bluuebunny/crossref_metadata_2025 huggingface dataset:
Deleterious effects of D-Amphetamine on functional recovery following Transient intraluminal suture MCAO in the Rat
Authors: Virley David , Hadingham Sarah J , Campbell Colin A , Hunter Jacqueline , Parsons Andrew A
Published: July 2021

P77

D-amphetamine can facilitate recovery after cortical injury, however, little is known of its neuroregenerative properties following proximal middle cerebral aretery occlusion (MCAO). The aim of this experiment was to investigate the recovery promoting effects of d-amphetamine following transient MCAO in the rat. Rats were pre-trained on the beam-walking test and then underwent 90 min of MCAO using an intraluminal filament and randomly assigned to receive either d-amphetamine (Amp, 2 mg/kg i.p) or vehicle (Veh, 0.9 % saline, i.p.) at 1, 3 and 5 days post-surgery. Performance on the beam-walking test was assessed at 1, 7, 14, 21 and 28 days post-surgery. A graded 21-point neurological score (21 = normal)and body weight were also assessed. There was a significant Group x Time Interaction [F (5,70) = 2.61, p = 0.032] for the effects of Amp on total distance travelled by MCAO rats. Post-hoc
t
-tests revealed both groups of rats were matched for impairments on the beam at 1 day prior to drug administration (Mean ± SEM (in cm): Amp = 8.90 ± 6.56; Veh = 21.56 ± 11.85, p s<0.001 relative to pre-op baseline, 100 ± 0), but the effect of Amp significantly impaired the recovery process throughout the post-operative testing period (7 days = 20.19 ± 11.75; 14 days = 36.94 ± 14.31; 21 days = 47.00 ± 15.72; and 28 days = 51.25 ± 15.04, p s < 0.05). The significant impairment displayed by Amp-treated animals was in direct contrast to Veh-treated animals which improved dramatically in performance from 7–28 days (7 days = 63.88 ± 16.73; 14 days = 86.25 ± 11.16; 21 days = 88.31 ± 11.68; and 28 days = 89.38 ± 10.62). The deficits attributed to Amp animals were also reflected in impaired neurological performance at 21 days (Median + IQR (total score): Amp = 14 ± 1.5; Veh = 16.5 ± 2.5; p<0.05) and 28 days (Amp = 15 ± 2; Veh = 17 ± 3; p<0.05). Total body weight for Amp-treated animals was significantly reduced relative to Veh-treated animals throughout post-operative testing, from 7 to 28 days (Mean ± SEM (in g): e.g 7 days, Amp = 316 ± 14, Veh = 361 ± 6; and 28 days, Amp = 377 ± 17, Veh = 449 ± 9, p s < 0.05). Results indicate amphetamine impairs neurological recovery in a model where extensive sub-cortical damage exists.
Hyperglycemic Transient Ischemia Induces Massive Neutrophil Deposition in Brain.
Authors: Lin Baowan , Ginsberg Myron D , Busto Raul , Li Lin
Published: July 2021

P80

Acute hyperglycemia worsens neurological signs and accentuates neuropathology after ischemia, but the mechanisms are poorly understood. In this study, we tested whether polymorphonuclear leukocytes (neutrophils) might be contributory. Anesthetized, physiologically monitored Wistar rats underwent global forebrain ischemia for 12.5 min by bilateral carotid artery occlusions plus hypotension (45 mm Hg). To induce hyperglycemia, rats received 2.5 ml of 25% dextrose i.p. 30 min prior to ischemia. Normoglycemic rats received saline. Plasma glucose levels were 340±66 and 133 ±21 mg/dl, respectively (mean±SD). Animals were sacrificed at either 24 h or 3 days by perfusion-fixation with FAM. Brain sections were reacted for the immunohistochemical visualization of myeloperoxidase (MPO), a specific and quantitative marker of neutrophil activity in the brain. In sham rats and in normoglycemic-ischemic animals, almost no MPO-positive cells were identified. In marked contrast, brains of hyperglycemic-ischemic rats studied at 24 h contained dramatic accumulations of MPO-positive cells within pial and parenchymal blood vessels as well as within cortical and subcortical parenchyma. MPO-positivity was most robust in areas of severe injury (on H&E sections), but MPO cells were also observed in areas without overt injury. Intravascular MPO-positive cells commonly obstructed the vascular lumen. Following 3-d survival, MPO-positivity of hyperglycemic-ischemic brains had significantly decreased. In hyperglycemic brains studied at 24 h, median numbers of MPO-positive cells were increased by 130-fold in cortex and 110-fold in striatum above values in normoglycemic-ischemic rats. In summary, this study shows that preischemic hyperglycemia triggers the early and dramatic deposition of polymorphonuclear leukocytes in the postischemic brain, with neutrophil adherence to cerebral blood vessels and their migration into brain parenchyma following brief forebrain ischemia. These events may contribute to the enhanced tissue destruction, extension of infarction, and BBB disruption observed in hyperglycemic ischemia. Supported by NIH Grant NS05820.
Spatio-temporal Dynamics of Perfusion during Transient Focal Ischemia: Sequential Experimental PET in Cats
Authors: Graf Rudolf , Wienhard Klaus , Dohmen Christian , Fujita Toshiaki , Heiss Wolf-Dieter
Published: July 2021

P88

Objective:
We studied the temporal evolution of regional dysfunction in transient focal ischemia using sequential positron emission tomography (PET), with special emphasis on postischemic hyperperfusion.
Methods:
Cerebral blood flow (CBF), oxygen metabolism (CMRO
2
), and oxygen extraction (OEF) were repeatedly measured before and up to 24 hours after 60 min middle cerebral artery (MCA) occlusion in 16 halothane anesthetized cats. PET results were compared to final histopathologic outcome.
Results:
In all animals, CBF decreased in the ischemic territory below 45% of preischemic controls. Recirculation was partially successful in 3 cats, and hypoperfused regions persisted resulting in gross infarction. 3 major types of hyperperfusion evolved in the other cats: 1. In 5 cats, hyperperfusion covering large parts of the MCA territory persisted throughout the experiment. During ischemia, CBF reduction was severe, and OEF increases were restricted to the surrounding of subsequently hyperperfused regions. At the final stage, large infarcts were observed. 2. In 6 cats, hyperperfusion was transient and often followed by hypoperfusion in parts of previously hyperperfused regions. During MCA occlusion, CBF reduction was more gradual, and OEF elevations covered not only the surroundings but partially also subsequently hyperperfused zones. Infarcts were normally restricted to the center of hyperperfused regions, or did not develop. 3. In 2 cats, hyperperfused regions grew progressively over time. In this type, CBF reduction was also more gradual, OEF increases were widely distributed in the ischemic territory, and infarcts were small.
Conclusion:
Sequential experimental PET revealed variable spatio-temporal patterns of postischemic perfusion following transient MCAO in cats. Regions with continued hyperperfusion have a particularly bad outcome, as have those with continued incomplete recirculation. Transient postischemic hyperperfusion, however, may be beneficial in zones with subcritical CBF reduction or spontaneous partial reperfusion during the ischemic episode.
“Silent” cerebral infarction due to vasospasm after SAH
Authors: Claassen Jan , Mayer Stephan A , Kreiter Kurt T , Bates Joseph E , Ostapkovich Noeleen , Mednick Adam S , Connolly E Sander , Carhuapoma J Ricardo
Published: July 2021

P97

Objective.
To determine frequency, impact on outcome, and determinants of clinically silent infarcts after aneurysmal subarachnoid hemorrhage (SAH) due to vasospasm.
Methods.
We prospectively studied a cohort of 326 patients with acute SAH. Delayed cerebral ischemia (DCI) was defined as (i) a new focal neurological deficit or decrease in level of consciousness otherwise unexplained, or (ii) a new infarct revealed by follow-up CT scans (within day 2–14 post hemorrhage) without other explanation. Angiography confirmed vasospasm in all patients.
Results.
DCI occurred in 18% (59/326) of patients. Of the 59 patients with DCI, 14 (24%) patients had an infarct on CT attributed to vasospasm without clinical deterioration, 25 had clinical symptoms and an infarct on CT, and 20 had clinical symptoms only. Compared to patients with symptomatic vasospasm, patients with “silent” infarcts more often had a Hunt-Hess score of 4–5 (64% vs. 27%, p=0.023), and blood in the 4th ventricle was found more often on the admission CT scan (86% vs. 45%, p=0.012). Variables that did not differ between symptomatic and asymptomatic patients included cisternal blood scores, hydrocephalus (bicaudate index), or edema on admission CT scans; aneurysm location; location of vasospastic infarcts; mean APACHE-2 scores; and mean TCD values. DCI patients without clinical symptoms had higher mortality at 3 months when compared with patients with clinical symptoms (60% vs. 14%, p=0.006).
Conclusions.
Clinically “silent” infarction occurs in approximately 25% of SAH patients with DCI, and is particularly common in poor grade patients with IVH. Because ischemia and infarction may go undetected in poor grade patients, prophylactic triple-H therapy, routine follow-up angiography with prophylactic angioplasty, and new monitoring techniques (e.g. continuous EEG) may lead to improved outcomes in these patients.
Late Thromboembolic Events after Treatment of Intracranial Aneurysms with Guglielmi Detachable Coils
Authors: Derdeyn Colin P , Moran Christopher J , Cross DeWitte T , Chicoine Michael R , Dacey Ralph G
Published: July 2021

P98

Purpose:
Thrombo-embolic complications associated with the endovascular treatment of intracranial aneurysms with Guglielmi Detachable Coils (GDC) generally occur at the time of the procedure or soon after. The purpose of this report is to determine the frequency of late thrombo-embolic events after GDC.
Methods:
The records of 189 patients who underwent GDC repair of one or more intracranial aneurysms at our institution were reviewed. The occurence of an ischemic event referrable to a coiled aneurysm was determined by clinical, angiographic, and imaging data. Events occuring within 2 days of the endovascular procedure were considered peri-procedural. Kaplan-Meier analysis of ischemic events over time was performed.
Results:
Two patients suffered documented thrombo-embolic events. One patient presented 5 weeks after coiling with a transient ischemic attack. Angiography demonstrated thrombus on the surface of the coils at the neck of a large ophthalmic artery aneurysm. The second patient presented with a posterior circulation stroke 4 weeks after coiling of a large superior cerebellar artery aneurysm. Angiography showed no significant proximal disease, with thrombus beginning at the neck of the treated aneurysm and extending out both P1 segments. No intra-procedural problems during the initial coiling had occured with either patient. There was no evidence for protrusion of coils into the parent artery in either patient. Both patients had been receiving daily aspirin (325 mg). One additional patient reporting symptoms suggesting possible ischemics event was evaluated and diagnosed as having atypical migraines. The frequency of a clinical thromboembolic event during the first year after coiling (excluding procedural complications) was 1.1%.
Conclusions:
Thrombo-embolic events may occur as late as 5 weeks after endovascular treatment of aneurysms with GDC.
The Role of Hypotension in Secondary Brain Injury after Intracerebral Hemorrhage
Authors: Besmertis Lavrentios , Bonovich David C , Hemphill J. Claude
Published: July 2021

P108

Objective:
Hypotension is known to exacerbate secondary brain injury and worsen outcome after head trauma and ischemic stroke. Optimal blood pressure management after spontaneous intracerebral hemorrhage (ICH) remains a point of debate. The purpose of this study was to determine the incidence and impact on outcome of hypotension early after ICH.
Methods:
Medical records were reviewed for all 89 patients admitted with acute non-traumatic ICH to the University of California, San Francisco and San Francisco General Hospital during 1997. Complete information was available in 75 patients, who formed the cohort for analysis. Occurrences of hypotension (defined as a mean arterial pressure (MAP) < 90 mmHg for greater than five minutes) were identified for the first 72 hours after emergency department presentation. Additional characteristics including ICH volume, Glasgow Coma Scale (GCS) score on presentation, and presence of intraventricular hemorrhage (IVH) were also recorded. Outcome was assessed as 30-day mortality.
Results:
Overall 30-day mortality was 49% (37 of 75). 30-day mortality was 57% for patients with at least one episode of hypotension during the first 3 days (n=47) compared with 36% of patients with no hypotensive episodes (n=28). Patients with a total duration of hypotension > 60 minutes during the first 3 days had a 30-day mortality rate of 61% (n=38) compared with a 30-day mortality rate of 38% in those with < 60 minutes of total hypotension (n=37) (
P
<0.05). In multivariate regression analysis, GCS score (
P
<0.001), ICH volume (
P
=0.05,) and IVH (
P
=0.04), but not occurrence or duration of hypotension, were independent predictors of 30-day mortality.
Conclusions:
Hypotension is common within the first several days after acute ICH and is associated with worsened 30-day mortality, especially when present for a total duration > 60 minutes. While blood pressure management after ICH is largely focused on management of hypertension, this suggests that low blood pressure negatively impacts on outcome. Whether hypotension after ICH creates secondary ischemic brain injury or is merely a secondary occurrence in severely affected patients remains to be clarified.
Pericytes Regulate Fibrinolytic Function of Brain Capillary Endothelial Cells
Authors: Kim Jeong A , Tran Nam D , Wang Shur-Jen , Fisher Mark
Published: July 2021

P110

Our prior work has shown that astrocytes inhibit fibrinolysis of brain capillary endothelial cells (eg, Stroke 1999:30;1671–1677). The complex cellular microenvironment at the blood-brain barrier includes pericytes, which are adjacent to and share basement membrane with brain capillary endothelial cells. We analyzed the hemostatic regulatory role of pericytes in a blood-brain barrier model consisting of human brain pericytes cultured on transwell membrane inserts with human brain capillary endothelial cells. We measured fibrinolysis proteins and function in media conditioned by 48 hour co-culture of human brain capillary endothelial cells and human brain pericytes, as well as brain capillary endothelial mono-cultures. Compared to endothelial mono-cultures, pericyte-endothelial co-cultures exhibited levels of tissue plasminogen activator (tPA) protein reduced by 50±15% (p<.05). Co-culture preparations showed 32±13% (p<.05) increase in levels of plasminogen activator inhibitor-1 (PAI-1) protein, the primary inhibitor of tPA. tPA activity of co-culture preparations was 54±17% (p<.05) of endothelial mono-culture preparations. These data demonstrate that human brain pericytes have an important hemostatic regulatory role for endothelial-dependent fibrinolysis in vitro. These findings provide further support for brain-specific hemostasis, with pericytes as well as astrocytes playing key regulatory roles.
Effects of Extracellular Superoxide Dismutase on Arterial Vascular Structural Changes After Acute Subarachnoid Hemorrhage in the Mouse
Authors: Parra Augusto , McGirt Matthew J , Sheng Huaxin , Pearlstein Robert D , Laskowitz Daniel T , Warner David S
Published: July 2021

P113

Background and Purpose:
Subarachnoid hemorrhage (SAH) is a known cause of cerebral vasospasm. Vasopasm may result from loss of endothelial NO synthesis. There is also evidence that Hgb products released after SAH bind NO and deplete its extracellular bioavailability. Cu/Zn superoxide dismutase (SOD) overexpression has been shown to provide protection against vasospasm presumably by reducing available superoxide to react with and deplete NO thereby increasing NO concentration. This study characterized the effects of extracellular SOD (EC-SOD) on vasospasm comparing transgenic EC-SOD overexpressing mice to wild type (WT) counterparts.
Methods:
Mice underwent halothane anesthesia and endovascular perforation of the right proximal anterior cerebral artery (ACA) using a 5–0 monofilament. Sham mice underwent surgery but no vascular perforation. Temperature, blood gases, & blood pressure were maintained within normal ranges. Three days after recovery, brains were sectioned and Gomori’s trichromic stained. Vascular wall thickness was measured in triplicate sections from the proximal and distal segments of the ACA with the observer blinded to genotype. N=5 per group.
Results:
There was no difference in wall thickness between EC-SOD overexpressors and wild type shams in either ACA segment (Proximal: EC-SOD = 64±22μm, WT = 72±8μm, p=0.62; Distal: EC-SOD = 77±13μm, WT = 68±9μm, p=0.2). For both genotypes, SAH caused increased wall thickness which was greater in the EC-SOD vs. wild type SAH groups in the proximal (EC-SOD = 164±9μm, WT = 108±27μm, p=0.01) but not distal (EC-SOD =136±37μm, WT = 106±38μm, p=0.28) ACA segments.
Conclusions:
We were unable to demonstrate amelioration of vasospasm by the five-fold increase of brain EC-SOD known to occur in these mutants. In fact, in the proximal ACA, wall thickness was greater in the EC-SOD overexpressors subjected to SAH. Absence of a beneficial EC-SOD effect might be attributable to the post-SAH measurement interval when processes other than NO metabolism are likely to account for vasospasm. The reason for the pattern of an adverse effect of EC-SOD overexpression is unknown.
Validating the Questionnaire to Verify Stroke-Free Status by Patient History and Physical Examination
Authors: Jones William J , Williams Linda S , Redmon Gayle , Meschia James F
Published: July 2021

P127

Background and Purpose:
The Questionnaire to Verify Stroke-Free Status (QVSFS) is an 8-item structured telephone interview designed to identify stroke-free individuals. Previously, the QVSFS was validated with medical record review to identify stroke status in a cohort with a low prevalence (7%) of stroke or TIA. The aim of this study was to evaluate the validity of the QVSFS using a face-to-face history and physical examination in a group with a higher prevalence of stroke.
Methods:
A research assistant administered the QVSFS to outpatients from VA stroke and general internal medicine clinics. Subjects were defined as QVSFS (-) if responses to all 8 questions were negative. Questions requiring clarification were noted. Neurologists, blinded to QVSFS scores, interviewed and recorded the NIH Stroke Scale in all subjects to determine stroke-free status, defined as no history or examination findings of previous TIA or stroke.
Results:
Ninety-one subjects were examined, mean age was 69 years, 98% were male. Twenty-five of the subjects were judged stroke-free by the examiners and 66 had a prior history of stroke (63) or TIA (3). The negative predictive value of the QVSFS was 0.93 with positive predictive value 0.86. No question required rephrasing in more than 3 subjects; only 12 subjects (13%) required rephrasing of at least one question. Years of education was not associated with need for question rephrasing.
Conclusions:
The QVSFS can effectively identify stroke-free individuals with a high degree of accuracy, even in a population including a large proportion of patients with prior stroke or TIA. Accuracy for identifying subjects with stroke is slightly lower but still high. The QVSFS is valid for interviewer administration but, because of the need for question clarification in some subjects, should be further evaluated before using self- or mail-completion.
Cigarette Smoking and Risk of Subarachnoid Hemorrhage: Does Cessation of Smoking Really Help?
Authors: Yahia Abutaher M , Qureshi Adnan , Suri M Fareed K , Ali Zulfiqar , Guterman Lee R , Hopkins L N , Tamargo Rafael J
Published: July 2021

P128

BACKGROUND AND PURPOSE:
Smoking has been shown to increase the risk of subarachnoid hemorrhage (SAH). It remains unclear whether cessation of smoking decreases this risk. To address this issue, we performed a case control study examining the effect of smoking and other known risk factors for cerebrovascular disease on the risk of SAH.
METHODS:
We reviewed the medical records of all patients with a diagnosis of SAH (n=323) admitted to the Johns Hopkins University hospital between January 1990 and June 1997. Controls matched for age, sex, and ethnicity (n=969) were selected from the nationally representative sample of the Third National Health and Nutrition Examination Survey. We determined the independent association between smoking (present and previous) and various cerebrovascular risk factors and SAH using logistic regression analysis.
RESULTS:
Of 323 patients admitted with SAH (mean age 52.7±14 years; 93 were men), 149 (46%) were currently smoking and 125(39%) were previous smokers. In the multivariate analysis, both previous cigarette smoking (OR = 3.4; 95% CI, 2.3–5.1) and present cigarette smoking (OR = 2.0; 95% CI, 1.3–3.0) were significantly associated with SAH. Hypertension was also significantly associated with SAH (OR = 2.4; 95% CI, 1.8–3.3).
CONCLUSION:
Cigarette smoking increases the risk for SAH as suggested in previous studies. However, the increased risk persists even after cessation of cigarette smoking suggesting the importance of early abstinence from smoking.
Reliability of Self-Reported Pre-Stroke Function
Authors: Lai Sue-Min , Duncan Pamela W , Tyler Denise A , Studenski Stephanie
Published: July 2021

P135

Purpose:
The purpose of this study was to examine the reliability of self-reported pre-stroke function when reported within 28 days post-stroke and again at 90 days post-stroke.
Methods:
Sixty consecutive patients who participated in the Kansas City Stroke Registry were included in this analysis. Pre-stroke function was self-reported by participants using the Lawton IADL and SF-36 Physical Function Index at baseline (within 28 days of stroke onset) and again at 90 days post-stroke. The Intra-class Correlation Coefficient (ICC) was used to examine the reliability of self-reported pre-stroke physical function. The Orpington Prognostic Scale was used to characterize stroke severity.
Results:
Sixty subjects (24 males and 36 females) with an average age of 75±8.2 years were included in this study. Stroke severity at baseline was mild in 19, moderate in 37, and severe in 4. When compared to pre-stroke function reported at baseline using the Lawton IADL, prior function reported at 90 days was lower in 17 subjects, no change in 21 subjects, and higher in 22. Similarly, when compared to pre-stroke physical function reported at baseline using the SF-36 PFI, prior function reported at 90 days was lower in 18 subjects, no change in 11 subjects, and higher in 30. The calculated ICCs were .53 for both measures.
Conclusions:
Recall of pre-stroke function is not consistent across time.
Serum Creatinine Concentration and the Risk of Stroke, Myocardial Infarction, and Vascular Death in Patients with Symptomatic Carotid Stenosis.
Authors: Merino Jose G , Eliasziw Michael , Spence J David , Barnett Henry Jm
Published: July 2021

P144

Background:
High serum creatinine (SCr) is a predictor of mortality in patients with hypertension, myocardial infarction (MI), and stroke. In men it is associated with stroke.
Objective:
Examine the relationship between SCr and the risk of stroke, MI, and vascular death (VD) in patients with symptomatic internal carotid artery (ICA) stenosis.
Methods:
Data from 1977 male NASCET patients with baseline SCr measurements were analyzed.
Results:
Increased levels of SCr were associated with older age and a higher prevalence of hypertension, history of MI or angina, and intermittent claudication. No association was found between the level of SCr and a history of diabetes or hyperlipidemia or with the type and location of prior cerebrovascular ischemic events. The Kaplan-Meier risk for the outcomes of stroke at 5 years, MI at 5 years, and the combined outcome of stroke, MI, or VD at 5 years increased with increasing levels of SCr (all at a p< 0.001, table). This increased risk was unconfounded and remained statistically significant after adjusting for all baseline characteristics using Cox proportional hazards regression model. The causes of stroke were similar in all SCr level groups (70% large artery, 22% lacunar, 8% cardioembolic). The risk of death from any cause at 5 years increased with increased SCr levels, cardiac disorders were the predominant cause of death.
Conclusion:
A mild to moderate elevation of serum creatinine level is an independent risk factor for stroke, MI, and VD in male patients with recent ischemic symptoms attributable to carotid artery stenosis.
Will Your Stroke Be Treated in Detroit?
Authors: Guyot Anne M , Schuster Alice , Daley Sheila , Ottney-Schweiss Carolyn , Skolnik Susan , Jacobs Bradley S , Lewandowski Chris A , Levine Steve R
Published: July 2021

P162

Background:
rt-PA is the only currently available FDA approved therapy for acute ischemic stroke. We sought to determine the type and frequency of challenges/barriers to offering this therapy 4 years after FDA approval.
Methods:
We performed a systematic survey in April, 2000 of all 34 hospitals in the Detoit Metropolitan area (population 3.9 million people) that have an acute care emergency facility. A standardized, structured questionnaire/interview was conducted with the directors of the emergency facilities. Questions included: volume of stroke, priority of care given, relationship with Emergency Medical Services (EMS), use of protocols, pathways, and NIH Stroke Scale,time to processes and personnel involved. Surveys were returned, data was tabulated and analyzed descriptively.
Results:
All 34(100%) of the hospitals responded and wished to participate. While EMS called the Emergency Department(ED) prior to their transport of a suspected stroke patient in 28 centers (82%)only 19 centers (68%) utilized this information to expedite the care of the stroke patient. Stroke patients are given top priority for CT scanning in only 22 centers (64%). The range of times from ED arrival to CT scan performance ranged from 5 minutes to one hour. CT technicians are available 24hrs/day in-house in 56%. In the 44% with on-call, out-of-the hospital CT technicians, time to their arrival ranges from 30–60 minutes. Only a radiologist reads the CT in 18 Hospital, ED physicians review the CT in 15 and only a neurologist in 1. Only 10 (30%) collected data on stroke patients in the ED. Once the patient is considered for treatment with rt-PA, the number of physicians involved in the process varied from 1 to 3. Most commonly involved were a neurologist (22 centers) and ED physicians(at nearly all the centers). Stroke teams were involved at only two hospitals. If more than one physician is involved the average response time is 27 minutes. An NIHSS is performed in 53% of the hospitals.
Conclusions:
While considerable progress has been made in many Detroit-area hospitals to deliver rt-PA therapy for acute stroke, several key process improvement areas have been identified that could increase the percentage of acute stroke patients treated with rt-PA.
Intracranial Arterial Reconstruction with Stent Placement and Combined Techniques
Authors: Lylyk Pedro , Ceratto Rosana , Cohen Jose E , Miranda Carlos , Aguilar Marcos Vilca , Ferrario Angel
Published: July 2021

P165

Purpose:
To report our experience with the use of intracranial stents in the treatment of intracranial aneurysms, atherosclerotic lesions and arterial dissections. Clinical Material and
Methods:
Between June 1996 and August 2000, 61 consecutive patients were selected and treated with intracranial stents. There were 37 male and 24 female patients with ages ranging from 3 to 73 years (mean age 50). Group 1 included 41 patients harboring 42 cerebral aneurysms (saccular, dissecting or fusiform). The most common presentation was subarachnoid hemorrhage in 20 patients (48.8%) and mass effect in 17 (41.4%). The most common locations were the distal VA in 10 cases (23.8%) and the cavernous ICA in 10 cases. Group 2 included 20 patients harboring atheromatose stenosis or arterial ischemic dissections. Mean stenosis varied from 70 to 95%.
Results:
Group 1: Of the 42 aneurysms treated with stents, 30 (71%) underwent combined endovascular stent implantation and endosaccular coil placement, in 11 cases at the same procedure, in 12 cases coiling was in a second procedure performed after stenting, and in 6 cases coiling preceded stenting. Complete occlusion was accomplished in all the cases. In 12 cases the strategy was stenting with no further coiling. Four aneurysms (33%), are completely occluded with this technique. Group 2: Nineteen (95%) were evaluated as having postoperative GOS 4–5 and improving the degree of stenosis to less than 50%. Good short–term clinical outcome (GOS 4 and 5) was achieved in 52 patients (85%).
Conclusions:
The technique of using a stent as a mechanical barrier to allow coil placement in the aneurysmal sac provides another treatment option for aneurysms not amenable for clipping or conventional GDC. Angioplasty and stenting of intracranial vessels keeps vessel patency and avoids recoiling of the plaque. Stenting reconstruction is a feasible and relatively safe procedure in trained hands.
Dramatic Recovery During IV-TPA Infusion: Time Course and Clinical Pattern
Authors: Felberg Robert A , Okon Nicholas J , El-Mitwalli Ashraf , Burgin W Scott , Grotta James C , Alexandrov Andrei V
Published: July 2021

P172

Background:
Dramatic recovery (DR) during TPA infusion is not well described.
Methods:
We compared clinical patterns and time course in patients with DR to Non-DR. We prospectively captured acute MCA strokes treated with standard NINDS IV-TPA protocols and performed serial NIHSS exams. DR was defined as a decrease by ≥ 10 NIHSS points or total score of ≤3 by end of TPA infusion.Intracranial flow signals were graded using the Thrombolysis in Brain Ischemia (TIBI) scale.
Results:
From 9/98–6/00, DR was observed in 12/53 patients(Table). With DR, there was a consistent pattern and time course of recovery: Gaze preference recovered first (8/11 complete; 2/11 partial; 1/11 none); followed by Sensory (4/7 complete; 3/7 partial recovery; 0/7 none) and Leg Strength (8/10 complete; 1/10 partial; 1/10 none). Arm Strength followed next, but was often incomplete (5/12 complete; 6/12 partial;1/12 none) Certain findings had partial improvement later during infusion: Facial strength (3/12 complete; 7/12 partial; 1/12 none);Aphasia (2/7 complete; 4/7 partial; 1/7 none). Dysarthria tended not to improve during infusion(2/7 complete; 0/7 partial; 5/7 none). DR was observed in 22% of patients during IV-TPA infusion and was sustained at 24 hours. The stroke severity and timing to bolus was similiar between DR and Non-DR groups. Early recanalization was the only noted difference.
Conclusion:
The clinical pattern of DR may result from reperfusion of the white matter tracts supplied by MCA perforators or improved collateral flow. With clot lysis, the observed recovery pattern is referable to vessel anatomy. How DR occurs and why some clinical deficits have delayed recovery needs further study.
Early CT Changes Do Not Predict Parenchymal Haemorrhage Following Streptokinase Therapy In Acute Stroke.
Authors: Gilligan Amanda K , Markus Romesh , Read Stephen J , Srikanth Velandai , Fitt Gregory , Chambers Brian R , Donnan Geoffrey A
Published: July 2021

P173

Aims Recent thrombolytic trials in acute stroke, and acute treatment in the USA, exclude patients with early CT changes of infarction affecting greater than one third of the middle cerebral artery (MCA) territory because of a possible increased risk of parenchymal haemorrhage. We reviewed CT scans of patients recruited into the Australian Streptokinase Trial to determine whether such changes or other factors were predictive in this group of patients. Methodology Acute CT scans were classified by three neurology research fellows according to ECASS criteria in 264 patients. Where consensus was not reached, a panel of ECASS trained physicians reviewed the scans. Haemorrhage on second CT were classified into haemorrhagic infarction or parenchymal haemorrhage. Results CT s showed no acute changes in 36%, minor ischaemic changes (<1/3 MCA territory) in 29%, and major ischaemic changes (>1/3 MCA territory) in 35%. Major early ischaemic changes were predictive of haemorrhagic infarction (p=0.037) and stroke death (p= <0.001). Major changes were not predictive of parenchymal haemorrhage (O.R.=0.70 95% C.I.= 0.30 - 1.66). Parenchymal haemorrhage was not more likely with any early CT changes or delays in time to therapy but was predictive of death and severe disability. Systolic blood pressure prior to treatment was significantly higher in patient s with secondary parenchymal haemorrhage(p = 0.03). Discussion Early CT changes were predictive of poor outcome but not predictive of parenchymal haemorrhage. The risk of parenchymal haemorrage was increased with moderately increased systolic blood pressure. Excluding patients with high risk of parenchymal haemorrhage, may improve the safety and overall efficacy of thrombolytic therapy. The findings of this study do not support the exclusion of patients on CT criteria.
Clinical Trials in Acute Stroke: Is it ethical to randomise patients to the placebo group?.
Authors: Serena Joaquin , Castellanos Mar , Silva Yolanda , Osuna Teresa , Alvarez Francisco , Davalos Antoni
Published: July 2021

P178

The ethics of randomising a patient to the placebo group in acute stroke clinical trials has been called into question in one study as these patients may be deprived of routinely applied therapies. No other study has previously analysed this hypothesis.
Objective:
To compare the prognosis at day 90 of patients included in clinical trials of acute stroke and randomised to the placebo group with patients not included in any clinical trial. Material and
Methods:
50 patients consecutively included in the placebo group (CLASS, ECASS-II, Trafermin, GAIN), and 50 patients not included in any clinical trial randomly selected from those sharing similar characteristics (age, sex, stroke severity and stroke subtype using the TOAST criteria) and hospitalised during the same period.
Results:
No differences were found in neurological attention delay, Canadian scale at admission, final infarct volume and length of hospital stay. The placebo group had a lower proportion of progressing stroke than the control group (14% vs. 25%). Infectious and cardiovascular complications were more frequent in the placebo group (12% vs. 6% and 15% vs. 8%, respectively). However, the placebo group displayed a more favourable outcome at day 90 (Figure).
Conclusions:
Inclusion in a placebo group in acute stroke clinical trials results in a significant benefit. This advantage may be explained by a more active intervention over progressing stroke, resulting from a higher rate of detection and control of the related factors.
Clinical Improvement at 24 Hours after MCA Occlusion Can be Predicted From the End of TPA Infusion NIH Stroke Scale Score
Authors: Burgin W Scott , El-Mitwalli Ashraf , Malkoff Marc , Grotta James C , Alexandrov Andrei V
Published: July 2021

P187

BACKGROUND:
Recanalization precedes clinical improvement in patients treated with IV TPA. Transcranial Doppler (TCD) can assess the timing and degree of recanalization. We studied how the degree of recanalization and the NIH stroke scale (NIHSS) at the end of infusion correlated with short-term clinical improvement at 24 hours. Subjects and
Methods:
We evaluated consecutive IV TPA treated patients with anterior circulation ischemic symptoms, TCD evidence of occlusion, and serial NIHSS assessments (baseline, end of infusion, 24 hours post infusion). TCD was interpreted at the end of infusion using validated criteria for degree of recanalization. Changes in the NIHSS were defined as improvement (≥4 point improvement or complete resolution)or deterioration(decline of ≥2).
Results:
52 patients met the criteria for inclusion (baseline NIHSS 17±6, median 18, range 5–29). By the end of infusion, NIHSS scores improved in 26 patients (50%). From the end of infusion to 24 hours, subsequent improvement by ≥4 points occurred in another 9 patients (17%), mostly in patients with partial recanalization (56%). NIHSS at end infusion correlated with NIHSS at 24 hrs in all patients (Adjusted R
2
=0.74). In patients with no recanalization, end-of-infusion NIHSS most highly predicted 24 hour scores (Adj.R
2
=.89) while correlation was less significant with partial(Adj.R
2
=.61) and complete(Adj.R
2
=.66) recanalization(all p<.00002). Deterioration following improvement at 24 hours was seen in 3 patients (2 reocclusions, 1 symptomatic hemorrhage).
Conclusions:
In patients with MCA occlusion, end of TPA infusion NIHSS scores accurately predict scores at 24 hours, especially in patients without vascular recanalization. This suggests that a majority of short term improvement occurs by the end of infusion. In patients without hemorrhagic transformation, deterioration of the NIHSS after infusion occurs mostly due to reocclusion.
Emergency Medical Service Transport Times for Acute Stroke and Myocardial Infarction
Authors: Evenson Kelly R , Legare Trent B , Schroeder Emily B , Brice Jane H , Rosamond Wayne D , Morris Dexter L
Published: July 2021

P188

It is currently recommended by the American Heart Association that both stroke and myocardial infarction (MI) patients be treated with urgency, as time dependent medical therapies are available for both conditions. Since stroke symptoms are often vague, it has been hypothesized that stroke patients may not be treated with the same urgency as MI patients by emergency medical services (EMS). To examine this hypothesis, EMS transport times were examined for both stroke and MI patients who used a paramedic-level, county based EMS system for transportation to a single hospital during 1999. Patients were identified by their hospital discharge diagnosis as stroke (ICD-9 430–438) or MI (ICD-9 410–414). Trip sheets with the corresponding transport times were retrospectively obtained from the 911 center. Thirteen patients with both a stroke and MI discharge diagnosis code were excluded from these analyses, leaving 75 stroke and 127 MI patients. While stroke patients were older than MI patients (median 81.1 vs. 73.3 years, p=0.01), the distribution of gender (56.9% women) and ethnicity (68.3% white) was not significantly different between stroke and MI patients. The use of lights and sirens to the scene (84.4%) and to the hospital (10.6%) also was not significantly different between stroke and MI patients. Mean EMS transport times are presented below in minutes, with the corresponding Wilcoxon rank sum test. In this study, all components of EMS transport times were similar for stroke and MI patients. Multiple linear regression predicting transport times confirmed these results. In this single county, EMS urgency for delivery of care was not different for stroke and MI patients.
Coadministration of bone marrow cells and an inhibitor of apoptosis (Z-VAD) promotes bone marrow cell survival and neurological functional recovery after focal cerebral ischemia in adult rat
Authors: Li Yi , Chen Jieli , Chopp Michael
Published: July 2021

P222

Most bone marrow cells (BMCs) transplanted into the ischemic brain of adult rodents die shortly after they are grafted, similar to the 90%-95% of the fetal cells that die after transplantation into Parkinson s patients. We tested whether coadministration of BMCs and Z-Val-Ala-DL-Asp-fluoromethylketone (Z-VAD), an inhibitor of apoptosis, into the ischemic boundary zone of the striatum and the cortex in rat brain promotes BMC survival. Adult Wistar rats were subjected to transient (2 h) middle cerebral artery occlusion (MCAo). At 1 d after ischemia, saline (n=9, Group 1); BMCs (1x10
6
in 10 :l, n=8, Group 2); or BMCs with Z-VAD (50 nM/ml, n=4, Group 3) were injected into brain. BMCs were harvested from donor adult rats injected with bromodeoxyuridine (BrdU, as a tracer). Rats were subjected to rotarod-motor and adhesive-removal somatosensory functional tests before MCAo and at 1 and 7 d after MCAo. Rats in Group 3 exhibited significant improvement (10.3±2.6 seconds, p<0.05) on the adhesive-removal test at 7 d, compared with those in Group 1 (29.3±9.4 seconds) and Group 2 (21.3±5.5 seconds), respectively. Immunohistochemistry staining was employed to identify BrdU-BMCs, and TUNEL staining was used to identify in situ DNA fragmentation of apoptotic cells. Even though the infarct volume in Group 3 (29.9±9.2%) did not change significantly, compared with Group 1 (34.3±4.0%) and Group 2 (26.6±3.8%); the number of BrdU-BMCs (88,200±7,400, ∼8.8% of 10
6
transplanted cells) increased significantly (p<0.05) in rats in Group 3, compared with that in Group 2 (31,700±9,100, ∼3.2% of 10
6
cells) at 7 d. In the grafting areas, apoptotic cells were less clustered (<90 vs.>240 per region) and apoptotic cells were significantly decreased (12.3±1.7/mm
2
vs. 25.9±2.1/mm
2
, ∼47%, p<0.05). Our data suggest that intracerebral coadministration of bone marrow cells and inhibitors of apoptosis enhance cellular survival of bone marrow cells and improves neurological functional recovery after cerebral ischemia.
The Role of Repeat CT for Predicting Fatal Outcome Following Massive Middle Cerebral Artery Territory Infarction
Authors: Barber Philip A , Zhang Jinijin , Krieger Derk M , Berrouschot Jorg , Schmutzhard Erich , Harms Lutz , Verro Piero , NJ  , Demchuk Andrew M
Published: July 2021

P233

Background
Large MCA ischemic stroke when associated with extensive mass effect can result in brain herniation and death. As yet there are no guidelines to aid the selection of patients for decompressive therapies, such as hemicraniectomy.
Methods
This was a multicentre retrospective study of large MCA infarction requiring neurocritical care. The repeat CT scans performed within 120 hours of stroke onset were assessed for horizontal displacement of septum pellucidum and pineal gland, the size of MCA infarction, involvement of other vascular territories and hydrocephalus. The primary outcome measure was death within 30 days.
Results
A total of 251 patients fulfilled entry criteria into the study of which 201 received conventional medical therapy alone. Univariate analysis identified the following predictors of early death: NIHSS >16 (P<0.03, OR 2.17 95% CI 1.12–4.2), anteroseptal shift >7 mm (P<0.001, OR 9.2 95% CI 4.1–20.63), pineal shift >3 mm (P<0.001, OR 12.1 95% CI 4.74–30.8), ischemia involving additional vascular territories (P<0.001, OR 7.02 95% CI 3.35–14.7), hydrocephalus (P<0.02, OR 2.13 95% CI 1.15–3.94), and temporal lobe involvement (P<0.001, OR 5.66 95% CI 2.58–12.4). Multivariate analysis was performed but no independent variables were identified because the CT variables were highly correlated. Anteroseptal shift dichotomised into < 7 and > 7 mm had sensitivity 53%, specificity 93%, positive predictive value (PPV) 88%, negative predictive value (NPV) 69% for neurological death. Pineal shift dichotomised <3 and = 3 mm had sensitivity 45%, specificity 94%, PPV 87% and NPV 66%.
Conclusions
We identified the role of follow-up CT in predicting early death following massive MCA infarction. Anteroseptal shift >7 mm and pineal shift >3 mm if present were strongly predictive of fatal outcome. These follow-up CT parameters require validation before they impact the decision to perform surgical intervention.
CLINICAL DETERIORATION FOLLOWING IMPROVEMENT IN THE NINDS rt-PA STROKE TRIAL
Authors: Grotta James C , Welch Kma , Fagan Susan C , Lu Mei , Frankel Michael R , Brott Thomas , Levine Steven R , Lyden Patrick D
Published: July 2021

P234

Background and Objective:
Little is known about cerebral arterial reocclusion after successful thrombolysis. In the absence of arteriographic information, the NINDS rt-PA Stroke Trial investigators prospectively identified clinical deterioration following improvement (DFI) as a possible surrogate marker of cerebral arterial reocclusion following rt-PA-induced recanalization. Also, we identified any significant clinical deterioration (CD) even if not preceded by improvement. We aimed to determine the incidence of DFI and CD in each treatment group, identify baseline or post-treatment variables predictive of DFI or CD, and determine any relationship between DFI, CD and clinical outcome.
Methods:
DFI was defined as any 2 point deterioration on the NIHSS following an initial 2 point improvement after treatment. CD was defined as any 4 point worsening after treatment compared to baseline. All data were collected prospectively by investigators blinded to treatment allocation. A non-contrast brain CT was mandated whenever a 2 point deterioration occurred. All cases were validated by a central review committee.
Results:
DFI was identified in 81 of the 624 patients (13%); 44 treated with rt-PA and 37 with placebo (p=0.48). DFI occurred more often in patients with higher baseline NIHSS. CD within the first 24 hours occurred in 98 patients (16% of all patients); 43 given rt-PA and 55 placebo (p=0.19). Baseline variables associated with CD were less frequent use of pre-stroke aspirin and higher incidence of early CT changes of edema or mass effect, or dense middle cerebral artery sign. Patients with CD had higher rates of increased serum glucose and fibrin degradation products (FDP), and they also had higher rates of symptomatic intracranial hemorrhage and death. Patients who experienced either DFI or CD were less likely to have a 3 month favorable outcome.
Conclusions:
We found no association between DFI, CD and rt-PA treatment, and no clinical evidence to suggest reocclusion. Deterioration was strongly associated with stroke severity and poor outcome, and was less frequent in patients whose stroke occurred while they were on aspirin.
ECG changes in malignant MCA infarction
Authors: Jauss Marek , Krieger Derk W , Kasner Scott E , Demchuk Andrew M
Published: July 2021

P241

Background and objective:
Patients with massive hemispheric strokes are threatened by cardiac arrhythmias secondary to autonomic dysregulation. We evaluated ECG abnormalities in patients with massive MCA infarction to identify patients at risk for cardiac complications.
Methods:
From the placebo arm of the LUB-INT-9 study we identified a group of 144 patients with massive anterior circulation stroke. Patients with a history of myocardial infarction, atrial fibrillation or with febrile infection within 96h after admission where excluded. 52 patients remained and were assigned according to presence or absence of temporal lobe involvement, multiple territory involvement, brainswelling in CT scan and according to outcome (death due to neurological deterioration) and side of infarction. A groupwise comparison of ECG findings between patients with presence or absence of the previous findings was performed using Wilcoxon rank sum test and considered significant with a p-value < 0.05. Incidence of critical bradycardia (<50 / min.) was tested using Fisher exact test.
Results:
HR was significantly lower in case of temporal involvement (n=15) after 48h , in case multiple territory involvement (n=11) after 12h and 48h and swelling in the initial CT scan (n=33, 1h-72h). PR interval was prolonged in patients with right hemispheric infarcts (n=28), while HR did not differ according to side of infarction. ECG parameters did not differ between the outcome groups. Critical bradycardia (< 50 / min.) was found in case of brain swelling in significantly higher incidence after 1h (11%), and after 48h (31%).
Conclusion:
Bradycardia is a potential complication in patients presenting with large hemispheric infarcts and mass effect with high incidence also in patients with no history of cardiac disease. Highest incidence 48h after infarction underlines that ECG-monitoring should extend the first 24h. The observed PR-prolongation is consistent with clinical studies and indicates a higher incidence of autonomic impairment in case of right sided infarction.