bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular Territorial Classification and Etiologies of Acute MCA Infarct by Diffusion-Weighted MRI
Authors: Han Moon-Ku , Kang Dong-Wha , Yoon Byung-Woo , Roh Jae-Kyu
Published: March 2022

P42

Background and Purpose
- The purpose of this study is to classify infarct subtypes of middle cerebral artery distribution (MCA) seen on diffusion-weighted MRI (DWI) and investigate infarct mechanisms and etiologies of MCA infarct subtypes.
Method
- We analysed 187 consecutive patients with acute MCA infarct who were studied by DWI/MRA within the first 4 days of stroke onset between 1997 and 1999, and stroke mechanism was determinedaccording to the criteria of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Infarct patterns from 128 patients except for lacunar infarcts (patients) were classified by the two types of multiple infarcts and large single infarcts: 2 types of multipleinfarcts; subcortical/cortical and cortical/cortical infarcts, 3 types of large single infarcts; subcortical, cortical and large infarcts including cortical and subcortical lesions
Results
-TOAST diagnostic subtypes were 78 large vessel strokes, 22 cardioembolic strokes, 59 lacune strokes, 4 other strokes, and 26strokes of unknown cause. We identified multiple infarcts (MI) in 41 patients: subcortical/cortical, 29 including 14 MCA disease (p=0.03); cortical/cortical, 7 including 6 ICA disease (p=0.005), and 87 large single infarcts (SI): subcortical, 32 including 13 MCA disease (p=0.02); cortical, 5 including 3 cardioembolism (p=0.03); large infarcts (cortical/subcortical), 50. There was no difference of etiologies among large infarcts (cortical/subcortical) in SI.
Conclusion
-MCA disease is the most important cause of subcortical and cortical multiple infarcts, and subcortical single infarcts. ICA disease is most frequent cause of cortical multiple infarcts and cardioembolism is more common cause in cortical single infarcts. We conclude that our classificationof MCA Infarct patterns using early DWI in acute ischemic stroke is useful to identify the causes of stroke according to subtypes and to consider the clinical decisions of etiologic investigations and to decide the early treatment modality in acute ischemic stroke.
Heterogeneous spatial-temporal evolution of DWI/PWI in human cerebral ischemia
Authors: Wu Ona , Schwamm Lee H , Koroshetz Walter J , Gonzalez Ramon G , Pan Vicky , Benner Thomas , Copen William A , Ostergaard Leif , Sorensen A. Gregory
Published: March 2022

P53

Purpose:
To characterize on a voxel-by-voxel basis salvageable from irreversibly-damaged ischemic tissue in human ischemic stroke using serial diffusion (DWI) and perfusion (PWI) weighted imaging. We sought to correlate tissue outcome with heterogeneity in the evolution of DWI and PWI.
Methods:
Patients with strokes involving the MCA territory who had been enrolled in a serial DWI and PWI study recording the natural history of human cerebral ischemia were retrospectively analyzed (n=6). Patients had received follow-up studies at predefined intervals. For each patient, maps of the apparent diffusion coefficient (ADC), fractional anisotropy (FA), cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and follow-up T2 FSE (F/U) were spatially coregistered (using AIR 3.08). Time to reach minimum/maximum values, time-to-normalization (or pseudonormalization), and minimum/maximum values were calculated for the DWI/PWI parameters. The ischemic core was operationally defined as the initial DWI abnormality, rim tissue as the mismatch between F/U and initial DWI, and salvaged-at-risk tissue as the mismatch between initial PWI and F/U. Values in core, rim and salvaged tissue were compared using standard two-sample t-tests. All significant findings were at p-values <0.05.
Results:
Pooling the six patients’ data, the depth of reduction at the acute stage of ADC, CBF and CBV values were found to be significantly greater in core than rim. MTT was found to be significantly elevated. Acutely, CBF was found to be significantly higher in salvaged tissue compared to rim; however no significant difference was found for MTT values (p=0.8). The time for ADC to reach its minimum value is faster in the core compared to rim as well as pseudonormalizing sooner. Elevated FA was found to occur earlier in core tissue than in the rim followed by a more rapid decrease. Pseudonormalization of FA occurred sooner than of ADC values. CBF and MTT recovered earlier in salvaged tissue versus rim tissue.
Conclusion:
Intralesional heterogeneity in the evolution of DWI/PWI may assist in the identification of salvageable tissue.
Angiogenic growth factor expression in stroke
Authors: Wang Michael M , Klaus Judy A , Joh Hung-Dong , Traystman Richard J , Hurn Patricia D
Published: March 2022

P66

Angiogenic growth factors play an essential role in the development and structural integrity of the cerebral vasculature, but their importance in stroke is poorly defined. Stroke prone hypertensive rats (SHRSP), a model for genetic stroke susceptibility, suffer spontaneous stroke and enhanced injury after experimental stroke, at least in part due to abnormal cerebrovascular development. We hypothesized that angiogenic genes in SHRSP may follow unique patterns of expression after experimentally induced stroke. Ribonuclease protection assays were used to determine expression levels of the angiogenic receptor Tie-2 and its ligands in the brain after reversible middle cerebral artery occlusion (2 hours, followed by 22 hours of reperfusion) in SHRSP, and in control SHR and WKY rats. The expression of Tie-2 and Ang-1, an agonist for Tie-2, dropped markedly after stroke in SHRSP animals (70% and 45%; p<0.05), but not in controls. In addition, enhanced expression of Ang-2, a Tie-2 antagonist, is significantly higher in SHRSP animals (50% versus WKY; p<0.05). Together, these data demonstrate that SHRSP may dramatically downregulate Tie-2 signaling after stroke. This suggests that in stroke prone animals, impairment of Tie-2 signaling contributes to stroke vulnerability.
Intranasal IGF-1 Protects against Transient Focal Cerebral Ischemia in Rats following Middle Cerebral Artery Occlusion (MCAO)
Authors: Liu Xin-Feng , Fawcett John R , Thorne Robert G , Frey William H
Published: March 2022

P71

Insulin-like growth factor-1 (IGF-1) has been shown to protect against stroke in rats when administered intracerebroventricularly. However, this administration method is not practical in humans as it requires surgery with the risk of infection. Intranasal (IN) delivery is a noninvasive method of bypassing the blood-brain barrier to deliver IGF-1 to the brain [Thorne et al. (1999) Growth Hormone and IGF Research 9: 387]. We have assessed the therapeutic potential of IN IGF-1 in rats following experimentally-induced focal cerebral ischemia and reperfusion. Rats were given a total of three 75 μg doses of IGF-1 (Chiron Corp.) IN over the course of the 72 hour study: 10 minutes after the onset of two hours of MCAO and then again 24 and 48 hours later. Five neurologic tests assessing motor, sensory, vestibulomotor and somatosensory functions were performed at 4, 24, 48 and 72 hours after the onset of MCAO under blinded conditions. Infarct volume, hemispheric swelling and pathological changes were evaluated at 72 hours after MCAO following euthanasia and coding for blind analysis. IGF-1 treatment significantly reduced the corrected infarct volume by 71 % (p=0.002) and hemispheric swelling by 37 % (p=0.017) when compared to vehicle-treated controls. In addition, the postural reflex and flexor response tests showed significant neurologic improvement with IGF-1 treatment (p=0.016 and 0.019 respectively). The adhesive-backed paper test showed borderline significance in both the contact and removal times (p=0.0573 and p=0.042 respectively). The forelimb placing and beam balance tests showed a clear recovery trend but did not reach statistical significance. While IGF-1 does not significantly cross the blood-brain barrier following traditional peripheral routes of administration, it can be delivered to the brain directly from the nasal cavity following intranasal administration. IN IGF-1 reduced both infarct volume and cerebral edema and also significantly reduced neurologic deficits following MCAO. Our study indicates IN delivery of IGF-1 holds significant promise as a noninvasive and efficacious method for treating stroke.
Intra and postischemic mild hypothermia : Effects on inducible nitric oxide synthase and peroxynitrite in experimental stroke
Authors: Han Hyung Soo , Sun Guo Hua , Yenari Midori
Published: March 2022

P86

Background:
Mild hypothermia is protective even when delayed hours after stroke onset. Because metabolic depletion and glutamate release occur early after ischemia onset, other mechanisms may underlie the protection, particularly when cooling is delayed. Inflammation and free radicals mediate delayed ischemic injury. We examined whether mild hypothermia alters induction and activity of inducible nitric oxide synthase (iNOS, found primarily in inflammatory cells) and peroxynitrite generation.
Methods:
Rats were subjected to transient middle cerebral artery occlusion for 2 hours. Mild hypothermia began immediately (intraischemic, 33
O
C-I, n=8) or 2 h (delayed, 33
O
C-D, n=8) after ischemia onset during the reperfusion phase. Hypothermia was maintained for 2 h. Normothermic animals were maintained at 37
O
C (n=8). Brains were examined 1 and 3 days later for infarction, NOS activity (NADPH diaphorase), iNOS induction and peroxynitrite (nitrotyrosine) production.
Results:
Mild hypothermia attenuated infarct size in both groups compared to normothermia (33
O
C-I: 26.8±7.7%, 33
O
C-D: 30.4±4.8%, 37
O
C: 70.8±3.3%, P<0.001). iNOS-positive cells appeared 1 d after ischemia in the infarct area and increased in number by 3 d, but NOS activity was only seen at 3 d. Nitrotyrosine-positive cells also increased by 3 d. Positive cells in all cases appeared microglia/monocyte/macrophage-like with ameboid morphology. Mild hypothermia significantly decreased NADPH diaphorase, iNOS and peroxynitrite densities at 3 d, but not 1 d. NADPH diaphorase-positive cells per hemisphere were: 37
O
C: 1028±68, 33
O
C-I: 152±12, 33
O
C-D: 101±1 (P<0.001). Densities of iNOS-positive cells were: 37
O
C: 1265±83/mm
2
, 33
O
C-I: 435±93/mm
2
, 33
O
C-D: 688±59/mm2 (P<0.001). Densities of nitrotyrosine-positive cells were: 37
O
C: 585±14/mm
2
, 33
O
C-I: 214±23/mm
2
, 33
O
C-D: 106±12mm
2
(P<0.001). No differences in any of the parameters were seen at 1 d.
Conclusion:
Mild hypothermic neuroprotection is related to attenuation of iNOS and peroxynitrite in inflammatory cells at 3 d but not earlier. This is evident even when cooling is delayed by 2 h.
INTRA-ARTERIAL INFUSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN NORMAL AND ISCHEMIC BRAINS HAS NO EFFECT ON ANGIOGENESIS
Authors: Manoonkitiwongsa Panya S , Jackson-Friedman Cathy , McMillan Paul J , Schultz Robert L , Lyden Patrick D
Published: March 2022

P95

INTRODUCTION:
Stimulation of angiogenesis in ischemic brains may be of major value in stroke therapy. Administration of vascular endothelial growth factor (VEGF) is considered particularly effective as an angiogenic factor for hypoxia-related injuries. We therefore quantitatively compared the effect of VEGF on microvessels of normal and ischemic brain cortices. Vascular parameters of microvessels measured included changes in numerical (N
A
), volume (V
v
), surface (S
v
) and length (L
v
) densities along with diameter.
METHODS:
VEGF
165
protein at 1μg/ml was infused into the common carotid artery of normal and ischemic adult male Sprague-Dawley rats with a miniosmotic pump for 7 days at 1 μl/hr (VEGF infusion therefore 1 ηg/hr). Animals (n = 3 or 4 per group) were sacrificed at 7 days post-surgery. Ischemia was induced by occlusion of the middle cerebral artery for 4 hours. Vascular parameters were quantitated by light microscopic morphometry. Normal and ischemic brains not infused by VEGF served as controls.
RESULTS:
Mean and S.D. of the vascular parameters (N
A
[# of vessels/mm
2
]; V
v
[%]; S
v
[mm
2
/mm
3
]; L
v
[mm/mm
3
];

D [μm]) of the different groups are as follows: A) Normal brains (462 ± 63; 2.00

± 0.2; 13.9 ± 1.7; 925 ± 127; 5.48 ± 0.5) B) Normal brains (480 ± 38; 2.25

± 0.3; 14.9 ± 0.8; 961 ± 76; 4.98 ± 0.3) + VEGF C) Ischemic brains (471 ± 47; 2.06

± 0.2; 14.3 ± 1.4; 942 ± 94; 5.11 ± 0.8) D) Ischemic brains (579 ± 102; 2.04 ± 0.3; 16.2 ± 2.7; 1159 ± 205; 4.64 ± 0.4) + VEGF There are no significant differences between the groups.
CONCLUSIONS:
Intra-arterial infusion of VEGF
165
protein for 7 days at 1 ηg/hr has no effect on the vascular parameters of normal or ischemic cortices. Infusion of VEGF alone may not be sufficient for inducing neovascularization in intact brain. Further studies specifically testing the appropriate concentration, duration, VEGF isoform(s), manner of administration (protein, plasmids or viral vectors), use of combinational angiogenic factors along with permeability or other side effects are critical to ascertain the angiogenic merits of VEGF for stroke therapy.
Occurrence of Secondary Brain Insults in Intracerebral Hemorrhage
Authors: Hemphill J. Claude , Besmertis Lavrentios
Published: March 2022

P105

Objective:
Secondary brain insults (SBIs) include hypotension, hypoxia, fever, and seizures. SBIs are known to worsen outcome after head trauma and ischemic stroke, but their role in intracerebral hemorrhage (ICH) has not been well studied.
Methods:
Records of patients presenting with acute ICH to San Francisco General Hospital from July 1 through December 31, 1997 were retrospectively reviewed for the occurrence of SBIs at any point during hospitalization. Episodes of hypoxia (P
a
O
2
< 60 mm Hg or an O
2
saturation < 90% for over 5 minutes), hypotension (systolic blood pressure (BP) < 90 mm Hg for greater than 5 minutes), fever (T > 38.5
O
C), or generalized seizures were noted.
Results:
Overall 30-day mortality was 39% (14 of 36 total patients). In-hospital seizures were uncommon as was systemic hypoxia, the latter perhaps due to early intubation in comatose patients. However, fever and hypotension were much more common in patients who died, despite the fact that most ICH patients presented acutely with elevated BP. Among patients who died, 57% had at least one episode of T > 38.5
O
C and 71% had at least one episode of BP < 90 mm Hg, compared to only 9% of surviving patients (
P
< 0.01).
Conclusions:
SBIs, especially hypotension and fever, are common after ICH and are associated with higher 30-day mortality. Whether this indicates worsened ICH-related brain injury, as in head trauma or ischemic stroke, or is a result of secondary complications in severely affected patients remains to be clarified.
Why Experimental Vasospasm Resolves
Authors: Dr. Robert L Macdonald , Dr. Zhen-du Zhang , Dr. Bryce K Weir
Published: March 2022

P112

It has been suggested that changes in the arterial wall contribute to the maintenance and resolution of vasospasm after subarachnoid hemorrhage (SAH). This study determined if such changes contribute to the resolution of vasosapsm after SAH, if vasospasm resolves because of loss of subarachnoid blood clot or if a combination of these mechanisms is involved. 27 monkeys underwent baseline angiography and unilateral (n = 17) or bilateral (n = 8) SAH. Animals with bilateral SAH underwent angiography 1, 3, 5 and 7 days later followed by euthanasia. Animals with unilateral SAH had angiography 7 days later. The clot then was removed in these animals and replaced with fresh clot (n = 7) or removed and not replaced (n = 5). The removed clot was placed on the left side (n = 12). Controls did not have clot removal (n = 5) and/or had fresh clot placed on the left on day 7 (n = 5). Angiography was repeated every 2 days until euthanasia on day 14. SAH caused significant middle cerebral artery vasospasm on day 7 that slowly resolved by day 14. Removal of clot on day 7 resulted in more rapid reversal of vasospasm suggesting that vasospasm depended on continued presence of subarachnoid clot rather than on or in addition to structural changes in the artery. Placing fresh clot on the right side on day 7 produced vasospasm that persisted without resolving suggesting that there is no preconditioning response in the artery that prevents or conributes to reversal of vasospasm. On the other hand, placing 7-day-old clot from the right onto the left caused significantly more rapid onset of severe vasospasm than placing fresh clot from animals 7 days after SAH, suggesting that breaking up the clot to replace it on the left increases release of spasmogens or that there is a negative adaptive response that exacerbates vasospasm. In conclusion, vasospasm resolves because of loss of subarachnoid clot. There is no evidence for a preconditioning response in cerebral arteries that renders them less responsive to subarachnoid clot. Spasmogen release from clot 7 days after SAH may be reduced in this model so that breaking up the clot increases spasmogen release resulting in rapid onset of severe vasospasm and/or that there is a negative adaptive response 7 days after SAH that worsens vasospasm.
Classification of Stroke Cases in Administrative Data using ICD-9 Codes
Authors: Tirschwell David L , Kukull Walter A , Longstreth W. T
Published: March 2022

P161

Background:
Using administrative data allows inexpensive evaluation of large patient datasets. An objection to such analyses is poor reliability of ICD-9 discharge codes and thus inaccurate case ascertainment.
Objective:
To identify reliable algorithms to classify stroke cases using ICD-9 discharge codes .
Methods:
From a population-based hospital discharge database with 20,803 cases, 206 medical records of probable stroke cases, from 3 community and 2 university hospitals, were randomly selected and abstracted. The gold standard was the medical record attending physician diagnosis with corroboration by a stroke neurologist (DLT).
Results:
Final gold standard diagnoses included 8 (4%) TIAs, 76 (37%) ischemic stroke, 47 (23%) intracerebral hemorrhage (ICH), 58 (28%) subarachnoid hemorrhage (SAH) and 17 (8%) no cerebrovascular event. Compared to algorithms that utilized either all possible or the first 2 ICD-9 discharge codes, an algorithm restricted to use of the first (principal) discharge code optimized specificity and positive predictive value (Table). Overall stroke classification based on the first discharge code showed substantial agreement with the gold standard (Kappa = 0.72, P < 0.0005). In the original 20,803 case database, the prevalence of ischemic stroke was 30%, ICH 4.6% and SAH 1.6%.
Conclusions:
An algorithm based on the principal ICD-9 discharge code can reliably identify and classify stroke cases. By optimizing specificity and positive predictive value, sensitivity is lost. Positive predictive value is influenced by prevalence.
Post-stroke Fever in Patients without Infectious Diseases: The Involvement of Hypothalamus Confirmed by Autopsy
Authors: Naritomi Hiroaki , Uno Hisakazu , Oe Hiroshi , Yamawaki Takemori , Yutani Chikao
Published: March 2022

P176

Background:
Post-stroke fever is known to occur even without infection presumably due to central mechanisms. In our rat study, a small hypothalamic infarction caused fever substantially (Stroke 30:2743, 1999). In human subjects, the hypothalamus is supplied by the posterior choroidal artery. Internal carotid artery (ICA) territory ischemia usually spares the hypothalamus except for large infarction which provides secondary damage to the hypothalamus by mass effects. The present study was performed to clarify whether the development of central type fever is related with the size of infarction and the involvement of hypothalamus.
Methods:
Subjected were 60 patients with acute embolic stroke in ICA territory who were admitted within 24 hours after stroke. Patients with infection were excluded from the study. The patients were divided into 3 groups according to the size of infarction on CT in the chronic phase (small, medium-sized or large). In all the patients, axillary temperature was recorded 4–6 times/day for 1 week. Daily average temperature was compared between the groups. In 6 fatal patients, autopsy studies were performed to find hypothalamic involvement.
Results:
In the group of small infarction, the average temperature never exceeded 37.0 degrees throughout the 1-week period. In the group of large infarction, the temperature was not elevated at the admission but showed rapid increase thereafter. The average temperature exceeded 37.0 degrees from the 2nd day through the 6th day. In the group of medium-sized infarction, the temperature showed a temporary elevation followed by rapid recovery. Of 6 autopsy patients, 3 had post-stroke fever and the others had no fever. In all the 3 febrile patients, the ipsilateral hypothalamus was involved by ischemia, while in the other 3 patients, the hypothalamus remained intact.
Conclusions:
Our results suggest that large ICA territory infarction may cause fever due to secondary damage to the hypothalamus. Fever may be a causative factor of poor clinical outcome. It can be said from the different viewpoint that fever may be the consequence of large lesion which likely brings about poor outcome.
Tissue Plasminogen Activator for Rural Referrals; the Effect of Stroke Team Notification Prior to Arrival
Authors: Merino Jose G , Silver Brian , Tamayo Arturo , Wong Edward H , Demaerschalk Bart , Devasenapathy Ashok , O’Callaghan Christina , Kertesz Andrew , Young G. Bryan , Spence J David , Hachinski Vladimir
Published: March 2022

P196

Background:
Many rural community hospitals (RCH) in Southwestern Ontario lack a CT scanner. The stroke team (ST) in London provides tertiary care to these RCH. Advance notification of transfer of non-London patients (NLP) from RCH allows the ST to manage them from arrival at the LER. In contrast, the ST is notified of London patients (LP) after their arrival and registration in the London ER (LER).
Objective:
Assess feasibility of tPA administration to rural patients transferred to a tertiary care center.
Methods:
Mean symptom to LER, door to imaging, imaging to tPA, and door to tPA (DtPA) for LP and NLP times were compared. In-patients were excluded from the analysis.
Results:
Between Dec 1, 98 and Jun 30, 00, 61 patients were treated with tPA in London: 16 (26%) were NLP, 45 (74%) were local (37 LP, 8 in-patients). For NLP the mean symptom to RCH time was 37 mins, the mean RCH to LER distance was 41 miles (range 11–80) and the mean transfer time was 90 mins. (range 46–138). Symptom onset to LER time was significantly longer for NLP, but door to imaging, imaging to tPA, and DtPA were significantly lower (p< 0.001, see table).
Conclusions:
1. The establishment of a network of RCH and a tertiary center can extend the benefits of tPA to a rural population. 2. DtPA can be shortened if the ST manages the patients from arrival to the ER. This strategy could be applied to local patients if EMS notifies the ST of potential candidates for tPA.
Stroke Recurrence in Patients with Patent Foramen Ovale after Cerebral Ischemia
Authors: Kunze Alexandra K , Wronka Tabitha , Buggle Florian , Ringleb Peter A , Lichy Christoph , Grau Armin J , Brandt Tobias
Published: March 2022

P207

Paradoxical embolism through a patent foramen ovale (PFO) is a potential cause for ischemic stroke, particularly in younger patients. Longterm data concerning stroke recurrence in patients with PFO is scarce. We performed a longterm follow-up in patients with PFO, diagnosed in association with cerebral ischemia in our department from 1991 to 1997. We performed telephone interviews with a standardized questionnaire and neurologic examinations. PFO-size was assessed semiquantitatively as described before (<10; 10–99; >99). Univariate and multivariate tests were performed for all potential risk factors of stroke recurrence in patients with PFO. We examined 281 patients with a mean age of 48 years and a mean follow-up interval of 39 months. Recurrent cerebral ischemia occured in 59 patients. Recurrence rate was 6.9% per year. In patients on warfarin, recurrence rate was significantly lower than in patients on aspirin or without therapy (4.2% per year, p= 0.001). In patients without therapy, stroke recurrence rate was significantly higher than in patients on warfarin or aspirin (13% per year, p= 0.002). Recurrence was not associated with PFO-size and spontaneous shunt. Ventricular septum aneurysm (VSA) was not more frequent in patients with recurrent stroke. Recurrence rate was significantly higher in patients with concurrent etiologies (p= 0.001). Stroke recurrence rate in patients with PFO after cerebral ischemia is higher in this large series than in some smaller previous series. Warfarin significantly lowers stroke recurrence rate. Surprisingly, recurrence rate was not associated with PFO-size, spontaneous shunt or VSA. Thererfore, no subgroups could be identified, which are at higher risk. Anticoagulation seems the treatment of choice for secondary prevention, independent from PFO-size or spontaneous shunt.
Late Administration of Human Recombinant Vascular Endothelial Growth Factor (rhVEGF
165
) Improves Functional Outcome after Embolic Stroke in Rat
Authors: Morris Daniel , Zhang Zheng G , Zhang Li , Jiang Quan , Zhang Ruilan , Davies Kenneth , van Bruggen Nicholas , Chopp Michael
Published: March 2022

P218

Transient and permanent middle cerebral artery (MCA) occlusion in rat evokes increased expression of VEGF in ischemic brain. The biological role of VEGF in stroke is unknown. We tested the hypothesis that administration of VEGF at a late stage of stroke enhances angiogenesis and improves functional outcome in stroke. Male Wistar rats (n=27) were subjected to MCA occlusion using a well described embolic stroke model. Forty-eight hours after embolization, rhVEGF
165
or saline was intravenously infused to rats at a dose of 1mg/kg over 4 hr interval. Angiogenesis was examined in three dimensions by a laser scanning confocal microscope. Functional neurological tests (rotarod and adhesive removal tests) were measured. To examine whether rhVEGF
165
enhances angiogenesis, rats were sacrificed 9 days after ischemia and to examine whether rhVEGF
165
improves long term functional recovery, rats were sacrificed 28 days after ischemia. Compared with the saline treated rats (n=5), treatment with rhVEGF
165
(n=5) significantly (p<0.05) increased numbers of capillaries with diameters within 3 μm in the penumbra of the cortex 9 days after ischemia. In addition, rats treated with rhVEGF
165
(n=7) exhibited significant (p<0.05) improvement on the rotarod test at 7, 14, and 28 days after stroke compared with the saline treated rats (n=10). The adhesive removal test showed significant (p<0.05) improvement at 28 days. Brain tissue obtained at 28 days after ischemia exhibited more small vessels in the ipsilateral ischemic border zone in rats treated with rhVEGF
165
when compared with the saline treated rats. Our data demonstrate that rhVEGF
165
significantly enhances angiogenesis in ischemic brain and improves functional neurological recovery when administered to rats 48 hr after stroke.
Lessons Learned in the Process of Stroke Quality Management: Revised tools and strategies in a follow-up study
Authors: Fedder Wende N , Book Diane S , Sunstrom Cindy , Bevington Mary
Published: March 2022

P229

Objectives
Written care protocols and quality improvement efforts have recently been included in published guidelines on care of the ischemic stroke patient. We describe revisions to the quality management process that resulted in increased protocol use at a 469-bed medical school affiliate private hospital.
Methods
An earlier clinical pathway for ischemic stroke was ineffectively implemented as shown by pathway use in less than half of appropriate cases. A multidisciplinary team addressed barriers identified in that early experience to modify strategies in the development of a new set of quality management tools (QMT) for ischemic stroke. The revised QMT included: standing orders, clinical pathway, NIH Stroke Scale flow sheet, diagnostic summary form, and variance tracking tool. QMT use rates were calculated by medical record abstraction during a 3-month pilot study and physician and nurse usage rates determined. Factors contributing to QMT usage were analyzed.
Results
Twenty-eight ischemic stroke patients were admitted to the pilot unit during the study. Usage rates for components of the QMT driven by physicians were: standing orders 93%; IV tPA standing orders 100%; and diagnostic summary form 46%. Nurse related QMT usage was: clinical pathway 96%; NIH Stroke Scale flow sheet 75%; and variance tracking tool 75%. Key strategies that contributed to improved implementation were: 1) early involvement and continuous communication between the expanded multidisciplinary team, staff nurses and physicians 2) empowerment of nurses through NIH Stroke Scale training 3) perception of mutual accountability between nurses and physicians through use of QMT documents 4) clearly defined administrative directives.
Conclusion
Effective implementation of quality management protocols for ischemic stroke requires active participation of related disciplines at working levels, clear administrative support, and mutual accountability of physicians and nurses. Continuous critical appraisal of the process can afford eventual strategic solutions.
Abstract 130: Deep Vein Thrombosis/Pulmonary Embolization in the Get With The Guidelines-Stroke Acute Ischemic Stroke Population: Incidence and Patterns of Prophylaxis
Authors: Douds G L , Hellkamp Anne S , Olson DaWai , Fonarow Gregg C , Smith Eric E , Schwamm Lee H , Cockroft Kevin M
Published: March 2022

Objective.
Venous thomboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolus (PE), represents a serious complication in hospitalized ischemic stroke patients. This study was undertaken to determine the incidence and patterns of prophylaxis for VTE in the GWTG-Stroke population.

Methods.
From 323,363 adult ischemic stroke patients enrolled in GWTG-Stroke, patients who were not admitted, had their stroke as an inpatient, died or discharged by day 2, ambulatory by day 2, ambulatory status unknown, VTE prophylaxis contraindicated, and comfort care by day 2 were excluded leaving 149,916 patients from 1,259 sites, of whom 136,432/149,916 (91%) had information on DVT/PE occurrence. Analysis of patient variables and site characteristics were performed in relation to reported administration of VTE prophylaxis. Multivariable models were constructed based on demographics, initial NIHSS, medical history, receipt of tPA or other therapy, and hospital characteristics.

Results.
The overall rate of DVT/PE was 3.01% (4,100/136,432). Excluding sites with VTE rates = 0% or >50% reduced this rate to 2.81% (3,408/121,276). The overall rate of VTE prophylaxis in the analysis cohort was 93% (139,476/149,916). Site prophylaxis rates were median 95% (25
th
-75
th
percentiles, 89%-98%) and ranged from 17% (1 site) to 100% (101 sites). Factors associated with increased likelihood of VTE prophylaxis in the multivariable model included history of atrial fibrillation/flutter (OR 1.50; 95% CI 1.42-1.59), receipt of IV (OR 1.24; 95% CI1.15-1.35) or IA tPA (OR 1.34; 95% CI 1.13-1.59), and admission to an academic hospital (OR 1.68; 95% CI 1.44-1.97). Increasing age (OR 0.95; 95% CI 0.94-0.96) and black race (OR 0.92; 95% CI 0.86-0.98), as well as history of peripheral vascular disease (OR 0.84; 95% CI 0.78-0.90), diabetes (OR 0.92; 95% CI:0.88-0.95), or prior stroke/TIA (OR 0.92; 95% CI 0.87-0.97) were associated with lower likelihood of prophylaxis. Patients receiving care in the Midwest region were less likely to receive prophylaxis compared to other regions (OR 0.73; 95% CI 0.61-0.88).

Conclusions:
Despite a high overall rate of prophylaxis, DVT/PE continue to occur in approximately 3% of GWTG-Stroke patients. Reported rates of VTE prophylaxis differ among hospitals by region, and among different patients by age, race, and medical co-morbidities.
Abstract 132: In-hospital Versus Out-of-hospital Code Stroke: Iv Tpa Rate And Clinical Outcomes.
Authors: Bruce Nhu , Raman Rema , Ernstrom Karin , Ovbiagele Bruce , Meyer Dawn M , Meyer Brett C , Hemmen Thomas M
Published: March 2022

Background:
Patients with Code Stroke alert in the hospital may have different risk factors, demographics and differential diagnoses than patients who are admitted with Code Stroke Alert to the ED. Hospitals and health care systems use considerable resources to provide 24/7 acute stroke care access to in-hospital Code Stroke alerts. Most of the utility analyses are based on data from out-of-hospital stroke. We analyzed the frequency of IV tPA use and the likelihood of home discharge in patients with Code Stroke alert in the hospital versus out-of-hospital.

Methods:
All adult patients with Code Stroke alerts in the UCSD SPOTRIAS Database from 2004 to 2011, excluding patients transferred from acute care facilities; grouped into 1: out-of-hospital Code Stroke alerts (EMS or ED) and 2: in-hospital (all inpatient units) and analyzed by baseline demographics; time to treatment decision; frequency of IV tPA use; diagnosis (Acute Ischemic Stroke, SAH, ICH, TIA, mimic, unknown); discharge disposition (home versus other), 90 day modified Rankin Scale (mRS) and adjusted for multiple co-variables.

Results:
We identified 2,699 Code Stroke alerts; 2,498 in group 1 and 201 in group 2. Patients in group 2 were younger (63.6±15.5 vs 66.8±16.8 years of age, p=0.005), more likely to have diabetes (27.9 vs 21.3%, p=0.03), had higher baseline NIHSS (11.6±11.6 vs 9.0±10.0, 0.007) and likelihood to have a pre-stroke mRS >1 (35.8 vs 27.4%, p=0.01); had fewer acute ischemic strokes (38.8 vs 46.6%), but more stroke mimics (39.8 vs 29.5%), p=0.01,had shorter time from stroke onset to treatment decision (202.2±282.3 vs 275.2±423.1 min, p<0.0001) and were less likely to receive IV tPA (10.0 vs 16.0%, p=0.03). The time from onset to IV tPA treatment in Group 2 was 162.9±69.8 min; vs 150.1±106.0, p=0.07. Multivariable logistic regression analysis adjusting for age, history of diabetes and admission NIHSS show that the rates of being discharge home (OR=0.83, 95%CI = 0.59, 1.17, p=0.29) and having a 90-day mRS of 0-1 (OR-1.35, 95% CI = 0.64, 2.86), p=0.44) are similar in the two groups.

Conclusion:
In-hospital are less likely to lead to IV tPA treatment than out-of-hospital Code Stroke alerts. Patient outcome based on discharge disposition and 90-day mRS is not significantly different from out-of-hospital Code Stroke.
Abstract 138: The Interim Results Of The Multicenter Prospective Registry Of Acute Cerebral Large Vessel Occlusion In Japan: The Impact Of Rescue Endovascular Treatment For Intravenous Tissue Plasminogen Activator-failed Patients
Authors: Yoshimura Shinichi , Sakai Nobuyuki ,   RESCUE-Japan Prospective Registry Study Group
Published: March 2022

Background:
The multicenter prospective registry of Japan (RESCUE-Japan Registry) was performed to clarify the clinical impact of endovascular treatment (EVT) on acute cerebral large vessel occlusion.

Methods:
Patients admitted within 24 h after stroke onsets were prospectively registered from July, 2010 to June, 2011. The efficacy of rescue EVT for intravenous intravenous tissue plasminogen activator (IV-tPA)-failed patients was analyzed.

Results:
Among a total of 1,385 patients registered in this study, 940 patients (520 women, 420 men) with 3 months outcome were investigated as the interim analysis. Mean age was 74.5 years (range 22-99 years). The mean arrival time was 237.4 min after onset, and mean NIHSS was 15.6 points. The first treatment within 3 hours was IV-tPA in 51%, conservative therapy in 33%, EVT in 16%. In the patients treated with IV-tPA (n=148), significant recanalization (TICI 2B, 3 or modified Mori’s grade 3) was obtained in approximately 40% in M1 distal and M2 of MCA, but less than 20% in ICA 1-3 hours after IV-tPA. Rescue EVT after IV-tPA was performed in 72/285 patients (25.3%), which was significantly increased the previous study in 2008. Rescue EVT contributed significant recanalized the affected arteries (TICI 2B-3: 17% to 68%) (
Fig
.1) and increased the ratio of favorable outcome (modified Rankin scale:0-2) in ICA (0% vs 50%, p=0.037) (
Fig
. 2), and M1 proximal occlusion (33% vs 83%, p=0.033) (
Fig
.3).

Conclusions:
The interim analysis of this nationwide registry suggested the efficacy of rescue EVT in IV-tPA failed patients with occlusion of the ICA and M1 proximal portion.
Abstract 150: Outpatient Cardiac Telemetry Detects A High Rate of Atrial Fibrillation Among Patients with Cryptogenic Cerebral Ischemia
Authors: Miller Daniel J , Khan Muhib , Schultz Lonni , Simpson Jennifer R , Russman Andrew , Panayiotis Mitsias
Published: March 2022

Introduction:
In one-third of patients discharged with stroke or TIA the etiology of the event remains undetermined. Occult paroxysmal atrial fibrillation (PAF) was reported as a potential etiology. The factors predicting PAF in these patients have not been defined.

Hypothesis:
1) A high rate of PAF can be detected during 21 days of mobile cardiac outpatient telemetry (MCOT). 2) There will be a set of risk factors which can predict the detection of PAF with MCOT.

Methods:
We performed a retrospective analysis on patients evaluated by MCOT monitoring within 6 months of a cryptogenic stroke or TIA. The ECG data were analyzed with an algorithm verified against the MIT-BIH arrhythmia database. Multivariate analysis with survival regression analysis was performed using demographic, clinical, neuroimaging and cardiac imaging characteristics to determine predictive risk factors for detection of PAF on MCOT. Kaplan-Meier estimates were computed for the 21-day PAF rates.

Results:
We analyzed 156 records; 97% of patients were not on anticoagulation. PAF occurred in 27 of 156 (17.3%) patients during MCOT monitoring of up to 30 days. The rate of PAF detection significantly increased from 3.9% in the initial 48hrs, to 9.2% at 7 days, to 15.1% at 14 days, and to 19.5% by 21 days (p<0.05) (
figure
). Multivariate analysis defined several independent predictors of PAF detection (
table
). Premature atrial complex (PAC) on baseline ECG held the strongest correlation with PAF (HR 13.65, p=0.001).

Conclusion:
MCOT is a robust diagnostic tool for the identification of PAF in patients with cryptogenic stroke and TIA. Length of monitoring is strongly associated with the likelihood of detection of PAF. Female gender, PAC on ECG, increased left atrial diameter (LAD), reduced left ventricular ejection fraction (LV EF) and greater NIHSS increase the likelihood of PAF detection.
Abstract 152: Predictors of Intracranial Hemorrhage Among Anticoagulated Patients with Atrial Fibrillation: Insights from the Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)
Authors: Hankey Graeme J , Stevens Susanna , Piccini Jonathan P , Lokhnygina Yuliya , Mahaffey Kenneth W , Halperin Jonathan L , Patel Manesh R , Breithardt Gunter , Singer Daniel E , Becker Richard C , Paolini John F , Nessel Christopher C , Hacke Werner , Fox Keith A , Califf Robert M
Published: March 2022

Background:
For patients with atrial fibrillation (AF) at moderate to high risk of stroke, oral anticoagulation reduces the risk of ischemic stroke but may increase hemorrhagic stroke and offset the intended benefits in certain individuals. Identifying individuals with AF at high risk of stroke who are likely to have an intracranial hemorrhage (ICH) if treated with anticoagulants remains a challenge.

Methods:
We investigated factors associated with ICH in 14,264 patients with nonvalvular AF randomized to rivaroxaban or dose-adjusted warfarin in ROCKET AF. The endpoint of interest was ICH in the entire intention-to-treat population. Cox proportional hazards modeling was used to identify factors associated with ICH.

Results:
Over a median follow-up of 1.94 years, 136 patients experienced ICH events (intracerebral hemorrhage [n=98], subarachnoid hemorrhage [n=5], subdural hemorrhage [n=32], extradural hemorrhage [n=1]). The average annual rate of ICH was 0.55 per 100 patient-years. The significant independent predictors of increased risk for ICH were increased age, history of prior stroke or TIA, black or Asian race, decreasing serum albumin, and decreased platelet count below 210 x 10
9
/l (Table, C-index=0.677). Creatinine clearance was not associated with the occurrence of ICH after accounting for other variables in the model (P=0.3181). Aspirin and thienopyridine use at baseline were associated with an increased risk of ICH whereas randomization to rivaroxaban (versus warfarin) was protective.

Conclusions:
Among patients with AF at moderate to high risk of stroke who were treated with anticoagulation, the average annual rate of ICH was 0.55 per 100 patient-years. Risk of ICH was increased among those who were non-white, older, had prior stroke or TIA, had low platelet counts, low serum albumin, and were taking antiplatelet therapy. Rivaroxaban was associated with a significantly lower risk of ICH compared with warfarin. The external validity of these findings requires testing in other AF populations.
Abstract 155: Risk of Seizures after Malignant MCA Stroke and Decompressive Hemicraniectomy
Authors: Creutzfeldt Claire J , Schubert Glenn B , Tirschwell David L , Longstreth WT , Becker Kyra J
Published: March 2022

Background
Post-stroke seizures (PSS) have a devastating effect on morale and may further impair an already compromised quality of life. The reported incidence of PSS is 5-12%, but may be higher in patients with malignant MCA stroke requiring decompressive hemicraniectomy. Seizure prophylaxis for stroke survivors is not recommended, and little guidance exists about the use of prophylactic antiepileptic drugs (AEDs) after neurosurgical procedures. We aimed to determine the incidence of seizures after hemicraniectomy in stroke survivors and to identify risk factors for development of seizures after stroke. Via telephone interview, we explored patients own experience after their stroke.

Methods
We reviewed charts of patients aged 18-99 with malignant MCA infarction who underwent decompressive hemicraniectomy from Jan 1, 2002 to Dec 31, 2008. We looked for seizures that occurred after their stroke and for clinical and imaging factors related to those. All patients who consented to a telephone interview were contacted to inquire about seizure history. Seizure-free survival analysis was used, with log rank testing for associations.

Results
We identified 38 patients, mean follow-up time was 504 days (IQR 140-857). Nearly half of patients suffered a seizure (18/38) and the seizures were difficult to control in 9/18. Four patients suffered their first seizure during initial hospitalization. For 14/18, the first seizure occurred after or around cranioplasty and mostly at home. Perioperative seizure prophylaxis was variable and did not influence seizure occurrence. Older age showed a trend towards increased seizure risk (log rank p=.09). Neither gender, race, severity, location or hemorrhagic transformation were associated with development of post-stroke seizures. Modified Rankin Scale score (mRS) at discharge was 4 or above in all patients. By last follow-up, 17/38 patients had a mRS of 3 or better. Patients who suffered a seizure did not feel well prepared for the possibility of PSS, and for some the seizures were considered a major setback. Among those who responded to the questionnaire (n=14, 12 had seizures), all would have wanted to know whether or not they were at high risk for developing PSS, and would have opted to take anti-epileptic medications for seizure prophylaxis.

Conclusions
The frequency of seizures after malignant MCA stroke requiring decompressive hemicraniectomy is higher than expected, and the seizures often difficult to control.
Abstract 170: Pharmacological Stroke Prophylaxis and Correlates among Patients with Atrial Fibrillation: The US National Health and Wellness Survey
Authors: Goren Amir , Liu Xianchen , Gupta Shaloo , Simon Teresa A. , Phatak Hemant
Published: March 2022

Purpose:
To describe pharmacological stroke prophylaxis and identify patient characteristics associated with vitamin K antagonist (VKA) and/or aspirin (ASA) use among adult patients with atrial fibrillation (AF).

Methods:
Data were analyzed from the 2009 U.S. National Health and Wellness Survey, a self-administered, internet-based epidemiological study of a nationwide sample of 75,000 adults (aged 18+) stratified by gender, age, and race/ethnicity. Included were a total of 1,290 participants (1.72%) who checked AF diagnosis among their condition(s) that have “been diagnosed by a physician” (mean age=64.9 years, 65% male). AF patients were asked about their current treatments for AF or stroke prevention. Stroke prophylaxis patterns were identified as VKA only (VKA), ASA only (ASA), both VKA and ASA (VKA+ASA), and no VKA or ASA (non-VKA/ASA). Logistic regressions were used to examine factors associated with prophylaxis patterns, including demographics, health insurance, smoking, exercise, alcohol use, body mass index (BMI), modified Charlson comorbidity index , and CHADS
2
score (0, 1, or 2+).

Results:
Among AF participants, 343 (26.6%) were treated with VKA, 445 (34.5%) with ASA, 199 (15.4%) with VKA+ASA, and 303 (23.5%) with neither. Compared with non-VKA/ASA users, VKA or ASA users were more likely to be male, older, obese, and have a higher CHADS
2
score. Compared with VKA users, ASA users were younger and had more comorbidities. Multivariate logistic regression models showed that, compared with non-VKA/ASA use, obesity (OR=2.03, p=0.02), being married (OR=3.24, p=0.02), and male gender (OR=2.00, p=0.002) were associated with VKA+ASA use, and CHADS
2
≥1 was associated with VKA or ASA use (OR≥1.69, p≤0.017). Comorbidities were associated with ASA versus VKA use (OR=1.68-3.79, p≤0.01). CHADS
2
score was not associated with VKA versus ASA use (p>0.4).

Conclusions:
More than half of AF patients were not treated at all (23%) or treated with ASA only (34.5%) for stroke prevention. While older age, male gender, obesity, and stroke risk were associated with VKA or ASA treatment, CHADS
2
score was not related to VKA versus ASA treatment. Further study is needed to examine the clinical and economic consequences of VKA and ASA treatment among AF patients in a real-world setting.