bluuebunny/crossref_metadata_2025 huggingface dataset:
Delayed Ischemic Hyperintensity on T1-Weighted MRI in the Caudoputamen and Cerebral Cortex of Humans After Spectacular Shrinking Deficit
Authors: Fujioka Masayuki , Taoka Toshiaki , Hiramatsu Ken-Ichiro , Sakaguchi Syouji , Sakaki Toshisuke
Published: June 2011

Background and Purpose
—Transient internal carotid artery (ICA)–middle cerebral artery (MCA) occlusion caused by cardiogenic embolus can lead to spectacular shrinking deficit (SSD): sudden hemispheric stroke syndrome followed by rapid improvement. The aim of this study was to investigate sequential neuroradiological changes in the brains of patients after SSD compared with those after brief cardiac arrest and hypoglycemia, which we previously studied with the same methods.

Methods
—We serially studied CT scans and MR images obtained at 1.5 T in 4 patients with SSD. All 4 patients suffered from transient neurological deficits due to cardiogenic embolus in ICA-MCA. The symptoms began to disappear from 25 to 50 minutes after onset.

Results
—Repeated CT scans demonstrated no abnormal findings in the affected cerebral hemisphere in 3 of the 4 patients and a small cortical infarct in the remaining 1. In each patient, repeated MRI between day 7 and month 23 after stroke showed basal ganglionic and cortical lesions. These lesions were hyperintense on T1-weighted and relatively hypointense on T2-weighted imaging. These ischemic lesions of hyperintensity on T1-weighted MRI subsided with time.

Conclusions
—Transient ICA-MCA occlusion leading to SSD produces a specific ischemic change with delayed onset in the basal ganglia and cerebral cortex in humans on MRI but not CT scans. We speculate that the lesions represent incomplete ischemic injury, including selective neuronal death, proliferation of glial cells, paramagnetic substance deposition, and/or lipid accumulation. Unlike brief cardiac arrest or hypoglycemia, the localized lesions on MRI of patients after SSD seem to be incomplete and to differ from infarction or hemorrhage.
P
2u
Receptor–Mediated Release of Endothelium-Derived Relaxing Factor/Nitric Oxide and Endothelium-Derived Hyperpolarizing Factor From Cerebrovascular Endothelium in Rats
Authors: You Junping , Johnson T. David , Marrelli Sean P. , Mombouli Jean-Vivien , Bryan Robert M.
Published: June 2011

Background and Purpose
—Stimulation of P
2u
purinoceptors by UTP on endothelium dilates the rat middle cerebral artery (MCA) through the release of endothelium-derived relaxing factor/nitric oxide (EDRF/NO) and an unknown relaxing factor. The purpose of this study was to determine whether this unknown relaxing factor is endothelium-derived hyperpolarizing factor (EDHF).

Methods
—Rat MCAs were isolated, cannulated, pressurized, and luminally perfused. UTP was added to the luminal perfusate to elicit dilations.

Results
—Resting outside diameter of the MCAs in one study was 209±7 μm (n=10). The MCAs showed concentration-dependent dilations with UTP administration. Inhibition of NO synthase with
N
G
-nitro-
l
-arginine methyl ester (L-NAME) (1 μmol/L to 1 mmol/L) did not diminish the maximum response to UTP but did shift the concentration-response curve to the right. Scavenging NO with hemoglobin (1 or 10 μmol/L) or inhibition of guanylate cyclase with ODQ (1 or 10 μmol/L) had effects on the UTP-mediated dilations similar to those of L-NAME. In the presence of L-NAME, dilations induced by 10 μmol/L UTP were accompanied by 13±2 mV (
P
<0.009) hyperpolarization of the vascular smooth muscle membrane potential (−28±2 to −41±1 mV). Iberiotoxin (100 nmol/L), blocker of the large-conductance calcium-activated K channels, sometimes blocked the dilation, but its effects were variable. Charybdotoxin (100 nmol/L), also a blocker of the large-conductance calcium-activated K channels, abolished the L-NAME–insensitive component of the dilation to UTP.

Conclusions
—Stimulation of P
2u
purinoceptors on the endothelium of the rat MCA released EDHF, in addition to EDRF/NO, and dilated the rat MCA by opening an atypical calcium-activated K channel.
Treatment in a Combined Acute and Rehabilitation Stroke Unit
Authors: Indredavik B. , Bakke F. , Slørdahl S. A. , Rokseth R. , Håheim L. L.
Published: June 2011

Background and Purpose
—We have previously shown that treatment of acute stroke patients in our stroke unit (SU) compared with treatment in general ward (GWs) improves short- and long-term survival and functional outcome and increases the possibility of earlier discharge to home. The aim of the present study was to identify the differences in treatment between the SU and the GW and to assess which aspects of the SU care which were most responsible for the better outcome.

Methods
—Of the 220 patients included in our trial, only 206 were actually treated (SU, 102 patients; GW, 104 patients). For these patients, we identified the differences in the treatment and the consequences of the treatment. We analyzed the factors that we were able to measure and their association with the outcome, discharge to home within 6 weeks.

Results
—Characteristic features in our SU were teamwork, staff education, functional training, and integrated physiotherapy and nursing. Other treatment factors significantly different in the SU from the GW were shorter time to start of the systematic mobilization/training and increased use of oxygen, heparin, intravenous saline solutions, and antipyretics. Consequences of the treatment seem to be less variation in diastolic and systolic blood pressure (BP), avoiding the lowest diastolic BP, and lowering the levels of glucose and temperature in the SU group compared with the GW group. Univariate analyses showed that all these factors except the level of glucose were significantly associated with discharge to home within 6 weeks. In the final multivariate Cox regression model, shorter time to start of the mobilization/training and stabilized diastolic BP were independent factors significantly associated with discharge to home within 6 weeks.

Conclusions
—Shorter time to start of mobilization/training was the most important factor associated with discharge to home, followed by stabilized diastolic BP, indicating that these factors probably were important in the SU treatment. The effects of characteristic features of an SU, such as a specially trained staff, teamwork, and involvement of relatives, were not possible to measure. Such factors might be more important than those actually measured.
The Natural History of CADASIL
Authors: Desmond David W. , Moroney Joan T. , Lynch Timothy , Chan Stephen , Chin Steven S. , Mohr J. P.
Published: June 2011

Background and Purpose
—Although numerous families with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) have been reported, our understanding of the disease remains incomplete. Thus, we performed this study to investigate the phenotypic range and natural history of CADASIL.

Methods
—We performed a pooled analysis of previously published cases.

Results
—We identified 105 symptomatic patients in 33 families. Vascular risk factors were uncommon, with hypertension reported in only 8 patients. The mean age of symptom onset was 36.7±12.9 years. Stroke or transient ischemic attack was an initial symptom in 45 patients, with a mean age of onset of 41.2±9.2 years. Migraine was also a common initial symptom, reported by 42 patients at a younger mean age of 28.3±11.7 years. Other initial symptoms included depression in 9 patients, cognitive impairment in 6 patients, and seizures in 3 patients. Regarding clinical course, 71 patients experienced a stroke or transient ischemic attack, and 52 of those patients had 1 or more recurrent ischemic events. Dementia was reported in 44 patients. Only 3 additional patients experienced migraine at a later time, while 13 additional patients developed depression. Six patients had seizures. Twenty-two of the 105 patients had died, with a mean age of death of 54.8±10.6 years. Nineteen of those 22 patients had experienced a stroke or transient ischemic attack and 19 patients were demented.

Conclusions
—CADASIL typically becomes evident in early or middle adulthood with migraine or an ischemic event, later manifests itself through recurrent subcortical ischemic strokes leading to a stepwise decline and dementia, and results in reduced survival.
Primary Hypoxic Tolerance and Chemical Preconditioning During Estrus Cycle in Mice
Authors: Kasischke Karl , Huber Roman , Li Hongge , Timmler Melanie , Riepe Matthias W.
Published: June 2011

Background and Purpose
—Exogenous application of estrogens or progesterone ameliorates hypoxic/ischemic cell damage. This study investigates whether values of primary and induced hypoxic tolerance vary endogenously during the estrus cycle in female mice.

Methods
—Population spike amplitude (PSA) and NADH were measured during hypoxic hypoxia and recovery in hippocampal slices from untreated control animals (C slices) and slices prepared from animals pretreated in vivo with a single intraperitoneal injection of 3-nitropropionate (3NP) (3NP slices) or acetylsalicylate (ASA) (ASA slices).

Results
—Posthypoxic recovery of PSA was dose dependent in 3NP slices from males, with maximal recovery on pretreatment attained with 20 mg/kg 3NP (82±32% [mean±SD]; C slices, 38±29%;
P
<0.01). PSA recovered to 17±12% in C slices during proestrus, 43±23% during estrus, and 63±44% during diestrus. In 3NP slices, recovery of PSA increased to 57±36% (
P
<0.05) during proestrus. Hypoxic tolerance was not increased in other stages of the estrus cycle. Hypoxic NADH increase during proestrus declined from 212±76% in C slices to 133±11% in 3NP slices (
P
<0.05). Recovery of PSA in ASA slices was 75±36% (
P
<0.01 versus control) in males and 48±34% during proestrus (
P
<0.05 versus ASA slices from males).

Conclusions
—Primary and induced hypoxic tolerance are endogenously modulated during the estrus cycle. Differences in hypoxic oxidative energy metabolism mediate part of the differential tolerance. Experimental and clinical therapeutic strategies against cerebral ischemia/hypoxia need to consider sex-related dependence.
Differential Time-Course Decreases in Nonselective, μ-, δ-, and κ-Opioid Receptors After Focal Cerebral Ischemia in Mice
Authors: Boutin Hervé , Dauphin François , MacKenzie Eric T. , Jauzac Philippe
Published: June 2011

Background and Purpose
—Neuroprotection studies have demonstrated the involvement of opioids in ischemia, and we have previously demonstrated alterations in B
max
of opioidergic receptors after 2 post-MCAO time points in mice.

Methods
—In the present study, we have investigated in a detailed manner the postischemic time course of variations in [
3
H]diprenorphine (nonselective), [
3
H]DAMGO (μ), [
3
H]DADLE (δ), and [
3
H]U69593 (κ) relative binding densities after focal cerebral ischemia (0 to 48 hours) in mice.

Results
—In frontoparietal cortices, our results demonstrate decreases in (1) δ receptor densities at 1 to 3 hours after MCAO, (2) μ and nonselective binding sites at 6 to 12 hours after MCAO, and (3) κ receptor densities between 6 and 24 hours after MCAO. In the rostral part of the infarct border zone, a decrease in δ-receptors was found concomitant with the extension of the infarct core; conversely, the decrease in δ-receptors appeared before (6 to 12 hours) macroscopic histological damage, which occurred between 12 hours and 24 hours after MCAO in the caudal part of this area. In this frontier, μ- and especially κ-binding sites were decreased later (12 to 48 hours after MCAO).

Conclusions
—These differential alterations in opioidergic receptors could be due to the selective sublocalization of receptors, postsynaptically on cortical interneurons for μ- and δ-receptors versus presynaptically on cortical afferent pathways for the κ subtype. Further, our results suggest that δ- and μ-opioidergic receptors could be markers of infarct extension and neuronal death; the study of [
3
H]diprenorphine and selective binding sites argues in favor of the use of receptor-specific ligands. Finally, the relative preservation of κ-receptors might be correlated with the neuroprotective role of κ-agonists, as previously reported.
Excess Stroke Among Hypertensive Men and Women Attributable to Undertreatment of Hypertension
Authors: Klungel Olaf H. , Stricker Bruno H. C. , Paes Arsenio H. P. , Seidell Jacob C. , Bakker Albert , Vokó Zoltán , Breteler Monique M. B. , Anthonius de Boer
Published: June 2011

Background and Purpose
—Most population-based studies indicate that a considerable proportion of hypertensive subjects are undertreated and that undertreatment is more prevalent among hypertensive men than among hypertensive women. The aim of our study was to investigate the consequences of undertreatment of hypertension for women and men in terms of stroke occurrence.

Methods
—Approximately 45 000 men and women aged ≥20 years were examined in 2 population-based studies in the Netherlands. A cohort of 2616 hypertensive subjects (pharmacologically treated hypertensives and untreated hypertensives who needed pharmacological treatment according to the severity of their hypertension and the coexistence of additional cardiovascular risk factors) was selected for a follow-up study. Follow-up (mean duration, 4.6 years) was complete for 2369 (91%) of the enrolled hypertensive subjects.

Results
—Compared with treated and controlled hypertensives, the relative risks of stroke for treated and uncontrolled hypertensives and for untreated hypertensives who needed treatment were 1.30 (95% CI, 0.70 to 2.44) and 1.76 (95% CI, 1.05 to 2.94), respectively. These relative risks and the prevalence of (undertreated) hypertension in the total population of 45 000 subjects were used to estimate the number of strokes in the Netherlands attributable to undertreatment. Among hypertensive men and women aged ≥20 years in the Netherlands, the proportions of strokes attributable to treated but uncontrolled blood pressure were 3.1% (95% CI, −5.2% to 18.7%) and 4.1% (95% CI, −7.2% to 20.7%), respectively. For untreated hypertensive men and women who should have been treated, these proportions were 22.8% (95% CI, 0.8% to 38.4%) and 25.4% (95% CI, 0.5% to 42.5%), respectively.

Conclusions
—Increasing the detection of hypertension and improving adherence to current guidelines might prevent a considerable proportion of the incident strokes among hypertensives. The potential impact of achieving control of blood pressure in patients already being treated on the reduction of strokes requires further investigation.
Improving Outcomes for Persons With Aphasia in Advanced Community-Based Treatment Programs
Authors: Aftonomos Lefkos B. , Appelbaum James S. , Steele Richard D.
Published: June 2011

Background and Purpose
—Studies have yet to document that community-based aphasia treatment programs routinely produce results comparable or superior to published research protocols. We explore this issue here in an outcome study of individuals with aphasia enrolled in 2 community-based, comparably managed and equipped therapy programs, which use a specially designed computer-based tool that is employed therapeutically in adherence to an extensive, detailed, and formally trained patient care algorithm.

Methods
—Patients (n=60) were assessed before and after treatment with standardized instruments at both the impairment and the disability levels. Pretreatment and posttreatment means were calculated and compared, with statistical significance of differences established with the use of 1-tailed matched
t
tests. One-way ANOVAs were used to analyze the comparability of patient performance changes among various subgroups, eg, patients in acute versus chronic stages of aphasia, patients by aphasia diagnostic type at start of care, patients by severity level at start of care, and patients by treatment location.

Results
—Analysis shows that patients spanned a wide range of aphasia diagnostic types, impairment severity levels at start of care, and times after onset. Patients’ mean performance scores improved significantly in response to treatment in all measures assessed at both the impairment level and the functional communication level. Mean overall improvements ranged from 6.6% to 19.8%, with statistical significance ranging from
P
=0.0006 to
P
<0.0001. ANOVAs revealed no significant differences between improvements in patients in the acute versus chronic stages of aphasia, between those at different impairment severity levels at start of care, between those treated at different locations, or, at the functional level, between those with different diagnostic types of aphasia at start of care.

Conclusions
—–Measures of both language impairment and functional communication can be broadly, positively, and significantly influenced by therapy services that are delivered to persons with aphasia in these community-based programs. The significant improvements are shown to be available to individuals with chronic as well as acute aphasia and independent of diagnostic type of aphasia, impairment severity at start of care, or geographic program location.
Structural Fragility and Inflammatory Response of Ruptured Cerebral Aneurysms
Authors: Kataoka Kazuo , Taneda Mamoru , Asai Toshiharu , Kinoshita Akira , Ito Mamoru , Kuroda Ryotaro
Published: June 2011

Background and Purpose
—Despite technical advances in endovascular and microsurgical treatment, patients with aneurysmal subarachnoid hemorrhage still have a high mortality and morbidity rate. To improve the treatment results in patients with aneurysms, we must better understand the pathophysiology of cerebral aneurysms and the mechanisms leading to their rupture. Therefore, we studied the pathological differences between unruptured and ruptured aneurysms.

Methods
—Ruptured (n=44) and unruptured (n=27) aneurysms were obtained at surgery. The aneurysmal endothelium was scored from 0 (normal) to 5 (complete disruption) by using a scanning electron microscope. The aneurysmal wall was evaluated by immunohistochemical methods. The wall structure was scored from 1 (dense collagen and rich, smooth muscle cells) to 5 (hyaline-like structure). The degree of inflammatory cell invasion into the wall was also scored from 0 (very few cells) to 3 (many cells).

Results
—Ruptured aneurysms manifested significant endothelial damage (score of 3.7 versus 0.8; Mann-Whitney
U
test,
P
<10
−3
), significant structural changes of the wall (3.7 versus 1.7,
P
<10
−5
), and significant inflammatory cell invasion (2.2 versus 0.8,
P
<10
−4
) compared with unruptured aneurysms. There was a significant correlation between the score for wall structure and the score for inflammatory cell invasion (
R
s
=0.63; Spearman rank correlation test,
P
<10
−5
). The pathophysiology of several symptomatic unruptured aneurysms was similar to that of ruptured aneurysms.

Conclusions
—We conclude that the pathophysiology of unruptured, asymptomatic and ruptured aneurysms is different. The wall of ruptured aneurysms was found to be fragile, possibly because macrophage infiltration into the aneurysmal wall resulted in loss of smooth muscle cells and in degradation of matrix proteins.
Multivariate Analysis of Predictors of Cerebral Vasospasm Occurrence After Aneurysmal Subarachnoid Hemorrhage
Authors: Charpentier Claire , Audibert Gerard , Guillemin Francis , Civit Thierry , Ducrocq Xavier , Bracard Serge , Hepner Henri , Picard Luc , Laxenaire Marie Claire
Published: June 2011

Background and Purpose
—The role of type of treatment on cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage (SAH) has not been studied. Through multivariate analysis we determined the independent prognostic factors of the occurrence of symptomatic vasospasm following aneurysmal SAH in a study cohort of 244 patients undergoing either surgical or endovascular treatment. The prognostic factors of sequelae after aneurysmal SAH were studied as well.

Methods
—Symptomatic vasospasm was defined as the association of deterioration in a patient’s neurological condition between 3 and 14 days after SAH with no other explanation and an increase in mean transcranial Doppler velocities of >120 cm/s. The prognostic factors were registered on admission and during the intensive care stay.

Results
—Symptomatic vasospasm occurred in 22.2% surgical patients compared with 17.2% endovascular treatment patients (
P
=0.37). Multivariate analysis revealed that the probability of occurrence of symptomatic vasospasm decreased with age >50 years (relative risk [RR], 0.47 [0.25 to 0.88]) and severe World Federation of Neurological Surgeons (WFNS) grade measured on admission (RR, 0.43 [0.20 to 0.90]) and increased with hyperglycemia occurring during the intensive care stay (RR, 1.94 [1.04 to 3.63]). No difference in risk of symptomatic vasospasm could be identified between surgical and endovascular treatment. Symptomatic vasospasm (OR, 4.73 [CI, 1.77 to 12.6]) as well as WFNS grade of >2 (OR, 8.95 [3.46 to 23.2]), treatment complications (OR, 8.39 [3.16 to 22.3]), and secondary brain insults were associated with an increased risk of 6-month sequelae.

Conclusions
—Age <50 years, good neurological grade, and hyperglycemia were all associated with an increased risk of cerebral vasospasm whereas treatment was not. This provides a basis for future clinical prospective randomized trials comparing both treatments.
Safety of Intrathecal Sodium Nitroprusside for the Treatment and Prevention of Refractory Cerebral Vasospasm and Ischemia in Humans
Authors: Thomas Jeffrey E. , Rosenwasser Robert H. , Armonda Rocco A. , Harrop James , Mitchell William , Galaria Irfan
Published: June 2011

Background and Purpose
—The delayed type of cerebral vasoconstriction known as cerebral vasospasm (DCV) remains an important cause of permanent neurological injury and death following aneurysmal subarachnoid hemorrhage despite best current medical therapy. The mechanism of DCV remains unknown. A new treatment for refractory DCV using intrathecally delivered sodium nitroprusside and results in 21 patients is reported.

Methods
—Candidates for treatment were patients with secured cerebral aneurysms presenting with clinical or radiographic SAH of grade 3 or higher. Patients with and without established DCV were treated. In 57% (12/21 patients) the diagnosis of severe DCV refractory to conventional treatment (HHH therapy and nimodipine) was established before treatment. Ten patients received ITSNP prophylactically. All patients with established DCV were in grave neurological condition before treatment. Procedures for vasospasm reversal were performed under simultaneous angiographic control with extensive hemodynamic and neurophysiologic monitoring. ITSNP was delivered by intraventricular or subdural catheter or by direct intraoperative suffusion. End points of intervention for established DCV were (1) durable angiographic reversal of vasoconstriction, (2) failure to effect reversal within 30 minutes, and (3) adverse effect. End points for DCV prevention were (1) post-SAH day 10 without evidence of vasoconstriction and (2) adverse effect. Cerebral angioplasty was used concomitantly in 9 treatments. The total number of treatments recorded was 171.

Results
—The overall neurological outcome was good or excellent in 76% of patients (16/21) overall and in 88.9% of patients (16/18) having at least a 1-month follow-up. Of the 5 patients with less-than-good outcome, 4 had presented initially with severe neurological injury (clinical SAH grade 4). Angiography demonstrated reversal or amelioration of vasoconstriction in 83% (5/6 cases) of established DCV treated by ITSNP alone. Among patients treated prophylactically, none developed clinical DCV.

Conclusions
—These results suggest that ITSNP is a safe and potentially effective treatment for established DCV and cerebral ischemia refractory to conventional treatment. The preliminary results of prophylactic treatment are also favorable with regard to safety.
Nimodipine and Perfusion Changes After Stroke
Authors: Infeld Bernard , Davis Stephen M. , Donnan Geoffrey A. , Yasaka Masahiro , Lichtenstein Meir , Mitchell Peter J. , Fitt Gregory J.
Published: June 2011

Background and Purpose
—Meta-analysis of previous trials of oral nimodipine in acute stroke has suggested a benefit when commenced within 12 hours of onset. We sought to study the effect of oral nimodipine on reperfusion after acute stroke and the relation between reperfusion and outcome.

Methods
—Fifty patients with acute middle cerebral artery territory cortical infarction were blindly randomized within 12 hours of onset to either oral nimodipine (30 mg every 6 hours) or placebo. Treatment was continued for 2 weeks. Cerebral blood flow was assessed with the use of
99m
Tc–hexamethylpropyleneamine oxime single-photon emission CT before therapy, 24 hours later, and at 3 months. Hypoperfusion was measured by a validated volumetric technique. Neurological impairment and functional outcome were assessed with the Canadian Neurological Scale and Barthel Index, respectively. Tissue loss was measured with CT at 3 months. Four patients were excluded from analysis for technical reasons.

Results
—Twenty-three patients received nimodipine, and 23 received placebo. In the nimodipine group, there was early reperfusion that was not maintained at outcome (
P
=0.01). In the placebo group, mean infarct hypoperfusion volumes showed no overall change. Nonnutritional reperfusion in nimodipine-treated patients was associated with adverse neurological (
P
=0.05) and functional outcome (
P
=0.06). There was, however, no difference in clinical outcome between the 2 groups.

Conclusions
—Oral nimodipine administered within 12 hours enhanced acute reperfusion, but this was largely nonnutritional. Larger studies using a shorter treatment delay are required to evaluate the clinical efficacy of nimodipine in acute ischemic stroke.
A Decrease in Regional Cerebral Blood Volume and Hematocrit in Crossed Cerebellar Diaschisis
Authors: Yamauchi Hiroshi , Fukuyama Hidenao , Nagahama Yasuhiro , Okazawa Hidehiko , Konishi Junji
Published: June 2011

Background and Purpose
—The pathophysiology of crossed cerebellar diaschisis (CCD) remains to be elucidated. In CCD, the metabolic suppression resulting from deafferentation may cause vasoconstriction, which may result in a decrease in cerebral blood volume (CBV) and may differentially affect the flows of red blood cells and of plasma. The purpose of this study was to investigate whether CCD decreases the total CBV (cerebral red blood cell volume [CRCV] plus cerebral plasma volume [CPV]) and, if so, whether CCD differentially affects the CRCV and CPV, resulting in a change in hematocrit.

Methods
—We used positron emission tomography to study 7 patients with a unilateral supratentorial infarct and CCD. The distributions of CRCV and CPV were assessed by using
15
O-labeled carbon monoxide and
62
Cu-labeled human serum albumin–dithiosemicarbazone tracers, respectively. The CRCV, CPV, and calculated hematocrit values were compared between the cerebellar hemispheres.

Results
—In the cerebellar cortex contralateral to the supratentorial infarct, the values of CRCV, CPV, and total CBV were significantly decreased compared with those in the ipsilateral cerebellar cortex. The CRCV was decreased to a greater degree than the CPV, and the value of the hematocrit was decreased in the contralateral cerebellar cortex.

Conclusions
—CCD may decrease the total CBV, which may reflect vasoconstriction caused by decreased metabolism due to deafferentation. In addition, the more pronounced decrease in CRCV than in CPV may result in a decrease in hematocrit in CCD.
Asymptomatic Embolization Predicts Stroke and TIA Risk in Patients With Carotid Artery Stenosis
Authors: Molloy Jane , Markus Hugh S.
Published: June 2011

Background and Purpose
—Improved methods of identifying patients at high risk of thromboembolism would allow improved targeting of therapy. One such situation is carotid artery stenosis. This is associated with an increased risk of stroke, which can be reduced by carotid endarterectomy. However, the risk-benefit ratio is low in patients with tight asymptomatic stenosis and moderate symptomatic stenosis. Most stroke in patients with carotid stenosis is believed to be embolic. Therefore, the detection of asymptomatic cerebral emboli using Doppler ultrasound may allow identification of a high-risk group.

Methods
—Transcranial Doppler ultrasound was used to record for 1 hour the ipsilateral middle cerebral artery in 111 patients with >60% carotid artery stenosis (69 symptomatic, 42 asymptomatic). The Doppler audio signal was recorded onto digital audio tape for later analysis for embolic signals (ES) by an individual blinded to clinical details. In 67 subjects the relationship between ES and angiographically determined plaque ulceration was investigated. All subjects were followed up prospectively, and the relationship between ES and risk of future ipsilateral carotid artery territory ischemic events (TIA and stroke) was determined.

Results
—ES were detected in 41(36.9%) subjects. In symptomatic patients there was a significant inverse relationship between the number of ES per hour and time elapsed since last symptoms (Spearman’s ρ=−0.2558,
P
=0.034). ES were more common in subjects with plaque ulceration, with a relative risk of 4.94 (95% CI, 1.23 to 19.84;
P
=0.025) after controlling for both symptomatic status and degree of stenosis. The presence of ES at entry was predictive of TIA and stroke risk during follow up in both symptomatic (
P
=0.02) and asymptomatic patients (
P
=0.007). Considering all 111 patients, the presence of asymptomatic embolization was predictive of a further ischemic event, with an adjusted OR of 8.10 (95% CI, 1.58 to 41.57;
P
=0.01) after controlling for other cardiovascular risk factors, degree of stenosis, symptomatic status, and aspirin or warfarin use.

Conclusions
—Asymptomatic embolization in patients with carotid artery stenosis correlates with known markers of increased stroke risk and is an independent predictor of future stroke risk in patients with both symptomatic and asymptomatic carotid stenosis. It may allow identification of a high-risk group of patients who will particularly benefit from carotid endarterectomy. A large multicenter study is now required to confirm these findings.
Success Rate of Transcranial Color-Coded Duplex Ultrasonography in Visualizing the Basal Cerebral Arteries in Vascular Patients Over 60 Years of Age
Authors: Hoksbergen A. W. J. , Legemate D. A. , Ubbink D. T. , Jacobs M. J. H. M.
Published: June 2011

Background and Purpose
—Clinically important atherosclerotic cerebrovascular disease is mainly found in patients aged >60 years. Transcranial color-coded duplex ultrasonography (TCCD) is a relatively new technique for investigating the basal cerebral arteries; however, it is often hampered by impenetrable ultrasound windows. The aim of this study was to ascertain the as yet unknown success rate of TCCD regarding visualization of the basal cerebral arteries in patients >60 years, to provide reference data, and to compare any possible male/female differences.

Methods
—In 112 atherosclerotic white patients >60 years of age, the anterior, middle, and posterior cerebral arteries and the vertebral and basilar arteries were insonated.

Results
—In men, 99% of the temporal and 94% of the suboccipital windows could be penetrated by ultrasound compared with 77% and 95%, respectively, in women. The male versus female vessel detection rates were 91% versus 58% for the anterior cerebral artery, 97% versus 73% for the middle cerebral artery, 97% versus 68% for the posterior cerebral artery, 94% versus 93% for the vertebral artery, and 91% versus 79% for the basilar artery. In 77% of men but only 33% of women could all vascular segments be investigated. All intracranial arteries were insonated at a deeper level in men. The women showed significantly higher blood flow velocities than the men.

Conclusions
—In elderly white men the vessel detection rate is >90%. In women there is a much lower detection rate, due to impenetrable temporal windows. Visualization of all major intracranial arteries is possible in only one third of female patients >60 years of age.
Decompressive Craniectomy, Reperfusion, or a Combination for Early Treatment of Acute “Malignant” Cerebral Hemispheric Stroke in Rats?
Authors: Engelhorn Tobias , Doerfler Arnd , Kastrup Andreas , Beaulieu Christian , Alexander de Crespigny  , Forsting Michael , Moseley Michael E.
Published: June 2011

Background and Purpose
—Both early reperfusion and decompressive craniectomy have proved beneficial in the treatment of large space-occupying “malignant” hemispheric stroke. The aim of this study was to directly compare the benefit of reperfusion with that of craniectomy and to study the effects of combined treatment in a rat model of focal cerebral ischemia.

Methods
—Cerebral ischemia was introduced in 28 rats. Four groups were investigated: (1) no treatment, (2) decompressive craniectomy, (3) reperfusion, and (4) reperfusion and craniectomy as treatment at 1 hour after middle cerebral artery occlusion. Perfusion- and diffusion-weighted MRI were performed serially from 0.5 to 6 hours after middle cerebral artery occlusion.

Results
—The 6-hour DWI-derived hemispheric lesion volumes in the reperfusion group (10.2±3.9%), the craniectomy group (23.0±6.4%), and the combination group (21.8±12.4) were significantly smaller than that in the control group (44.1±5.4%) (
P
<0.05). Reperfusion, craniectomy, and combined treatment led to higher perfusion in the cortex compared with the control group, whereas only reperfused animals achieved significantly higher perfusion in the basal ganglia. In 5 animals, combined reperfusion and decompressive craniectomy resulted in an early contrast media enhancement.

Conclusions
—Early reperfusion and craniectomy were shown to be effective in decreasing infarction volume by improving cerebral perfusion. Reperfusion remains the best therapy in malignant hemispheric stroke. Combined treatment yields no additional benefit compared with single treatment, probably because of early blood-brain barrier breakdown.
Stroke Unit Treatment
Authors: Indredavik B. , Bakke F. , Slørdahl S. A. , Rokseth R. , Håheim L. L.
Published: June 2011

Background and Purpose
—We have previously shown that treatment in our combined acute and rehabilitation stroke unit (SU) improves the outcome during the first 5 years after onset of stroke compared with that for stroke patients treated in general wards (GW). The aim of the present trial was to examine the effects of SU care after 10 years of follow-up.

Methods
—In a randomized controlled trial, 110 patients with symptoms and signs of an acute stroke were allocated to the SU and 110 to GW. No significant differences existed in baseline characteristics between the groups. The outcome after 10 years was measured by the proportion of patients at home, the proportion of patients in an institution, the mortality, and the functional state as assessed by the Barthel Index, in which a Barthel Index score of ≥60 was classified as independent or partly independent and a score of ≥95 was classified as independent.

Results
—After 10 years, 21 (19.1%) of the patients randomized to the SU and 9 (8.2%) of the patients randomized to the GW were at home (
P
=0.0184). Eighty-three (75.5%) of the patients from the SU and 96 (87.3%) of the patients from the GW were dead (
P
=0.0082), and 6 (5.4%) and 5 (4.5%), respectively, were in an institution (eg, nursing home; NS). Twenty-two (20.0%) of the SU patients and 9 (8.2%) of the GW patients had a Barthel Index score of ≥60 (
P
=0.0118), and 14 (12.7%) and 6 (5.4%), respectively, had a score of ≥95 (
P
=0.0606).

Conclusions
—For the first time it has been shown that SU care improves survival and functional state and increases the proportion of patients able to live at home 10 years after their stroke. Treatment in combined acute and rehabilitation SU seems to have important long-term effects on outcome for stroke patients.
Elevated Anticardiolipin Antibody Titer Is a Stroke Risk Factor in a Multiethnic Population Independent of Isotype or Degree of Positivity
Authors: Tuhrim Stanley , Rand Jacob H. , Wu Xiao-Xuan , Weinberger Jesse , Horowitz Deborah R. , Goldman Martin E. , Godbold James H.
Published: June 2011

Background and Purpose
—Previous studies have produced conflicting results regarding the putative association between anticardiolipin antibodies (aCL) and infarction in the general stroke population. These inconsistencies may be a function of sample size and methodological differences among the studies. The purpose of the present study, the largest case-control study of this issue to date, was to assess aCL status as an independent risk factor for ischemic stroke in a multiethnic, urban population.

Methods
—We obtained aCL titers in 524 hospitalized acute stroke patients and 1020 community controls enrolled in the Minorities Risk Factors and Stroke Study. The results were interpreted as negative (≤22.9 IgG phospholipid [GPL] or 10.9 IgM phospholipid [MPL] units), low positive (22.9 to 30.0 GPL or 10.9 to 15.0 MPL units), or high positive (>30.0 GPL or 15.0 MPL units). Odds ratios (ORs) were adjusted for age, sex, race/ethnicity, history of diabetes, hypertension, atrial fibrillation, coronary artery disease, and current cigarette smoking.

Results
—A positive aCL titer was present in 11% (111/1020) of controls and 34% (180/524) of cases. The adjusted OR for any positive aCL titer was 4.0 (95% CI, 3.0 to 5.5). For any positive IgG aCL titer this value was 3.9 (95% CI, 2.8 to 5.5), and for any positive IgM aCL titer it was 3.4 (95% CI, 2.1 to 5.5). There were no significant differences in ORs associated with high- or low-positive IgG or IgM aCL titers.

Conclusions
—In the largest study of its kind to date, aCL antibodies were demonstrated to be independent stroke risk factors across the 3 ethnic groups studied, conferring a 4-fold increased risk of ischemic stroke. IgG and for the first time IgM aCL were each shown to be associated with increased stroke risk. The prevalence of these antibodies and the stroke risk associated appear greater than previously reported.
Measurement of Initial
N-
Acetyl Aspartate Concentration by Magnetic Resonance Spectroscopy and Initial Infarct Volume by MRI Predicts Outcome in Patients With Middle Cerebral Artery Territory Infarction
Authors: Pereira Anthony C. , Saunders Dawn E. , Doyle Victoria L. , Bland J. Martin , Howe Franklyn A. , Griffiths John R. , Brown Martin M.
Published: June 2011

Background and Purpose
—
1
H MR spectroscopy can be used to study biochemical changes occurring in the brain in stroke. We used it to examine the relationship between metabolite concentration (
N
-acetyl aspartate [NAA], lactate, cholines and creatines), size of infarct, clinical deficit, and 3-month clinical outcome in patients with middle cerebral artery (MCA) territory infarction.

Methods
—Thirty-one patients with acute MCA territory infarction were recruited within 72 hours of the onset of symptoms. Single-voxel short echo time stimulated echo acquistion mode spectroscopy was used to obtain metabolite data from the infarct core. Metabolite concentrations were determined with use of variable projection time domain-fitting analysis. Infarct size was determined with T2-weighted images. Patient outcome groups at 3 months were “independent,” “dependent,” or “dead.”

Results
—All patients (100%; 95% CI 75% to 100%) who had an infarct >70 mL did poorly. Eighteen of 20 patients (90%; 95% CI 68% to 99%) with a core NAA concentration <7 mmol/L did poorly at 3 months, whereas 7 of 11 patients (64%; 95% CI 31% to 89%) with an initial NAA concentration >7 mmol/L did well. Combining these results showed that all patients who had an initial infarct volume >70 mL did poorly, irrespective of the NAA concentration. Of those patients with infarcts <70 mL, those who had a core NAA concentration >7 mmol/L did well (88%; 95% CI 47% to 100%), whereas those with a lower NAA concentration did poorly (80%; 95% CI 44% to 97%). There was no association between other metabolite concentrations and outcome.

Conclusions
—Infarct volume and NAA concentration can together predict clinical outcome in MCA infarction in humans.
Effect of Intravenous Dipyridamole on Cerebral Blood Flow in Humans
Authors: Ito Hiroshi , Kinoshita Toshibumi , Tamura Yoshikazu , Yokoyama Ikuo , Iida Hidehiro
Published: June 2011

Background and Purpose
—Dipyridamole increases the concentration of circulating adenosine, which is a potent vasodilator, by inhibition of uptake of adenosine into the erythrocytes, and hence produces coronary vasodilation. However, the effects of dipyridamole on cerebral circulation is not pronounced. This study investigates the effects of intravenous dipyridamole on cerebral blood flow (CBF) in humans with use of positron emission tomography (PET).

Methods
—In each of 13 healthy subjects, CBF was measured using
15
O-labeled water and PET at rest and during hypercapnia, hypocapnia, and dipyridamole stress; corresponding CBF values were then compared.

Results
—CBF values during dipyridamole stress were significantly lower than those measured at rest. The dipyridamole stress Pa
co
2
was also significantly lower than the resting Pa
co
2
. The change in CBF during dipyridamole stress relative to Pa
co
2
closely followed the relationship between CBF and Pa
co
2
during hypocapnia.

Conclusions
—These results indicate that the observed decrease in CBF during dipyridamole stress was caused by a decrease in Pa
co
2
rather than by any direct action of dipyridamole on CBF. The decrease in Pa
co
2
during dipyridamole stress was most likely due to hyperventilation, which was a side effect of adenosine. These results support the hypothesis that circulating adenosine is largely prevented from binding to adenosine receptors of cerebral vessels by the blood-brain barrier.
Type III Collagen Deficiency in Saccular Intracranial Aneurysms
Authors: van den Berg J. S. P. , Pals G. , Arwert F. , Hennekam R. C. M. , Albrecht K. W. , Westerveld A. , Limburg M.
Published: June 2011

Background and Purpose
—We sought to determine whether there are mutations in the
COL3A1
gene in patients with saccular intracranial aneurysms with a type III collagen deficiency and whether there is an association between a marker in the
COL3A1
gene and saccular intracranial aneurysms. One of the heritable factors possibly involved in the pathogenesis of saccular intracranial aneurysms is a reduced production of type III collagen, demonstrated earlier by protein studies.

Methods
—We analyzed the type III collagen gene in a group of 41 consecutive patients with an intracranial aneurysm, of whom 6 patients had shown a reduced production of type III collagen in cultured diploid fibroblasts from a skin biopsy.

Results
—No mutations could be demonstrated in the
COL3A1
gene, especially not in the globular N- and C-terminal regions. A null allele was excluded in 25 patients, including 1 patient with a decreased type III collagen production. No differences were found between 41 patients and 41 controls in allele frequencies of a DNA tandem repeat polymorphism located in the
COL3A1
gene.

Conclusions
—It is concluded that the
COL3A1
gene is not directly involved in the pathogenesis of most of intracranial aneurysms. The reduced type III collagen production in cultured fibroblasts found in some patients with an intracranial aneurysm is not explained by the present study and needs further exploration.
Angiitis of the Central Nervous System After Allogeneic Bone Marrow Transplantation?
Authors: Padovan Claudio S. , Bise Karl , Hahn Joachim , Sostak Petra , Holler Ernst , Kolb Hans-Jochem , Straube Andreas
Published: June 2011

Background and Purpose
—There is only limited information about late neurological complications after bone marrow transplantation (BMT). The purpose of this study is to describe a cerebral angiitis-like syndrome after allogeneic BMT.

Methods
—Clinical and diagnostic findings of 5 BMT patients with chronic graft versus host disease and neuropathological data of 1 patient were reported.

Results
—In the described patients, focal neurological signs and neuropsychological abnormalities occurred years after BMT. MRI revealed periventricular white matter lesions, lacunar or territorial infarctions, leukoencephalopathy, and hemorrhages. Angiitis of the central nervous system was confirmed in 1 patient at autopsy, and an angiitis-like syndrome was suspected in the other patients because of the clinical course and response to treatment. Three patients received cyclophosphamide and steroids (2 improved, 1 died), 1 patient improved after steroids alone, and 1 patient without immunosuppressive therapy deteriorated further.

Conclusions
—–We propose that an angiitis-like syndrome of the central nervous system can be a neurological manifestation of graft versus host disease, which should be considered a possible cause of cerebral ischemic episodes and pathological MRI scans in BMT patients with graft versus host disease.
Medical Complications Associated With Carotid Endarterectomy
Authors: Paciaroni Maurizio , Eliasziw Michael , Kappelle L. Jaap , Finan Jane W. , Ferguson Gary G. , Barnett Henry J. M.
Published: June 2011

Background and Purpose
—Carotid endarterectomy (CE) has been shown to be beneficial in patients with symptomatic high-grade (70% to 99%) internal carotid artery stenosis. To achieve this benefit, complications must be kept to a minimum. Complications not associated with the procedure itself, but related to medical conditions, have received little attention.

Methods
—Medical complications that occurred within 30 days after CE were recorded in 1415 patients with symptomatic stenosis (30% to 99%) of the internal carotid artery. They were compared with 1433 patients who received medical care alone. All patients were in the North American Symptomatic Carotid Endarterectomy Trial (NASCET).

Results
—One hundred fifteen patients (8.1%) had 142 medical complications: 14 (1%) myocardial infarctions, 101 (7.1%) other cardiovascular disorders, 11 (0.8%) respiratory complications, 6 (0.4%) transient confusions, and 10 (0.7%) other complications. Of the 142 complications, 69.7% were of short duration, and only 26.8% prolonged hospitalization. Five patients died: 3 from myocardial infarction and 2 suddenly. Medically treated patients experienced similar complications with one third the frequency. Endarterectomy was ≈1.5 times more likely to trigger medical complications in patients with a history of myocardial infarction, angina, or hypertension (
P
<0.05).

Conclusions
—Perioperative medical complications were observed in slightly fewer than 1 of every 10 patients who underwent CE. The majority of these complications completely resolved. Most complications were cardiovascular and occurred in patients with 1 or more cardiovascular risk factors. In this selected population, the occurrence of perioperative myocardial infarction was uncommon.