bluuebunny/crossref_metadata_2025 huggingface dataset:
THE ”MAKING“ OF A PARENCHYMAL HEMATOMA. An early coagulopathy and specific risk factors contribute to grave intracerebral bleeding after intravenous rtPA thrombolysis.
Authors: Trouillas Paul , Philippeau Frederic , Nighoghossian Norbert , Derex Laurent , Honnorat Jerome , Adeleine Patrice
Published: March 2022

P34

Background :
Several factors are suspected in the occurrence of hemorrhages after rtPA thrombolysis in cerebral infarcts, but little is known about coagulation in these patients. Methods and results : One hundred consecutive patients had rtPA at the dose of 0.8 mg/kg infused for 90 minutes.We studied the values of fibrinogen, FDP, aPTT, INR and thrombocyte count before thrombolysis and at 2 and 24 hours.
Results:
Cerebral bleeding at 24 hours included 16 hemorrhagic infarcts (HI) and 7 parenchymal hematomas (PH). 1. Cerebral bleeding in general. Univariate analysis comparing patientswith HI+PH vs patients without bleeding detected 2 significant factors : severity at entry (p=0.03) and and increased values of FDP at 2 hours (p=0.05). Each early CT symptom and pooled early CT symptoms did not appear as factors of bleeding. Multivariate analysis showed that values of FDP>150mg/L multiplicate the odds of bleeding by 6.9, being then a more powerful factor than severity at entry. 2. Factors of seriousness of bleeding. FDP values>150 mg/L multiplicate the odds of parenchymal hematoma by 17. Comparison of patients with PH and HI only showed one potential factor, the lack of hypercholesterolemia (p=0.06). Interestingly, age, delay, severity at entry, early CT signs of ischemia were not factors of parenchymal invasion. Heparin in the fist 24 hours was a potential factor, but not reaching statistical significance. In a logistic regression model, the lack of hypercholesterolemia multiplicates the risk of PH by 10. Conclusion : The ”making“ of a parenchymal hematoma involves at least 2 phases : (1) an early ”acquired coagulopathy“ characterized by increased FDP values at 2 hours (ie a particularly intense thrombolysis); and (2) an increased vulnerability of the arteriolar wall, possibly related to the lipid content of the vessels. The observation of the ”coagulopathy“ should contraindicate any antithrombotic drug during the first 24 hours and imply a surveyance of haemostasis and cerebral bleeding with T2* gradient-Echo MRI during the following days.
Improved Reliability of Stroke Classification Using the TOAST Criteria
Authors: Goldstein Larry B , Jones Michael R , Matchar David B , Edwards Lloyd J , Hoff Jennifer , Chilukuri Vani , Armstrong S. Beth , Horner Ronnie D
Published: March 2022

P35

PURPOSE.
Improve the reliability of stroke subtype classification.
BACKGROUND.
We previously found that the reliability of stroke subtype assignment using the TOAST criteria was only fair. In a two phase process to improve inter-rater agreement, we first developed a computerized algorithm for diagnositic categorization (Neurology 1999; 52: A243). In this second phase, residual variability related to differences in data abstraction was systematically assessed and reduced.
METHODS.
To assess baseline levels of inter-rater agreement, 4 physicians first retrospectively assigned TOAST subtype diagnoses for a randomly selected series of 14 patients. These diagnoses were then compared with those assigned by the computerized algorithm. Critical disagreements in data abstraction were identified and remaining variability reduced with the development of standardized abstraction procedures. Inter- and intra-rater reliability were reassessed in separate randomly selected groups of cases.
RESULTS.
There was fair to moderate agreement between the algorithm-based and physician-assigned diagnoses for the baseline cases (kappa, k = 0.41, 95% CI: 0.28, 0.54), reflecting variation in the abstracted data and/or its interpretation. The development of standardized abstraction procedures improved reliability to a moderate level (k=0.54, 95% CI: 0.26, 0.82). Critical disagreements (primarily due to differences in the interpretations of CT and MRI scans, cardiovascular evaluations, and ultrasound results) were identified and abstraction procedures revised accordingly. Reliability then improved to substantial levels of both inter-rater (k=0.68, 95% CI: 0.44, 0.91) and intra-rater (k=0.74, 95% CI 0.61,0.87) agreement. Half of remaining disagreements were due to ambiguities in the medical record and half related to errors in data abstraction.
CONCLUSION.
TOAST subtype classifications can be reliably assigned using a computerized algorithm with data obtained through standardized medical record abstraction. This residual variability can be addressed by having two raters classify each case and then identifying and resolving the reason(s) disagreements.
Soluble intercellular adhesion molecule-1 in patients with recent cerebral ischemic events
Authors: Minuk Jeffrey , Durcan Liam , Wolfson Christina , Blinkina Anna , Mackey Ariane , Lucy Viera , Berger Leo , Cote Robert
Published: March 2022

P46

Objective:
To determine whether serum levels of soluble intercellular adhesion molecule-1 (sICAM) differ between individuals with recent acute ischemic stroke (AIS) or transient ischemic attack (TIA) and control subjects.
Methods:
sICAM levels were measured in patients with recent (≤ 7 days) AIS or TIA and in patients with asymptomatic carotid stenosis and control subjects. Demographic information was collected and all subjects underwent complete neurological evaluations, routine blood tests and baseline cervical ultrasonography. Subjects with either a qualifying AIS or TIA also underwent cranial CT. sICAM levels were compared between different patient groups and correlated with carotid stenosis in those with AIS or TIA using analysis of variance (ANOVA) and logistic regression.
Results:
sICAM levels were measured in 288 patients (48.6% males). Of these, 91 had either a recent AIS or TIA. There were 75 control subjects. The remainder (n=122) had an asymptomatic carotid stenosis. Mean follow-up for all patients was 25.1 months. Mean age and distribution of cardiovascular risk factors were similar across all groups of patients. Mean sICAM levels were higher in those with recent AIS or TIA than in control subjects but without quite reaching statistical significance (p=0.10). For those with either AIS or TIA, mean sICAM levels did not differ on repeat measurement nor did initial levels correlate with the degree of carotid stenosis homolateral to the side of the ischemic event. During follow-up, 30 patients overall, (10.4%), experienced a recurrent ischemic event (either TIA, AIS, myocardial infarction and/or vascular death). Patients with either AIS or TIA, experienced a higher recurrence rate (24.6%). Mean sICAM levels were higher in those patients with a recurrent ischemic event (375.9 ng/mL) than in those without (332.1 ng/mL).
Conclusion:
There was a trend for higher sICAM levels in patients with recent AIS or TIA compared with control subjects. In addition, higher initial sICAM levels were associated with an increased risk of recurrent ischemic events for all patients.
Impaired cerebral vasoreactivity correlates with recent symptomaticity in severe carotid artery disease
Authors: Marshall Randolph S , Sproule Douglas M , Rudnik Tanja , Fitzsimmons Brian-Fred M , Sia Roque M , Lazar Ronald M
Published: March 2022

P62

OBJECTIVE:
Impaired cerebral vasomotor reactivity has been proposed as a measure of exhausted vascular reserve in patients with carotid artery stenosis or occlusion. We tested this hypothesis by measuring vasoreactivity in patients with asymptomatic or recently symptomatic severe carotid artery disease.
METHODS:
Fourteen patients with severe carotid artery disease (5 with occlusion, 9 with stenosis 80–99%, 8 symptomatic, 6 asymptomatic within 2 years) and 7 healthy controls had continuous bilateral monitoring of mean flow velocity (MFV) in the MCAs by transcranial Doppler (TCD). End-tidal CO2 was measured continuously with an in-line capnometer connected via snorkel mouthpiece, nasal airway occluded by noseclip. After baseline measurements, subjects held their breath for 30 seconds. A breath holding index (BHI) was calculated (% change in MFV/seconds held). After return to baseline MFV, subjects breathed a 5% CO2 gas mixture for 2 minutes. CO2 reactivity was calculated as percent rise in MFV per mmHg PCO2 once the MFV curve plateaued. ANOVA was used to calculate differences between symptomatic, asymptomatic and control groups for CO2 reactivity and BHI.
RESULTS:
There was a highly significant difference in vasoreactivity by CO2 inhalation in the symptomatic group (2.02±.80 %/mmHg) versus the asymptomatic group (4.45±1.9 %/mmHg) and controls (3.69±.95 %/mmHg) (F
2,18
=7.85, p=.004). A linear relationship was seen between MFV and PCO2, taking multiple MFV measurements at various PCO2 levels throughout the study period (average r
2
=.60 for patients, .77 for controls). BHI did not distinguish between the groups (p=.37).
CONCLUSIONS:
Measuring cerebral vasoreactivity by CO2 inhalation with continuous TCD monitoring provides an important physiological index of the clinical status of patients with carotid artery disease which may help guide treatment algorithms. The linear relationship between MCA MFV and end-tidal CO2 enables confirmation of the baseline and maximum measurements used to calculate CO2 reactivity, and provides the opportunity to investigate further the link between physiology and clinical state.
Molecular Analysis of Factors Contributing to Carotid Atherosclerotic Plaque Instability: Atheromatous versus Fibrous Plaques
Authors: Jacob Theresa , Ascher Enrico , Khandros Yevgeniy , Hingorani Anil , Gunduz Yilmaz , Yorkovich William
Published: March 2022

P63

Introduction:
The molecular events in atherosclerotic carotid disease that trigger responses within the plaque resulting in plaque instability and thromboembolic cerebrovascular sequelae are unclear. Plaque instability may be related to apoptosis and extracellular matrix degradation. We compared atheromatous and fibrous plaques in terms of apoptosis, apoptosis-related proteins, cell cycle regulatory genes, death substrates for apoptosis, proteolytic activity and infiltrating cells.
Methods:
Apoptosis was detected in carotid endarterectomy plaques by the TUNEL assay. Immunohistochemical studies were performed to identify macrophages and infiltrating cells, localize the expression of bcl-2, bax, cyclin D-1, caspases, Fas, PARP, MMP-2 and MMP-9. Zymography was used to compare the proteolytic activity levels in the two types of plaques.
Results:
There were no inflammatory cells in the fibrous plaques. Apoptotic cell death was significantly higher (p<0.001) in atheromatous plaques as compared to fibrous plaques. Elevated levels of proteinases in atheromatous plaques were noted. There were significant increases in the expression of pro-apoptotic protein, bax (p<0.01), Fas (p<0.04), and CPP-32 (p<0.001) in atheromatous plaques as compared to fibrous plaques. Localization of bcl-2 in atheromatous as well as fibrous plaques was similar. There was differential expression of cell cycle protein, cyclin D-1.
Conclusions:
The greater amount of apoptosis and overexpression of mediators of apoptosis seen in atheromatous plaques suggest that deregulated apoptosis may be involved in the pathogenesis of unstable atherosclerotic plaques. Immunoreactivity to cytoplasmic death domain, Fas, and CPP-32, a prominent mediator of apoptosis, was consistent with the amount of apoptosis detected. Inflammatory cells and increased number of T-lymphocytes producing apoptotic stimuli could contribute to plaque instability. The increased levels of proteolytic activity in atheromatous plaques may make them vulnerable to rupture, and result in a cascade of thromboembolic cerebrovascular events.
Temporal evolution of Diffusion / Perfusion Mismatch in a Rat Stroke Model
Authors: Omae Tsuyoshi , Silva Matthew D , Mayzel-Org Orna , Kazemi Mark , Li Fihai , Sotak Christopher H , Fisher Marc
Published: March 2022

P69

Background and Purpose:
Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) can rapidly detect lesions in acute ischemic stroke. Studies show that lesions by PWI are sometimes larger than those of DWI in patients with acute ischemic stroke, suggests that the mismatch between DWI and PWI is potentially predictive of tissue at high risk for evolving into infarction. The aims of this study were to detect the evolution of the DWI/PWI mismatch in permanent focal experimental ischemia and transient focal experimental ischemia.
Methods:
Rats were subjected to permanent (n=8) and 60 minutes of temporary ischemia (n=8) using the intraluminal middle cerebral artery occlusion method and then underwent DWI and PWI after occlusion. Rats in the transient ischemic experiments were reperfused 60 minutes after occlusion. An apparent diffusion coefficient map and a cerebral blood flow index map were used to calculate the percent hemispheric lesion volume (%HLV) for each MRI parameter.
Results:
In permanent ischemia, %HLVs by DWI were 21%, 45%, 60%, 87%, and 101% of %HLV by PWI at 15, 30, 60, 90 and 120 minutes after ischemia, respectively. The ratio did not change after 120 minutes. With 60 minutes of temporary ischemia, the changes were almost the same as those in permanent ischemia before reperfusion. After reperfusion the lesions on PWI were smaller than those on DWI. The DWI lesion did not increase after reperfusion, and was the almost the same size as just before reperfusion.
Conclusions:
The DWI/PWI mismatch disappears at 2 hours after permanent ischemia, and the region of DWI/PWI mismatch can be saved from ischemic damage if reperfused early, but ischemic lesions seen on DWI can not be reduced by reperfusion after 60 minutes of temporary ischemia in this rat stroke model.
Death inducing ligands are critical for the selective vulnerability of the inner retina to transient global ischemia.
Authors: Cohen Bella , Singh Manjeet , Gupta Gaurav , Savitz Sean , Ocava Lenore C , Rosenbaum Pearl S , Rosenbaum Daniel M
Published: March 2022

P72

We have previously demonstrated that the delayed cell death that occurs in the inner retina following transient global ischemia is in part apoptotic.In non-neuronal cells, death-inducing ligands(DILs) such as TNF-α and FasL are important in the induction of apoptosis.The purpose of this study was to investigate the role of DILs in the selective vulnerability of the inner retina to ischemic injury. Four groups of mice were subjected to transient global retinal ischemia (high intraocular pressure model) for a period of 45 minutes : wild type, TNFR(p55)-knock out, TNFR(p75)-knock out and lpr(loss of function of Fas receptor). The degree of retinal damage was assessed by measuring the thicknesses of the inner retinal layers. Additionally, electrophysiology (ERG) was performed following ischemia to assess functional outcome. There were TUNEL positive cells within the vulnerable inner retina seen maximally at 24 hours following ischemia. At 7 days subsequent to ischemia,in all groups of mice there was marked thinning of the inner retinal layers with morphological characterstics of apoptosis. ERG at 7 days demonstrated diminished amplitude of the ERG-b wave.In all three groups of mutant mice, there was significantly less morphological damage(mean inner retinal thickness) as well as significant preservation of the ERG-b wave as compared to the wild type animals.The lpr animals demonstrated the greatest protection.These data suggest that DILs play a critical role in the selective vulnerability of the inner retina to transient global ischemia and offer new strategies for the treatment of ischemic neuronal injury.
Enhanced Susceptibility to Fever After Subarachnoid Hemorrhage
Authors: Commichau Christopher , Mayer Stephan A , Scarmeas Nikolaos
Published: March 2022

P100

Background:
Fever exacerbates ischemic neuronal injury and may adversely affect outcome after stroke. Unexplained or “central” fever is a particularly common and poorly-understood phenomenon after stroke. Risk factors for fever in critically-ill stroke patients are poorly defined.
Methods:
We prospectively studied the frequency and causes of fever, defined as a patient’s first temperature ≥101° F (38.3° C), among 387 patients admitted to our NICU over a 4 month period. The cause of fever was evaluated using a standard protocol in all patients. After identifying risk factors for infectious and unexplained fever in a logistic regression analysis, we calculated disease-specific adjusted odds ratios for developing each type of fever among 12 diagnostic groups, including cerebral infarction (INF), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH).
Results:
Fever developed in 23% (87/387) of patients; 52% of fevers were related to infection, and 28% were unexplained despite a complete diagnostic evaluation. Fever occurred in 65% of patients with SAH (n=41), 31% with ICH (n=43), and 27% with INF (n=25). NICU length of stay (LOS) was a risk factor for both infectious and unexplained fever (P<.004); other risk factors included depressed level of consciousness (LOC) (P=.048) and intubation (P=.01) for infectious fever, and intra-ventricular catheterization (IVC) for unexplained fever (P=.004). SAH was the only diagnosis associated with an increased risk of infectious (P=.02) or unexplained fever (P=.05) after adjusting for these risk factors.
Conclusion:
Fever occurs in 65% of SAH patients, a rate almost three times higher than that of other NICU patients. In NICU patients, depressed LOC and intubation are risk factors for infectious fever, and IVC is a risk factor for unexplained fever, suggesting a role for ventricular hemorrhage in the pathogenesis of “central” fever. SAH increases the risk of both infectious and unexplained fever even after accounting for these risk factors, which may reflect abnormal thermoregulation in these patients.
Associations between age, vasospasm, and cognitive deficits after ruptured aneurysm repair
Authors: Hillis Argye E , Razumovsky Alexander , Ulatowski John A , Banker Piyush , Sheikh Kiran , Rigamonti Daniele
Published: March 2022

P101

Although vasospasm has been postulated as a risk for development of neuropsychological deficits after rupture and repair of intracerebral aneurysms, there is little empirical support for this hypothesis. To determine the risk of vasospasm for persistent cognitive deficits, we studied 16 patients, age 30–77, with daily TCD evaluations after aneurysm clipping, and administered a battery of neuropsychological tests (clusters of language, spatial, and memory tests) 3 months post-operatively. We calculated Pearson correlations between neuropsychological test cluster scores (age-corrected) and: (1) #days in vasospasm by TCD criteria; (2) #vessels in vasospasm by TCD; and (3) maximum velocity in each major vessel.
Results:
Vasospasm in left or right ICA (C1) or MCA (M1) was negatively correlated with both language (
r
=.57-.64;
p
<.02)and spatial(
r
=.53-.57;
p
<.02), but not memory, test scores compared to age norms. Paradoxically, however, both #days in vasospasm (any vessel) and #vessels in vasospasm were
positively
correlated with both language and spatial scores (
r
=.56-.60;
p
<.03 each). That is, more diffuse/longer duration vasospasm was associated with better scores. This result was entirely accounted for by age. Age was
negatively
correlated with both #days in vasospasm (
r
=-.564;
p
<.03) and #vessels in vasospasm (
r
=-.555;
p
<.030). Likewise, age was negatively correlated with age-corrected scores on all neuropsychological tests. That is, older patients had less diffuse vasospasm, for fewer days, but nevertheless had more severe cognitive deficits (relative to age norms) at 3 months post surgery. When we controlled for age, there were no significant correlations between #days or #any vessels in vasospasm and neuropsychological scores.
Conclusions:
Across all ages, severity of vasospasm in left or right ICA (C1) or MCA (M1) was associated with lower age-corrected scores on language and spatial tests. Older patients had fewer vessels and fewer days in vasospasm of any vessel(possibly due to lower vascular reactivity or attenuated inflammatory response associated with aging), but nonetheless showed more significant deficits on neuropsychological tests.
Soluble CD39 but not Aspirin Decreases Platelet Deposition and Improves Outcome in Reperfused Murine Stroke
Authors: Kiss Szilard , Marcus Aaron J , Broekman M Johan , Nair M Nathan , D’Ambrosio Anthony L , Liao Hui , Maliszewski Charles R , Connolly E Sander , Pinsky David J
Published: March 2022

P109

Acute ischemic stroke evokes progressive microvascular thrombosis, largely driven by platelet recruitment, at sites distal to the primary site of vascular obstruction. Aspirin (ASA), which blocks thromboxane-mediated platelet aggregation, is of limited efficacy in ischemic stroke and may increase intracerebral hemorrhage. CD39, an integral endothelial protein with enzymatic (apyrase) activity, degrades ADP released by platelets to suppress platelet-mediated platelet recruitment. We recently reported that the CD39 gene is a critical thromboregulator in ischemic cerebral vessels. The current study was designed to determine whether soluble CD39 (solCD39) can limit the accumulation of radiolabeled platelets in stroke and to compare these effects with those of ASA. Twenty C57/BlJ6 mice were used; platelets were isolated from 10 mice and radiolabeled using
111
Indium-oxyquinoline. The remaining mice were divided into 2 groups and given 10
6
cpm platelets and a separate intravenous injection of ASA (5 mg/kg, n=6) or solCD39 (4 mg/kg, n=4) prior to 45 minutes of intraluminal right middle cerebral artery occlusion, followed by suture withdrawal/reperfusion. Ipsilateral/contralateral blood flow, measured by laser doppler at 24 hrs, was significantly greater (44%) in the solCD39- vs the ASA-treated mice (p=0.002). Accumulation of
111
Indium-platelets in the ischemic hemispheres, measured as the ipsilateral/contralateral cpm ratio, was 1.02 ± 0.058 for solCD39-treated mice, whereas aspirin failed to limit platelet accumulation and was similar to historic platelet accumulation in untreated murine stroke (2.99 ± 1.88 for ASA, p=0.0002 vs solCD39). Not only was platelet accumulation reduced and cerebral blood flow improved by solCD39, but mortality was significantly reduced by solCD39 vs ASA (0% vs 67%, respectively, p=0.04). CD39-mediated catabolism of ADP in the platelet releasate appears to be a more potent means to reduce postischemic platelet recruitment and improve outcome than ASA-mediated inhibition of the cyclooxygenase pathway.
The cerebral microcirculation in focal ischemia and reperfusion
Authors: Beck Juergen , Eckhoff Jens , Lehmberg Jens , Baethmann Alexander , Uhl Eberhard
Published: March 2022

P111

The role of the microcirculation and of the inflammatory response in secondary brain damage from cerebral ischemia is hardly understood. Objective of the study was to assess leukocyte-endothelium interactions (LEI), functional capillary density (FCD), and the microvascular patency in the reperfusion period after an acute ischemic insult. Focal ischemia was induced in gerbils by transient (2 h) ligation of the left CCA. Only animals with a reduction of rCBF to < 10 % baseline (n=8) were studied in comparison with sham operated controls (n=7) as determined by laser-doppler flowmetry. A transdural window was implanted for observation of the brain surface by intravital microscopy before, during and up to 3 h following ischemia. FITC-Dextran and Rhodamine 6G were i.v. administered as fluorescence dyes for contrast enhacement of blood vessels and labeling of leukocytes. A brief but significant increase in the number of rolling leukocytes (rollers) was found at 5 (7.7 ± 4.2) and 30 min (6.4 ± 2.4 / 100 μm x min) of postischemic reperfusion. Subsequently, however, the number of rollers declined reaching the control level. Leukocytes firmly attached to the endothelium of postcapillary venules were also shortly increased after ischemia, albeit without reaching statistical significance. The number of perfused postcapillary venules (8–20 μm) was decreased to 44 ± 18 % at 2 h of ischemia. The recovery of the venular patency and, thus, perfusion was significantly delayed, i.e. until 1h of reperfusion. With onset of ischemia FCD decreased from 168 ± 10 cm
-1
to 7 ± 5 cm
-1
(p<0.05) and did not recover with the ongoing reperfusion during the whole postischemic observation period (3 h). Activation of LEI as inflammatory response was limited to the immediate reperfusion period (5–30 min) only, rendering its pathophysiological significance questionable. On the other side FCD was drastically reduced and did not recover in animals with dense focal ischemia (<10%), with a delay of reperfusion of small venules for 1h or more. The marked disturbances of the microcirculation are most likley involved in the maturation of ischemic brain damage and may, thus, represent a promising target for therapeutic intervention.
TRAIL Mediated Apoptosis Increases Carotid Plaque Vulnerability
Authors: Hernandez Ambrosio , Xue Xiang Y , Westerband Alex , Killewich Lois A , Hunter Glenn C
Published: March 2022

P116

Background:
TRAIL, a TNF family protein, and its receptors DR 4 and 5 (TNF-R) are known to induce apoptosis in tumor cells via caspase activation. In this study, we examined the relationship between TRAIL, its effector caspases and apoptosis in carotid plaque (CP). Materials and
Methods:
Forty CPs were examined by immunohistochemistry, Western blotting and RNA protection assay for evidence of apoptosis (Tunel), TRAIL, caspase 3, 8 and PARP. We compared the expression of these pro-apoptotic proteins within plaque (P), and in areas of intimal thickening (IT) adjacent to the plaque to that of normal intima (N).
Results:
Apoptosis was detected in 10–25% of ECs, SMCs, macrophages and T lymphocytes in complex CP, but only in 1–3% SMCs in fibrous plaques. TRAIL and TNF-R, as well as caspases 3, 8, and PARP were present in all complex lesions. In N, there were focal areas of caspase 3 expression localized to ECs, whereas both caspase 3 and TRAIL were detected in all 3 regions of complex CP. There was a significant increase in the expression of TRAIL, TNF-R and caspase 8 in areas of IT compared to N (Fig. 1).
Conclusions:
The increased expression of TRAIL, TNF-R and caspases 3 and 8 in areas of IT and caspase 3 in ECs from N suggest that the mechanisms for ongoing EC injury and TRAIL-mediated cell death are present in complex CP. Modulation of these pro-apoptotic proteins and/or their inhibitors could potentially result in the introduction of therapeutic agents to attenuate plaque vulnerability.
MRI predicts area of increased plasminogen activation in permanent focal cerebral ischemia
Authors: Pfefferkorn Thomas , Wiessner Christoph , Allegrini Peter R , Liebetrau Martin , Kloss Christian , Hamann Gerhard F
Published: March 2022

P117

Background:
Increased proteolytic activity after ischemic stroke may promote brain edema and secondary hemorrhage. Increased plasminogen activation has previously been detected in infarcted regions after focal cerebral ischemia. In our study, we investigated whether areas of increased plasminogen activation can be related to and therefore later be predicted by intravital magnetic resonance imaging.
Methods:
Permanent occlusion of the middle cerebral artery (MCA) in male Fisher rats was achieved by electrocoagulation after subtemporal craniectomy. After 48 hours the extent of the ischemic lesion was determined by T
2
-weighted in vivo MRI. The animals were sacrificed after 72 (n=4) and 168 (n=4) hours. Areas of plasminogen activation were then detected in 10 μm brain slices by in situ zymography using an overlay containing plasminogen and the plasmin substrate casein. The area of the MRI lesion was compared to the area of increased plasminogen activation in respective brain sections using an advanced videoimaging system.
Results:
MRI at 48 hours consistently revealed extensive lesions affecting most of the basal ganglia and the cortex (84.9 ± 8.6 % and 86.6 ± 10.1 %, respectively). After 72 hours of permanent ischemia, plasminogen activation in respective sections measured 67.5 ± 14.6 % and 80.5 ± 6.8 % of total basal ganglia and cortex area. After 168 hours respective values were 81.8 ± 7.3 % and 88.1 ± 2.7 %. There was no significant difference in the extent of plasminogen activation between the two time intervals. Comparing individual animals, MRI lesion and plasminogen activation showed close overlapping. This colocalisation was significantly higher than expected if areas were randomely distributed (p<0.005). Discussion: In vivo MRI at day two of permanent focal ischemia predicts the extent of increased plasminogen activity. MRI may therefore reveal areas at risk for plasminogen/plasmin mediated reperfusion injury including edema and secondary hemorrhage.
Can Transcranial Ultrasonication Increase Recanalization Flow Ratio with Tissue Plasminogen Activator?
Authors: Ishibashi Toshihiro
Published: March 2022

P119

Purpose:
The enhancement by a newly developed method of transcranial ultrasonication (TU) of thrombolysis with tissue plasminogen activator (TPA) was investigated in acute ischemic stroke (AIS) with an in vivo rabbit femoral artery occlusion model.
Method:
The femoral arteries of 36 rabbits were exposed, and stenosis was produced with 5–0 silk suture to reduce the flow to 77.3±6.9%. Poststenotic flow was measured with a flow meter at proximal segments of the femoral artery. Thrombosis was achieved by injecting thrombin through the cannulated branching artery into a 1-cm segment proximal to the stenosis which was isolated for 30 minutes. After the stability of the occlusion was confirmed, TPA was infused intravenously and ultrasound was applied through a piece of cadaver temporal bone (4 mm thick) to the thrombosis. The continuous wave ultrasound frequency was 490 kHz, and the intensity through the skull was 0.13 W/cm
-2
. Four groups were studied in a blinded fashion: 1.2 mg TPA with TU (1.2TU) (n=9), 1.2 mg TPA alone (1.2TPA) (n=12), 3.2 mg TPA with TU (3.2TU) (n=7), 3.2 mg TPA alone (3.2TPA) (n=8). All animals were observed for the 60 minutes of treatment. In this study, recanalization flow ratio (RFR) was defined as recanalization flow divided by poststenotic flow.
Results:
The RFR of the 1.2TU group (46.0±40.4%) was significantly greater than that of the 1.2TPA group (8.7±24.2%) (p<0.02). There were no significant differences in RFR among the 1.2TU, 3.2TPA, and 3.2TU groups (46±40.4%, 42.1±39.6% and 56.8±30.6%) (p>0.3).
Conclusions:
This study demonstrates that low-frequency and low-intensity TU with low-dose TPA is as effective as high-dose TPA in vivo and suggests that TU enhances thrombolysis in AIS.
Arterial wall properties in multiple spontaneous cervical artery dissection. An ultrasound study.
Authors: Berthet Karine , Tzourio Christophe , Benslamia Lamia , Guillon Benoit , Bousser Marie-Germaine , Touboul Pierre Jean
Published: March 2022

P120

Background:
An underlying arteriopathy related to a generalized extracellular matrix defect is suspected in spontaneous cervical artery dissection. We selected patients with multiple spontaneous cervical artery dissection (MSCAD) to study carotid arteries morphology and common carotid arteries hemodynamic properties.
Method:
12 patients with MSCAD (mean age 48±6, 50% of women) were consecutively and prospectively included during an eighteen month period and were compared with 12 ischemic stroke patients matched for age and sex. Cases and controls had ultrasound measurement of each common carotid artery diameter change in systole and diastole, during 3 to 5 cardiac cycles. This parameter was expressed as percentage. Post-processing of the ultrasonic signals was performed using computer-assisted image analysis.
Results:
There was no difference in diameter of common carotid and internal carotid arteries between cases and controls, just as intima-media thickness measurement. Whereas, the average of common carotid artery relative diameter change was significantly higher in cases than in controls (13.6% versus 10.6%, p=0.005)
Conclusion:
As common carotid artery relative diameter change is a one-dimensional assessment reflecting the elastic properties of the artery wall, our preliminary results suggest that an underlying arteriopathy may be present in multiple spontaneous cervical artery dissection.
Stability of Plasma Homocyst(e)ine in Acute Stroke Patients (SHASP)
Authors: Howard Virginia J , Sides Elizabeth G , Newman George C , Howard George , Malinow M. Rene , Toole James F
Published: March 2022

P121

INTRODUCTION.
Elevated plasma homocyst(e)ine concentration [H(e)] has been associated with an increased risk of stroke. Clinical trials such as the Vitamin Intervention for Stroke Prevention trial (VISP) are underway to determine whether lowering H(e) will reduce recurrent stroke. VISP limits enrollment to stroke patients who meet the H(e) criterion of > 9.5 μmol/L for men and > 8.5 μmol/L for women. VISP allows blood for H(e) analysis to be drawn up to 100 days following the qualifying stroke, however the appropriate earliest time is not known. The literature suggests that H(e)levels increase from the acute to the convalescent phase after stroke but changes during the acute phase have not been studied.
METHODS.
A prospective, multicenter study was conducted to examine changes in H(e)over two-weeks following an incident stroke. Blood samples for H(e) analysis were collected at days 1 (24–48 hrs), 3, 5, 7, and between 10–14 days after the stroke. Total plasma H(e) was determined by high-performance liquid chromatography and electrochemical detection at a Central Lab. Analyses were performed using the mixed models of Laird and Ware.
RESULTS.
Eighty-one patients (54 men, 27 women, mean age 66.8) were enrolled at 9 sites from 02/97 to 06/98. The estimated mean H(e) level at the five time periods increased with time from stroke (see table). Differences between any two time periods were significant (p<0.02) with the exception of days 3 vs. 5 and days 7 vs. 10–14. Change in H(e) was not affected by age group (< 67 vs. ≥ 68), sex, current smoker, alcohol use, hypertension, diabetes, or Rankin Score (< 2 vs. ≥ 3).
CONCLUSONS.
Plasma H(e) levels are frequently measured following stroke. These data suggest that: 1) interpretation of observed values of H(e) require an adjustment for time since stroke; 2) case-control studies assessing H(e) after stroke may be biased in overestimating its impact as a risk factor.
Ischemic Stroke Mechanism and Likelihood of Having a Positive Family History of Stroke
Authors: Meschia James F , Brown Robert D , Brott Thomas G , Hardy John , Atkinson Elizabeth J , O’Brien Peter C
Published: March 2022

P122

Introduction:
It is not known whether the magnitude of the inherited component to ischemic stroke risk varies according to presumed mechanism. Differences in familial aggregation of stroke might imply differences in the magnitude of inherited stroke risk.
Methods:
Probands were eligible for entry into a two-center prospective consecutive patient registry if they presented with an ischemic stroke within 180 days of onset of symptoms. Stroke was defined using WHO criteria. A stroke was considered ischemic if CT or MR imaging done within 7 days of onset of symptoms failed to reveal an alternative diagnosis. Probands were excluded if they had onset of symptoms within 48 hours of a cerebrovascular or cardiovascular proceedure or within 60 days of a nontraumatic subarachnoid hemorhage. Probands were also excluded if they were known to have: CADASIL, Fabry’s disease, homocysteinuria, MELAS, sickle cell disease, mechanical aortic or mitral valve, or biopsy-proven CNS vasculitis. Proband family history was obtained by systematic interview of the proband or next-of-kin. Proband past medical history was obtained by proband interview, record review, or both. A neurologist confirmed the diagnosis of and assigned a TOAST subtype to all index ischemic strokes. A positive family history was defined as a history of stroke in at least one parent or full sibling.
Results:
We enrolled 283 probands (median age, 75 yrs; male, 52%). Frequencies of TOAST subtypes were: cardioembolic, 17.0% (n=48); large-vessel, 24.7% (n=70); small-vessel, 23.0% (n=65); other, 2.5% (n=7); and unknown, 32.9% (n=93). Frequencies of positive family history by proband ischemic stroke subtype were: cardioembolic, 43.8% (95%CI, 29.5–58.8); large-vessel, 40.0% (95%CI, 28.5–52.4); small-vessel, 47.7% (95%CI, 35.1–60.5); other, 42.9% (95%CI, 9.9–81.6%); and unknown 48.8% (95%CI, 37.9–59.0). Frequencies were not significantly different among subtypes (P=0.718, chi square).
Conclusions:
The magnitude of inherited risk may not differ dramatically for various clinical subtypes of ischemic stroke. Qualitative differences in inherited stroke risk may exist at the molecular level.
Abnormalities of cerebral white matter and stroke risk in the Framingham Offspring Study
Authors: DeCarli Charles , Beiser Alexia , Seshadri Sudha , D’Agostino Ralph B , Kase Carlos S , Au Rhoda , Kelly-Hayes Maggie , Wolf Philip A
Published: March 2022

P131

Background:
MRI Abnormalities of cerebral white matter (WMH) are associated with multiple cerebral vascular risk factors, such as hypertension. The association between WMH and risk for stroke, however, has been investigated only in a limited fashion. The Framingham stroke risk profile (FSRP), based on information from the original Framingham Study Cohort (FHS), has been shown to estimate age- and gender specific probability of stroke in a number of populations. To test the utility of WMH to predict future stroke, we related the FSRP to WMH in 909 offspring of the original FHS (FHS
o
) who were free of clinical stroke.
Methods:
Quantification of MRI WMH was performed in the years 1999–2000 on 919 individuals of the FHS
o
who had taken Exam 5 during 1991–95 when they were ages 35–74 (mean age 55 ±9 years). None were demented. Data from 10 individuals with prior stroke were excluded. FSRP was computed using Exam 5 risk factor data. Using linear regression, age-related differences in WMH volume, corrected for differences in head size, were computed. WMH volumes >1 sd above the age-predicted mean were considered large. Analyses employed T-test comparison according to WMH category (large vs normal) as well as multiple logistic regression analysis to predict category.
Results:
43 individuals (4.7%) were identified as having large volumes of WMH. These individuals had significantly higher SBP (132 ±19 mmHg vs 124 ±18 mmHg; p=0.003) and significantly higher FSRP (0.070 ±0.057 versus 0.040 ±0.043; p=0.002) at Exam 5. Using logistic regression, the odds of having large WMH volumes increased by 1.26 (95% CL 1.08–1.48; p=0.004) for each 10mmHg increase of SBP and 1.09 (95% CL 1.05–1.14; p=0.001) for each 1% increase in FSRP. Analysis by gender showed a similar pattern although SBP did not reach statistical significance for WMH in women (128.4 +19.1 versus 121.7 +18.7, p=0.068).
Conclusion:
Large WMH are seen in men and women with previously measured, significantly increased predicted stroke risk. Further prospective evaluation will be important to determine if the extent of WMH is a predictor of risk for stroke as suggested by the increased values of FSRP amongst those with large WMH.
Cardiovascular risk factors for and prevalence of silent brain infarcts in the elderly:
the Rotterdam Scan Study
Authors: Vermeer Sarah E , Koudstaal Peter J , Oudkerk Matthijs , Hofman Albert , Breteler Monique Mb
Published: March 2022

P137

Background
Silent brain infarcts are commonly seen on MRI in patients with a first stroke, and in healthy elderly as well. They seem to be associated with an increased risk of stroke. It is unclear whether risk factors for silent infarcts are identical to those for symptomatic stroke. We investigated the prevalence of and cardiovascular risk factors for silent brain infarcts.
Methods
The Rotterdam Scan Study is a population based cohort study among 1077 participants, aged 60–90 years. All participants underwent cerebral MRI. Infarcts were scored blind to history of stroke and TIA. We assessed cardiovascular risk factors by interview and physical examination. We analysed the associations between risk factors and presence of infarcts by logistic regression, adjusted for age, sex and relevant confounders.
Results
In 262 participants (24%) infarcts showed on MRI. Of them, 216 persons had silent and 46 symptomatic infarcts. Prevalence of both silent and symptomatic infarcts increased with age (OR 1.08 per year (95%CI 1.06–1.10) and 1.08 (1.03–1.12), respectively). Silent infarcts were more frequent in women than men (OR 1.4 (1.0–1.9)). We found no sex difference for symptomatic infarcts. Hypertension was associated with silent infarcts (OR 2.3 (1.6–3.2)), as was pulse pressure (OR 1.2 per 10 mm Hg increase (1.1–1.3)). Diabetes mellitus, smoking and myocardial infarction tripled the odds only of symptomatic infarcts.
Conclusions
Prevalence of silent brain infarcts is higher with increasing age and in women. Hypertension and high pulse pressure are associated with silent infarcts. Other cardiovascular risk factors are related only to symptomatic infarcts.
Is Cerebral Microembolism in Prosthetic Heart Valves Clinically Relevant?
Authors: Nadareishvili Zurab G , Beletsky Vadim , Black Sandra , Fremes Steven , Freedman Morris , Kurzman David , Leach Larry , Norris John W
Published: March 2022

P138

Background.
High intensity transient signals (HITS) are frequently detected by TCD ultrasound in patients with mechanical PHV, but the published data about their clinical relevance is controversial. This study was undertaken to determine whether the presence of HITS is related to clinical and neuropsychological changes in patients with mechanical PHV.
Methods.
Patients with mechanical PHV had bilateral 30 minute TCD monitoring for microemboli (HITS) detection with and without oxygen (O
2
) inhalation. Cognitive testing of patients included MMSE, DRS, and Microcog with two measures: General Cognitive Performance (GCP) and General Cognitive Functioning (GCF).
Results.
We studied 36 patients (20 females, mean age 58±13 years), 20 with mitral, 9 with aortic, and 7 with a combined PHV after median of 1.5 years of valve insertion. HITS were detected in 72% of patients. There was no difference in HITS frequency between 16 symptomatic and 20 asymptomatic patients. HITS counts were significantly decreased after O
2
inhalation (21.7±30.6 vs. 3.3±9.1 s, p=0.009 ). Table shows that no relationship exists between the number of HITS and cognitive scores of patients.
Conclusion.
Decreased frequency of HITS after oxygen inhalation confirms their gaseous origin. Lack of relationship between the HITS and cognitive performance suggests that cerebral microembolism in PHV is a benign epiphenomenon without any clinical neurological and neuropsychological sequalae.
Medical Complications Following Cerebral Infarction: Frequency, Timing, and Predictors in a Population-Based Study.
Authors: Brown Robert D , Sejvar James J , Vernino Steven A , Petty George W , Sicks JoRean D , O’Fallon W. Michael
Published: March 2022

P142

The purpose of this study was to determine the frequency, timing of occurrence, and predictors of selected complications and medical disorders following cerebral infarction (CI) in a population-based study. The Rochester Epidemiology Project medical records linkage system was used to identify all first cerebral infarctions (CI) among Rochester, Minnesota residents during 1985–1989. The comprehensive medical records were reviewed; past history and demographic data, post-CI complications, and cause of death were recorded. CI subtype, severity, and site were determined. The frequency, timing and predictors of complications after CI were determined using the Kaplan-Meier product limit method and Cox proportional hazards regression analysis. A total of 444 first cerebral infarctions (181 men, 263 women; mean age 75.3 years) were identified among residents of Rochester, Minnesota, during 1985–1989. During a follow-up of up to 10 years, some of the complications and other medical disorders included chest infection in 194 (44%), a fall requiring medical attention in 122 (27%), myocardial infarction in 84 (19%), seizure in 38 (9%), and PE in 14 (3%). The risk of chest infection after CI was 11% at 30 days, 22% at 1 year, and 40% at 5 years. The risk of seizure was 2% at 30 days, 4% at one year, and 9% at 5 years. Regression analysis revealed that stroke severity, prior history of COPD, older age, swallowing dysfunction requiring a PEG, and stroke recurrence were significant independent predictors of chest infection after first CI. Use of aspirin after CI was inversely related to occurrence of chest infection. Complications are common after cerebral infarction. Some of the complications are more likely to occur early after the CI. Increased awareness of these issues may lead to enhanced complication prevention techniques, and surveillance for the complications. The study provides unique population-based data regarding predictors of the important causes of morbidity and mortality following cerebral infarction, and may be compared to other non-population based data.
Incidence Rates of Ischemic Stroke in Diabetics: Preliminary Race-Specific Results from the Greater Cincinnati/Northern Kentucky Stroke Study
Authors: Kissela Brett M , Khoury Jane C , Miller Rosie , Alwell Kathleen , Woo Daniel , Brott Thomas G , Pancioli Arthur M , Shukla Rakesh , Jauch Edward C , Gebel James , Kothari Rashmi U , Broderick Joseph P
Published: March 2022

P146

Intro:
The Greater Cincinnati/Northern Kentucky Stroke Study provides epidemiologic data regarding stroke in blacks and whites. We present the incidence rates of ischemic stroke in diabetics.
Methods:
All strokes occurring between 1/1/93–12/31/93 for blacks and 7/1/93–12/31/93 for whites were identified by suveillance of ICD-9 discharge codes from hospitals (430–438, 1
o
or 2
o
), coroner’s records, and surveillance of outpatient settings previously described
(Stroke 31; 280, 2000)
. Patient-medical encounters for all possible strokes/TIAs were reviewed and abstracted by a study nurse who determined diagnosis and stroke subtype using strict criteria (agreement with study physicians=87%, κ=0.71 on records completed by MD’s to date). For calculating incidence rates, the numerator consisted of cases determined to be a stroke by the study nurse. The denominator was calculated using self-reported age and gender specific rates of diabetes obtained from a 1995 random-digit dialing survey of 1850 study area residents proportionate to the stroke population
(JAMA 279:1288–1292;1998
). Reported incidence rates are adjusted to the 1990 US population.
Conclusion:
A preliminary analysis of our population-based study data reveals that diabetics have approximately a three-fold higher incidence of stroke as compared to non-diabetics, with slightly higher relative risk for whites. Diabetes is thus an important risk factor for ischemic stroke in both races although the prevelance of diabetes is higher in blacks.