bluuebunny/crossref_metadata_2025 huggingface dataset:
Data analysis in behavioral cerebral blood flow activation studies using xenon-133 clearance.
Authors: Lagrèze H L , Hartmann A
Published: June 2011

Three mainstream strategies exist to detect the responses of regional cerebral blood flow to functional activation. We tested the significance of changes in raw regional cerebral blood flow data, regional cerebral blood flow data normalized by division by global cerebral blood flow (dependent model of the regional-to-global cerebral blood flow relation), and regional cerebral blood flow data treating global cerebral blood flow as a covariate (independent model). Both latter models attempt to enhance regional sensitivity by removing global effects. We examined the sensitivity and pitfalls of these three strategies in behavioral activation studies.

These three strategies of data analysis were applied to changes in regional cerebral blood flow induced by a visuospatial problem-solving task in 38 healthy subjects as measured by the intravenous xenon-133 method with 32 stationary detectors.

Mental activation increased blood flow in all regions of interest. Raw data were most sensitive and reliable to detect responses to mental stimulation. Both the independent and dependent models to remove global effects were less sensitive and falsely indicated deactivation in regions that were clearly stimulated.

In behavioral activation paradigms, safe data analysis should be restricted to using raw regional cerebral blood flow increases without normalization or separation of global from regional effects. Studies using complex stimulation tasks should be scrutinized for global cerebral blood flow effects confounding regional responses.
Measurement of cerebrovascular changes in cats after transient ischemia using dynamic magnetic resonance imaging.
Authors: Hamberg L M , Macfarlane R , Tasdemiroglu E , Boccalini P , Hunter G J , Belliveau J W , Moskowitz M A , Rosen B R
Published: June 2011

Hemodynamic changes associated with acute ischemia cannot be measured with conventional nuclear magnetic resonance imaging. In this study, we used dynamic susceptibility-contrast magnetic resonance imaging to measure the changes in vascular transit time and relative cerebral blood volume in a feline occlusion-reperfusion model.

Dynamic susceptibility-contrast measurements were obtained before and during 10 minutes of global cerebral ischemia and for up to 3 hours after the onset of reperfusion. A cerebral blood flow index was calculated from the vascular transit time and relative cerebral blood volume measurements. Functional maps were constructed to demonstrate the regional hemodynamic differences resulting from the induced ischemia.

During the early phase after reperfusion, both the relative cerebral blood volume and blood flow index rose sharply, followed by a fall to near-basal levels at 45 minutes (1 x control and 1.3 x control, respectively). Thereafter, the volume rose slowly, whereas the flow index continued to drop. At 3 hours, cerebral blood volume had reached 1.6 times its control value, whereas the flow index had returned to its base value.

The hemodynamic behavior we observed in our model reflects the independent responses of the cerebral blood volume and flow index to ischemic insult. Measurements acquired by our method were consistent with the temporal behavior reported in previous radionuclide studies. Susceptibility-contrast nuclear magnetic resonance tomographic imaging proved to be valuable in detecting and quantifying both immediate and subsequent changes in the hemodynamic state of the ischemic and hyperemic feline brain.
Effects of repeated cerebral ischemia on extracellular amino acid concentrations measured with intracerebral microdialysis in the gerbil hippocampus.
Authors: Nakata N , Kato H , Kogure K
Published: June 2011

To clarify the role of elevated extracellular amino acid concentrations during ischemia on the cumulative neuronal damage after repeated cerebral ischemic insults, using a microdialysis technique we measured concentrations of the amino acids glutamate, glutamine, glycine, taurine, and gamma-aminobutyric acid in the gerbil hippocampus over three 2-minute forebrain ischemic insults induced at 1-hour intervals.

Under light anesthesia, the bilateral common carotid arteries were occluded with aneurysm clips at 1-hour intervals. Samples were collected by microdialysis at 10-minute intervals, and the amino acid concentrations were determined using a high-performance liquid chromatography system.

During and immediately after the first ischemic insult, concentrations of glutamate, glycine, and taurine, but not glutamine, increased significantly. Glutamate and taurine concentrations rose again during the second and third ischemic insults, but the increases were smaller than those during the first insult. By contrast, glutamine concentrations increased slightly but significantly during the second and third ischemic insults. The extracellular concentration of gamma-aminobutyric acid before the ischemic insults was below the level of detectability but increased markedly during each ischemic insult, with similar declines in the amounts released during later insults. Concentrations of all amino acids returned to baseline after 10 minutes of reperfusion and remained at baseline until the subsequent ischemic insult was induced.

It is well established that glutamate released during ischemia plays a crucial role in ischemia-induced neuronal death. However, the present results indicate that cumulative neuronal damage following sublethal ischemic insults is not caused by an exaggerated release of excitatory amino acids during subsequent ischemic insults but strongly suggest that increased intracellular reactions leading to cell death play a major role.
Myocardial infarction, thrombolytic therapy, and stroke. A community-based study. The MITI Project Group.
Authors: Longstreth W T , Litwin P E , Weaver W D
Published: June 2011

Thrombolytic therapy used in patients with acute myocardial infarction may increase the risk of stroke. Scant information is available from community-based studies.

Among 5,635 consecutive patients admitted with acute myocardial infarction to hospitals in Seattle and surrounding suburban King County, Washington, 116 (2.1%) experienced strokes during hospitalization. Of these strokes, 82 (71%) were ischemic and 34 (29%) were hemorrhagic, defined by a patient's having had a computed tomographic scan of the head that showed blood. Thrombolytic therapy was given to 1,413 of these patients (25%) and was associated with increased risk of hemorrhagic stroke but reduced risk of ischemic stroke. The relative risk of stroke with thrombolytic therapy was estimate using multiple logistic regression to adjust for potential confounding factors. The adjusted relative risk for hemorrhagic stroke was 3.6 (95% confidence interval [CI], 1.7-8.0); for ischemic stroke, 0.4 (95% CI, 0.2-0.9); and for overall stroke, 1.0 (95% CI, 0.6-1.7). The adjusted risk for death from any cause following stroke was 3.0 (95% CI, 1.4-6.4).

Although thrombolytic therapy had little effect on the overall occurrence of stroke, thrombolytic therapy increased the risk of stroke death because more patients with hemorrhagic than ischemic strokes died during their hospitalization. The rates of hemorrhagic stroke with thrombolytic therapy reported in the present study are higher than those reported in clinical trials in which treatment is given to select patients under strict protocols.
An unusual cause of cerebral venous thrombosis in a four-year-old child.
Authors: Rich C , Gill J C , Wernick S , Konkol R J
Published: June 2011

Inherited protein S deficiency has been associated with an increased risk of thromboembolic disease. It is possible that such a coagulopathy could predispose children to the development of strokes by permitting clot formation in response to stimuli that ordinarily would be insufficient to cause thrombus formation.

We evaluated a previously well 4-year-old boy who developed cerebral venous thrombosis after suffering minor head trauma. Crossed-immunoelectrophoresis of his plasma showed a marked decrease of the free, active form of protein S. Family studies revealed that the patient's father and other paternal relatives had a similar abnormality of protein S.

We suggest that the cerebral venous thrombosis in this child was initially precipitated by minor head trauma and pathological thrombus formation was then potentiated by inherited protein S deficiency. This case extends the clinical spectrum for protein S deficiency and emphasizes the importance of evaluating family members to establish a specific diagnosis and therapeutic intervention.
Prevalence of apolipoprotein E phenotypes in ischemic cerebrovascular disease. A case-control study.
Authors: Couderc R , Mahieux F , Bailleul S , Fenelon G , Mary R , Fermanian J
Published: June 2011

Apolipoprotein E polymorphism may influence the early development of coronary artery disease. We investigated the putative role of apolipoprotein E phenotypes in cerebral infarction.

The apolipoprotein E phenotypes of 69 patients (mean +/- SD age, 72 +/- 11 years) who had suffered completed stroke or a transient ischemic attack and 68 sex- and age-matched control subjects free of cerebrovascular disease were determined by isoelectric focusing. The relative frequency of the apolipoprotein E phenotypes in the general population was estimated in 498 healthy blood donors (mean age, 37 years).

The prevalences of hypertension, diabetes mellitus, obesity, and intermittent claudication were significantly higher in patients than in control subjects. Serum lipid and apolipoprotein B concentrations and the composition of very low density lipoproteins were not significantly different between patients and control subjects. Apolipoprotein A-I and E levels were significantly lower in patients. Cholesterol levels were higher in male patients than in male control subjects (5.10 +/- 1.46 versus 4.41 +/- 0.80 mmol/L; p = 0.036), and the ratio of apolipoprotein A-I to B was lower (0.77 +/- 0.29 versus 1.03 +/- 0.37; p < 0.001). The E3/E3 phenotype was more frequent in control subjects (85%) than in patients (72.5%; p < 0.05) and healthy blood donors (64%; p < 0.02). The E3/E2 phenotype was more frequent in patients (10.1%) than in control subjects (1.4%; p < 0.05). A stepwise logistic regression showed that the presence of stroke was significantly related to high blood pressure (p < 0.0001), low apo E levels (p < 0.008), obesity (p < 0.041), the apo E phenotype (p < 0.05), and diabetes mellitus (p < 0.05).

The E3/E3 phenotype may protect against early vascular morbidity, and the epsilon 2 gene may be a risk factor for cerebrovascular morbidity, possibly related to diabetes, hypertension, and/or obesity.
Reactivity of cerebral blood flow to carbon dioxide in various types of ischemic cerebrovascular disease: evaluation by the transcranial Doppler method.
Authors: Maeda H , Matsumoto M , Handa N , Hougaku H , Ogawa S , Itoh T , Tsukamoto Y , Kamada T
Published: June 2011

The response of cerebral blood flow to changes in the arterial carbon dioxide partial pressure (i.e., carbon dioxide reactivity) has been evaluated as a parameter of cerebral perfusion reserve in patients with cerebrovascular disease. In this study, variations in this reactivity in various ischemic cerebrovascular diseases were evaluated by a newly established method, a transcranial Doppler technique.

Thirty-three patients with symptomatic cerebrovascular disease, 13 patients with asymptomatic cerebral infarction, and 25 age-matched normal control subjects were investigated. The symptomatic patients were divided into three groups; those with unilateral carotid artery obstruction, those with cortical infarction, and those with lacunar infarction. The carbon dioxide reactivity of each subject was determined by simultaneously measuring the mean spatial Doppler frequency in the middle cerebral artery and the end-tidal carbon dioxide partial pressure under normocapnic, hypercapnic, and hypocapnic conditions.

In the patients with carotid obstruction, the carbon dioxide reactivity of the hemisphere ipsilateral to the obstruction was more impaired than the reactivity of the symptomatic hemispheres in any other group, and was significantly less than in the contralateral asymptomatic hemisphere (p < 0.01). In patients with cortical infarction, the carbon dioxide reactivity of the symptomatic hemisphere was significantly less than in normal control subjects (p < 0.05) and was also less than that of the contralateral asymptomatic hemisphere (p < 0.05). In patients with lacunar infarction, the carbon dioxide reactivity of both hemispheres was significantly less than that in normal controls (p < 0.01), although there was no difference between the symptomatic and asymptomatic hemispheres. In patients with asymptomatic infarction, the carbon dioxide reactivity was also less than that in normal controls (p < 0.01).

The carbon dioxide reactivity of cerebral blood flow measured by this transcranial Doppler technique may be useful for characterizing the hemodynamic changes that occur in various types of ischemic cerebrovascular disease.
Effect of the 21-aminosteroid tirilazad on cerebral pH and somatosensory evoked potentials after incomplete ischemia.
Authors: Maruki Y , Koehler R C , Kirsch J R , Blizzard K K , Traystman R J
Published: June 2011

Postischemic evoked potential recovery correlates with acidosis during ischemia and early reperfusion. Acidosis promotes lipid peroxidation in vitro. We tested the hypothesis that the 21-aminosteroid tirilazad mesylate (U74006F), an inhibitor of lipid peroxidation in vitro, ameliorates somatosensory evoked potential recovery and acidosis during reperfusion after severe incomplete cerebral ischemia.

Cerebral perfusion pressure was reduced to 11 +/- 1 mm Hg (+/- SEM) for 30 minutes by cerebral ventricular fluid infusion in anesthetized dogs. Cerebral intracellular pH and high-energy phosphates were measured by magnetic resonance spectroscopy. Dogs were randomized to receive vehicle (citrate buffer; n = 8) or tirilazad (1 mg/kg; n = 8) before ischemia in a blinded study.

Cerebral blood flow was reduced to 6 +/- 1 mL/min per 100 g during ischemia, resulting in nearly complete loss of high-energy phosphates and an intracellular pH of 6.0-6.1 in both groups. Initial postischemic hyperemia was similar between groups but lasted longer in the vehicle group. Tirilazad accelerated mean recovery time of intracellular pH from 31 +/- 5 to 15 +/- 3 minutes and of inorganic phosphate from 13 +/- 2 to 6 +/- 1 minutes. Recovery of somatosensory evoked potential amplitude was greater with tirilazad (49 +/- 3%) than vehicle (33 +/- 6%). Fractional cortical water content was less with tirilazad (0.819 +/- 0.003) than vehicle (0.831 +/- 0.002).

Tirilazad attenuates cerebral edema and improves somatosensory evoked potential recovery after incomplete ischemia associated with severe acidosis. Accelerated pH and inorganic phosphate recovery indicates that this antioxidant acts during the early minutes of reperfusion.
Suppression of protein synthesis in the reperfused brain.
Authors: Krause G S , Tiffany B R
Published: June 2011

Brain ischemia and reperfusion produce profound protein synthesis alterations, the extent and persistence of which are dependent on the nature of the ischemia, the brain region, the cell layer within a region, and the particular proteins studied. After transient ischemia, most brain regions recover their protein synthesis capability; however, recovery in the selectively vulnerable areas is poor. It is unknown whether this phenomenon itself provokes or is a consequence of the process of neuronal death.

Protein synthesis suppression during ischemia is due to energy depletion, but this is quickly reversed upon recirculation. Reperfusion does not appear to damage DNA or transcription mechanisms, although there are changes in the profile of transcripts being made. Similarly, purified ribosomes isolated from reperfused brains can make the normal repertoire of proteins and heat-shock proteins. However, during early reperfusion, newly synthesized messenger RNAs appear to accumulate in the nucleus; this alteration in RNA handling could reflect disruption at any of several steps, including posttranscriptional processing, nuclear pore transport, cytoskeletal binding, or formation of the translation initiation complex. Another mechanism that may be responsible for protein synthesis suppression during late reperfusion is progressive membrane destruction, with consequent shifts in the concentration of ions crucial for ribosomal function.

Protein synthesis suppression after ischemia likely involves a progression of multiple mechanisms during reperfusion. Although the recent work reviewed here offers new insight into the potential mechanisms disrupting protein synthesis, detailed understanding will require further investigation.
Pattern of cerebral atherosclerosis in Hong Kong Chinese. Severity in intracranial and extracranial vessels.
Authors: Leung S Y , Ng T H , Yuen S T , Lauder I J , Ho F C
Published: June 2011

The clinical pattern of stroke and the angiographic distribution of cerebral atherosclerosis in Chinese are different from those in Caucasians. Pathological data from autopsy studies are lacking.

The intracranial and extracranial arteries supplying the brains of 114 consecutive Chinese patients undergoing autopsy in a regional general hospital were examined by computer-assisted morphometric analysis under a microscope as well as by macroscopic grading for atherosclerotic narrowing. The severity was correlated with various atherosclerosis-related factors.

Atherosclerosis of the intracranial cerebral vessels was more severe than that of the extracranial vessels. The distal branches of the intracranial vessels were also commonly involved. Hypertension and diabetes mellitus were identified as factors associated only with intracranial atherosclerosis (p < 0.001), whereas ischemic heart disease was associated with atherosclerosis in both the intracranial (p < 0.001) and extracranial (p = 0.012) vessels. Smoking was associated with narrowing of the extracranial vessels only (p = 0.0054).

Compared with figures from Caucasian and Japanese populations, the extent of intracranial atherosclerosis is much more severe in Hong Kong Chinese, whereas atherosclerotic narrowing of the extracranial carotid artery is less severe in Hong Kong Chinese than in Caucasians.
Paw-reaching, sensorimotor, and rotational behavior after brain infarction in rats.
Authors: Grabowski M , Brundin P , Johansson B B
Published: June 2011

Functional tests that are stable and consistent over time are an advantage for long-term evaluation of treatment in experimental stroke research. Because little information on this subject is available in rodents with focal cerebral ischemia, we investigated the outcome of three behavioral tests for a period of 3 months after the insult.

Spontaneously hypertensive rats were sham-operated (n = 27) or underwent an occlusion (n = 36) of the right middle cerebral artery. Before surgery all rats were tested for amphetamine-induced rotational behavior, and half of the rats were trained in a paw-reaching task. One, 2, and 3 months after surgery the tests were repeated, together with a test for sensorimotor function. Infarct size was measured morphometrically.

In the lesion group, total hemisphere area was reduced by 22%, caudate putamen by 47%, and the thalamus by 24%. Contralateral to the lesion, paw-reaching was highly impaired, regardless of whether or not the rats had been pretrained, and lesion size correlated significantly to paw-reach performance. Ipsilateral rotation increased and sensorimotor function recovered with time in infarcted rats.

In contrast to amphetamine-induced rotation and sensorimotor behavior, the paw-reaching test provides a stable behavioral parameter after a middle cerebral artery occlusion. Moreover, the lesion-induced deficit in paw-reaching is highly correlated to the extent of the infarct, suggesting that this test is useful in evaluating treatment effects for a longer period of time.
A case of tinnitus and hearing loss after cerebellar hemorrhage.
Authors: Matsuda Y , Inagawa T , Amano T
Published: June 2011

Approximately 10% of cases of hypertensive intracerebral hemorrhage are cerebellar hemorrhage. We report a case of intracerebellar hemorrhage in which the initial symptoms were hearing loss and tinnitus.

A 45-year-old man suddenly complained of hearing loss and tinnitus on the right side. Computed tomography demonstrated a high-density area 1.2 cm in diameter in the right cerebellar peduncle. Because of enlargement of the high-density area, the patient underwent surgery based on the diagnosis of hypertensive intracerebellar hemorrhage, and the hematoma was evacuated. The right-sided acoustic nerve was remarkably swollen by a subpial hematoma.

In this case, hemorrhage of the right cerebellar peduncle extended to the eighth nerve through the subpial space, causing hearing loss and tinnitus.
Left atrial spontaneous echo contrast is highly associated with previous stroke in patients with atrial fibrillation or mitral stenosis.
Authors: Chimowitz M I , DeGeorgia M A , Poole R M , Hepner A , Armstrong W M
Published: June 2011

Spontaneous echo contrast is a dynamic smokelike signal that is detected by transesophageal echocardiography in patients with stasis of blood in the left atrium. We designed this study to determine if spontaneous echo contrast is associated with an increased risk of previous stroke or peripheral embolism.

Forty-two patients with spontaneous echo contrast were identified (34 had atrial fibrillation or mitral stenosis; 8 had neither). Control subjects comprised 40 patients randomly selected from patients with atrial fibrillation or mitral stenosis who did not have spontaneous echo contrast at transesophageal echocardiography. The frequency of vascular risk factors, echocardiographic features, and stroke or peripheral embolism within 1 year of echocardiography were compared in the two groups.

The frequency of traditional risk factors for stroke were the same in both groups, yet 9 of 42 patients with spontaneous contrast had stroke or peripheral embolism compared with only 1 of 40 control subjects (P < .02; relative risk, 10.6; 95% confidence interval, 1.3 to 88.4). In patients with nonvalvular atrial fibrillation, 6 of 12 patients with spontaneous contrast had a stroke or peripheral embolism compared with 1 of 28 patients without spontaneous contrast (P < .001; relative risk, 27.0; 95% confidence interval, 2.7 to 267.8).

Spontaneous echo contrast is highly associated with previous stroke or peripheral embolism in patients with atrial fibrillation or mitral stenosis. Transesophageal echocardiography may enable stratification of cardioembolic risk in patients with nonvalvular atrial fibrillation.
BW619C89, a glutamate release inhibitor, protects against focal cerebral ischemic damage.
Authors: Leach M J , Swan J H , Eisenthal D , Dopson M , Nobbs M
Published: June 2011

The excitatory amino acid neurotransmitter glutamate is involved in excitotoxic brain injury and neurodegeneration after cerebral ischemia. Therefore, compounds that block the release of glutamate may be useful as cerebroprotective agents. The purpose of this study was to evaluate the cerebroprotective properties of a glutamate release inhibitor, BW619C89.

In the studies reported here, the effect of BW619C89 [4-amino-2-(4-methyl-1-piperazinyl)-5-(2,3,5-trichlorophenyl)pyrimidine] on neurotransmitter release (endogenous amino acids, gamma-aminobutyric acid, and acetylcholine) from slices of rat brain cerebral cortex in vitro has been determined. The neuroprotective efficacy of BW619C89 has been evaluated using the middle cerebral artery occlusion model of focal cerebral ischemia in the Fischer 344 rat.

In the in vitro studies, BW619C89 inhibited veratrine- (but not potassium-) evoked release of both endogenous glutamate and aspartate from rat cerebral cortex slices with IC50 values of approximately 5 microM. BW619C89 was approximately 10-fold less potent to inhibit veratrine-evoked 3H-gamma-aminobutyric acid release (IC50 = 51 microM), fourfold less potent to inhibit 3H-acetylcholine release (IC50 = 21 microM), and at 10 microM had only weak activity at excitatory amino acid (N-methyl-D-aspartate, kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) binding sites. When administered intravenously to Fischer 344 rats 5 minutes after permanent middle cerebral artery occlusion, BW619C89 produced marked reductions of both total (cortex and basal ganglia) and cortical infarct volumes. Cortical infarct size was reduced by 20% at a dose of BW619C89 of 5 mg/kg (n = 6, not significant); 43% at 10 mg/kg (n = 8, P < .01); 59% at 20 mg/kg (n = 8, P < .001); 61% at 30 mg/kg (n = 8, P < .001), and 53% at 40 mg/kg (n = 8, P < .001). BW619C89 at doses of 20 and 30 mg/kg also significantly reduced noncortical (basal ganglia) infarct volumes, demonstrating that a proportion of this tissue also appears to be salvageable. Behavioral effects observed were dose related, generally minor, and at doses of 20 mg/kg IV and above consisted of body tremor and mild ataxia lasting approximately 2 hours.

These results suggest that glutamate release inhibitors such as BW619C89 may provide an alternative to excitatory amino acid receptor antagonists in the treatment of focal cerebral ischemia and stroke.
Associations of serum total cholesterol, different types of stroke, and stenosis distribution of cerebral arteries. The Akita Pathology Study.
Authors: Konishi M , Iso H , Komachi Y , Iida M , Shimamoto T , Jacobs D R , Terao A , Baba S , Sankai T , Ito M
Published: June 2011

The relation between serum total cholesterol levels and stroke is controversial. The Akita Pathology Study provides data on the association of serum total cholesterol, different types of stroke, and distribution of stenosis in cerebral arteries.

The data are based on 750 autopsied men aged 30 years and older who were admitted to a local hospital in northeast Japan between 1966 and 1984. The overall autopsy rate was 88%. The grade of stenosis in the cerebral arteries was determined blindly by one pathologist using Baker's method for basal cerebral arteries (atherosclerosis scores) and using microscopic examination of a single basal ganglion slide for the intracerebral penetrating arteries (arteriolosclerosis scores).

The age-adjusted mean value of serum total cholesterol concentration was 164 mg/dL for cerebral hemorrhage, 177 mg/dL for infarction in penetrating artery regions, and 200 mg/dL for infarction in cortical artery regions. Mean serum cholesterol was lower in deaths caused by cerebral hemorrhage than in those caused by myocardial infarction and other cardiovascular disease. Mean atherosclerosis score of basal cerebral arteries was low for cerebral hemorrhage, intermediate for penetrating artery infarction, and high for cortical artery infarction. Stenosis of both basal and penetrating arteries was minimum or absent in cases of cerebral hemorrhage. Only the basal arteries were stenotic in cases of cortical artery infarction, whereas both basal and penetrating arteries were stenosed in cases of penetrating artery infarction. There were positive associations of serum cholesterol with stenosis of basal and penetrating arteries. Among cases of cerebral hemorrhage, serum total cholesterol levels were even lower in men with no significant stenosis in either basal or penetrating arteries than in men with stenosis in either type of artery.

The association of serum cholesterol with pathogenesis varies among stroke types. Elevated serum cholesterol levels were associated with the presence of cortical artery infarction, while low serum cholesterol levels were associated with cerebral hemorrhage.
High serum lipoprotein(a) levels are an independent risk factor for cerebral infarction.
Authors: Shintani S , Kikuchi S , Hamaguchi H , Shiigai T
Published: June 2011

This study was conducted to evaluate the role of high serum lipoprotein(a) levels in a group of patients with a relatively early onset of cerebral infarction as a whole and in a subgroup with the perforating artery occlusion subtype of cerebral infarction.

Fifty-four patients with cerebral infarction, the onset of which was before age 65 years (37 men, 17 women; mean age, 61.9 +/- 7.7 years) were examined in this study. When patients with atrial fibrillation were excluded to omit cardiac embolic strokes from analysis, the group consisted of 45 patients. The patients were classified into two subtype groups, the perforating artery occlusion group and the cortical artery occlusion group, by using magnetic resonance imaging. Lipoprotein(a) levels were measured by an enzyme-linked immunosorbent assay. Four biochemical variables (serum levels of lipoprotein(a), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides) and other potential risk factors such as hypertension, diabetes mellitus, smoking habits, alcohol intake, and family history were analyzed by stepwise logistic regression to determine the independent and significant risk factors for cerebral infarction without atrial fibrillation.

The incidence of subjects with serum lipoprotein(a) levels > or = 42.6 mg/dL, which is the 95th percentile level of the control subjects, was significantly increased in the total cerebral infarction group (P < .025) and the perforating artery occlusion group (P < .025) compared with the control group. In addition, by using stepwise logistic regression analysis in the total and perforating artery occlusion patient groups we identified three independent and significant risk factors: hypertension, a low high-density lipoprotein cholesterol level, and a high serum lipoprotein(a) level. In the cortical artery occlusion group, the sample size was not large enough for the statistical analysis. Diabetes mellitus is the only known factor that correlates with serum lipoprotein(a) levels, but there were no significant correlations between serum lipoprotein(a) levels and history of diabetes mellitus or fasting blood sugar.

These findings indicate that high serum lipoprotein(a) levels are an independent risk factor in the development of cerebral infarction when subjects with atrial fibrillation were excluded from the total group and the perforating artery occlusion subtype group.
Fibrinogen and the albumin-globulin ratio in recurrent stroke.
Authors: Beamer N , Coull B M , Sexton G , de Garmo P , Knox R , Seaman G
Published: June 2011

In following patients initially recruited for a cross-sectional study of blood viscosity in ischemic cerebrovascular disease, it was noted that those having a low albumin-globulin ratio appeared to experience the majority of subsequent vascular events. Accordingly, a prospective study in which subjects were assigned to a high or low albumin-globulin cohort was undertaken to examine the relation between a low albumin-globulin ratio, the presence of clinical risk factors for stroke, and the occurrence of subsequent stroke, myocardial infarction, or vascular death.

Three groups of subjects were followed for an average of 1.5 +/- 0.8 years to ascertain vascular end points. Group 1 consisted of 126 patients with acute ischemic stroke; group 2 included 109 subjects matched with group 1 for age, medications, and recognized clinical risk factors for stroke; and group 3 was composed of 84 healthy volunteers, matched for age with groups 1 and 2. The median albumin-globulin ratio for group 1 at enrollment, 1.45, was used to dichotomize patients into two cohorts: all subjects with an albumin-globulin ratio of 1.45 or less were assigned to the "low" albumin-globulin cohort; those whose ratio was greater than 1.45 were assigned to the "high" albumin-globulin cohort. The occurrence of vascular end points was verified during subsequent hospitalizations and outpatient clinic visits and by telephone interviews of patients and providers.

A total of 51 vascular events occurred, including 39 in group 1, 8 in group 2, and 4 in group 3. Subjects in either group 1 or 2 who were in the low albumin-globulin cohort had at least double the risk for a subsequent vascular event compared with their counterparts in the high albumin-globulin cohort (P < .01 and P < .03, respectively). In comparison with the high albumin-globulin cohort, significantly more patients in the low albumin-globulin cohort in group 1 had a history of prior stroke (P < .03). When groups 1 and 2 were combined, both a low albumin-globulin ratio and diabetes had a significant independent association with increased risk for subsequent vascular events in a Cox proportional-hazards model (P < .01 and P < .03, respectively).

The results of this study indicate that significantly increased risk for subsequent vascular events in stroke patients and in subjects with clinical risk factors for stroke is associated with a shift in the concentrations of blood proteins to a prothrombotic environment characterized by lower levels of albumin and an increased concentration of globulins and fibrinogen.
Factors influencing return to work after stroke in Japan.
Authors: Saeki S , Ogata H , Okubo T , Takahashi K , Hoshuyama T
Published: June 2011

Few studies have identified factors that predict return to work after stroke in Japan. Our aim in this study was to determine the predictors of return to work after stroke in Japan.

We performed a retrospective cohort study on the association between patients' characteristics at admission and return to work in 230 first-stroke patients, adjusting for potential confounding factors. The patients were all aged younger than 65 years and were working, students, or housewives at the time of their stroke. Return to work was evaluated by a follow-up questionnaire. Data were analyzed using forward logistic regression analysis to compute odds ratios of return to work.

The adjusted odds ratios (and 95% confidence intervals) for patients with normal muscle strength vs severe muscle weakness, without apraxia vs with apraxia, and with white-collar vs blue-collar occupation were 4.50 (1.04 to 19.42), 4.87 (1.28 to 18.54), and 3.33 (1.34 to 8.30), respectively.

Significant predictors of return to work after stroke were no muscle weakness, absence of apraxia, and white-collar occupation.
The effects of long-term rehabilitation therapy on poststroke hemiplegic patients.
Authors: Dam M , Tonin P , Casson S , Ermani M , Pizzolato G , Iaia V , Battistin L
Published: June 2011

Rehabilitation therapy is believed to be useful during the first few months after stroke when recovery usually takes place. However, evidence exists that this may not be the rule for all stroke victims. Therefore, we investigated, in a selected group of poststroke patients, the profile of recovery in response to long-term rehabilitation therapy.

Fifty-one hemiplegic subjects unable to walk 3 months after stroke were enrolled in this study. Patients underwent consecutive periods of rehabilitation up to 2 years after the cerebrovascular accident. Autonomy in daily living activities and the degree of neurological compromission were periodically assessed with the Barthel Index and a neurological scale designed for hemiplegic subjects. The main features of the patients were also evaluated as a possible predictor of outcome.

In a consistent percentage of the patients, significant gains in gait and daily living abilities were observed during the first year and, in individual cases, during the second year after stroke. At the end of the study, 74% of the patients regained their capacity to walk without assistance, and up to 79% had a Barthel Index score above 70. Sphincter function, level of neurological impairments, and capacity in daily living activities are significantly related to the outcome of the patients as a whole but were not useful to anticipate the outcome of each patient.

These results suggest that disabled poststroke subjects may attain significative functional improvements in response to prolonged restorative therapy. However, the possibility of predicting the outcome of individual patients appears the major problem to solve in order to assign to long-term rehabilitation programs only patients who will benefit from the therapy.
The effects of hypertension on cerebral atherosclerosis in the cynomolgus monkey.
Authors: Hollander W , Prusty S , Kemper T , Rosene D L , Moss M B
Published: June 2011

There is substantial clinical, pathological, and experimental evidence that hypertension aggravates atherosclerosis of the extracranial vessels. The present study assesses the effects of hypertension on the development of cerebral atherosclerosis in nonhuman primates fed an atherogenic diet.

The extent and severity of cerebral atherosclerosis were evaluated morphologically, morphometrically, and biochemically in atherosclerotic monkeys with and without hypertension. Atherosclerosis was induced by feeding a hypercholesterolemic diet for 12 months; hypertension was produced by surgical coarctation of the thoracic aorta.

At autopsy, gross atherosclerotic lesions of the major cerebral arteries were observed in 15 of 16 atherosclerotic monkeys with hypertension compared with 5 of 16 atherosclerotic animals without hypertension. In the hypertensive-atherosclerotic group, 38.5% of the vessels examined showed gross involvement compared with only 3.4% of the vessels involved in the atherosclerotic group (P < .001). The lesions in the atherosclerotic group were generally mild, whereas those in the hypertensive-atherosclerotic group were severe and resulted in significant luminal narrowing and occlusion of vessels (P < .001). The small branches of the cerebral arteries also showed severe disease with luminal obstruction in the hypertensive-atherosclerotic group. The extent and severity of cerebral atherosclerosis were significantly related to the severity of the hypertension (P < .05).

Hypertension is an important factor in cerebral atherosclerosis because of its accelerating effect on the disease. Nonhuman primate models may be useful in clarifying the role of hypertension and atherosclerosis in cerebral vascular disease.
Cocaine-induced platelet defects.
Authors: Jennings L K , White M M , Sauer C M , Mauer A M , Robertson J T
Published: June 2011

Numerous studies have demonstrated an association between acute cardiac events, cerebrovascular accidents, and cocaine use. The underlying mechanisms leading to these complications have not been well defined. Using various in vitro model systems, it has been reported that cocaine, up to or greater than an order of magnitude of the lethal dose, causes either inhibitory or proaggregatory effects on platelet function.

To address these reported discrepancies, we examined the effect of cocaine and its carrier on the activation and aggregation of human platelets in vitro.

We found that cocaine inhibited platelet aggregation when platelets were challenged with ADP, collagen, or arachidonic acid. This inhibition was due to a direct effect on fibrinogen binding to the activated platelet. Cocaine also caused the dissociation of preformed platelet aggregates. At these same concentrations, cocaine did not inhibit agonist-mediated increases in cytosolic calcium or inhibit platelet shape change, suggesting that its effect on platelet aggregation was a selective process and not due to a total destruction of platelet function. Interestingly, the organization of the cytoskeleton of activated platelets, a secondary event critical to cell receptor clustering and clot retraction, was disrupted by cocaine treatment. In addition, alterations in platelet protein electrophoretic patterns were observed on preincubation of platelets with cocaine.

We conclude that cocaine may have a direct inhibitory effect on the ability of platelets to participate in thrombus formation. The contribution of this effect as an underlying mechanism of sudden death in cocaine abusers is unknown.
The prognostic value of admission blood pressure in patients with acute stroke.
Authors: Carlberg B , Asplund K , Hägg E
Published: June 2011

Patients with acute stroke are often found to have high blood pressures at hospital admission. Previous studies have shown variable results regarding the prognostic value of high blood pressure in acute stroke. The aim of this study was to investigate the prognostic value of admission blood pressure in a population-based sample of patients with acute stroke.

Eighty-five patients with intracerebral hemorrhage and 831 with ischemic disease were included in the study. The relations between admission blood pressure and 30-day mortality were studied by logistic regression analyses.

High blood pressure in patients with impaired consciousness on hospital admission was significantly related to 30-day mortality in patients with intracerebral hemorrhage (P = .037) and in patients with ischemic disease (P < .0001). In patients without impaired consciousness, high blood pressure at time of admission was not related to increased mortality at 30 days.

High admission blood pressure in alert stroke patients was not related to increased mortality. Stroke patients with impaired consciousness showed higher mortality rates with increasing blood pressure. However, this does not provide a basis for recommending antihypertensive therapy for such patients.
Screening for neuroborreliosis in patients with stroke.
Authors: Hammers-Berggren S , Gröndahl A , Karlsson M , von Arbin M , Carlsson A , Stiernstedt G
Published: June 2011

Borrelia burgdorferi, the etiologic agent of Lyme disease, can cause different neurological manifestations. We studied the prevalence of Lyme neuroborreliosis in patients with stroke.

During a 1-year period, sera from patients with cerebral thrombosis or transient ischemic attack without cardioembolism were investigated for antibodies against B burgdorferi.

One of 281 patients had a positive serum immunoglobulin M titer and 23 of 281 (8%) had positive serum immunoglobulin G titers against B burgdorferi. One of the 24 seropositive patients, with a diagnosis of transient ischemic attack due to dysphasia, had a lymphocytic pleocytosis and intrathecal antibody production against B burgdorferi. The medical history revealed a 9-month period of general and neurological symptoms compatible with Lyme neuroborreliosis before the strokelike incidents.

We conclude that Lyme neuroborreliosis may imitate stroke, but screening for antibodies against B burgdorferi seems to be of little value and may be replaced by a careful medical history.
Subcortical infarction in children.
Authors: Powell F C , Hanigan W C , McCluney K W
Published: June 2011

This report examines the occurrence of subcortical infarction in 5 children, reviews the English literature, and discusses evaluation of this uncommon childhood illness.

Clinical characteristics and neurological follow-up were examined in children who presented with subcortical infarction within the past 7 years. The English literature over the previous 20 years was reviewed to identify similar patients with radiological documentation of subcortical infarction.

Mean age of the patients in this series was 4.8 years (range, 4 months to 12 years); 3 children were female. Three patients presented with the sudden onset of hemiparesis, 1 with dystonia, and 1 with fever and focal seizures. Protein C deficiencies were demonstrated in 2 children; a cardiomyopathy was seen in 1 patient. Mean follow-up was 1.5 years. Two patients were neurologically normal, mild residual symptoms persisted in 2, and 1 patient showed severe dystonia. The literature analysis indicated that specific risk factors were described in 79 patients; complete clinical analysis was available for 51 patients. In the latter group, the mean age was 5.7 years; 26 children were female. Forty-six presented with hemiplegia, 4 with dystonia, and 1 with focal seizures. Follow-up greater than 5 months in 29 patients showed complete or good resolution of deficits in 23. Specific risk factors such as infection, trauma, hematologic disorders, or cardiac or vascular abnormalities were identified in 62 of 79 children.

This analysis indicates that children with subcortical infarction usually presented with acute hemiparesis. Risk factors were identified in the majority of children, and follow-up demonstrated good or complete resolution of neurological deficits in 80% of the patients.
Responses of cerebral arterioles to activation of beta-adrenergic receptors during diabetes mellitus.
Authors: Mayhan W G
Published: June 2011

Diabetes mellitus impairs reactivity of large peripheral arteries and arterioles to activation of beta-adrenergic receptors. The goal of this study was to determine whether diabetes mellitus alters dilatation of cerebral arterioles to activation of beta-adrenergic receptors.

In vivo diameter of pial arterioles was measured in nondiabetic and diabetic (streptozotocin 50 to 60 mg/kg IP) rats during superfusion with isoproterenol, forskolin, and nitroglycerin. In addition, we examined the contribution of nitric oxide or a nitric oxide-containing compound in dilatation of pial arterioles in response to the agonists.

Dilatation of pial arterioles in response to isoproterenol was significantly less in diabetic compared with nondiabetic rats (3 +/- 2% versus 14 +/- 1%, respectively, for 1.0 mumol/L isoproterenol). In contrast, dilatation of pial arterioles in response to nitroglycerin and forskolin was similar in nondiabetic and diabetic rats. Furthermore, dilatation of pial arterioles in nondiabetic rats in response to isoproterenol and forskolin was not related to the synthesis and release of nitric oxide or a nitric oxide-containing compound.

The findings of the present studies suggest that diabetes mellitus impairs dilatation of cerebral resistance arterioles in response to activation of beta-adrenergic receptors. Impairment of beta-adrenergic-mediated dilatation of cerebral arterioles during diabetes mellitus does not appear to be related to an alteration in cyclic adenosine monophosphate, since forskolin produced similar vasodilatation in nondiabetic and diabetic rats.
Impaired relaxation of the carotid artery during activation of ATP-sensitive potassium channels in atherosclerotic monkeys.
Authors: Faraci F M , Orgren K , Heistad D D
Published: June 2011

This study examined the hypotheses that (1) atherosclerosis impairs relaxation of the carotid artery in response to activation of adenosine triphosphate (ATP)-sensitive potassium channels and (2) regression of atherosclerosis restores the response toward normal.

Isometric tension was measured in rings of carotid artery taken from normal, atherosclerotic, and regression monkeys and precontracted submaximally with prostaglandin F2 alpha.

Relaxation in response to acetylcholine was less in atherosclerotic compared with normal arteries (5 +/- 6% versus 54 +/- 4% [mean +/- SE] in response to 3 x 10(-8) mol/L acetylcholine, P < .01). Relaxation in response to aprikalim, a direct activator of ATP-sensitive potassium channels, was also less in atherosclerotic than in normal arteries (32 +/- 7% versus 69 +/- 5% during 10(-6) mol/L aprikalim, P < .01). Relaxation in response to aprikalim but not to acetylcholine or nitroprusside was inhibited almost completely by glibenclamide (4 mumol/L), a selective inhibitor of ATP-sensitive potassium channels. Relaxation in response to low but not high (10(-6) to 10(-5) mol/L) concentrations of sodium nitroprusside was less in atherosclerotic than in normal arteries. Regression of atherosclerosis tended to restore responses to acetylcholine, but not responses to nitroprusside or aprikalim, toward normal.

These findings suggest that atherosclerosis impairs relaxation of the carotid artery in response to activation of ATP-sensitive channels. Impaired responses may be due, in part, to nonspecific impairment of relaxation. Regression of atherosclerosis did not restore responses of the carotid artery toward normal.