bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 93: The Radiation Mitigator MMS350 Prevents Bradyarrhythmias in Irradiated Mice
Authors: Morgan Gina M , Kutschke William J , Matasic Daniel S , Epperly Michael W , Greenberger Joel S , Kalen Amanda L , Waldron Timothy J , Schoenfield Joshua D , McCormick Michael L , Yoon Jin-Young , Wipf Peter , Spitz Douglas R , London Barry
Published: July 2021

Introduction:
Radiation exposure is a health hazard and the potential exposure from healthcare and other anthropogenic sources necessitates radioprotective therapy. MMS350, a water soluble oxetanyl sulfoxide, is a radiation mitigator which has protective effects on pulmonary and bone marrow cells following irradiation. We have previously shown that radiation exposure causes cardiac conduction damage including bradyarrhythmia and atrioventricular (AV) block in mice. This study investigates whether MMS350 protects against cardiac conduction damage in C57Bl/6 mice following radiation exposure.

Methods:
Mice were treated with MMS350 (400 μM) in drinking water
ad libitum
for 14 days prior to and for 30 days following irradiation, and were injected with MMS350 (20 mg/kg IV) 30 minutes prior to irradiation. Control (n=12) and MMS350-dosed (n=8) mice were total body irradiated (TBI) using a Pantak HF-320 Orthovoltage X-ray machine for a total dose of 6 Gy (1.38 Gy/min). Four-lead ECGs were performed on anesthetized mice at baseline and at day 30; PR, QRS, and QTc (QT normalized to heart rate) intervals were analyzed.

Results:
TBI control mice had PR (51.2 ± 5.8 vs. 43.4 ± 2.6 ms, P=0.003) and QRS (13.7 ± 0.2 vs. 13.0 ± 0.6 ms, P=0.02) interval prolongation at 30 days compared to baseline, while QTc trended towards a significant lengthening (88.4 ± 6.8 vs. 80.1 ± 10.4 ms, P=0.06). TBI MMS350 mice had no significant PR (46.2 ± 7.8 vs. 42.9 ± 5.1 ms, P=0.41) or QRS (14.0 ± 2.4 vs. 13.7 ± 0.8 ms, P=0.71) interval prolongation at 30 days compared to baseline, while QTc trended towards a significant lengthening (86.1 ± 7.9 vs. 73.0 ± 15.2 ms, P=0.05). New prolonged pauses and/or AV block occurred by day 30 post-irradiation in a third of TBI control mice but not in TBI MMS350 mice. Additionally, compared to baseline, day 6 post- irradiation TBI-only mice lost weight (males: 25.0 ± 1.8 to 24.2 ± 1.6g, P=0.004; females: 21.2 ± 1.0 to 19.2 ± 1.3g, P=0.01) while MMS350-dosed mice did not (males: 25.4 ± 1.7 to 27.8 ± 0.5g, P=0.12); females: 19.3 ± 0.2 to 21.0 ± 1.2g, P=0.08).

Conclusion:
Our results suggest that MMS350 protects irradiated mice from bradyarrhythmias, cardiac conduction damage, and radiation-associated weight loss. These findings lend further support to MMS350 as a radiation mitigator.
Sodium Transport in the Toad Bladder
Authors: FRAZIER HOWARD S.
Published: July 2021

The isolated urinary bladder of the toad transports sodium actively across its epithelial layer and responds to the hormones vasopressin and aldosterone, properties which make it a useful model for the study of certain functions of the renal tubule. Sodium transport in the granular cells of the bladder is thought to involve first an energetically passive but selective entry step at the mucosal surface, the rate of which is increased after vasopressin administration. The second step in transport is considered to be active extrusion of the ion across the serosal boundary of the cell.

Recent evidence concerning the cellular pool of sodium and the site and mode of action of vasopressin suggests that this description is at best incomplete. No equally simple alternative hypothesis for the organization of sodium transport in this system is available at present.
Effects of Normobaric Hyperoxia in a Rat Model of Transient Focal Cerebral Ischemia and Reperfusion
Authors: Singhal Aneesh B , Wang Xiaoying , Lo Eng H
Published: July 2021

3

Background:
The role of therapeutic oxygen in treatment of acute stroke is controversial. Oxygen improves cellular aerobic metabolism and can salvage ischemic tissue. However, oxygen free radicals can increase blood brain barrier (BBB) damage, and oxygen can induce vasoconstriction, which could worsen stroke outcome. We studied the effects of normobaric oxygen in cerebral ischemia and reperfusion.
Methods:
Rats were subjected to normobaric hyperoxia (FiO2 100%) or normoxia (FiO2 30%) during two hour filament occlusion and one hour reperfusion of the middle cerebral artery. Twenty-four hour infarct volumes, regional cerebral blood flow (rCBF) using laser Doppler flowmetry, and severity of BBB damage (assessed by quantifying Evan’s Blue dye (EB) leakage after one hour of reperfusion) were compared between groups.
Results:
Physiological parameters were similar in hyperoxic and control groups, except for paO2, which was expectedly higher in the hyperoxic group (pO2 484 mm Hg) as compared to controls (pO2 118 mm Hg). Mean rCBF dropped to 25% after onset of ischemia and recovered to 75–90% after arterial unocclusion, indicating successful reperfusion. Mean total (right hemispheric) infarct volume was 65 mm
3
in the hyperoxia group and 209 mm
3
in controls, p<0.001. The reduction in infarct volume was mostly in the cortex, where mean infarct volume was 11 mm
3
in hyperoxic rats and 129 mm
3
in controls (p<0.001). Mean striatal infarct volume was 54 mm
3
in hyperoxic rats and 80 mm
3
in controls (p<0.06). Mean total EB leak was 1592 ng/g in hyperoxic and 3955 ng/g in control rats (p<0.02), suggesting reduced BBB damage in hyperoxia. However, BBB damage and EB leak are likely related to infarct volume; after normalising for infarct volume, mean EB leak was 17 ng/mm3 in the hyperoxia group and 14 ng/mm3 in controls (p=0.5).
Conclusion:
Total and cortical infarct volumes can be significantly reduced with normobaric hyperoxia during transient cerebral ischemia and reperfusion. Hyperoxia does not decrease blood flow to ischemic brain, and its benefit in reducing infarct volume may outweigh any potential damage from BBB damage.
Familial frequency of ischaemic stroke and transient ischaemic attack in relation to clinical subtype and intermediate phenotypes
Authors: Rothwell Peter M , Warlow Charles P
Published: July 2021

28

Susceptibility to cerebral ischaemia is influenced by genetic factors. However, although a number of rare Mendelian syndromes have been characterised, there have been few studies of the genetic epidemiology of the common forms of ischaemic stroke and TIA. Previous studies have not reported familial frequency in the specific clinical subtypes of ischaemic stroke, and have not assessed the extent to which familial susceptibility is related to intermediate phenotypes such as hypertension, diabetes and hyperlipidaemia. We studied family history of stroke in 544 ischaemic strokes (Oxfordshire Community Stroke Project: OCSP) and 469 TIAs (hospital-referred case series in Oxford). Information on history of stroke in first degree relatives (FDR) was obtained in 535 stokes and 467 TIAs. Stroke had occurred in a FDR of 40 (8%, 95% CI = 6 - 10) stroke cases. Positive family history was unrelated to clinical subtype (OCSP classification). In particular, it was no more common in lacunar than non-lacunar stroke. In the TIAs, there was a history of stroke in at least one FDR in 98 (21%, 95% CI = 17 - 25) cases: 80 (17%) with one FDR, 16 (3.4%) with two FDRs and 2 (0.4%) with 3+ FDRs. The frequency of hypertension increased with the number of FDRs affected (P=0.003): nil - 105/373 (28%), one - 32/78 (41%); two or more - 12/18 (67%). Mean (SD) systolic blood pressure (mmHg) also increased across these groups (P=0.02): 157 (31), 162 (30) and 177 (36). In the strokes, a history of hypertension was also more frequent in those with a family history of stroke (P=0.02), and this was also shown by differences in measured blood pressure. In both cohorts, cases without hypertension, diabetes or hyperlipidaemia were least likely to have a family history of stroke. A history of stroke in a FDR was relatively infrequent, and was not related to the clinical subtype of stroke. However, in both the strokes and TIAs, family history of stroke was strongly related to intermediate phenotypes, particularly hypertension. These data suggest that genetic susceptibility to hypertension might account for a substantial proportion of the familial clustering of ischaemic stroke and TIA.
The effect of socioeconomic status on access to care and mortality following stroke
Authors: Kapral Moira K , Wang Hua , Mamdani Muhammad , Tu Jack V
Published: July 2021

36

Background:
Socioeconomic status has been associated with increased mortality from ischemic heart disease as well as decreased access to interventions such as coronary angiography, even in countries with universal health care. We undertook a study to determine whether a similar association between socioeconomic status and mortality exists in the setting of stroke.
Methods:
We linked hospital discharge abstracts and vital-status data for all patients with acute stroke who were admitted to hospitals in Ontario between April 1994 and March 1997. Socioeconomic status for each patient was imputed based on their median neighborhood income as documented in Canada’s 1996 census. We determined the risk of death at thirty days and one year based on neighborhood income. Secondary analyses compared use of medications and carotid endarterectomy by income level. We used multivariate analyses to adjust for age, sex, stroke type, comorbid conditions and hospital and physician characteristics.
Results:
Overall, 39,545 patients were admitted with stroke during the study time frame. The crude 30-day and 1-year mortality rates were 19% and 33%, respectively. Thirty-day mortality was higher in those in the lowest income quintile than in the highest quintile (20% vs. 17%, P=0.002), with an adjusted hazard ratio of 1.1. One-year mortality was also higher in the lowest compared to the highest income quintile (34% vs. 31%, P=0.001), with an adjusted hazard ratio of 1.1. Each $10,000 increase in median neighborhood income was associated with a 9% reduction in the risk of death at 30 days (adjusted hazard ratio 0.91) and a 5% reduction in the risk of death at one year (adjusted hazard ratio 0.95). There were no differences in the use of medications (aspirin, ticlopidine, warfarin) or carotid endarterectomy based on socioeconomic status. However, waiting times for carotid surgery were significantly longer in the lowest income quintile compared to the highest (90 days vs. 60 days, P=0.001).
Conclusion:
Socioeconomic status affects mortality following stroke, even in a province with universal health care. The exact reasons for this effect on survival remain topics for future research.
Magnesium Therapy for Subarachnoid Hemorrhage Induced Cerebral Vasospasm as Assessed by In Vitro Studies on the Porcine Carotid Artery
Authors: Pyne Gail J , Nakayama Shinsuke , Choutka Ondrej J , Cadoux-Hudson Thomas Ad , Clark Joseph F
Published: July 2021

82

Background:
Mg
2+
has been used therapeutically in the treatment of eclampsia and it has recently become a novel avenue in the treatment of stroke because it can relax vascular smooth muscle. Currently there is a clinical trial, on going in England, involving Mg
2+
administration to stroke patients. But relatively little is known regarding the function or mechanism of Mg2+ treatment following subarachnoid hemorrhage (SAH). We therefore set out to determine if Mg
2+
could be used to prevent or reverse the
in vitro
vasospasm caused by the CSF from vasospastic (SAH) patients.
Methods:
Oxygen consumption and isometric force measurements of the isolated porcine carotid artery were used to assess the functional and metabolic responses of the vascular smooth muscle following stimulation by CSF from SAH patients with cerebral vasospasm. We used a method of exposing the vascular smooth muscle to 12 mM MgCl
2
for 1 hour to increase intracellular magnesium. This method has been shown to increase intracellular Mg
2+
to levels reached with two to three days of Mg
2+
therapy.
Results:
CSF from SAH patients with vasospasm will cause vasospasm when applied to vessels
in vitro
. Following this
in vitro
vasospasm, Mg
2+
caused a dose dependant decrease in tension (relaxation) following exposure to CSF from vasospasm patients. Exposure of vessels to 12 mM Mg
2+
normalized the rate of relaxation in the presence of CSF from SAH patients was normalized (2.70±0.71 Nm
-2
s
-1
in the presence of CSF; 15.8±4.20 Nm
-2
s
-1
with CSF and Mg
2+
; and 16.1±4.85 Nm
-2
s
-1
without CSF). Mg
2.
significantly (P≤0.05) decreased the rate of oxygen consumption observed when stimulated by CSF (0.70±0.03 μmol O
2
min
-1
g
-1
with CSF alone and 0.46±0.08 μmol O
2
min
-1
g
1
with CSF and Mg
2+
).
Conclusion:
These results suggest that Mg
2+
is a potent vasodilator that helps to normalize contractile behavior and metabolism of the porcine carotid artery exposed to the CSF of SAH patients with vasospasm. Therefore, Mg
2+
therapy is a possible avenue for treating patients with cerebral vasospasm by causing a relaxation of vascular smooth muscle.
Plasma C-Reactive Protein, Systolic Hypertension and Risk of Ischemic Stroke and TIA: The Framingham Study
Authors: Rost Natalia S , Kase Carlos S , Wolf Philip A , Massaro Joseph M , Kelly-Hayes Margaret , D’Agostino Ralph B , Wilson Peter W F
Published: July 2021

83

Background:
The role of plasma C-reactive protein (CRP) as marker of cerebrovascular risk is currently under investigation. We evaluated relative risk of developing first ischemic stroke and TIA among the patients with elevated systolic blood pressure (SBP) and/or elevated plasma CRP levels versus those patients with unelevated SBP and unelevated CRP.
Methods:
We studied 591 men and 868 women of the original Framingham Study cohort who were free of stroke and TIA at the time of their 1980–1982 clinic exam. Sex-specific Cox proportional hazards regressions were used to quantify the risk of 14-year incidence of ischemic stroke/TIA associated with elevated SBP and CRP. Unadjusted models and models adjusted for age, smoking, total & HDL cholesterol, and diabetes were used. SBP and CRP were included in the Cox models as sex-specific quartiles. Risk ratios of first ischemic stroke/TIA for individuals with elevated (in the upper quartile) SBP (SBP+) and CRP (CRP+) were determined using the SBP-/CRP- individuals as a reference group. Similarly, simultaneous evaluation of the risk of first ischemic stroke/TIA was done for SBP+/CRP- and SBP-/CRP+ using the individuals in SBP-/CRP- as a reference group.
Results:
Relative to SBP-/CRP- men (incidence of first ischemic stroke/TIA of 36/328, or 11.0%), SBP+/CRP+ men (where incidence was 8/32, or 25.0%) had unadjusted risk ratio of 3.56 (p=0.001). This ratio was nearly twice that for SBP+/CRP- men (incidence=20/115, or 17.4%; RR=1.89, p=0.023). Relative to SBP-/CRP- women (incidence= 45/485, or 9.3%), the unadjusted risk ratio increased from 2.03 in SBP+/CRP- women (incidence=27/166, or 16.3%; p=0.001) to 3.44 in SBP+/CRP+ women (incidence=15/58, or 25.9%; p<0.001). Adjustment for age did not significantly alter this relationship. Following multivariate adjustment, risk of developing first ischemic stroke/TIA remained significantly elevated in SBP+/CRP+ men (RR=2.7; p=0.018) and women (RR=2.06; p=0.027).
Conclusion:
Having both CRP levels and systolic BP above the 75
th
percentile for each of these parameters significantly increased risk of developing first ischemic stroke/TIA in both sexes.
Adherence to Post-Acute Rehabilitation Guidelines Improves Functional Recovery in Stroke
Authors: Duncan Pamela W , Horner Ronnie D , Reker Dean M , Ctr VA Medical , City Kansas , KS  , Samsa Gregory P , Hoenig Helen , Hamilton Byron , LaClair Barbara J , Dudley Tara K
Published: July 2021

97

Purpose & Methods:
To assess if compliance with post-stroke rehabilitation guidelines improves functional recovery. The design of the study was an inception cohort of stroke patients followed prospectively for 6 months. The setting was eleven Department of Veteran Affairs Medical Centers providing care to stroke patients. The subjects included 288 selected patients with stroke admitted between January 1998 - March 1999. Data were abstracted from medical records and telephone interviews. Primary outcome was the Functional Independence Motor Score (FIM). Secondary outcomes included Instrumental Activities of Daily Living (IADL), SF-36 physical functioning, and the Stroke Impact Scale (SIS). Acute and post-acute rehabilitation composite compliance scores (range 0–100) were derived from an algorithm. All outcomes were adjusted for case mix.
Results:
Average compliance scores in acute and post acute care settings were 68.2% (+ 14) and 69.5% (+ 14.4), respectively. After case-mix adjustment, level of compliance with post-acute rehabilitation guidelines was significantly associated with FIM motor, IADL, and the SIS physical domain scores. SF-36 physical function scores and mortality were not affected by compliance with post-acute rehabilitation guidelines. Level of compliance with rehabilitation guidelines in acute settings was unrelated to any of the outcome measures.
Conclusion:
Process of care in post-acute stroke rehabilitation affects 6-month functional recovery. Our findings support the use of guidelines as means of assessing quality of care and improving outcomes. These quality indicators are needed to ensure that quality of care is not comprised with new organizational and funding changes involving post-acute stroke care.
Effects of Acute ICH on Hemispheric Blood Flow and Metabolism
Authors: Zazulia Allyson R , Diringer Michael N , Videen Tom O , Adams Robert E , Yundt Kent , Aiyagari Venkatesh , Grubb Robert L , Powers William J
Published: July 2021

122

Background:
Increased oxygen extraction fraction (OEF) suggesting reduced cerebral perfusion pressure below the autoregulatory limit has been reported in subacute hypertensive (HTN) ICH. We sought to confirm this finding in acute ICH.
Methods:
Nineteen HTN patients aged 63±15 years with spontaneous supratentorial ICH (.3–99 cc; median 12) were studied with PET 5–22 hours after onset. Five patients were re-studied after BP was lowered 23±9 mm Hg. Subsets of patients were age-matched to normal and HTN controls. Cerebral blood flow (CBF), metabolic rate (CMRO
2
), and OEF for each hemisphere were derived from a 2-cm cortical rim. All measurements were corrected for partial volume effect.
Results:
Ipsilateral OEF was elevated and CBF and CMRO
2
reduced compared to normal controls, but not to levels sufficient to produce infarction. (Table.) OEF was no different from HTN controls, however. There was no correlation between OEF and size of clot or ventricles, suggesting that elevated OEF was not due to increased ICP or mass effect. Lowering of BP did not change CBF (-1.7±2.2 ml/100g/min); thus, there was no evidence for autoregulatory failure.
Conclusions:
Elevated hemispheric OEF in acute ICH may reflect the effects of chronic hypertension rather than increased ICP or other effects of the hematoma.
Echo-Enhanced Transcranial Color Coded Duplexsonography versus Digital Subtraction Angiography for Diagnosis of Intracranial Vascular Diseases
Authors: Kunz Alexander
Published: July 2021

P7

Objective:
To assess the diagnostic efficacy of echo-enhanced transcranial color coded duplexsonography (eTCCD) for noninvasive evaluation of the intracranial vasculature in patients with cerebrovascular symptoms.
MATERIAL AND METHODS:
We prospectively evaluated 35 consecutive patients (10 women, 25 men, mean age 58,8 ± 9,7) with eTCCD (galactose palmitic acid based echo-enhancing agent) and digital subtraction angiography (DSA). All patients were admitted to our neurology department for acute onset of cerebrovascular symptoms.
RESULTS:
In 34/35 patients eTCCD visualized the circle of Willis. In 15/17 patients with critical symptomatic internal carotid artery obstruction (lumen diameter reduction of >85% or occlusion) eTCCD correctly identified collateral flow patterns through the circle of Willis. DSA and eTCCD showed MCA-occlusion in 4 patients. In one of these patients eTCCD correctly identified a contralateral severe MCA-stenosis, which was first missed by DSA but confirmed by angiographic reevaluation. In 1 patient eTCCD missed occlusion of a M3-segment. In 2/3 patients eTCCD showed intracranial ICA-stenosis. In 3 patients with symptoms suggestive for basilar artery thrombosis DSA and eTCCD showed severe basilar stenosis in 1 patient and intracranial vertebral artery occlusion in 2 patients. DSA and eTCCD were normal in 3 patients with atypical intracranial hemorrhages and in 1 patient with subarachnoid hemorrhage. In another patient eTCCD correctly suggested a left parietooccipital AVM. DSA and eTCCD were normal in 4 other patients.
CONCLUSION:
eTCCD reliably detects occlusion, stenosis and collateral flow patterns of the basal cerebral arteries in patients with cerebral ischemia. For patients with cerebral hemorrhage our data are limited.
Continuous Monitoring of Jugular Bulb Oxygenation during Carotid Temporary Balloon Occlusion
Authors: Schwamm Lee H , Bellon Richard , Norbash Alexander , Budzik Ronald , Ogilvy Christopher , Putman Christopher
Published: July 2021

P19

Background:
Temporary balloon occlusion (TBO) helps assess the safety of ICA sacrifice in the treatment of aneurysms and head/neck cancers. Several techniques have been used in combination with the clinical exam during TBO to predict low flow ischemia after permanent occlusion (SPECT, MR, Xenon-CT, EEG, TCD). All have poor predictive value. Continuous jugular bulb oximetry (SjvO
2
) provides easily interpretable, real-time data about cerebral oxygen extraction. It is a surrogate measure for CBF under steady-state conditions and can identify hemispheric hypoperfusion.
Methods:
An oximetric catheter was placed in the jugular bulb that preferentially drained the hemisphere in question. In the setting of systemic heparinization and continuous neurologic monitoring, TBO of the ICA was performed for 30 min. Hypotension to 70% of baseline BP was induced with nitroprusside for the last 15 min of the TBO. SjvO
2
and MAP were sampled at 0.5 Hz. A slope changepoint for the MAP vs. SjvO
2
relationship was calculated with a two-phase linear regression model, to identify the point at which SjvO2 became independent of MAP. This inflection point defines the autoregulatory portion of the MAP vs. SjvO
2
curve. SPECT tracer (5 patients) was injected during hypotension when available. TBO failure was based on SPECT and symptoms, blinded to the SjvO
2
data.
Results:
10 consecutive patients (mean age 57, 30% male, 40% with hypertension) were studied, 3 of whom failed TBO. Two showed ischemic symptoms referable to the ICA tested (1 with normal SPECT), and 1 had equivocal symptoms but hemispheric hypoperfusion on SPECT. All 3 developed SjvO
2
≤ 45% at a MAP > 70 mmHg. In the 3 patients who failed TBO, the changepoint on the MAP vs. SjvO
2
curves occurred at a higher MAP value than in the patients who passed TBO (mean MAP 100 vs. 72; p=. 05). The 7 patients without symptoms or abnormal SPECT tolerated sacrifice.
Conclusion:
Continuous SjvO
2
monitoring may help identify patients who are still at risk for delayed ischemia despite subtle or no neurologic symptoms during TBO. It may also help guide post-occlusion hemodynamic management in patients with changepoints above 70 mmHg. Further study is warranted.
Utility of T2* Gradient-Echo Magnetic Resonance Imaging in Routine Imaging of Ischemic Stroke
Authors: Muthukumaran Abirami , Cohen Stanley N , El-Saden Suzie , Hathout Gasser
Published: July 2021

P27

Objective:
To determine the utility of routine T2* weighted gradient-echo magnetic resonance imaging (MRI) in evaluating patients with ischemic stroke.
Methods:
One hundred stroke patients with CT scans negative for hemorrhage were prospectively evaluated with T1, T2, FLAIR, and T2* weighted gradient-echo imaging.
Results:
Ten T2* scans showed evidence of prior hemorrhage, 9 asymptomatic. Seven had abnormalities seen only on T2* imaging. Three had evidence of blood products on T2 as well as T2* (1 subacute). In one patient, a T2* done 2 hours after giving tPA showed abnormality consistent with amyloid angiopathy. She had a subsequent hemorrhagic complication. Discussion: Ten percent of our patients with negative CT scans showed evidence of prior hemorrhage on MRI. Seven percent showed abnormality consistent with hemorrhage only on T2* imaging. T2* sequences are rapidly obtained and readily available on most existing scanners with no additional hardware or software requirements. The information obtained may not be available clinically or with other imaging studies and may alter both acute and chronic management decisions.
Conclusion:
While our sample size is small, our data indicate that T2* gradient-echo MRI may a valuable tool in the routine imaging evaluation of ischemic stroke.
A stroke neurologist/nurse operated acute stroke TCD service can reliably identify MCA occlusion when compared to MRA.
Authors: Demchuk Andrew M , Beaupre Derek , Barber Philip A , Hill Michael D , Button Allison , Morrish Will , Hudon Mark E , Frayne Richard
Published: July 2021

P39

Background:
Hyperacute neurovascular imaging has great potential to help clinicians better tailor stroke therapy. Future decisions to use intravenous and/or intra-arterial lytics may depend on site of MCA occlusion. TCD has not been seriously considered as such a technique because of the misconception TCD is too operator dependent and not reliable. We evaluated if our acute stroke TCD service could accurately and reliably identify MCA occlusion.
Methods:
A series of acute stroke patients underwent TCD examination by 1 of 3 stroke physicians or 1 stroke nurse. MRA was also performed at a time closely corresponding to TCD exam. Blind to MRA findings and patient info except symptom side, all 4 sonographers independently interpreted the TCD exam for presence of MCA occlusion using previously established TCD criteria and evaluated TIBI flow grades (5 normal waveform, 4 stenotic, 3 dampened, 2 blunted, 1 minimal, 0 absent) at 65, 55, 45 mm MCA depths. This result was compared to blinded neuroradiologists MRA interpretation for M1-MCA and distal MCA occlusion.
Results:
37 cases compared. Mean age 67, median baseline NIHSS 8. Median symptom onset to TCD 5.9 hours and MRA 6.3 hours. Median time between TCD and MRA 1.3 hours. TPA treatment preceded or occurred during TCD or MRA imaging in 27% of cases. MRA identified 19 MCA occlusion (12 M1-MCA, 7 distal MCA) and 18 no MCA occlusion. Comparing all sonographer TCD interpretations (n=148) with MRA the sensitivity, specificity, PPV, NPV for MCA occlusion was: 82%, 81%, 82%, 81% respectively. Intraclass correlation coefficent for TIBI flow grades at prox, mid, distal MCA depths was : 0.73,0.84,0.83. Median TIBI scores at these 3 MCA depths respectively were: 5,5,5 when no MCA occlusion on MRA, 3,3,3 if distal MCA occlusion and 2,2,2 if M1-MCA occlusion.
Conclusion:
TCD showed good accuracy at identifying MCA occlusion compared to MRA when TCD was performed and interpreted by a stroke clinician/nurse. TIBI flow grades were reliably identified and appear potentially useful to discriminate between normal MCA, and proximal or distal MCA occlusion. TCD is a useful bedside tool that could aid future stroke treatment.
Lateral venous sinus thrombosis associated with MRI abnormalities in the mastoid air sinus.
Authors: Fink John N , McAuley David L
Published: July 2021

P45

Background:
Lateral venous sinus thrombosis can be associated with mastoiditis. We encountered several cases of lateral sinus thrombosis associated with MRI abnormalities in the ipsilateral mastoid air sinus that had no clinical evidence of mastoiditis. The relationship between lateral sinus thrombosis and mastoid abnormalities was evaluated systematically.
Method:
The clinical records and radiology of all adult cases of cerebral venous sinus thrombosis (CVT) diagnosed or treated at Auckland Hospital 1990–1999 were reviewed retrospectively.
Results:
Twenty-six cases of CVT were identified. Thrombosis was present in 23 lateral sinuses in 20 cases. Mastoid abnormalities were detected ipsilateral to nine of 23 thrombosed lateral sinuses (39%) and were associated with none of 29 unaffected lateral sinuses (p<0.001). Clinical evidence of mastoiditis was not present in any case. One case with mastoid abnormality and lateral sinus thrombosis received antibiotics; eight did not. All made uneventful recoveries. Reversal of the MRI abnormality after anticoagulation but without antibiotic treatment was demonstrated.
Conclusion:
Lateral venous sinus thrombosis is commonly associated with ipsilateral MRI abnormalities in the mastoid air sinus. These abnormalities are most likely to be due to venous congestion as a consequence of venous thrombosis and do not inevitably represent infective mastoiditis. Patients presenting with lateral sinus thrombosis and mastoid congestion should have a thorough clinical assessment for the presence of mastoiditis. When there is no clinical evidence of infection, treatment should be directed at the underlying cerebral venous thrombosis; additional treatment with antibiotics is not required.
EVALUATION OF ABNORMAL HEMODYNAMICS IN INTRACRANIAL ARTERY OCCLUSION USING DYNAMIC SPECT
Authors: Mizumura Sunao , Kumita Shin-ichiro , Kojima Toyoyuki , Nakajo Hidenobu , Akiyama Kazuyoshi , Toba Masahiro , Takasu Masaru , Kumazaki Tatsuo
Published: July 2021

P55

We evaluated the hemodynamics under ischemic state to examine cerebral blood flow tracer processing toward equilibrium using Tc-99m ethyl cysteinate dimer (Tc-99m ECD) dynamic SPECT. Dynamic SPECT studies were performed in 32 patients with unilateral chronic internal carotid artery or middle cerebral artery occlusion and 16 controls in the absence of arterial stenosis on MR angiography. Dynamic SPECT data (30sec′24frames) were acquired immediately after the administration of Tc-99m ECD. Although the radioactivity of both cerebral hemispheres reached plateau phase within 180sec after the injection based on time-activity curve, the radioactivity of affected cerebral hemisphere showed slower build-up than that of contralateral unaffected hemisphere. The build-up (0–180sec) and plateau phase (540–720sec) images were analyzed statistically. Twenty of 32 patients demonstrated reduced accumulation of the affected hemisphere on the build-up phase images, although all patients showed normal accumulation on plateau phase images. In 17 of 32 patients, the discrepancy of the accumulation on the affected hemisphere between the build-up and plateau phase images was corresponded to that with reduced reactivity to acetazolamide, reflecting the impairment of vasucular reseve in brain tissue. We speculate that the reduced accumulation of the affected hemisphere in the build-up phase image was derived from flow delay due to arterial occlusion and the collateral flow. Our finding suggests that dynamic SPECT allow detecting the compensatory vasodilatation by means of the evaluation of tracer s equilibrium process in brain tissue where ischemic change such as misery perfusion is present. In conclusion, not only tracer extraction (plateau phase) image but also intra-vascular tracer delivery (build-up phase) image would provide important information of abnormal hemodynamics.
Correlation of neuronal cell death, functional image and electrical activity after a focal cerebral ischemia in the mouse
Authors: Wei Ling , Langsdorf Jennifer , Zeng Jinsong , Yu Shan Ping
Published: July 2021

P70

Functional loss and recovery are critical issues after an ischemic insult. The focal ischemia in the cerebral barrel cortex is an ideal model for studying short- and long-term functional alterations of sensory cortex. We extend the “mini-stroke” model from rat to mouse by studying the correlation between neuronal injury and functional activities, intrinsic optical signals (IOS) and evoked potentials in response to whisker stimulation in the ischemic barrel cortex of the mouse. Methods. Adult mice were anesthetized and multiple branches of the middle cerebral artery (MCA) that supply the right side of the barrel cortex were permanently ligated. IOS were used for identifying the barrel cortex; a recording electrode was placed in multiple sites of the barrel cortex in and around the ischemic region. Local cerebral blood flow (LCBF) was measured by Laser Doppler and quantitative autoradiography. Cell injury was determined by immunohistochemistry after the ischemia. Results. Immediately after MCA ligations LCBF was markedly reduced to 10% of control levels followed by simultaneous losses of IOS and evoked potentials in the ischemic side of the cortex. IOS responses and evoked potential were closely matched in all cases. TUNEL positive and/or CM-1 positive cell death and lack of cytochrome oxidase staining in the ischemic core were found 2 days after ischemia and continued for up to 10 days later. With the exception of ischemic injury, IOS image and evoked potential were partially recovered 30 days after the ischemia. Conclusion. The small focal stroke in the mouse barrel cortex shows high reliability for functional assays and their correlation to LCBF. Apoptosis may contribute to the ischemic barrel injury. The functional recovery 30 days after ischemia implies a neurovascular plasticity that is beneficial for long-term rehabilitation after a focal ischemic stroke. Supported by grants from NIH (NS37372) and AHA (IBN-9817151).
A PPARγ agonist reduces proinflammatory cytokine immunoreactivity and infarct size following transient focal ischemia in rats
Authors: Sundararajan Sophia , Lust W David , Landreth Gary E
Published: July 2021

P82

Inflammation plays a critical role in the generation of ischemic injury. Ischemic insult results in the activation of microglia and secretion of proinflammatory products including the cytokines interleukin-1β and tumor necrosis factor-α. Both of these cytokines exacerbate ischemic injury. Microglial proinflammatory gene expression is regulated by the transcription factor peroxisome proliferator activated receptor (PPAR). PPARγ is a member of the nuclear hormone receptor family and upon binding of agonist acts to inhibit proinflammatory gene expression. We hypothesized that PPARγ agonists reduce the inflammatory reaction seen following stroke and limit infarction size. We utilized a reversible model of middle cerebral artery occlusion to induce two hours of ischemia in rats to test our hypothesis. Blood pressure, blood gases and temperature were monitored and maintained within normal ranges throughout the procedure. Vehicle (DMSO) or troglitazone, a PPARγ agonist previously approved by the FDA, was administered to rats twenty-four hours before and again at the time of occlusion in doses of 35, 70 or 100 mg/kg in DMSO. Twenty-four hours after occlusion animals were euthanized. Infarct volume was calculated from fixed frozen sections and additional sections were processed for immunocytochemistry. Results show over sixty percent reduction in infarct volume in rats treated with 35 mg/kg and 70 mg/kg troglitazone. These data were statistically significant (n≥5;p<0.05). Interestingly the 100 mg/kg dose of troglitazone did not protect against ischemia. Immunoreactivity against the proinflammatory cytokines Il-1β and TNFα was reduced in the peri-infarct region of troglitazone treated rats. Furthermore, immunoreactivity against other markers of inflammation, intracellular adhesion molecule, major histocompatibility complex antigen I and cyclooxygenase-2 was also reduced in troglitazone treated animals compared with vehicle treated animals. These data indicate that the PPARγ agonist, troglitazone, reduces infarct size following cerebral ischemia likely due to the drug’s anti-inflammatory properties.
Fever is Associated With Third Ventricular Shift in Intracerebral Hemorrhage
Authors: A De Georgia Michael , Charles Bae , Andrefsky John C , Abou-Chebl Alex , Derk Krieger W
Published: July 2021

P104

Introduction:
Several studies have shown the detrimental effect of fever on brain injury. Recently, the incidence and prognostic significance of fever after intracerebral hemorrhage (ICH) was reported. The underlying cause of fever remains speculative. We present data on fever after ICH, volume of ICH, 3rd ventricular shift, and patient outcome.
Methods:
Data from 61 patients with ICH were collected prospectively from August 1999 to April 2000 including age, admission Glasgow Coma Scale (GCS) score, ICH volume, 3rd ventricular shift, maximum temperature (Tmax) and fever (T >38.5 °C) at 24, 48, 72 and 96 hours. Patients were screened for common causes of fever. Outcome was determined by mortality at discharge and National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel Index (BI) at 3 months. Spearman correlation coefficient, Mann-Whitney test, and logistic regression were used to assess relationships. No adjustment was made to significance criterion for multiple comparisons over time.
Results:
The average age was 65 ± 16 years. The mean admission GCS score was 8.8 ± 4.8. The mean ICH volume was 48.9 ± 52.4 cc. The mean 3rd ventricular shift was 3.6 ± 4.5 mm. The mean Tmax was 38.0 ± 0.9°C. There was a correlation between ICH volume and Tmax at 24 hours (p= 0.04) and at 72 hours (p= 0.03) and fever at 24 hours (p=0.039) and at 72 hours (p=0.036). Tmax at 72 hours correlated with 3rd ventricular shift (p= 0.01). Patients with 3rd ventricular shift > 1 mm were more likely to have a fever within the first 72 hours (p= 0.049). Multivariate logistic regression analysis showed no confounding effects from intubation status, presence of infection (positive blood, sputum, or urine culture/urinalysis), abnormal chest x-ray, or DVT. Fever at 72 hours was associated with a higher mortality at discharge (p=0.046). Fever within 72 hours was associated with a trend of a worse NIHSS score (p=0.06) at 3 months but no worse outcome by BI or mRS score at 3 months.
Conclusion:
Fever after ICH correlates with 3rd ventricular shift and ICH volume. The underlying mechanism may be hypothalamic dysfunction. Fever may be associated with a worse outcome but more studies are needed.
Ischemic Stroke in the Very Old: The Lausanne Stroke Registry
Authors: R de Freitas Gabriel , Gaigalaite Virginija , van Melle Guy , Devuyst Gerald , Bogousslavsky Julien
Published: July 2021

P145

Background:
Although the population of developed countries is changing and the very old represent the fastest-growing group, there are few studies on ischemic stroke in this age group. The aim of this study was to investigate characteristics of ischemic stroke in very old patients (VOP).
Methods:
We studied risk factors, etiology, clinical findings, lesion topography and short-term (one month) outcome in patients aged 80 years or older presenting with a first ever ischemic stroke compared to younger patients (YP), aged between 45 and 79 years. Logistic regression analysis was used to identify whether very old age was an independent predictor of poor outcome (mRS 4–6).
Results:
452 patients (13%) were older than 80 years, and 2,889 (87%) between 45 and 79 years. There was a higher proportion of females in the VOP than in the YP (53% vs. 34%; P<0.001). The VOP group had lower frequencies for smoking (7% vs. 32%; P<0.001), hypercholesterolemia (16% vs. 27%; P<0.001) and an elevated hematocrit (12% vs. 19%; P<0.001). In contrast, a history of atrial fibrillation (23% vs. 9%; P<0.001) and coronary artery disease (30% vs. 22%; P<0.001) was more common in the VOP. Cardioembolic stroke was more frequent in the VOP (28% vs. 21%; P<0.001), whereas large artery disease was less frequent (18% vs. 24%; P<0.001). The frequency of small artery disease was comparable in the two groups. VOP more often presented an abrupt onset of symptoms (81% vs. 73%; P<0.001) and isolated Wernicke-type aphasia (4% vs. 1%; P<0.001), but a lower frequency of headache (7% vs. 14%; P<0.001). Except for a higher proportion of lesions in the left posterior superficial branch of the middle cerebral artery in VOP (9% vs. 6%; P=0.03), there was no difference in the cerebral territories involved. A poor outcome was more frequent in VOP than in YP (17% vs. 12%; P=0.003), but this was not seen after correction for confounding factors.
Conclusions:
Patients older than 80 years have different risk factors and stroke features compared with patients between 45 and 79 years. Although VOP have a poorer prognosis, age
per se
is not a predictor of short-term disability and death. Knowledge of these findings may improve stroke prevention and acute treatment in VOP.
Triggers of Ischemic Stroke: Results from the Stroke Onset Pilot Study
Authors: Mittleman Murray A , Voetsch Barbara , Caplan Louis R
Published: July 2021

P153

Despite progress in the identification of risk factors for stroke, relatively little is known about the immediate precipitants or triggers of acute ischemic stroke (IS). We therefore conducted a pilot study to determine the presence of potential triggers within 24 hours preceding the onset of IS to establish the feasibility of conducting a case-crossover study of potential triggers of IS. The case-crossover design is an epidemiologic method that uses each patient as his/her own control, developed to evaluate the effect of potential triggers on the incidence of acute events. During the time of the pilot, we recruited 50 patients (88% of all eligible hospitalized patients) mean age 62±16 years, including 32% women. Patients were typically interviewed in hospital within 2 or 3 days of the onset of IS. The structured interview covered use of medications, caffeinated beverages, alcohol, smoking behavior, illicit drugs including marijuana and cocaine, timing of meals particularly unusually large meals, episodes of straining for defecation or urination, sexual intercourse and heavy physical exertion. Separate questions emphasized lifting heavy objects, and psychometric evaluations of anger, anxiety and depression. Large vessel atherothrombotic lesions were responsible for 39% of strokes, cardioembolic sources for 28%, small vessel disease (lacunar infarcts) for 22%, and other etiologies for 11%. The prevalence of exposure in the year prior to stroke varied from 10% for marijuana to 88% for caffeinated beverages. Exposure to potential triggers in the 24 hours before stroke onset was reported in over 30% of cases, including heavy exertion ≥ 6 METs (8%), lifting ≥ 50lbs (10%), straining for urination or defecation (4%), sexual intercourse (2%), outbursts of anger (4%), alcohol (28%), and marijuana (6%). The Stroke Onset Study Pilot demonstrates that potential triggers are present in approximately one-third of patients with IS. A larger study is required to assess whether external stressors can trigger the onset of stroke. Identifying and understanding the mechanisms by which particular exposures trigger the onset of stroke may lead to novel preventive strategies.
Emergency Medical Services (EMS)Response and Transport Time for Stroke in an Urban African-American Population: Effect of Socio-demographics of the Patient’s ZIP Code
Authors: Graus Jessica A , Khoury Jane C , Jauch Edward C , Miller Rosie , Kothari Rashmi U , Gebel James , Pancioli Arthur M , Qi Rong , Woo Daniel , Kissela Brett M , Brott Thomas G , Broderick Joseph P
Published: July 2021

P166

Introduction:
Our hypothesis is that the total time between a 911 call and arrival at the Emergency Department (ED)(EMS time) varies by the socio-demographics of a stroke patient’s ZIP code, controlling for distance to the ED (EMS distance). This study considers an urban African-American (AA) population.
Methods:
We identified all hospitalized and autopsied strokes/TIAs between 1/1/93 and 6/30/93 for AA residents in the Greater Cincinnati/ Northern Kentucky area. Address and timing of stroke and emergency care were abstracted from the medical chart. We obtained socio-demographic data for the ZIP code of residence from 1990 Census files: income, % AA, % on public assistance, and % below poverty. Location of residence and ED and estimation of EMS distance were calculated using ARCVIEW software. Linear regression was used for analysis.
Results:
Of 352 strokes, 268 occurred at home, 123 used EMS transport, and 81 had complete time data. Longer EMS time was associated with percent of the residents in the ZIP code on public assistance (p=.03), controlling for EMS distance (p=.02, Table). No other personal or socio-demographic attributes of the ZIP code were significant.
Conclusion:
ZIP codes with a higher percentage of residents on public assistance had significantly longer EMS times than ZIP codes with a lower percentage. Issues that may influence this relationship will be discussed.
Atrial Fibrillation and Intra-arterial Thrombolysis
Authors: Liebeskind David S , Saver Jeffrey L , Duckwiler Gary R , Kidwell Chelsea S , Carneado Joaquin , Starkman Sidney , Vespa Paul M , Gobin Y. Pierre , Jahan Reza , Kasner Scott E , Vinuela Fernando
Published: July 2021

P169

Background:
Atrial fibrillation (AF) is associated with increased stroke severity and mortality. Intra-arterial thrombolysis may be of particular benefit for these patients.
Methods:
Review of 90 consecutive intra-arterial thrombolysis cases (mean age 69 years, range 25–94; 53% female) performed at UCLA from July 1992 to June 2000. Clinical, radiologic, and angiographic variables were analyzed in relation to AF.
Results:
AF (56% paroxysmal, 44% chronic) was identified in 53% of all cases. Only 54% of AF was present on admission, with delayed onset in 17% (median 3 days), and no observed in-hospital AF in 29% despite a history of AF. AF was new-onset in 23% of cases. At time of admission, only 30% of known AF patients were receiving antithrombotic treatment for stroke prevention per ACCP guidelines. Anticoagulation was subtherapeutic at presentation in all 11 chronically anticoagulated patients. Time to presentation was shorter for AF patients, 50 minutes vs 67 minutes, p<.03. The recanalization rate (TIMI ≥ 2) in AF patients was 67% (vs 69% in non-AF patients, p=.81). Hemorrhage rates trended higher in AF (46% vs 31%, p=.15), including parenchymal hematomas (38% vs 21%, p=.10) and symptomatic hemorrhages (25% vs 10%, p=.06). Deficit severity at presentation in patients with AF was median NIHSS 16 (vs 15 in non-AF patients, p=.29). Deficit severity improved at day 7 in AF patients to median NIHSS 12 (vs 6 in non-AF patients, p=.32). Functional outcomes at day 7 were similar between groups, with percent dead or disabled (mRS > 2) 60% in AF patients and 52% in non-AF patients, p=.44. AF was associated with a trend toward elevated in-hospital mortality (19% vs 7%, p=.11). Among AF patients, AF was classified as etiologic of stroke in 79% and not etiologic in 21% (SPAF III classification algorithm). No cases of recurrent symptomatic ischemia occurred during hospitalization.
Conclusions:
In this series, intra-arterial therapy among patients with AF achieved recanalization in 67%, with symptomatic hemorrhagic transformation in 25%, and good functional outcome in 40%. Intra-arterial thrombolysis is a promising treatment for patients with ischemic stroke and atrial fibrillation.