bluuebunny/crossref_metadata_2025 huggingface dataset:
Dementia associated with lacunar infarction.
Authors: Loeb C , Gandolfo C , Croce R , Conti M
Published: June 2011

The purpose of this study was to assess the number of patients with lacunar lesions who develop dementia and to evaluate in patients with and without dementia the relevance of risk factors for cerebrovascular disease, the occurrence of leukoaraiosis, the volume and location of vascular lesions, the size of ventricular and subarachnoid spaces, and stroke recurrence.

One hundred eight patients in whom computed tomograms revealed lacunar lesions that could account for their clinical neurological pictures were followed up for an average of 4 years after their first lacunar stroke.

Twenty-five patients (23.1%) developed dementia. The prognosis regarding occurrence of dementia during the follow-up period, evaluated by the Kaplan-Meier method, was significantly worse in subjects with the greatest evidence of cerebral atrophy (p less than 0.009) and in subjects who underwent new focal cerebrovascular episodes (p less than 0.000001). No differences were seen in the frequency of vascular risk factors or the site or volume of lesions between the demented and nondemented groups.

Patients with lacunar infarcts suffer from dementia 4-12 times more frequently than the normal population. Cerebral atrophy and recurrent stroke, as well as other as-yet unclarified factors, are involved in producing dementia.
Cigarette smoking, alcohol use, and subarachnoid hemorrhage.
Authors: Longstreth W T , Nelson L M , Koepsell T D , van Belle G
Published: June 2011

Subarachnoid hemorrhage remains a devastating disease. Identification of etiologic risk factors would allow the possibility of prevention.

We conducted a population-based case-control study in King County, Washington. Patients whose bleeds originated from a source other than an aneurysm were excluded. Two age- and gender-matched control subjects were identified for each case through random digit telephone dialing. A standardized in-person interview was conducted with the patient whenever possible, a proxy respondent for the case in all instances, the two control subjects, and their proxies. Analyses involved conditional logistic regression taking into account matching on age, gender and respondent type.

Over 2 years, 169 cases were identified, and 149 participated in the case-control study. Compared with those who never smoked, the odds ratio for current heavy smokers (greater than 20 cigarettes/day) was 11.1 (95% confidence interval [CI], 5.0-24.9); for current light smokers (less than or equal to 20 cigarettes/day), 4.1 (95% CI, 2.3-7.3); and for former smokers, 1.8 (95% CI, 1.0-3.2). The risk associated with smoking was greatest in the 3 hours after a cigarette (odds ratio [OR] = 7.0; 95% CI, 3.7-13.1) and then fell, not reaching the risk in those who had never smoked until more than 10 years had passed since the last cigarette. Heavy alcohol use (greater than 2 drinks/day) was also associated with bleeds (OR = 2.2; 95% CI, 0.9-5.1, after adjusting for smoking status). These associations were not substantially altered after adjusting for several possible confounding factors, including a history of hypertension.

Cigarette smoking and heavy alcohol use are associated with the occurrence of subarachnoid hemorrhage.
Laser doppler flowmetry in CA1 sector of hippocampus and cortex after transient forebrain ischemia in gerbils.
Authors: Kuroiwa T , Bonnekoh P , Hossmann K A
Published: June 2011

Local differences in the hemodynamic response to transient ischemia could be involved in the development of selective vulnerability. These differences were studied in vulnerable and nonvulnerable regions of the brain.

Five gerbils were subjected to 10 minutes of bilateral forebrain ischemia, and cerebral blood flow was measured continuously in the frontal cortex and CA1 sector of the hippocampus using laser Doppler flowmetry. Carotid artery pressure was recorded simultaneously with a pressure transducer.

After induction of ischemia, blood flow in the cortex and CA1 sector decreased to 11.8% and 18.0% of the baseline value, respectively. After release of the vascular occlusion, blood flow in the cortex returned to the preischemic level at 7.5 minutes (recovery time), reached the hyperemic peak (123.8%) at 12.4 minutes (peak latency), and again decreased to the preischemic level at 27.2 minutes. In the CA1 sector, blood flow returned to the preischemic level at 2.1 minutes, reached the hyperemic peak (122.2%) at 5.7 minutes, and decreased again to the preischemic level at 21.3 minutes. In both the cortex and CA1 sector, recovery time and peak latency correlated inversely with the amount of residual blood flow during ischemia. Histologically, cortical neurons were not injured but only 14.6% of CA1 neurons survived 1 week after ischemia.

CA1 neurons were selectively injured despite the milder percentage decrease of blood flow during ischemia and the more prompt recovery of flow after ischemia. These findings stress the importance of intrinsic rather than hemodynamic factors in the pathogenesis of selective vulnerability of CA1 neurons after transient bilateral forebrain ischemia.
Ipsilateral hypohidrosis in brain stem infarction.
Authors: Korpelainen J T , Sotaniemi K A , Myllylä V V
Published: June 2011

The brain stem is the most important autonomic processing center, but very little attention has been given to clinical manifestations of autonomic failure in brain stem stroke. Our purpose was to evaluate the prevalence, characteristics, and prognostic significance of sweating dysfunction in brain stem infarctions.

We carried out a prospective study using quantitative evaporimetry to investigate spontaneous and heat-stimulated sweating in 18 healthy control subjects and 18 patients with ischemic brain stem stroke in the acute phase and at 1 and 6 months after infarction.

The sweating response induced by a heating stimulus was significantly lower on the ipsilateral side to the infarction than on the contralateral side. Constant ipsilateral hypohidrosis was established in 83% of the patients in the acute phase, in 100% at 1 month, and in 76% at 6 months after infarction. No differences of sweating response were found between medullary and pontine infarcts.

Hypohidrosis throughout the whole ipsilateral side of the body, a long-lasting phenomenon that has not previously been described, is an essential feature of autonomic failure in brain stem infarction.
Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats.
Authors: Lin T N , He Y Y , Wu G , Khan M , Hsu C Y
Published: June 2011

Infarct volume is one of the common indexes for assessing the extent of ischemic brain injury following focal cerebral ischemia. Accuracy in the measurement of infarct volume is compounded by postischemic brain edema that may increase brain volume in the infarcted region. We evaluated the effect of brain edema on infarct volume determined by triphenyltetrazolium chloride and hematoxylin and eosin stains in a focal cerebral ischemia model in rats.

In a middle cerebral artery occlusion model in rats, infarction is confined to the cerebral cortex. The infarct was delineated by triphenyltetrazolium chloride stain and, in selected samples, by hematoxylin and eosin stain. We determined infarct size at different times after the ischemic insult (6 hours to 7 days) in relation to the evolution of brain edema by the direct measurement of infarct volume. Indirect measurement to reduce the effect of edema on infarct volume was also conducted in the same brain samples.

Direct measurement showed that infarct volume fluctuated with the evolution of brain edema (one-way analysis of variance, p < 0.0001). Infarct volume determined by indirect measurement was independent of the extent of brain edema and remained stable from 6 hours to 3 days after ischemia. There was a good correlation between triphenyltetrazolium chloride and hematoxylin and eosin stains in delineating infarct volume with both direct and indirect measurement.

Traditional direct measurement of infarct volume is associated with an overestimation of infarct volume during the development of brain edema in the first 3 days after ischemia. This artifact can be reduced with indirect measurement, which is based on noninfarcted cortex volume.
Platelet-activating factor acetylhydrolase in red cell membranes. Does decreased activity impair erythrocyte deformability in ischemic stroke patients?
Authors: Yoshida H , Satoh K , Takamatsu S
Published: June 2011

Platelet-activating factor acetylhydrolase hydrolyzes platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine). It also hydrolyzes oxidized derivatives of phosphatidylcholine that have a short-chain acyl residue at the sn-2 position. This enzyme may act mainly in the degradation of oxidized phospholipids and may play a role in maintaining erythrocyte deformability. Therefore, we assessed the activity of red cell membrane platelet-activating factor acetylhydrolase in patients with ischemic stroke and studied the relation of the enzyme activity to red cell deformability.

Enzyme activity was measured in the detergent extract of red cell membranes from 38 patients with cerebral thrombosis and 38 age-matched healthy volunteers. Red cell filterability, an index of red cell deformability, was also measured.

The enzyme activity in patients and control subjects was 100 +/- 74 and 148 +/- 128 nmol/g protein per minute (2.68 +/- 2.11 and 3.79 +/- 2.46 pmol/10(9) cells per minute) (mean +/- SD), respectively, and the difference was significant (p < 0.05 by the Mann-Whitney U test, two-sided test). Enzyme activity was correlated positively with red cell filterability in the patients (n = 20, r = 0.565, p < 0.01).

Red blood cells from stroke patients have lower levels of platelet-activating factor acetylhydrolase activity when compared with those from healthy subjects. This may result in the accumulation of oxidized lipids in the cell membrane and lead to impaired red cell deformability in patients with cerebral thrombosis.
Atrial fibrillation after acute stroke.
Authors: Vingerhoets F , Bogousslavsky J , Regli F , Van Melle G
Published: June 2011

Atrial fibrillation (AF) is a risk factor for stroke, although it may not always be directly responsible for the stroke. On the other hand, cardiac arrhythmias and electrocardiographic changes have been reported after ischemic stroke and numerous other intracranial pathologies. We tested the hypothesis that some patients with acute stroke may develop transient AF as a consequence of the stroke.

This study was based on 1,661 patients with first-ever stroke consecutively hospitalized and prospectively included into the Lausanne Stroke Registry. "Recent AF" was defined as AF discovered at or after ("after-admission" AF) admission in patients without any previous history of AF. Populations with recent AF and after-admission AF were compared for AF evolution, risk factors, and lesion type and distribution with patients with previous history of AF (known AF) and with patients with another recognized cardiac source of embolism (cardioembolic).

Twenty-four patients had recent AF on admission, and 17 developed it a few hours to 3 days after stroke. AF disappeared after a few days in 26 (63%; 94% of after-admission AF) patients. Stroke was a primary hematoma in 9.8% of patients with recent AF, 2.8% of patients with known AF, and 0.9% (p < 0.001) of patients with cardiac source of embolism. Parietoinsular (32%) and brain stem (11%) involvement were more common in recent AF than in cardioembolic stroke in general (16.7% and 6.7%, respectively; p < 0.05).

AF discovered after an acute stroke lasted no more than a few days, suggesting that it may have occurred as a consequence of the stroke. This possibility is emphasized by the significant predominance in patients with recent AF of primary hematoma, which cannot be caused by AF, and of parietoinsular and brain stem involvement, which are experimentally known as arrhythmogenic. This hypothesis should be considered in patients with acute stroke and previously unknown AF before therapeutic decisions are made.
Callosal atrophy with reduced cortical oxygen metabolism in carotid artery disease.
Authors: Yamauchi H , Fukuyama H , Nabatame H , Harada K , Kimura J
Published: June 2011

In cerebrovascular disease, brain atrophy may be a reflection of ischemic changes. Minor changes that are not detectable as infarction on computed tomography may result in atrophy with metabolic depression. We evaluated the relation between size of the corpus callosum and cerebral cortical oxygen metabolism in carotid artery disease.

We used magnetic resonance imaging and positron emission tomography to evaluate 13 right-handed male patients with transient ischemic attacks or minor strokes and unilateral internal carotid artery occlusive disease, two with stenosis and 11 with occlusion. Computed tomography showed only minor subcortical abnormalities in the affected hemisphere. Midsagittal corpus callosum areas on T1-weighted magnetic resonance images, white matter lesions on T2-weighted images, and the cerebral metabolic rate of oxygen measured by the oxygen-15 steady-state technique were analyzed.

Compared with 13 age- and sex-matched control subjects showing the same degree of white matter areas of high intensity, the patients had significantly decreased callosal areas. The degree of corpus callosum atrophy was significantly correlated with the mean cortical oxygen metabolic rate. The same tendency was also found in five patients without infarcts on computed tomography. However, neither the callosal area nor the hemispheric metabolic rate was correlated with the extent of white matter lesions.

These findings indicate that atrophy of the corpus callosum occurs in association with a decrease in cortical oxygen metabolism. Corpus callosum atrophy may be a useful morphological index that reflects the cerebral cortical metabolic state in carotid artery occlusive disease.
Improved neurological recovery of cerebral infarctions after plasmapheretic reduction of lipids and fibrinogen.
Authors: Walzl M , Lechner H , Walzl B , Schied G
Published: June 2011

High fibrinogen levels have been assessed in cerebrovascular disease with a direct relation to both plasma and whole-blood viscosity, as well as cerebral blood flow. Heparin-induced extracorporeal low density lipoprotein precipitation (HELP) is a new method that safely and effectively reduces fibrinogen and plasma lipoproteins and improves blood flow properties.

We studied 26 patients with acute embolic stroke and 22 with multi-infarct dementia. Each received two treatments with HELP within 8 days. Each patient had measurement of the important blood constituents and evaluation of changes in clinical signs and symptoms related to their cerebrovascular disease.

Each HELP treatment safely produced an immediate and significant reduction in rheological measures, including fibrinogen (P < .001), whole-blood viscosity at high and low shear rates, plasma viscosity, and red cell transit time (P < .01 each). Total cholesterol, low density lipoprotein (P < .0001 each), lipoprotein(a) (P < .003), and triglycerides (P < .0001) were also reduced. The treated group in both the acute stroke group and the multi-infarct group showed improvement relative to the untreated control subjects in Mathew scale, Mini-Mental State Examination, and activities of daily living test scores. These uniform improvements persisted at least 3 days past the second HELP treatment.

These results support the hypothesis that the improved hemorheologic property of blood is an important factor in clinical recovery as well as basic neurological function.
Improving stroke rehabilitation. A controlled study.
Authors: Kalra L , Dale P , Crome P
Published: June 2011

Assessment of stroke rehabilitation is complicated by the heterogeneity of patients and settings and by difficulties in disentangling effects of organization from effects of types and amounts of treatment input.

A prospective controlled study was undertaken in 245 stroke patients stratified into three groups according to prognosis and managed on a stroke rehabilitation unit (n = 124) or general medical wards (n = 121). Patients were randomly allocated to either setting 2 weeks after stroke and were comparable for baseline characteristics.

Patients on general medical wards received more physiotherapy on average (16.2 +/- 7.2 versus 14.3 +/- 3.2 hours; P < .05) but similar amounts of occupational therapy (9.3 +/- 2.8 versus 9.5 +/- 3.2 hours) compared with stroke unit patients. More time was spent on individual rehabilitation on the stroke unit compared with general wards (P < .001). Functional abilities at discharge, destination of discharge, and length of hospital stay in patients with good prognosis were comparable in both settings. Patients with poor prognosis managed on general wards showed higher mortality (P < .05) and longer hospital stay (123.2 +/- 48.2 versus 52.3 +/- 19.8 days; P < .001), but functional abilities at discharge in survivors were comparable with those of stroke unit patients. Patients with intermediate prognosis had significantly better outcome on the stroke unit, with more patients being discharged home (75% versus 52%; P < .001), shorter average length of hospital stay (48.7 +/- 17.2 versus 104.6 +/- 28.6 days; P < .001), and better functional abilities at discharge (P < .05).

Stroke units improve outcome and reduce hospital stay without increasing therapy time. Their effectiveness may be enhanced by patient selection.
Between-method correlation in quantifying internal carotid stenosis.
Authors: Sitzer M , Fürst G , Fischer H , Siebler M , Fehlings T , Kleinschmidt A , Kahn T , Steinmetz H
Published: June 2011

The degree of internal carotid stenosis has emerged as the most important predictor of ischemic stroke in extracranial carotid artery disease. The purpose of this study was to assess the validity of the noninvasive techniques for quantifying internal carotid stenosis with respect to the accepted standard of intra-arterial angiography.

We measured the maximum percentage reduction in luminal diameter on the intra-arterial digital subtraction angiograms of 56 symptomatic patients with extracranial internal carotid stenosis (n = 77) or occlusion (n = 20). These data were compared with independent measurements based on continuous-wave Doppler ultrasonography, pulsed-wave Doppler spectrum analysis, color Doppler-assisted duplex imaging, and magnetic resonance angiography.

Correlations with intra-arterial angiography were equally strong (r > .90) for magnetic resonance angiography, continuous-wave Doppler, and color duplex analysis. Positive and negative predictive values for (therapeutically relevant) 70% to 99% stenosis were higher for continuous-wave Doppler (.82, .97) and color duplex (.84, .98) than for magnetic resonance angiography (.79, .81). Also, accuracy in quantifying high-grade stenosis was better for both of these ultrasonographic techniques, mainly due to the frequent occurrence of a "flow gap" on the magnetic resonance angiograms. Continuous-wave Doppler and magnetic resonance angiography, but not color duplex, failed to detect slow residual arterial flow in one and two cases of symptomatic "pseudo-occlusion" of the internal carotid, respectively.

(1) Several noninvasive methods compare well with intra-arterial angiography in identifying and quantifying high-grade internal carotid stenosis; (2) the use of these noninvasive methods may suffice for treatment decisions; and (3) because residual between-method disagreement is partly explained by principles of physics, the validity of continuous-wave Doppler and color duplex in quantifying 60% to 99% stenosis is likely to be underestimated by correlation with intra-arterial angiography.
Impairment of anti-platelet-aggregating activity of endothelial cells after experimental subarachnoid hemorrhage.
Authors: Ohkuma H , Ogane K , Fujita S , Manabe H , Suzuki S
Published: June 2011

Serial changes of anti-platelet-aggregating activity in the endothelial cells after experimental subarachnoid hemorrhage were studied in 30 feline two-hemorrhage models.

One hour or 2, 4, 7, or 14 days after mimic subarachnoid hemorrhage, ADP (40 mg/kg) was infused into the basilar artery via the right vertebral artery to activate circulating platelets. Immediately after ADP infusion, the basilar artery was fixed by intra-arterial perfusion with 1.5% glutaraldehyde in 0.1 mol/L phosphate buffer and was removed. The luminal surface was examined under a scanning electron microscope.

One hour after subarachnoid hemorrhage, no platelets adhered or aggregated on the luminal surface. However, 4 to 7 days after subarachnoid hemorrhage, many platelets were observed adhering or aggregating on the luminal surface.

These findings suggest the impairment of anti-platelet-aggregating activity of endothelial cells after subarachnoid hemorrhage. This impairment may be involved in inducing cerebral ischemia during cerebral vasospasm by causing platelet adhesion and aggregation.
Effects of flunarizine on neurological recovery and spinal cord blood flow in experimental spinal cord ischemia in rabbits.
Authors: Johnson S H , Kraimer J M , Graeber G M
Published: June 2011

The lipophilic calcium channel antagonist flunarizine has been demonstrated to be neuroprotective in several models of cerebral ischemia. Ischemic spinal cord injury may have a similar pathophysiology and hence may respond in a similar fashion. This study was designed to investigate the effects of pretreatment with flunarizine on systemic hemodynamics, spinal cord blood flow, and neurological recovery in a rabbit model of ischemic spinal cord injury.

New Zealand White rabbits were anesthetized with ketamine and xylazine and instrumented for systemic blood pressure monitoring and spinal cord blood flow measurements using the microsphere method. After pretreatment with flunarizine or vehicle, ischemic spinal cord injury was created selectively in the caudal regions of the spinal cord by cross-clamping the abdominal aorta for a period of 25 minutes. Spinal cord blood flow was measured before, during, and 15 minutes after cross-clamp removal. Animals were allowed to recover and were graded neurologically at 18 and 24 hours after ischemia.

Flunarizine injection was associated with hypotension that was both transient and dose related. Animals pretreated with flunarizine 0.4 mg/kg had significantly improved neurological recovery scores at 18 hours after ischemia (P = .017) compared with vehicle controls. At 24 hours this effect was lessened (P = .095); however, 60% of flunarizine-treated animals retained their ability to hop, whereas all of the vehicle-treated animals were nonambulatory.

Flunarizine has a protective effect on neurological recovery after experimental ischemic spinal cord injury. The therapeutic window is narrow, and dosing is limited by untoward hypotension. The mechanism of protection likely involves inhibition of pathological cytosolic calcium accumulation rather than a direct effect on vascular smooth muscle.
Angiotensin converting enzyme inhibitors attenuate ischemic brain metabolism in hypertensive rats.
Authors: Sadoshima S , Fujii K , Ooboshi H , Ibayashi S , Fujishima M
Published: June 2011

Angiotensin converting enzyme (ACE) inhibitors are expected to modulate neuronal activities. The present study was designed to examine the beneficial effects of ACE inhibitors on microcirculation and metabolism in the ischemic brain.

Cerebral ischemia was developed for 60 minutes in spontaneously hypertensive rats (SHR, n = 35) by bilateral carotid artery occlusion. ACE inhibitor (0.1 or 10 mg/kg SQ 29,852 or captopril) were intravenously injected 15 minutes before cerebral ischemia. Cerebral blood flow to the parietal cortex was measured with the H2 clearance technique. Lactate, pyruvate, and ATP in the brain were estimated by the enzymatic method.

Before cerebral ischemia, high doses of both SQ 29,852 and captopril significantly decreased mean arterial pressure by 15 to 25 mm Hg and reduced cerebral vascular resistance by 13% to 17% of the resting values. Cerebral blood flow and arterial pressure during ischemia were not altered by these ACE inhibitors. After 60 minutes of cerebral ischemia, tissue lactate in vehicle-treated SHR increased 6.6-fold and ATP decreased to 65% of the control values. Administration of SQ 29,852 or captopril significantly reduced the lactate levels to 1.6- to 3.1-fold and well preserved the ATP levels to 82% to 93% of the control.

These results suggest that inhibition of ACE activities may be protective for cerebral metabolism against ischemic insult.
Fructose-1,6-bisphosphate reduces infarct volume after reversible middle cerebral artery occlusion in rats.
Authors: Kuluz J W , Gregory G A , Han Y , Dietrich W D , Schleien C L
Published: June 2011

We tested the hypothesis that fructose-1,6-bisphosphate, when administered 10 minutes before the end of 2 hours of reversible middle cerebral artery occlusion, reduces ischemia-reperfusion injury and infarct volume measured after a 3-day survival period in rats.

After 1 hour and 50 minutes of middle cerebral artery occlusion by the intraluminal suture method, fructose-1,6-bisphosphate, 500 mg/kg in group 1 and 350 mg/kg in group 2 (or an equivalent volume of 1.8% saline as placebo in each group), was given intravenously for a period of 15 minutes to fasted adult Sprague-Dawley rats. After 2 hours of ischemia, the suture was withdrawn and the rats allowed to survive for 3 days. The areas of infarction in 10 hematoxylin-eosin-stained coronal sections of the brain were measured and used to calculate infarct volume.

In group 1, fructose-1,6-bisphosphate decreased total cerebral hemispheric infarct volume by 43% (from 199.6 +/- 11.2 to 114.2 +/- 35.8 mm3, P < .04; mean +/- SEM). Cerebral cortical and subcortical infarct volumes were decreased by 46% (from 137.3 +/- 7.5 to 74.1 +/- 28.6 mm3, P < .04) and 36% (from 62.3 +/- 5.1 to 40.0 +/- 8.3 mm3, P < .04), respectively. In group 2, fructose-1,6-bisphosphate had no effect on infarct volume in rats that developed mild intraischemic hyperthermia, but in rats kept normothermic during ischemia, fructose-1,6-bisphosphate reduced subcortical infarct volume from 53.7 +/- 8.1 to 18.4 +/- 8.0 mm3 (P < .03).

Fructose-1,6-bisphosphate improves functional neurological outcome and reduces infarct volume after reversible middle cerebral artery occlusion in rats.
Mild hypothermia after cardiac arrest in dogs does not affect postarrest multifocal cerebral hypoperfusion.
Authors: Oku K , Sterz F , Safar P , Johnson D , Obrist W , Leonov Y , Kuboyama K , Tisherman S A , Stezoski S W
Published: June 2011

Although mild resuscitative hypothermia (34 degrees C) immediately after cardiac arrest improves neurological outcome in dogs, its effects on cerebral blood flow and metabolism are unknown.

We used stable xenon-enhanced computed tomography to study local, regional, and global cerebral blood flow patterns up to 4 hours after cardiac arrest in dogs. We compared a normothermic (37.5 degrees C) control group (group I, n = 5) with a postarrest mild hypothermic group (group II, n = 5). After ventricular fibrillation of 12.5 minutes and reperfusion with brief cardiopulmonary bypass, the ventilation, normotension, normoxia, and mild hypocapnia were controlled to 4 hours after cardiac arrest. Group II received (minimal) head cooling during cardiac arrest, followed by systemic bypass cooling (to 34 degrees C) during the first hour of reperfusion after cardiac arrest.

The postarrest homogeneous transient hyperemia was followed by global hypoperfusion from 1 to 4 hours after arrest, with increased "no-flow" and "trickle-flow" voxels (compared with baseline), without group differences. At 1 to 4 hours, mean global cerebral blood flow in computed tomographic slices was 55% of baseline in group I and 64% in group II (NS). No flow (local cerebral blood flow < 5 mL/100 cm3 per minute) occurred in 5 +/- 2% of the voxels in group I versus 9 +/- 5% in group II (NS). Trickle flow (5 to 10 mL/100 cm3 per minute) occurred in 10 +/- 3% voxels in group I versus 16 +/- 4% in group II (NS). Cerebral blood flow values in eight brain regions followed the same hyperemia-hypoperfusion sequence as global cerebral blood flow, with no significant difference in regional values between groups. The global cerebral metabolic rate of oxygen, which ranged between 2.7 and 4.5 mL/100 cm3 per minute before arrest in both groups, was at 1 hour after arrest 1.8 +/- 0.3 mL in normothermic group I (n = 3) and 1.9 +/- 0.4 mL is still-hypothermic group II (n = 5); at 2 and 4 hours after arrest, it ranged between 1.2 and 4.2 mL in group I and between 1.2 and 2.6 mL in group II.

After cardiac arrest, mild resuscitative hypothermia lasting 1 hour does not significantly affect patterns of cerebral blood flow and oxygen uptake. This suggests that different mechanisms may explain its mitigating effect on brain damage.
Familial cerebrovascular accidents due to concomitant hyperhomocysteinemia and protein C deficiency type 1.
Authors: Franken D G , Vreugdenhil A , Boers G H , Verrips A , Blom H J , Novakova I R
Published: June 2011

Hyperhomocysteinemia and protein C deficiency are risk factors for thromboembolism. Hyperhomocysteinemia has been reported to inhibit the expression of thrombomodulin and to inactivate both thrombomodulin and protein C irreversibly, leading to decreased protein C activity.

In a 16-year-old girl, who developed a sinus sagittalis thrombosis, and in her father, who experienced a transient ischemic attack, both hyperhomocysteinemia and protein C deficiency type 1 were present. Protein C deficiency alone was found in one of the two sisters, who was without any clinical vascular history.

In this family with independently inherited hyperhomocysteinemia and protein C deficiency, clinical cerebrovascular disease occurred only in those members with a combination of both risk factors, suggesting a synergistic interaction between these thrombogenic risk factors.
Headache in stroke.
Authors: Vestergaard K , Andersen G , Nielsen M I , Jensen T S
Published: June 2011

The etiology of headache in stroke is not known, and its relation to migraine and tension-type headache is unclear. The aim of our study was to investigate and classify headache appearing in stroke patients prospectively, using the new headache classification as determined by the Headache Classification Committee of the International Headache Society (1988).

Two hundred eighty consecutively admitted patients aged younger than 81 years with acute stroke were examined and questioned about headache and prior headache complaints; 238 (85%) were able to communicate.

Sixty-five (27%) of the 238 patients experienced headache from 3 days before to 3 days after stroke. Headache occurred in 50% of patients with intracerebral hemorrhage, in 26% with infarction, and in 15% of patients with lacunar infarction. Headache was more common when stroke occurred in posterior circulation than anterior circulation (P < .02). Fifty-six patients were able to give further information about headache characteristics. The headache in thromboembolic stroke was classified as tension-type headache (25 patients), migraine-like headache (14 patients), and other headache (12 patients). Migraine was more frequent in vertebrobasilar stroke. Headache was lateralized in 33% of cases. In patients with unilateral headache and unilateral stroke lesion, the headache was ipsilateral in 14 of 17 cases. In infarction, severity of headache showed no relation to lesion size or lesion localization. Patients with previous tension-type headache and migraine experienced reactivation of known headache equally often.

(1) Headache occurs in one fourth of patients with acute stroke. (2) Unilateral headache is usually ipsilateral to stroke lesion. (3) Headache severity is not related to size of ischemic stroke lesion.
Impact of early surgery on outcome after aneurysmal subarachnoid hemorrhage. A population-based study.
Authors: Fogelholm R , Hernesniemi J , Vapalahti M
Published: June 2011

Population-based patient materials have not been used earlier in assessing the effects of neurosurgical treatment on survival and functional outcome of subarachnoid hemorrhage. Moreover, the proportion of all subarachnoid hemorrhage patients who might be candidates for neurosurgical treatment has not been estimated.

We compared the survival and functional outcome of two population-based patient materials from Central Finland in 1976 through 1978 (n = 146) and 1980 through 1987 (n = 351). The most important basic characteristics of both materials were similar. In the 1970s, only patients aged < 60 years with carotid territory aneurysms were operated on after an interval of 2 weeks from the bleeding. In the 1980s, early surgery was attempted, and the other exclusion criteria were abandoned. Allocation to medical or surgical treatment was not randomized.

During the 1970s, only 14% of the patients had surgical treatment, with a median delay of 15 days after the bleeding; in the 1980s, the corresponding figures were 46% and 4 days. Despite these fundamental changes in the treatment policy, the survival up to 3 years in the 1980s was only marginally improved compared with the 1970s. Conversely, the functional outcome at 4 years after the bleeding was significantly better in the 1980s than the 1970s, with 82% and 64% of the survivors, respectively, being independent in the activities of daily living (P = .002). We estimated that 60% of all patients with subarachnoid hemorrhage might be candidates for neurosurgical treatment, provided that there are no delays in admission or evaluation.

An active treatment policy of subarachnoid hemorrhage including early surgery only marginally improves survival, but the quality of life of the survivors is significantly better. Only 60% of all patients in the population with subarachnoid hemorrhage can, at least theoretically, benefit from surgical treatment.
Activation of healthy hemisphere in poststroke recovery. A transcranial Doppler study.
Authors: Silvestrini M , Caltagirone C , Cupini L M , Matteis M , Troisi E , Bernardi G
Published: June 2011

The possible involvement of the healthy hemisphere in functional recovery in stroke hemiplegia is still controversial. This study of patients who had suffered ischemic stroke assessed circulatory changes in the healthy hemisphere by transcranial Doppler ultrasonography during opposition exercise of fingers that had recovered movement.

Measurements of flow velocity in the middle cerebral arteries were recorded in 12 recovered hemiplegic stroke patients and 12 healthy sex- and age-matched control subjects during a 2-minute sequential thumb-to-finger opposition task, alternatively performed with normal and recovered fingers. The effects of the motor task on heart rate, blood pressure, and end-tidal PCO2 were also evaluated.

With respect to the basal values, a comparable increase of flow velocity (%mean +/- SD) in the contralateral middle cerebral artery occurred in patients during movement of normal (9.7 +/- 2.7%) and recovered fingers (10.4 +/- 5.1%) and in controls (11.3 +/- 4.9%). However, in the middle cerebral artery ipsilateral to the hand performing the motor task, the increase of flow velocity was significantly higher (P < .001, two-way analysis of variance) during movement of the recovered hand in patients (10.5 +/- 4.6%) than during the movement of the normal hand in both patients (1.7 +/- 3.7%) and controls (1.8 +/- 4.5%). No significant difference of changes in heart rate, blood pressure, and end-tidal PCO2 was observed for patients or normal control subjects during the various phases of the study.

Our data suggest that activation of the healthy hemisphere contributes toward functional recovery of motor deficit after stroke and confirms the ability of transcranial Doppler ultrasonography to correlate cerebral artery flow dynamics with selective cerebral activation.
Nitric oxide production during focal cerebral ischemia in rats.
Authors: Kader A , Frazzini V I , Solomon R A , Trifiletti R R
Published: June 2011

Nitric oxide has been implicated as a mediator of glutamate excitotoxicity in primary neuronal cultures.

A number of indicators of brain nitric oxide production (nitric and cyclic guanosine monophosphate [cGMP] concentrations and nitric oxide synthase activity) were examined after bilateral carotid ligation and right middle cerebral artery occlusion in adult rats.

Brain nitrite was significantly increased in the right versus left cortex 5, 10, and 20 minutes after middle cerebral artery occlusion (P < .05), with a return to baseline at 60 minutes. There were no significant changes in cerebellar concentrations. Cortical levels of cGMP were increased at 10, 20, and 60 minutes after occlusion, with significant right-to-left differences (P < .05). Cerebellar concentrations of cGMP were also increased but without significant side-to-side differences. Nitric oxide synthase activity increased approximately 10-fold from baseline 10 minutes after occlusion in the right cortex but decreased markedly by 60 minutes from its peak at 10 minutes. The right-to-left difference in nitric oxide synthase activity was significant at 20 minutes (P < .05). Pretreatment of rats with NG-nitro-L-arginine, a nitric oxide synthase inhibitor, abolished the rise in nitrite and cGMP.

These results suggest that a sharp transient increase in the activity of nitric oxide synthase occurs during the first hour of cerebral ischemia, which leads to a burst in nitric oxide production and activation of guanylate cyclase.
Effect of nitric oxide synthase inhibition on cerebral blood flow and injury volume during focal ischemia in cats.
Authors: Nishikawa T , Kirsch J R , Koehler R C , Bredt D S , Snyder S H , Traystman R J
Published: June 2011

We tested the hypothesis that inhibition of nitric oxide synthase activity in brain before ischemia alters cerebral blood flow and decreases brain injury after 4 hours of middle cerebral artery occlusion in cats.

Halothane-anesthetized cats underwent 4 hours of left middle cerebral artery occlusion after they were randomly assigned to receive either intravenous N omega-nitro-L-arginine methyl ester, at a dose that completely inhibited cortical nitric oxide synthase activity (10 mg/kg, n = 10), or an equal volume of diluent (10 mL saline, n = 10). Serial blood flow measurements were made with radiolabeled microspheres, and injury volume was measured by triphenyltetrazolium staining.

Blood flow to caudate nucleus and inferior temporal cortex decreased to the same extent in both groups during middle cerebral artery occlusion. Somatosensory evoked potential amplitude was reduced to less than 10% of baseline values in both groups. Injury volume of ipsilateral caudate nucleus in cats pretreated with nitroarginine (52 +/- 5%, mean +/- SE) was less (P < .05) compared with the saline group (80 +/- 4%), whereas ipsilateral cerebral hemispheric injury volume was similar between the two groups (30 +/- 6% and 32 +/- 4% of hemisphere in saline and nitroarginine groups, respectively).

These results suggest that inhibition of nitric oxide synthase decreases caudate injury volume at 4 hours of middle cerebral artery occlusion without an alteration in distribution of cerebral blood flow.
Mice expressing a bovine basic fibroblast growth factor transgene in the brain show increased resistance to hypoxemic-ischemic cerebral damage.
Authors: MacMillan V , Judge D , Wiseman A , Settles D , Swain J , Davis J
Published: June 2011

Cerebral intraventricular infusion of acidic or basic fibroblast growth factor has been shown to attenuate ischemic damage to hippocampal CA1 neurons in the gerbil. The purpose of the present study was to determine if the basic fibroblast growth factor transgenic mouse has an enhanced ability to resist the effects of severe cerebral hypoxemia-oligemia.

Mice that were transgenic for bovine basic fibroblast growth factor were exposed to right carotid artery ligation, hyperglycemia, and 20 minutes of 1% carbon monoxide. After 5 days' recovery, brains were examined for histological damage.

Counts of CA1 neurons in the right hippocampus showed a significantly higher number of neurons per millimeter CA1 in hypoxic-ischemic transgenic mice compared with nontransgenic controls (transgenic, 260 +/- 33; nontransgenic, 151 +/- 37 neurons per millimeter CA1; P < .05).

The results indicate that basic fibroblast growth factor transgenic mice, as judged by CA1 hippocampal neuronal survival, have an enhanced ability to resist the effects of a complex hypoxic-ischemic cerebral insult.
Progressive intracranial occlusive disease associated with deficiency of protein S. Report of two cases.
Authors: Barinagarrementeria F , Cantú Brito C , Izaguirre R , de la Peña A
Published: June 2011

Deficiency of the free fraction of protein S has been associated with arterial or venous stroke. The pathogenesis of vascular occlusion in patients with protein S deficiency is not known. We present two cases of cerebral infarction and deficiency of protein S in which the subjects had progressive intracranial occlusions.

A 16-year-old girl was admitted because of left brain stem infarction and protein S deficiency. Cerebral angiography disclosed stenosis of the right intracranial vertebral artery and occlusion of the left posterior cerebral artery. A second angiogram performed 18 months later disclosed occlusion of the right vertebral intracranial artery. In the second case, a 17-year-old girl was admitted because of left hemispheric cerebral infarction and protein S deficiency. Cerebral angiography showed stenosis of the left anterior cerebral artery, left supraclinoid internal artery, and left middle cerebral artery. A second cerebral angiogram performed 5 months later disclosed occlusion of the left anterior cerebral artery and poor hemispheric perfusion through the left middle cerebral artery.

Based on our cases, we postulate that some patients with prothrombotic states may develop progressive intracranial arterial occlusions, possibly secondary to a permanent thrombogenic stimulus. We suggest routinely searching for prothrombotic states in young patients with intracranial occlusion, especially if the occlusion is progressive and other causes are not obvious.
One-year reduction and longitudinal analysis of carotid intima-media thickness associated with colestipol/niacin therapy.
Authors: Mack W J , Selzer R H , Hodis H N , Erickson J K , Liu C R , Liu C H , Crawford D W , Blankenhorn D H
Published: June 2011

The Cholesterol Lowering Atherosclerosis Study has reported significant reduction of coronary artery disease and of carotid arterial intima-media thickness (IMT) at 2 and 4 years with colestipol/niacin therapy. We now report on treatment effects on carotid IMT at 6 months and 1 year.

One hundred eighty-eight nonsmoking men, aged 40 to 59 years, with prior coronary artery bypass graft surgery were randomized to colestipol/niacin plus diet therapy or placebo plus diet therapy. Computerized image processing of carotid ultrasound films was used to measure IMT in the right common carotid artery. Treatment group comparisons were made at 6 months and 1 year (46 and 33 subjects, respectively, with baseline and 6-month or 1-year ultrasound measures). The time course of the treatment effect on carotid IMT was estimated using the complete sample of 78 subjects with baseline and on-trial data.

No significant treatment group differences on carotid IMT were found at 6 months. At 1 year, the treated group showed significant reduction of carotid IMT (P = .01 between groups). The placebo group showed continuing progression of IMT during the 4-year study period (estimated progression rate, 0.018 mm/y). The treated group showed reduction of IMT during the first 3 years and a plateau during the remainder of the study.

Reduction of carotid IMT was found with aggressive lipid-lowering therapy. Ultrasound measures of IMT offer a noninvasive and precise measure of early carotid atherosclerosis that will decrease sample size requirements, potentially decrease dropout rates, and widen the study population of antiatherosclerotic clinical trials.
Predicting length of stay, functional outcome, and aftercare in the rehabilitation of stroke patients. The dominant role of higher-order cognition.
Authors: Galski T , Bruno R L , Zorowitz R , Walker J
Published: June 2011

Research in recent years has revealed factors that are important predictors of physical and functional rehabilitation: demographic variables, visual and perceptual impairments, and psychological and cognitive factors. However, there is a remaining uncertainty about prediction of outcome and a need to clinically apply research findings. This study was designed to identify the relative importance of medical, functional, demographic, and cognitive factors in predicting length of stay in rehabilitation, functional outcome, and recommendations for postdischarge continuation of services.

The influence of these factors was determined by comparing diagnostic, medical, demographic, functional, and neuropsychological information that was retrospectively obtained by reviewing the records of 86 patients admitted for comprehensive rehabilitation due to stroke (n = 36) or orthopedic injury (n = 50). Multiple linear regression with statistical adjustment to control for overprediction of variance was used to predict outcomes.

The study revealed the primary importance of higher-order cognitive impairments (comprehension, judgment, short-term verbal memory, and abstract thinking) in extending length of stay and increasing referrals for outpatient therapies and home services after discharge for the cerebrovascular accident patients in comparison with orthopedic cohorts.

The need is discussed for early, comprehensive assessment of deficits in cognition that affect a stroke survivor's ability to participate in a rehabilitation program and remediation that facilitates functional improvement by building on residuals of impaired abilities or teaching compensatory behaviors.
Relation of laboratory and clinical variables to the grade of carotid atherosclerosis.
Authors: Szirmai I G , Kamondi A , Magyar H , Juhász C
Published: June 2011

To clarify diagnostic entities in ischemic stroke we analyzed the relation between the severity of carotid atherosclerosis, coagulation parameters, lipoproteins, neurological status, and risk factors in 232 patients.

Duplex ultrasonography, computed tomography scan, and laboratory investigations were performed between the third and tenth days after stroke. Based on carotid ultrasound scores, we categorized the patients into four groups (A, B, C, and D) according to severity of atherosclerosis. Corresponding laboratory variables and clinical data were statistically analyzed.

Ultrasound scores were significantly (P < .05) higher in the male (n = 126) versus female (n = 106) patients. The hematocrit was significantly higher and thrombin time was significantly shorter in the male group compared with the female group. Severe atherosclerosis (group C) and occlusion (group D) of the internal carotid artery was associated with smoking (C = 56%; D = 78%), hypertension (C = 43%; D = 35%), claudication (C = 13%; D = 5%), and antecedent myocardial infarction (C = 9%; D = 13%). There was no statistical correlation between ultrasound scores and the patients' neurological condition. Cholesterol and plasma fibrinogen levels were significantly higher and high-density lipoprotein cholesterol was significantly lower in groups with severe atherosclerosis compared with patients with slight intimal damage. The presence of multiple plaques or thrombosis of the internal carotid artery was concordant with the prevalence of single cerebral infarcts.

Severity of carotid atherosclerosis corresponded well with the following factors: age, smoking, and low concentration of high-density lipoprotein cholesterol. Elevation of plasma fibrinogen combined with a loss of high-density lipoprotein cholesterol is strongly associated with severe atherosclerosis and results in brain infarction.