eosin for evaluation of ischemic cell damage.

Infarct volume in normothermic rats involved 20.9 +/- 4.6% of the hemisphere, whereas hypothermic rats exhibited a significantly smaller (P < .001) infarct volume of 11.1 +/- 2.7%. The numbers of surviving (or structurally intact) neurons within large sections of the cortex and striatum were significantly greater for hypothermic compared with normothermic rats (P < .01).

Our data suggest that postischemic induction of hypothermia significantly reduces ischemic cell damage after 2 hours of middle cerebral artery occlusion in the rat, and that an interval of time of at least 1 hour after ischemia exists in which hypothermic intervention is effective in either salvaging or postponing irreversible neuronal injury.
Transcranial Doppler detection of circulating cerebral emboli. A review.
Authors: Markus H
Published: June 2011

The identification of gaseous emboli using Doppler ultrasound was described as early as the 1960s. Recently it has been demonstrated that this method can also detect solid emboli such as thrombi and platelet aggregates. This may make this technology useful in a large number of patients with, or at risk of, embolic stroke.

Emboli appear as short-duration, high-intensity signals in the Doppler spectrum. The intensity of the Doppler signal from an artery containing an embolus depends on the density difference between the embolic material and blood. This difference is greatest for gaseous emboli, which are therefore the most easy to detect. Gaseous emboli have been demonstrated during deep-sea diving, and their presence correlates with the occurrence of decompression sickness. Similar signals have been detected during cardiopulmonary bypass. A relation has been demonstrated between the number of emboli detected by transcranial Doppler and a decline in neuropsychological function after cardiopulmonary bypass. Solid emboli such as thrombi and platelet aggregates result in less intense signals than air emboli. Their detection, using Doppler ultrasound, has recently been described in patients with prosthetic heart valves, atrial fibrillation, and carotid artery disease. It may also help in the detection and localization of embolic sources in patients with stroke. Studies in in vitro and in vivo models demonstrate that this technique provides information on the size and type of emboli. Larger emboli produce signals of greater intensity and duration. Practical patient monitoring will require automatic emboli detectors incorporated into the Doppler machine; such programs are being developed.

Detection of solid emboli using Doppler techniques offers an exciting new diagnostic tool. It has been demonstrated that the technique can detect solid emboli. The prognostic significance of such emboli remains to be determined. It is hoped that the technique will allow detection of patients at high risk of embolic stroke in whom appropriate prophylactic treatment can then be instituted.
Predicting complications of carotid endarterectomy.
Authors: McCrory D C , Goldstein L B , Samsa G P , Oddone E Z , Landsman P B , Moore W S , Matchar D B
Published: June 2011

Carotid endarterectomy has been shown to be beneficial in patients with high-grade carotid stenosis and ipsilateral transient ischemic attack or stroke. This benefit will be realized only if the operation is performed safely. We sought to determine the extent to which clinically significant adverse events occurring after carotid endarterectomy can be predicted from clinical data available before surgery.

Eleven hundred sixty patients were randomly selected from all patients who underwent carotid endarterectomy and were discharged during the calendar years 1988, 1989, and 1990 in 12 academic medical centers in 10 states. Clinical data abstracted from hospital charts were analyzed retrospectively. A model was developed and validated to predict the occurrence of stroke, myocardial infarction, or death during the postoperative period of hospitalization.

Eight patients (6.9%) suffered at least one adverse event. Rates for individual complications were as follows: death, 1.4%; nonfatal stroke, 3.4%; nonfatal myocardial infarction, 2.1%; and nonfatal stroke or death, 4.8%. Significant predictors of adverse events were age 75 years or older, symptom status (ipsilateral symptoms versus asymptomatic or nonipsilateral symptoms), severe hypertension (preoperative diastolic blood pressure of greater than 110 mm Hg), carotid endarterectomy performed in preparation for coronary artery bypass surgery, history of angina, evidence of internal carotid artery thrombus, and internal carotid artery stenosis near the carotid siphon. The presence of two or more of these risk factors was associated with a nearly twofold increase in risk of an adverse event (relative risk, 1.7; 95% confidence interval, 1.0 to 3.0).

Clinical data can be used to stratify patients undergoing carotid endarterectomy according to risk of postoperative in-hospital stroke, myocardial infarction, or death.
The relevance of detecting carotid artery calcification on plain radiograph.
Authors: Doris I , Dobranowski J , Franchetto A A , Jaeschke R
Published: June 2011

The aim of this study was to determine the potential value of carotid artery calcification observed on plain radiographs in patients referred for carotid angiogram in the diagnosis of carotid artery stenosis.

One hundred sixty consecutive patients with suspected carotid artery stenosis underwent both plain radiographs of the carotid arteries and digital subtraction angiography of the same vessels. In addition, 108 of these patients also had duplex ultrasound of the same vascular area. The clinical usefulness of the carotid artery calcification was assessed by calculating the likelihood ratios for different test results against results of angiography and duplex ultrasound.

There is a statistically significant association between the degrees of calcification and carotid disease as demonstrated by angiography (P = .0001), although positive correlations of the degrees of stenosis and calcification was only fair (Spearman correlation coefficient r = .4). The sensitivity of carotid calcification in detecting clinically significant stenosis assuming any calcification is abnormal was 89% with a specificity of 46%. The likelihood ratios for 50% stenosis by angiography varied from 0.24 (no calcification) to 3.41 (level III) and for 50% stenosis by duplex ultrasound varied from 0.21 (no calcification) to more than 5.87 (level III). Assessments of the degree of calcification based on plain radiographs had excellent reproducibility (all intraclass correlation coefficients were greater than .9).

In this population with a high prevalence of carotid artery disease, there is an association between the presence of carotid calcification and atheromatous disease. If subsequent studies were to show this to apply in the general population, this could be of value in identifying asymptomatic patients at increased risk.
Lack of asymmetry of middle cerebral artery blood velocity in unilateral migraine.
Authors: Zwetsloot C P , Caekebeke J F , Ferrari M D
Published: June 2011

A recent transcranial Doppler study found reduced blood velocity in seven patients during migraine attacks in the middle cerebral artery at the headache side. This would implicate vasodilation of the middle cerebral artery in the pathogenesis of headache in migraine. We attempted to confirm this finding.

We determined blood velocity with transcranial Doppler ultrasonography in the middle cerebral arteries of 51 migraine patients with unilateral headache (5 with aura, 46 without aura) and of 14 patients with bilateral headache, during and outside attacks. During attacks, median time from onset of attack to transcranial Doppler examination was 6 hours (range, 1 to 35 hours).

We found no difference between blood velocity at the headache and nonheadache sides nor between blood velocity during and outside attacks. Similar results were obtained in a subgroup of 11 patients who were investigated in the first 4 hours of an attack. There were also no differences between attacks with unilateral or bilateral headache.

We cannot support the hypothesis that migraine is associated with vasodilation of the middle cerebral artery ipsilateral to the headache.
Familial aggregation of stroke. The Framingham Study.
Authors: Kiely D K , Wolf P A , Cupples L A , Beiser A S , Myers R H
Published: June 2011

Family history is perceived to be an important risk factor for stroke despite conflicting published data. We examined patterns of familial aggregation of stroke among three generations using data from the Framingham Study.

Cox proportional hazards analyses, adjusting for known stroke risk factors, were used to examine familial concordance in three groups: (1) members of the original Framingham cohort using reported parental stroke death; (2) members of the Framingham Offspring Study and their parents (members of the original Framingham Study); and (3) sibships within the original Framingham cohort.

We found no association between stroke or transient ischemic attack among original cohort members and their reported parental stroke death (n = 4933; relative risk [RR] = 1.07). Using verified cases of parental stroke or transient ischemic attack, the Offspring analyses revealed that both paternal (n = 1762; RR = 2.4; 95% confidence interval [CI], 0.96 to 6.03) and maternal (n = 2074; RR = 1.4; 95% CI, 0.60 to 3.25) histories were associated with an increased risk. Parental history of coronary heart disease was strongly associated with stroke or transient ischemic attack among Offspring Study members (RR = 3.33; 95% CI, 1.27 to 8.72). Sibling history of stroke or transient ischemic attack was not associated with stroke or transient ischemic attack among original cohort members, although a non-statistically significant increased risk associated with sibling history of atherothrombotic brain infarction was observed (RR = 1.8; 95% CI, 0.68 to 4.94).

These analyses suggest that parental history of stroke may be a risk factor for stroke. As more stroke or transient ischemic attack events develop among the Offspring Study members, it will be valuable to reexamine these associations.
Suppressed sympathetic skin response in brain infarction.
Authors: Korpelainen J T , Tolonen U , Sotaniemi K A , Myllylä V V
Published: June 2011

Autonomic failure is known to manifest commonly in stroke, but very little attention has been given to various features of sympathetic dysfunction such as sudomotor dysregulation in cerebrovascular diseases. In the present study, our purpose was to assess quantitatively sympathetic reflex activity in brain infarction by measuring the sympathetic skin response.

We recorded the sympathetic skin response to electric and auditory stimulations simultaneously on both hands in 58 patients with brain infarction and in 36 healthy control subjects.

The response amplitudes were significantly decreased and the latencies prolonged in both hemispheral (n = 49) and brain stem (n = 9) infarctions compared with the control subjects. The amplitudes were diminished in both the acute and late phases of infarction, but the latencies were prolonged only in the acute phase.

Sympathetic dysfunction in brain infarction seems to be much more extensive than has previously been thought. In the present study, we have demonstrated impaired sympathetic skin responses, reflecting definite suppression of the reflex activity of the sympathetic nervous system.
Intracerebral hemorrhage caused by transmural dissection of the anterior cerebral artery.
Authors: Guridi J , Gállego J , Monzón F , Aguilera F
Published: June 2011

Spontaneous dissection of the intracranial carotid artery or its main branches is an unusual condition.

A 72-year-old hypertensive woman after an intense nuchal rigidity showed a subarachnoid hemorrhage and an interhemispheric hematoma by computed tomography. The neuropathological study revealed a transmural dissection of the pericallosal artery.

The authors suggest that the dissection origin is an atheromatous plaque that bleeds, producing a dissection plane from the lumen to the adventitial artery.
Autonomic consequences of cerebral hemisphere infarction.
Authors: Barron S A , Rogovski Z , Hemli J
Published: June 2011

Recently, supraventricular tachycardia has been reported following right hemisphere stroke, suggesting a reduction in parasympathetic cardiac innervation after stroke of the right hemisphere. We performed power spectrum analysis of fluctuations in RR interval duration in the electrocardiogram in an attempt to determine how ischemic stroke influences autonomic cardiac innervation.

Power spectrum analysis of the variation in 256 consecutive electrocardiographic RR intervals was performed using the fast-Fourier transformation. The area under the spectral curve from 0 to 0.5 Hz and the area under the portion of the curve produced by parasympathetically mediated respiratory variations were determined in 20 patients with right-hemisphere and 20 patients with left-hemisphere ischemic stroke confirmed by computerized tomography. Data were compared with 40 age- and sex-matched healthy controls.

Total cardiac autonomic innervation was reduced after a stroke of either hemisphere without regard to laterality. Cardiac parasympathetic innervation was reduced after stroke of either hemisphere with a significantly greater reduction after stroke on the right (P = 2.9 x 10(-5).

Power spectral analysis of heart rate variability can detect autonomic consequences of stroke. The spectral data predict that, to the degree that cardiac arrhythmia is produced by unbalanced cardiac autonomic activity favoring the sympathetic system, such arrhythmias could be seen after stroke of either hemisphere and would be more common after cerebral infarction on the right. This is consistent with evidence from the recent literature.
Recovery of sensorimotor function after distal middle cerebral artery photothrombotic occlusion in rats.
Authors: Markgraf C G , Green E J , Watson B , McCabe P M , Schneiderman N , Dietrich W D , Ginsberg M D
Published: June 2011

The purpose of the present study was to delineate the behavioral correlates of focal thrombotic occlusion of the distal middle cerebral artery in rats and to compare the pattern of deficits and subsequent recovery to that following proximal middle cerebral artery occlusion.

Ten Sprague-Dawley rats underwent photothrombotic occlusion of the distal middle cerebral artery with tandem occlusion of the common carotid arteries (dMCAO group); 10 animals served as operated controls. Beginning on postischemia day 2, animals were given a battery of five tests that assessed sensorimotor integration, attentional mechanisms, and muscle strength; testing continued twice weekly until day 30. Nine days of cognitive testing on the learning set of the water maze task were then given. Infarct volume and hemispheric atrophy were determined for each dMCAO animal.

After ischemia, the dMCAO group exhibited significant behavioral deficits in posture reflex, ability to place a forelimb to various stimuli, limb adduction during rearing, and neglect of contralateral space. These deficits showed variable recovery rates. No deficits were observed in muscle strength or cognitive performance. The deficits and patterns of recovery were related to infarct location and to degree of hemisphere atrophy.

The present study suggests that a battery of tests is necessary to fully characterize the pattern of behavioral deficits after focal cerebral ischemia. Location of infarct damage and associated degree of hemispheric atrophy were important variables in determining behavioral outcome. The present results are compared with those of the more traditional model of electrocoagulation of the proximal middle cerebral artery.
P-selectin and intercellular adhesion molecule-1 expression after focal brain ischemia and reperfusion.
Authors: Okada Y , Copeland B R , Mori E , Tung M M , Thomas W S , del Zoppo G J
Published: June 2011

Polymorphonuclear leukocytes have been implicated in the development of the "no-reflow" phenomenon after focal cerebral ischemia and reperfusion. To further understand the role of granulocytes in microvascular occlusions, the responses of the granulocyte-endothelial cell adhesion molecules P-selectin and intercellular adhesion molecule-1 during middle cerebral artery ischemia and reperfusion were examined in a primate model.

Twelve adolescent male baboons were used for 2-hour middle cerebral artery occlusion (n = 3) or for 3-hour occlusion with 1-hour (n = 3), 4-hour (n = 3), and 24-hour (n = 3) reperfusion, and three separate unoperated primates served as controls. A quantitative immunohistochemical study of the microvascular distribution of P-selectin and intercellular adhesion molecule-1 was performed using 10-microns frozen sections from basal ganglia analyzed with computerized light microscopy video imaging.

Significant (P < .05) persistent upregulation of P-selectin (beginning during ischemia) and transient upregulation of intercellular adhesion molecule-1 (at 1 and 4 hours of reperfusion) were observed on endothelium of selected post-capillary microvessels of the ischemic lenticulostriate artery territory. Platelet accumulation also occurred in this territory and was responsible for a significant proportion of the nonendothelial P-selectin signal at 24 hours after reperfusion.

Focal cerebral ischemia/reperfusion stimulates endothelial P-selectin and intercellular adhesion molecule-1 expression in brain microvessels in the ischemic zone, which may contribute to enhanced leukocyte adherence and persistent activation.
Venous sinus thrombosis associated with androgens in a healthy young man.
Authors: Jaillard A S , Hommel M , Mallaret M
Published: June 2011

Cerebral venous sinus thrombosis is rare and can be promoted by various conditions. We report the case of cerebral venous thrombosis in a patient using androgens.

A 31-year-old man using androgens for bodybuilding was admitted for headache and vomiting. He had cerebral venous sinus thrombosis, but extensive examinations did not reveal any known cause.

We suggest that androgens may promote cerebral venous thrombosis. The mechanisms of venous thrombosis related to androgens may be platelet activation or an increase in coagulation factors. Because androgen use may be frequent and hidden in athletes, it may be an underestimated cause of cerebral venous sinus thrombosis in the young.
Involuntary tonic spasms of a limb due to a brain stem lacunar infarction.
Authors: Kaufman D K , Brown R D , Karnes W E
Published: June 2011

Although repetitive involuntary movements are a well-recognized manifestation of carotid occlusive disease, similar movements have not been reported with a lacunar infarction outside of the basal ganglia or subthalamic nucleus. We describe a man with tonic spasms associated with a lacunar infarction in the right ventral pons.

Involuntary tonic spasms of a paretic limb developed acutely in a 69-year-old hypertensive man with a clinical presentation of pure motor hemiparesis. Magnetic resonance imaging demonstrated a lacunar infarction of the ventral pons. There was no evidence for carotid occlusive disease. An electroencephalogram recorded during the movements showed no abnormality. The abnormal movements responded well to treatment with oral diazepam.

A brain stem lacunar infarction may be associated with involuntary tonic limb spasms clinically similar to those reported as paroxysmal symptoms of multiple sclerosis.
Transesophageal echocardiographic findings in stroke subtypes.
Authors: Albers G W , Comess K A , DeRook F A , Bracci P , Atwood J E , Bolger A , Hotson J
Published: June 2011

Transesophageal echocardiography has a high yield for detecting potential cardiac sources of embolism in patients with clinical risk factors for cardioembolism or unexplained stroke. The yield in other stroke subtypes is unknown.

We classified 145 consecutively admitted patients into stroke subtypes based on clinical findings, brain imaging, and carotid ultrasound. Both transesophageal and transthoracic echocardiography were performed to detect left atrial thrombi, spontaneous echo contrast, atrial septal aneurysm, interatrial shunts, ventricular thrombus or aneurysm, and myxomatous mitral valve.

Transesophageal echocardiography documented at least one of these findings in 46% of the patients compared with an 8% yield on the transthoracic study (P = .002). The yield of transesophageal echocardiography was substantial in all stroke subgroups. Patients with clinical risk factors for cardiac embolism had the highest frequency of spontaneous echo contrast (P = .001). Atrial septal aneurysms were most frequent in patients with lacunar syndromes (P = .012), and interatrial shunts were common in all stroke subtypes.

Transesophageal echocardiographic findings vary considerably between stroke subgroups.
The role of lifestyle factors in the etiology of stroke. A population-based case-control study in Perth, Western Australia.
Authors: Jamrozik K , Broadhurst R J , Anderson C S , Stewart-Wynne E G
Published: June 2011

We sought to examine risk factors for all strokes and for ischemic stroke and primary intracerebral hemorrhage separately.

This was a population-based case-control study. Each case subject meeting World Health Organization criteria for stroke (n = 536) from a population-based register of acute cerebrovascular events compiled in Perth, Western Australia, in 1989 to 1990 was matched for age and sex with up to five control subjects drawn from the same geographical area. Objective confirmation of the type of stroke was available from computed tomography, magnetic resonance imaging, or necropsy for 86% of the case subjects. Data on medical history and lifestyle factors were collected from case and control subjects by interview of the subject or a proxy informant.

Current smoking, consumption of meat more than four times weekly, and a history of hypertension or intermittent claudication were each associated with increased risk in multivariate models for all strokes and for all first-ever strokes. Consumption of 1 to 20 g/d alcohol in the preceding week was associated with a significant reduction in the risk of all strokes, all ischemic strokes, and of primary intracerebral hemorrhage, while eating fish more than two times per month appeared to protect against first-ever stroke and against primary intracerebral hemorrhage. Diabetes mellitus was associated with a significantly increased risk of ischemic stroke but a decreased risk of hemorrhagic stroke.

Risk factors for ischemic and hemorrhagic stroke are not exactly the same. Changes in lifestyle relating to tobacco and diet might make important contributions to further reductions in the incidence of stroke.
Reperfusion after thrombolytic therapy in ischemic stroke measured by single-photon emission computed tomography.
Authors: Baird A E , Donnan G A , Austin M C , Fitt G J , Davis S M , McKay W J
Published: June 2011

We used 99mTc-hexamethylpropyleneamine oxime single-photon emission computed tomography (SPECT) to study cerebral perfusion in patients treated with streptokinase for acute ischemic stroke in an open and prospective study. Our primary aims were (1) to compare the extent of reperfusion between patients who had received thrombolytic therapy and a control group studied during the same period who were ineligible to receive such therapy and (2) to determine if, among all patients, reperfusion led to improved outcome.

Fifty-seven patients (22 treated with streptokinase) had two SPECT studies performed, the first before streptokinase administration and the second 24 hours later.

On the first SPECT study hyperfusion was present in the middle cerebral artery or anterior cerebral artery territories in 40 patients (17 treated with streptokinase). Patients in the treatment and control groups with initial hypoperfusion on SPECT were well matched for the volume of the perfusion defect and the severity of neurological deficit. A greater number of patients who received streptokinase developed at least partial reperfusion (streptokinase, 65%; control, 52%) on the second study but not significantly so (P = .43). Similarly, the proportion of each hypoperfused region that reperfused (P = .74) and the reduction in the size of the perfusion defect (P = .06) were higher in the streptokinase group but did not reach statistical significance. When all patients were considered, those who did not reperfuse had higher mortality rates (P = .008), less neurological improvement (P = .016), and more functional disability (P < .001) than patients who had reperfusion or normal perfusion initially.

These findings suggest that at least some reperfusion during the first 48 hours of ischemic stroke is a common natural occurrence and is of prognostic significance. The observed trend toward better reperfusion indexes among patients treated with streptokinase is encouraging, but larger controlled trials are required to answer this definitively.
Effect of carotid endarterectomy on patterns of cerebrovascular reactivity in patients with unilateral carotid artery stenosis.
Authors: Hartl W H , Janssen I , Fürst H
Published: June 2011

Patients with unilateral significant carotid artery stenosis present with a variable intracranial hemodynamic status. In the majority of patients, hemodynamics are normal because of sufficient collateral flow. One subgroup shows poor ipsilateral hemodynamics because of a severely reduced blood supply, whereas in another subgroup of patients a steal phenomenon from the contralateral to the ipsilateral hemisphere can be observed during pharmacological provocation. The present study examined the effect of carotid endarterectomy (CEA) on these patterns of cerebrovascular hemodynamics in patients with carotid artery stenosis.

The CO2 reactivity of the cerebral resistance index (CRi) was determined with transcranial Doppler sonography in 63 patients with unilateral high-grade to threadlike carotid artery stenosis before and 3 months after CEA and in 37 control subjects. The interhemispheric asymmetry of CRi reactivity of the control group was used to differentiate between normal and abnormal findings.

In patients with normal CRi asymmetry (comparable CRi reactivities at both hemispheres, n = 41), CEA did not change hemispheric CRi reactivity. In patients in whom CRi reactivity was absent at the contralateral hemisphere (intracerebral steal during hypercapnia, n = 12), CEA abolished the steal phenomenon by significantly increasing CRi reactivity at the contralateral hemisphere (preoperative, -1.0 +/- 2.1 %CRi/vol%CO2; postoperative, 5.2 +/- 0.7 %CRi/vol%CO2; P < .01). Patients who showed severely diminished ipsilateral CRi reactivity, compatible with a significantly reduced perfusion pressure at the poststenotic hemisphere (n = 10), demonstrated an improvement of ipsilateral CRi reactivity after surgery (preoperative, 0.6 +/- 0.8 %CRi/vol%CO2; postoperative, 3.7 +/- 1.1 %CRi/vol%CO2; P < .01).

Most patients do not respond significantly to CEA. One small subgroup of patients who presented with severely disturbed ipsilateral hemodynamics demonstrated postoperative improvement at the poststenotic hemisphere, whereas in another small subgroup, who showed a steal phenomenon at the contralateral hemisphere, CEA improved contralateral hemodynamics. Determination of preoperative CRi reactivity allowed precise prediction of the effect of CEA on intracerebral hemodynamics.
Atherosclerosis of the ascending aorta. Prevalence and role as an independent predictor of cerebrovascular events in cardiac patients.
Authors: Dávila-Román V G , Barzilai B , Wareing T H , Murphy S F , Schechtman K B , Kouchoukos N T
Published: June 2011

The cause of cerebral and peripheral embolism remains undetermined in a significant number of patients. An atherosclerotic thoracic aorta has thus far been considered to be an uncommon one.

To define the potential role of the ascending thoracic aorta as an embolic source, intraoperative ultrasonic aortic imaging was performed in 1200 of 1334 consecutive patients aged 50 years and older who were undergoing cardiac surgery. Patients were divided into two groups according to the results of the ultrasound study in terms of presence or absence of atherosclerotic disease. The prevalence of previous neurological events in the two groups was characterized and compared.

Ascending aortic atherosclerosis was present in 231 (19.3%) of the patients studied. Patients in this category were older (P < .0001). A higher percentage of them were smokers (P < .0001) compared with patients with less severe disease. Coronary artery disease was more extensive (P = .012), and a higher percentage of these patients had a history of peripheral vascular disease (P < .0001). Univariate analysis of the subjects with (n = 158) and without (n = 1042) previous neurological events indicated that age, body mass index, atrial fibrillation, hypertension, and atherosclerosis of the ascending aorta were associated significantly with previous occurrence of a cerebrovascular accident. For the group as a whole, multiple logistic regression analysis demonstrated that hypertension (odds ratio, 1.81; P = .002), atherosclerosis of the ascending aorta (odds ratio, 1.65; P = .013), and atrial fibrillation (odds ratio, 1.54; P = .060) were significantly and independently associated with the occurrence of previous neurological events.

Atherosclerosis of the ascending aorta is an independent risk factor for cerebrovascular events. An atherosclerotic ascending aorta may represent a potential source of emboli or may be a marker of generalized atherosclerosis.