bluuebunny/crossref_metadata_2025 huggingface dataset:
The neuroprotective efficacy of NXY-059 in permanent MCAo in the rat: Dose response and therapeutic window
Authors: Sydserff S G , Borrelli A R , Cross A J
Published: March 2022

P78

Introduction.
NXY-059 (disodium 4-[(tert-butylimino)methyl] benzene-1,3-disulfonate N-oxide) is a nitrone with free radical trapping properties and is being developed for the treatment of acute ischemic stroke. NXY-059 possesses proven neuroprotective efficacy in rat transient models of middle cerebral artery occlusion (MCAo) (J Cereb Blood Flow Metab 1999;19:778–87), however its efficacy in permanent models of focal cerebral ischemia has not been as extensively tested. In the present study we have examined the efficacy of NXY-059 at three doses and further examined the therapeutic window of the mid-range dose.
Methods.
Adult male Wistar rats (300–330g) were given a unilateral permanent MCAo using an intraluminal suture technique. To assess efficacy of three doses of NXY-059, vehicle or NXY-059 (30, 50 or 70 mg/kg/h) was infused using minipumps for 24 hours. Dosing began 5 minutes after the MCAo with a bolus injection of vehicle or NXY-059 (30, 50 or 70 mg/kg). To assess the therapeutic window, treatment with 50 mg/kg (loading dose) and 50 mg/kg/h (over 24 hours) NXY-059 was commenced at 5, 30, 60, 120 and 240 minutes after MCAo. For both assessments, brains were removed 24 hours after commencing treatment and volume of damage was calculated from 5 x 2mm sections stained with triphenyl tetrazolium chloride.
Results.
NXY-059 (30, 50 and 70 mg/kg/h) reduced the volume of damage by 23%, 57% and 81% respectively (p<0.05). Treatment with NXY-059 (50 mg/kg/h) beginning at 5, 30, 60, 120 and 240 minutes after permanent MCAo reduced the volumes of damage by 52%, 45%, 50%, 43% and 35% respectively (p<0.05).
Conclusions.
In rats given a permanent MCA occlusion, NXY-059 at doses of 30–70 mg/kg/h given for 24 hours significantly (p<0.05) reduced the volume of cerebral damage, and significant protection was seen when treatment was delayed for as long as 4 hours after permanent MCAo.
ANESTHETIC AGENT CHOICE INFLUENCES OUTCOME FROM EXPERIMENTAL PERIOPERATIVE STROKE
Authors: Bhardwaj Anish , Castro Alejandro , Traystman Richard J , Hurn Patricia D , Kirsch Jeffrey R
Published: March 2022

P81

It is unclear if damage during perioperative stroke is linked to the anesthetic agent employed during prior surgical procedure. We examined 2 representative agents, propofol and halothane, to test the hypothesis that anesthetic “preconditioning” improves outcome from middle cerebral artery occlusion (MCAO) induced on emergence from short or prolonged anesthesia. Male Wistar rats (200–300 g) were anesthetized briefly (<1 h) with halothane (1–2%) for placement of a femoral arterial and venous catheter and of a retaining sleeve for chronic laser Doppler perfusion (LDP) probe on the cranium. Twenty fours hours following instrumentation, spontaneously ventilated rats were reanesthetized with either halothane (1–2%) or intravenous propofol (10 mg/kg bolus and 30 mg/kg/hr infusion). Rats were subjected to 2 h of MCAO following exposure to either short (< 1 hr;n=8, Short-Hal; n=8, Short-Prop) or long (8 hr) (n=8, Long-Hal; n=8, Long-Prop) anesthetic. Anesthesia was discontinued after the first 15 min of cerebral ischemia, which was documented by abrupt fall in LDF-signal during suture placement. Pericranial temperature, PaO
2
, PaCO
2
and blood pressure were maintained in a normal range, without differences between groups. LDP-signal between groups was silmiar during MCAO and reperfusion. At 22 h of reperfusion, brain infarction volume was determined by TTC-staining. Preconditioning with short duration of halothane resulted in smaller infarction in cortex (87.5 ± 16.6 mm
3
, 23.5 ± 4.4% of ipsilateral cortex) and caudoputamen complex (CP) (38.3 ± 13.7 mm
3
, 46.0 ± 5.2% of ipsilateral CP) than in rats preconditioned with equivalent propofol (cortex 177.5 ± 16.9 mm
3
; 46.6 ± 4.4%; CP 47.8 ± 2.9 mm
3
, 60.8 ± 3.7%). There was no difference in rats preconditioned with Long-Hal or Long-Prop. Halothane but not propofol preconditioning of <1 hour decreases brain vulnerability to subsequent ischemic insults initiated during emergence from anesthesia. Exposure to longer durations of halothane may activate secondary pathways which negate the protective effects of short-term halothane preischemic conditioning.
ICAM-1 Expression, Neutrophil & Monocyte Infiltration and Microglia Activation Reduced by Mild Hypothermia in a Rat Model of Transient Focal Cerebral Ischemia
Authors: Wang Gerald J , Deng Holly Y , Maier Carolina M , Sun Guo Hua , Yenari Midori A
Published: March 2022

P84

BACKGROUND:
Inflammation potentiates ischemic injury especially with reperfusion, while mild hypothermia is an effective neuroprotectant. We studied whether mild hypothermia’s protective effect may be due to blunting the inflammatory response.
METHODS:
We compared endothelial intracellular adhesion molecule (ICAM-1) expression, neutrophil & monocyte infiltration, and microglia activation under normothermic (38C n=24) and hypothermic (intraischemic brain cooling to 33C for 2h n=24) conditions 1,3, and 7 days following transient (2h) focal cerebral ischemia in rats. ICAM-1, ED-1 (to detect cells of monocyte lineage including activated microglia) and myeloperoxidase (MPO, to identify neutrophils) were detected using immunohistochemistry on brain sections. We measured cell densities of ICAM-1, ED-1, and MPO in the peri-infarct region. Infarct size was also measured from histology derived sizes of the ipsilateral hemisphere.
RESULTS:
Mild hypothermia reduced infarct size 1–7 days after stroke onset. 1d: 38C: 28±12%, 33C 8±6%; 3d: 38C: 39±23%, 33C: 11±11%; 7d: 38C: 37.3±5.8% vs 33C: 19.4±5.7% (p<0.05). The number of ICAM-1 positive vessels per high power field (HPF) decreased under hypothermia 1–7 days later. 1d: 38C: 35.8±1.7 vs 33C: 24.4±1.4 (p<0.01); 3d: 38C: 36.6±5.0 vs 33C: 23.5 1.3 (p=0.07); 7d: 38C: 69.9±2.7, 33C: 43±5.2 (p<0.001). In addition, neutrophil density (cells/12 HPF) decreased under hypothermic conditions at 1 and 3 days. 1d: 38C: 48±3.0 vs 33C: 1.3±0.6 (p<0.001), 3d: 38C: 75±3.5 vs 33C: 20.3±8.1 (p<0.001). Monocyte and microglial density (cells/HPF) was decreased by mild hypothermia at 3 and 7, but not 1 day. 1d: 38C: 17.5±0.9, 33C: 16.6±0.8, NS; 3d: 38C: 45.5±1.7, 33C: 19.2±0.9, (p<0.0001); 7d: 38C: 75.0 ±2.6, 33C: 24.8±3.0, (p<0.0001).
CONCLUSIONS:
Mild hypothermia reduces adhesion molecule expression, acute (neutrophil) and subacute (monocyte) leukocyte infiltration and microglial activation. These changes are present even days after hypothermic treatment, and suggest that hypothermia significantly attenuates the inflammatory response.
Intrinsic differences in local cerebral blood flow yield higher vulnerability to transient focal ischemia in Balb/C than C57B1/6 or SV129J mice.
Authors: Wei Ling , Pawa Swati , Nagaraja Tavarekere , Hsu Chung Y , Fenstermacher Joseph D
Published: March 2022

P85

Stroke is a vascular disease in which brain cell death is initiated by a great reduction in blood flow. Only a few minutes of markedly lowered local blood flow (focal ischemia) may injure neurons and non-neuronal cells (e.g., endothelial cells and astrocytes) and lead to their death. The size and type of lesion depend on the duration and extent of flow reduction plus other local, mainly intrinsic variables. To understand the interplay between flow reduction and intrinsic factors in short-term, focal ischemic damage, blood flow and cell injury were assessed in three strains of mice.
Method:
The middle cerebral artery (MCA) was unilaterally occluded for 15 min in SV129, C57Bl/6, and Balb/C mice. Local cerebral blood flow (LCBF) was measured at the end of MCA occlusion by quantitative autoradiography (N=6 per strain). In other mice, cell damage and infarct size were assayed after 1–7days of reperfusion.
Results:
LCBF in the ischemic core region during MCA occlusion was greatly and similarly reduced in all three strains (range=3–20 ml/100g/min); LCBF in the penumbra, however, differed among the strains (LCBF in descending order: SV129>C57Bl/6>Balb/c mice). In addition, the penumbral zone was strikingly narrow in Balb/C mice. After 24 hr of reperfusion, the frequency of TUNEL positive cells in the ischemic core was highest (and most widespread) in Balb/C mice, much less in C57B1/6 mice, and nil in SV129 mice. Consistently, infarcts were seen after 3-day reperfusion in Balb/C and C57B1/6 mice but not in SV129 mice; increasing MCA occlusion to 30 min, however, caused infarction in the cerebral cortex of SV129 mice.
Conclusion:
These results indicate considerable dependence of brain cell damage on LCBF reduction with transient focal ischemia and suggest that there are intrinsic differences in cerebrovascular structure and/or function among these three mouse strains. Other differences in genetic background may, however, contribute to this interstrain variation in vulnerability to transient focal ischemic. Supported by NIH grants NS37372 and NS25545.
Activation of MAP kinase (ERK-1/ERK-2), tyrosine kinase and VEGF in the human brain following acute ischaemic stroke
Authors: M Jurek A Krupinski , F Eulalia Marti Puig , M Mark A Slevin , F Agnieszka Slowik , M Andrzej Szczudlik
Published: March 2022

P89

We examined expression of vascular endothelial growth factor (VEGF), together with phosphorylation of mitogen activated protein kinase (MAP) kinase (ERK1 and ERK2) and tyrosine phosphorylation in post-mortem material taken from 19 patients and in serum taken serially from 29 patients after acute ischaemic stroke. Expression of VEGF was significantly increased in the majority of patients following acute stroke at all of the time points, compared to normal controls. Highest expression occurred at day 7 (value 588± 688 ng/ml; p=0.005), and it remained elevated at 14 days after stroke. Expression of VEGF correlated with infarct volume, clinical disability (SSS) and peripheral leukocytosis, and was significantly higher in patients with atherothrombotic large vessel disease and ischaemic heart disease (p<0.05 in all cases). In the grey matter penumbra, 13 out of 19 patients showed an increase in MAP kinase tyrosine phosphorylation. In almost all cases, ERK-2 phosphorylation was higher than ERK1. Of these 13 patients, 11 also showed a general increase in tyrosine kinase phosphorylation, whilst 8 expressed increased levels of VEGF protein. In tissue examined directly from the infarct core, activation of the above proteins was not observed in the majority of patients. There was no relationship between activation of MAP kinase and expression of VEGF. We also examined expression of phosphorylated MAP kinase by immunohistochemistry, and found increased immunoreactivity in neurones, astroglial cells, reactive microglia and endothelial cells in areas surrounding infarcts, especially in areas with the highest density of microvessels. In conclusion, chronic activation of tyrosine phosphorylated events, in particular MAP kinase (ERK1/ERK2) occurs consistently in the grey matter penumbra of brain tissue following ischaemic stroke, and may be associated with increase in expression of VEGF. These signal transduction events could be important determinants of the extent of neuronal survival and/or angiogenic activity in the recovering brain tissue.
Initial reperfusion level determines brain infarct size after transient focal ischemia in mice
Authors: Mies Guenter , Olah Laszlo
Published: March 2022

P90

The intraluminal middle cerebral artery (MCA) thread occlusion model in mice was modified to allow reperfusion at different levels after an epsiode of 1 h transient focal cerebral ischemia. This was achieved by keeping the ipsilateral common carotid artery (CCA) either patent or ligated after thread withdrawal. Our aim was to examine to what extent the degree of initial reperfusion influences brain infarct evolution and neurological outcome. C57Black/6 mice were subjected to 1 h MCA occlusion, followed by 0, 1,3, 6, 24, and 72 h reperfusion, with ligated or open CCA (n=4/group). Prior to termination of the experiment by in situ freezing with liquid nitrogen, cerebral protein synthesis (CPS) and blood flow (CBF) were measured simultaneously using H3-leucine and C14-iodoantipyrine, respectively. Multiparametric imaging of H3-CPS and C14-CBF was achieved by double tracer autoradiography, and regional ATP levels by bioluminescent imaging. ATP-depleted and CPS-suppressed areas were expressed as percentage of hemisphere. Relative CBF was calculated in the area of inhibited CPS and expressed as percent of the contralateral homotopic area. In addition, the neurological score of animals was monitored after reperfusion. At the end of ischemia, metabolic disturbances were the same in both experimental groups. After 1 h recirculation, ATP initially recovered despite lower relative CBF in the CCA-ligated (57±9%) as compared to the CCA open group (82 ± 12%; p<0.05). With increasing recirculation time, however, the areas of secondary ATP depletion and CPS suppression in the CCA-ligated (ATP:54±12%; CPS: 58±11%) were significantly larger than in the CCA-open group (ATP: 24±22%; CPS: 33±22; p<0.05) at comparable relative CBF values (80%). Metabolic improvement also correlated with significantly better neurologic scores at 24 h (1.3±0.5 vs. 2.4±0.6 points; p<0.05) and 72 h (1.8±0.5 vs. 2.6±0.6; p<0.05) after reperfusion. Our data suggest that improved initial reperfusion decreases infarct size and ameliorates functional recovery after transient ischemia probably by prevention of relative hypoxia in the presence of ongoing mitochondrial dysfunction.
Hemorrhagic Transformation: Influence of occlusion duration, infarct size and tissue plasminogen activator in experimental stroke
Authors: Fagan Susan C , Knight Robert A , Kinnaird Alex
Published: March 2022

P93

Introduction:
The availability of reperfusion therapy for acute ischemic stroke patients has made the causes and significance of hemorrhagic transformation an area of intense interest and controversy.
Methods:
Seventy-four male Wistar rats underwent temporary middle cerebral artery occlusion (MCAO) of between 1 and 6 hours. Twenty-two animals received 10 mg/kg of tissue plasminogen activator (tPA), infused over 20 minutes, starting 5 minutes before reperfusion. At 18–24 hours, the animals were sacrificed and tissue collected for analysis. The presence of grossly observable hemorrhagic transformation (HT)was recorded and total ischemic lesion area was quantified using image analysis software (Zeiss - KS 300). Stepwise logistic regression was used to quantify the important contributors to HT development.
Results:
Thirty animals developed HT. The development of HT was significantly associated with occlusion duration (p=0.0004),with every hour of delay increasing the risk of HT by 1.9. The times associated with 25%,50% and 75% HT were 2.5, 4 and 5.5.hours, respectively. Infarct size (sum of lesion areas) was also signficantly associated with HT (p=0.02) but in the step wise regression, neither infarct size nor tPA contributed significantly to the model. The overall predictive value of the model was 77% but it was higher (81%) when predicting no HT.
Conclusions:
Duration of occlusion is a more important predictor of HT than either the infarct size or the presence of tPA in temporary MCAO in the rat. Duration of occlusion most closely predicts the degree of damage to the vasculature necessary for the development of HT.
Dynamic Single-Section Contrast CT Measures Cerebral Blood Flow in Acute Intracerebral Hemorrhage
Authors: Rosand Jonathan , Eskey Clifford , Gonzalez Ramon G , Knudsen Katherine A , Greenberg Steven M , Koroshetz Walter J
Published: March 2022

P102

Objective:
Investigate presence of reduced rCBF in hyperacute ICH using contrast CT.
Background:
Reduced rCBF has been reported in ICH. Its extent and precise pattern, however, remain uncertain. Hyperacute ICH patients are difficult to study as they are often critically ill. Dynamic CT is rapid, easily performed and offers superior spatial resolution to PET, SPECT and MRI.
Methods:
CT scans were performed within 12 hrs of symptom-onset in 3 acute ICH patients during high-speed injection of standard iodinated contrast via the antecubital vein. Two 10 mm thick target sections were imaged continuously for 60 sec. After ICH volumes were measured, regions of interest (ROIs) for determination of rCBF were selected in serially expanding 2 mm sections around each hematoma and compared to similarly measured expanding 2 mm sections around a hypothetical hematoma in the contralateral hemisphere.
Results:
Three patients were studied at 3, 8 and 11 hrs post symptom-onset respectively. Hematoma locations were: putamen (9 ml) frontal lobe (64 ml) and thalamus (10 ml). Regional CBF (ml/min/100g) was decreased in the rim of tissue immediately adjacent to the hematomas (4.2, 2.1, 5.5, respectively) and increased in serially measured concentric ROIs as they expanded around each hematoma. When values obtained 2 and 8 mm from the hematoma periphery were compared, rCBF increased by 440%, 582%, 454%, respectively (graph), compared to 71%, 128%, 4% in the opposite hemisphere.
Conclusion:
Single-section dynamic CT is a promising technique for measuring rCBF around acute intracerebral hematomas. There appears to be a rim of reduced rCBF surrounding these hematomas. Further study is necessary to determine its clinical significance.
Dilation to Tissue Plasminogen Activator of Middle Cerebral Arteries is Prevented by Actin Cytoskeletal Stabilization
Authors: Cipolla Marilyn J , Curry Amy B
Published: March 2022

P115

Background:
Tissue plasminogen activator (tPA) is the only FDA approved treatment for acute ischemic stroke, however, the effects of tPA on the cerebral circulation are unknown. We have previously shown that perfusion of isolated middle cerebral arteries (MCAs) with 400μg/mL tPA inhibits pressure-induced myogenic constriction (
Stroke
2000;31:940–45). In the present study, we investigated the effect of increasing concentrations of tPA on myogenic tone and whether or not treatment of MCAs with jasplakinolide (JASP), a cell-permeable compound that stabilizes the actin cytoskeleton of smooth muscle, could prevent tPA-induced vasodilation.
Methods:
MCAs were isolated from male Wistar rats and mounted on two glass microcannulas in a specialized arteriograph chamber that allowed control of transmural pressure (TMP) and continuous measurement of lumen diameter. Arteries were pressurized to 75mmHg and tone allowed to develop. One group of MCAs (JSP, n=8) were treated with 10
-7
M JASP and the other group left untreated (CTL, n=6) as controls. Increasing concentrations of tPA (0.1, 1.0, 5.0mg/mL) were then added to the arteriograph bath and lumen diameter recorded at each concentration.
Results:
Addition of tPA caused a concentration-dependent dilation in CTL arteries, decreasing myogenic tone from 28.5±2.8% to 26.7±3.2% in 0.1mg/mL (p<0.05), 22.7±2.3% in 1.0mg/mL (p<0.01) and 20.4±2.3% in 5.0mg/mL (p<0.01) tPA. Treatment of MCAs with JASP significantly prevented this loss of tone, diminishing tone from 25.5±3.0% to only 23.3±3.9% in 0.1mg/mL, 23.3±4.1 in 1.0mg/mL and 22.3±4.3 in 5.0mg/mL tPA (p>0.05 for all).
Conclusions:

It appears that tPA has a direct effect on the arterial wall of MCAs that interferes with myogenic reactivity. Whether this effect is beneficial or not is unclear, however, treatment of arteries to stabilize smooth muscle contractile proteins may prevent this vasodilation and loss of myogenicity. Understanding how tPA affects the cells within the vascular wall is an important step that could lead to improved treatment and stroke outcome.
Variation in health care utilization and outcomes in ischemic stroke
Authors: Williams Linda S , Weinberger Morris , Eckert George , L’Italien Gilbert J , Lapuerta Pablo
Published: March 2022

P125

Objectives:
Little data is available about regional variation in utilization and outcomes during and after ischemic stroke (IS). Examining these relationships can lead to better understanding of the patient and process characteristics that influence stroke outcomes.
Methods:
Index IS admissions were identified using primary position ICD-9 codes 434 and 436 in a national cohort of veterans hospitalized at any VAMC from 10/90 to 10/97. Demographic, admission, mortality and outpatient data were extracted from VA administrative databases for the regions Northeast (NE), South (S), Midwest (MW) and West (W). Discharge diagnoses were used to assess risk factors and to construct the Charlson Index (CI), a predictor of mortality risk (↑ CI = ↑ risk). Time to death was modeled with Cox regression.
Results:
We identified 55,094 IS patients (98% male, 73% white, mean age 68). Regional data are summarized in the Table. NE patients were sicker (higher CI), had longer LOS and higher in-hospital mortality. However, adjusted subsequent mortality was lower in the NE and W (hazard ratio NE = .82, W = .91, p<.001 for both). More NE and W patients had a neurology or primary care visit within 60 days or 1 year.
Conclusions:
Regional variations exist in outcomes and patterns of care after IS. Adjusted subsequent mortality is lower in regions where more patients have follow-up. Prospective studies evaluating these variations are needed to determine the best strategies for providing optimal stroke care.
Depression and Mental Health Disorders Increase Adjusted Risk of Death Post-Stroke
Authors: Ghose Sushmita S , Williams Linda S
Published: March 2022

P140

Background/Objectives:
Post-stroke depression (PSD) has been linked to higher mortality after stroke. Whether PSD and other mental health (MH) diagnoses are independent risks for mortality is not known. The purpose of this study was to examine the relationship of depression and other MH diagnoses to mortality post-stroke.
Methods:
We examined a national cohort of veterans hospitalized at any VA Medical Center from 10/90–10/98. Index ischemic stroke admissions were defined as the first admission with primary discharge ICD-9 diagnosis code 434 or 436. Demographic, admission and all-cause mortality data were abstracted from VA administrative databases. ICD-9 codes at discharge were used to assess risk factors and to construct the Charlson Index, a measure of mortality risk. PSD within 1-year post-stroke was identified using ICD-9 codes. Other MH diagnoses during the entire period were also ascertained. We analyzed the data with and without patients who died < 365 days post-stroke, as patients with early death have less chance of receiving a 1-year PSD diagnosis. Hazard ratios (HR) were modeled using Cox regression.
Results:
We identified 55,094 patients with ischemic stroke, 40,171 survived > 365 days post-stroke. Mean age = 67 and 30% were non-white. 2,537 (6%) had depression within 1 year and 6,761 (17%) had another MH diagnosis. PSD increased adjusted relative mortality risk by 25% (HR 1.25, 95% CI 1.16–1.34). This increase was exceeded only by congestive heart failure (HR 1.39 95% CI 1.31, 1.48), was equal to that of atrial fibrillation (HR 1.25, 95%CI 1.18,1.32) and exceeded age, hypertension, diabetes and coronary artery disease (all HR < 1.21). Other MH diagnoses also increased adjusted relative mortality risk (HR 1.20, 95% CI 1.14, 1.26). Similar results were obtained with the model including patients who died < 365 days after stroke.
Conclusions:
PSD independently increases adjusted risk of all-cause mortality post-stroke. The magnitude of this risk equals many chronic cardiovascular conditions. Other MH diagnoses also increase adjusted mortality risk. Future studies should address whether treatment of these conditions can decrease mortality risk after stroke.
Patients′ Knowledge of Stroke Does Not Influence Time to Hospital Presentation
Authors: Cheung Raymond T F
Published: March 2022

P143

Purpose:
The treatment time window for stroke is narrow. Little is known about patients′ knowledge of stroke, their beliefs, their recognition of warning symptoms, and how these factors affect the time of hospital presentation.
Methods:
A prospective interview of consecutive patients admitted with acute stroke was conducted over an 8-week period. Data recorded included demographic information, history of previous stroke or transient ischemic attack (TIA), the patient′s knowledge of stroke, recognition of warning symptoms and risk factors, and the delay from symptom onset to hospital arrival. Early arrival was defined as within 6 hours of symptom onset. Statistical comparisons were made using two-tailed student′s t test, Mann-Whitney U test, or Fisher′s exact test, depending on the nature of the data.
Results:
The patients′ general knowledge of stroke was fair, and early arrival was seen in 40 (56.3%) of 71 patients. Early presentation was associated with male sex (P=0.028) and a lower initial Glasgow coma scale score (P=0.072) but not with age, a better general knowledge of stroke, a previous history of stroke or TIA, Rankin score upon discharge, and level of education. On the other hand, late presentation was associated with a belief in permanent disability (P=0.056). Of 29 patients who claimed to know about stroke, 22 (75.9%) correctly described about stroke. The stroke warning symptoms were recognized by 45.1 to 76.1% of patients, whereas the recognition of individual risk factor was correct in 36.6 to 76.1% of patients.
Conclusions:
Early arrival was seen in a good proportion of stroke patients in Hong Kong. Nevertheless, our results suggest that improving the general knowledge of stroke among Hong Kong people may not reduce delay in hospital presentation of stroke patients. (Supported by the CRCG Research Grant 10202658 of the University of Hong Kong)
ACUTE Vs LATE POST-STROKE MOOD DISORDERS
Authors: Carota Antonio , Nicola Alain , Aybek Selma , Guex Patrice , Ghika-Schmid Florence , Berney Alexandre , van Melle Guy , Bogousslavsky Julien
Published: March 2022

P149

Background and Methods:
We studied emotional behaviors and mood disorders in 165 consecutive patients with acute first-ever hemispheral stroke. In all patients, a specifically designed observational scale for behavioral appraisal (Emotional Behaviour Index Form or EBIF) was assessed daily for four days, starting within 48 hours. The EBIF, which is independent of language abilities, includes 38 rated items, divided in the categories of overt sadness, passivity, aggressiveness, indifference, disinhibition, denial and adaptation. Prospective evaluation, including a standardized neuropsychological battery, Hamilton depression and anxiety rating scales, Rankin scale, Barthel index, and psychiatric interview with DSM-IV diagnosis , was also performed 3 and 12 months after stroke.
RESULTS:
In the acute phase, observed depressive behaviors and mood verbal scores were not significantly associated with lesion side. However, in patients with left hemispheral lesion, we found a significant relation between aphasia, overt sadness and passivity (p<0.04), while in patients with right lesion, anosognosia was associated with both indifference and depressive behaviors (p<0.04). Only aphasic patients showed catastrophic reactions, and only patients with anosognosia showed extreme indifference reactions. At 3 and 12 months, prevalence of depression was respectively 35% (22/62) and 30% (18/51), while prevalence of anxiety was 33% (16/48) and 27% (12/46). At 12 months, major depression (HDRS>18) was found in 2 patients (3%). Left hemispheral (p=0.05) and subcortical lesions (38% p=0.06) were associated with delayed, but not acute, mood disorders. Anxiety (p=0.05), but not depression (p=0.8), was related to poorer functional impairment (dependency).
CONCLUSIONS:
In acute stroke, observed emotional behaviors are related to specific cognitive impairment (i.e. aphasia and anosognosia), but not to lesion site and side. Acute mood changes are not a strong indicator of delayed post-stroke depression. Post-stroke depression, which is preferentially associated with left or subcortical involvement, may have a different origin from post-stroke anxiety.
Cervical Arterial Dissection:Is It Always Traumatic?
Authors: Beletsky Vadim Yu
Published: March 2022

P154

Background
Cervical arterial dissections are one of the leading causes of stroke in the young. Role of trauma in the pathophysiology of dissection is underestimated, especially since neurological presentation may be delayed and traumatic cases are often judged as “spontaneous”. Role of genetic predisposition is unclear.
Methods
The Canadian Stroke Consortium is presently conducting a prospective national study of arterial cervical dissections. We are collecting data on the mechanism of dissection (spontaneous or traumatic) and therapeutic strategies. All cases have angiographic confirmation.
Results
In 94 patients so far (m/f:52/42;mean age 43.2,range 16–87) there were 62 vertebral artery (VA) and 32 carotid artery (CA) dissections. “Violent” trauma (e.g.neck manipulation) caused 20 dissections in VA and 6 in CA group. Trivial trauma (e.g.various head turns, heavy lifting, etc.) included 32 cases in VA and 12 in CA group. The median time between trauma and clinical presentation was 24 hours (minutes-49 days in VA and minutes-25 days in CA group). Fibromuscular dysplasia or Marfan’s syndrome were observed in 14 patients. There were 6 (10%) cases of recurrent episodes in VA group vs. 5(16%) in carotid [12% overall] despite pharmaceutical intervention before discharge. The severity varied from TIAs to devastating strokes.
Conclusions
The majority of cervical arterial dissections are traumatic. Careful history taking is essential in deciding the mechanism of dissection. Neurological symptoms may occur within months after trauma due to the permanent vascular damage consequent to dissection. Detailed assessment of underlying vascular structural fragility is needed to define patients at risk.
Need For And Clinical Effectiveness Of A Neurologist Supervised, Nurse Case Managed Stroke Risk Reduction Program
Authors: Lafranchise E. Frank , Widener Wallette G , Franklin Barry A , Salmon Richard D , Leighton Richard F , English Carla D , Gordon Neil F
Published: March 2022

P157

Patients who have suffered a previous stroke or TIA and those with carotid artery disease are at a heightened risk for a first or recurrent stroke. In this study, we investigated the prevalence of potentially modifiable CVD risk factors in 247 consecutive patients at a private practice neurology clinic who had previously suffered a stroke or TIA and/or had documented carotid artery disease. We also evaluated the clinical effectiveness of 12 weeks (n=125) and 1 year (n=36) of participation by these patients in a neurologist supervised, nurse case managed stroke risk reduction program. At baseline, potentially modifiable CVD risk factors included physical inactivity (68% of patients), elevated systolic BP (54% of patients), elevated LDL cholesterol (46% of patients), obesity (36% of patients), elevated diastolic BP (32% of patients), and cigarette smoking (15% of patients). On completion of 12 weeks and 1 year of program participation, clinically relevant improvements were observed for select CVD risk factors in patients with abnormal baseline values (Table). These data demonstrate that potentially modifiable CVD risk factors are often suboptimally controlled in patients at high risk for stroke. Our results further document the clinical effectiveness of a neurologist supervised, nurse case managed stroke risk reduction program.
Plasma longitudinal changes of carotenoids and malondialdehyde in stroke patients: relationship to outcome
Authors: Polidori Maria Cristina , Cherubini Antonio , Stahl Wilhelm , Reimann Annette , Ingegni Tiziana , Sies Helmut , Senin Umberto , Mecocci Patrizia
Published: March 2022

P158

Experimental research suggests the association between ischemic stroke and increased oxidative stress. Carotenoids are lipid-soluble molecules with antioxidant activity, but changes of their plasma concentrations during stroke have been never evaluated. Twenty-eight consecutive patients (19M, 9F, mean age 77 y) with acute ischemic stroke (onset < 24 hrs) were divided in subgroups according to the functional outcome at one week as assessed by Barthel Index: group 1 - pts who died or experienced functional decline; group 2 - pts who remained functionally stable. Plasma levels of carotenoids including lutein, zeaxanthin, b-cryptoxanthin, lycopene, α- and β-carotene, and of malondialdehyde (MDA), a marker of lipid peroxidation, were measured on admission, after 6 and 24 hrs, and then on days 3, 5 and 7, by HPLC. Levels on admission were compared to those of age- and sex-matched controls (ctrls). On admission, plasma carotenoid levels were significantly lower (lutein, p<.005; zeaxanthin, p<.05; lycopene, p<.001; α-carotene, p<.004; β-carotene, p<.001) and plasma MDA significantly higher (p<.001) in pts than in ctrls. Plasma carotenoids showed a trend towards a decrease during the first 24 hrs after admission, independently of dietary intake and cholesterol levels. The time-course changes of lutein, α-carotene and lycopene plasma levels up to one week showed higher concentrations in group 2 as compared to group 1 patients. Differences reached statistical significance for lutein (p<.01). Plasma MDA levels tended to decrease over time and were significantly lower in group 2 as compared to group 1 (p<.005). We conclude that carotenoids, which are lipophilic antioxidants, are significantly lower in plasma from stroke patients compared to controls, and are reduced immediately after stroke. Lutein, lycopene and α-carotene are particularly reduced in patients with the worst outcome at one week. MDA is significantly higher in stroke patients on admission compared to controls and is highest in patients who died or declined functionally. A specific carotenoid and lipid peroxidative pattern is associated with a poor early outcome in ischemic stroke.
Intravenous tissue plasminogen activator for acute ischemic stroke in patients ≥80 years old: The London, Canada experience
Authors: Demaerschalk Bart , Merino Jose G , Silver Brian , Tamayo Arturo , Wong Edward H , Devasenapathy Ashok , O’Callaghan Christina , Kertesz Andrew , Young G. Bryan , Spence J David , Hachinski Vladimir
Published: March 2022

P163

Background:
Although, elderly patients (≥80 years) are not excluded from receiving tPA for acute ischemic stroke (AIS), uncertainty still exists regarding the effectiveness and safety of tPA in this age group.
Objective:
To compare baseline characteristics, outcomes, and complications of AIS patients treated with iv tPA aged ≥80 with their younger counterparts (<80).
Methods:
Patients ≥80 were compared to the younger group aged <80 in the prospective London Canada registry of iv tPA use for AIS. Patients presenting with AIS within three hours of symptom onset were treated according to the 1995 National Institute of Neurological Disorders and Stroke (NINDS) guidelines but excluded if >1/3 middle cerebral artery territory was involved. Findings: To date 62 patients have been treated. Median ages of the young group (n=46) are 68 years (range of 37–79) and of the older group (n=16) are 85 years (range of 80–93). Thirty-one of 46 younger patients and eleven of 16 older patients have reached the 3 month follow-up mark. The elderly group had a statistically significant higher mean pre-stroke Modified Rankin Score (mRS) of 1.5 compared to 0.6 for the younger group (p=0.01). The mean initial National Institutes of Health Stroke Scale Scores (NIHSSS), and mean time to tPA from stroke onset do not differ significantly: 14 (young) and 17 (old) (p=0.07), and 151 minutes (young) and 155 minutes (old) (p=0.67). Percent of patients achieving ≥4 point improvement in NIHSS 24 hours post tPA, a 3 month NIHSS of 0–1, and a 3 month MRS of 0–1 are 63 V.S. 44 (p=0.29), 35 V.S. 36 (p=0.80)and 41 V.S. 9 (p=0.12) for the young and old groups respectively. Only one patient (age 81) had a fatal intracranial hemorrhage (ICH). No other patients in the registry suffered a symptomatic ICH. Of the younger group, 11% and of the elderly group, 19% had an asymptomatic ICH (p=0.71).
Conclusions:
Despite the elderly patients having greater pre-stroke disability, iv tPA for AIS in this group does not significantly differ in effectiveness and complications compared to the same treatment in patients under age 80. TPA should not be withheld from AIS patients on the basis of age alone.
The Feasibility of Neuroprotective Agent Administration by Pre-hospital Personnel in an Urban Setting
Authors: Crocco Todd J , Gullett Travis C , Jauch Edward C , Hornung Richard W , Chenier Thomas C
Published: March 2022

P167

Previous studies have demonstrated the importance of early stroke recognition and treatment. Emergency medical service (EMS) personnel are often the stroke patient’s first contact with medical personnel. If clinical trials involving neuroprotective agents (NAs) are successful, prehospital initiation of NAs may allow early administration of these agents.
Objective:
To determine the potential time reduction to administration of NAs if initiated by EMS personnel in the urban prehospital setting.
Method:
23 urban EMS agencies volunteered to participate in this study. Prehospital personnel completed a stroke assessment checklist on any patient considered to be a potential stroke victim. The checklist collected demographic information, clinical inclusion/exclusion criteria for NA administration (including a prehospital stroke scale), and event/decision times. The time data included: scene arrival, scene departure, emergency department (ED) arrival, and estimated time of NA administration. Patients with checklists meeting the hypothetical clinical inclusion criteria (but none of the exclusion criteria) and with completed time data were enrolled in this study. Data analyses were performed using regression analysis and Student’s t-test.
Results:
Of the 30 patients enrolled in this study to date, 13 met criteria to receive NAs. On average, EMS personnel documented the theoretical NA administration 9.8±7.6 minutes prior to ED arrival (during a mean prehospital course of 33±12 minutes). In 6 cases, the NA would have been administered on scene and the remainder en route to the hospital. The EMS providers’ years of experience did not affect the theoretical NA administration time (p=0.705). Study enrollment continues, and approximately 100 enrolled patients are expected by January 1, 2001. Accuracy of EMS stroke recognition will be included in the final analysis.
Conclusion:
In the urban prehospital setting, all patients deemed eligible for NA administration could have been initiated on this therapy by EMS personnel prior to ED arrival.
ASPECT Scores and Lesion Location, Volume and Improvement in TPA treated Patients
Authors: Malkoff Marc , Piriyawat Paisith , Al-Senani Fahmi M , Hamilton Scott
Published: March 2022

P168

Background:
Early ischemic changes on head CT have been reliably recorded with ASPECT scores, but have not correlated with lesion volume. We studied the effect of ASPECT score on lesion volume and how acute recanalization affected late ASPECT score and lesion volume.
Methods:
We evaluated consecutive patients with MCA occlusion by TCD who received IV TPA. Patients were matched with respect to persistent occlusion (GRP1) or complete recanalization of the MCA and clinical improvement (NIH stroke scale (NIHSS)improvement >4)(GRP2). ASPECT scores were measured on the acute and a subsequent CT scan. Lesion volume was calculated using the (A * B *C)/2 method. NIHSS were measured at baseline and at 24 hours.
Results:
16 patients were studied. Baseline NIHSS were (mean±SD) 20 ± 4 vs 15 ± 7 (NS) and ASPECT scores were 8.4 ± 1.2 vs 8.6 ± 1.7 (NS) in GRP 1 and 2 respectively. Age and time to TPA were similar. The distribution and types of abnormalities in both ASPECT scores and groups were similar. In GRP 1, 24 hr NIHSS were higher (22± 7 vs 5 ± 7 p<0.05) and ASPECT scores tended to be lower (6.4 ± 1.7 vs 8.4 ± 2.2 p=0.054). Lesion volumes were higher in GRP 1 (172.8 ± 130 vs 15.9 ± 32.2 p<0.05). Baseline ASPECT score did not correlate with lesion volume or 24 hr NIHSS, whereas, outcome ASPECT score correlated with lesion volume (r=-0.74 p<0.01) and tended to correlate with 24 hr NIHSS (r=-0.46 p<0.10). The change in ASPECT correlated with lesion volume (r=-0.73 p<0.01). 62%of the total abnormalities in ASPECT scores were noted in the caudate, lentiform, insula, and thalamus. The lentiform was abnormal in 75%. Reversibility was seen in the insula(4 patients), and in one patient each in the caudate, lentiform and MCA2,3, and 4 for a total of 9 areas.
Conclusion:
Baseline ASPECT scores are very sensitive to MCA ischemia and the most common areas involved have relatively small tissue volumes. Outcome ASPECT scores may differ from baseline and correlate with lesion volume. Patients with improvement have smaller volumes of infarcted tissue in similar locations compared to non responders. Our study shows that early ischemic changes may not predict lesion volume due to the confounding effect of recanalization.
CT Angiography Use in Acute Stroke Patients Undergoing i.v. TPA
Authors: Rordorf Guy A , Koroshetz Walter J , Buonanno Ferdinando , McDonald Colin T , Greer David , Ougorets Igor , Rosand Jonathan , Schwamm Lee H
Published: March 2022

P170

Background:
IV rt-PA has been demonstrated to be an effective treatment for selected cases of acute ischemic stroke. Unfortunately, there is a substantial risk of cerebral hemorrhage when thrombolytic agents are used in the setting of cerebral ischemia. Because of this risk it would be useful to identify a subgroup of patients with increased likelihood to benefit from rt-PA. . The NINDS rt-PA Stroke Study Group failed to identify such a subgroup. We postulated that patients without occlusive lesions of a major intracranial artery (e.g., MCA stem, ICA, Basilar) may be better candidates for IV rt-PA because of decreased hemorrhage risk and increased recanalization rates.
Methods:
We analyzed prospective data in all acute stroke patients from 10/97 -3/00 treated with IV rt-PA. All patients had urgent Helical CT angiography (CTA) at 3 mm slices from skull base to vertex. Patients eligible for rt-PA by NINDS criteria received drug if CTA did not show a major vessel occlusion, as assessed by raw data viewed on the scanner by the Stroke Team within 5 minutes post acquisition.
Results:
14 patients (mean age 62; 58% male) were treated according to this protocol. Strokes were classified by TOAST criteria as 8 embolic, 5 cryptogenic, 1 small vessel. Mean time to drug was 125 min (range; 30–180 min). The initial head CT scan was without hypodensity in 12/14 patients. The mean initial NIHSS score improved from 12.1 to 4.2 ( at 24 hrs) and to 1.8 (at 7 d). The NIHSS at 24 hours improved by ≥4 points in 12 patients and did not deteriorate in any. At day 7 the NIHSS had improved by ≥4 points in all patients and was back to 0 in 6. The modified Rankin index at day seven was 0 in 7 patients, 1–2 in 6 patients, and 3 in one patient. All strokes but one were located in the anterior circulation. There were no symptomatic or asymptomatic intracranial hemorrhages or systemic complications.
Conclusions:
IV rt-PA may be most useful in patients with small distal emboli and/or lacunar stroke. The smaller size clot and smaller area of ischemia in these patients may reduce risk of hemorrhage, and patent proximal arteries may increase chances of recanalization.
Prehospital Timecourse of Stroke Patients: Baseline Houston Experience
Authors: Wojner Anne W , Persse David , Rodriquez Diana , Morris Gloria , Malkoff Marc , Wicklander Michael , Wells Mary , Davis Liesha , Morgenstern Lewis , Grotta James C
Published: March 2022

P175

Background:
Paramedic diagnostic accuracy in stroke and designation of stroke centers may improve treatment of acute stroke. We studied patients transported from the scene by paramedics with suspected acute stroke to 6 hospital candidate “ stroke center” sites in Houston as part of pre-intervention data collection for a study funded by the American Stroke Association aimed at increasing the number of patients that receive effective urgent stroke therapy.
Methods:
Candidate sites consisted of 2 university affiliated tertiary care and 4 community hospitals. Total time from suspected symptom onset to arrival in a study site emergency center, patient demographics, definitive diagnosis, and use of thrombolytic therapy were collected prospectively from September 1999 through March 2000.
Results:
The sample consisted of 446 patients with a paramedic diagnosis of acute stroke. Patient distribution to study sites was as follows: Hospital 1, n=153 (34.3%); Hospital 2, n=71 (15.9%); Hospital 3, n=72 (16.1%); Hospital 4, n=59 (13.2%); Hospital 5, n=64 (14.3%); Hospital 6, n=27 (6.1%). Average time from onset of symptoms suggestive of stroke to arrival in the emergency center was 226 minutes + 348 minutes (median 95 minutes; 234 patients (52%) arrived within 150 minutes of stroke symptom onset. Definitive stroke diagnosis was confirmed in 321 (72%) EMS transported cases; in 125 cases (28%) EMS misdiagnosed stroke for seizures, altered mental status, headache and syncope. Of valid stroke cases, 260 (81%) were ischemic and 61 (19%) were hemorrhagic. Total time from symptom onset to arrival in the emergency center was 196 ±240 minutes with a median of 90 minutes for ischemics, and 154 ±171 minutes with a median of 90 minutes for hemorrhages. Of this group, 216 (71%) of ischemic, and 43 (70%) hemorrhages arrived within 150 minutes of stroke symptom onset. A total of 21 (8%) patients received thrombolysis.
Conclusions:
Paramedic accuracy in diagnosing stroke is reasonable. Community and paramedic awareness of stroke and stroke-like symptoms in Houston already leads to over half of stroke patients arriving within the window for thrombolysis. An ongoing study will try to improve these statistics.
Routine screening for IV tPA therapy less than 3 hours with MRI: initial clinical experience
Authors: Warach Steven , Rodriguez Susan Unipan , Olan Wayne J
Published: March 2022

P177

Background:
Acute MRI imaging including diffusion, perfusion, angiography, and FLAIR provides useful information in the diagnosis of stroke. It has been proposed that the stroke MRI exam may improve patient selection and outcome for tPA therapy. An alternate view holds that MRI may excessively delay times to treatment and lead to worse outcomes. To look for any evidence of adverse effects of MRI screening, we examined our initial experience using MRI as a screening exam for tPA therapy.
Methods:
The critical care pathway for stroke at our hospital mandates both CT and MRI for all patients under consideration for IV tPA therapy within 3 hours of onset. Delays are minimized by 24 hour in-house MRI technologists and immediate availability of both the MRI and CT scanners when a stroke code is called. Scans are monitored by a stroke neurologist and/or radiologist to minimize delays in image interpretation. MRI exclusion criteria for tPA are: (1) presence of subacute lesions not suspected from history or CT (2) normal DWI, PWI and MRA of good technical quality (3) any evidence of hemorrhage.
Results:
Twelve patients were treated with tPA; 4 were excluded based on MRI
Results:
2 had subacute lesions, 1 had evidence of chronic hemorrhage, 1 had a normal MRI (final diagnosis: Guillain-Barre Syndrome). Four of the treated patients had no MRI because of contraindications (n=3) or scanner unavailability (n=1). One patient was treated based on MRI results only; CT was unavailable. Median door-to-needle time (MDTNT) for the 8 MRI screened patients was 83 minutes; median time-to-treatment (MTTT) was 134 minutes. Four of these 8 patients achieved a modified Rankin Score of 0 or 1 (mRS12) on follow-up. One had a symptomatic hemorrhage and died (time-to-treatment was 116 minutes).
Conclusion:
In this small series, door to needle times and outcomes are well within benchmark values (STARS Study: MDTNT - 96 minutes, MTTT - 164 minutes, mRS12 at outcome - 43%; G. Albers, et al, JAMA. 2000;283:1145). There is no evidence to date that MRI screening for iv tPA leads to excessive delays or worse outcomes. A larger series is necessary to demonstrate the safety and efficacy of MRI screening for IV thrombolysis.