bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac sources of embolism in patients with pial artery infarcts and lacunar lesions.
Authors: Mast H , Thompson J L , Völler H , Mohr J P , Marx P
Published: June 2011

On the assumption that the majority of lacunes are caused by small-vessel diseases and that pial artery infarcts arise from cardio-embolic or large-vessel diseases, 194 patients from the Berlin Cerebral Ischemia Data Bank with either lacunar or pial artery infarcts were analyzed for the frequency of cardiac sources of embolism. The primary hypothesis was that the frequency of cardiac sources of embolism is higher among pial artery infarct subjects.

The presence of cardiac sources of embolism was estimated by electrocardiographic and transthoracic and transesophageal echocardiographic studies. Cranial computed tomography scans were evaluated by two masked observers.

The overall rate of cardiac sources of embolism did not differ significantly between the lacunar and the pial artery infarct group (66% versus 71%; odds ratio, 0.80; confidence interval, 0.43 to 1.50). Echocardiographic evidence of cardiac thrombi was positively associated with pial artery infarcts (odds ratio, 0.18; confidence interval, 0.04 to 0.80); atrial fibrillation and all other cardiac sources were not.

Left cardiac thrombi are significantly associated with pial artery infarcts. Other presumed cardiac sources of embolism, including atrial fibrillation, may often represent coincidental findings or have a less strong tendency to result in pial artery infarcts.
Anterior choroidal artery territory infarcts. Study of presumed mechanisms.
Authors: Leys D , Mounier-Vehier F , Lavenu I , Rondepierre P , Pruvo J P
Published: June 2011

A previous study suggested that occlusive diseases of small penetrating arteries account for most anterior choroidal artery (AChA) territory infarcts, but half of the patients did not have an echocardiogram. Cases of AChA territory infarcts associated with internal carotid artery stenosis or atrial fibrillation suggest that this hypothesis may be wrong. The aim of this study was to determine the mechanism of 16 nonselected consecutive AChA territory infarcts.

The study population consisted of 8 men and 8 women aged 17 to 89 years. They underwent a computed tomographic scan at the acute stage, Doppler ultrasonography and B-mode echotomography of the cervical arteries, bidimensional transthoracic echocardiography, and cerebral magnetic resonance imaging, replaced by a second computed tomographic scan in 3 patients. Ten patients underwent cerebral angiography. We defined the presumed cause of stroke according to the criteria used in the trial of Org 10172 in acute stroke treatment.

The presumed cause of stroke was definite cardio-embolism in 4 patients (atrial fibrillation in 2, paradoxical embolism in 1, and left ventricular akinesia in 1); definite large-vessel atherosclerosis in 2; dissection of the internal carotid artery in 2; and definite small-vessel occlusion in 1. Seven patients had a negative diagnostic workup. Six patients had no risk factors for small-vessel occlusion. The AChA was not visible on angiography in 4 patients. One patient had two arterial cutoffs, suggestive of emboli in other cerebral arteries.

This study suggests that AChA territory infarcts are rarely related to small-vessel occlusion and therefore require a complete diagnostic workup.
Diffusion-weighted imaging differentiates ischemic tissue from traumatized tissue.
Authors: Hanstock C C , Faden A I , Bendall M R , Vink R
Published: June 2011

Diffusion-weighted magnetic resonance imaging (MRI) has been shown to be particularly effective in detecting early (0 to 4 hours) pathophysiological changes in localized brain regions after cerebral ischemia. The present study sought to establish whether diffusion-weighted MRI would be similarly effective in predicting outcome after traumatic brain injury.

Diffusion-weighted MRI images and T2-weighted MRI images were obtained over 4 hours after either moderate fluid percussion-induced traumatic brain injury or unilateral carotid ligation in rats.

Diffusion-weighted MRI images of traumatic brain injury demonstrated focal regions of image hypointensity as early as 1 hour after trauma. The relative diffusion coefficient in these hypointense regions was significantly increased (P < .005) by 4 hours after trauma compared with the noninjured hemisphere, but only in the transverse plane in the x direction. In contrast, induction of diffuse, nonfocal ischemia by unilateral carotid ligation resulted in scattered regions of hyperintensity with a significant (P < .001) decrease in relative diffusion coefficient as early as 1 hour after ligation compared with the noninjured hemisphere. This decrease exhibited no directionality.

We conclude that traumatic brain injury results in an increased water diffusion distance with the directionality indicative of bulk flow of extracellular fluid toward the lateral ventricles (vasogenic edema). In contrast, the decreased water diffusion distance with no apparent directionality observed in ischemia is most likely indicative of cytotoxic edema. Diffusion-weighted MRI therefore has the potential to differentiate cases of traumatic brain injury with no focal ischemia from those instances of traumatic brain injury in which focal ischemia is a complication.
Superoxide dismutase ameliorates neuronal death from hypoxia in culture.
Authors: Rosenbaum D M , Kalberg J , Kessler J A
Published: June 2011

Studies showing efficacy with free radical scavengers have been conflicting, and when protection was demonstrated it was attributed to action at the level of the vascular endothelium. The purpose of this study was to test the hypotheses that neuronal free radical formation plays a role in the ischemic cascade and occurs intracellularly and that free radical scavengers, if taken up intracellularly, will protect against hypoxic damage.

A tissue culture model of hypoxia followed by restoration of oxygen was employed, using both superior cervical ganglia and hippocampal neurons. Cells were exposed to an anoxic atmosphere of 95% N2 and 5% CO2 and examined 2 to 24 hours later after restoration of oxygen. Determination of survival was measured by trypan blue exclusion. Nitroblue tetrazolium stain was used to assess free radical formation.

Pretreatment with free superoxide dismutase did not decrease cell death after hypoxia as measured by trypan blue exclusion. However, when superoxide dismutase was taken up intracellularly under depolarizing conditions (55 mmol/L KCl in the medium), cell death was decreased significantly compared with hypoxic controls (28.7 +/- 4.34 versus 40.3 +/- 4.33; P < .03). During hypoxia neurons reduced nitroblue tetrazolium to form the blue precipitate formazan, and the color change was blocked in neurons pretreated with superoxide dismutase in depolarizing medium. Similar findings occurred in both superior cervical ganglia and hippocampal neurons.

These findings provide evidence to support the role of neuronal free radical formation in cell death secondary to hypoxia. In addition, free radical scavengers, if taken up intracellularly, may partially ameliorate their deleterious effect.
Surgically induced angiogenesis to compensate for hemodynamic cerebral ischemia.
Authors: Nariai T , Suzuki R , Matsushima Y , Ichimura K , Hirakawa K , Ishii K , Senda M
Published: June 2011

The ischemic brain may stimulate angiogenesis to compensate for impaired circulation. We examined the conditions promoting such angiogenesis to provide the basis for surgical treatment.

The degree of cerebral hemodynamic stress was studied in patients with moyamoya disease using the stable xenon-enhanced computed tomographic acetazolamide tolerance test and positron emission tomography. Patients were subjected to surgery in which scalp arteries were placed on the cerebral cortex without vessel-to-vessel anastomosis. Formation of the newly vascularized collateral network connecting the implanted artery to cortical arteries was assessed angiographically 12 to 17 months after surgery.

Preoperative average resting cerebral blood flow for cortex that developed revascularization of cortical arteries was not significantly different from that for cortex that did not. However, cortex that developed revascularization had an average preoperative increase of blood flow by acetazolamide treatment of -3.29 +/- 4.6 mL/min per 100 cm3 (n = 20), which was significantly less (P = .0034) than that of cortex that did not show revascularization (20.7 +/- 4.3 mL/min per 100 cm3; n = 9). Good revascularization developed when the cortex showed increase of blood flow by acetazolamide treatment of less than 0 (steal phenomenon). Preoperative positron emission tomography data indicated that revascularization developed when the cortex was under "misery perfusion." Postoperative hemodynamics were ameliorated by revascularization.

Angiogenesis to connect the implanted scalp arteries to the cerebral cortical arteries was selectively initiated when ischemia of hemodynamic origin existed.
Cardiac arrhythmia associated with reversible damage to insula in a patients with subarachnoid hemorrhage.
Authors: Svigelj V , Grad A , Tekavcic I , Kiauta T
Published: June 2011

The insular cortex has been shown experimentally to contain an arrhythmogenic center that may play an important role in the genesis of cardiac arrhythmias and electrocardiographic changes in patients with intracranial (eg, cerebrovascular) lesions. The description of our case is intended to substantiate this claim with a clinical observation.

A 37-year-old woman with subarachnoid hemorrhage suffered a severe reversible cardiac arrhythmia after neurosurgical clipping of an arterial aneurysm and removal of an intracerebral hematoma from the region of the left insula.

The observed association of a neurosurgical intervention in the region of the left insular cortex with a cardiac arrhythmia supports but does not prove the suggested role of the insulin in the causation of heart rhythm disturbances after stroke.
Long-term follow-up of cerebral infarction patients with proton magnetic resonance spectroscopy.
Authors: Gideon P , Sperling B , Arlien-Søborg P , Olsen T S , Henriksen O
Published: June 2011

With proton magnetic resonance spectroscopy it is possible to measure the content of various brain metabolites in vivo, including N-acetylaspartate (which may be used as a neuronal marker), creatine, choline, and lactate. The content of these brain metabolites was measured serially from the acute stage to the chronic stage of infarction. Regional cerebral blood flow was also measured within the affected areas. These factors were compared with the clinical outcome.

Six patients with ischemic stroke were examined serially from the acute stage (< or = 2 days) to the chronic stage (> 6 months) with proton magnetic resonance spectroscopy. Cerebral blood flow was measured with single-photon emission-computed tomography with 99mTc-labeled d,l-hexamethylenepropyleneamine oxime as flow tracer.

Lactate was found in all patients in the acute stage of stroke. Lactate was also found in the 3 largest lesions in the chronic stage; in 2 of these patients lactate was not found in the subacute stage. Reduced levels of N-acetylaspartate were found in 5 patients; in the sixth patient with a small lesion no reduction was found. In all lesions reduced blood flow was found in the acute and chronic stage, whereas hyperemia was found in 4 patients in the subacute stage.

In this preliminary study no clear correlation was found between the level of N-acetylaspartate or lactate in the acute stage of stroke and the clinical outcome; however, there does appear to be some connection between the reduction of cerebral blood flow and the spectroscopic findings in the chronic stage and to some extent the clinical outcome. Studies of larger clinical groups will be necessary to further elucidate the prognostic potential of proton magnetic resonance spectroscopy in human stroke.
Extent of pontine pyramidal tract Wallerian degeneration and outcome after supratentorial hemorrhagic stroke.
Authors: Fukui K , Iguchi I , Kito A , Watanabe Y , Sugita K
Published: June 2011

Pyramidal tract Wallerian degeneration has been detected on magnetic resonance imaging (MRI) as T2-weighted high-intensity areas. We analyzed the relation between the extent of brain stem Wallerian degeneration and activities of daily living (ADL) after supratentorial hemorrhagic stroke.

Twenty-six patients with supratentorial hemorrhage were examined on the coronal T2-weighted image of the pons 3 months or later after stroke, and the percentage of Wallerian degeneration in the pons was calculated. The patients were divided into three groups. In group A (n = 6), MR films were taken 3 to 6 months from the onset, and the ADL assessment was done within 2 months from the MRI. In group B (n = 11), MR films were taken 3 to 6 months from the onset, and the ADL assessment was done within 10 months from the MRI (mean, 15.5 months from the onset). In group C (n = 9), MR films were taken after 10 to 17 months (mean, 12.0 months) from the ictus, and the ADL assessment was done simultaneously. Barthel Index score was used for quantitative ADL assessment.

All patients showed various degrees of pontine pyramidal tract Wallerian degeneration associated with capsular involvement by the hematoma. In group A, the percentage of degeneration did not correlate with the Barthel Index score (r = .2101, P = .6895). An inverse relation between percentage of degeneration and Barthel Index score was seen in groups B (r = .7354, P = .0099) and C (r = .888, P = .0014). In groups B and C, Wallerian degeneration was higher in patients with Barthel scores less than 60 (P = .005).

The extent of pontine Wallerian degeneration on MRI 3 months or later after the stroke correlated with the patient's Barthel Index score 1 year after the stroke.
Cerebral blood flow in migraine accompaniments and vertebrobasilar ischemia.
Authors: Ramadan N M , Levine S R , Welch K M
Published: June 2011

Transient neurological symptoms of brain stem or occipital lobe origin may be caused by transient ischemic attack in the vertebrobasilar territory (VB-TIA) or late-onset (or late-life) migraine accompaniment (LOMA). It is often clinically difficult to distinguish between VB-TIA and LOMA.

Cerebral blood flow of 23 patients with VB-TIA, 24 with LOMA, and 28 age-matched control subjects was measured using the 133Xe inhalation regional cerebral blood flow (rCBF) technique.

After adjusting for differences in baseline variables such as blood pressure, hematocrit, and PCO2, patients with VB-TIA had (1) lower mean rCBF than control subjects (P < .003) as measured by the initial slope index method; (2) more frequent anterior rCBF asymmetries than control subjects and patients with LOMA (P < .03 for both comparisons); and (3) higher mean interhemispheric rCBF differences compared with patients with LOMA (P = .08) and control subjects (P < .02).

Regional CBF patterns in patients with VB-TIA and LOMA differ, with lower rCBF and more asymmetry of the anterior blood flows in patients with VB-TIA, probably reflecting the effects of stroke risk factors on the cerebral circulation. Patients with LOMA have rCBF patterns more closely resembling those of age-matched healthy subjects. rCBF measurements may assist in the clinical diagnosis of VB-TIA and late-onset migrainous events.
Brain ischemia decreases phosphatidylcholine-phospholipase D but not phosphatidylinositol-phospholipase C in rats.
Authors: Nishida A , Emoto K , Shimizu M , Uozumi T , Yamawaki S
Published: June 2011

Phosphatidylcholine (PC)-phospholipase D (PLD) is an important intracellular signaling pathway in response to a variety of agonists, but little is known about the effects of brain ischemia on the PC-PLD system. We thus have examined the effects of global cerebral ischemia on PLD in rats.

We have examined the effects of global ischemia (decapitation or four-vessel occlusion) on PLD and PLC activity in the membrane fraction of rat brains. We measured the PLD and PLC activity in detergent-mixed micelle assay systems using 3H-labeled exogenous substrate.

The results demonstrate that basal PLD activity showed a gradual decrease with increased duration (5 to 30 minutes) of ischemia by decapitation in the hippocampus; after 30 minutes of ischemia, PLD activity was significantly decreased compared with the control. Lineweaver-Burk plots showed that the apparent Vmax value of PLD in ischemia was one half of that in the control without changes in Km value. Ischemia by decapitation significantly decreased PLD activity in the brain stem as well as the hippocampus, whereas in four-vessel occlusion study, ischemia significantly decreased PLD activity in the hippocampus but not in the brain stem. Lowered temperature (30 degrees C and 22 degrees C) during ischemic incubation did not reverse the ischemia-induced PLD activity decrease. In contrast to PLD, ischemia by decapitation had no effect on basal phosphatidylinositol-phospholipase C activity or the amount of phospholipase C beta 1 in the membrane fractions from 30-minute ischemic hippocampus by immunoblots probed with the antibody.

These results suggest that PC-PLD is one of the target enzymes of ischemia; its decrease may cause a perturbation of PC hydrolysis and/or disorders of intracellular transduction of signals or choline metabolism for acetylcholine formation in brain.
Vertebrobasilar junction fenestration associated with dissecting aneurysm of intracranial vertebral artery.
Authors: Zhang Q J , Kobayashi S , Gibo H , Hongo K
Published: June 2011

Vertebrobasilar junction fenestration is considered to be a subtype of fenestration of the proximal basilar artery, which has been described only in autopsy cases. The fenestration associated with a dissecting vertebral aneurysm is extremely rare.

A 47-year-old man presented with subarachnoid hemorrhage. The four-vessel angiogram showed a fusiform dilatation with an intimal flap of the left vertebral artery distal to the origin of the posterior inferior cerebellar artery and a fenestration at the vertebrobasilar junction, in which a small limb of the fenestration arising from the distal portion of the left vertebral artery bridged the proximal basilar trunk, while another limb had a large diameter showing the same diameter as the basilar artery. The dissecting aneurysm was treated with body clipping by directly clipping the ruptured portion of the aneurysm via a suboccipital approach in an early operation 48 hours after the ictus. The patient had a good recovery and returned to his work. He is well at a 5-year follow-up.

The relevant angiographic features of the vertebrobasilar junction fenestration and the surgical treatment of such associated aneurysms are discussed.
Bilateral infarction in the anterior cerebral artery vascular territory due to an unusual anomaly of the circle of Willis.
Authors: Borggreve F , De Deyn P P , Mariën P , Cras P , Dierckx R A
Published: June 2011

Bilateral infarction in the anterior cerebral artery vascular territory is rare and usually results from rupture of an aneurysm of the anterior communicating artery. In the case of an anomaly of the anterior part of the circle of Willis, thrombosis also may lead to bilateral infarction.

A 73-year-old right-handed man presented with a complete loss of communicative behavior and an almost complete quadriplegia. 99mTc-hexamethylpropyleneamine oxime single-photon emission-computed tomography (HMPAO SPECT) of the brain showed a "horseshoe" image, reflecting bilateral perfusion defects in areas supplied by the anterior cerebral arteries. Postmortem examination of the brain revealed an unusual anomaly of the circle of Willis in which the postcommunicating part of the right anterior cerebral artery was absent.

In our patient a unique developmental anomaly of the circle of Willis indirectly contributed to bilateral infarction in the territory of the anterior cerebral artery. The patient's neuropsychological profile, dominated by akinetic mutism, was highly suggestive of involvement of the receptive language modalities. For the first time, 99mTc-HMPAO SPECT of the brain revealed a horseshoe image in bilateral infarction in the territory of the anterior cerebral artery.
Comparison of clinical and neuroradiological findings in first-ever stroke. A population-based study.
Authors: Lindgren A , Norrving B , Rudling O , Johansson B B
Published: June 2011

To determine how a recently proposed clinical stroke subclassification corresponds to specific findings on computed tomography (CT) and magnetic resonance imaging (MRI) of the brain.

Two hundred twenty-eight patients with first-ever stroke were divided into four clinical subgroups: (1) total anterior circulation syndrome: both cortical and subcortical symptoms from anterior and middle cerebral artery territory; (2) partial anterior circulation syndrome: more restricted and predominantly cortical symptoms from the same arterial territories; (3) lacunar syndrome; and (4) posterior circulation syndrome: vertebrobasilar or posterior cerebral artery symptoms. The imaging protocol included CT of the brain on day 0 through 15 and a second CT and an MRI of the brain on day 16 through 180 after acute stroke onset.

There were 200 patients with cerebral infarction and 28 patients with intracerebral hemorrhage. Intracerebral hemorrhage was found in 19% of patients with total anterior circulation syndrome and in no patients with lacunar syndrome (chi 2 test; P < .01 for the difference between the four clinical subgroups). Of the 200 patients with cerebral infarction, 27% had total anterior circulation, 30% partial anterior circulation, 26% lacunar, and 16% posterior circulation syndromes. CT within 2 days revealed a visible lesion in about two thirds of patients with infarctions of total or partial anterior circulation syndrome type, compared with only 22% of patients with lacunar infarction (chi 2 test; P = .02 for the difference between the four subgroups). The mean volume of the symptomatic infarction on CT within 15 days was 95 mL for total anterior circulation, 20 mL for partial anterior circulation, and 2.5 mL for lacunar syndrome (one-factor ANOVA; P = .0001). A cortical involvement of the infarction on CT day 16 through 180 was seen in 81% of patients with total anterior circulation syndrome and 58% of those with partial anterior circulation syndrome, compared with only 8% of patients with lacunar syndrome (chi 2 test; P = .0001). MRI more often than CT showed a cortical involvement of lacunar infarctions and also revealed more silent lesions.

The described clinical subgroups significantly differed in frequencies of intracerebral hemorrhage, cortical involvement, and lesion volume on CT and MRI.
Spectrum of lateral medullary syndrome. Correlation between clinical findings and magnetic resonance imaging in 33 subjects.
Authors: Kim J S , Lee J H , Suh D C , Lee M C
Published: June 2011

Computed tomography is insufficient in evaluation of medullary lesions. Although lateral medullary infarction is a relatively common type of cerebrovascular disease, detailed correlation between clinical findings and magnetic resonance imaging (MRI) has not yet been reported.

We studied 33 consecutive patients with lateral medullary infarction who showed appropriate MRI lesions and correlated their clinical findings with the MRI results.

Gait ataxia (88%), vertigo/dizziness (91%), nausea/vomiting (73%), dysphagia (61%), hoarseness (55%), Horner sign (73%), and facial (85%) and hemibody (94%) sensory changes were frequent clinical findings. MRI results showed that the lesions located in the rostral part of the medulla were usually diagonal band-shaped and were associated with more severe dysphagia, hoarseness, and the presence of facial paresis, whereas the caudal lesions, situated usually in the lateral surface of the medulla, appeared to correlate with more marked vertigo, nystagmus, and gait ataxia. Nausea/vomiting and Horner sign were common regardless of the lesion location, and lesions extending ventromedially correlated with facial sensory change on the contralateral side of the lesion.

Analysis of MRI findings in rostrocaudal and dorsoventral aspects allows us, although not unequivocally, to make anatomicoclinical correlations in the evaluation of patients with lateral medullary stroke syndrome.
Effects of recombinant superoxide dismutase on manganese superoxide dismutase gene expression in gerbil hippocampus after ischemia.
Authors: Matsuyama T , Shimizu S , Nakamura H , Michishita H , Tagaya M , Sugita M
Published: June 2011

We reported that recombinant human superoxide dismutase ameliorates delayed neuronal death in the postischemic gerbil hippocampus. Since postischemic induction of copper-zinc superoxide dismutase messenger RNA was abolished by this treatment, oxygen radicals generated on reperfusion may induce the expression of this gene. In the present study we examined whether oxygen radicals also induce the expression of manganese superoxide dismutase messenger RNA in the postischemic brain.

We induced transient cerebral ischemia by occluding the bilateral common carotid arteries of gerbils. Recombinant human superoxide dismutase (8 x 10(5) U/kg) or apo-superoxide dismutase was administered intravenously 1 minute before a 5-minute occlusion of the carotid arteries. We analyzed both copper-zinc and manganese superoxide dismutase RNA by in situ hybridization histochemistry and by Northern and dot blot analyses using radioisotope-labeled oligonucleotide probes.

Hybridization with the manganese superoxide dismutase messenger RNA occurred at the limit of detection in normal CA1 neurons. We observed striking increases in the labeling of CA1 up to 24 hours after 5 minutes of ischemia. The hybridization occurred anew in glial cells of the CA1 layer during 3 to 7 days. Pretreatment with recombinant human superoxide dismutase had no effect on the postischemic induction of manganese superoxide dismutase messenger RNA, whereas the same treatment significantly attenuated (P < .01) the increase in copper-zinc superoxide dismutase messenger RNA.

Our results demonstrated temporal postischemic induction of manganese superoxide dismutase messenger RNA. The inducer may not be superoxide radicals but may be other chemical mediators such as cytokines.
Effects of local reduction in pressure on endothelium-dependent responses of cerebral arterioles.
Authors: Baumbach G L , Faraci F M , Heistad D D
Published: June 2011

The goal of this study was to examine effects of local reductions in intravascular pressure and dP/dt on endothelium-dependent responses of cerebral arterioles in normotensive Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP).

WKY and SHRSP underwent clipping of one carotid artery at 1 month of age. At 6 months of age, responses of pial arterioles were examined in vivo in anesthetized rats. Bilateral craniotomies were performed to expose pial arterioles in the sham-operated and clipped cerebral hemispheres. Pressure (servo-null) was measured in sham-operated and clipped pial arterioles, and arteriolar diameter was measured before and during suffusion with bradykinin, A23187, and nitroprusside.

Carotid clipping normalized pial arteriolar pulse pressure but not mean pressure in SHRSP. Responses of sham-operated pial arterioles to bradykinin and A23187 were less in SHRSP than in WKY. Responses of sham-operated pial arterioles to nitroprusside were greater in SHRSP than in WKY. Carotid clipping in SHRSP normalized responses of pial arterioles to bradykinin but not A23187 and had no effect on responses to nitroprusside.

These findings suggest that elevated intravascular pressure per se may contribute to impairment of endothelium-dependent relaxation to at least some agonists in cerebral arterioles during chronic hypertension. Furthermore, the findings lead us to speculate that arteriolar pulse pressure may play a more important role than mean pressure in development of impaired endothelium dilatation during chronic hypertension.
Role of angiotensin receptor subtypes in the response of rabbit brain arterioles to angiotensin.
Authors: Haberl R L
Published: June 2011

Angiotensin II has been reported to induce either constriction or dilation in the cerebral microcirculation. The goal of this study was to determine whether binding to different angiotensin II receptor subtypes may account for the divergent responses.

Pial arterioles ranging a diameter from 28 to 136 microns were observed through a microscope in a closed cranial window preparation in anesthetized rabbits. Arteriolar responses to topical application of 10(-5) mol/L angiotensin II or the vasoactive angiotensin II degradation products L-arginine/angiotensin-(3-8) were measured by videometry. The effect of the subtype 1 receptor antagonist losartan and the subtype 2 antagonist PD 123319 on these responses was examined in separate groups of animals.

Topical coapplication of 10(-5) mol/L losartan or 10(-5) mol/L PD 123319 produced 55% and 62% inhibition of the dilator response to 10(-5) mol/L angiotensin II, respectively. Combined application of the antagonists caused 79% inhibition. Each of the antagonists almost completely blocked the response to L-arginine/angiotensin-(3-8). Acetylcholine-induced dilation of rabbit brain arterioles was unaffected by the antagonists.

Both of the known angiotensin II receptor subtypes appear to be involved in angiotensin II-induced dilation of rabbit cerebral arterioles. These results argue against the assumption that vasodilation is a specific function of one of these receptor subtypes, which might have explained the equivocal effects of angiotensin II by predominance of a certain receptor subtype in a given vascular bed.
Endogenous angiotensin II inhibits production of cerebrospinal fluid during posthypoxemic reoxygenation in the rabbit.
Authors: Maktabi M A , Faraci F M
Published: June 2011

The choroid plexus, the major source of cerebrospinal fluid (CSF), contains receptors for angiotensin II and a very high concentration of angiotensin converting enzyme. Circulating angiotensin II decreases blood flow to the choroid plexus and the production of CSF. During recovery from hypoxia, marked increases in circulating angiotensin II have been described in some studies. We tested the hypothesis that CSF production decreases during posthypoxemic reoxygenation and examined related changes in plasma concentrations of angiotensin II. We also determined whether effect of posthypoxic reoxygenation on production of CSF is due to endogenous release of angiotensin II.

We measured production of CSF in chloralose-anesthetized rabbits using ventriculocisternal perfusion of artificial CSF containing blue dextran. After control measurements, rabbits were subjected to one of the following interventions: (1) 30 minutes of hypoxia (PaO2 = 36 +/- 1 mmHg [mean +/- SE]) followed by 90 minutes of reoxygenation; (2) 30 minutes of hypoxia (PaO2 = 37 +/- 2 mmHg) followed by 90 minutes of reoxygenation in the presence of the angiotensin II antagonist saralasin; (3) hypoxia for 120 minutes (PaO2 = 35 +/- 1 mmHg); and (4) infusion of vehicle under normoxic conditions for 120 minutes (time control). Plasma concentrations of angiotensin II were also measured (radioimmunoassay) under control conditions, during hypoxia, and during posthypoxic reoxygenation (first intervention) and at corresponding time intervals in time control animals (fourth intervention).

Under control conditions, the rate of production of CSF averaged 6.7 +/- 0.1 microL.min-1. During posthypoxemic reoxygenation, production of CSF decreased by 31 +/- 4% (P < .05). In the presence of sarlasin, CSF production did not change significantly during posthypoxemic reoxygenation (-12 +/- 6%, P > .05). In time control animals and during prolonged hypoxia, CSF production did not change significantly (-12 +/- 5% [P > .05] and 9 +/- 7% [P > .05], respectively). Plasma concentrations of angiotensin were below the threshold of sensitivity of the assay under control conditions and during interventions in animals that were made hypoxic and then reoxygenated and in time control animals.

CSF production decreases during posthpoxemic reoxygenation. Since plasma concentrations of angiotensin II did not change during posthypoxic reoxygenation, this effect does not appear to be mediated by increases in circulating angiotensin II. We speculate that endogenous release of angiotensin II, perhaps in the choroid plexus epithelium, decreases production of CSF after hypoxic brain injury.
Spontaneous echo contrast and hemorheologic abnormalities in cerebrovascular disease.
Authors: Briley D P , Giraud G D , Beamer N B , Spear E M , Grauer S E , Edwards J M , Clark W M , Sexton G J , Coull B M
Published: June 2011

Spontaneous echo contrast (SEC) is thought to represent a risk factor for cardioembolic stroke. In vitro studies suggest that SEC results from interaction between red cells and fibrinogen. To better understand the relation between SEC and stroke and to investigate the in vivo genesis of SEC, we examined the relation between SEC, the constituents of the blood, and plasma and serum viscosity in patients with acute stroke or chronic cerebrovascular disease.

Fifty patients with acute stroke or chronic cerebrovascular disease referred for transesophageal echocardiogram (TEE) were studied by transthoracic echocardiography and TEE. Complete blood count, fibrinogen, albumin, gamma-globulin, and plasma and serum viscosity determinations were made. Left atrial SEC was graded as absent, mild, or marked by means of TEE.

SEC was absent in 31 patients, mild in 10 patients, and marked in 9 patients. Higher grade of SEC was associated with a significantly greater percentage of patients with atrial fibrillation and larger left atrial dimension. Atrial fibrillation was present in 23% of the patients in the SEC absent group, 50% of the patients in the mild SEC group, and 78% of the patients in the marked SEC group (P < .01). Left atrial diameter averaged 3.8 +/- 0.6 cm in the SEC absent group, 4.3 +/- 1.1 in the mild SEC group, and 4.9 +/- 0.7 in the marked SEC group (P < .001). Hematocrit, white blood cell count, and platelet count did not differ among the three groups. Fibrinogen, gamma-globulin, plasma viscosity, and serum viscosity values were all significantly higher in the presence of SEC (P < .05). Fibrinogen values were 361 +/- 97 mg/dL in the SEC absent group and 427 +/- 135 mg/dL in the marked SEC group. gamma-Globulin levels were 0.75 +/- 0.23 g/dL in the SEC absent group and 1.06 +/- 0.48 g/dL in the marked SEC group. Both plasma viscosity (1.97 cp) and serum viscosity (1.64 cp) were higher in the marked SEC group than in the SEC absent group (1.77 and 1.50 cp, respectively).

In patients with acute stroke or chronic cerebrovascular disease, the severity of SEC was not related to albumin, hematocrit, white cell count, or platelet count but rather to elevated fibrinogen levels and concomitant increases in both plasma and serum viscosity. Moreover, increasing grade of SEC was associated with significantly increased left atrial diameter and a higher percentage of patients in atrial fibrillation.
Cerebrospinal fluid and therapy of isolated angiitis of the central nervous system.
Authors: Oliveira V , Póvoa P , Costa A , Ducla-Soares J
Published: June 2011

Serial cerebral angiograms, computed tomography, and magnetic resonance imaging are among the proposed methods for monitoring disease activity and response to therapy in isolated angiitis of the central nervous system. Cerebrospinal fluid has not proved to be useful in monitoring clinical course.

We describe a 45-year-old man with histological diagnosis of isolated angiitis of the central nervous system that was treated with prednisone plus azathioprine and monitored for 2 years. Samples of the cerebrospinal fluid were obtained for cytological and routine chemical examination, as well as albumin and immunoglobulin content. Before treatment, cerebrospinal fluid showed marked plasmatic transudation of albumin and intrathecal synthesis of immunoglobulins. During the first year of immunosuppression no events were noticed, and the previously abnormal aspects of the cerebrospinal fluid showed improvement. During the weaning of azathioprine, a new stroke occurred in conjunction with a marked deterioration of cerebrospinal fluid parameters. Immunosuppression was resumed at previous levels, and during the following year no further events occurred. Once again, abnormal cerebrospinal fluid values improved significantly.

We report a case of isolated angiitis of the central nervous system in which the serial cerebrospinal fluid examinations (albumin and immunoglobulin content) showed a close correlation with clinical course. This method may be useful in monitoring response to therapy.
Ensuring reliability of outcome measures in multicenter clinical trials of treatments for acute ischemic stroke. The program developed for the Trial of Org 10172 in Acute Stroke Treatment (TOAST).
Authors: Albanese M A , Clarke W R , Adams H P , Woolson R F
Published: June 2011

Ensuring the reliability and validity of outcome measures used in clinical trials is essential to the success of the trial. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) is a multicenter clinical trial that is recruiting patients with acute ischemic stroke seen at medical centers across the United States.

This paper describes an approach to train physicians to use three clinical measures: the National Institutes of Health (NIH) Stroke Scale, a supplemental motor examination, and the Glasgow Outcome Scale. The program included education, certification, remediation when needed, monitoring, and reliability assessment. The goal was to ensure that interrater assessments were as equivalent to one another as possible.

Of the first 95 clinicians who began the certification process, 75 passed during the first evaluation. Eighteen of the other physicians were able to complete the process after remediation. The intraclass correlations of both the NIH Stroke Scale and supplemental motor examination exceeded 0.95. The kappa values for the Glasgow Outcome Scale were 0.61 and 0.62 for the first and second ratings of the videotape, respectively.

Our experience suggests that a program that includes educational and certification processes can be performed as part of the design of a multicenter clinical trial. The method of providing educational and testing videotapes to each site so that physicians can be trained and certified is an effective, inexpensive, and practical approach for enhancing and certifying the expertise of the large number of physicians involved in a multicenter study.
Incidence of stroke among inpatients in a large Italian hospital.
Authors: Azzimondi G , Nonino F , Fiorani L , Vignatelli L , Stracciari A , Pazzaglia P , D'Alessandro R
Published: June 2011

The incidence of stroke among inpatients is not known. The aim of our study was to investigate the incidence of stroke not preceded by evident iatrogenic factors such as surgical or medical procedures in a cohort of inpatients in a large Italian general hospital.

From January 1, 1992, to December 31, 1992, we evaluated patients referred to our neurology department with a suspected diagnosis of stroke that occurred during hospitalization. Patients presenting with stroke as a complication of iatrogenic causes were excluded. We calculated the incidence rate of first-ever stroke in our cohort (crude and among patients aged older than 50 years), thereafter adjusting these rates for age to the general population of the city district of Bologna (Italy).

In 1992, 22 inpatients had a first-ever stroke with no evidence of iatrogenic factors. The crude stroke incidence rate was 11.08/1000 per year (95% confidence interval, 6.95 to 16.73). The age-adjusted rate was 5.46 (95% confidence interval 3.42 to 8.24).

The incidence rate of first-ever stroke among hospitalized patients is higher than those reported in community-based studies. Higher frequency of coronary artery disease among our patients could explain our findings. Further studies are needed to identify possible predisposing factors (individual or environmental) for stroke among inpatients.
Correlation of xenon-enhanced computed tomography-defined cerebral blood flow reactivity and collateral flow patterns.
Authors: Smith H A , Thompson-Dobkin J , Yonas H , Flint E
Published: June 2011

A chronic compromise of cerebral hemodynamics has been shown to identify a group of patients at an increased risk for stroke. Because a "steal phenomenon" induced by a vasodilatory challenge has characterized the group at greatest risk, it was hypothesized that these individuals would also have a severe compromise of primary collaterals and an increased dependence on leptomeningeal collaterals.

Twenty-three patients with symptomatic cerebrovascular disease underwent angiography and xenon-enhanced computed tomographic cerebral blood flow studies before and after 1 g IV acetazolamide within 6 months of each other. Cerebral blood flow vasoreactivity was classified by whether cerebral blood flow increased (> 5%) or was unchanged (+/- 5%) (group 1) or fell by > 5% (group 2) in any vascular territory. Angiographic collateralization was classified into four types: normal (type 1), willisian (type 2), ophthalmic (type 3), and leptomeningeal (type 4).

Twenty percent (2/10) of group 1 patients and 69% (9/13) of group 2 patients (P = .0009) had leptomeningeal collaterals.

A negative flow reactivity is significantly associated with a dependence on leptomeningeal collaterals and implies a state of maximal hemodynamic compromise.
Magnetic resonance imaging study on the effect of levemopamil on the size of intracerebral hemorrhage in rats.
Authors: Elger B , Seega J , Brendel R
Published: June 2011

Beneficial effects of calcium antagonists in cerebral ischemia and trauma have been attributed in part to improved cerebral blood flow. Enhancement of cerebral blood flow, however, could aggravate the pathological situation if brain injury is associated with intracerebral hemorrhage. In this study we used high-field magnetic resonance imaging in an animal model of intracerebral hemorrhage to determine noninvasively the effect of the calcium and serotonin antagonist levemopamil [international nonproprietary name for (S)-emopamil] when infused in a dose (6 mg/kg) that is known to increase cerebral blood flow.

Intracerebral hemorrhage was induced in rats by stereotaxic microinfusion of collagenase into the caudate putamen. Two series of experiments were performed. (1) Levemopamil was intravenously infused 30 minutes after intracerebral infusion of collagenase (0.05 U), which represents the time of intracranial bleeding. Another group of animals was given heparin (55 IU.kg-1.min-1) to evaluate the capability of this animal model to demonstrate drug-induced worsening of intracerebral hemorrhage. (2) The effects of hyperacute infusion of levemopamil (30 minutes after infusion of 0.5 U of collagenase) were compared with those of a 2-hour delayed administration. In both experimental settings, the extent of intracerebral hemorrhage was determined by T1-weighted magnetic resonance images (spin-echo; repetition time, 400 milliseconds; echo time, 23 milliseconds) taken in vivo in a coronal and a transverse brain plane 24 hours after collagenase infusion.

(1) Hemorrhagic brain areas measured 10.1 +/- 2.9 mm2, 8.5 +/- 2.1 mm2, and 18.8 +/- 2.5 mm2 in the coronal brain plane (10 mm anterior to the interaural line) of control, levemopamil-, and heparin-infused rats, respectively (8 animals per group, mean +/- SD). In the transverse brain plane (6 mm dorsal to the interaural line) the hemorrhagic area was 11.5 +/- 3.6 mm2, 9.7 +/- 2.4 mm2, and 19.9 +/- 3.3 mm2 in control, levemopamil-, and heparin-infused rats, respectively. (2) Animals with 2-hour delayed levemopamil infusion displayed intracerebral hemorrhage similar in size to that of control rats. (3) Neither small nor large hemorrhagic lesions were increased by levemopamil.

Aggravation of intracerebral hemorrhage was not observed by magnetic resonance imaging in levemopamil-infused animals. However, infusion of heparin caused a significant (P < .05), almost twofold increase in the size of intracerebral hemorrhage. These results justify clinical trials with levemopamil in cerebral disorders such as stroke, brain trauma, and peritumoral brain edema, which may be accompanied by intracerebral hemorrhage from the beginning or where transition to intracerebral hemorrhage may occur.
Arterial microsphere concentrations in cats are not affected by changes in hematocrit.
Authors: DeWitt D S , Prough D S , Deal D D , Hoen H M
Published: June 2011

Acute anemia may lead to erroneously low arterial reference sample concentrations of radioactive microspheres, depending on the sampling rate and the size of the artery from which the reference samples are withdrawn. Because this error would lead to falsely high cerebral blood flow values in studies involving hemodilution caused by hemorrhage and fluid resuscitation, we studied the effects of hematocrit, withdrawal rate, and vessel location and size on arterial microsphere concentrations in anesthetized adult cats.

Cats were anesthetized with ketamine, isoflurane, and nitrous oxide; both brachial arteries were cannulated with polyethylene tubing, as was the abdominal aorta through the femoral artery. Sequential left atrial microsphere injections were made using several doses of each of five isotopes. The rate of reference sample withdrawal from the three sampling catheters was randomized to 1.03 mL.min-1 or 2.06 mL.min-1. We analyzed the ratio of the number of microspheres in paired reference samples using the factors hematocrit, rate of withdrawal, and site. A ratio less than 1 indicates an underestimation of arterial microsphere concentration, which would lead to erroneously high cerebral blood flow values. The procedure was repeated after isovolemic hemodilution with 10% hetastarch to hemoglobin levels approximating 85%, 70%, 55%, and 40% of baseline.

No significant effects of hematocrit on ratios of microsphere concentrations existed at any withdrawal rate or site. Ratios of microsphere concentrations in reference samples withdrawn slowly (1.03 mL.min-1) from the aorta and ratios of microsphere concentrations withdrawn either rapidly (2.06 mL.min-1) or slowly from the brachial arteries were significantly (P < .001) less than 1.

Hemodilution did not affect microsphere concentrations in arterial reference samples at any withdrawal site or rate and therefore does not affect the accuracy of microsphere blood flow determinations. However, slow withdrawal from a large vessel may underestimate actual microsphere concentrations.
Interrater Reliability of an Etiologic Classification of Ischemic Stroke
Authors: Johnson C. J. , Kittner S. J. , McCarter R. J. , Sloan M. A. , Stern B. J. , Buchholz D. , Price T. R.
Published: June 2011

Background and Purpose
Precise identification of the cause of stroke is critical to research and clinical practice. Published series of ischemic stroke show considerable variation in the proportion of cases classified as atherosclerotic large-vessel disease, lacunar infarct, cardioembolic stroke, stroke of other known cause, and stroke of undetermined etiology. We describe the development and use of an etiology-specific classification of ischemic stroke. The interrater reliability of the classification is then evaluated.

Methods
A total of 160 cases of ischemic strokes in young adults were reviewed by paired neurologists who assigned cases to prioritized categories. The results of paired ratings were evaluated for each of the potential causes. Interrater agreement was assessed by means of κ, which is the chance-adjusted percent agreement.

Results
For standard pairs, κ was fair to good for all causes except lacunar stroke (κ=0.31); however, pair-to-pair variation was greatest for lacunar strokes. Strokes of undetermined cause and hematologic/other cause were of borderline fair reliability.

Conclusions
The utility of a stroke classification system is dependent on its intended use. An etiologic classification is useful in studies of the epidemiology and pathophysiological basis of stroke. Fair to good reliability for an etiologic classification of stroke can be obtained when criteria are explicit.