bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP111: Early Venous Thromboembolism Prophylaxis in Patients with External Ventricular Drains Does Not Increase Hemorrhagic Complications
Authors: Tanweer Omar , Boah Akwasi , Huang Paul
Published: March 2022

Background:
Patients undergoing placement of an external ventricular drain (EVD) are at increased risk of developing venous thromboembolisms (VTEs). Early chemical prophylaxis has shown to decrease VTE rates. However, the risks of bleeding and time of initiation have not been clearly defined in patient populations requiring EVDs.

Purpose:
To evaluate the safety and bleeding risks of starting chemical prophylaxis for VTEs within 24 hours of EVD placement compared to the hemorrhage rates in patients who did not receive prophylaxis within 24 hours.

Methods:
An IRB approved retrospective review was for performed patients who had an EVD placed with post-procedural imaging at Bellevue Hospital from January 2009 to April 2012. Demographics, diagnosis, coagulation profile, time to VTE prophylaxis and imaging, and occurrences of VTEs were collected. EVD-associated hemorrhages were graded as: Grade 0, no hemorrhage; Grade 1, petechial hyperdensity in proximity to the catheter; Grade 2, 1ml to 15ml volume of hematoma; Grade 3, greater than 15ml or epidural or subdural hematoma; or Grade 4, interventricular hemorrhage or hematoma requiring surgical intervention. Differences between groups were assessed by the Mann-Whitney U test, and a p value of ≤ 0.05 was used to identify significant differences.

Results:
One hundred and eleven EVDs were placed in 99 patients. Fifty-six patients received low dose unfractionated heparin (LDUH) within 24 hours of admission (early prophylaxis). Fifty-five patients received LDUH > 24 hours after admission (delayed prophylaxis). There were no statistical differences across all Grades (0 to 4) amongst the early prophylaxis (n= 45, 5, 5, 1, and 0 respectively) versus delayed prophylaxis (n= 46, 4, 1, 1, and 3 respectively) groups (p=0.658). In the early prophylaxis group, 3 VTEs were discovered in 32 of 56 patients who underwent screening for suspected VTEs. In the delayed prophylaxis group, 6 VTEs were discovered in 33 of 55 patients screened for clinically suspected VTEs (p= 0.488).

Conclusion:
There were no increases in hemorrhagic complications with starting chemical prophylaxis within 24 hours of EVD placement. Larger randomized controlled trials are needed to assess a possible decrease in VTEs with earlier prophylaxis.
Abstract WMP116: Incidental Diffusion-weighted Imaging Lesions In Patients With Cognitive Decline
Authors: Auriel Eitan , Martinez-Ramirez Sergi , Gurol Mahmut Edip , Schwab Kristin , Edlow Brian , Boulouis Gregoire , Dumas Andrew , Greenberg Steven M , Viswanathan Anand
Published: March 2022

Objectives:
Incidental diffusion-weighted imaging (DWI) hyperintense lesions on MRI, indicative of incident silent infarcts, are not uncommon in patients with advanced cerebral small vessel disease (SVD). SVD has been increasingly recognized as playing an important role in cognitive decline in the elderly. We thus examined the prevalence and associated risk factors for DWI hyperintense lesions in a cohort of patients followed in a memory clinic.

Methods:
We retrospectively analyzed MRI scans from 251 patients (43% females, mean age 73.3±8.3) with cognitive impairment enrolled in an ongoing prospective longitudinal study at the Massachusetts Alzheimer’s Disease Research Center (MADRC) between 2001 and 2010. Clinical and demographic data including the presence of specific vascular risk factors and degree of cognitive impairment (as measured by the Clinical Dementia Rating (CDR) Scale) were recorded. DWI and apparent diffusion coefficient (ADC) images were inspected for the presence of DWI-hyperintense lesions. Associated MRI markers of SVD including white matter hyperintensities (WMH), whole-brain mean global ADC, cerebral microbleeds (CMB) and lacunar infarcts were quantified.

Results:
We identified 16 DWI-hyperintense lesions in 13 (5.2%) patients. The 14 individuals with at least one DWI lesion did not differ from the 237 without lesions by age, gender, vascular risk factors, CDR, moderate to severe WMH, mean global ADC or number of CMB (p>0.05). Assuming a 10-day post-stroke period when DWI lesions remain hyperintense, their estimated annual prevalence would be 2.3 new infarcts per person-year.

Conclusions:
Incident DWI-hyperintense lesions, consistent with subacute cerebral infarcts, are not uncommon in unselected patients with cognitive decline. These lesions do not appear to be associated with other markers of SVD nor with degree of impairment. Our results suggest that the cumulative lifetime burden of these lesions may be substantial. These findings may support a role for small infarcts in age-related cognitive impairment.
Abstract WMP119: Comparisons of Neurobehavioral Dysfunction in Small-vessel and Large-vessel Vascular Dementia
Authors: Kim Meyung Kug , Yoo Bong Goo
Published: March 2022

Background:
Behavioral and psychological symptoms may be the presenting manifestations of dementia syndrome, appearing before cognitive alterations and heralding the onset of the dementia. Behavioral and psychological symptoms in vascular dementia (VaD) are rarely reported. We investigated the prevalence and related factors of behavioral and psychological symptoms in VaD and compared the severity and relative frequency of symptoms between small-vessel VaD and large-vessel VaD.

Methods:
Behavioral and psychological symptoms of 67 patients in VaD were determined using the Korean version of neuropsychological inventory (K-NPI). The following parameters were recorded and analyzed: education level, dementia duration, Korean version of Mini-mental Status Examination (K-MMSE), clinical dementia rating (CDR), global deterioration scale (GDS), Barthel index (BI), instrumental activity of daily living (IADL) and geriatric depression scale.

Results:
Based on MRI, patients were classified as having small-vessel and large-vessel VaD. The study group was composed of 27 large-vessel and 40 small-vessel disease. No differences were found between small-vessel and large-vessel VaD in the severity of cognition and ADL, use of psychotrophic medication and risk factors for stroke. Apathy was most prevalent (60%), followed by depression (43%), anxiety (37%), aberrant motor (34%), irritability (33%), night-time behavior (30%), agitation (28%) and disinhibition (28%) in VaD. Apathy was more common in small-vessel VaD than large-vessel VaD (P=0.011). Total K-NPI score was correlated with severity of deep white matter changes, CDR, GDS, BI and IADL. Multiple regression analysis revealed that total K-NPI score and prevalence of individual K-NPI sub-items were independently associated with number of microbleeds, severity of white matter changes, GDS and diabetes mellitus.

Conclusions:
Behavioral and psychological symptoms are relatively common in VaD. Patients with small-vessel and large-vessel VaD reveal different profiles of neurobehavioral symptoms. Apathy are more common in small-vessel VaD, reflecting disruption of white matter tracts.
Abstract WMP2: Computed Tomography or Magnetic Resonance Perfusion Imaging Benefits Selection of Acute Ischemic Stroke Patients for Endovascular Treatment
Authors: Kochar Arshneel S , Jung Richard S , Manjila Sunil , Kim Benny S , Koo Brian B , Blackham Kristine A , Sunshine Jeffrey L
Published: March 2022

Background:
Perfusion imaging to guide selection of patients for endovascular treatment of acute ischemic stroke (AIS) remains controversial. CT and MR perfusion have been performed at our institution during evaluation of AIS in order to triage patients who are more likely to benefit from endovascular therapy. The purpose of this study was to compare the clinical outcome between patients who did and did not receive advanced perfusion imaging prior to treatment.

Methods:
From April 2004 to July 2012, 330 patients with large vessel AIS were retrospectively reviewed and divided into three cohorts: 1) perfusion imaging followed by mechanical thrombectomy (MT) and/or intra-arterial thrombolysis (IAT) (n= 98), 2) no perfusion imaging followed by MT and/or IAT (n= 191) and 3) perfusion imaging without endovascular treatment (n = 41). Cohorts were compared based on neurologic improvement (≥4 point change in NIHSS), successful revascularization (TIMI 2-3), symptomatic intracranial hemorrhage (sICH), discharge modified rankin score (mRS) ≤3 and in-hospital mortality. Multivariate regression was performed to determine the predictive value of perfusion imaging prior to endovascular therapy.

Results:
Of 289 treated patients, mean age was 67 and median initial NIHSS was 17. The treated groups were matched in baseline characteristics and had no difference in the outcomes of successful revascularization, discharge mRS≤3 and improvement in NIHSS. However, 10 of 98 with perfusion imaging expired compared to 48 of 191 without perfusion (p=0.01). Logistic regression showed patients who had perfusion imaging prior to endovascular therapy were less likely to die during hospitalization (OR = 0.267; 95% CI = 0.170, 0.364) or to develop sICH (OR = 0.269; CI = 0.182, 0.356) Other predictors of mortality included advanced age (OR= 1.08; CI = 1.04, 1.13) and high initial NIHSS (OR = 1.14; CI = 1.09, 1.19). There was no mortality difference between treated and untreated cohorts.

Conclusion:
Patients who underwent CT or MR perfusion imaging prior to neurointervention for AIS were significantly less likely to suffer sICH or in-hospital mortality, providing evidence for the positive role of advanced imaging in selecting patients for endovascular treatment.
Abstract WMP22: Third International Stroke Trial (IST-3): Effect Of iv rt-pa < 6 Hours In Acute Ischaemic Stroke On Living Circumstances And Health Related Quality Of Life At Six Months
Authors: Sandercock Peter A , Wardlaw Joanna M , Lindley Richard I , Dennis Martin S ,   IST-3 collaborative Group
Published: March 2022

Aim:
describe the effects of thrombolysis with iv rt-PA < 6hrs on health related quality of life (HRQoL) & living circumstances at 6 months.

Methods:
Randomised trial of iv rt-PA (0.9mg/kg) (n=1515) versus control (n=1520). At 6 months, patients were assessed by postal questionnaire or blinded telephone interview to determine living circumstances and HRQoL with the EQ5D-3L (including its visual analogue scale (VAS)(100=best, 0=worst) assessment of overall self-rated health. We: a) calculated the mean between-group difference in VAS self-rated health, b) analysed the 5 3-level domains of EQ5D by ordinal logistic regression. Analyses were adjusted for baseline prognostic factors (age, NIHSS, hours delay from onset to randomisation, and presence of visible ischaemia on the baseline scan). IST-3 is registered
ISRCTN25765518
.

Results:
At 6 months, 408 [27%] vs 407 [27%]allocated rt-PA vs control had died; in survivors, mean VAS was significantly higher, indicating better HRQoL, with rt-PA (60.7 vs 57.8, mean adjusted difference 3.3, p=0.008). Across the 5 3-level domains of the EQ5D, allocation to rt-PA was associated with reduced adjusted proportional odds of having greater problems with: Self-care (odds ratio 0.79, 95% CI 0.66-0.94, p =0.008) and usual activities (0.74, 95% CI 0.63-0.88, p=0.001), but not mobility (0.88, 95% CI 0.74-1.05), anxiety depression (0.94, 95% CI 0.79-1.11) or pain or discomfort (1.01, 95% CI 0.85-1.20). The adjusted mean difference in VAS among patients randomised 0-2, 2-3, 3-4, 4-5, 5-6 hours was: 8.9, 3.5, 2.0, 0.8, 6.2. There was no difference in the proportions living in their own home 805/1058 (76%) vs 799/ 1050 (76%), nor in the proportions living in the home of a relative, in a residential home or a nursing home.

Conclusion:
Thrombolysis with iv rt-PA up to six hours after onset was associated with a statistically significant improvement in overall HRQoL in survivors, and the differences applied across a number of clinically significant individual domains. The decline in HRQoL(VAS) benefit with increasing time to randomisation matches the decline in benefit on functional outcome, except for the unanticipated increase at 5-6hrs.
Abstract WMP27: Prevalence of Non-responsiveness to Antiplatelet Therapy in Patients Undergoing Treatment of Cerebral Aneurysms Utilizing Flow Diversion with the Pipeline Embolization Device
Authors: Rutledge W C , Dannenbaum Mark J , Webb Adam C , Skukalek Susana L , Schuette Albert J , Case Daniel B , Asbury Bill , Tong Frank C , Dion Jacques E , Cawley C M , Winkler Anne M
Published: March 2022

Introduction:
Flow-diversion has emerged as a novel treatment for complex cerebral aneurysms. Although preliminary reports suggest flow-diverting devices are safe and effective, the risk of thromboembolic and hemorrhagic complications must be balanced with the added risk of dual antiplatelet therapy. Although the prevalence of antiplatelet therapy non-responsiveness (NR) has been associated with adverse cardiac events in patients with acute coronary syndrome (ACS), it has has not been studied in patients treated with these devices.

Methods:
All patients received clopidogrel 75mg and aspirin 325mg prior to modified light transmittance platelet aggregometry (LTA) using 4 agonists (ADP 5 and 20 uM, arachidonic acid (ACA), and
U46619
). NR was defined as a maximum amplitude (MA) > 60% with ADP 20uM and 40% with ADP 5uM for clopidogrel and a MA >20% with ACA for aspirin. Patients were also assessed for known drug interactions. Chi-square or Fisher’s exact tests were used for univariate analyses, and logistic regression was used to identify potential predictors of NR.

Results:
79 patients with 98 cerebral aneurysms were treated with the pipeline embolization device (PED). The prevalence of clopidogrel and aspirin NR was 27.6% and 30.3%, respectively. In univariate and multivariate analyses, age, gender, race, presence of drug interactions, history of hypertension, diabetes, ischemic stroke, subarachnoid hemorrhage and smoking were not significant predictors of NR.

Conclusions:
In our cohort, the prevalence of clopidogrel and aspirin NR was high and similar to that reported in ACS patients. As a result of the rate of NR, patients were evaluated by a virtual antiplatelet clinic and patients with suboptimal LTA results underwent modification of a drug interaction, received double doses of clopidogrel and/or aspirin, or were transitioned to an alternative P2Y12 inhibitor (prasugrel or ticagrelor). The mechanisms underlying antiplatelet NR remain to be further explored to minimize the risk of hemorrhagic complications if more potent antiplatelet therapy is required.
Abstract WMP31: Neamine, A Angiogenin Inhibitor, Induces Neuroprotection After Acute Ischemic Stroke In Type One Diabetic Rats
Authors: Ning Ruizhuo , Chopp Michael , Zacharek Alex , Yan Tao , Zhang Chunling , Roberts Cynthia , Chen Jieli
Published: March 2022

Introduction:
Angiogenin is a member of the ribonuclease superfamily and promotes degradation of basement membrane and extracellular matrix. After stroke in Type one diabetes (T1DM) rats, Angiogenin is significantly increased and the increased Angiogenin is correlated with worse functional outcome. Neamine, an aminoglycoside antibiotic, blocks nuclear translocation of Angiogenin thereby abolishing the biological activity of Angiogenin. In this study, we therefore investigated the effect and underlying protective mechanisms of Neamine treatment of stroke in T1DM.

Methods:
T1DM was induced in male Wistar rats by streptozotocin (60mg/kg, ip) and T1DM rats were subjected to embolic middle cerebral artery occlusion (MCAo). Neamine (10 mg/kg i.p.) was administered at 2h, 24h and 48h after MCAo. A battery functional outcome tests were performed. Brain blood barrier (BBB) leakage, lesion volume, brain hemorrhage volume, were evaluated and immunostaining, Western blot and ELISA were performed.

Results:
Neamine treatment of stroke in T1DM rats significantly decreased Evans Blue dye leakage (Neamine: 16.38±2.14 ng/mg vs contro:30.57± 5.88 ng/mg); and lesion volume (23±2% vs 35±3%) as well as improved functional outcome compared to T1DM-control. Neamine also significantly decreased apoptosis (34.2±0.8 vs 42.5±3.6) and cleaved caspase-3 (28.7±3.7 vs 45.2±3.7) in the ischemic brain. Neamine treatment decreased MIP-1, MCP-1 and MMP9 levels in the ischemic brain measured by ELISA array. Using immunostaining, we found that Neamine treatment significantly decreased nuclear Angiogenin (26.7±1.7 vs 57.1±3.6) number, and the positive area of Angeopoietin-2 (7.4±0.3 vs 10.9±0.5), toll-like receptor 4 (TLR4) (5.4±0.9 vs 10.5±1.2), MMP9 (0.29±0.04 vs 0.48±0.09) expression compared to T1DM-MCAo control rats. In vitro data also show that Neamine treatment significantly decreased tPA, Angiogenin, MMP9 and advanced glycation endproducts receptor (RAGE) expression (2-3 fold) in cultured astrocytes and oligodendrocytes.

Conclusion:
Neamine treatment of stroke is neuroprotective in T1DM rats. Inhibition of neuroinflammatory factor expression and decrease of BBB leakage may contribute to Neamine induced neuroprotection effects after stroke in T1DM.
Abstract WMP33: Synergistic Effect Of Dehydroascorbic Acid, Glutathione And Melatonin On Brain Endothelium Protection In Ischemic Rats
Authors: Lee Jong Eun , Kim Jae Young , Choi Ja Young
Published: March 2022

Introduction:
Stroke (cerebral ischemia) is the second leading cause of death worldwide. Antioxidant strategies have been used successfully to diminish ischemic cerebral tissue damage in animals but the utility of a pharmacological agent as a clinically relevant therapeutic strategy may depend, in part, on its ability to cross the BBB. To optimally improve the therapeutic window this present study investigated whether the intravenous administration of dehydroascorbic acid (DHA), glutathione (GSH) and melatonin potentially elevates the level of cerebroprotection.

Methods:
Male rats were subjected to 60 min middle carotid artery occlusion (MCAO) using an intraluminal filament. Single dose of DHA (100mg/kg/ml), glutathione (500 mg/kg/ml) and melatonin (10 mg/kg/ml) was administered intravenously immediately after MCAO at a time interval of 5 min each. Western blotting was performed to delineate the effects of antioxidant treatment on the proliferation and neurogenesis in the ischemic region. We also examined the neuroprotective dosing regimen of triple antioxidants treatment and its effects on the functional outcomes following cerebral ischemia.

Results:
Triple antioxidant treatment significantly reduced the infarct volume and improved behavioral performance evidenced by TTC staining and neurological test score results. The significant increase in the claudin-5 and occludine expressions in the antioxidant treatment group depicts the preservation of blood-brain barrier (BBB) integrity via a reduction in the enormous amount of stroke-induced free radical production. Moreover, treatment with triple antioxidants after stroke dramatically enhanced endogenous neurogenesis (doublecortin positive) and cell proliferation (ki67 positive) in the peri-infarct regions. These outcomes were in the favor of rescuing the damaged neurons at the injury site defining the neuroprotective effects of triple antioxidants treatment following experimental stroke.

Conclusion:
The results from this study demonstrate that triple antioxidant treatment prevents brain edema, BBB hyperpermeability, and tight junction proteins disruption, possibly through its antioxidant effects thereby offering optimal neuroprotection in rat MCAO model.
Abstract WMP39: Co-transplantation of Neural Stem cells and Vascular Progenitor Cells Enhances Post-ischemic Recovery in Cerebral Ischemia in Rats
Authors: tang Yaohui , Li Jia , Tang Rongbiao , Wang Yongting , Gao Weiqiang , Yang Guoyuan
Published: March 2022

Introduction:
Neuronal and vascular regeneration is important for post-ischemic recovery. In this study we investigated whether co-transplantation of neural stem cells (NSCs) and vascular progenitor cells (VPCs) could promote the therapeutic efficacy of stem cell based therapy after transient middle cerebral artery occlusion (tMCAO).

Methods:
tMCAO was generated in adult male SD rats. One day after MCAO, NPCs (1x106), VPCs (1x106) or NPCs (5 x105) and VPCs (5x105) were transplanted into the cortical perifocal region. Neurobehavioral outcomes, infarct volume, cell differentiation, angiogenesis and neurogenesis were examined within 14 days following tMCAO.

Results:
MRI analysis and behavioral tests showed that co-transplantation of NSCs and VPCs significantly decreased infarct volume and improved neurobehavioral recovery at 7 and 14 days after ischemia compared to NPCs group and VPCs group (p<0.05). Immunostaining showed that angiogenesis and neurogenesis were increased in ipsilateral hemisphere in NPCs/VPCs co-transplantation rats compared to single cell transplanted groups (p<0.05). Fourteen days after ischemia, NPCs and VPCs were detected in the ipsilateral cortex, which differentiated into neurons, astrocytes and incorporated into host blood vessels as endothelial cells (ECs) and smooth muscle cells (SMCs).

Conclusion:
We demonstrated that co-transplantation of NPCs and VPCs had great benefits for post-ischemic recovery. Our findings suggest that combined transplantation of different types of stem cells may constitute a novel therapeutic strategy for improving the treatment of ischemic diseases.
Abstract WMP40: Tumorigenesis of Induced Pluripotent Stem Cells in Ischemic Mouse Model
Authors: Abe Koji , Yamashita Toru , Kawai Hiromi , Tian Fengfeng , Ohta Yasuyuki
Published: March 2022

Objectives:
Recent studies have indicated that induced pluripotent stem (iPS) cells may provide cures for various neurological diseases. However tumorigenesis of iPS cells is serious problem which should be overcome for clinical application. In this study, we evaluated the tumorigenesis of iPS cells in a mouse model of transient middle cerebral artery occlusion (MCAO).

Methods:
Adult (20-25g, 8-10 week old) male C57BL/6N mice were used. The iPS cells (5×105) were injected into the ipsilateral striatum and cortex, which were considered as the ischemic boundary zone, at 24 hour after MCAO. We used the two different murine iPS cell lines. One was established with a retrovirus introducing four transcriptional factors, c-Myc, Sox2, Oct3/4 and Klf4 (classical iPS cells). The other was established with plasmid vectors expressing above four transcriptional factors (virus-free iPS cells). Histological analysis was performed 28 days after the cell transplantation.

Results:
Classical iPS cells transplanted in brain after MCAO, formed teratoma with higher probability (p <0.05) and larger volume (p <0.01) compared with those in intact brain. Among of four transcriptional factors, c-Myc, Sox2 and Oct3/4 expression were significantly increased in iPS-derived tumors in ischemic brain (p <0.01). On the other hand, virus-free iPS cells formed teratoma but there was no significant difference in tumor volume.

Conclusions:
Our findings suggested that these four transcriptional factors which were integrated into the genome by retrovirus vectors, activated and promoted tumorigenesis in the ischemic brain condition. Virus-free iPS cells may be safer for transplantation therapy.
Abstract WMP45: Incidence and Outcome of Vertebral Artery Dissection in Trauma Setting: Analysis from National Trauma Data Base (NTDB)
Authors: Majidi Shahram , Rahman Haseeb A , Adil Malik M , Qureshi Adnan I
Published: March 2022

Background:
Vertebral artery dissection (VAD) is an important cause of stroke in young adults. The natural history and epidemiological aspects of traumatic VAD are not fully understood. We determined the prevalence and outcome of dissection of the vertebral artery in a trauma setting.

Methods:
All patients who were admitted with traumatic brain injury or head and neck injury were identified by ICD-9-CM codes from the National Trauma Data Bank (NTDB), using data files from 2009 to 2010. NTDB represents one of the largest trauma databases and contains data from over 900 trauma centers across the United States. Presence of VAD was identified in these patients by using ICD-9-CM codes. Admission Glasgow Coma Scale (GCS), Injury Severity Score (ISS), in-hospital complications and treatment outcomes were compared between patients with VAD to patients without vascular dissection.

Results:
A total of 84 VAD patients were identified which comprised 0.1% of all patients admitted with head and neck injury. The mean age for patients with VAD was significantly higher than patients without dissection [46 (95% CI: 41-50) versus 41.3 (95% CI: 41.2-41.4); p= 0.003]. The admission GCS score was significantly lower in patients with VAD with 31% of these patients presenting with GCS<9 (p=<.0001). Patients with VAD had higher rate of in-hospital stroke than the patients without dissection (5% versus 0.2%; p=<.0001). Numbers of ICU days, ventilator days, and hospital length of stays were all significantly higher in patients with VAD. These differences remained significant after adjusting for the demographics, admission GCS and ISS (p=<.0001). Only 8% of the patients with VAD received endovascular treatment and there was no in-hospital stroke in these patients. Discharge destination and in-hospital mortality was not different in patients with VAD compared with other patients with head and neck injury.

Conclusion:
Although infrequent, vertebral artery dissection in head and neck trauma is associated with higher rates of in-hospital stroke and greater length of ICU and hospital stay. Considering the risks associated with anticoagulation in trauma setting, endovascular treatment may be an alternate option to reduce in-hospital complications in these patients.
Abstract WMP47: Burden of Intracranial Steno-occlusive Lesions on Initial CT Angiography is Predictive of Poor Outcomes in Patients with Stroke And TIA
Authors: Lau Alexander Y , Wong K.S. Lawrence , Lev Michael , Furie Karen , Smith Wade , Kim Anthony S
Published: March 2022

Background:
CT-angiography (CTA) is an accurate non-invasive method to diagnose intracranial steno-occlusive disease (ICAD) at initial presentation for stroke. We aimed to identify CTA features associated with unfavorable outcome.

Methods:
We identified patients with ICAD in the STOP-Stroke Study, a prospective imaging-based study of stroke outcomes in consecutive patients with ischemic stroke or transient ischemic attack (TIA) presenting to two academic medical centers. All patients underwent CTA which were graded by two neuroradiologists independently. Univariate and multiple logistic regression was used to evaluate predictors of favorable outcome at 6-months, defined as a modified Rankin Scale ≤2.

Results:
Among 539 patients that met study entry criteria, ICAD was identified in 212 (39%); 116 (22%) had concurrent extra-intracranial lesions, and 66 (12%) had multiple sites of ICAD. Patients with ICAD had more severe stroke (median NIHSS 9 vs. 3, p<0.001), worse outcomes at 6-months (mRS 0-2, 57% vs. 73%, p<0.001), and higher mortality (18% vs. 8%, p=0.001). In the multivariate model, age (OR 0.75 per decade, 95% CI 0.65-0.87), female sex (OR 0.49, 95% CI 0.32-0.73), multiple sites of ICAD (OR 0.53, 95% CI 0.29-0.97), complete occlusion (OR 0.42, 95% CI 0.25-0.72), and concurrent extra-intracranial lesions (OR 0.51, 95% CI 0.31-0.84) negatively predicted favorable outcome.

Conclusion:
CTA findings of multiple sites of ICAD, concurrent extra-intracranial lesions, and complete occlusion are independent predictors of unfavorable outcome at 6-months.
Abstract WMP50: The Distribution of White Matter Hyperintensities by Age in Persons with Familial Cardiovascular Risk
Authors: Nyquist Paul , Bigel Murat , Yanek Lisa , Moy Taryn F , Kral Brian G , Prince Jerry , Becker Diane M , Becker Lewis C , Vaidya Dhananjay
Published: March 2022

Introduction:
Subclinical brain disease manifested as white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) are putatively due to microvascular ischemic damage based on correlations with autopsy specimens. Because the vascular architecture of white matter differs in the subcortical (SC) and periventricular (PV) region, we hypothesized that the vasculopathic effects of aging will be differential by brain regions. We therefore studied the association of age with the ratio of SC to total WMH volume (SC/T ratio) in individuals at risk for premature cardiovascular disease.

Methods:
We enrolled 593 asymptomatic family members of probands with premature coronary artery disease (<60 years). The location and volume of WMH was determined from 3T cranial MRI using automated software. WMH was considered PV if it was confluent with the ventricles, and SC otherwise. The non-linear association of age with Laplace-smoothed SC/T ratio was examined using spline generalized estimating equation regression adjusted for sex, race and familial correlations.

Results:
Participants were 58% women, 37% African-American, aged 29-74 years. The figure shows that the median SC/T ratio was relatively larger and stable during the younger decades, while it was successively smaller in later decades. The non-linearity was best modeled using a linear spline at 56 years of age. The slope of SC/T ratio with respect to age was 0.0% (p=0.94) for age ≤ 56, but for age > 56, 1.4% lower per year of age (p<0.001).

Conclusions:
This is the first study showing that SC/T WMH ratio is high in younger adults at high familial cardiovascular risk. This finding suggests that subclinical premature vascular pathology at ages ≤ 56 years is predominantly SC. This differs from the aging-dependent pathology at ages > 56 years, which is predominantly non-SC, thus reducing the SC/T ratio at older ages.
Abstract WMP56: Utility of Bubble Test with Cervical Internal Carotid Artery Triplex Ultrasound in Detection of Right-to-left Shunts
Authors: Topcuoglu Mehmet Akif , Arsava Ethem Murat
Published: March 2022

BACKGROUND:
Transcranial Doppler (TCD) ultrasound with bubble test is a dependable method to detect cardiac right-to-left shunts (RLS). In patients with insufficient temporal bone windows, cervical internal carotid artery (ICA) recording can be used as an alternative method for detection of RLS. However, bubble tests performed via insonation of cervical ICA have issues with probe fixation, signal differentiation and breathing/swallowing artifacts. To overcome these problems, we developed a new technique for bubble test with cervical ICA and compared its utility with traditional middle cerebral artery (MCA) TCD studies.

METHODS:
MCA and ICA recordings were compared in 156 bubble studies obtained from 78 patients. ICA bubble study was performed by hand-held 1-3 MHz phase-arrayed sector transducer and triplex ultrasound technology. RLS volume was graded according to the International Consensus Criteria (ICC) [grade-0: no micro bubble (MB), grade-1: 1-20 MB, grade-2: >20 MB or shower, and grade-3: curtaining].

RESULTS:
In 133 studies there was concordance of MCA and ICA studies. In 11 patients ICC grade was higher with MCA monitoring, while in 12 patients, ICA method showed higher RLS grade. Overall MB number was higher in ICA than MCA (33 vs. 20 MB). Bubble test with triplex ICA was reliable (Cronbach’s alpha: 0.87) and well correlated (weighted quadratic kappa: 0.874) with traditional MCA method. There was no signal loss during Valsalva’s maneuver with ICA recording, where triplex technique provided timely relocation of the signal with real-time color imaging.

CONCLUSION:
The bubble test performed with triplex ICA recording is a sensitive and specific alternative of traditional bubble studies performed by MCA recording. This method is feasible not only in patients with poor ultrasonic bone windows but also for all cases evaluated for RLS presence and grading.
Abstract WMP58: The Portable Sleep Study as an Early Obstructive Sleep Apnea Screening Tool In Acute Ischemic Stroke
Authors: CHERNYSHEV OLEG Y , Moul Douglas E , Liendo Cesar , McCarty David E , Caldito Gloria , Munjampalli Sai K , Kelley Roger , Chesson Andrew
Published: March 2022

Background:
Prompt diagnosis of obstructive sleep apnea (OSA) after acute ischemic stroke (AIS) is critical for optimal clinical outcomes, but full bedside polysomnograms are not routinely practical. To validate a potentially practical diagnostic portable cardiopulmonary sleep study (PSS) after such strokes, we compared it to conventional polysomnography (PSG).

Methods:
Simultaneous bedside Level 3 (Embletta X100) PSS and PSG studies were performed in patients <72 hours from stroke onset. The accuracy of PSS was compared to PSG using: Chi-square tests, Receiver-Operatory Characteristic curves, Bland-Altman plot, paired Student t-test /Wilcoxon signed rank test and calculation of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV).

Results:
Twenty one out of 23 acute ischemic stroke patients (age 61+ 9.4; 52% male; 58% African-American), successfully completed both of the simultaneous screenings (9% technical failure). Ten AIS patients (48%) were diagnosed with OSA. Nearly all (90%) had Mallampati IV posterior oropharynx; the mean neck circumference was 17.3± 1.3 inches; the mean BMI was 35.1 ±5 kg/m
2
. The Apnea Hypopnea Index (AHI) provided by PSS was similar to that provided by PSG (29.1± 16.8 vs. 27.6 + 20.2, respectively; p=0.10). In identifying patients with AHI ≥ 5 on PSG, PSS screening had the following parameters: sensitivity 100%; specificity 85.7%; PPV 91%; NPV 100%. For AHI ≥ 15 on PSG, PSS screening parameters were as follows: Sensitivity 100%; Specificity 83.3%; PPV 71.4%; NPV 100%. Bland-Altman plotting showed overall diagnostic agreement between PSS and PSG modalities for an AHI cutoff of > 5, despite finer-grained differences in estimated AHIs.

Conclusions:
Compared with PSG, PSS provides similar diagnostic information when run simultaneously in acute ischemic stroke patients. PSS potentially can serve as a reliable screening tool for early diagnosis of obstructive sleep apnea in acute ischemic stroke patients.
Abstract WMP60: Automatic Embolic Signal Detection Using Adaptive Wavelet Packet Transform and Adaptive Neuro-Fuzzy Inference System
Authors: Lueang-on Charoenchai , Tantibundhit Charturong , Muengtaweepongsa Sombat
Published: March 2022

Introduction:
Transcranial Doppler(TCD) can be used to detect emboli in cerebral circulation. To classify the measured TCD as an embolic signal (ES) or artifact is usually done by a well-trained physician. However, inter-rater reliability among those physicians is variable. Also,in countries where skilled physicians are scarce, an automatic ES detection system can be useful as a medical support system.

Method:
We propose a two-step algorithm based on adaptive Wavelet Packet Transform (WPT) and Adaptive Neuro-Fuzzy Inference System (ANFIS) described as follows. First, the TCD signal is windowed using a 256-sample Gaussian window with 80% overlap. A 3-level WPT is used to transform each windowed TCD signal. The best basis algorithm is applied to find the best binary tree from which the entropy and normalized energy are calculated. The entropy and normalized energy are used as features to classify each windowed TCD signal as normal or abnormal. Second, the abnormal TCD windows are classified further as ES or artifact. Specifically, standard deviation of level 3 WPT coefficients from frequency index 1 to 6 are calculated and used as inputs of ANFIS where each standard deviation can be combined with others resulting in 64 rules. After training the ANFIS, ES and artifact can be differentiated.

Results:
Six hundred and sixty abnormal signals in vivo are used to evaluate the algorithm, i.e., 176 ESs collected during emboli monitoring from patients undergoing carotid angioplasty with stenting and from patients with patent foramen ovale, 106 artifacts from normal subjects, and 378 artifacts from stroke patients with carotid stenosis. The signals are divided into training and validation sets. The training set is used to train the algorithm and the validation set is used to evaluate the validity of the algorithm. Experimental results show that the algorithm can differentiate abnormal from normal signals efficiently with 100% accuracy. A sensitivity of 96.6% and specificity of 96.5% can be achieved from the validation set.

Conclusions:
The automatic embolic signal detection algorithm has been developed. The experimental results suggested that the algorithm could detect emboli and differentiate artifacts efficiently and could be used as a medical support system.
Abstract WMP62: Organized Comprehensive Stroke Center Is Associated With Reduced Mortality After Acute Ischemic Stroke
Authors: Kim Dae-Hyun , Cha Jae-Kwan , Choi Seong-Ho , Kim Sang-Woo , Jun Seong-Man
Published: March 2022

Background and Purpose:
Organized inpatient stroke care is one of the most effective therapies to improve patient outcomes. For this purpose, many stroke centers have been established. However, there are limited data on the effectiveness of organized comprehensive stroke center (CSC) in the real-world setting. Our aim is to determine whether inpatients care after the establishment of CSC lowers mortality of patients with acute ischemic stroke (AIS).

Methods:
Based on our prospective stroke registry, we identified all patients with AIS within 7 days after the onset of symptoms to our hospital between January 2006 and December 2011. We divided the patients with AIS into two groups according to the hospitalization before and after the establishment of CSC. The outcome of interest was all-cause mortality within 30 days from time of admission. We analyzed 30-day case fatality by means of logistic regression to evaluate whether the establishment of CSC is independently associated with reduced 30-day all-cause mortality.

Results:
A total of 3,117 consecutive patients with AIS were admitted within seven days after the onset of the symptoms. Unadjusted 30-day mortality was lower after the establishment than ever before (5.9% vs 8,2%, p=0.012). On the unadjustment analysis, advanced age, female gender, previous coronary artery disease, no current smoking, stroke subtype, admission on holiday, referral from other hospitals, higher NIHSS score on admission, and admission before the establishment of CSC were associated with 30-day stroke case fatality. After the adjustment of these factors, stroke inpatients care after the establishment of CSC was independently associated with lower 30-day mortality (OR, 0.57; 95% CI, 0.412-0.795).

Conclusions:
Patients admitted after the establishment of CSC had lower risk-adjusted 30-mortality rates than ever before. The present study has revealed that organized stroke care in CSC could improve the outcome after AIS.
Abstract WMP65: The Quality of Pre-hospital Acute Stroke Care: Data from a Pilot Surveillance System
Authors: Oostema John A , Reeves Mathew J
Published: March 2022

Background:
Evaluation of prehospital stroke care quality has been limited by the inability to link EMS and hospital data. The Prehospital Acute Stroke Surveillance System (PASSS) is designed to assess prehospital stroke care in Kent Country, Michigan through linkage of EMS and hospital data for patients transported with suspected or confirmed stroke.

Methodology:
EMS transported patients were eligible for inclusion if stroke was suspected by EMS dispatchers or providers prehospital or confirmed after hospital admission. Electronic records containing data elements derived from the National EMS Information System (NEMSIS) were obtained from all three EMS agencies in the county and manually linked to in-hospital data from 2 stroke center hospitals. Outcome measures included the accuracy of prehospital stroke recognition by EMS dispatchers and providers and the proportion of runs with documentation of symptom onset time, scene time ≤ 10 minutes, pre-hospital stroke screen, blood glucose, and hospital pre-notification.

Results:
In the first three months, 167 EMS transported patients were entered into PASSS; 58 (35%) were confirmed as stroke cases after admission. Emergency dispatchers missed 36% (n=21) of confirmed strokes and EMS providers missed 22% (n=13). The false positive rate for stroke identification was 69% (82/119) among dispatchers and 54% (53/98) among EMS providers. Among 98 cases identified by EMS as suspected stroke, documentation rates were 82% for symptom onset time, 86% for prehospital stroke screen, 87% for blood glucose, 10% for scene time ≤10 minutes, and 61% for hospital prenotification. Among 26 patients with a positive prehospital stroke screen and onset of symptoms < 120 minutes, the prenotification rate increased to 77%. Two patients received IV tPA.

Conclusions:
The PASSS illustrates that substantial opportunities for improvement in EMS prehospital stroke care exist, including stroke recognition and compliance with quality measures. The high rate of false-positive prehospital stroke identification has important implications for the development of regional stroke systems.
Abstract WMP76: Predictors of Systemic Inflammatory Response in Acute Ischemic Stroke Patients Treated with IV tPA
Authors: Boehme Amelia K , Kapoor Niren , Albright Karen C , Lyerly Michael J , Rawal Pawan V , Shahripour Reza Bavarsad , Alvi Muhammad , Shiue Harn J , Houston J. Thomas , Sisson April , Alexandrov Anne W , Alexandrov Andrei V , Miller David W
Published: March 2022

Background:
Systemic Inflammatory Response Syndrome (SIRS) is a generalized inflammatory state in which cytokines are elevated. SIRS in the setting of AIS has been associated with poor outcomes. However, no study to date has investigated what predicts SIRS in AIS patients treated with tPA.

Methods:
Consecutive patients were retrospectively reviewed for evidence of SIRS during their admission. SIRS was defined as the presence of two or more: fever >38° C, HR >90, respiratory rate >20 and WBC <4 or >12. Patients diagnosed with infection (via positive culture) were excluded as well as those with evidence of pneumonia or UTI on admission. A scoring system was created to predict SIRS based on patient characteristics available at the time of admission. Logistic regression was used to evaluate potential predictors of SIRS using a sensitivity cut-off of ≥65% or area under the curve (AUC) ≥0.6.

Results:
Out of 212 patients, 44 had evidence of SIRS (21%). Patients with SIRS were more likely to be Black (61% vs 54%; p=0.011), had lower median total cholesterol at baseline (143 vs.167 mg/dL; p=0.0207), and had a nonsignificant difference on prior history of stroke (51% vs. 35%; p=0.0810). Ranging from 0-6, the SIRS prediction score consists of Black race (2 points), history of hypertension (1 point), history of prior stroke (1 point) and admission total cholesterol < 200 (2 points). As shown in Figure 1, 80% of patients with a SIRS score ≥4 have SIRS. Patients with a SIRS score ≥ 4 were 3 times as likely to develop SIRS when compared to patients with a score of ≤ 3 (OR=2.815, 95% CI 1.43-5.56, p=0.0029).

Conclusion:
In our sample of IV tPA treated patients, clinical and laboratory characteristics available on presentation were able to identify patients likely to develop SIRS during their acute hospitalization. Validation is required in other populations. If validated, this score could assist providers in predicting who will develop SIRS after treatment with IV tPA.
Abstract WMP79: Catheter Placement and Surgical Training in the Minimally Invasive Surgery Plus rt-PA for Intracerebral Hemorrhage Evacuation Trial
Authors: Ullman Natalie L , Muschelli John , Li Matthew , Morgan Timothy C , Awad Issam A , Zuccarello Mario , Lane Karen , Hanley Daniel F ,   MISTIE Investigators
Published: March 2022

INTRODUCTION:
One goal of the Minimally Invasive Surgery Plus rt-PA for Intracerebral Hemorrhage Evacuation (MISTIE) trial was to assess variability in surgical performance. We hypothesized that less variability in surgical technique and catheter placement would improve ICH removal.

Methods:
Upon review of catheter placements in stage 1 of the MISTIE trial, we developed a 150-point scoring system to assess the catheter engagement with the parenchymal clot and analyzed this compared to clot volume reduction. We also explored whether ideal clot engagement would be more likely using one of three predetermined trajectories. To improve surgical performance in the second stage of the trial, surgeons were systematically retrained via webinars, teleconferences and consensus presentations emphasizing the importance of choosing the ideal trajectory. Additionally, prior to surgey, the surgical team was required to plan catheter placement by choosing one of the three trajectories. This choice was prospectively reviewed by the trial’s centralized surgical center to optimize surgical technique.

Results:
Pre-surgery ICH was similar across stage 1 (46.2 cc, n=46) and stage 2 (42.1 cc, n=35). In stage 1, a higher catheter placement score correlated to a higher percentage of clot removed (Spearman r = 0.569, p < 0.001). Following surgical standardization, mean catheter placement score (±SD) improved from 80.3 (±4.2) in stage 1 to 99.3 (±5.9) in stage 2 (p=0.011). Surgical patients in stage 2 experienced a 59.4% clot reduction on average compared to 47.5% in stage 1 (trend, p=0.083). Also, more patients from stage 2 (54%) had less than 15 cc of blood remaining at the end of treatment compared to stage 1 (35%, one-sided p=0.063), which has been shown to predict good functional outcomes.

Conclusion:
Controlling the catheter trajectory can optimize catheter engagement with the clot and improve ICH removal. Reliable catheter placement can be achieved in a multicenter clinical trial through surgical training.
Abstract WMP80: Enhancement Of Antioxidative Activity Facilitates Neural Stem Cell Transplantation Therapy For Hemorrhagic Stroke
Authors: Wakai Takuma , Sakata Hiroyuki , Narasimhan Purnima , Maier Carolina M , Chan Pak H
Published: March 2022

Background:
We focused on the effect of oxidative stress against grafted neural stem cells (NSCs) and hypothesized that conferring antioxidant properties to NSCs may overcome cell death in the hostile host environment and enhance neuroprotection after transplantation for hemorrhagic stroke.

Methods:
NSCs were obtained from the striatum of copper/zinc-superoxide dismutase transgenic (Tg) mice and wild-type (Wt) mice. The NSCs were exposed to various forms of oxidative stress (hemoglobin, H2O2 and FeCl2). Cell viability and oxidative damage were assessed with WST-1, Live/Dead assay, and hydroethidine (HEt) staining. Intraparenchymal NSC transplantation was performed 3 days after autologous blood was injected into mouse striatum for NSC efficacy after transplantation. We performed 8-hydroxyguanosine (8-OHG) staining 4 hours after transplantation to assess oxidative damage in the grafted NSCs. Striatum size was measured to evaluate atrophy, and surviving neurons in the striatum were counted 35 days after hemorrhagic insult. Neurological evaluation was performed 1, 3, 7, 14, 21, 28, and 35 days after hemorrhagic insult.

Results:
Cell viability of Tg NSCs was significantly increased compared with Wt NSCs. Both HEt and 8-OHG signals were suppressed in Tg NSCs. Tg NSC transplantation showed a significant reduction in striatum atrophy (86±3% vs 82±4%, n=7, p<0.05, striatum size/contralateral) and showed an increase in surviving neurons in the striatum (73±12% vs 57±12%, n=6, p<0.05, number of neurons/contralateral) compared with Wt NSC transplantation. In the Tg group, progressive improvement was observed 35 days after hemorrhagic insult compared with the Wt group (n=9, p<0.05).

Conclusion:
Our results suggest that enhanced antioxidative activity in NSCs improves efficacy of stem cell therapy for the hemorrhagic stroke brain.