bluuebunny/crossref_metadata_2025 huggingface dataset:
Overall results of a pooled analysis of individual patient data from trials of endarterectomy for symptomatic carotid stenosis
Authors: Rothwell Peter M , Gutnikov Sergei A , Eliasziw Michael , Fox Alan J , Taylor Wayne , Mayberg Marc R , Barnett Henry Jm , Warlow Charles P
Published: March 2022

64

Carotid endarterectomy (CEA) is beneficial for severe symptomatic stenosis, but trial results for moderate stenosis have been conflicting. This may be due to the differences between trials in the method of measurement of carotid stenosis, differences in outcome definitions, or chance. We used the same definitions of outcomes and the same method of measurement of stenosis to pool individual patient data on over 95% of patients ever randomised in trials of CEA for symptomatic stenosis: European Carotid Surgery Trial (ECST); North American Symptomatic Carotid Endarterectomy Trial; Veterans Administration trial #309. The degree of stenosis was remeasured on the 3018 pre-randomisation ECST angiograms by the method used in the other two trials. Remeasurements correlated well with the original measurements (r=0.94, P<0.00001). Data were merged on 6092 patients with 1711 strokes and 1493 deaths during 35,000 patient years of follow-up. Patients were categorised according to the degree of symptomatic stenosis: <30% (n=1755); 30–49% (n=1441); 50–69% (n=1547); 70–99% (n = 1338); occlusion (n = 9); unknown (n=2). Surgery was harmful in patients with <30% stenosis, and was of no benefit in patients with 30–49% stenosis. Surgery reduced the risk of
any stroke or surgical death
in patients with 50–69% stenosis (NNT = 14, 95% CI = 8–30), and this was consistent across the individual trials. Surgery was highly beneficial in patients with 70–99% stenosis (NNT = 8, 95% CI = 5–12), but had no effect on overall survival. Operative mortality was 1.1% (95% CI = 0.9–1.4) and the operative risk of stroke and death was 7.0% (95% CI = 6.2–8.0). In contrast to interpretations of the original trial reports, by using the same outcome definitions and the same method of measurement of stenosis we have demonstrated that the trial results are entirely consistent. By combining all available trial data we have determined the effect of surgery with greater precision. CEA reduces the risk of
any stroke or death
in patients with 50–99% carotid stenosis, although benefit is less than for 70–99% stenosis.
Outpatient Dalteparin Peri-Procedure Bridge Therapy In Patients Maintained On Long Term Warfarin
Authors: Nutescu Edith , Helgason Cathy
Published: March 2022

70

Background:
Peri-operative anticoagulation management for patients maintained on chronic warfarin therapy in need for surgery or invasive procedures is controversial. Such data is lacking in patients with documented hypercoagulable states and history of ischemic stroke.
Methods:
This prospective cohort study evaluated the feasibility, efficacy, safety, and cost-effectiveness of peri-operative dalteparin bridge therapy in patients maintained on long-term warfarin undergoing surgical or invasive diagnostic procedures. Twenty one consecutive patients with documented hypercoagulable states (protein C defficiency, protein S defficiency, antiphospholipid antibody syndrome) and a history of ischemic stroke were included in the study. Warfarin was stopped 4 days prior to surgery and was restarted the night of surgery , once hemostasis was achieved, at the pre-operative dose. Dalteparin 100 IU/Kg given subcutaneously every 12 hours was initiated 3 days prior surgery and continued until a therapeutic international normalized ratio was reached after surgery. On the day of surgery, the morning dalteparin dose was held. Data was recorded at the completion of dalteparin therapy and at 3 months of follow-up on recurrent thromboembolic events, and major and minor bleeding events. An economic analysis compared outpatient dalteparin bridge therapy with inpatient intravenous unfractionated heparin therapy.
Results:
The 21 patients underwent 29 surgical procedures: dental surgery (15), colonoscopy (5), eye surgery (3), vascular surgery (4), surgical biopsies (2). No patients suffered an embolic event during the 3 month follow-up period. There were no major bleeding events, and there were 8 (38%) patients with a minor bleeding event (bruising at injection site). All patients self administered the injections. An average of 6.5 hospital days were avoided per patient. This resulted in cost savings of $3250.00 per patient treated with dalteparin.
Conclusion:
Dalteparin appears to be a feasible, safe, and cost-effective alternative to inpatient intravenous heparin for peri-procedure bridge anticoagulation therapy in stroke patients.
Apolipoprotein E Transgenic Mouse Model of Cerebral Amyloid Angiopathy
Authors: Sullivan Patrick , Schmechel Donald , Hulette Christine , Ange Ruby , Alberts Mark J
Published: March 2022

76

Background:
Cerebral amyloid angiopathy (CAA) is the second most common etiology for non-traumatic intracerebral hemorrhage (ICH). There is a significantly increased frequency of the apolipoprotein E (apoE) ε4 and ε2 alleles in patients with CAA and CAA-related ICH. This suggests a role for apoE in the pathogenesis of CAA and ICH. We have developed a unique transgenic mouse model using the human apoE gene to study the molecular mechanisms underlying CAA.
Methods:
The transgenic mouse model was created by gene targeting, which results in the expression of each human apoE isoform at physiologic levels in a correct spatial and temporal pattern. These mice do not contain any mutations in the amyloid precursor protein or cystatin C gene. Mice of all apoE genotypes were bred, and were matched for age and sex. Brains from aged mice were analyzed for gross ICH. Brain sections were stained with anti-mouse A-beta antibody (4G8) to detect vascular amyloid. Sections were also stained for blood using hematoxylin and eosin (H&E), and a Prussian Blue stain was used to detect iron and hemosiderin deposition. A thioflavin-S stain was used to determine if the vascular amyloid was fibrillar.
Results:
Brains from sacrificed aged (mean age=80 weeks) apoE transgenic mice showed positive staining for CAA in predominantly neocortical vessels. The apoE ε2/ε2 mice had the highest occurrence of CAA (70%, 7 of 10), followed by the ε4/ε4 mice (40%, 4 of 10). Only 10% (1 of 10) of the ε3/ε3 mice had CAA. Two aged mice homozygous for apoE ε4 had gross ICH at post-mortem inspection. Brain sections from these mice demonstrated red blood cell infiltration and iron/hemosiderin deposition in the brain parenchyma when examined by light microscopy.
Conclusions:
This human apoE transgenic mouse model provides a genetically well defined and environmentally controlled animal model for the study of CAA that closely resembles the condition found in humans. This model may be useful for the study of therapies for the prevention and treatment of CAA.
Reducing tissue injury in acute ischemic stroke by targeting NF-κB with transcription factor decoys.
Authors: Hess David C , Carroll James , Hill William D , Meadows Angeline , Wakade Mohan , Cheng Charles , Fagan Susan , Brailer Joanna , Noah Chris
Published: March 2022

77

Background:
The transcription factor, NF-κB, plays a pivotal role in the inflammatory cascade. Transcription factor decoys (TFDs)are phosphorothioated oligonucleotides that bind activated NF-κB and prevent the transcription of inflammatory genes. We have shown that TFDs can be delivered into brain endothelial cells
in vitro
using mannitol and that an NF-κB TFD can block the upregulation of the ICAM-1 gene(Stroke 2000;31:1179–86). Objectives:1.) To determine if intra-arterial mannitol can deliver TFDs into endothelial cells
in vivo
2.) To determine if an NF-κB decoy delivered with intra-arterial mannitol reduces cerebral infarct size.
Methods:
The temporary middle cerebral artery suture occlusion (2 hrs) model was performed in male Wistar rats. Intra-arterial mannitol was used to transfect phosphorothiaoted oligonucleotide decoys into brain endothelial cells. Decoy was detected using fluoroscein-tagged TFDs with immunohistochemical amplification. Infarct size was measured at 48 hours by TTC staining. The NF-κB decoy was a 38 mer with 3 NF-κB binding sites. A scrambled decoy (38 mer with same base composition but random sequence) was used as control.
Results:
With intra-arterial mannitol, the TFD was visualized in cerebral vessels in the injected hemisphere only. Double-labeling studies using a lectin (Griffonia simplicifolia) to label endothelial cells indicated that much of this labeling was in endothelial cells. Without mannitol or with a cationic liposome preparation, no decoy could be visualized. Animals treated with NF-κB decoy (at reperfusion) had significantly smaller infarcts than control animals (saline treatment)p=.036 Fishers PLSD [Control (N=6) 33.8 ± 1.1 (mean + SE) % of hemisphere vs NF-κB decoy with mannitol (N=4) 25.9 ± 3.4; mannitol alone (N=3)33.8 ± 4.3 , scrambled decoy with mannitol (N=3)32.3 ± 2.0]
Conclusions:
Intra-arterial mannitol permits the delivery of phosphorothioated oligonuclotides into brain endothelial cells
in vivo
. An NF-κB decoy delivered with intra-arterial mannitol may decrease infarct size. This approach may have clinical application as an adjunctive treatment to intra-arterial tPA
Increased intracranial resistance as reflected by low end diastolic velocity, high resistance index, and increased diameter of extracranial carotid arteries has better power than extracranial carotid atherosclerosis in predicting ischemic stroke in Chinese of Taiwan
Authors: Bai Chyi-Huey , Chen Jiunn-Rong , Pan Wen-Harn , Chiu Hou-Chang
Published: March 2022

86

Background:
Peak systolic velocity (PSV) has been considered a good index of detecting high degree stenosis (>50%) of carotid arteries and has been used in combination with stenosis percentage to identify high risk individual for ischemic stroke (IS). Fewer studies focused on other parameters such as end diastolic velocity (EDV), flow volume (FV), resistance index (RI), and diameter (DIA). We aimed to compare the predictive power of various Duplex ultrasonography indices on ischemic stroke in Chinese.
Methods:
We conducted a case-control study on 251 first-ever IS patients (age≥40) and 242 age and sex matched outpatient controls. Duplex indices of spectral analysis and image were obtained. Percentage of stenosis, plaque score (PS), PSV, EDV, RI, DIA, and FV of right carotid arteries were included the analysis.
Results:
Parameters of common carotid artery (CCA) were used due to its stronger predictive power of IS risk than those of internal and external CA. Higher sensitivity and specificity for IS were demonstrated for each of EDV, RI and DIA than PS, stenosis percentage, PSV, and FV. Factor analysis extracted two factors out of 5 best indices, which were intracranial resistance factor (composed of EDV, RI, and DIA) and carotid atherosclerosis factor ( PS and stenosis percentage). Significantly high age-and-sex-adjusted odds ratios for IS appeared on those subjects with low EDV (OR=4.93, p=0.0001), high RI (OR=3.26, p=0.0001), large DIA (OR=2.82, p=0.0001), or positive PS (OR=2.51, p=0.0001). Higher odds ratios (OR=10.16, p=0.0000) were occurred in those subjects with low EDV, high RI, and large DIA combined.
Conclusion:
An intracranial resistance component may be described by low EDV, high RI, and large DIA. We found strong associations of IS risk with EDV, RI, and DIA separately or combined. This association was much stronger than that of PS or that of stenosis percentage, indicating the significance of intracranial resistance in the pathogenesis of ischemic stroke in Chinese.
Surgical Closure of Patent Foramen Ovale for Stroke Prevention: Vancouver General Hospital Experience
Authors: Teal Philip A , Yip Samuel , Woolfenden Andrew R , Huckell Victor H , Gin Kenneth , Jue John , Fradet Guy
Published: March 2022

95

Background and Purpose
Patent foramen ovale (PFO) is implicated as a potential cause of stroke, particularly in young patients with otherwise cryptogenic events. The natural history, risk of stroke recurrence and optimal secondary stroke prevention remains uncertain. Therapeutic options include long-term antiplatelet therapy, anti-coagulation therapy, and PFO closure by surgery or device. We report the results of 53 patients treated with surgical closure.
Methods and Materials
We have followed 53 consecutive surgically treated patients (23 men and 30 female). All patients were evaluated by a stroke neurologist, a cardiologist with expertise in adult congenital disease and a cardiovascular surgeon. Patients who met the following criteria were included: 1) embolic TIA or stroke, 2) PFO or PFO and atrial septal aneurysm (ASA), 3) investigations included cerebral angiography, transesophageal echocardiography, and hypercoagulable studies, 4) presumptive clinical diagnosis of paradoxical embolism with no other etiology detected. Follow up was obtained by clinic visit and standardized telephone questionnaire.
Results
Prior to surgery 27 patients had stroke and 26 had TIAs; 12 had multiple cerebrovascular events. The mean age at symptom onset was 41.8 ± 9.3 yrs (range 19 to 59). 22 patients had an isolated PFO and 31 had both a PFO and an ASA. Average PFO size measured at surgery was 8.8 ± 7.7 mm. 40 were treated with primary closure, 13 with suture and patch closure. Average post-surgical hospital stay was 4 days. There was no surgical mortality or major morbidity. Minor perioperative morbidity occurred in 13 patients. Average follow up postsurgery was 22.2 ± 17.4 months (range 0.7 to 90.8 months). There were no recurrent strokes and 1 recurrent TIA.
Conclusions
Surgical closure of PFO can be safely performed with low morbidity and mortality. In this group of carefully selected patients, there have been no recurrent strokes. Further studies are necessary to define high-risk patients for recurrent stroke who may benefit from surgical closure.
Safety of Post-operative Intra-arterial Thrombolysis
Authors: Chalela Julio A , Katzan Irene L , Rasmussen Peter A , Liebeskind David S , Zaidat Osama , Suarez Jose , Chiu David , Klucznick Richard P , Jauch Edward C , Kasner Scott E
Published: March 2022

112

Objectives
Limited systemic fibrinolysis and reduced dosage are features of intra-arterial thrombolyis (IAT) that may be advantageous in the treatment of post-operative (post-op) strokes. However, IAT may increase the risk of surgical bleeding. We sought to determine the safety of post-op IAT. Methods Retrospective case series from 6 university hospitals. All cases of IAT within 2 weeks of surgery were identified. Demographics, stroke mechanism, stroke severity, imaging and angiographic findings, time between surgery and lysis, thrombolytic agent used, surgical site bleeding, intracranial bleeding, and mortality were determined. Death or complications directly related to IAT were determined.
Results
35 patients (median age 72 y; range 48–85)were identified. Median time from surgery to stroke was 21 h (range 1–120). Open heart surgery was done in 18 (51%), carotid endarterectomy 6 (17%), craniotomy 3 (9%), ophthalmologic-ENT surgery 3 (9%), urologic-gynecologic surgery 2 (6%), orthopedic surgery 1 (3%), plastic surgery 1 (3%)and spinal surgery 1 (3%). The stroke causes were cardioembolism in 24 (69%), large-vessel atherosclerosis 4 (11%), dissection 3(9%), and post-endarterectomy occlusion 4 (11%). Median time to angiogram was 2.6 h (0.1–5.5).Occlusion sites were M1 in 18 (52%), M2 9 (26%), ICA 5 (14%), basilar 2 (6%)and PCA 1(3%). Thrombolysis was completed at a median of 4.5 h (range 1–7.6). TPA was used in 18 (51%) and urokinase in 17 (49%). Nine (26%) patients died. Surgical site bleeding occurred in 9 (26%) cases (minor in 6, major in 3).The major surgical bleeds were 2 post-craniectomy intracranial hemorrhages and 1 hemopericardium post-CABG; all fatal. Six deaths were non-IAT related: 3 due to cerebral edema and 3 from systemic causes. Major bleeding complications were significantly more common among patients with craniotomy (p<0.02).
Conclusions
Post-op IAT carries a risk of bleeding in up to 26% of patients but is usually minor surgical site bleeding. Avoiding IAT in intracranial surgery patients may reduce complications. Mortality in this series was similar to that reported in prior IAT trials. IAT remains a viable therapeutic option for post-op strokes.
Mechanisms of cerebral hemorrhage after carotid endarterectomy
Authors: Henderson Robert D , Phanh Thanh G , Piepgras David G , Wijdicks Eelco FM
Published: March 2022

115

Background:
Intracerebral hemorrhage (IH) following carotid endarterectomy (CEA) has a high morbidity and mortality. Traditionally attention has focussed on the cerebral hyperperfusion (HP) syndrome as the leading cause of IH following CEA. Other mechanisms such as an intraoperative event, reperfusion into an old infarct and anticoagulation may also be important.
Methods:
We performed a case-control study to identify factors leading to IH following CEA. Over a ten year period (1990–9), all CEAs at the Mayo Clinic were assessed for the occurrence of IH within 30 days of the CEA. The relationship of IH to known cerebrovascular risk factors, perioperative EEG and xenon-133 cerebral blood flow (CBF) studies was compared with a control group of CEA patients. Clinical history and imaging of ischemic events and the IH were carefully reviewed in order to determine the possible underlying mechanism(s). HP was defined as the occurrence of doubling of CBF or the presence of hypertension with confusion, severe headache or seizures.
Results:
Twelve of 2747 (0.4%) CEAs had a subsequent IH. The most common underlying mechanism was HP. Doubling of xenon-133 CBF values were more likely to occur in patients with HP than controls but only one of three patients with a likely hyperperfusion IH had clinical features of the described syndrome. IH associated with HP occurred into the hemisphere surrounding the infarct except in one case of a recent infarct in which the hemorrhage occurred directly into the infarct. A peri-operative event and anticoagulation contributed to IH alone or in combination with other mechanisms in multiple patients. Seven of the 12 IH patients died or remained severely disabled.
Conclusion:
IH following CEA is an uncommon complication with a high mortality and morbidity. It usually occurs in the setting of HP, peri-operative event or anticoagulation with HP identifiable in the majority of cases. Identification of doubling of CBF at surgery may assist in identifying patients likely to develop HP following CEA and in these patients careful control of blood pressure and avoidance of anticoagulation is important.
Deep Vein Thrombosis Prophylaxis in Medicare Patients with Ischemic Stroke: Results from the National Stroke Project
Authors: Kresowik Timothy F , Nilasena David S , Piskac Anton F , Hemann Rebecca A , Brenton Marian A , Wilwert June M , Hendel Marc E , Nevins Lynnette E
Published: March 2022

116

Background:
Patients with ischemic stroke (IS) often have impaired mobility that can increase their risk of deep vein thrombosis (DVT). Current guidelines recommend prophylactic treatment for DVT in immobile IS patients. As part of HCFA’s National Stroke Project, we examined national patterns of DVT prophylaxis for Medicare patients hospitalized with IS.
Methods:
Project data were abstracted from a national sample of Medicare inpatient charts (discharge dates 4/98 - 3/99). All U.S. states, the District of Columbia and Puerto Rico were sampled using a systematic random approach. All medical records had a principal diagnosis of one of the following ICD-9-CM codes: 362.34, 433.xx, 434.xx, 435.0, 435.1, 435.3, 435.8, 435.9 or 436. Eligible cases had a confirmed diagnosis of IS and were non-ambulatory on the second hospital day. For DVT prophylaxis, we included the administration of warfarin or heparin (including low molecular weight), or the use of an intermittent pneumatic compression device (IPCD).
Results:
Of the 36,650 cases reviewed, 3,500 met the inclusion criteria. Nationwide, 694 (unadjusted rate 19.8%) had DVT prophylaxis initiated by the second hospital day. The data show that 75 (10.8%) patients utilized an IPCD, 602 (86.7%) were given warfarin, 36 (5.2%) received heparin and 19 (2.7%) utilized more than one form of DVT prophylaxis. Of the patients receiving warfarin for DVT prophylaxis, 263 (43.7%) were on warfarin prior to arrival. The state-specific rates of DVT prophylaxis utilization ranged from 7.8% to 33.3% (chi-square, p<0.001). Univariate analyses showed that DVT prophylaxis was utilized less frequently (p<0.002) for adults 85 years and over (rate=16.2%, OR=0.72, 95% CI=0.59–0.88) and African-Americans (rate=14.6%, OR=0.65, 95% CI=0.50–0.85).
Conclusions:
For non-ambulatory Medicare patients with IS, recommended prophylaxis for DVT is not given in the majority of cases. There is a large opportunity to improve this aspect of IS care and to reduce DVT as a complication of IS for non-ambulatory patients.
Extracellular markers of impending malignant brain edema in large hemispheric stroke
Authors: Schneweis Susanne , Staub Frank , Dohmen Christian , Brinker Gerit , Neveling Michael , Graf Rudolf , Heiss Wolf-Dieter , Grond Martin
Published: March 2022

117

Background:
The development of malignant brain edema is a life-threatening complication of large hemispheric stroke. Hemicraniectomy and hypothermia are two invasive therapeutic options aiming to reduce mortality and to improve outcome in space-occupying MCA-infarction. The earlier such interventions are initiated the better is the chance of favourable outcome. However, therapeutic decision making is quite arbitrary as clinical observation, imaging or ICP measurement do not yield reliable prognostic criteria. Objective: To assess potential predictors of evolution of malignant brain edema in large MCA-infarction by microdialysis. Subjects and
Methods:
Following an ongoing prospective clinical trial invasive monitoring was performed in eight patients with large MCA-infarction. 18–36 hours after stroke onset a microdialysis probe was inserted in the parenchyma of the ipsilateral frontal lobe together with an ICP measuring device. Extracellular concentrations of glutamate, lactate, pyruvate, glycerol and various aminoacids were measured continuously for five days. CCT scans were performed on admission, after 6–12 h and at day 5. Scans were scrutinized for presence of mass-effect and size of infarction. Neurological deficit was assessed using the National Institutes of Health Stroke Scale (NIHSS).
Results:
Median NIHSS at baseline was 18 pts. (range 15–29 pts.). All patients suffered from a large stroke covering more than two thirds of the MCA-territory. In 4/8 patients an infarction of the entire territory of the MCA developed, in 3 of them with fatal space-occupying brain edema. The dynamics of the different substances varied in accordance with the clinical course, size of infarction and local brain edema: in patients with a massive edema in CCT an increase in glutamate concentrations and lactate/pyruvate-ratio was found, whereas patients without mass-effect demonstrated generally low and stable concentrations of these substances.
Conclusion:
In patients with large hemispheric infarction, bedside monitoring with microdialysis is feasible and may be valuable to predict impending malignant brain edema.
The Effect of Concurrent Arterial Aneurysms on the Risk of Hemorrhagic Presentation in Brain Arteriovenous Malformations
Authors: Stapf C , Mohr J P , Pile-Spellman J , Sciacca R R , Hartmann A , Mast H
Published: March 2022

119

Background and Purpose:
To assess the effect of concurrent arterial aneurysms on the risk of hemorrhagic presentation in brain arteriovenous malformations (AVMs).
Methods:
The 463 consecutive, prospectively enrolled patients from the New York AVM Databank were analyzed. Concurrent arterial aneurysms on brain angiography were classified as (1) flow-related feeding artery aneurysms, (2) intranidal aneurysms, and (3) aneurysms unrelated to blood flow to the AVM. Clinical presentation (diagnostic event) was categorized as (1) intracranial hemorrhage proven by imaging or (2) non-hemorrhagic presentation. Univariate and multivariate statistical models were applied to test the effect of age, gender, AVM size, venous drainage pattern, and the three different types of aneurysms on the risk of AVM hemorrhage at initial presentation.
Results:
Arterial aneurysms were found in 117 (25%) AVM patients. In 93 cases, a single aneurysm type was found (54 had feeding artery aneurysms, 21showed intranidal aneurysms, 18 had unrelated aneurysms), 24 patients had more than one aneurysm type. Overall, 204 (44%) patients presented with hemorrhage. Concurrent arterial aneurysms were significantly more frequent in patients with incident AVM hemorrhage (34%) as compared to those without hemorrhage (18%, p=0.001). In the multivariate model an independent effect for flow-related aneurysms (OR 2.1 , 95% CI: 1.2 to 3.8) on hemorrhagic AVM presentation was found. No effect was seen for intranidal and unrelated aneurysms. The attributable risk of incident hemorrhage in AVM patients harbouring flow-related aneurysms is 0.059 (95% CI: 0.01 to 0.105).
Conclusions:
The findings suggest that flow-related arterial aneurysms are an independent determinant for increased risk of incident AVM hemorrhage.
Detection of critical oligemia in patients with traumatic intracerebral hemorrhage using continuous quantitative electroencephalography and cerebral microdialysis
Authors: Vespa Paul M , Gonzalez Nestor , Kidwell Chelsea S , Saver Jeffrey L , Nuwer Marc , Glenn Thomas , Martin Neil
Published: March 2022

121

Introduction:
Serial changes in cerebral blood flow after intracerebral hemorrhage may influence tissue viability in regions surrounding the hematoma. Non invasive monitoring may assist titration of systolic blood pressure. Purpose: To determine if continuous quantitative electroencephalography percent alpha variability(EEGPAV)can discriminate areas of critically reduced cerebral blood flow (CBF).
Methods:
Ten patients with traumatic intracerebral hemorrhage underwent combined monitoring of cerebral microdialysis, EEGPAV, and intermittent xenon-computerized tomograhpy to determine if EEGPAV monitoring could determine and monitor cellular distress in the context of oligemia. Critical oligemia was defined as CBF < 25. Time and regional matched samples of EEG, microdialysis and CBF were used to correlate across modalities. Regions adjacent to the hematoma only were studied.
Results:
Six patients had regional CBF < 25 and 4 > 30 cc/100gm/min. In the low CBF group, the mean regional EEGPAV was 0.11 ± 0.4 compared to 0.22 ± 0.3 in the high-normal CBF group(p < 0.01). The low CBF group had lower extracellular levels of glucose (0.33±0.27) compared to the high-normal CBF group (1.9±1.0) (p < 0.001). Extracellular glutamate levels were higher in the low CBF group (14.5 ±23 uM) compared to the high-normal CBF group (1.34±0.8) (p < 0.001). Lactate and glycerol levels were not statistically different between groups (p < 0.8)
Conclusion:
EEGPAV can discriminate brain regions that have critical oligemia and neurochemichal evidence of cellular distress.
Influence of Depression on Return to Work after Subarachnoid Hemorrhage
Authors: Kreiter Kurt T , Claassen Jan , Rosengart Axel J , Du Evelyn , Bates Joseph E , Peery Shelley , Ostapkovich Noeleen , Mednick Adam S , Connolly E Sander , Carhuapoma J Ricardo , Mayer Stephan A
Published: March 2022

123

Depression occurs in about 30% of subjects with subarachnoid hemorrhage (SAH) and is associated with impaired quality of life (QoL). However, the influence of depression on return to work (RTW) after SAH is not known. We prospectively studied a consecutive series of 121 SAH subjects, working premorbidly, who completed a Center for Epidemiological Studies-Depression Scale (CES-D) at 3 months post-SAH (63% women, mean age = 47 years). Depression was defined as a score ≥ 16 on the CES-D, and work status as working vs. not working. Potential predictors of post-SAH depression and RTW were screened with univariate tests and included: basic demographics, pre- and post-SAH psychiatric status, and acute physiologic parameters of SAH. Variables deemed significant in the univariate models (p<.05) were entered into a forward, stepwise binary logistic model with 3-month work status as the dependent measure. In our population, premorbid lifetime diagnosis or treatment for depression was present in 17% of the subjects (20/121), but rose to 40% (48/121) at 3 months post-SAH (M3). Only 42% (51/121) reported that they had resumed their pre-morbid work status either at the same level (36/121) or at a decreased level (15/121). For non-depressed subjects, half (38/73) were able to return to work, however, only 27% (13/48) of the depressed subjects were able to return (p<.008). Significant univariate predictors of RTW were: education (p<.007), race (p<.044), admission Hunt Hess grade (p<.006), and cerebral edema (p<.001). The final multivariate model for the prediction of return to work identified 3 risk factors: cerebral edema (OR=9.4, 95% CI 2.51–35.46, p<.001), lower education (OR=1.1, 95% CI 1.02–1.29, p<.025), and depression at M3 (OR=2.4, 95% CI 1.01–5.73, p<.048). Overall, depression occurred in about 40% of subjects when assessed 3 months after SAH. The association of depression with work status remains significant, even after controlling for factors that contribute to occupational disability, including lower education and cerebral edema. Early diagnosis and treatment of acute edema and delayed depression in these patients may lead to significant improvement in employment rates after SAH.
An Analysis of Factors Associated with Early Intracerebral Hemorrhage (ICH) Growth
Authors: Jauch Edward C , Barsan William G , Khoury Jane C , Brott Thomas G , Pancioli Arthur M , Kothari Rashmi U , Broderick Joseph P
Published: March 2022

124

Introduction:
Early hemorrhage growth and clinical deterioration has been shown to occur in at least 25% of patients with spontaneous ICH. This study investigated potential baseline clinical factors associated with early hemorrhage growth in spontaneous ICH patients.
Methods:
We performed a post-hoc analysis of a prospective observational study of patients with spontaneous ICH within 3 hours of onset. CT scans were performed at presentation and 1 hour. Demographic variables (diabetes, smoking, hypertension, alcohol use, and antiplatelet medication) and clinical variables [systolic and diastolic blood pressure (SDP, DBP), mean arterial pressure (MAP), pulse pressure(PP) and combinations of these with heart rate (HR)] were analyzed using univariate analyses. Principle components analysis and logistic regression modeling were also performed.
Results:
Complete data sets were available for 97 of the 103 patients. Univariate analyses of demographic and clinical variables failed to identify an association with those patients who experienced hemorrhage growth in the first hour of management. Multivariate and multivariable analyses similarly failed to identify factors associated with early hemorrhage growth (Table 1).
Conclusion:
No single demographic or clinical variable or combination increased risks of early hemorrhage growth. Specifically, no blood pressure or heart rate parameter, individually or in combination, were associated with early ICH growth.
Retrospective NIH Stroke Scale: Not Applicable Without Initial Evaluation by a Neurologist
Authors: Bushnell Cheryl D , Johnston Dean C C , Goldstein Larry B
Published: March 2022

P5

Background and Purpose:
The NIH Stroke Scale (NIHSS) and the Canadian Neurological Scale (CNS) have been reported to be useful for the retrospective assessment of initial stroke severity. However, the NIHSS requires detailed neurological assessments that may not be reflected in all patient records, potentially limiting its applicability. We assessed the reliability of the retrospective algorithms and the proportions of missing items for the NIHSS and CNS in stroke patients admitted to an academic medical center and 2 community hospitals.
Methods:
Randomly selected records of patients with ischemic stroke admitted to an academic medical center (AMC, n=20), and community hospitals with (CH1, n=19) and without (CH2, n=20) acute neurological consultative services were reviewed. NIHSS and CNS scores were assigned independently by two neurologists using published algorithms. Inter-rater reliability of the scores was determined with the intraclass correlation coefficient (ICC), and numbers of missing items were tabulated.
Results:
The ICCs for NIHSS and CNS respectively were 0.93 (95% CI 0.82–1.0) and 0.97 (0.90–1.0) for the AMC, 0.89 (0.75–1.0) and 0.88 (0.73–1.0) for CH1, and 0.48 (0.26–0.70) and 0.78 (0.6–0.96) for CH2. More NIHSS items were missing at CH2 (62%) vs. the AMC (27%) and CH1 (23%, p=0.0001). In comparison, 33%, 0%, and 8%, of CNS items were missing from records from CH2, AMC, and CH1, respectively (p=0.0001). The ICCs for NIHSS missing items were 0.53 (95% CI 0.31–0.75), 0.7 (0.5–0.9), 0.64 (0.42–0.85), for the 3 hospitals, respectively.
Conclusions:
There are substantial levels of agreement for retrospectively-assigned NIHSS and CNS scores for patients initially evaluated by a neurologist at both an AMC and a CH. However, the proportions of missing items are higher for the NIHSS in each setting, effectively reducing it to the items captured on the CNS, and particularly limiting the NIHSS application in hospitals without acute neurological consultative services.
Predictive model for MCA and ICA cerebral blood flow velocities(CBFV)changes following aneurysmal subarachnoid hemorrhage(SAH)
Authors: Torbey Michel T , Hauser Till-Karsten , Bhardwaj Anish , Williams Michael , Ulatowski John , Mirski Marek , Razumovsky Alexander
Published: March 2022

P11

Objectives:
Current TCD criteria for VSP is based on CBFV alone but factors such as age and day after SAH also affect CBFV, making the current criteria unreliable. Our objective is to describe MCA and ICA CBFV trend taking into account clinically significant variables.
Methods:
Patients with the diagnosis of aneurysmal SAH between 1991 and 1999 were identified using a prospective TCD database. Linear and non-linear regression analysis were performed. We included the following variables in the model: 1)age, 2)age
2
=(Age-38)
2
, 3)PSAHD:post SAH day, 4)SAHC=0 if SAH day<12 and =SAH-12 if SAH>12 day , 5)CSPASM: clinical spasm (0,1 for absent, present respectively).
Results:
We identified 399 TCD examinations that included the vessels of interest. Curve fit analysis demonstrated that the quadratic model for both MCA(R2=0.14,P<0.0001) and ICA(R2=0.093,p<0.0001) fit the data best. (1)MCA CBFV Quadratic model equation: Y=52.6+1.3 Age - 0.017 Age
2
+ 2.65 PSAHD - 5.05 SAHC + 14.5 CSPASM (2)ICA CBFV quadratic model equation: Y=96.37–1.12 Age + 0.007 Age
2
+ 2.97 PSAHD-8.08 SAHC+ 12.95 CSPASM When controlling for other variables in the model, we report: 1)A daily increase of 2.65 cm/s(MCA)and 2.97 cm/s(ICA) up to day 12, a daily decrease by 2.4 cm/s(MCA) and 5.1 cm/s(ICA)after day 12. 2)Effect of age on MCA CBFV is an increase of 1.3 cm/s per year of age until 38 and a 3.4% decrease after 38 at any given day after SAH. 3)Effect of age on ICA CBFV is a decrease of 1.1 cm/s per year of age until 38 and a 1.4% decrease after 38 at any given day after SAH. 4)When clinical vasospasm is present the CBFV increases by 14.5 cm/s(MCA) and 12.95 cm/s(ICA).
Conclusion:
our model suggests that the TCD criteria for VSP may be dependent on multiple variables. Prospective evaluation may lead to improved TCD criteria for the diagnosis of VSP.
Acute Ischemic Stroke of Undetermined Etiology in a University Hospital
Authors: Dulli Douglas A , Dixit Shanker N , Levine Ross L , Dempsey Robert J
Published: March 2022

P8

Objectives:
Ischemic stroke is classified as of undetermined etiology in approximately 30% of cohorts in many clinical studies of stroke, including the Trial of ORG 10172 in Acute Stroke Treatment (TOAST). We investigated this undetermined etiology classification in our own in-hospital ischemic stroke population, and sought to determine clinical features of acute ischemic stroke which may be more or less predictive of an undetermined etiology.
Methods:
The medical records of patients admitted to the University Hospital with ischemic stroke between 1990 and 1998 were reviewed. Etiologic classification was determined based on imaging and other studies according to the TOAST criteria as atherothrombotic, embolic, lacunar, of other determined etiology, and of undetermined etiology (UND). The last category was then subdivided into negative evaluation (UND-1), more than one cause identified (UND-2), and incomplete evaluation (UND-3). Clinical features that might predict undetermined etiology were assessed, including severity, age, gender, and previously known ischemic stroke risk factors.
Results:
Of 690 patients with ischemic stroke, 163 (23.6%) had undetermined etiology. Men and women had a similar rate of UND. In the categories UND-1, UND-2, and UND-3 there were 39 (5.7%), 52 (7.5%), and 72 (10.4%) patients respectively. Stroke with severe paresis and diminished sensorium had a low frequency of undetermined etiology (13%, p < 0.01), with the majority of the UND as UND-3. A determination of UND was made in 34% of patients under 50 (p < 0.01), and in 32% of patients without known ischemic stroke risk factors (p < 0.05). These 2 patient groups combined were 24.3% of the cohort and more than 55% of their UND diagnoses were UND-1. Patients with lacunar syndrome had a high rate of UND-2 (10.8%, p < 0.05), and patients over age 75 had a low rate of UND-1 (1.4%, p < 0.01).
Conclusions:
In clinical studies of ischemic stroke a determination of undetermined etiology may be due to an incomplete evaluation, or more than one likely cause, rather than a negative evaluation. There are clinical features on presentation of ischemic stroke that are predictive of a classification of undetermined etiology.
Clinical Utility of CMRO2 Obtained with MRI in Determining Ischemic Brain Tissue at Risk
Authors: Lin Weili , Lee Jin-Moo , Vo Katie D , An Hongyu , Celik Azim , Lee Yueh , Hsu Chung Y
Published: March 2022

P16

It has been suggested that the relationship between oxygen delivery and oxygen demand defines brain tissue at risk during cerebral ischemia. We have recently demonstrated that a quantitative estimate of cerebral blood oxygen saturation (and thereby oxygen extraction fraction, OEF) can be obtained using MRI in vivo. When combined with MR estimated cerebral blood flow (CBF), a quantitative measure of MR-CMRO2 can be calculated. In this study, we sought to explore the potential clinical utility of MR-CMRO2 in determining brain tissue at risk during cerebral ischemia. Seven patients with acute ischemic strokes were imaged at 4.5±.9 hrs (tp1) and 6 of the patients were imaged 3–5 days after stroke onset (tp2) with diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI). In addition, a 2D multiecho gradient/spin echo sequence was employed to acquire images which were subsequently used to estimate MR-OEF. Singular value decomposition was used to obtain a quantitative estimate of CBF to calculate MR-CMRO2 (= MR-OEF x MR-CBF). At tp1, 5/7 patients showed a DWI-PWI mismatch (PWI>DWI) while 2/7 patients exhibited match. At tp2, only 1 patient showed PWI<DWI, and the remaining patients had matched defects. In addition, 4/6 patients had DWI lesion volumes similar to tp1 abnormal PWI volumes, while 2/6 had smaller lesion volumes at tp2. Regional measurements of MR-CMRO2 were obtained in the regions where PWI and DWI abnormalities coincided (“core”), regions where PWI were abnormal (“core+penumbra”), and the corresponding regions on the contralateral hemisphere. In patients who demonstrated mismatched PWI-DWI defects at tp1, CMRO2 in the “core” regions was 35.3±3.4% of the contralateral region. In contrast, CMRO2 in the “core+penumbra” was 48.9±5.4% of the contralateral region, which was significantly different from “core” CMRO2 (p<0.003). Furthermore, the two patients with matched DWI-PWI at tp1 had CMRO2 values 16.6±14.1% of the contralateral regions. Analysis of tp2 images revealed that all “core” regions became infarcted. These results suggest that brain regions with CMRO2 above 35.3% of the contralateral hemisphere may represent salvageable tissue.
Intravenous thrombolytic therapy and DWI/PWI mismatch development
Authors: Schleper Bert , Fiehler Jens , Kucinski Thomas , Foth Mascha , von Michael Bezold , Weiller Cornelius , Zeumer Hermann , Roether Joachim
Published: March 2022

P21

Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) are MR techniques increasingly used in acute stroke. The aim of this study was to evaluate the DWI/PWI mismatch volumes in acute stroke patients before and after intravenous thrombolytic therapy.
METHODS:
Seven patients with ischemic stroke were treated with intravenous recombinant tissue plasminogen activator (rtPA) and imaged with DWI, PWI, MRA, and conventional MRI within 3 hours of symptom onset and on day 1 and 7. Clinical scores (National Institutes of Health Stroke Scale [NIHSS] and Barthel Index) were assessed on each time point. The perfusion deficit was defined using a threshold function measuring the volumes of regions with “time-to-peak” (TTP) delays of 2–4s, 4–6s, 6–8s and above 8 s; these volumes were compared with the DWI lesion volumes, infarct progression and final infarct size.
RESULTS:
In all patients (n=7) the DWI lesion (< 3 hrs) was significantly smaller (45%) as compared to the PWI lesion volume. The mismatch area decreased from day 0 (113 ml) to day 7 (3 ml) in all patients except for two. Mean NIHSS in these two patients improved by 5 and 2 points, while the other patients improved by a mean of 12 points from day 0 to day 7. The DWI lesion volume - measured by manually outlining the lesion - increased from a mean of 78 ml (day 0) to 136 ml (day 7) measured on T2-weighted imaging. Contributing 31% to the PWI lesion on day 0, TTP delay interval of 2–4 s was found to increase to 47% by day 7 while the region with severely delayed perfusion (> 8 s) underwent a decrease of 13%. Overall the perfusion deficit on day 7 showed a reduction by 27%. The infarct volume measured by manually outlining the DWI-lesion on day 0 increased from a mean of 78 ml to 136 ml on day 7 measured on T2-weighted imaging.
CONCLUSIONS:
1.) Intravenous thrombolytic therapy in selected patients with a severe PWI/DWI mismatch is associated with lesion enlargement taking in account that not all of the “tissue at risk” will be safed by thrombolytic therapy. 2.) Temporal development of the PWI/DWI mismatch serves as a parameter of the therapeutic efficacy of thrombolysis.
Hemispheric Infarct Volume Prediction by CT perfusion imaging
Authors: Ezzeddine Mustapha A , Koroshetz Walter J , Lah Sam , Gonzalez Gilberto , Lev Michael H
Published: March 2022

P24

Objective:
The ability to predict infarct volume when evaluating acute stroke patients is difficult. Bolus contrast CT perfusion imaging (CTP) with fast helical scanning, can identify that portion of ischemic brain with vasculature that does not fill with CT contrast. We evaluated the ability of this acute CTP lesion volume to predict final infarct volume.
Methods:
18 patients were selected from our acute stroke database. Inclusion criteria were a CT Angiogram within 6 hours of a major stroke-like symptoms, a follow up brain imaging study no later than 30 days and no earlier than 36 hours, no thrombolytic treatment, and a hemispheric infarct. Initial non-contrast CT (NCCT), CTP and follow-up imaging volumes were measured using image analysis software.
Results:
Volume of infarct as determined by follow-up brain imaging is significantly predicted by CTP volume with a p value <0.001. The slope of the regression line was 2.02 and r
2
equal to 0.660. NCCT volume also predicted follow-up infarct volume, p<0.001, slope 2.13 and r
2
0.193.
Conclusion:
The volume of the infarct is surprisingly well predicted by the measured volume of CTP deficit. This occurs despite the variability due to secondary vascular events, edema and spontaneous reperfusion. NCCT also predicts the infarct volume but with much greater variability than the CTP. CT perfusion is a widely available technique to predict final infarct size in the acute setting.
Differential evolution of tissue mean transit time, relative blood volume and flow deficits in acute ischemic stroke
Authors: Phan Thanh G , Huston John , Campeau Norbert G , Brown Robert D
Published: March 2022

P28

Background and Aim:
The presence of a perfusion-weighted imaging (PWI) volume deficit greater than diffusion-weighted imaging (DWI) volume predicts the presence of salvageable tissue. The aim of this prospective study was to determine the evolution of various parameters of perfusion within the ischemic volume using serial MR imaging during the first 48 hours after stroke.
Method:
Five patients with middle cerebral artery (MCA) territory ischemic stroke were imaged (echoplanar DWI, PWI, MR angiography) within 6–10 hours of stroke onset, then at 15–18 hours, 22–24 hours and 48 hours. No patient received thrombolytic or neuro-protective agents.
Results:
Four of the 5 patients had a MCA occlusion on the initial MR angiogram. Recanalization of the MCA was observed by the second scan in one patient and by the fourth scan in the remaining 3 patients. Significant DWI and tissue mean transit time (tMTT) volume mismatch (>75%) was observed in 4 patients and moderate mismatch in 1 patient on the initial scan. A significant mismatch between DWI and tMTT volume (>70%) was observed in 2 patients by the second and third scan. By the fourth scan no patient had a significant DWI and tMTT volume mismatch. Significant mismatch (>50%) between DWI and relative blood volume/ relative blood flow (rCBV/rCBF) volume was observed in 3 of the 5 patients on the initial scan. Matched DWI and rCBV was observed by the third scan in all patients. Matched DWI and rCBF was observed by the second scan in all patients. A decrease in the size of the tMTT volume prior to the recanalization of the MCA was likely due to opening of collateral channels but the most dramatic decrease in the size of tMTT volume occurred following recanalization of the MCA.
Conclusion:
The serial changes in tMTT, rCBV, rCBF progress at different rates following acute ischemic stroke. These results have implications for future studies basing thrombolytic therapy on DWI/PWI. We caution that treatment based only on a tMTT/DWI mismatch may overestimate the size of the salvageable tissue.