bluuebunny/crossref_metadata_2025 huggingface dataset:
The Hemodynamic Importance of the Geometry of Bifurcations in the Circle of Willis (Glass Model Studies)
Authors: Roach Margot R. , Scott Susan , Ferguson Gary G.
Published: June 2011

The critical Reynolds number, Re
c
, at which turbulence developed in glass model bifurcations was measured with an Evans blue indicator for bifurcations with a branch/trunk area ratio of unity, and bifurcation angles of 45°, 90°, 135°, and 180°. The Re
c
dropped from 2,500 in a straight tube to 1,200 in the 180° bifurcation. Further drops occured with pulsatile flow (if the mean flow rate was used to calculate the velocity). Three sizes of aneurysms at the apex of the 90° bifurcation lowered the Re
c
at small bifurcations, and less in the 180° ones. The curves for steady and pulsatile flow crossed at 135°. We did qualitative, but not quantitative, assessments of axial stream impingement on the apex of the bifurcation in the site of aneurysm formation, and of boundary layer separation and vortex shedding at the lateral angles. Both appeared to vary with the angle of the bifurcation and the Reynolds number. We also studied flow profiles in glass models of anterior cerebral-anterior communicating artery bifurcations and the posterior communicating artery origin from the internal carotid. The relevance of these studies to localization of intimal cushions, aneurysms, and atherosclerosis was discussed.
Validation of Jugular Venous Flow as an Index of Total Cerebral Blood Flow
Authors: Wilson Edwin M. , Halsey James H. , Vitek Jiri J.
Published: June 2011

Values of total cerebral blood flow in man measured by the indicator dilution method are compared with values of total internal jugular venous flow measured by the thermal dilution method. Except in the case of an extremely labile cerebral hemodynamic state, the results agree within the accuracy of the two methods, suggesting that for the supine patient total internal jugular venous flow provides a good index of total cerebral flow.

The relatively short measurement time associated with nondiffusible indicators (dye or thermal dilution) facilitates detection of transient changes in total CBF or differential jugular flow that would tend to be averaged out with diffusible indicator methods.

A mathematical analysis of the potential errors in the computation of total flow using the average of bilateral jugular venous dilution curves from a unilateral internal carotid injection is presented. This error can be partially corrected if the ratio of flow in one internal jugular to total flow is known.

An analysis of potential computational errors under nonsteady state flow conditions (change in flow during the period between alternate carotid injections) is presented. Such flow changes can effect substantial errors in the computation of individual hemispheric or internal jugular flow and smaller errors in the computation of total flow.
Spontaneous Dissecting Aneurysm of the Internal Carotid Artery
Authors: OJEMANN ROBERT G. , FISHER C. MILLER , RICH J. CHARLES
Published: June 2011

A case of spontaneous dissection of the internal carotid artery is presented and the ten other reported cases are reviewed. It is most common in males aged 35 to 41 years. Of eight patients with neurological symptoms, two had transient hemiplegia and five of six first seen with a severe neurological deficit had prodromal symptoms. Angiography revealed a typical "string sign." A method of surgical treatment is illustrated. The importance of emergency angiography and surgery in patients with acute onset of progressive symptoms of cerebral vascular disease is emphasized by this case.

The surgical specimen was studied pathologically by serial section. At its origin the dissection measured 3 mm in width and 0.3 mm in length. Proximally the dissection was in the media but distally it lay at the medial-adventitial interface. There was no evidence of cystic medial necrosis but the muscle and elastic tissue of the media had a disorganized arrangement.
Preparation and Analysis of 4-lodoantipyrine-(I
131
)
Authors: DIMATTIO JOSEPH , HOCHWALD G. M.
Published: June 2011

4-Iodoantipyrine was prepared from antipyrine according to the reaction equation:

3C
11
H
12
N
2
O+2KI+KIO
3
+3HCl→3C
11
H
11
N
2
OI+3KCl+3H
2
O

The product was separated from the reaction mixture and purified by recrystallization. The iodoantipyrine was labeled with I
131
by means of an exchange reaction with NaI
131
. It was separated from the unbound radioactivity by anion exchange chromatography.

The purity of the product was determined by cellulose thin layer chromatography using ethanol-chloroform-water (45:45:10) as the solvent system. The purity of the 4-iodoantipyrine-I
131
decreased with time due to a splitting off of the I
131
atom and subsequent formation of NaI
131
. This spontaneous deiodination was best minimized by storage in methanol at low temperatures.
Studies on Mechanisms of Impairment of Cerebral Circulation Following Ischemia: Effect of Hemodilution and Perfusion Pressure
Authors: FISCHER EDWIN G. , Ames Adelbert
Published: June 2011

Reperfusion of cerebral vessels is impaired following total cerebral ischemia of more than five minutes; this is possibly the initial factor responsible for neurological sequela. Failure of cellular ion transport mechanisms during ischemia was thought to lead to swelling of endothelial cells and perivascular glia and this, in turn, was thought to be the primary cause of the impairment of recirculation. A method of quantitating this circulatory impairment in rabbits was devised after infusing carbon black into the ischemic cerebral vasculature in a standardized way. The amount of circulatory impairment was shown to be unaffected by heparin, inversely related to the infusion pressure of the carbon black, and greatly reduced by acute hemodilution with saline. This latter observation does not support the theory that cellular swelling is the major cause of the postischemic vascular impairment, but rather implicates changes in the blood itself, possibly erythrocyte aggregation which is responsible for increased blood viscosity in low flow and no flow states.
The Hypoglossal Nerve in Carotid Arterial Reconstructions
Authors: Imparato Anthony M. , Bracco Aldo , Kim Geun Eun , Bergmann Louis
Published: June 2011

The importance of hypoglossal nerve in performing carotid arterial reconstructions has been illustrated by two case reports. Unilateral palsy is troublesome but bilateral damage may result in upper airway obstruction. Simple surgical maneuvers consisting of division of the sternocleidomastoid artery and vein and freeing up of the descendens hypoglossus permit nontraumatic retraction of the nerve, avoiding tongue paralysis.
Cerebral Arteriovenous Shunts Re-examined
Authors: Rowed David W. , Stark Violet J. , Hoffer Paul B. , Mullan Sean
Published: June 2011

Cerebral arteriovenous (A-V) shunts have been described in some histological studies, but their existence has been denied in others. Previous attempts to detect the presence and amount of A-V shunting using radioactive microspheres have suggested that large amounts of blood could bypass cerebral capillaries in this fashion. A reappraisal seemed indicated.

The present study, using the radioactive microsphere technique, confined the injected spheres specifically to the cerebral circulation of a nonhuman primate. The conclusion of this study is that structural, noncapillary A-V shunting definitely occurs, but is very small and variable in amount.

The implications of this finding in relation to previous studies and to the clinical phenomena of red cerebral veins and early venous filling are discussed.
Oxygen Availability in Ischemic Brain Following Hypocarbia and Hypercarbia
Authors: HARRINGTON TIMOTHY , MAJOR MITCHELL , OMMAYA AYUB K. , DI CHIRO GIOVANNI
Published: June 2011

Acutely implanted oxygen-recording polarographical depth electrodes were used to appraise changes in oxygen availability (O
2
a) in the brain of the Rhesus monkey. Modifications of oxygen availability induced by hypocarbia and hypercarbia in the normal and the infarcted brain are described. The most consistent finding was a reversal of the expected effects of low and high Paco
2
values during the acutely ischemic period (evolving stroke) and an incomplete return to the normal response by five days (completed stroke).
Identification of Individuals With Covert Ischemic Thrombotic Cerebrovascular Disease: A Discriminant Function Analysis
Authors: GERTLER MENARD M. , ROSENBERGER JAMES L. , LEETMA HILLAR E.
Published: June 2011

Sixty-one men with ischemic thrombotic cerebrovascular disease (ITCVD) and 61 age-matched controls (±three years) were studied to select risk factors which would identify ITCVD-prone individuals from a healthy population. Numerous clinical and biochemical measurements were made on all subjects including a three-hour oral glucose tolerance test concomitant with the immunoreactive insulin response (IRI). The following parameters were selected as risk factors for ITCVD from the many variables assessed: elevated systolic blood pressure; triglycerides; uric acid; glucose one-hour, two-hour and three-hour levels; and IRI two-hour and three-hour levels. There is also a higher prevalence of abnormal lipoproteins (mostly type IV), abnormal EKG, and hypertension in ITCVD. A stepwise linear discriminant function analysis was used to select the risk factors which best separate and classify the ITCVD and control subjects. These primary risk factors are the IRI three-hour level, systolic blood pressure, abnormal lipoproteins, and glucose two-hour level. Utilizing only these four primary risk factors in a discriminant function, 84.4% of the subjects were correctly classified. The contribution of the other variables is minimal in the discriminant function, but they are applicable as individual risk factors of ITCVD.
Superoxide Generation Links Protein Kinase C Activation to Impaired ATP-Sensitive K
+
Channel Function After Brain Injury
Authors: Armstead William M.
Published: June 2011

Background and Purpose
—Endothelin-1, in concentrations similar to that present in cerebrospinal fluid after fluid percussion brain injury (FPI), increases superoxide anion (O
2
−
) production. Endothelin-1 also contributes to altered cerebral hemodynamics after FPI through impairment of ATP-sensitive K
+
(K
ATP
) channel function through protein kinase C (PKC) activation. Generation of O
2
−
additionally occurs after FPI. Nitric oxide and cGMP elicit pial artery dilation through K
ATP
channel activation. The present study was designed to determine whether PKC activation generates O
2
−
, which, in turn, could link such activation to impaired K
ATP
channel function after FPI.

Methods
—Injury of moderate severity (1.9 to 2.1 atm) was produced by the lateral FPI technique in anesthetized newborn pigs equipped with a closed cranial window. Superoxide dismutase–inhibitable nitroblue tetrazolium (NBT) reduction was determined as an index of O
2
−
generation.

Results
—Phorbol 12,13-dibutyrate (10
−6
mol/L), a PKC activator, increased superoxide dismutase-inhibitable NBT reduction from 1±1 to 37±5 pmol/mm
2
. Staurosporine (10
−7
mol/L), a PKC antagonist, blocked the NBT reduction after phorbol 12,13-dibutyrate and blunted the NBT reduction observed after FPI (1±1 to 15±2 versus 1±1 to 5±1 pmol/mm
2
after FPI in the absence versus presence of staurosporine). Exposure of the cerebral cortex to a xanthine oxidase O
2
−
-generating system increased NBT reduction in a manner similar to FPI and blunted pial artery dilation to the K
ATP
channel agonists cromakalim and calcitonin gene–related peptide, the nitric oxide releasers sodium nitroprusside and
S
-nitroso-
N
-acetylpenicillamine, and the cGMP analogue 8-bromo-cGMP (10±1% and 21±1% versus 4±1% and 9±1% for 10
−8
and 10
−6
mol/L cromakalim before and after activated oxygen-generating system exposure).

Conclusions
—These data show that PKC activation increases O
2
−
production and contributes to such production observed after FPI. These data also show that an activated system that generates an amount of O
2
−
similar to that observed with FPI blunted pial artery dilation to K
ATP
channel agonists and nitric oxide/cGMP. These data suggest, therefore, that O
2
−
generation links PKC activation to impaired K
ATP
channel function after FPI.
Clomethiazole Acute Stroke Study (CLASS)
Authors: Wahlgren N.G. , Ranasinha K.W. , Rosolacci T. , Franke C.L. , van Erven P.M.M. , Ashwood T. , Claesson L.
Published: June 2011

Background and Purpose
—The efficacy and safety of the neuroprotective drug clomethiazole was tested in a double blind placebo controlled trial in patients with a clinical diagnosis of acute hemispheric stroke.

Methods
—Patients with symptom onset of ≤12 hours before the start of treatment were included in the study. Clomethiazole (75 mg/kg) or placebo was given as an intravenous infusion over a 24-hour period. Patients were followed up for 90 days. The primary efficacy variable was the proportion of patients reaching relative functional independence (≥60 points on the Barthel Index) at 90 days.

Results
—A total of 1360 patients were included. In the main efficacy analysis (n=1353), 56.1% of patients taking clomethiazole and 54.8% of placebo patients reached relative functional independence. The difference was not statistically significant. An analysis of the effect of time since onset of symptoms showed no difference between the treatment groups. Clomethiazole was generally well tolerated and appeared safe in the population studied. Sedation was the most common adverse event, leading to treatment withdrawal that occurred in 15.6% of clomethiazole-treated patients compared with 4.2% of placebo-treated patients. In a subgroup classified before randomization as having total anterior circulation syndrome (TACS) (n=545, or 40% of all randomized patients), the percentage of those reaching relative functional independence was 40.8% on clomethiazole and 29.8% on placebo, a difference of approximately 11 percentage units. TACS patients have clinical symptoms suggesting a “large” stroke.

Conclusions
—Clomethiazole had no adverse or beneficial effect on long-term outcome for all patients but produced sedation. The hypothesis that clomethiazole is effective in patients with large strokes will be tested in a further study.
Serum Glucose Level and Diabetes Predict Tissue Plasminogen Activator–Related Intracerebral Hemorrhage in Acute Ischemic Stroke
Authors: Demchuk Andrew M. , Morgenstern Lewis B. , Krieger Derk W. , Linda Chi T. , Hu William , Wein Theodore H. , Hardy Robert J. , Grotta James C. , Buchan Alastair M.
Published: June 2011

Background and Purpose
—Five pretreatment variables (
P
<0.1 univariate analysis), including serum glucose (>300 mg/dL), predicted symptomatic intracerebral hemorrhage (ICH) in the National Institute of Neurological Disorders and Stroke rtPA trial. We retrospectively studied stroke patients treated <3 hours from onset with intravenous rtPA at 2 institutions to evaluate the role of these variables in predicting ICH.

Methods
—Baseline characteristics, including 5 prespecified variables (age, baseline glucose, smoking status, National Institutes of Health Stroke Scale [NIHSS] score, and CT changes [>33% middle cerebral artery territory hypodensity]), were reviewed in 138 consecutive patients. Variables were evaluated by logistic regression as predictors of all hemorrhage (including hemorrhagic transformation) and symptomatic hemorrhage on follow-up CT scan. Variables significant at
P
<0.25 level were included in a multivariate analysis. Diabetes was substituted for glucose in a repeat analysis.

Results
—Symptomatic hemorrhage rate was 9% (13 of 138). Any hemorrhage rate was 30% (42 of 138). Baseline serum glucose (5.5-mmol/L increments) was the only independent predictor of both symptomatic hemorrhage [OR, 2.26 (CI, 1.05 to 4.83),
P
=0.03] and all hemorrhage [OR, 2.26 (CI, 1.07 to 4.69),
P
=0.04]. Serum glucose >11.1 mmol/L was associated with a 25% symptomatic hemorrhage rate. Baseline NIHSS (5-point increments) was an independent predictor of all hemorrhage only [OR, 12.42 (CI, 1.64 to 94.3),
P
=0.01]. Univariate analysis demonstrated a trend for nonsmoking as a predictor of all hemorrhage [OR, 0.45 (CI, 0.19 to 1.08),
P
=0.07]. Diabetes was also an independent predictor of ICH when substituted for glucose in repeat analysis.

Conclusions
—Serum glucose and diabetes were predictors of ICH in rtPA-treated patients. This novel association requires confirmation in a larger cohort.
Elevated Tissue Plasminogen Activator Antigen and Stroke Risk
Authors: Macko Richard F. , Kittner Steven J. , Epstein Anne , Cox D. Kim , Wozniak Marcella A. , Wityk Robert J. , Stern Barney J. , Sloan Michael A. , Sherwin Roger , Price Thomas R. , McCarter Robert J. , Johnson Constance J. , Earley Christopher J. , Buchholz David W. , Stolley Paul D.
Published: June 2011

Background and Purpose
—Abnormalities in endogenous fibrinolysis are associated with an increased risk for stroke in men and older adults. We tested the hypothesis that elevated plasma tissue plasminogen activator (tPA) antigen, a marker for impaired endogenous fibrinolysis, is an independent risk factor for stroke in young women.

Methods
—Subjects were 59 nondiabetic females ages 15 to 44 years with cerebral infarction from the Baltimore-Washington area and 97 control subjects frequency-matched for age who were recruited by random-digit dialing from the same geographic area. A history of cerebrovascular disease risk factors was obtained by face-to-face interview. Plasma tPA antigen was measured by enzyme-linked immunosorbent assay.

Results
—Mean plasma tPA antigen levels were significantly higher in stroke patients than control subjects (4.80±4.18 versus 3.23±3.67 ng/mL;
P
=0.015). After adjustment for age, hypertension, cigarette smoking, body mass index, and ischemic heart disease, there was a dose-response association between tPA antigen and stroke with a 3.9-fold odds ratio of stroke (95% CI, 1.2 to 12.4;
P
=0.03) for the upper quartile (>4.9 ng/mL) of tPA antigen compared with the lowest quartile. The dose-response relationship between tPA antigen and stroke was equally present in white and nonwhite women, and further adjustment for total and HDL cholesterol levels only modestly attenuated this association.

Conclusions
—This population-based case-control study shows that elevated plasma tPA antigen level is independently associated with an increased risk for ischemic stroke in nondiabetic females 15 to 44 years of age. These findings support the hypothesis that impaired endogenous fibrinolysis is an important risk factor for stroke in young women.
Ischemic Core and Penumbra in Human Stroke
Authors: Kaufmann Anthony M. , Firlik Andrew D. , Fukui Melanie B. , Wechsler Lawrence R. , Jungries Charles A. , Yonas Howard
Published: June 2011

Background and Purpose
—The ischemic core and penumbra have not been thoroughly characterized after acute cerebral thromboembolic occlusion in humans. Differentiation between areas of potentially viable and irreversibly injured ischemic tissue may facilitate assessment and treatment of stroke patients.

Methods
—Cerebral blood flow (CBF) was measured in 20 patients with acute middle cerebral artery (MCA) occlusion between 60 and 360 minutes after stroke onset, with the stable xenon computerized tomography (CT) technique. Threshold displays were generated at a single level, and the percentages of hemisphere with CBF ≤6, ≤10, 11 to 20, 21 to 30, and >30 cm
3
· 100 g
−1
· min
−1
were measured. The corresponding images on 12 available follow-up CT scans were similarly assessed to determine the area of final infarct. Comparisons were analyzed with a paired Student’s
t
test and Pearson’s correlation coefficient.

Results
—Discrete and confluent areas of CBF ≤20 cm
3
· 100 g
−1
· min
−1
were identified in all patients, ipsilateral to the symptomatic MCA territory. The average area of CBF ≤20 cm
3
· 100 g
−1
· min
−1
within the ipsilateral hemisphere was 66±17% compared with 36±12% contralaterally (
P
<0.001). A difference in the extent of low CBF was due primarily to areas with CBF ≤10 cm
3
· 100 g
−1
· min
−1
(48±18% versus 16±7%,
P
<0.001). The area of most severe ipsilateral ischemia (≤6 cm
3
· 100 g
−1
· min
−1
) best corresponded to the final area of infarction (37±18% versus 40±24%; correlation coefficient, 0.866;
P
<0.01). The acute ischemic core destined to infarction was not surrounded by a widened rim of moderate ischemia because the area with CBF 11 to 20 cm
3
· 100 g
−1
· min
−1
was similar bilaterally (19±4% versus 20±7%,
P
=0.792, thus not significant).

Conclusions
—Our study in acute human stroke involving MCA occlusion indicates that a severely ischemic core (CBF ≤6 cm
3
· 100 g
−1
· min
−1
), observed between 1 to 6 hours after stroke onset, corresponds to the cerebral tissue destined to infarction. The ischemic penumbra with flow values between 7 and 20 cm
3
· 100 g
−1
· min
−1
surrounding the ischemic core is very narrow. Therefore, strategies to improve the outcome of many patients with acute MCA occlusion must either include interventions to reverse the ischemic process within a few minutes of onset or increase the cerebral tolerance of ischemia and thereby prolong the potential therapeutic window.
What Determines Good Recovery in Patients With the Most Severe Strokes?
Authors: Jørgensen Henrik S. , Reith Jakob , Nakayama Hirofumi , Kammersgaard Lars P. , Raaschou Hans O. , Olsen Tom Skyhøj
Published: June 2011

Background and Purpose
—Even patients with the most severe strokes sometimes experience a remarkably good recovery. We evaluated possible predictors of a good outcome to search for new therapeutic strategies.

Methods
—We included the 223 patients (19%) with the most severe strokes (Scandinavian Stroke Scale score <15 points) from the 1197 unselected patients in the Copenhagen Stroke Study. Of these, 139 (62%) died in the hospital and were excluded. The 26 survivors (31%) with a good functional outcome (Barthel Index ≥50 points) were compared with the 58 survivors (69%) with a poor functional outcome (Barthel Index <50 points). The predictive value of the following factors was examined in a multivariate logistic regression model: age; sex; a spouse; work; home care before stroke; initial stroke severity; blood pressure, blood glucose, and body temperature on admission; stroke subtype; neurological impairment 1 week after onset; diabetes; hypertension; atrial fibrillation; ischemic heart disease; previous stroke; and other disabling disease.

Results
—Decreasing age (odds ratio [OR], 0.50 per 10-year decrease; 95% CI, 0.25 to 0.99;
P
=0.04), a spouse (OR, 3.1; 95% CI, 1.1 to 8.8;
P
=0.03), decreasing body temperature on admission (OR, 1.8 per 1°C decrease; 95% CI, 1.1 to 3.1;
P
=0.01), and neurological recovery after 1 week (OR, 3.2 per 10-point increase in Scandinavian Stroke Scale score; 95% CI, 1.1 to 7.8;
P
=0.01) were all independent predictors of good functional outcome.

Conclusions
—Patients with the most severe strokes who achieve a good functional outcome are generally characterized by younger age, the presence of a spouse at home, and early neurological recovery. Body temperature was a strong predictor of good functional outcome and the only potentially modifiable factor. We suggest that a randomized controlled trial be undertaken to evaluate whether active reduction of body temperature can improve the generally poor prognosis of patients with the most severe strokes.
Chlamydia pneumoniae
Antibodies and High Lipoprotein(a) Levels Do Not Predict Ischemic Cerebral Infarctions
Authors: Glader Christine Ahlbeck , Stegmayr Birgitta , Boman Jens , Stenlund Hans , Weinehall Lars , Hallmans Göran , Dahlén Gösta H.
Published: June 2011

Background and Purpose
—An association between high lipoprotein(a) [Lp(a)] levels and positive
Chlamydia pneumoniae
IgG titers in coronary artery disease has been described. The possibility of predicting ischemic stroke by measurements of plasma Lp(a) and
C pneumoniae
antibodies was investigated.

Methods
—This incident case-control study included 101 case subjects (cases) who had suffered ischemic cerebral infarctions and 201 matched control subjects (controls). The study population was nested within the Västerbotten Intervention Program or the WHO MONICA project. Plasma samples were measured for
C pneumoniae
–specific IgG and IgA antibodies and Lp(a).

Results
—A significantly higher mean Lp(a) level was found in female cases than in female controls. However, plasma Lp(a) was unable to predict ischemic cerebral infarctions in either women or men. The proportion of individuals with positive
C pneumoniae
–specific IgG or IgA titers did not differ between cases and controls. Antibody titers were unable to predict a future stroke. The proportion of individuals with a positive
C pneumoniae
IgG titer in combination with a high Lp(a) level did not differ significantly between cases and controls.

Conclusions
—These data suggest that there is no association between baseline plasma Lp(a) levels, presence of
C pneumoniae
antibodies, and future ischemic cerebral infarctions. Furthermore, no evidence of an interactive effect between high Lp(a) levels and
C pneumoniae
IgG titers was found. However, selection bias and a recent
C pneumoniae
epidemic may have influenced the results.
Lack of Evidence of Acute Ischemic Tissue Change in Transient Global Amnesia on Single-Shot Echo-Planar Diffusion-Weighted MRI
Authors: Gass A. , Gaa J. , Hirsch J. , Schwartz A. , Hennerici M. G.
Published: June 2011

Background and Purpose
—There is uncertainty concerning the etiology of transient global amnesia (TGA). Previous CT and MRI studies have indicated that permanent structural abnormality is rare in TGA. Diffusion-weighted (DW) MRI is very sensitive to early ischemic parenchymal changes and has recently demonstrated embolic infarction in the posterior cerebral artery territory in 2 TGA patients. We report the findings of DW MRI in 8 patients in acute stages of TGA.

Methods
—Conventional and echo-planar DW MRI was performed in 2 patients in the active phase and 6 patients in the recovery phase (1 to 8 hours after cessation of anterograde memory dysfunction) of spontaneously occurring TGA.

Results
—None of the patients showed signs of hyperintensity on DW images or hypointensity on quantitative apparent diffusion coefficient (ADC) maps to suggest regional decreases of water mobility or acute T2 changes on transverse or coronal slices.

Conclusions
—We were unable to detect ADC or acute T2 changes with echo-planar DW MRI in patients with TGA, which suggests that mechanisms other than ischemic infarction may cause TGA. We did not identify spreading depression–associated changes of the ADC. Further refinement of MRI sequences may be necessary to detect subtle or transient signal change in brain parenchyma.
Treatment of Posterior Circulation Ischemia With Extracranial Percutaneous Balloon Angioplasty and Stent Placement
Authors: Malek Adel M. , Higashida Randall T. , Phatouros Constantine C. , Lempert Todd E. , Meyers Philip M. , Gress Daryl R. , Dowd Christopher F. , Halbach Van V.
Published: June 2011

Background and Purpose
—Vertebrobasilar territory ischemia (VBI) leads to disabling neurological symptoms and poses a risk for stroke by an embolic or flow-related mechanism. We present our clinical experience in the endovascular treatment of patients with symptomatic VBI from severe atherosclerosis or dissection of the vertebral and subclavian arteries that was unresponsive to medical therapy.

Methods
—Twenty-one patients (9 female, 12 male) with a mean age of 65.7 years (range 47 to 81 years) underwent treatment with percutaneous endovascular balloon angioplasty and stent placement. Sixteen patients (76.2%) had evidence of contralateral involvement, and 9 (42.8%) demonstrated severe anterior-circulation atherosclerosis. Nine patients had a previous infarct in the occipital lobe, cerebellum, or pons before treatment. Follow-up was available for all patients.

Results
—Balloon angioplasty with intravascular stent placement was performed in 13 vertebral artery lesions (10 at the origin, 3 in the cervical segment) and in 8 subclavian lesions. The prestenting stenosis was 75% (50% to 100%) and was reduced to 4.5% (0% to 20%) after stenting. Six of the patients with proximal subclavian stenosis demonstrated angiographic evidence of subclavian steal, which resolved in all cases after treatment. All patients showed improvement in symptoms after the procedure except for 1 who developed a hemispheric stroke after thrombotic occlusion of an untreated cavernous carotid artery stenosis (rate of major stroke and mortality=4.8%). One patient (4.8%) had a periprocedural transient ischemic attack (TIA), and none had minor stroke. At long-term follow-up (mean=20.7±3.6 months) of the surviving 20 patients, 12 (57.1%) remained symptom-free, 4 (19%) had at most 1 TIA over a 3-month period, 2 (9.5%) had at most 1 TIA per month, and 2 (9.5%) had persistent symptoms. There were no clinically evident infarcts during the follow-up period.

Conclusions
—Endovascular treatment using balloon angioplasty with intravascular stent placement for symptomatic stenotic lesions resulting in VBI that is unresponsive to medical therapy appears to be of benefit in this high-risk subset of patients with poor collateral flow.
The Stroke Impact Scale Version 2.0
Authors: Duncan Pamela W. , Wallace Dennis , Lai Sue Min , Johnson Dallas , Embretson Susan , Laster Louise Jacobs
Published: June 2011

Background and Purpose
—To be useful for clinical research, an outcome measure must be feasible to administer and have sound psychometric attributes, including reliability, validity, and sensitivity to change. This study characterizes the psychometric properties of the Stroke Impact Scale (SIS) Version 2.0.

Methods
—Version 2.0 of the SIS is a self-report measure that includes 64 items and assesses 8 domains (strength, hand function, ADL/IADL, mobility, communication, emotion, memory and thinking, and participation). Subjects with mild and moderate strokes completed the SIS at 1 month (n=91), at 3 months (n=80), and at 6 months after stroke (n=69). Twenty-five subjects had a replicate administration of the SIS 1 week after the 3-month or 6-month test. We evaluated internal consistency and test-retest reliability. The validity of the SIS domains was examined by comparing the SIS to existing stroke measures and by comparing differences in SIS scores across Rankin scale levels. The mixed model procedure was used to evaluate responsiveness of the SIS domain scores to change.

Results
—Each of the 8 domains met or approached the standard of 0.9 α-coefficient for comparing the same patients across time. The intraclass correlation coefficients for test-retest reliability of SIS domains ranged from 0.70 to 0.92, except for the emotion domain (0.57). When the domains were compared with established outcome measures, the correlations were moderate to strong (0.44 to 0.84). The participation domain was most strongly associated with SF-36 social role function. SIS domain scores discriminated across 4 Rankin levels. SIS domains are responsive to change due to ongoing recovery. Responsiveness to change is affected by stroke severity and time since stroke.

Conclusions
—This new, stroke-specific outcome measure is reliable, valid, and sensitive to change. We are optimistic about the utility of measure. More studies are required to evaluate the SIS in larger and more heterogeneous populations and to evaluate the feasibility and validity of proxy responses for the most severely impaired patients.
Role for Telemedicine in Acute Stroke
Authors: Shafqat Saad , Kvedar Joseph C. , Guanci Mary M. , Chang Yuchiao , Schwamm Lee H.
Published: June 2011

Background and Purpose
—Immediate access to physicians experienced in acute stroke treatment may improve clinical outcomes in patients with acute stroke. Interactive telemedicine can make stroke specialists available to assist in the evaluation of patients at multiple urban or remote rural facilities. We tested whether interrater agreement for the NIH Stroke Scale (NIHSS), a critical component of acute stroke assessment, would persist if performed over a telemedicine link.

Methods
—One bedside and 1 remote NIHSS score were independently obtained on each of 20 patients with ischemic stroke. The bedside examination was performed by a stroke neurologist at the patient’s bedside. The remote examination was performed by a second stroke neurologist through an interactive high-speed audio-video link, assisted by a nurse at the patient’s bedside. Kappa coefficients were calculated for concordance between bedside and remote scores.

Results
—Remote assessments took slightly longer than bedside assessments (mean 9.70 versus 6.55 minutes,
P
<0.001). NIHSS scores ranged from 1 through 24. Based on weighted κ coefficients, 4 items (orientation, motor arm, motor leg, and neglect) displayed excellent agreement, 6 items (language, dysarthria, sensation, visual fields, facial palsy, and gaze) displayed good agreement, and 2 items (commands and ataxia) displayed poor agreement. Total NIHSS scores obtained by bedside and remote methods were strongly correlated (
r
=0.97,
P
<0.001).

Conclusions
—The NIH Stroke Scale remains a swift and reliable clinical instrument when used over interactive video. Application of this technology can bring stroke expertise to the bedside, regardless of patient location.
Analysis of the Perception of and Reactivity to Pain and Heat in Patients With Wallenberg Syndrome and Severe Spinothalamic Tract Dysfunction
Authors: Rousseaux M. , Cassim F. , Bayle B. , Laureau E.
Published: June 2011

Background
—The aim of the study was to assess the consequences of severe spinothalamic tract lesions resulting from lateral medullary infarct and to show that a specific pain perception can be elicited by strong thermal stimulation.

Case Descriptions
—
Both patients examined presented with severe thermoalgic dissociation of the limbs contralateral to the lesion, with normal discriminative somatosensory perception and motor strength. They reported pain perception when touching very warm (>50°C to 60°C) objects and a brisk, occasionally uncontrolled withdrawal reaction of the arm and hand under the same conditions, without any perception of the heat nature of the stimulus. Warm stimulation, <45°C, elicited no thermal perception or discrimination. Pain perception could be elicited in both patients by increasing the temperature, with a reproducible threshold of 47°C to 49°C. Pain always occurred after a prolonged delay of 8 to 10 seconds in response to threshold heat, and was described as deep and osseous, and clearly different from that perceived on the nonaffected side. The delay was much shorter when the temperature was increased by 4°C to 5°C. Cold stimulation elicited similar pain perception in one patient. Analysis of subjective perception of laser stimulation showed a much higher pain threshold on the affected hand. There were no laser-evoked potentials on this side, which suggested major spinothalamic injury. Assessment of the RIII noxious reflex revealed persistent response withdrawal reactions, with an increased threshold on the affected side, and partial consciousness of the noxious nature of the stimulus.

Conclusions
—To our knowledge, this is the first description of the appearance of pain perception of high temperatures in patients with severe spinothalamic injury who are suffering from a complete loss of temperature perception. This implies that noxious thermal stimulation can still be perceived via extra spinothalamic pathways (which are slow and multisynaptic), such as the spinoreticulothalamic tract. Patients with Wallenberg syndrome should be informed and made aware of their residual perception of and reactions to noxious stimulation.
Long-Term Prognosis of Cerebral Ischemia in Young Adults
Authors: Marini Carmine , Totaro Rocco , Carolei Antonio
Published: June 2011

Background and Purpose
—Prognosis of ischemic stroke in young adults is reported as favorable, and transient ischemic attack (TIA) is commonly considered a benign event. We investigated long-term outcome and prognostic predictors of cerebral ischemia in patients under 45 years of age.

Methods
—Three hundred thirty-three patients aged 15 to 44 years who suffered from a first-ever TIA or ischemic stroke were prospectively followed up with annual clinical evaluation or complete phone interview. End points were the composite outcome event of stroke, myocardial infarction, and vascular or nonvascular death and death from all causes. The probability of event-free survival was estimated by the Kaplan-Meier method. Univariate and multivariate estimates of hazard ratios were calculated according to the Cox proportional hazards analysis.

Results
—An average follow-up of 96 months was available in 330 patients (99.1%). Survival was worse in patients with stroke at entry (86.5%) than in those with TIA (97.1%). Mortality in both groups was significantly higher than in the general population (standardized mortality ratio [SMR] 14.5,
P
<0.0001, Poisson distribution test, and SMR 7.9,
P
=0.002). The average annual mortality rate was higher during the first (3.94%, 95% CI 1.84 to 6.04) than in the subsequent years. The average annual incidence rate of new stroke was higher in patients with stroke than in those with TIA at entry, and it declined from 1.56% (95% CI 0.21 to 2.91) during the first year to 0.06% (95% CI 0.04 to 0.08) at the end of the follow-up. Myocardial infarction occurred later, after the first year, with similar rates in patients with stroke and TIA at entry. The average annual rates of new stroke (2.36%), myocardial infarction (1.68%), and death (3.05%) were higher in patients with the mixed atherothrombotic and cardioembolic etiology than in the remaining patients. Male gender, age >35 years, stroke at entry, and cardiac diseases were independent predictors of the composite outcome event at the Cox regression analysis, whereas only stroke at entry and cardiac diseases predicted death from all causes.

Conclusions
—Stroke and TIA in young adults have severe prognostic implications, because the mortality risk was highly increased with respect to the general population. Preventive measures are strongly recommended in the presence of any unfavorable prognostic profile.
Underlying Structure of the National Institutes of Health Stroke Scale
Authors: Lyden Patrick , Lu Mei , Jackson Christy , Marler John , Kothari Rashmi , Brott Thomas , Zivin Justin
Published: June 2011

Background and Purpose
—No stroke scale has been validated as an outcome measure using data from a clinical trial demonstrating a positive therapeutic effect. Therefore, we proposed to use data from the National Institute of Neurological Disorders and Stroke (NINDS) tPA Stroke Trial to determine whether the National Institutes of Health Stroke Scale (NIHSS) was valid in patients treated with tissue plasminogen activator (tPA) and to explore the underlying clinimetric structure of the NIHSS.

Methods
—We performed an exploratory factor analysis of NIHSS data from Part 1 (n=291) of the NINDS tPA Stroke Trial to derive a hypothesized underlying factor structure. We then performed a confirmatory factor analysis of this structure using NIHSS data from Part 2 of the same trial (n=333). We then tested whether this final factor structure could be found in tPA- and placebo-treated patients serially over time after stroke treatment. Using 3-month outcome data, we tested for an association between the NIHSS and other measures of stroke outcome.

Results
—The exploratory analysis suggested that there were 2 factors underlying the NIHSS, representing left and right brain function, confirming the content validity of the scale. An alternative structure composed of 4 factors could be derived, with a better goodness of fit: the first 2 factors could represent left brain cortical and motor function, respectively, and the second 2 factors could represent right brain cortical and motor function, respectively. The same factor structures were then found in tPA and placebo patient groups studied serially over time, confirming the exploratory analysis. All 3-month clinical outcomes were associated with each other at subsequent time points, confirming predictive validity.

Conclusions
—This is the first study of the validity of a stroke scale in patients treated with effective stroke therapy. The NIHSS appeared to be valid in patients with acute stroke and for finding treatment-related differences. The scale was valid when used serially over time after stroke, up to 3 months, and showed good agreement with other measures of outcome.
Does the National Institutes of Health Stroke Scale Favor Left Hemisphere Strokes?
Authors: Woo Daniel , Broderick Joseph P. , Kothari Rashmi U. , Lu Mei , Brott Thomas , Lyden Patrick D. , Marler John R. , Grotta James C.
Published: June 2011

Background and Purpose
—The National Institutes of Health Stroke Scale (NIHSS) is a valid, reproducible scale that measures neurological deficit. Of 42 possible points, 7 points are directly related to measurement of language compared with only 2 points related to neglect.

Methods
—We examined the placebo arm of the NINDS t-PA stroke trial to test the hypothesis that the total volume of cerebral infarction in patients with right hemisphere strokes would be greater than the volume of cerebral infarction in patients with left hemisphere strokes who have similar NIHSS scores. The volume of stroke was determined by computerized image analysis of CT films and CT images stored on computer tape and optical disks. Cube-root transformation of lesion volume was performed for each CT. Transformed lesion volume was analyzed in a logistic regression model to predict volume of stroke by NIHSS score for each hemisphere. Spearman rank correlation was used to determine the relation between the NIHSS score and lesion volume.

Results
—The volume for right hemisphere stroke was statistically greater than the volume for left hemisphere strokes, adjusting for the baseline NIHSS (
P
<0.001). For each 5-point category of the NIHSS score <20, the median volume of right hemisphere strokes was approximately double the median volume of left hemisphere strokes. For example, for patients with a left hemisphere stroke and a 24-hour NIHSS score of 16 to 20, the median volume of cerebral infarction was 48 mL (interquartile range 14 to 111 mL) as compared with 133 mL (interquartile range 81 to 208 mL) for patients with a right hemisphere stroke (
P
<0.001). The median volume of a right hemisphere stroke was roughly equal to the median volume of a left hemisphere stroke in the next highest 5-point category of the NIHSS. The Spearman rank correlation between the 24-hour NIHSS score and 3-month lesion volume was 0.72 for patients with left hemisphere stroke and 0.71 for patients with right hemisphere stroke.

Conclusions
—For a given NIHSS score, the median volume of right hemisphere strokes is consistently larger than the median volume of left hemisphere strokes. The clinical implications of our finding need further exploration.
Serial Magnetic Resonance Imaging of Rat Brain After Induction of Renal Hypertension
Authors: Del Bigio Marc R. , Yan Hui Jin , Kozlowski Piotr , Sutherland Garnette R. , Peeling James
Published: June 2011

Background and Purpose
—Hypertension is a major risk factor for ischemic and hemorrhagic stroke and may also cause more chronic and subtle brain injury. Progressive brain changes in a rat model of renal hypertension have been assessed to better understand the pathogenesis of hypertensive brain damage.

Methods
—Young adult rats were made hypertensive by partial occlusion of both renal arteries. MR images of brain were obtained weekly, and histopathological outcome was assessed. A separate group of rats was used to measure brain specific gravity and Evans blue dye content as an indicator of extravasation.

Results
—Rats developed maximal mean systolic blood pressures of 173 to >300 mm Hg, reaching a plateau in 6 to 8 weeks. Rats whose mean systolic pressure never exceeded 210 mm Hg never had brain lesions, while rats whose mean systolic pressure exceeded 276 mm Hg consistently developed brain lesions. Brain T2 values increased with increasing blood pressure. Lesions seen on MRI corresponded to those seen histologically. MRI also demonstrated transient brain expansion, probably due to diffusely increased water content, and rarely demonstrated focal cortical edema, which had no histological correlate. These transient phenomena, as well as hemorrhagic and ischemic infarcts, occurred mainly during the phase of climbing blood pressure and early stages of stable hypertension.

Conclusions
—Serial MRI reveals aspects of hypertensive brain disease that cannot be studied by histological examination alone. The observed phenomena are likely related to loss of autoregulation and/or blood-brain barrier integrity. Breach of blood vessel integrity is less likely once the vessels become accustomed to high pressures.
Nuclear Factor-κB and Cell Death After Experimental Intracerebral Hemorrhage in Rats
Authors: Hickenbottom Susan L. , Grotta James C. , Strong Roger , Denner Larry A. , Aronowski Jaroslaw
Published: June 2011

Background and Purpose
—Nuclear factor-κB (NF-κB) is a ubiquitous transcription factor that, when activated, translocates to the nucleus, binds to DNA, and promotes transcription of many target genes. Its activation has been demonstrated in chronic inflammatory conditions, cerebral ischemia, and apoptotic cell death. The present study evaluated the presence and activation of NF-κB in relation to cell death surrounding intracerebral hemorrhage (ICH).

Methods
—Striatal ICH was induced in rats by the double blood injection method. Animals were killed 2, 8, and 24 hours and 4 days after ICH. To examine changes in NF-κB protein, Western blot was performed on brain extract. We determined NF-κB activity using electrophoretic mobility shift assay (EMSA) and immunohistochemistry, using an antibody that only recognizes active NF-κB. DNA fragmentation was detected with terminal deoxynucleotidyl transferase–mediated uridine 5′-triphosphate-biotin nick end-labeling (TUNEL) staining.

Results
—Western blot analysis of the NF-κB p65 subunit showed that there was no difference in p65 protein levels in the control, 2-hour, 8-hour, or 24-hour groups. However, ipsilateral perilesional samples from the 4-day group revealed a 1.8- to 2.5-fold increase compared with the contralateral hemisphere. Western blotting showed no differences in the inhibitor of NF-κB, IκBα, in any group. EMSA showed 1.3-, 2.1-, and 3.6-fold increased NF-κB activation in the ipsilateral striatum from the 8-hour, 24-hour, and 4-day groups, respectively, compared with the contralateral hemisphere. Immunohistochemistry, in which an activation-dependent anti–NF-κB antibody was used, demonstrated perivascular NF-κB activation as early as 2 hours after ICH with more generalized activation at 8 hours, in agreement with the EMSA results. NF-κB activation colocalized to cells containing fragmented DNA measured by TUNEL.

Conclusions
—The present study suggests a relationship between NF-κB and the pathobiology of perilesional cell death after ICH.