bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2675: Acute Curcumin Treatment Reduces Cerebrovascular Injury and Neurological Deficit in Stroked Type 2 Diabetic Rats
Authors: Cobbs Aisha , Li Weiguo , Prakash Roshini , Ergul Adviye
Published: March 2022

Background:
Curcumin, a derivative of the rhizome
Curcuma longa
, has antioxidant, anti-inflammatory, and anti-apoptotic properties that make it an attractive potential threrapeutic agent for acute ischemic stroke. Studies using curcumin have shown that it provides neuroprotection when administered prior to focal cerebral ischemia or within 30 min to 1h after middle cerebral artery occlusion (MCAO) in normoglycemic animals. We previously reported that 3 h MCAO followed by 21 h reperfusion induces greater edema, hemorrhage, and neurological deficits in type 2 diabetic rats when compared to normoglycemic controls. Therefore, the goal of this study was to test the hypothesis that curcumin, when administered at recanalization, will decrease neurovascular injury, incidence of bleeding, and improve functional outcome in diabetic rats.

Methods:
Focal ischemia was induced by 3 h MCAO and 21 h reperfusion in sham, untreated, and curcumin-treated groups (n=5-7 per group). A single dose of curcumin (250 mg/kg, i.p.) or vehicle (EtOH + ethyl oleate) was administered at recanalization in control or diabetic (Goto-Kakizaki) rats. Percent (%) infarct, edema ratio (edema/infarct), and incidence of macroscopic bleeding was assessed in all groups. Neurological tests were performed at baseline and 23 h after MCAO to assess locomotor ability (beam walk), grip strength, and the presence or absence of postural reflexes (circling, resistance to push, forearm flexion, and hindlimb extension).

Results:
Within the untreated groups, % infarct was greater in controls (57.7±5.8% vs. 9.1±1.0%), while edema ratio was greater in diabetic animals (1.8±0.2 vs. 0.2±0.03). Bleeding was present in the ischemic hemispheres of all diabetic rats and in 43% of the controls. Compared to controls, neurological deficits were greater in diabetic animals after focal ischemia (p<0.05). Curcumin reduced % infarct in controls (30.0±9.9% vs. 9.8±1.8%) and improved edema ratio in diabetic rats (0.7±0.05 vs. 0.2±0.04). Curcumin also reduced the incidence of bleeding in both control and diabetic animals (20% vs. 50%). Incidence of pathological postural reflexes in both control and diabetic animals was decreased following curcumin treatment however it did not improve beam walk scores or grip strength in either group (p<0.05). Vehicle-treated animals were similar to untreated controls at all endpoints.

Conclusion:
Curcumin provides protection against infarct in normoglycemic animals and vascular protection in diabetic animals when administered at recanalization, suggesting that its use as a therapeutic agent at this clinically relevant time point may be beneficial in both groups but through different mechanisms. Additional long-term studies are needed to determine whether acute curcumin treatment at recanalization is sufficient to improve locomotor ability and grip strength deficits beyond 24 h post-MCAO.
Abstract 27: Antioxidant Carbon-based Nanomaterials:
In-vitro
Protection and
In-
vivo Effects on the Neurovascular Unit
Authors: Kent Thomas A , Bitner Brittany R , Berlin Jacob M , Robertson Claudia R , Marcano Daniela C , Fabian Roderic H , Pautler Robia G , Tour James M
Published: March 2022

Introduction:
Dysfunction of the cerebrovasculature, manifested by poor reperfusion and loss of autoregulation, is a feature of ischemia and traumatic brain injury (TBI). Oxidative stress is implicated in this effect. Conventional antioxidants have not proven clinically effective. Nanomaterials are an emerging class of antioxidants with potential advantages including quenching of oxidative radicals without need for enzymatic transformation.

Objectives:
We tested whether the carbon nanomaterials, poly(ethylene gylcol)-functionalized hydrophilic carbon clusters (PEG-HCCs) are antioxidants and determined their effect on the cerebrovasculature following mild experimental TBI and hypotension.

Methods:
HCCs were generated by treating single wall carbon nanotubes with oleum and nitric acid. HCCs were functionalized with PEG via coupling to carboxcylic acids. The ability to quench superoxide anion (SO) was determined in solution and b.End3 cultured brain endothelial cells after administering the electron chain transport inhibitor Antimycin A (AntA) using dihydroethidium (DHE) fluorescence flow cytometry.
In-vivo
studies were performed in Long Evans rats following mild TBI (3m/s; 2.5 mm deformation; 80 ms duration) and 50 mins. hemorrhagic hypotension followed by resuscitation with Lactated Ringers (
Figure
:
Resus
) then by shed blood (
Hospital
). Treatment with 2 mg/kg PEG-HCCs in 1 mL or PBS was initiated prior to the “Hospital” phase. Laser Doppler perfusion (LDF) was measured to 6 hours post-TBI.

Results:
DHE fluorescence induced by AntA was eliminated by post-treatment with PEG-HCCs (2-4 mg/L; 15 min post-AntA). At that concentration, there was no innate toxicity in cells determined by clonogenic and trypan blue assay. Only pre-treatment with a 10X excess of SO dismutase (SOD) achieved comparable DHE effect. PEG-HCC post-treatment improved cell survival after a higher dose of AntA, to 65% of baseline compared to 23% for SOD.
In-vivo
following TBI, hypotension reduced relative LDF to approximately 30% (
Fig
). Administered just prior to shed blood nanotubes restored LDF to 100% of baseline while the vehicle group remained significantly lower at 56%. LDF declined in all groups over time.

Conclusions:
PEG-HCCs are biocompatible with b.End3 cells and rapidly protected these cells from oxidative stress. PEG-HCCs at a clinically realistic time point improved cerebrovasculature dysfunction post-TBI/hypotension. The duration of effect is consistent with blood half life after a single dose. Longer term dosing studies are underway to establish the effect on outcome and reperfusion injury.
Abstract 2700: What Is The Expected Distribution of Ischemic Stroke Severity? Population-based Estimates of NIHSS From The Cincinnati/Northern Kentucky Stroke Study.
Authors: Reeves Mathew J , Khoury Jane , Alwell Kathleen , Moomaw Charles J , Flaherty Matthew L , Woo Daniel , Khatri Pooja , Adeoye Opeolu , Ferioli Simona S , Kissela Brett M , Kleindorfer Dawn
Published: March 2022

Background:
There is little data concerning the distribution of stroke severity in contemporary ischemic stroke populations. Changes in the prevalence of stroke risk factors, as well as in the secondary prevention of stroke could be expected to influence the distribution of stroke severity at the population level . The collection of National Institute of Health Stroke Scale (NIHSS) data are frequently missing in clinical registries, and more complete data are often limited to clinical trial settings which typically include a select patient sample. We describe the distribution of NIHSS across major demographic sub-groups in a nationally representative, population-based study of ischemic stroke.

Methods:
Within a biracial population of 1.3 million, all strokes among area residents in 2005 were ascertained by screening discharge records at local hospitals and clinics. A sampling scheme was developed to ascertain additional cases in physician offices and nursing homes. All confirmed ischemic stroke cases underwent comprehensive chart abstraction, including generation of a retrospective NIHSS score (range 0 - 42), which described symptom severity on presentation. Descriptive statistics of NIHSS (median, IQR) were generated by demographic subgroup and surveillance location (hospital admission, in-hospital stroke, or out-of-hospital). To account for the sampling design and multiple stroke events within some subjects, statistically significant differences were tested using age-adjusted GEE-based linear models.

Results:
There were 2210 ischemic stroke cases identified during the 12-month study period. The overall median NIHSS score was 3.0 (IQR 1.0 - 7.0). The distribution of NIHSS by age, sex, race, and surveillance source are summarized in the
Table
. NIHSS score was statistically significantly higher in older age groups, and also differed significantly by surveillance location. There were no significant differences in NIHSS by sex or race.

Conclusions:
More than half of all ischemic stroke cases have mild symptom severity upon initial presentation (i.e., NIHSS < 5). Ischemic stroke severity increases with age and, as expected, varies greatly depending on the location where cases are first identified. Given the potential for secular changes in the natural history of ischemic stroke severity, the monitoring of NIHSS across population sub-groups and by time represents a legitimate target for population-based surveillance efforts.
Abstract 2703: In-hospital Versus Out-of-hospital Stroke Treated With Iv Tpa And 3 Month Outcomes.
Authors: Bruce Nhu , Raman Rema , Ernstrom Karin , Ovbiagele Bruce , Meyer Dawn M , Meyer Brett C , Hemmen Thomas M
Published: March 2022

Background:
Most hospitals set up Code Stroke alert teams in the Emergency Departments. Expanding sufficient Code Stroke coverage to in-hospital areas requires additional resources, often through Neuro-hospitalist teams. Most data on outcomes after stroke are based on out-of-hospital stroke. We evaluated the outcomes of patients with stroke that occurs in the hospital versus out-of-hospital.

Methods:
We included all adult patients with Code Stroke alerts, diagnosis of acute ischemic stroke, who had 90-days post Code Stroke modified Rankin Scale from the UCSD SPOTRIAS database (2004 to 2011) and excluded patients transferred from acute care facilities. The patients were 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, 90-day modified Rankin Scale (mRS) and adjusted for multiple co-variables. Symptomatic intracranial hemorrhage (SICH) was defined as ≥4 point increase in NIHSS and ICH that was deemed the cause of the clinical change.

Results:
We identified 590 Code Stroke alerts; 563 in group 1 and 27 in group 2. Baseline demographics were balanced, except group 2 patients younger (64.26±16 vs 70.2±15.5 years of age, p=0.0497) and were more likely to be Hispanic (29.6 vs 14.2%, p=0.047). IV tPA was given in 13/27 (48.2%) patients in Group 2 and 266/563 (47.3%) in Group 1 (NS). Anticoagulation was the reason for exclusion in 4/14 (28.6%) of patients in Group 2 vs 18/266 (6.5%) (p=0.017). The frequency of other diagnoses and reasons for exclusion were similar between groups. The time from stroke onset to tPA treatment in group 2 was 135.1±57.9 vs 151.4±121.2 min (NS). A 90-day mRS of 0 or 1 was achieved in 9/27 (33.3%) patients in Group 2 and 221/563 (39.3%) patients in Group 1 (NS); in tPA treated patients: Group 2 3/13 (23.1%), Group 1 83/266 (31.2%) (NS). SICH occurred in the tPA treated patients: Group 2 1/13 (7.7%); Group 1 9/266 (3.4%) (NS).

Conclusion:
We identified a relatively small group of ischemic stroke patients with in-hospital onset. In those patients, however, rates of tPA use and outcomes were similar to out-of-hospital stroke.
Abstract 2706: Patients with the Malignant Profile Within 3 Hours of Symptom Onset have Very Poor Outcomes Following IV tPA Therapy
Authors: Inoue Manabu , Mlynash Michael , Straka Matus , Lansberg Maarten , Bammer Roland , Albers Gregory W
Published: March 2022

Background:
The “Malignant profile” is an MRI pattern that is associated with poor outcomes (mRS 5-6) following reperfusion in the 3-6 hr time window. The aim of this study was to estimate the incidence and prognostic implications of the Malignant profile, as identified by CT perfusion (CTP), in patients treated with tPA <3 hrs from stroke onset.

Methods:
Consecutive patients treated with iv tPA at the Stanford Stroke Center from May 2009 to May 2011 who had CTP performed prior to tPA therapy, and within 3 hrs of symptom onset, were included. Perfusion data were acquired in cine mode on 16 and 64-row CT scanners; 2 separate scans were done yielding either 4 cm or 8 cm coverage depending on the scanner type. The incidence of the Malignant profile, based on the previously published definition of a Tmax >8 sec perfusion lesion > 85 mL, was assessed using a fully automated software program (RAPID). This program also estimates the infarct core based on cerebral blood flow (rCBF) and cerebral blood volume (rCBV) thresholds <30% of the contralateral hemisphere. Poor outcome was defined as a mRS of 5-6 at 30 days. A receiver operating characteristic (ROC) curve analysis was done to identify Tmax and core volume thresholds that optimally define the Malignant profile (high specificity for poor outcome).

Results:
121 patients were treated with iv tPA. Of these, 42 patients had an interpretable CTP performed within 3 hrs of symptom onset. Mean age was 75±14 years and median (IQR) NIHSS was 13 (6-19). Five patients (11%) met the pre-specified criteria for the Malignant profile and all 5 died during the acute hospitalization. ROC analysis determined that the optimized criteria were either a PWI Tmax >8 sec lesion >86 mL or an infarct core >53 mL (both criteria had 100% specificity and 56% and 67% sensitivity respectively). The optimized criteria identified 6 patients as Malignant (14%). The poor outcome rate in these patients was 100% vs. 8.3% in the 36 patients non-malignant patients (p<0.001).

Conclusion:
The incidence of the Malignant Profile is about 10-15% in tPA eligible patients imaged within 3 hrs of symptoms onset. The clinical outcome of these patients is very poor despite iv tPA therapy. This finding is consistent with data from patients treated with iv tPA in the 3-6 hr window. Further study is warranted to verify if CTP can reliably identify a subgroup of patients who do not benefit from iv tPA within 3 hours.
Abstract 2751: Cost-effectiveness of Carotid-Artery Stent Placement versus Endarterectomy in Patients with Carotid Stenosis
Authors: Khan Asif A , Chaudhry Saqib A , Sivagnanam Kamesh , Hassan Ameer E , Suri M. F , Qureshi Adnan I
Published: March 2022

Introduction:
The Stenting versus Endarterectomy for treatment of carotid stenosis trial (CREST) demonstrated that the risk of the composite primary outcome of stroke, myocardial infarction (MI), or death did not differ significantly in the average surgical risk patients undergoing carotid-artery stent placement (CAS) and those undergoing carotid endarterectomy (CEA). However, the cost associated with CAS may limit its broad applicability.

Objective:
To determine the cost-effectiveness of CAS with emboli-protection device versus CEA in average surgical risk patients with moderate-severe carotid stenosis.

Methods:
The probability of primary endpoint was obtained from the results of the CREST trial. The quality-adjusted life year (QALYs) associated with each treatment modality were estimated by adjusting for the incidence of each quality adjusted outcome (QALY weights of ipsilateral stroke, MI, death and post-procedure QALYs). Total cost associated with each intervention was derived from hospitalization cost and cost associated with primary endpoints including stroke, MI and death in each group. Costs are expressed in US dollars accounting for inflation up to October 2010. Incremental cost-effectiveness ratios (ICERs) were estimated for the four year period following the procedure. All values are expressed as means and 95% percentile intervals.

Results:
The estimated net costs for patients after treatment with CAS and CEA after consideration of primary endpoint were $ 18,335 and $ 13,276, respectively from definitive pre-simulation analysis. Post simulation values were $19,210 ($18,264- $ 20,156) and $14,080 ($13,076 - $15,084). Overall QALYs for the CAS and CEA groups were 0.712 and 0.702 respectively (ranging from 0.0 meaning death to 0.815 meaning no adverse events). The estimated ICER for CAS versus CEA treatment was $229,429.

Conclusions:
Although, the CREST demonstrated equivalent results with CAS (compared with CEA) in average surgical risk patients with severe carotid stenosis, broad applicability of CAS might be limited by the higher cost associated with this procedure.
Abstract 2782: Prospective Multicenter Study On Prevention Using Cilostazol From Acute Stroke Progression: Kumamoto Pentagon Study
Authors: Hirano Teruyuki , Yonehara Toshiro , Terasaki Tadashi , Takita Tomohiro , Hashimoto Yoichiro ,   Kumamoto-PENTAGON study group
Published: March 2022

Background and purpose:
About 20% of patients with acute ischemic stroke experience symptom progression resulting in poor outcome. We have evaluated the effect of cilostazol compared with aspirin on preventing acute symptom progression, and on clinical outcome.

Methods:
A multi-center, open, randomized, prospective comparative study conducted from April 2009 to March 2011. Inclusion criteria: non-cardioembolic ischemic stroke admitted within 48 hours of onset, neurologically stable, and with written informed consent. Exclusion criteria: contraindicated or previous exposure to aspirin and/or cilostazol. Patients were administered either cilostazol 200 mg daily (group C) or aspirin 200 mg daily (group A) within 48 hours of onset. Primary endpoint: occurrence of acute symptom progression (ΔNIHSS ≥2) within 7 days. Secondary endpoints: 3-month outcome (mRS 0-2), occurrence of vascular events (ischemic stroke, brain hemorrhage, myocardial infarction), bleeding events, and other adverse events. UMIN Clinical Trial ID: UMIN000004016.

Results:
In total, 209 patients (126 men, 71.2 years, NIHSS median 3) were recruited. After excluding 11 patients with a final diagnosis of cardioembolic stroke or stroke mimics, 104 and 94 patients were allocated to group C and group A, respectively. No statistical differences in clinical backgroud were observed between the groups. Acute symptom progression was observed 10 patients each in group C (9.6%) and group A (10.6%) (n.s). mRS 0-2 at 3 months was achieved in 84.4% (54/64) of group C and 69.1% (38/65) of group A (p=0.07). Subgroup analysis showed that patients with small vessel occlusion (preictal mRS ≤2, n=80) had better clinical outcome with cilostazol (p=0.03). No vascular or bleeding events occurred except for one intraabdominal bleed in group C. One patient in group C experienced headache. Liver dysfunction was reported one each patient in groups A and C.

Conclusions:
Effect of cilostazol on preventing symptom progression was comparable with that of aspirin. Cilostazol is one option for acute stroke therapy, especially for patients with small vessel occlusion.
Abstract 2791: Bone Marrow Derived Mononuclear Cells Are Neuroprotective By Modulating Microglia In A Rodent Model Of Ischemic Stroke
Authors: Yang Bing , Xi Xiaopei , Savitz Sean.I
Published: March 2022

Background:
Bone marrow mononuclear cells (MNCs) are an investigational, autologous cell-based therapy for acute ischemic stroke. These cells are easily obtained by bone marrow harvest and exert neuroprotective and immunomodulatory effects in the injured rodent brain after stroke. We have investigated a new mechanism in which MNCs exert neuroprotective effects by modulating microglia.

Methods:
Microglia and neurons were isolated and cultured from E20 pregnant rats. Microglia were activated by oxygen-glucose deprivation (OGD) and then were cultured with neurons (n=4). At the time microglia were placed into culture with neurons, bone marrow MNCs or media vehicle was injected directly into the co-cultures or placed in transwells with the neuron-microglia cultures. The number of NeuN positive cells was quantified at 24 hrs afterwards. In another experiment, adult rats were subjected to middle cerebral artery occlusion for 90 minutes, and then treated with autologous bone marrow MNCs or saline IV at 24 hours after stroke (N=5). Three days later, brain samples were analyzed by immunohistochemistry to investigate the microglial response.

Results:
Adding activated microglia to neuronal cultures resulted in 36.2%±1.8% neuronal survival while adding non-activated microglia led to 85.1±15.6% neuronal survival (
p
=0.001). Treatment with MNCs improved survival of neurons cultured with activated microglia to 64.0%±19.9% (
p
=0.037) compared with neuronal-microglia cultures treated with media vehicle alone (36% neuronal survival). However, MNCs in transwell did not alter neuronal death as there was 31.9%±11.7% neuronal survival in co-cultures with activated microglia. All data were normalized to controls. In the
in vivo
study, there were significantly more OX-42 positive microglial cells in the peri-infarct area from animals treated with MNCs compared with saline treatment (43±3.9 vs.29±3.1 per high power field,
p
<0.05). However, the percentage of iNOS positive cells among OX-42 positive cells was less in the same regions from animals treated with MNCs compared with saline treatment (9.1%±1.1% vs. 61.5%±7.8%,
p
<0.05). There were also significantly more cells co-stained with Iba-1 and SDF-1α (13.8±1.5 vs. 7.4±0.8,
p
<0.05) in the peri-infarct region of animals treated with MNCs compared with saline controls.

Conclusion:
MNCs administered 24h after stroke increase the number of microglia in the peri-infarct area. MNCs decrease the number of pro-inflammatory microglia and increase the number of SDF-1a expressing microglia. Furthermore, MNCs reduce microglial-mediated neurotoxicity
in vitro
. Thus, the results of these studies suggest that MNCs may exert cytoprotective effects in animal models of stroke by modulating microglia. MNCs may protect neurons not only by directly reducing microglial toxicity but also by upregulating neuroprotective microglia in the post-ischemic brain.
Abstract 28: Detrimental Effect of Leptin on Intracerebral Hemorrhage via STAT3 signal pathway
Authors: Kim Chi K , Lee Seung-Hoon , Ryu Wi-Sun , Oh Mi-Young , Kim Beom J , Ko Sang-Bae , Yoon Byung-Woo
Published: March 2022

Background:
Leptin, one of the most alleged adipokines, is a key regulator of energy balance and body weight. Leptin exerts its tissue protective effect in ischemic injuries via anti-apoptotic mechanisms. However, few studies have elaborated on the association between leptin and tissue damages in intracerebral hemorrhage (ICH).

Methods:
We induced ICH in ICR mice via the infusion of collagenase, and recombinant leptin or PBS was administered intraperitoneally. To determine the effects of leptin deficiency, ICH-induction was done in wild-type (WT) or leptin-deficient

Lep
ob
/Lep
ob

(
ob/ob
) mice. Brain water content, reflecting peri-hematomal edema, and hemorrhage volume were measured at 72 hours. The number of inflammatory cells (OX6-positive cells) was measured at 48 hours, and western blotting was performed at 24 hours. To identify the role of STAT3, a phosphorylated-STAT3 (pSTAT3) inhibitor,
NCS74859
, was administered after inducing ICH in hyperleptinemic mice. To localize the working site of pSTAT3, we performed double-staining with a pSTAT3 antibody and a marker of neuron, astrocyte, or macrophage.

Results:
We compared two doses of leptin and the brain water contents were increased dose-dependently (ρ=0.53, p<0.01). The water contents were 81.5±0.2% in leptin-injected group (8 mg/kg) and 80.1±0.3% in control group (p<0.01). The water content of
ob/ob
mice was decreased, compared to WT mice in hemorrhagic hemispheres (WT mice: 79.7±0.6%,
ob/ob
mice: 78.8±0.6%; p<0.05). Mean hemorrhage volumes were not different respectively between
ob/ob
and WT mice, and between leptin-injected and control groups. The leptin-injected group exhibited a higher number of OX6-positive cells (leptin-injected group: 129±13 cells/mm
3
; control group: 88±10 cell/mm
3
; p<0.05). Western blotting revealed that the exogenous-leptin had affected an increase in the levels of pSTAT3, and the relative optical-density was higher, by 1.8-fold, in leptin-injected group than in control group (p<0.05). After inhibiting pSTAT3 using
NSC74859
, the brain water content of pSTAT3-inhibiting group was decreased, compared to non-inhibiting group (pSTAT3-inhibiting group: 79.8±0.8%, non-inhibiting group: 81.5±0.2%; p<0.05). Ox6-positive cells were co-localized by pSTAT3, but in neurons and astrocytes, pSTAT3 was not detected.

Conclusion:
Our study documented that peri-hematomal edema and inflammation were increased by leptin via STAT3 signal pathway. These results may indicate the potentially detrimental role of leptin on ICH.
Abstract 2800: Focal Dorsolateral Basal Ganglia Lesions Impair Identification Of Facial Emotions Signaling Threat
Authors: Jaillard Assia , Naegele Bernadette , Saint Martin Magali , Zeffiro Thomas A , Hommel Marc J
Published: March 2022

Background:
Survival may depend on the ability to efficiently identify threats signaled by the emotional content of facial expressions. While current neural models of facial emotion processing do not prominently feature the basal ganglia, evidence from clinical and functional imagi¬ng studies suggest involvement of the ventral striatum.

Methods:
To assess the specific role of the basal ganglia in emotion processing, we compared basic facial emotion identification in 23 young patients with a pure focal basal ganglia stroke (mean age 44.9 ± 11.6; 10 males) to 68 matched healthy controls (43.8 years ± 14.0; 27 males). We used quantitative MRI lesion analysis to assess the relationship between basal ganglia location and basic emotion identification. To assess whether facial emotion identification might be related to non-specific lesion effects, we also assessed a wide range of cognitive and motor abilities and screened participants for co-morbid conditions such as depression or anxiety. In addition, we assessed social behavior in terms of social adaptability and the ability to return to work.

Results:
(1) Basic emotion identification was impaired following focal lesions limited to the basal ganglia. (2) The identification impairment was limited to threat-related emotions, including anger, fear and disgust identification, suggesting a role for the basal ganglia in threat detection. These findings may reflect altered gating mechanisms for facial emotion displays conveying threat signals, with the basal ganglia selecting information relevant to safety. (3) We found that emotion identification impairments adversely affect social behavior, suggesting that emotion identification skills may be of substantial practical importance, and should be considered in the clinical assessment and rehabilitation of patients with basal ganglia lesions.

Conclusions:
Dorsolateral striatal lesions may affect threat-related emotion identification by disrupting limbic basal ganglia-thalamocortical loop functions associating threat detection with selection of appropriate escape or defensive actions that can preserve individual safety. From a clinical perspective, while the impact of emotion identification impairment on social behavior should be more thoroughly examined in further studies, the consequences of basal ganglia damage appear to be detectible at the individual level.

Figure legend:

Lesion overlap for patients with identification impairments for anger (red); fear (blue) disgust (green) and all threat emotion (yellow).
Abstract 2811: Effects of EMS Routing to Stroke Centers and Participation in a Prehospital Neuroprotective Trial on Door to Needle Times for IV tPA
Authors: Kim-Tenser May A , Sanossian Nerses , Liebeskind David S , Starkman Sidney , Eckstein Marc , Pratt Franklin D , Stratton Sam , Conwit Robin , Hamilton Scott , Saver Jeffrey L
Published: March 2022

Introduction:
IV tPA is an effective therapy for acute ischemic stroke and better outcomes occur with earlier lytic start. Prehospital initiation of neuroprotective therapies may stabilize penumbral tissue until reperfusion occurs. Prehospital neuroprotective treatments might modify start times of thrombolysis, including accelerating start by galvanizing receiving stroke teams or delaying start by requiring greater care time in the field. Door to needle (DTN) times are a target of improving stroke care nationwide with a goal of <60 minutes according to guidelines.

Hypothesis:
Participating in prehospital research does not delay appropriate thrombolysis and may actually improve treatment times by focusing attention and local resources on eligible patients. We expect primary stroke centers (PSC) to have shorter DTN times.

Methods:
We analyzed consecutive patients enrolled in the Field Administration of Stroke Therapy - Magnesium (FAST-MAG), phase 3, NIH-sponsored trial of magnesium sulfate started prehospital within 2h of symptom onset. Parameters examined in IV tPA treated patients included: time from ED arrival to IV tPA start (DTN), type of hospital (PSC/non PSC), enrollment before and after start of LA EMS policy routing patients directly to PSCs, and arrival in ED within 60 minutes of last known well time (LKWT).

Results:
Among the first 1324 enrollments, 300 received IV tPA and 292 had complete data of LKWT’s and tPA initiation times. Mean DTN was 88.7 minutes with 290 (99%) treated in the 3h and 2 (1%) treated in the 3-4.5 hour time window. Overall, DTN <60 minutes was 17% and 55% received tPA ≤ 90 minutes from ED arrival. DTN times were faster (79 vs. 96 min, p<0.0001) and a greater proportion received treatment ≤ 90 minutes (72% vs. 46%, p<0.0001) in hospitals that were PSCs at the time of enrollment. DTN within 60 minutes in PSC vs. non PSC was 27% vs 11%, P=0.001. Overall onset to tPA initiation was reduced at PSC hospitals (147 vs. 156 min p=0.046). Trialwide, DTN times were reduced after implementation of a countywide PSC triage system in November of 2009(84 vs. 92 min, p=0.024).

Conclusions:
Acute stroke patients can be enrolled in a prehospital treatment trial without delaying start of IV tPA compared with national norms. Compared with non-PSC hospitals, certified hospitals achieved shorter door to needle times and faster overall onset to needle times when administering thrombolytic stroke therapy.
Abstract 2818: Safety, Feasibility and Signal of Activity of Intra-carotid Allogenic Mesenchymal Stem Cell therapy in a Large Animal Stoke Model
Authors: Yavagal Dileep R , Lewis Natashia N , Amatangelo Steven , Garza Phillip , Giannini Alessandra , Pham Tienlong , Raval Ami P , Cesar Lillian , McNiece Ian , Hare Joshua
Published: March 2022

INTRODUCTION:
Promising pre-clinical data shows benefits of intra-carotid allogenic mesenchymal stem cell (MSCs) therapy in ischemic stroke (IS) in small animal stroke models. Intra-carotid (IC) delivery of MSCs may be superior to intravenous (IV) delivery. However, due to the large size (15-50 microns) of MSCs, there is a concern that they may cause microvascular occlusion during IC administration. There is a need for large animal experiments to confirm positive results in small animal models as has been recommended by STAIR and STEPS consortia.

HYPOTHESIS:
We tested the hypothesis that IC administration of allogeneic mesenchymal stem cells (MSCs) is feasible and safe in a large animal (canine) stroke model..

METHODS:
We performed 1-3 hrs of reversible middle cerebral artery occlusion (rMCAo), in10 female mongrel dogs weighing 40-60 lbs, using an endovascular retrievable coil occlusion of the MCA with a transfemoral arterial approach. At 1 - 72 hrs after rMCAo, animals were assigned to the following treatment groups: A. IC saline placebo (saline) or B. IC allogeneic MSCs or C. IV allogeneic MSCs. Primary outcome measures were: development of angiographic occlusion post-IC MSC or saline infusion, change in MRI infarct volume or new ischemic lesions, and neurological deficit score (NDS) at 4 weeks. Dosing of MSCs was based on extrapolated maximum tolerated dose calculated in a rat study of IC MSCs in our laboratory.

RESULTS:
Successful IC administration of MSCs was possible in all animals assigned to the treatment group. Animals receiving IC MSCs at 1× 10^6 or 10 × 10^6 (n=6) there were no clinical adverse events or neurological worsening during or 4 weeks post treatment. There were no angiographic decreases in flow or occlusions during or after IC MSC delivery. In the two animals with additional TCD monitoring during IC MSC delivery there were no changes in flow velocity or HITS signals indicating emboli. There was no worsening in MRI infarct volume (
Fig 1
.) amongst the IC MSC groups. A dramatic decrease in infarct volume was noted, in 2 animals in the IC MSC group with minimal infarct related atrophy at one month. None of the animals in the IV MSC or IC saline groups (n=2 in each group) showed a significant change in MRI infarct volume, and major infarct related atrophy was noted.

CONCLUSION:
IC MSC administration in a large animal rMCAo model is feasible & safe.
Fig1
: In vivo coronal MRI FLAIR sequences in IC delivery of MSCs in canine stroke model. There is a signal of biologic activity seen with IC MSC delivery. A. Baseline infarct at 48 hours after rMCAo. B. Infarct evolution at 29 days after IC administration of 10×10^6 MSCs.
Abstract 2836: Emergency Department Nursing Shift Change and Adverse Outcomes in Patients with Intracranial Hemorrhage
Authors: Jones Erica M , Boehme Amelia K , Albright Karen C , Aysenne Aimee , Chang Tiffany , Burns Christopher , Beasley T. Mark , Martin-Schild Sheryl
Published: March 2022

Introduction:
Extended time in the emergency department (ED) has been related to adverse outcomes among stroke patients. Previous research reported higher rates of pneumonia and poorer outcomes in ischemic stroke patients present during an emergency department nursing shift change (SC). We examined the association between SC and adverse outcomes in patients with intracerebral hemorrhage (ICH).

Methods:
Data were collected on all spontaneous ICH patients admitted to Tulane Medical Center from 7/1/08-12/31/10. Records were reviewed for pertinent times, demographics, and clinical variables. Baseline characteristics were evaluated using Chi-square and t-tests with non-parametric methods used when appropriate. Outcomes were compared between patients experiencing an ED SC and those that did not experience SC. Frequency of pneumonia, modified Rankin Scale (mRS) score at discharge, NIHSS score at discharge, and mortality rate were examined using linear regression, logistic regression, and cumulative logit models adjusting for potential confounding variables.

Results:
Of the 110 patients, 41(36.9%) were present in the ED during a SC. Patient demographics and clinical data are provided in Table 1. The frequency of pneumonia was similar in the two groups. Exposure to an ED SC was not a significant independent predictor of discharge mRS (p=0.75), discharge NIHSS (p=0.49), or mortality (OR 1.24, 95% CI 0.41-3.77, p =0.70). Length of stay in the ED dichotomized into <5 hours and ≥5 hours was not a significant independent predictor of death (OR=0.590, 95%CI 0.201-1.733, p=0.337), discharge mRS (OR=0.566, 95%CI 0.263-1.218, p=0.1456) or discharge NIHSS (OR=0.602, 95%CI0.128-1.966, p=0.4003).

Discussion:
Our study found no association between nursing SC and adverse outcome in patients with ICH. We speculate that our findings in ICH differ from findings in ischemic stroke due to head of bed positioning recommended for each type of stroke.
Abstract 2852: Hyperdense MCA Sign- Objective Criteria for Measurement
Authors: Mittal Manoj , Seet Raymond , Yi Zhang , Rabinstein Alejandro
Published: March 2022

Background and Objective
Hyperdense middle cerebral artery (HDMCA) sign is an early sign seen on CT head after acute ischemic stroke indicating acute arterial thrombosis. We aimed to measure HDMCA sign objectively.

Methods
We conducted a retrospective analysis of prospectively collected data from 151 cases of acute ischemic stroke eligible for IV rt-PA by time criteria, admitted to Mayo Clinic from March, 2002 through June, 2011. Admission CT Head was studied to identify HDMCA sign. All patients had either 24 hour CT head or MRI head to confirm the stroke in the same vessel territory. MCA was measured in Hounsfield units and was compared to the contralateral MCA. Receiver Operating Characteristic (ROC) curve analysis was performed to calculate sensitivity and specificity.

Results
Mean admission NIHSS score was 11±7. HDMCA sign was seen in 93 (62%) patients. ROC curve analysis for ipsilateral MCA Hounsfield units had an area under the curve 0.88 (p<0.001, CI 0.83-0.94) which showed 50 HU or more had 48% sensitivity and 98% specificity. Ratio of ipsilateral to contralateral MCA HU had an area under the curve 0.94 (p<0.001, CI 0.90-0.98) which showed ratio of 1.23 had 67% sensitivity and 98% specificity. A combination of either ipsilateral HU more than equal to 50 or a ratio of ipsilateral to contralateral MCA HU more than equal to 1.23 had 77% sensitivity, 95% specificity, 96% positive predictive value and 72% negative predictive value.

Conclusion
A combination of ipsilateral HU more than equal to 50 or a ratio of ipsilateral to contralateral MCA HU more than equal to 1.23 can objectively identify HDMCA sign with good sensitivity and high specificity.
Abstract 2859: Comparison Of Four-dimensional Ct Angiography (4d-cta) With Mra In Acute Ischemic Stroke Patients With Probable Internal Carotid Artery Occlusion
Authors: Miyazaki Yuichi , Mori Takahisa , Tajiri Hiroyuki , Iwata Tomonori , Nakazaki Masahito
Published: March 2022

Background and Purpose :
Emergency MR angiography (MRA) can provide useful information to find the internal carotid artery (ICA) occlusion in an acute stroke setting. However, the usefulness of four-dimensional CT angiography (4D-CTA) using 320 rows area detector CT remains uncertain for emergency diagnosis of cerebral vasculature in acute ischemic stroke. The aim of our retrospective study was to investigate whether or not there were some differences between 4D-CTA and MRA findings in acute ischemic stroke patients with probable internal carotid artery occlusion.

Materials and Methods :
Included for analysis were acute ischemic stroke patients 1) who were admitted to our institution within 48 hours of stroke onset from September 2010 to July 2011, 2) who underwent whole brain 4D-CTA within 24 hrs following emergency MRA on admission and 3) in whom the affected ICA was absolutely not visualized on MRA. We compared 4D-CTA findings with MRA findings. Result : During study period, 391 acute ischemic stroke patients were admitted within 48 hours from symptom onset and emergency MRA showed no visualization of the affected ICA in 36 of them. Among the 36 patients, 21 patients underwent 4D-CTA following MRA.4D-CTA demonstrated delayed antegrade flow of the affected ICA as time-sequence dynamic images in 9 of the 21 patients and the affected ICA supplied via collateral flow in one of them. In the rest, 4D-CTA could not visualize the affected ICA at all.

Conclusion :
In an acute stroke setting, 4D-CTA can provide more accurate information of the affected ICA which is absolutely not visualized in MRA.
Abstract 2869: Misdiagnosis Of Stroke Among IV tPA-treated Patients: A Two-year Experience In A Primary Stroke Center And Satellite Hospitals
Authors: Zand Ramin , Al-Wafai Ameer , Jacewicz Michael
Published: March 2022

Background:
In the setting of acute stroke, the decision to treat a patient with IV tPA is typically based on a brief pertinent history, neurological examination, urgent labs and head CT. Because “time is brain,” the evaluation is rushed and the diagnosis is occasionally erroneous. In this study we investigated the characteristics of patients who received IV tPA when the final diagnosis was not ischemic stroke.

Methods:
We conducted a retrospective study of 113 patients who presented from January 2009 to January 2011with acute stroke symptoms and received IV tPA either in our primary stroke center or one of the three satellite hospitals in our stroke network.

Results:
Of 113 patients, 23 had post-tPA negative diffusion weighted images (DWI) on MRI and a discharge diagnosis other than ischemic stroke. Other discharge diagnoses included: TIA (10 cases), complicated migraine (4 cases), post-ictal Todd’s paralysis (3 cases), conversion disorder (3 cases), and toxic/metabolic encephalopathy (3 cases). The misdiagnosis rate of stroke was higher in the satellite hospitals compared to our primary stroke center (39% vs. 11%; P<.0.001). The diagnosis of acute stroke in our satellite hospitals was made by an emergency department (ED) physician after a phone consultation with one of our stroke neurologists. Other differences between patients with and without final diagnosis of stroke included: mean age (61 vs. 52 years; P<0.02), median admission NIHSS score (11 vs. 6 points; P<0.001), psychiatric co-morbidities (3% vs. 17%; P<0.05), history of hypertension (84% vs. 56%; P<0.01), and mean length of hospitalization (11 vs. 6 days; P<0.001). There were two cases of uncomplicated gingival and nose bleeding at the time of tPA infusion among patients who did not have stroke.

Conclusion:
This study suggests that ED physicians working outside of the major stroke centers have difficulty distinguishing between stroke and its mimics. In the future, telemedicine may improve stroke diagnosis in satellite and rural hospitals. The results are also consistent with other studies that IV tPA causes relatively little harm in stroke mimics. Further study is warranted.
Abstract 2872: Should Recent Stroke Patients be Routinely Screened for Kidney Disease?
Authors: Ovbiagele Bruce
Published: March 2022

Background:
Since chronic kidney disease is a risk factor for the progression of cardiovascular disease, as well as recurrent cardiovascular events, a 2006 AHA Science Advisory recommends that all patients with cardiovascular disease be screened for evidence of kidney disease. Although several studies have related CKD as defined by a low estimated glomerular filtration rate (eGFR) to increased primary stroke risk, no studies have so far assessed the association of low eGFR with secondary vascular risk after stroke.

Objective:
To evaluate the role of baseline low eGFR as an independent predictor of vascular risk after occurrence of an index ischemic stroke.

Methods:
Observational analysis of multicenter trial data comprising recent ischemic stroke patients enrolled from September 1996 to May 2003 and followed for 2 years. Low GFR was defined as GFR < 60 mL/min per 1.73m2. We assessed the prevalence of high FCRS among only among subjects without known CHD. Association between baseline vascular risk factors and low eGFR were assessed using multivariable logistic regression. Cox models with and without competing risks were used to determine the relationship between low eGFR and outcome. The primary outcome was time to first stroke, myocardial infarction, or vascular death, and secondary outcome was time to first stroke.

Results:
Of 3673 subjects (99.8% of cohort) who with complete data, 34.3% had low eGFR. Subjects with low eGFR were significantly more likely to be female, of White race, older, have a history of prior stroke, CHF, diabetes, MI, hypertension, coronary bypass surgery or coronary angioplasty, as well as higher baseline systolic BP, total cholesterol and triglycerides compared to subjects with normal eGFR. On the other hand, subjects with low eGFR were significantly less likely to drink, smoke, or use antithrombotics at baseline compared to subjects with normal eGFR. In unadjusted analyses, low eGFR (vs normal eGFR) was associated with higher rate of the primary (HR=1.77, 95% CI: 1.48-2.13, p<0.001) and secondary (HR=1.35, 95% CI: 1.08-1.70, p=0.01) outcomes. After adjusting for confounders, low GFR was related to the primary outcome (HR=1.54, 95% CI: 1.27-1.86, p<0.001) but its association with the secondary outcome did not reach significance (HR=1.26, 0.90-1.78, p=0.179). There were no significant interactions between low eGFR and any of the covariates in predicting outcome.

Conclusions:
Baseline CKD is independently associated with a higher risk of secondary vascular events over 2 years among patients with a recent ischemic stroke. Consideration should be given to routinely screening all recent ischemic stroke patients for CKD. For those stroke patients with CKD, frequency of vascular events and progression of CKD might be ameliorated by prompt and appropriate intervention.
Abstract 2885: Predictors of Poor Outcome in Moderate to Severe Strokes in a Statewide Telestroke Network
Authors: Yaghi Shadi , Hinduja Archana , Keyrouz Salah G
Published: March 2022

Objective:
to determine the predictors of poor outcome after IV thrombolysis for moderate to severe strokes in a statewide telestroke network.

Background:
The Arkansas SAVES (Stroke Assistance through Virtual Emergency Support) telestroke network provided emergency evaluation and therapy for acute stroke to 22 spoke sites statewide between November 2008 and May 2011. The spoke hospitals range from large, yet lacking neurologist’s support, to critical access hospitals. Following thrombolysis, patients are cared for at the spoke, or get transferred to one of the hub PSC hospitals. Predictors of poor outcome after IV thrombolysis in a PSC are established. There is no available literature on such predictors in a hub and spoke model of a telestroke network, in which variables such as post thrombolysis care location could impact outcome.

Methods:
Institutional IRB approval was obtained to review the prospective database of the Arkansas SAVES program. We included patients with admission NIHSS ≥ 8. They were divided into two groups, based on 90-day outcome, dichotomized into mRS ≤ 2 and mRS > 2. Baseline characteristics, risk factors, time intervals, laboratory data, and post thrombolysis care location (hub vs. spoke) were compared between the two groups. For statistical analysis, we used independent T, and fisher’s exact tests. A multivariate logistic regression analysis was performed.

Results:
The cohort included 562 patients receiving a teleconsultation between November 2008 and May 2011, of whom 116 underwent IV thrombolysis. Sixty-seven patients with admission NIHSS ≥ 8 were included in this analysis. Results are depicted in table 1. In multivariate regression analysis (table 2), patients with a 90-day mRS > 2 were more likely to have atrial fibrillation (OR = 6.76, p = 0.038), admission blood sugar > 8 mmol/L (OR = 7.45, p = 0.01), and an admission NIHSS > 12 (OR = 5.12, p = 0.017). Patients with a worse outcome at 90 days were more likely to have received post thrombolysis care at a spoke hospital (OR = 15.63, p = 0.019).

Conclusion:
In a hub and spoke model of a telestroke network, patients with moderate to severe strokes may benefit from transferring to a PSC after IV thrombolysis, a variable that could improve their functional outcome. Larger studies to confirm those results are needed.