bluuebunny/crossref_metadata_2025 huggingface dataset:
Atrial fibrillation as an independent risk factor for stroke: the Framingham Study.
Authors: Wolf P A , Abbott R D , Kannel W B
Published: June 2011

The impact of nonrheumatic atrial fibrillation, hypertension, coronary heart disease, and cardiac failure on stroke incidence was examined in 5,070 participants in the Framingham Study after 34 years of follow-up. Compared with subjects free of these conditions, the age-adjusted incidence of stroke was more than doubled in the presence of coronary heart disease (p less than 0.001) and more than trebled in the presence of hypertension (p less than 0.001). There was a more than fourfold excess of stroke in subjects with cardiac failure (p less than 0.001) and a near fivefold excess when atrial fibrillation was present (p less than 0.001). In persons with coronary heart disease or cardiac failure, atrial fibrillation doubled the stroke risk in men and trebled the risk in women. With increasing age the effects of hypertension, coronary heart disease, and cardiac failure on the risk of stroke became progressively weaker (p less than 0.05). Advancing age, however, did not reduce the significant impact of atrial fibrillation. For persons aged 80-89 years, atrial fibrillation was the sole cardiovascular condition to exert an independent effect on stroke incidence (p less than 0.001). The attributable risk of stroke for all cardiovascular contributors decreased with age except for atrial fibrillation, for which the attributable risk increased significantly (p less than 0.01), rising from 1.5% for those aged 50-59 years to 23.5% for those aged 80-89 years. While these findings highlight the impact of each cardiovascular condition on the risk of stroke, the data suggest that the elderly are particularly vulnerable to stroke when atrial fibrillation is present.(ABSTRACT TRUNCATED AT 250 WORDS)
Hemorheological factors in cerebral ischemia.
Authors: Fisher M , Meiselman H J
Published: June 2011

We investigated 100 consecutive cerebral ischemia patients for hemorheological alterations. We measured whole and adjusted blood viscosity at 75 and 1,500 sec-1, plasma viscosity, red blood cell aggregation by the zeta sedimentation ratio, and red blood cell deformability using the centrifugal deformability technique. Patients were studied within 72 hours of the acute ischemic event, and 66 were available for follow-up evaluation approximately 2 months later. Two age- and sex-matched control groups were evaluated: 20 nonvascular neurological inpatients (patient controls) and 45 normal volunteers (normal controls). Compared with normal controls, we found significant acute increases in whole blood viscosity (1,500 sec-1), plasma viscosity, fibrinogen concentration, and zeta sedimentation ratio; the latter two variables were also increased at follow-up. Fibrinogen concentration was significantly associated with zeta sedimentation ratio and plasma viscosity and was increased for patient controls. There was a trend toward normalization of acute abnormalities over the 2-month follow-up period, and patients with more severe strokes tended to have more extensive hemorheological abnormalities. Among patients with severe stroke, fibrinogen concentration was significantly associated with the platelet activation peptide beta-thromboglobulin acutely (r = 0.63, p less than 0.005). We conclude that hemorheological abnormalities in cerebral ischemia are largely nonspecific findings, with the likely exception of patients with severe stroke.
Quicker metabolic recovery after forebrain ischemia in rats treated with the antioxidant U74006F.
Authors: Haraldseth O , Grønås T , Unsgård G
Published: June 2011

We used phosphorus-31 nuclear magnetic resonance spectroscopy in a rat model of 10 minutes' severe incomplete forebrain ischemia (two-vessel occlusion with hypotension) to study the effects of preischemic and postischemic treatment with 3 mg/kg i.v. U74006F on the recovery of high-energy phosphates and intracellular pH during early reperfusion. The mean +/- SD time to 85% recovery of phosphocreatine was 14.1 +/- 8.4 minutes in the control group (n = 10) compared with 6.6 +/- 3.5 minutes (p less than 0.05) in the preischemic (n = 8) and 4.2 +/- 1.0 minutes (p less than 0.001) in the postischemic (n = 11) treatment groups. The mean +/- SD time to 80% recovery of adenosine triphosphate was 15.4 +/- 8.5 minutes in the control group compared with 6.3 +/- 1.8 (p less than 0.005) and 5.4 +/- 2.8 (p less than 0.001) minutes in the preischemic and postischemic treatment groups, respectively. There were no differences in intracellular pH between the control and either of the treatment groups. We conclude that U74006F led to quicker recovery of high-energy phosphates during early reperfusion, and this beneficial effect was also seen with postischemic treatment.
Recurrent embolic stroke and cocaine-related cardiomyopathy.
Authors: Sauer C M
Published: June 2011

Ischemic stroke temporally related to cocaine abuse has become increasingly common in young adults. Despite this relation, however, the pathogenesis of infarction in many of these patients remains obscure. I report the case of a 39-year-old man who developed occlusion of the frontopolar branches of the left middle cerebral artery 1 hour after intravenous cocaine use. Eleven days later he developed occlusion of the superior division of the right middle cerebral artery. In this case the mechanism of infarction was clearly cardiogenic embolization. Chest radiograph and echocardiogram revealed dilated cardiomyopathy with left ventricular thrombi. No cause other than cocaine abuse was found for his cardiomyopathy. This is the second reported case of cocaine-related cardiomyopathy presenting as embolic stroke and associated with intracavitary thrombus. Such an association may be more common than previously thought. Thorough cardiac evaluation in all patients with ischemic stroke related to cocaine abuse is appropriate.
Early computed tomographic findings for thrombolytic therapy in patients with acute brain embolism.
Authors: Okada Y , Sadoshima S , Nakane H , Utsunomiya H , Fujishima M
Published: June 2011

The benefits and safety of thrombolytic therapy was studied in patients with acute brain embolism.

We intravenously administered recombinant tissue plasminogen activator (20-30 MU for 1 hour) to 10 patients with acute (less than 6 hours) brain embolism and examined the neurological outcomes in relation to the findings on computed tomography and angiography.

The symptoms ameliorated in four patients within 24 hours after onset, and reopening of the occluded arteries occurred in two of the patients immediately after recombinant tissue plasminogen activator infusion. On the initial computed tomographic scan (less than 3 hours), four patients had already demonstrated early indications of brain ischemia, that is, an obscure margin of the lentiform nuclei, reduced tissue attenuation, or effacement of cortical sulci. These patients failed to demonstrate reopening of the occluded arteries, and one developed a massive brain hemorrhage with clinical deterioration. Of the remaining six patients, two obtained clinical improvement with recanalization soon after the therapy and demonstrated little to slight hemorrhagic complications. The outcomes at 1 month were favorable in five patients and poor in three; death occurred in two.

Thrombolytic therapy with recombinant tissue plasminogen activator may be safe and effective when there are no early computed tomographic findings within 3 hours from the onset of embolic stroke.
A model of acute focal ischemia in the territory of the anterior cerebral artery in baboons.
Authors: Liu X G , Branston N M , Kawauchi M , Symon L
Published: June 2011

We developed a model of acute focal ischemia in the territory of the anterior cerebral artery in baboons to study the ischemic pattern following occlusion and changes in regional cerebral blood flow.

In nine anesthetized animals, a Scoville clip was placed on the proximal segment of the common anterior cerebral artery via a unilateral transorbital approach. Regional cerebral blood flow was measured by hydrogen clearance in the cortex and corpus callosum. Postexperimentally, arteries were selectively injected.

The resulting ischemia involved both hemispheres symmetrically and the corpus callosum. Cortical flows were significantly reduced within a region 15 mm from the midline on each side (p less than 0.01). A gradient of cortical flow reduction was produced between 10 and 25 mm from the midline. This area defines the boundary region between the territories of the anterior and middle cerebral arteries, and is identified as the "penumbra" of the ischemic core, which itself lies within 10 mm of the midline. Blood flows in the corpus callosum decreased from an average of 21.0 to 6.7 ml/100 g/min in the body (p less than 0.01) and from 22.5 to 10.7 ml/100 g/min in the genu (p less than 0.05).

This ischemic model has close physiological and morphological relevance to stroke-related clinical circumstances, in particular the acute conditions of focal cerebral ischemia associated with vascular surgery. It also provides a new framework for experimental investigation of the ischemic penumbra.
Reduction in ischemic brain injury in rabbits by the anion transport inhibitor L-644,711.
Authors: Kohut J J , Bednar M M , Kimelberg H K , McAuliffe T L , Gross C E
Published: June 2011

We studied the anion transport inhibitor L-644,711, which is known to reduce astrocyte swelling and excitotoxin release in primary astrocyte culture, in two models of thromboembolic stroke to assess its capacity to influence ischemic brain injury.

New Zealand White rabbits were used in this study. The two models include autologous clot embolized to the brain via the carotid artery, with one model using a transient period of systemic hypotension. Cerebral blood flow was determined by the hydrogen clearance method, intracranial pressure was measured with a fiberoptic transducer, and infarct size was assessed with triphenyltetrazolium chloride staining of the coronally sectioned brain. Both models received a 2-hour infusion of L-644,711 (total dose, 12 mg/kg) beginning 20 minutes before embolization.

In both the normotensive (p less than 0.01) and the hypotensive (p less than 0.05) model, treatment with L-644,711 resulted in a significant reduction in infarct size and a significant improvement in regional cerebral blood flow (p less than 0.03, normotensive model, and p less than 0.05, hypotensive model). Raised intracranial pressure, unique to the hypotensive model, was abolished by the administration of L-644,711 (p less than 0.05). A hyperglycemic response associated with embolization, also unique to the hypotensive model, was significantly reduced by the administration of L-644,711 (p less than 0.05).

The ability of L-644,711 to limit brain injury in two related models of thromboembolic stroke suggests a potential therapeutic role for anion channel blockers in cerebral ischemia.
Assessment of intracranial hemodynamics in sleep apnea syndrome.
Authors: Klingelhöfer J , Hajak G , Sander D , Schulz-Varszegi M , Rüther E , Conrad B
Published: June 2011

Sleep apnea syndrome may lead to changes in cerebral hemodynamics due to altered alveolar ventilation. We investigated the dynamics of CO2- and blood pressure-regulated alterations of cerebral blood flow velocities during apneic episodes and evaluated CO2 reactivity during different sleep stages.

A computer-assisted pulsed Doppler system (2 MHz) was used for continuous overnight recordings of middle cerebral artery flow patterns together with simultaneous polysomnography, continuous blood pressure recordings, and measurements of end-expiratory CO2 in six patients with sleep apnea syndrome.

Increases in mean flow velocity of 19-219% and in blood pressure of 12.5-83.1% could be observed during the apneic episodes, with maximum increases during rapid eye movement (REM) sleep. CO2 reactivity was in the normal range (4.4 +/- 1.2%) in the waking state and was markedly increased during sleep stages 1 and 2 (p less than 0.005 compared with awake). The greatest increase was found during REM sleep, with a rise of up to three times the waking value (p less than 0.0001 compared with sleep stage 2).

The changes of mean flow velocity could be interpreted as reactive adaptation processes because of CO2 and blood pressure increases corresponding to apnea. The increased CO2 reactivity during sleep may indicate a "hypersensitivity" of intracranial vascular CO2 or pH receptors and a disturbance of central catecholaminergic and cholinergic systems. The pronounced velocity changes during apneic episodes and the concomitant alterations of vessel wall tension might lead to microangiopathies and macroangiopathies due to chronic strain on the brain vessels.
Leukoaraiosis in relation to prognosis for patients with lacunar infarction.
Authors: Miyao S , Takano A , Teramoto J , Takahashi A
Published: June 2011

Close relations between leukoaraiosis detected by computed tomography or magnetic resonance imaging and stroke, particularly lacunar infarction, have been reported. We studied whether leukoaraiosis is related to long-term prognosis for patients with lacunar infarction.

We examined monthly 215 patients with lacunar infarction after their first stroke. They comprised 95 patients with leukoaraiosis disclosed by computed tomography on admission (58 men and 37 women; mean age, 71.3 +/- 9.0 years) and 120 patients without leukoaraiosis (81 men and 39 women; mean age, 65.5 +/- 8.9 years). These patients had no previous history of either stroke or obvious dementia before their index stroke. We compared the prognosis with and without leukoaraiosis based on analysis of recurrent stroke, survival, and the prevalence of dementia and rate of dependence in activities of daily living.

Life table analysis revealed that the recurrent stroke rate was significantly higher in the patients with leukoaraiosis than in those without it (p = 0.004). The prevalence of dementia and rate of dependence in activities of daily living both 1 month after the index stroke and at the end of the follow-up period were significantly higher in the patients with leukoaraiosis (all parameters, P less than 0.001). Their survival rate was significantly lower than in those not suffering from leukoaraiosis (p = 0.012). Significant differences in these comparisons were also observed after matching for age and sex.

The presence of leukoaraiosis as identified by computed tomography indicates a poor prognosis for patients with lacunar infarction.
Secular trends in stroke incidence and mortality. The Framingham Study.
Authors: Wolf P A , D'Agostino R B , O'Neal M A , Sytkowski P , Kase C S , Belanger A J , Kannel W B
Published: June 2011

The reduction in US stroke mortality has been attributed to declining stroke incidence. However, evidence is accumulating of a trend in declining stroke severity.

We examined secular trends in stroke incidence, prevalence, and fatality in Framingham Study subjects aged 55-64 years in three successive decades beginning in 1953, 1963, and 1973.

No significant decline in overall stroke and transient ischemic attack incidence or prevalence occurred. In women, but not men, incidence of completed ischemic stroke declined significantly. Stroke severity, however, decreased significantly over time. Stroke with severe neurological deficit decreased in later decades, with a fall in rates of severe stroke cases in which patients were unconscious on admission to the hospital. There was no substantial change in the case mix of infarcts and hemorrhages and no decline in hemorrhage to account for the decline in severity. The proportion of isolated transient ischemic attacks increased significantly over the 30 years studied, yielding an apparent and significant decline in case-fatality rates in men only.

Secular trends in stroke incidence and fatality did not follow a clear or definite pattern of decline. While a significant decline in stroke severity occurred over three decades, incidence of infarction fell only in women. The decline in total case fatality rates occurred only in men and resulted largely from an increased incidence of isolated transient ischemic attacks. The severity of completed stroke was significantly lower in the later decades under study.
Release of proinflammatory and prothrombotic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar-Kyoto rats.
Authors: Sirén A L , Heldman E , Doron D , Lysko P G , Yue T L , Liu Y , Feuerstein G , Hallenbeck J M
Published: June 2011

We reported previously that stroke risk factors prepared the brain stem for the development of ischemia and hemorrhage and induced the production of tumor necrosis factor following an intrathecal injection of lipopolysaccharide, a prototypic monocyte-activating stimulus. This study evaluates whether blood or brain cells of hypertensive rats produce more proinflammatory and prothrombotic mediators than do blood or brain cells of normotensive rats.

Levels of tumor necrosis factor, platelet-activating factor, 6-ketoprostaglandin F1 alpha, and thromboxane B2 in the cerebrospinal fluid and blood of spontaneously hypertensive and normotensive Wistar-Kyoto rats were monitored before and after a challenge with lipopolysaccharide.

Little or no activity from these mediators was found in the cerebrospinal fluid or blood of saline-injected control animals. Intravenous administration of lipopolysaccharide (0.001, 0.1, and 1.8 mg/kg) produced dose-dependent increases in blood levels of all mediators in hypertensive rats. In normotensive rats the levels were less than in hypertensive rats and were not clearly dose-related. When lipopolysaccharide was injected intracerebroventricularly, more tumor necrosis factor was measured in the cerebrospinal fluid than in the blood, suggesting local synthesis of this cytokine. Levels of tumor necrosis factor and platelet-activating factor in the cerebrospinal fluid were higher in hypertensive than in normotensive rats. The thromboxane A2/prostacyclin ratio was not altered significantly between the two rat strains.

It is suggested that the higher incidence of brain stem ischemia and hemorrhage after the intrathecal injection of lipopolysaccharide in hypertensive rats than in normotensive rats might be related to the higher levels of the two cytotoxic factors tumor necrosis factor and platelet-activating factor produced in response to such challenge.
Leukoaraiosis and dementia in hypertensive patients.
Authors: Yao H , Sadoshima S , Ibayashi S , Kuwabara Y , Ichiya Y , Fujishima M
Published: June 2011

Although our previous study demonstrated that dementia of the Binswanger type may be a disconnection dementia caused by leukoaraiosis, some hypertensive patients with marked leukoaraiosis do not develop dementia. The goal of the present study is to elucidate the pathophysiology of nondemented hypertensive patients with leukoaraiosis.

We performed clinical and neuroradiological studies, including positron emission tomography, in eight hypertensive patients with leukoaraiosis.

Four patients were demented, and two among the other four who were not demented at the first examination developed dementia during the follow-up period. Digital subtraction angiography of the cervical and intracranial arteries demonstrated stenotic lesions in only one patient. Cerebral blood flow and oxygen metabolism in patients with dementia were markedly reduced in the white matter (59-67% of control values). In contrast, cerebral blood flow in the white matter of patients without dementia was reduced less markedly (74% of control), oxygen extraction fraction in the white matter was significantly increased (130% of control), and oxygen metabolism remained at almost-normal levels not only in the white matter but also in the cortical area.

Hypertension-caused arteriosclerotic changes of the long penetrating medullary arteries may cause misery perfusion and later ischemic damage in the periventricular white matter. Preserved oxygen metabolism in hypertensive patients with leukoaraiosis may represent the early stage of vascular dementia of the Binswanger type.
Longitudinal study of regional cerebral blood flow changes in depression after stroke.
Authors: Yamaguchi S , Kobayashi S , Koide H , Tsunematsu T
Published: June 2011

We studied 60 patients longitudinally to examine relations between regional cerebral blood flow and depressive states after stroke.

Poststroke depressive states were assessed by the Zung Self-Rating Depression Scale (SDS). Regional cerebral blood flow was measured using the 133xenon inhalation method with patients in the resting state on the same day as the SDS assessment. All patients were followed for an average of 14 months after the initial assessment.

Severity of depression was inversely correlated with regional cerebral blood flow values in the parieto-occipital regions of the right hemisphere and in the anterior temporal region of the left hemisphere at the initial evaluation. Patients with lesions in left frontal or right parieto-occipital regions were more depressive in comparison with those with other brain lesions. Follow-up study showed significant inverse correlations between changes in SDS score and changes in regional cerebral blood flow at all scalp sites. Furthermore, higher inverse correlations were observed at specific brain regions in each hemisphere, including the parietal and parieto-occipital regions of the right hemisphere and the anterior temporal and inferior frontal regions of the left hemisphere. This relation was independent of recovery from neurological deficits.

These results suggest that dysfunction of specific cortical and subcortical regions in both hemispheres asymmetrically contributes to depressive state after stroke.
Critical limits of pressure-flow relation in the human brain.
Authors: Njemanze P C
Published: June 2011

This study was designed to determine the minimal mean flow velocity and pressure-flow relation necessary to preserve human consciousness.

Passive upright tilt provocation was used in conjunction with transcranial Doppler in 80 patients with a history of syncope of unknown etiology. Cerebral blood flow velocity, blood pressure, and heart rate were monitored noninvasively.

Forty patients remained asymptomatic, and the rest had clinically induced true syncope or premonitory symptoms. In the asymptomatic group, there was a 23 +/- 16% (p = 0.000) drop in mean flow velocity, but no significant changes in systolic and diastolic blood pressures. In the symptomatic patients, there was a 58 +/- 14% (p = 0.000) drop in mean flow velocity, 37 +/- 23% (p = 0.000) fall in systolic pressure, and 31 +/- 20% (p = 0.000) fall in diastolic pressure. In 80% of symptomatic patients, the critical lower limit of mean flow velocity was at -50% of resting baseline while patients were lying supine. The symptomatic group had lower mean flow velocity and blood pressure responses as compared with the asymptomatic group. The slope and intercept values of the pressure (y axis) to flow velocity (x axis) regression curves indicate a greater degree of impaired autoregulation in the symptomatic group (y = 0.529 x-6.11, r2 = 0.108, p = 0.038) as compared with the asymptomatic (y = 0.317 x + 0.966, r2 = 0.14, p = 0.017).

The critical lower limit of cerebral perfusion lies at 50% below baseline supine mean flow velocity.
Effects of retrograde perfusion of the brain with combined drug therapy after focal ischemia in rat brain.
Authors: Shimauchi M , Yamamoto Y L
Published: June 2011

The ischemic edema associated with blood-brain barrier permeability changes and the excess production of free radicals are serious complications in prolonged cerebral ischemia. We examined the efficacy of transvenous perfusion of the brain, starting treatment 5 hours after occlusion of the middle cerebral artery for a period of 2 hours in rats with the combined agents mannitol (10 ml/2 hr) and dexamethasone (1 mg/2 hr) to counter edema and verapamil (0.05 mg/kg/2 hr) for vasodilation.

In experiment 1, blood-brain barrier permeability changes were examined in five groups with six rats each: group C rats underwent 7 hours of middle cerebral artery occlusion with no treatment; group V, treatment with verapamil alone; group VD, treatment with verapamil and dexamethasone; group VM, treatment with verapamil and mannitol; and group VDM, treatment with verapamil, dexamethasone, and mannitol. In experiment 2, we examined local cerebral blood flow, ischemic tissue damage volume, and water content of cerebral hemispheres in two groups of 16 rats each subjected to the same treatment as groups C and VDM rats in experiment 1.

There was a significant reduction of blood-brain barrier permeability changes in the ischemic cortex of rats in group VDM compared with rats in the other groups. In the group undergoing transvenous perfusion of the brain with the three combined agents, there was a significant improvement of cerebral blood flow (39-58%, p < 0.05) in the ischemic cortex and reduction of ischemic cerebral damage volume (22%, p < 0.01) and water content of the ischemic hemisphere (p < 0.05) compared with the control group.

The therapeutic approach using combined agents is effective treatment when initiated within 5 hours of focal cerebral ischemia in rats.
Long-term prognosis of infratentorial transient ischemic attacks and minor strokes.
Authors: Hornig C R , Lammers C , Büttner T , Hoffmann O , Dorndorf W
Published: June 2011

This study was performed to gather information about long-term prognosis after infratentorial transient ischemic attacks and minor strokes and about the factors influencing it.

We included 226 patients with transient ischemia and 169 patients with a minor stroke of the brain stem/cerebellum consecutively admitted to a neurological department. Medical records and the findings of computed tomography, Doppler ultrasonography, and angiography were evaluated retrospectively. Follow-up information was gathered from the patients and their physicians by questionnaires. Complete follow-up information was available for 381 patients.

During a mean follow-up of 3.9 years, 15.7% of the 381 patients suffered a stroke and 6.8% a myocardial infarction; 15% died. Kaplan-Meier estimates revealed a cumulative stroke rate of 5.1% within the first year and a risk of stroke, myocardial infarction, or death of any cause of 9.8%. In a proportional hazards model, the time-dependent risk of stroke was significantly increased by increasing age (p = 0.018), minor stroke (p = 0.0005), hypertension (p = 0.022), previous stroke (p = 0.0006), and carotid artery occlusive disease (p = 0.0065). The probability of stroke, myocardial infarction, or death was influenced by age (p = 0.0001), minor stroke (p = 0.006), diabetes (p = 0.015), previous stroke (p = 0.002), infarct on a computed tomogram (p = 0.041), and carotid artery disease (p = 0.032).

Long-term prognosis after brain stem/cerebellar transient ischemic attacks and minor strokes is significantly influenced by age, diabetes, hypertension, previous stroke, and concomitant carotid artery disease. Patients with transient ischemic attacks have a better prognosis than those with minor stroke.
Delayed onset hand tremor caused by cerebral infarction.
Authors: Kim J S
Published: June 2011

Hand tremor has been rarely described as a manifestation of stroke.

Three patients developed delayed onset hand tremor due to cerebral infarctions on the contralateral side, two in the caudate nucleus and the third in the thalamus. The tremors of all three patients were similar to parkinsonian tremor, but less monotonous.

Delayed-onset hand tremor should be considered as one of the movement disorders caused by cerebral infarction.
Cerebral infarction in young men with nephrotic syndrome.
Authors: Fuh J L , Teng M M , Yang W C , Liu H C
Published: June 2011

Thrombosis is one of the main complications of nephrotic syndrome; however, cerebral infarction associated with nephrotic syndrome has been rarely reported.

We describe acute cerebral infarction in two young men with nephrotic syndrome. Both had a hypercoagulable state based on hemostatic studies. By retrospectively reviewing the medical records of the past 10 years at our hospital, we found an additional five cases of cerebral infarction with nephrotic syndrome. Two of the patients were found to have nephrotic syndrome during admission for stroke.

Hypercoagulability may be the major contributing factor of cerebral infarction in patients with nephrotic syndrome.
Blood flow and vascular permeability during motor dysfunction in a rabbit model of spinal cord ischemia.
Authors: Jacobs T P , Kempski O , McKinley D , Dutka A J , Hallenbeck J M , Feuerstein G
Published: June 2011

Delayed deterioration of neurological function after central nervous system ischemia is a well-documented clinical problem. The purpose of our study was to elucidate the role of spinal cord blood flow and spinal cord-blood barrier integrity in the evolution of delayed neurological deterioration after transient spinal cord ischemia in rabbits.

Anesthetized rabbits were subjected to lumbar spinal cord ischemia (25 minutes) and variable periods of reperfusion (30 minutes to 48 hours after ischemia). Regional spinal cord blood flow was monitored by carbon-14-labeled iodoantipyrine autoradiography; vascular permeability was assessed by quantitative microhistofluorescence of Evans blue-albumin in frozen sections of spinal cord. Hindlimb motor function was assessed by standard scoring system and tissue edema by wet/dry weight method.

Hindlimb motor function indicated complete paralysis during ischemia and partial gradual recovery upon reperfusion (up to 8 hours), followed by progressive deterioration to severe deficits over 48 hours. Severe vascular permeability disruption was noticed early (30 minutes) after reperfusion, but almost complete recovery reestablished at 8 hours was followed by a secondary progressive increase in vascular permeability. Blood flow was reduced by 20-30% (p less than 0.01) 4 hours after ischemia in the gray matter, but hyperemia (200-300%, p less than 0.01) was observed 12-24 hours after ischemia. Spinal cord water content increased by 5.7% (p less than 0.05) 24 hours after ischemia.

This study demonstrates that delayed neurological and motor deterioration after spinal cord ischemia is associated with severe progressive breakdown of spinal cord-blood barrier integrity that develops late (hours) after the injury. Our data suggest that no ischemic insult in early or late reperfusion is associated with delayed motor deterioration.
Tissue plasminogen activator cerebrovascular thrombolysis in rabbits is dependent on the rate and route of administration.
Authors: Russell D , Madden K P , Clark W M , Zivin J A
Published: June 2011

The main aim of our study was to assess the cerebrovascular thrombolytic efficacy of different tissue plasminogen activator treatment protocols with Doppler ultrasound.

We occluded one internal carotid artery in 48 New Zealand White rabbits with whole blood emboli. Five minutes later the rabbits were assigned to receive one of the following tissue plasminogen activator protocols: 1) intravenous square-wave infusion in a total dose of 10 mg/kg, 2) intravenous constant infusion in a total dose of 10 mg/kg, 3) intravenous square-wave infusion in a total dose of 3 mg/kg, or 4) regional intra-arterial square-wave infusion in a total dose of 3 mg/kg. Blood flow velocities in the internal carotid arteries were continuously monitored during the study with Doppler ultrasound.

In all 12 animals treated with a 10-mg/kg square-wave intravenous tissue plasminogen infusion, internal carotid artery blood flow was reestablished within 2 hours (57.9 +/- 33.3 minutes) after the initiation of treatment, whereas this was the case for only six (50%) of the 12 animals treated with a constant 10-mg/kg intravenous tissue plasminogen activator infusion (p less than 0.05, Fisher's exact test). Internal carotid artery blood flow was restored within 2 hours (33.5 +/- 40.4 minutes) in all animals treated with a regional intra-arterial tissue plasminogen infusion in a total dose of 3 mg/kg and in only three (50%) of the six animals treated with the same dosage intravenously (p less than 0.05, signed rank test).

The thrombolytic efficacy of tissue plasminogen activator in the rabbit cerebral vasculature was superior when the same intravenous dose was given as a square-wave rather than a constant infusion and when the drug was given as a regional intra-arterial infusion rather than intravenously.
Effect of hemodilution on cerebral hemodynamics and oxygen metabolism.
Authors: Hino A , Ueda S , Mizukawa N , Imahori Y , Tenjin H
Published: June 2011

To evaluate the effects of hemodilution on cerebral hemodynamics and oxygen metabolism in the normal human brain, we measured regional cerebral blood flow, oxygen extraction fraction, oxygen metabolic rate, and regional cerebral blood volume in eight normal volunteers before and after hemodilution using positron emission tomography and oxygen-15-labeled gas inhalation technique.

Hemodilution was accomplished by phlebotomy of 400 ml and drip infusion of 500 ml low molecular weight dextran, which reduced hematocrit from 42.5% to 37.2% and arterial oxygen content from 19.1 to 16.9 ml/dl (both p less than 0.005). It also increased mean cerebral blood flow from 45.2 to 47.7 ml/100 ml/min (p less than 0.025), but decreased tissue oxygen delivery from 8.7 to 8.0 ml/100 ml/min (p less than 0.05) and cerebral blood volume from 4.9% to 4.6% (p less than 0.025) in the overall cortical gray matter.

Our results indicate that hemodilution in the tested range does not improve oxygen transport or tissue oxygenation in the normal human brain, although it increases cerebral blood flow.
Protective effects of felbamate against hypoxia in the rat hippocampal slice.
Authors: Wallis R A , Panizzon K L , Fairchild M D , Wasterlain C G
Published: June 2011

Felbamate is a new dicarbamate anticonvulsant with low toxicity currently being investigated in human clinical epilepsy trials. In this study, we examined the protective effects of felbamate against hypoxia.

We exposed paired rat hippocampal slices to hypoxia with and without felbamate treatment while monitoring the CA1-evoked population spike.

Felbamate provided dose-dependent neuroprotection against hypoxia at concentrations of 45 mg/l and greater (p less than 0.05). At a felbamate concentration of 300 mg/l, recovery of CA1 evoked population spike amplitude after hypoxic exposure was 99% compared with 0.5% for unmedicated paired slices. The appearance and disappearance of the hypoxic injury potential was delayed in slices treated with 300 and 400 mg/l (p less than 0.05).

In this model of hypoxia, felbamate provided neuroprotection against hypoxia at concentrations similar to serum felbamate levels currently being used in human clinical epilepsy trials.
Surgical correction and SPECT imaging of vertebrobasilar insufficiency due to unilateral vertebral artery stenosis.
Authors: Comerota A J , Maurer A H
Published: June 2011

Incapacitating vertebrobasilar insufficiency is generally associated with bilateral vertebral artery disease, whereas unilateral vertebral artery stenosis usually is clinically silent. Regional brain perfusion has not been part of the routine evaluation of patients with vertebrobasilar insufficiency. This report describes two patients who had isolated unilateral vertebral artery stenosis operatively corrected to eliminate their incapacitating vertebrobasilar insufficiency. Hindbrain hypoperfusion was identified preoperatively and evaluated postoperatively, then correlated with patient presentation and response to revascularization.

Two patients with incapacitating vertebrobasilar insufficiency presented with isolated unilateral vertebral artery stenosis with patent, nonstenotic internal carotid arteries. Hindbrain hypoperfusion was demonstrated by iodine-123-iodoamphetamine single-photon emission computed tomography preoperatively and demonstrated significant improvement following vertebral-carotid reimplantation. The patients' symptoms resolved following revascularization.

Although unusual, unilateral vertebral artery stenosis can cause incapacitating vertebrobasilar insufficiency. These cases demonstrate the value of imaging with single-photon emission computed tomography to evaluate regional brain hypoperfusion and to evaluate objectively the results of therapy.
Urgent therapy for stroke. Part I. Pilot study of tissue plasminogen activator administered within 90 minutes.
Authors: Brott T G , Haley E C , Levy D E , Barsan W , Broderick J , Sheppard G L , Spilker J , Kongable G L , Massey S , Reed R
Published: June 2011

Thrombolytic agents hold theoretical promise as therapy for cerebral infarction. This study was designed to evaluate the safety of tissue plasminogen activator, to accomplish urgent patient treatment, and to estimate potential efficacy of tissue plasminogen activator.

Following neurological evaluation and computed tomography of the brain, patients with acute ischemic stroke were evaluated and treated with intravenous tissue plasminogen activator under an open-label, dose-escalation design within 90 minutes from symptom onset. End points examined included symptomatic and asymptomatic intracranial hematoma, systemic hemorrhage, and neurological outcome at 2 hours, 24 hours, and 3 months.

Seventy-four patients were treated within 90 minutes of symptom onset over seven dose tiers of tissue plasminogen activator, ranging from 0.35 mg/kg to 1.08 mg/kg. Intracranial hematoma with associated neurological deterioration occurred in three patients and was related to increasing doses of tissue plasminogen activator (p = 0.045). Intracranial hematoma did not occur in any of the 58 patients treated with less than or equal to 0.85 mg/kg. Major neurological improvement occurred in 22 patients (30%) at 2 hours from the initiation of tissue plasminogen activator and in a total of 34 patients (46%) at 24 hours, but major neurological improvement was not related to increasing doses of tissue plasminogen activator or to stroke type.

Patients with acute stroke can be evaluated and treated within 90 minutes. Tissue plasminogen activator for acute ischemic infarction is not without risk, but the potential for clinical benefit justifies a randomized clinical trial. To date, differences in hemorrhagic risk or neurological benefit of tissue plasminogen activator for particular ischemic stroke types are not apparent.
Transesophageal echocardiographic detection of aortic arch disease in patients with cerebral infarction.
Authors: Amarenco P , Cohen A , Baudrimont M , Bousser M G
Published: June 2011

Ulcerated plaques in the aortic arch are frequent autopsy findings in patients with cerebral infarctions, particularly those of unknown cause. It has been suggested that they could be a source of cerebral emboli. Using transesophageal echocardiography, we prospectively studied 12 consecutive patients with cerebral infarction of undetermined cause after noninvasive workup to evaluate the frequency of aortic plaques or mural thrombi that could embolize in cerebral arteries.

Six patients (50%) had an intraluminal echogenic mass of the aortic arch, mainly located at the junction of the ascending aorta and arch. This material was pedunculated (in one patient) or broad based (in five patients) with a markedly irregular surface and intraluminal extension from 3 to 15 mm. In addition, we found cholesterol emboli in two of the four patients who underwent quadriceps biopsy.

These results show that transesophageal echocardiography has capabilities in detecting such lesions and point to the aortic arch as a possible source of cerebral emboli in patients with cerebral infarction of unknown cause.
Critical carotid and vertebral arterial occlusive disease and cough syncope.
Authors: Linzer M , McFarland T A , Belkin M , Caplan L
Published: June 2011

Cough syncope typically occurs in patients with known chronic lung disease. The mechanism usually involves a combination of decreased venous return, increased cerebrospinal fluid pressure, and secondary hypocapnia, all resulting in cerebral arterial vasoconstriction. Cough syncope has not in the past been associated with occlusive cerebrovascular disease.

We describe a 50-year-old man with a 6-month history of episodes of loss of consciousness during paroxysms of coughing. Physical examination showed asymmetrical upper extremity blood pressures and carotid and subclavian artery bruits. Pulmonary function studies were normal. Ultrasound and angiography showed total occlusion of the left common carotid artery, right internal carotid artery, and right vertebral artery; tight stenosis of the right subclavian artery; and a hypoplastic left vertebral artery. The patient had a left subclavian-to-left common carotid artery bypass and has had no syncope since that time.

To our knowledge, this is the first reported case of cough syncope and severe cerebrovascular disease in which surgery led to amelioration of symptoms. Cerebrovascular occlusive disease may contribute to cough syncope.
Discharge outcome after stroke rehabilitation.
Authors: Granger C V , Hamilton B B , Fiedler R C
Published: June 2011

The purpose of this study was to examine the relations between host characteristics (age and side of body affected) and program variables (lengths of stay in acute care and rehabilitation, levels of functional ability at admission and discharge, and rates of community discharge).

A sample of 7,905 patients was drawn from medical rehabilitation facilities enrolled in the Uniform Data System for Medical Rehabilitation who were admitted and discharged for the first time between January 1988 and June 1989. Data were analyzed using either chi 2 tests or z normal tests of proportions, and analyses of variance (ANOVA) and/or t tests. Significance was set at p less than 0.05, and statistically significant F ratios were examined using Student-Newman-Keuls tests.

The average age of patients was 70.7 years (24% less than 65 years, 53% 65-79 years, and 23% greater than 79 years). Lengths of stay in acute care and rehabilitation, admission and discharge functional independence ratings, and rates of community discharge were generally inversely related to patient age. Patients with bilateral paresis had lower rates of community discharge than those with unilateral paresis, although this distinction was not evident in the older group.

Results showed that older age and bilateral paresis are negatively associated with levels of independence at admission and discharge and with rates of community discharge.
Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke.
Authors: Kochanek P M , Hallenbeck J M
Published: June 2011

The extent to which polymorphonuclear leukocytes and monocytes/macrophages contribute to the pathobiology of cerebral ischemia and stroke is an issue of long-standing contradiction and controversy. Recent developments in the ability to selectively modify leukocyte adhesion with antiadhesion antibodies and the potential clinical application of this therapeutic approach have spurred a resurgence of experimental studies examining the role of leukocytes in cerebral ischemia and stroke.

We review studies examining leukocyte accumulation, initiation of thrombosis, and exacerbation of ischemic brain injury in stroke, and we examine other proposed contributions of leukocytes to cerebrovascular pathophysiology.

The importance of specific characteristics of a given ischemia model and of underlying stroke risk factors in determining the degree of leukocyte involvement and effectiveness of therapies directed against these cells is discussed.
Differentiation between different pathological cerebral embolic materials using transcranial Doppler in an in vitro model.
Authors: Markus H S , Brown M M
Published: June 2011

The detection of circulating particulate cerebral emboli using transcranial Doppler ultrasonography has been recently reported. It has been suggested that this method might allow discrimination between different embolic materials; this would be very useful for selecting specific pharmacological treatment in individual patients. This study was designed to identify those parameters of the Doppler signal that might prove useful in discriminating between different types and sizes of particulate cerebral emboli.

An extracorporeal circuit filled with a saline/Tween solution and driven by a peristaltic pump was used. The tubing was placed in a skull in the position of the middle cerebral artery. Using transcranial Doppler ultrasound, flow was insonated via the transtemporal window. The following embolic materials of measured sizes (range of maximum dimension, 0.5-5.0 mm) were introduced into the circuit: thrombus (n = 20), platelet-rich aggregates (n = 15), atheromatous material (n = 20), and fat (n = 20). The Doppler signal was recorded during the passage of each embolus. Off-line analysis was performed to measure the maximum amplitude and duration of the signal.

For all embolic materials there was a highly significant relation between embolus size and maximum amplitude of the Doppler signal. The closest correlation was obtained when the logarithm of maximum amplitude was used (for thrombi, r = 0.74; for platelet, r = 0.87; for atheroma, r = 0.46; and for fat, r = 0.68). The slope of the regression line differed for the different embolic materials and was significantly steeper for platelets than for atheroma (p < 0.01). Platelet emboli of maximum dimension < or = 1.5 mm resulted in a significantly lower maximum amplitude than similarly sized atheroma emboli (157 dB versus 206.7 dB, p < 0.01). For larger emboli (> 2 mm) there was little further increase in maximum amplitude with increases in embolus size. For all embolic materials there was a highly significant linear relation between embolus size and duration of the high-amplitude (> 150 dB) signal (for thrombi, r = 0.75; for platelet, r = 0.90; for atheroma, r = 0.77; and for fat, r = 0.86).

Platelet emboli result in lower-amplitude signals, and therefore analysis of maximum amplitude may provide information on the type of embolic material. However, it may be difficult to determine whether a given signal is associated with a large platelet embolus or a small atheroma embolus. Duration of the high-amplitude signal will allow accurate estimation of the size of emboli, particularly where the emboli are all of the same material.
Patent foramen ovale: is stroke due to paradoxical embolism?
Authors: Ranoux D , Cohen A , Cabanes L , Amarenco P , Bousser M G , Mas J L
Published: June 2011

A patent foramen ovale has been reported to be significantly more frequent in young stroke patients than in matched control subjects, and paradoxical embolism has been suggested as the main mechanism of stroke in this situation. The present study was designed to test this hypothesis.

Sixty-eight consecutive patients under 55 years of age presenting with an ischemic stroke had an extensive workup, including transesophageal echocardiography with contrast. We compared the prevalence of criteria for the diagnosis of paradoxical embolism in patients with and without a patent foramen ovale.

A patent foramen ovale was found in 32 patients (47%). A Valsalva-provoking activity was present at stroke onset in six patients with a patent foramen ovale and in eight patients with no patent foramen ovale (chi 2 = 0.1, nonsignificant). Clinical/radiological features suggestive of an embolic mechanism were not more frequent in patients with a patent foramen ovale. Clinical evidence of deep vein thrombosis was present in one patient with a patent foramen ovale and in none of the others. No occult venous thrombosis was found in a subgroup of patients with a patent foramen ovale and no definite cause for stroke who underwent venography (n = 13).

Our results do not support the hypothesis that paradoxical embolism is the primary mechanism of stroke in patients with a patent foramen ovale.