bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatal Cerebral Reperfusion Hemorrhage After Carotid Stenting
Authors: McCabe Dominick J. H. , Brown Martin M. , Clifton Andrew
Published: June 2011

Background
—The hyperperfusion syndrome is a recognized complication of carotid endarterectomy. Reports of cerebral hyperperfusion injury following internal carotid artery (ICA) angioplasty are few, and this complication has never been reported following internal carotid stenting.

Case Description
—A 68-year-old normotensive man was referred to our hospital for assessment 5 months after experiencing a left hemispheric ischemic stroke. Angiography confirmed 95% stenosis of the left ICA. Left carotid percutaneous transluminal stenting was performed without any initial complications. Color Doppler ultrasound of the ICA immediately after stenting revealed an elevated peak systolic velocity of 2.3 m/s, in the absence of significant vessel stenosis or spasm on angiography. Seven hours after the procedure, the patient suddenly deteriorated. CT of the brain revealed extensive intracerebral hemorrhage (ICH), and he subsequently died 18 days later. There was no history of headache or seizure activity, and his blood pressure was only mildly elevated at the time of the deterioration. This is the first report of ICH after internal carotid stenting.

Conclusions
—ICH may occur as a hyperperfusion phenomenon after internal carotid stenting, in the presence of mild to moderate arterial hypertension, without being heralded by any of the typical symptoms of the hyperperfusion syndrome. Patients with increased velocities on color Doppler ultrasound of the ICA after angioplasty should be monitored closely for features of cerebral hyperperfusion injury. Further studies are warranted to determine whether more aggressive treatment of mild to moderate hypertension after carotid stenting would reduce the likelihood of this potentially fatal complication.
Stroke Location Is Not Associated With Return to Work After First Ischemic Stroke
Authors: Wozniak M. A. , Kittner S. J. , Price T. R. , Hebel J. R. , Sloan M. A. , Gardner J. F.
Published: June 2011

Background and Purpose
—In prior studies, age, race, job category, disability, and cortical functions such as praxis, language, and memory have been associated with vocational outcome, but the influence of stroke location on return to work has never been critically examined.

Methods
—We examined the influence of stroke location on vocational outcome in patients with clinically confirmed acute ischemic stroke from the National Institute of Neurological Disorders and Stroke Stroke Data Bank.

Results
—Of 143 patients working full time at the time of first ischemic stroke, 23 patients were dead and 120 were alive at 1 year. Employment status was known in 109 (mean age, 55 years; 51 [47%] were white, and 82 [75%] were male). Fifty-eight (53%) had returned to work; most (85%) worked full time. Younger age was positively associated with return to work (
P
<0.05). In an age-adjusted analysis, stroke severity as measured by the Barthel Index 7 to 10 days after stroke was negatively associated with return to work (
P
<0.001). Higher household income and absence of cortical neurological dysfunction 7 to 10 days after stroke were positively but less strongly associated with return to work (
P
<0.08). Stroke location, sex, and depression at time of stroke were not associated with vocational outcome.

Conclusions
—Our data suggest that stroke location may be less important than other more easily measured factors in predicting vocational outcome.
Helicopter Transfer Offers a Potential Benefit to Patients With Acute Stroke
Authors: Conroy Molly B. , Rodriguez Susan U. , Kimmel Stephen E. , Kasner Scott E.
Published: June 2011

Background and Purpose
—Rapid transport of patients to specialized centers is widely used in the management of myocardial infarction, trauma, and more recently, acute stroke. We evaluated the role of helicopter transportation as it relates to the availability of acute stroke therapies and patients’ perceptions of care.

Methods
—We reviewed records of all patients transferred to a university hospital within 24 hours of stroke onset from January 1996 to December 1997. Data were collected on demographics, neurological deficit, treatment, and outcome. In addition, a questionnaire was sent to all patients with items about perceived reasons for helicopter transfer, expected and actual treatment, outcome, and overall impression.

Results
—Helicopter transfer was used for 73 stroke patients. Before transfer, 8 patients (11%) received tissue plasminogen activator (tPA). On arrival, no patient received tPA, 38 patients (52%) were enrolled in acute stroke studies, and 35 patients (48%) received no specific medication. All but 2 patients were managed in a specialized stroke unit. Of the 35 patients who received no specific therapy, 24 (69%) were ineligible for treatment or study enrollment owing to 1 or more exclusion criteria, but rarely (3%) because of time. Of the 45 respondents to the survey, most (84%) were transferred at the suggestion of the physician at the originating hospital because of a possible treatment that was unavailable there. Most patients (93%) believed that there was a benefit from emergent helicopter transfer to a stroke center, although 40% of respondents received no specific therapy.

Conclusions
—Interhospital transfer by air may benefit a substantial number of acute stroke patients by offering potential therapies and intensive management not available elsewhere.
Randomized Controlled Trial of a Comprehensive Stroke Education Program for Patients and Caregivers
Authors: Rodgers Helen , Atkinson Catherine , Bond Senga , Suddes Michael , Dobson Ruth , Curless Richard
Published: June 2011

Background and Purpose
—We report the findings of a randomized controlled trial to determine the effectiveness of a multidisciplinary Stroke Education Program (SEP) for patients and their informal carers.

Methods
—Two hundred four patients admitted with acute stroke and their 176 informal carers were randomized to receive an invitation to the SEP or to receive conventional stroke unit care. The SEP consisted of one 1-hour small group educational session for inpatients followed by six 1-hour sessions after discharge. The primary outcome measure was patient- and carer-perceived health status (SF-36) at 6 months after stroke. Knowledge of stroke, satisfaction with services, emotional outcome, disability, and handicap and were secondary outcome measures.

Results
—Only 51 of 108 (47%) surviving patients randomized to the SEP completed the program, as did 20 of 93 (22%) informal carers of surviving patients. Perceived health status (Short Form 36 [SF-36] health survey) scores were similar for SEP patients and controls. Informal carers in the control group scored better on the social functioning component of the SF-36 than the SEP group (
P
=0.04). Patients and informal carers in the SEP group scored higher on the stroke knowledge scale than controls (patients,
P
=0.02; carers,
P
=0.01). Patients in the SEP group were more satisfied with the information that they had received about stroke (
P
=0.004). There were no differences in emotional or functional outcomes between groups.

Conclusions
—Although the SEP improved patient and informal carer knowledge about stroke and patient satisfaction with some components of stroke services, this was not associated with an improvement in their perceived health status. Indeed, the social functioning of informal carers randomized to the SEP was less than in the control group.
Mitochondrial Potassium Channel Opener Diazoxide Preserves Neuronal-Vascular Function After Cerebral Ischemia in Newborn Pigs
Authors: Domoki Ferenc , Perciaccante James V. , Veltkamp Roland , Bari Ferenc , Busija David W.
Published: June 2011

Background and Purpose
—
N
-Methyl-
d
-aspartate (NMDA) elicits neuronally mediated cerebral arteriolar vasodilation that is reduced by ischemia/reperfusion (I/R). This sequence has been preserved by pretreatment with the ATP-sensitive potassium (K
ATP
) channel opener aprikalim, although the mechanism was unclear. In the heart, mitochondrial K
ATP
channels (mitoK
ATP
) are involved in the ischemic preconditioning-like effect of K
+
channel openers. We determined whether the selective mitoK
ATP
channel opener diazoxide preserves the vascular dilation to NMDA after I/R.

Methods
—Pial arteriolar diameters were determined with the use of closed cranial window/intravital microscopy in anesthetized piglets. Vascular responses to NMDA were assessed before and 1 hour after 10 minutes of global cerebral ischemia induced by raising intracranial pressure. Subgroups received 1 of the following pretreatments before I/R: vehicle; 1 to 10 μmol/L diazoxide; and coapplication of 100 μmol/L 5-hydroxydecanoic acid (5-HD), a K
ATP
antagonist with diazoxide.

Results
—NMDA-induced dose-dependent pial arteriolar dilation was not affected by diazoxide treatment only but was severely attenuated by I/R. In contrast, diazoxide dose-dependently preserved the NMDA vascular response after I/R; at 10 μmol/L, diazoxide arteriolar responses were unaltered by I/R. The effect of diazoxide was antagonized by coapplication of 5-HD with diazoxide. Percent preservation of 100 μmol/L NMDA–induced vasodilation after I/R was 53±19% (mean±SEM, n=8) in vehicle-treated controls versus 55±10%, 85±5%, and 99±15% in animals pretreated with 1, 5, and 10 μmol/L diazoxide (n=8, n=8, and n=12, respectively) and 60±15% in the group treated with 5-HD+diazoxide (n=5).

Conclusions
—The mitoK
ATP
channel opener diazoxide in vivo preserves neuronal function after I/R, shown by pial arteriolar responses to NMDA, in a dose-dependent manner. Thus, activation of mitoK
ATP
channels may play a role in mediating the protective effect of other K
+
channel openers.
Contribution of 20-HETE to Vasodilator Actions of Nitric Oxide in the Cerebral Microcirculation
Authors: Alonso-Galicia Magdalena , Hudetz Antal G. , Shen Hui , Harder David R. , Roman Richard J.
Published: June 2011

Background and Purpose
—The present study examined the contributions of a rise in cGMP versus a fall in 20-HETE levels to the vasodilator response to nitric oxide (NO) in the cerebral circulation of the rat.

Methods
—Intact rat middle cerebral and basilar arteries were bathed in physiological saline solution containing indomethacin (5 μmol/L) and baicalein (0.5 μmol/L) and pressurized at 90 mm Hg. Relaxations to sodium nitroprusside (SNP) were studied before and after addition of [1H-[1,2,4]oxadiazole[4,3-
a
]quinoxalin-1-one] (ODQ, a guanylyl cyclase blocker), 8
R
,9
S
,11
S
-(−)-9-methoxy-carbamyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7
b
,11
a
-trizadibenzo-(
a
,
g
)-cycloocta-(
c
,
d
,
e
)-trinden-1-one (KT5823, a protein kinase G blocker), and 20-hydroxyeicosatetraenoic acid (20-HETE). Cerebral blood flow was measured by using a laser Doppler flow probe over a thin cranial window in anesthetized rats, and the effects of intracerebroventricular infusion of 1-hexamine,6-(2-hydroxy-1-methyl-2-nitrosohydrazino)
N
-methyl (MAHMA nonoate) and dibromododecenyl methylsulfimide (DDMS) were determined.

Results
—SNP-induced dilation of serotonin-preconstricted (0.2 μmol/L) middle cerebral arteries (10
−7
to 10
−3
mol/L) was attenuated in arteries treated with ODQ (10 μmol/L) or KT5823 (1 μmol/L) by 52% and 27%, respectively. Preventing the NO-induced fall in intracellular 20-HETE, by adding 20-HETE (100 nmol/L) to the bath, reduced the dilation to SNP by 62%. Simultaneous administration of ODQ and 20-HETE markedly attenuated the SNP-induced dilation by 90%. In basilar arteries, ODQ (10 μmol/L) alone completely blocked the response to SNP. Infusion of MAHMA nonoate (10 nmol/min ICV) in anesthetized rats increased cerebral blood flow by 52% before and 8% after blockade of the endogenous production of 20-HETE with DDMS (50 pmol/min).

Conclusions
—These results suggest that NO dilates cerebral arteries through both cGMP-dependent and cGMP-independent pathways and that inhibition of 20-HETE formation contributes to the cerebral vasodilator response to NO both in vitro and in vivo.
Risk of Cerebral Angiography in Patients With Subarachnoid Hemorrhage, Cerebral Aneurysm, and Arteriovenous Malformation
Authors: Cloft Harry J. , Joseph Gregory J. , Dion Jacques E.
Published: June 2011

Background and Purpose
—A well-defined complication rate of cerebral angiography in patients with subarachnoid hemorrhage (SAH), cerebral aneurysm, and arteriovenous malformation (AVM) would be useful to physicians making decisions regarding the imaging of these patients. We sought to define a statistically significant complication rate through meta-analysis of prospective studies in the literature.

Methods
—Meta-analysis of 3 published prospective studies of complications in cerebral angiography was performed to specifically define the risk of cerebral angiography in patients presenting with SAH, cerebral aneurysm, and AVM. The complication rates for cerebral angiography in patients with SAH and AVM/aneurysm without SAH were compared with the complication rates in patients who underwent cerebral angiography for transient ischemic attack (TIA)/ischemic stroke with use of the Fisher exact test.

Results
—The combined risk of permanent and transient neurological complication was significantly lower in patients with SAH compared with patients with TIA/stroke (1.8% versus 3.7%;
P
=0.03). The combined risk of permanent and transient neurological complication was significantly lower in patients with aneurysm/AVM without SAH compared with patients with TIA/stroke (0.3% versus 3.7%;
P
=0.001). When the patients with SAH and cerebral aneurysm/AVM were combined, the overall risk of permanent and transient neurological complication was significantly lower than for the TIA/stroke patients (0.8% versus 3.0%;
P
=0.001), as was the risk of permanent neurological complication (0.07% versus 0.7%;
P
=0.004).

Conclusions
—The risk of permanent neurological complication associated with cerebral angiography in patients with SAH, cerebral aneurysm, and AVM is quite low (0.07%). This risk is lower than previously recognized.
Epidemiology of Recurrent Cerebral Infarction
Authors: Samsa Gregory P. , Bian John , Lipscomb Joseph , Matchar David B.
Published: June 2011

Background and Purpose
—Because recurrent strokes will tend to leave patients with greater disability than first strokes, patients with recurrent strokes should have poorer outcomes on average than those with first strokes. The extent of this difference has, however, not yet been estimated with precision.

Methods
—Using a random 20% sample of Medicare patients aged 65 years and older admitted with a primary diagnosis of cerebral infarction during calendar year 1991, we used historical data from the previous 4 years to classify patients as having either first or recurrent stroke and followed survival and direct medical costs for 24 months after stroke. First and recurrent stroke groups were compared with the log-rank test (survival) and
t
test (cost) and also multivariate modeling.

Results
—Survival from first stroke is consistently better than that for recurrent stroke: 24-month survival was 56.7% versus 48.3%, respectively. Costs were similar for the initial hospital stay and in months 1 to 3 after stroke. During months 4 to 24 after stroke, total costs were higher among those with recurrent stroke by approximately $375/mo across all patients, with this difference being greatest for younger patients and least for patients aged 80 years or older. Most of the difference in total monthly cost was attributable to nursing home utilization (averaging approximately $150/mo) and acute hospitalization (averaging approximately $120/mo).

Conclusions
—Patients with recurrent stroke have, on average, poorer outcomes than those with first stroke. To be as accurate as possible, clinical policy analyses should use different estimates of health and cost outcomes for first and recurrent stroke.
Prevalence and Associations of MRI-Demonstrated Brain Infarcts in Elderly Subjects With a History of Transient Ischemic Attack
Authors: Bhadelia Rafeeque A. , Anderson Melissa , Polak Joseph F. , Manolio Teri A. , Beauchamp Norman , Knepper L. , O’Leary Daniel H.
Published: June 2011

Background and Purpose
—MRI is more sensitive than CT, but the significance of brain abnormalities seen on MR images obtained in older subjects with transient ischemic attack (TIA) is not clear. We studied the prevalence and risk factors associated with MRI-demonstrated infarcts in elderly subjects with a history of TIA.

Methods
—Participants of the Cardiovascular Health Study, aged 65 years or more and without prior stroke, were studied with brain MRI (n=3456). The prevalence of brain infarcts (≥3 mm) on MRI was determined in subjects with and without TIA. The cardiovascular risk factors and clinical and subclinical cardiovascular disease associated with MRI infarcts were studied in subjects with TIA.

Results
—Subjects with TIA (n=100) had a higher prevalence of MRI infarcts than subjects without TIA (46% versus 28%;
P
<0.001). The unadjusted odds ratio for having MRI infarcts in subjects with TIA was 2.20 (95% CI, 1.47 to 3.30) and remained significantly elevated after adjustments for risk factors and cerebrovascular disease (odds ratio, 1.86; 95% CI, 1.23 to 2.83). In subjects with TIA, diastolic blood pressure (
P
=0.01) and internal carotid artery intima-media thickness (
P
=0.01) were the only factors predictive of the presence of MRI infarcts by stepwise logistic regression analysis.

Conclusions
—MRI infarcts are imaging manifestations of clinically important cerebrovascular disease in subjects with a history of TIA, given their increased prevalence and positive association with increased diastolic blood pressure and internal carotid artery intima-media thickness.
Evaluation of Early Computed Tomographic Findings in Acute Ischemic Stroke
Authors: Marks Michael P. , Holmgren Eric B. , Fox Allan J. , Patel Suresh , von Kummer Rudiger , Froehlich Juergen
Published: June 2011

Background and Purpose
—Detection of large, hypoattenuated brain-tissue volume on hyperacute CT scan has been suggested as an exclusion criterion for early intravenous tissue plasminogen activator (IV-tPA) treatment. This study assessed the reliability of detection for these findings and their relationship to outcome.

Methods
—Fifty hyperacute CT scans (<6 hours after ictus) were selected from a randomized trial evaluating IV-tPA (ATLANTIS trial). Three neuroradiologists blinded to all clinical information evaluated scans for degree of MCA territory involvement (<33% or >33%) and the presence of a hyperdense MCA. Evaluations were compared with 24-hour scan results, 30-day infarct volumes, and baseline NIH stroke scale scores (NIHSS).

Results
—Readers reliably evaluated the degree of MCA territory hypodensity (intraclass correlation=0.53,
P
<0.001), with all 3 readers agreeing in 36 of 50 cases (72%). They correctly called >33% involvement with a sensitivity of 60% to 85% and a specificity of 86% to 97%. The baseline NIHSS was higher when >33% MCA hypodensity was seen (
P
=0.021). Detection of significant hypodensity (>33%) correlated with poorer outcome. When >33% hypodensity was not detected, mean 30-day infarct volumes were 27.0 to 33.0 cm
3
, versus 84.3 to 123.1 cm
3
when >33% hypodensity was present (
P
=0.002).

Conclusions
—Detection of MCA territory hypodensity on hyperacute CT scans is a sensitive, prognostic, and reliable indicator of the amount of MCA territory undergoing infarction.
Characterization of White Matter Damage in Ischemic Leukoaraiosis with Diffusion Tensor MRI
Authors: Jones Derek K. , Lythgoe David , Horsfield Mark A. , Simmons Andrew , Williams Steve C. R. , Markus Hugh S.
Published: June 2011

Background and Purpose
—Information on the neuropathological changes underlying ischemic leukoaraiosis is only available postmortem, and there are limited data on histological appearances early in the disease. Diffusion tensor imaging allows determination of the directionality of diffusion, which is greater in the direction of white matter bundles. Therefore, the technique might be expected to show loss of anisotropy (directional diffusion) in leukoaraiosis.

Methods
—Nine patients with ischemic leukoaraiosis (radiological leukoaraiosis and clinical lacunar stroke) and 10 age-matched controls were studied. Diffusion tensor imaging was performed, and maps of diffusion trace and fractional anisotropy were constructed. Mean values of trace and fractional anisotropy were determined in standard regions of the anterior and posterior white matter in both hemispheres.

Results
—In all patients with ischemic leukoaraiosis, a characteristic abnormal pattern was found, with loss of anisotropy and increased trace in the white matter. For example, in the right anterior white matter mean (SD) trace/3 was 1.12 (0.33) ×10
−3
mm
2
s
−1
in patients and 0.75 (0.11) in controls (
P
=0.001). In the same region, fractional anisotropy was 0.53 (0.11) in patients and 0.78 (0.09) in controls (
P
<0.001). Within the white matter regions, there was a strong negative correlation between mean diffusivity and anisotropy (
r
=−0.92,
P
<0.0001).

Conclusions
—The characteristic pattern found on diffusion tensor imaging in this patient group is consistent with axonal loss and gliosis leading to impairment to and loss of directional diffusion. The “in vivo histological” information obtained may be useful in monitoring disease progression and in investigating the pathogenesis of the cognitive impairment that may be present.
An Additional Monitoring of Regional Cerebral Oxygen Saturation to HMPAO SPECT Study During Balloon Test Occlusion
Authors: Kaminogo Makio , Ochi Makoto , Onizuka Masanari , Takahata Hideaki , Shibata Shobu
Published: June 2011

Background and Purpose
—To increase the reliability of
99m
Tc–hexamethyl propyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) study in the evaluation of hemodynamic change with balloon test occlusion (BTO) of the internal carotid artery, we attempted to clarify the usefulness of additional monitoring of regional oxygen saturation of the brain (rSO
2
).

Methods
—During BTO, rSO
2
monitoring with transcranial near infrared spectroscopy was performed 17 times on 16 patients. Asymmetrical distribution of the tracer was classified visually as follows: group 1, little or no asymmetry, and group 2, moderate or severe asymmetry. Seven regions of interest (ROI) were defined in the middle cerebral artery area of each hemisphere, and the asymmetry index (AI)=200×(C
non
−C
occl
)/(C
non
+C
occl)
), where C
non
=mean counts on the nonoccluded side, and C
occl
=mean counts on the occluded side were also calculated. Then, mean AI (MAI) was obtained from AI of 7 ROIs for each study.

Results
—Of the 17 procedures, 10 BTOs were in group 1 and 5 BTOs were in group 2. Two patients did not undergo SPECT study because of the immediate appearance of a neurological deficit with BTO; they were defined as group 3. The MAI in group 1 was 2.6±3.3%, which was significantly smaller than the MAI in group 2 (25.6±5.0%,
P
<0.02). The ΔrSO
2
(baseline rSO
2
−rSO
2
during ICA occlusion) with BTO in group 1 was 1.5±1.4% (n=10), which was statistically smaller than that in group 2 (5.5±1.3%, n=4,
P
<0.05). The ΔrSO
2
in group 3 was 9.0±0.0% (n=2). In group 1, however, rSO
2
began to decline when the stump pressure fell to 45 mm Hg and always declined when the stump pressure fell below 40 mm Hg. Furthermore, in group 1, a significant correlation was observed between the ΔrSO
2
and stump pressure (
r
=0.85,
P
<0.0001).

Conclusions
—This preliminary study reveals that an obvious asymmetrical SPECT pattern always accompanies a profound decrease in rSO
2
and that rSO
2
parallels a severe reduction in stump pressure in cases exhibiting a symmetrical SPECT pattern. Thus, the cerebral oximetry sensitively reflects the cerebral oxygenation, and simultaneous measurements of rSO
2
and stump pressure with
99m
Tc-HMPAO SPECT study apparently are useful in evaluating hemodynamic integrity with BTO.
Reduction of Apurinic/Apyrimidinic Endonuclease Expression After Transient Global Cerebral Ischemia in Rats
Authors: Kawase Makoto , Fujimura Miki , Morita-Fujimura Yuiko , Chan Pak H.
Published: June 2011

Background and Purpose
—To clarify the relationship between apurinic/apyrimidinic endonuclease (APE/Ref-1), a multifunctional protein in the DNA base excision repair pathway, and delayed neuronal cell death associated with apoptosis, we examined the expression of APE/Ref-1 before and after transient global ischemia in rats.

Methods
—Global ischemia was induced by bilateral common carotid artery occlusion and hypotension. Expression of the APE/Ref-1 protein was evaluated by Western blot and immunohistochemical analyses. Apoptosis after global ischemia was observed by DNA electrophoresis and terminal deoxynucleotidyl transferase–mediated uridine 5′-triphosphate-biotin nick end labeling (TUNEL) staining.

Results
—Immunohistochemistry showed the nuclear expression of APE/Ref-1 in the control brains. Nuclear immunoreactivity of APE/Ref-1 was significantly decreased 2 days after 10 minutes of ischemia in the hippocampal CA1 subregion. Western blot analysis of a sample from the normal brains showed a characteristic 37-kDa band, which was reduced in the hippocampal CA1 subregion after ischemia. A significant amount of DNA fragmentation was observed at 3 days but not at 1 day after ischemia. Double staining with APE/Ref-1 and TUNEL clearly showed that the neurons that lost APE/Ref-1 immunoreactivity became TUNEL positive.

Conclusions
—Our data provide evidence that APE/Ref-1 decreased in hippocampal CA1 neurons after transient global ischemia and that this reduction precedes DNA fragmentation, which is destined to cause apoptosis. Our results suggest the possibility that a decrease of APE/Ref-1 activity and the failure of DNA repair may underlie the mechanism of apoptosis after transient focal ischemia.
Cerebral Venous Thrombosis
Authors: Frey James L. , Muro Gerard J. , McDougall Cameron G. , Dean Bruce L. , Jahnke Heidi K.
Published: June 2011

Background and Purpose
—We chose to evaluate the safety and efficacy of combined intrathrombus rtPA and intravenous heparin in cerebral venous thrombosis (CVT).

Methods
—We treated 12 patients with symptoms of 1 to 40 days’ duration (eg, headache, somnolence, focal deficits, seizures, and nausea and vomiting). Pretreatment MRI disclosed subtle hemorrhagic venous infarction in 4 patients, obvious hemorrhagic infarction in 2, small parenchymal hemorrhage from recent pallidotomy in 1, and no focal lesion in 5. Magnetic resonance venography and contrast venography identified thrombi in the superior sagittal sinus (SSS) in 3 patients; transverse/sigmoid sinus (TS/SS) in 2; SSS and both TS/SS in 1; SSS and 1 TS/SS in 5; and SSS, 1 TS/SS, and straight sinus in 1 patient. A loading dose of rtPA was instilled throughout the clot at 1 mg/cm, followed by continuous intrathrombus infusion at 1 to 2 mg/h. Intravenous heparin was infused concomitantly.

Results
—Flow was restored completely in 6 patients and partially in 3, with a mean rtPA dose of 46 mg (range, 23 to 128 mg) at a mean time of 29 hours (range, 13 to 77 hours). Symptoms improved in these 9 patients concomitantly with flow restoration. Flow could not be restored in 3 patients. In 1 of them, treatment was stopped when little progress had been made, and fibrinogen level dropped to 118 mg/dL. In the other 2 patients, hemorrhagic worsening occurred, and treatment was abbreviated after initial rtPA dosing. In 1 of these, the hematoma was evacuated.

Conclusions
—Our experience with intrathrombus rtPA in conjunction with intravenous heparin in patients with CVT is encouraging. This therapy should probably be regarded as unsafe in patients with obvious hemorrhage. Time to restore flow may be faster than with urokinase (an average of 71 hours has been reported for 29 documented patients). Further evaluation of rtPA with heparin in CVT is warranted.
Dose Escalation Study of the NMDA Glycine-Site Antagonist Licostinel in Acute Ischemic Stroke
Authors: Albers Gregory W. , Clark Wayne M. , Atkinson Richard P. , Madden Kenneth , Data Joann L. , Whitehouse M. J.
Published: June 2011

Background and Purpose
—Licostinel (ACEA 1021; 5-nitro-6,7-dichloro-2,3-quinoxalinedione), a competitive antagonist of glycine at the
N
-methyl-
d
-aspartate (NMDA) receptor, is an effective neuroprotective agent in animal models of cerebral ischemia. The purpose of this study was to assess the safety, tolerability, and pharmacokinetics of licostinel in patients with acute stroke.

Methods
—In this 5-center dose escalation trial, patients were enrolled within 48 hours of an ischemic stroke and treated with ascending doses of a short infusion of licostinel or a placebo. Adverse effects were assessed with clinical and laboratory measurements, and patient outcome was determined with the National Institutes of Health Stroke Scale.

Results
—Sixty-four patients (44 treated with escalating doses of licostinel and 20 who received placebo) were treated. Lower doses of licostinel (0.03 to 0.60 mg/kg) were not associated with any significant adverse effects. Higher doses of licostinel (1.2 to 3.0 mg/kg) were associated with a variety of mild-to-moderate adverse effects including neurological and gastrointestinal complaints. No major psychotomimetic effects or significant safety concerns occurred. At the higher dose levels, peak plasma concentrations of licostinel were substantially higher than those required for neuroprotection in animal stroke models. A similar improvement in National Institutes of Health Stroke Scale scores over time was seen in both the placebo group and the licostinel-treated patients.

Conclusions
—A short infusion of licostinel in doses up to 3.0 mg/kg is safe and tolerable in acute stroke patients. Licostinel may be a safer and better tolerated neuroprotective agent than many of the previously evaluated NMDA antagonists.
Neuropsychological Impairment Correlates With Hypoperfusion and Hypometabolism but Not With Severity of White Matter Lesions on MRI in Patients With Cerebral Microangiopathy
Authors: Sabri Osama , Ringelstein Erich-Bernhard , Hellwig Dirk , Schneider Rolf , Schreckenberger Mathias , Kaiser Hans-Jürgen , Mull Michael , Buell Udalrich
Published: June 2011

Background and Purpose
—Cerebral microangiopathy, indicated on MRI by lacunar infarctions (LI) and deep white matter lesions (DWML), is said to lead to vascular dementia.

Methods
—Fifty-seven patients with proven cerebral microangiopathy were assessed for changes in regional cerebral blood flow (rCBF) and glucose metabolism (rMRGlu) and compared with 19 age-matched controls. The findings were correlated with results of extensive neuropsychological testing, as well as with MRI findings. A special head holder ensured reproducibility of positioning during rCBF (single-photon emission CT [SPECT]), rMRGlu (positron emission tomography [PET]), and MR imaging. White matter and cortex were quantified with regions of interest defined on MRI and superimposed to corresponding PET/SPECT slices. LI and DWML were graded by number and extent.

Results
—Even with severe DWML and multiple LI, rCBF and rMRGlu values were not reduced. ANOVAs identified brain atrophy and neuropsychological deficits as the main determinants for reduced rCBF and rMRGlu values in both cortex and white matter. Neuropsychological deficits correlated well with decreased rCBF and rMRGlu, whereas MRI patterns such as LI and DWML did not. Factor analysis revealed no correlation of LI and DWML with rCBF, rMRGlu, atrophy, and neuropsychological deficits, showing instead positive correlations between rCBF, rMRGlu, and neuropsychological performance and negative correlations of the latter 3 with brain atrophy.

Conclusions
—From these data, we conclude that LI and DWML are epiphenomena that may morphologically characterize cerebral microangiopathy but do not in themselves indicate cognitive impairment. Dementia or neuropsychological deficits, by contrast, are reflected exclusively by functional imaging parameters (rCBF, rMRGlu) and cerebral atrophy.
Randomized, Controlled Trial to Evaluate Increased Intensity of Physiotherapy Treatment of Arm Function After Stroke
Authors: Lincoln Nadina B. , Parry Ruth H. , Vass Catherine D.
Published: June 2011

Background and Purpose
—Many patients have impaired arm function after stroke, for which they receive physiotherapy. The aim of the study was to determine whether increasing the amount of physiotherapy early after stroke improved the recovery of arm function and to compare the effects of this therapy when administered by a qualified therapist or a trained, supervised assistant. The physiotherapy followed a typical British approach, which is Bobath derived. Ten hours of additional therapy were given over a 5-week period.

Methods
—The study design was a single-blind, randomized, controlled trial. Stroke patients were recruited from those admitted to the hospital in the 5 weeks after stroke. They were randomly allocated to routine physiotherapy, additional treatment by a qualified physiotherapist, or additional treatment by a physiotherapy assistant. Outcome was assessed after 5 weeks of treatment and at 3 and 6 months after stroke on measures of arm function and of independence in activities of daily living.

Results
—There were 282 patients recruited to the study. The median initial Barthel score was 6.5, and the median age of the patients was 73 years. The median initial Rivermead Motor Assessment Arm score was 1. There were no significant differences between the groups at randomization or on any of the outcome measures. Only half of the patients allocated to the 2 additional-therapy groups completed the program.

Conclusions
—This increase in the amount of physiotherapy for arm impairment with a typical British approach given early after stroke did not significantly improve the recovery of arm function in the patients studied. A number of other studies of interventions aimed at rehabilitation of arm function have reported positive results. Such findings may have been due to the content of these interventions, to the greater intensity of the interventions, or to the selection of patients to whom the treatments were applied.
Age and Stimulus Dependency of Visually Evoked Cerebral Blood Flow Responses
Authors: Panczel Gyula , Daffertshofer Michael , Ries Stephan , Spiegel Dagmar , Hennerici Michael
Published: June 2011

Background and Purpose
—During visual stimulation, the increased metabolic demand is coupled with an increase of cerebral blood flow velocity (pCBFV) in the posterior cerebral artery (PCA). Investigation of the visually evoked flow responses (VEFR, expressed as percentage of increase from baseline pCBFV values) was suggested for different conditions of vasoneuronal disorders in the absence of any systematic investigation in healthy subjects.

Methods
—We investigated VEFRs from both PCAs to various increasingly complex paradigms (diffuse light, alternating checkerboard patterns, and a color video movie stimulation; 5, 10, 20, and 30-second intervals) in 60 healthy volunteers (mean age, 41.5±14.9 years; range, 24 to 80 years; 28 male, 32 female) at different recording sites (P1 versus P2 segments of PCAs).

Results
—With increasing complexity of stimulation, the VEFRs increased significantly (24.3±10.3%, 28.5±13.5%, and 43.4±10.7%, respectively). Twenty-second stimulation intervals yielded maximal responses (41.5±13.2%) compared with 5-, 10-, and 30-second intervals (22.6±14.1%,
P
=0.001; 34.4±11.7%,
P
=0.0042; and 35.5±9.9%,
P
=0.0032, respectively). Significantly higher responses were gained from P2 segments than from P1 segments (42.7±7.2% versus 28.2±7.1%). Although VEFRs tended to decrease in amplitude with age (mean, 41.7±10.5% [20 to 40 years], 35±9.2% [40 to 60 years], and 33.9±8.6% [60 to 80 years]); without significant sex-related differences, only the percentage decrement of the pulsatility indices during stimulation were significant (mean, 24±10.7% [20 to 40 years], 20±7.3% [40 to 60 years], and 13±11.2% [60 to 80 years]).

Conclusions
—For optimal stimulus conditions for maximum VEFRs, a colored video stimulation of 20-second intervals should be used to combine responses not only from the primary visual projection fields (V
1
and V
2
) but also from temporal lobe areas (V
3
through V
5
) often supplied by the PCA.
Nicotine Increases Plasminogen Activator Inhibitor-1 Production by Human Brain Endothelial Cells via Protein Kinase C–Associated Pathway
Authors: Zidovetzki Raphael , Chen Peijia , Fisher Mark , Hofman Florence M.
Published: June 2011

Background and Purpose
—Smoking both increases stroke risk and reduces the risk of thrombolysis-associated intracerebral hemorrhage. Plasminogen activator inhibitor-1 (PAI-1) is a major regulator of fibrinolysis; elevation of PAI-1 is associated with an increased risk of thrombotic disorders. We studied the effect of nicotine, an important constituent of cigarette smoke, on PAI-1 production by human brain endothelial cells.

Methods
—Adult human central nervous system endothelial cells (CNS-EC) were used for tissue culture experiments. We analyzed culture supernatant for PAI-1 protein and measured PAI-1 mRNA (by Northern blot analysis) and protein kinase C (PK-C) activity.

Results
—Nicotine at 100 nmol/L increased PAI-1 protein production and mRNA expression by CNS-EC. After 72 hours of exposure to nicotine, the concentration of secreted PAI-1 in the cell supernatant was increased 1.90±0.2 fold compared with untreated cells. PAI-1 mRNA also increased approximately twofold. Inhibition of PK-C completely abolished this effect. Nicotine had no effect on the concentration of tissue plasminogen activator.

Conclusions
—Nicotine increases brain endothelial cell PAI-1 mRNA expression and protein production via PK-C–dependent pathway. These findings provide new insights into why smoking may be associated with predisposition to thrombosis and inversely associated with intracerebral hemorrhage after therapeutic tissue plasminogen activator therapy.
Intra-Arterial rtPA Treatment of Stroke Assessed by Diffusion- and Perfusion-Weighted MRI
Authors: Lansberg Maarten G. , Tong David C. , Norbash Alexander M. , Yenari Midori A. , Moseley Michael E.
Published: June 2011

Background
—Diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) are new techniques that can be used for the evaluation of acute ischemic stroke. However, their potential role in the management of patients treated with recombinant tissue plasminogen activator (rtPA) has yet to be determined.

Case Description
—The authors present the case of a 73-year-old man who was treated with intra-arterial rtPA, and they compare findings on DWI and PWI scans with angiography. PWI revealed decreased cerebral perfusion corresponding to an area that was not successfully recanalized, but revealed no abnormality in regions in which blood flow was restored. DWI was unremarkable in the region that was reperfused early (3 hours) but revealed hyperintensity in an area that was reperfused 3.5 hours after symptom onset and in the area that was not reperfused.

Conclusions
—Findings on PWI correlated well with angiography, and DWI detected injured tissue in the hyperacute stage, whereas conventional MRI findings were negative. This suggests that these techniques may be useful to noninvasively evaluate the success of thrombolytic therapy.
Economic Consequences of Early Inpatient Discharge to Community-Based Rehabilitation for Stroke in an Inner-London Teaching Hospital
Authors: Beech Roger , Rudd Anthony G. , Tilling Kate , Wolfe Charles D. A.
Published: June 2011

Background and Purpose
—In an inner-London teaching hospital, a randomized trial of “conventional” care versus early discharge to community-based therapy found no significant differences in clinical outcomes between patient groups. This report examines the economic consequences of the alternative strategies.

Methods
—One hundred sixty-seven patients received the early discharge package, and 164 received conventional care. Patient utilization of health and social services was recorded over a 12-month period, and cost was determined using data from provider departments and other published sources.

Results
—Inpatient stay after randomization was 12 days (intervention group) versus 18 days (controls) (
P
=0.0001). Average units of therapy per patient were as follows: physiotherapy, 22.4 (early discharge) versus 15.0 (conventional) (
P
=0.0006); occupational therapy, 29.0 versus 23.8 (
P
=0.002); speech therapy, 13.7 versus 5.8 (
P
=0.0001). The early discharge group had more annual hospital physician contacts (
P
=0.015) and general practitioner clinic visits (
P
=0.019) but fewer incidences of day hospital attendance (
P
=0.04). Other differences in utilization were nonsignificant. Average annual costs per patient were £6800 (early discharge) and £7432 (conventional). The early discharge group had lower inpatient costs per patient (£4862 [71% of total cost] versus £6343 [85%] for controls) but higher non-inpatient costs (£1938 [29%] versus £1089 [15%]). Further analysis demonstrated that early discharge is unlikely to lead to financial savings; its main benefit is to release capacity for an expansion in stroke caseload.

Conclusions
—Overall results of this trial indicate that early discharge to community rehabilitation for stroke is cost-effective. It may provide a means of addressing the predicted increase in need for stroke care within existing hospital capacity.
A Standardized MRI Stroke Protocol
Authors: Schellinger Peter D. , Jansen Olav , Fiebach Jochen B. , Hacke Werner , Sartor Klaus
Published: June 2011

Background and Purpose
—Diagnostic imaging in hyperacute ischemic stroke has been revolutionized by the introduction of diffusion- and perfusion-weighted MRI (DWI and PWI). CT, however, is still needed to exclude intracerebral hemorrhage (ICH). The purpose of our study was to determine the diagnostic accuracy of a standardized, multimodal MRI (mMRI) stroke protocol in the qualitative and quantitative assessment of hyperacute ICH (<6 hours).

Methods
—We investigated 9 patients with hyperacute ICH with CT followed immediately by a standardized mMRI stroke protocol (DWI, PWI [T2*-WI], FLAIR, T2-WI, and MRA). The time interval between MRI and symptom onset ranged from 3 hours to 5 hours 45 minutes. We analyzed and compared the size of the hematoma on CT and all mMRI images by semiautomatic volumetry.

Results
—ICH was unambiguously identified on the basis of all mMRI sequences. With increasing susceptibility effect (T2*-WI), the ICH, appearing as an area of hyperintensity with central signal loss, became qualitatively most evident. Regarding quantitation, T2*-WI overestimated (median and mean difference, 18.9%/17.8%; SD ς=24.4%) and DWI correlated best (median and mean difference, 3.97%/−4.36%; SD ς=37.42%) with hematoma size on CT.

Conclusions
—Multimodal stroke MRI is as reliable as CT in the assessment of hyperacute ICH. Therefore, additional CT is no longer necessary to rule out ICH in hyperacute stroke. The use of mMRI alone in the diagnostic workup of a hyperacute stroke patient saves time and costs while rendering all the critical information needed to initiate an optimal treatment.
“Tail Sign” Associated With Microembolic Signals
Authors: Furui Eisuke , Hanzawa Kazuhiko , Ohzeki Hajime , Nakajima Takashi , Fukuhara Nobuyoshi , Takamori Masaharu
Published: June 2011

Background and Purpose
—Transcranial Doppler ultrasound (TCD) can detect circulating microembolic signals (MES). We focused our attention on tail signs (TS), a signal associated with MES that appeared as a small reversal signal after MES on the high time resolution spectral display. We examined MES and artifacts in an animal study to determine whether TS were specific changes associated with MES and investigated the characteristics of TS in both animal and clinical studies.

Methods
—In an animal study, adult pigs with venoarterial extracorporeal membrane oxygenation and minimal anticoagulation therapy were used as a model for cerebral embolism. After performing TCD monitoring with a multigated approach, we did an offline analysis to investigate several parameters concerning MES and TS. We also examined TS in patients in a clinical study.

Results
—From a total of 362 MES investigated in the animal study, 72.9% were followed by TS. We could not find any TS associated with artifacts. The time delay between TS and MES was negatively correlated with the velocity of MES. MES almost always appeared first in the proximal channel, whereas TS conversely appeared first in the distal channel. In the clinical study, we were also able to observe TS associated with MES.

Conclusions
—TS may represent emboli passing down a branch vessel or twisted downstream vessel. TS are specific for MES and can be used as another criterion for MES identification.
Effect of Thrombin Inhibition in Vascular Dementia and Silent Cerebrovascular Disease
Authors: Kario Kazuomi , Matsuo Takefumi , Hoshide Satoshi , Umeda Yuji , Shimada Kazuyuki
Published: June 2011

Background and Purpose
—Silent cerebrovascular disease (CVD) has been proposed as a predisposing condition for clinically overt stroke and vascular dementia. Recently, we found increased thrombin generation in silent CVD patients. Here, we report the effect of thrombin inhibition using a potent selective thrombin inhibitor on the cerebral metabolism and function in peripheral arterial occlusive disease (PAOD) patients with or without silent CVD.

Methods
—We examined 17 mild chronic PAOD patients, including 2 cases of vascular dementia. We divided the patients into 2 groups: 1 was the advanced CVD group with multiple lacunar infarction and/or advanced periventricular hyperintensity detected by brain MRI (n=12), and the other was the no CVD group that had none of these abnormalities (n=5). We assessed the cerebral biochemical compounds in the deep white matter area and cerebellar hemisphere (8 cm
3
) by proton MR spectroscopy before and after infusion of argatroban (10 mg/d IV) over 2 hours for 7 days.

Results
—The ratio of
N
-acetylasparate (NAA) to total creatine (Cre) in the deep white matter area was significantly lower in the advanced CVD group than in the no CVD group, whereas there were no significant differences in this ratio in the cerebellar hemisphere between the 2 groups. In the former group, this decreased NAA/Cre ratio significantly increased after argatroban therapy, whereas there was no change in the latter group. The 2 patients with vascular dementia showed clinical improvement with marked increases in the NAA/Cre ratio and mini-mental score.

Conclusions
—These results suggest that increased thrombin generation may have some pathophysiological roles in developing vascular dementia and its chronic predisposing conditions. Thrombin inhibition may break this vicious cycle and lead to clinical improvement.