90-day Functional Outcome Research Articles

Comprehensive Stroke Centers and the ‘Weekend Effect’: The SPOTRIAS Experience

Background and Purpose: Previous studies have found mortality among ischemic stroke patients to be higher on weekends. We sought to evaluate whether weekend admission was associated with worse outcomes in a large comprehensive stroke center (CSC) cohort. Methods: Consecutive ischemic stroke patients presenting within 6 h of symptom onset were identified using the 8 CSC SPOTRIAS (Specialized Programs of Translational Research in Acute Stroke) database. Patients who received intra-arterial therapy or who were enrolled in a nonobservational clinical trial were excluded. All patients meeting the inclusion criteria were then divided into two groups: weekday admissions or weekend admissions. Weekend admission was defined as Friday 17:01 to Monday 08:59. The remainder were classified as weekday admissions. Multivariate logistic regression was used, adjusting for age, stroke severity on admission [according to the National Institutes of Health Stroke Scale (NIHSS)] and admission glucose, in order to compare the outcomes of the weekend versus the weekday groups. Results: Eight thousand five hundred and eighty-one subjects from the combined SPOTRIAS database were screened from 2002 to 2009; 2,090 (24.4%) of these met the inclusion criteria. There was no significant difference in tissue plasminogen activator treatment rates between the weekday and weekend groups (58.5 vs. 60.4%, p = 0.397). Weekend admission was not a significant independent predictor of inhospital mortality (8.4 vs. 9.9%, p = 0.056), length of stay (4 vs. 5 days, p = 0.442), favorable discharge disposition (38.0 vs. 42.2%, p = 0.122), favorable functional outcome at discharge (41.6 vs. 43.4%, p = 0.805), favorable 90-day functional outcome (54.2 vs. 46.9%, p = 0.301), or 90-day mortality (18.2 vs. 19.8%, p = 0.680) when adjusting for age, NIHSS and admission glucose. Conclusions: In this large cohort of ischemic stroke patients treated at CSCs, we did not observe the ‘weekend effect.’ This may be due to access to stroke specialists 24 h a day on 365 days a year, nurses with stroke experience and the organized system for delivering care that is available at CSCs. These results suggest that EMS protocol should be reexamined regarding the preferential delivery of weekend stroke victims to hospitals that provide all levels of reperfusion therapy. This further highlights the importance of organized stroke care.

The prognostic value of copeptin for acute intracerebral hemorrhage patients

The aim of the current study was to examine the prognostic value of copeptin for acute intracerebral hemorrhage (ICH) patients. A total of 120 patients were recruited. The plasma copeptin levels were measured using sandwich immunoassays. The hematoma volume, Glasgow coma scale (GCS) and ICH score were evaluated. The 90-day functional outcomes were measured with the modified Rankin scale (mRS). Copeptin correlated positively with hematoma volume (r=0.61, P=0.000), Hemphill scores (r=0.78, P=0.000) and white blood cell counts (r=0.58, P=0.000), whereas copeptin correlated negatively with GCS scores (r=−0.79, P=0.000). Copeptin levels were also higher in patients with an unfavorable functional outcome at 90 days than in patients with a favorable outcome (4.14±0.87 vs. 3.09±0.30 ng/ml; t=8.001, P=0.00). Monovariate logistic regression analysis results suggest that copeptin is a predictor of the 90-day functional outcomes of ICH patients (OR=3.17, 95% CI 2.01–4.35, P=0.003. Multivariate logistic regression analysis results indicate that copeptin is an independent predictor of the 90-day functional outcomes of ICH patients.

Relationship between acute stroke outcome, aspirin resistance, and humoral factors

BackgroundThe relationship between biochemical aspirin resistance (AR) and functional outcome of acute ischemic stroke is uncertain. MethodsProspectively, 269 patients with acute ischemic stroke were recruited. Their responsiveness to aspirin was evaluated by platelet function analyzer (PFA-100). All patients received blood tests for fibrinogen, high-sensitivity C-reactive protein (hs-CRP), CD40-ligand, P-selectin, intercellular adhesion molecule -1, von Willebrand factor (vWF), and D–dimer. The patients' National Institutes of Health Stroke Scale and modified Rankin Scale scores were recorded on admission, at 30 days, and at 90 days after stroke. ResultsClosure-time measured by PFA-100 equipped with epinephrine/collagen cartridge (Epi-CT) was <193 seconds (defined as AR) in 83 patients (30.9%). Patients with AR were less likely to have favorable outcome at 30 days (47.0%, p = 0.047; odds ratio: 0.69, 0.48–0.99) and 90 days (57.8%, p = 0.037; odds ratio: 0.69, 0.47–0.97) after stroke compared with those of patients without AR (60.2% and 71.0%, respectively). The Epi-CT correlated with closure-time measured by adenosine diphosphate/collagen cartridge (r = 0.241, p < 0.001), blood white cell count (r = −0.125, p = 0.041), low density lipoprotein cholesterol (r = 0.120, p = 0.050), hs-CRP (r = −0.150, p = 0.015), vWF (r = −0.134, p = 0.028), and body mass index (r = 0.143, p = 0.019). Multivariate logistic regression analysis showed that higher National Institutes of Health Stroke Scale at admission, atrial fibrillation, increased plasma levels of hs-CRP, and D–dimer were independent predictors for unfavorable stroke outcome at 90 days. ConclusionAspirin resistance evaluated by PFA-100 test was associated with unfavorable 90-day outcome. However, AR determined by PFA-100 dose not predict 90-day functional outcome. The results of PFA-100 testing represented a complex interaction between drug effect, inflammatory reaction, and prothrombotic activity.

Determinants of Recovery from Severe Posterior Reversible Encephalopathy Syndrome

ObjectiveFew outcome data are available about posterior reversible encephalopathy syndrome (PRES). We studied 90-day functional outcomes and their determinants in patients with severe PRES.Design70 patients with severe PRES admitted to 24 ICUs in 2001–2010 were included in a retrospective cohort study. The main outcome measure was a Glasgow Outcome Scale (GOS) of 5 (good recovery) on day 90.Main ResultsConsciousness impairment was the most common clinical sign, occurring in 66 (94%) patients. Clinical seizures occurred in 57 (81%) patients. Median mean arterial pressure was 122 (105–143) mmHg on scene. Cerebral imaging abnormalities were bilateral (93%) and predominated in the parietal (93%) and occipital (86%) white matter. Median number of brain areas involved was 4 (3–5). Imaging abnormalities resolved in 43 (88%) patients. Ischaemic and/or haemorrhagic complications occurred in 7 (14%) patients. The most common causes were drug toxicity (44%) and hypertensive encephalopathy (41%). On day 90, 11 (16%) patients had died, 26 (37%) had marked functional impairments (GOS, 2 to 4), and 33 (56%) had a good recovery (GOS, 5). Factors independently associated with GOS<5 were highest glycaemia on day 1 (OR, 1.22; 95%CI, 1.02–1.45, p = 0.03) and time to causative-factor control (OR, 3.3; 95%CI, 1.04–10.46, p = 0.04), whereas GOS = 5 was associated with toxaemia of pregnancy (preeclampsia/eclampsia) (OR, 0.06; 95%CI, 0.01–0.38, p = 0.003).ConclusionsBy day 90 after admission for severe PRES, 44% of survivors had severe functional impairments. Highest glycaemia on day 1 and time to causative-factor control were strong early predictors of outcomes, suggesting areas for improvement.

Safety of full-dose intravenous recombinant tissue plasminogen activator followed by multimodal endovascular therapy for acute ischemic stroke

Background and purposeThe optimal management of stroke patients who fail treatment with intravenous recombinant tissue plasminogen activator (rt-PA) remains unknown. A study was undertaken to establish whether treatment with a...

Initial stroke volume is an independent outcome predictor

A new study suggests that lesion volume assessed within 72 h of stroke onset is an important independent predictor of 90-day functional outcome and neurological recovery. If used in stroke trials, outcome models including stroke volume, age and NIH Stroke Scale scores could increase power for detecting treatment effect.

Proportion of Patients Treated With Thrombolysis in a Centralized Versus a Decentralized Acute Stroke Care Setting

Today, treatment of acute stroke consists of tissue-type plasminogen activator (tPA), admission to a stroke unit, and aspirin. Although tPA treatment is the most effective, there is substantial undertreatment. Centralized care may affect rate, timing, and outcome of thrombolysis compared to decentralized treatment in community hospitals. The present study aimed to assess the impact of organizational models on the proportion of patients undergoing tPA treatment. A prospective, multicenter, observational study among 13 hospitals in the North of the Netherlands was conducted. In the centralized model, tPA treatment for 4 hospitals was administered in 1 stroke center. The decentralized model comprised 9 community hospitals. Primary outcome was the proportion of patients treated with tPA. Secondary outcome measures were proportion of patients arriving within 4.5 hours, safety, 90-day functional outcome, and onset-to-door, door-to-needle, and onset-to-needle times. Potential confounders were adjusted using logistic regression analysis. Two hundred eighty-three and 801 ischemic stroke patients were enrolled in the centralized and decentralized settings. Numbers of patients treated with tPA were 62 (21.9%) and 113 (14.1%) (OR, 1.72; 95% CI, 1.22-2.43). Adjusting for potential confounders did not alter results (OR, 2.03; 95% CI, 1.39-2.96). In the centralized setting, significantly more patients arrived at the hospital within the 4.5-hour time window (P<0.01), and shorter door-to-needle times were reached (35 versus 47 minutes). Other secondary outcome measures did not differ across setting. In a centralized setting, the results demonstrate a 50% increased likelihood of treatment. Prehospital factors seem to contribute to this result.

Image Guided Patient Selection and Its Impact on Outcome: Results of the Penumbra Imaging Collaborative Study (PICS) (IN2-1.002)

Objective: The PICS registry sought to determine the impact of baseline imaging on patient functional outcome in acute ischemic stroke intervention. Background Several imaging techniques are currently used to triage patients in this setting but it is unclear which imaging modality (IM) is best for mechanical thrombectomy (MT). Design/Methods: Patients treated by the Penumbra System and had noncontrast CT (NCCT), CT perfusion (CT-P), and MRI diffusion weighted imaging (DWI) were enrolled across 35 centers in the US. The modified Rankin Scale (mRS) was used to assess 90-day functional outcome. Results: Among 305 patients enrolled in the PICS registry, 267 qualified for this analysis. Mean age was 66.6 ± 15.9 years; 49.4% were females, median NIHSS score was 17.0 (IQR 12-21). The median time from stroke onset to presentation was 2.3 hrs, and onset to arterial puncture was 4.8 hrs. Post-treatment, 83.5% of patients were successfully recanalized (TIMI 2/3 from 0/1) with 43.5% functionally independent at 90-days (mRS of 0-2). All cause mortality was 19.9% and rate of symptomatic intracranial hemorrhage was 4.5%. IM used for patient triage were NCCT (61.8%), CT-P (27.3%) and DWI (10.9%). There was no significant difference between groups for patient age, baseline NIHSS, and time from onset to presentation. The time from stroke symptom onset to groin puncture was significantly longer in the DWI cohort (median = 6.5 hrs) than for NCCT (4.4 hrs) or CTP (4.8 hrs) (p Conclusions: These data suggest that in the US, there is a wide variability in the types of imaging modality used to guide patient selection for acute stroke intervention by MT. In addition, the imaging approach appears to have little impact on patient functional outcome after treatment. Disclosure: Dr. Zaidat has received personal compensation for activities with Boston Scientific Corporation and Micrus Inc. Dr. Meagher has nothing to disclose. Dr. Brant-Zawadski has received personal compensation for activities with Penumbra Inc. as a consultant. Dr. Farkas has nothing to disclose. Dr. Malek has nothing to disclose. Dr. Crandall has nothing to disclose. Dr. Frei has received personal compensation for activities with Penumbra Inc. as a consultant. Dr. Hui has nothing to disclose. Dr. Alexander has received personal compensation for activities with Penumbra Inc as a consultant. Dr. Chong has nothing to disclose. Dr. Janjua has nothing to disclose. Dr. Shaff has nothing to disclose. Dr. Yavagal has received personal compensation for activities with Boston Scientific Corporation, Micrus Corporation, and Penumbra Inc., Dr. Heck has received personal compensation for activities with Penumbra Inc as a consultant. Dr. Malisch has nothing to disclose. Dr. Turk has received personal compensation for activities with Penumbra Inc as a consultant. Dr. Hayakawa has nothing to disclose. Dr. Miskolczi has nothing to disclose. Dr. Tarr has nothing to disclose. Dr. Ortiz has received personal compensation for activities with Penumbra Inc. as a consultant. Dr. Zauner has nothing to disclose. Dr. Klucznik has nothing to disclose. Dr. Zylak has nothing to disclose. Dr. Yoo has received research support from Penumbra Inc. Dr. Mualem has received personal compensation for activities with Penumbra Inc as an employee. Dr. Mualem holds stock and/or stock options in Penumbra Inc. Dr. Bose has received personal compensation for activities with Penumbra Inc. as an employee. Dr. Bose has received compensation for serving on the board of directors of Penumbra Inc. Dr. Bose holds stock and/or stock options in Penumbra Inc. Dr. Sit has received personal compensation for activities with Penumbra Inc as an employee. Dr. Sit holds stock and/or stock options in Penumbra Inc. Dr. Mualem has received personal compensation for activities with Penumbra Inc as an employee. Dr. Mualem holds stock and/or stock options in Penumbra Inc.

Abstract 3130: A 101 cm 3 Diffusion-Weighted Imaging (DWI) Cerebral Infarct Volume is the Maximum Volume Compatible with Good 30- Day Functional Outcome

Background: Several predictors of clinical outcome have been identified in acute ischemic stroke patients, including age, National Institutes of Health Stroke Scale scores (NIHSS), and large vessel occlusion. Predicted infarct volumes are thought to generally correlate with clinical outcome, however, to date, mostly small studies have failed to demonstrate a convincing relationship between Diffusion-weighted imaging (DWI) volumes and clinical outcome, and this correlation is controversial. Hypothesis: We hypothesized that final DWI infarction volumes would correlate with 30-day modified Rankin Score (mRS). We also sought to describe the maximum cerebral infarct volume compatible with a favorable 30 day (mRS of 0-2) outcome. Methods: We retrospectively reviewed a prospectively collected database of acute stroke patients with large vessel occlusion who were potential intra-arterial therapy candidate, which recently incorporated systematically collected imaging data at our large academic medical center. Additional inclusion criteria were MRI on admission as per our hyperacute stroke treatment protocol, and available 30-day mRS (n=91). Final DWI volume was obtained from the last MRI the patient had during their stroke treatment admission. Differences between final DWI volume and 30-day mRS were analyzed using the Kruskal-Wallis test. Results: See Table 1 for DWI volumes by individual mRS. There was a strong overall positive relationship between final DWI volume and 30-day mRS [Kruskall Wallis p= .0047]. No patient with an mRS of 0 had a DWI volume &gt;12.1 cm 3 . No patients with an mRS of ≤1 had an DWI volume over 85 cm 3 , and no patient with a mRS of ≤2 had a DWI volume over 101 cm 3 . Conclusions: Cerebral infarct volumes strongly correlate with 30-day functional outcome, but there is great individual variability. The maximum infarct volume compatible with survival and mild or less disability at 30 days was 101 cm 3 . In this study, the maximum cerebral infarct volume compatible with zero clinical symptoms or disability at 30 days was 12.1 cm 3 .

Abstract 3035: Thrombectomy In Acute Ischemic Stroke: A Single-Comprehensive Stroke Center Experience.

BACKGROUND In acute thromboembolic stroke, mechanical recanalization with stents may result in immediate flow restoration. In this single-center experience, we analiyze safety and efficacy data on the application of the thrombectomy devices. All cases of acute ischemic stroke in which a self-expandable fully retrievable intracranial stent was deployed as acute endovascular intervention were included in the analysis. Criteria for intervention were the onset of neurological symptoms a National Institute of Health Stroke Scale score ≥9 at presentation, large vessel occlusion stroke demonstrated by angio-CT, and failure of intravenous thrombolysis or exclusion criteria. MATERIALS AND METHODS: We performed an analysis of 72 consecutive patients with acute ischemic stroke treated with thrombectomy from April of 2010 to June of 2011. Forty patients were treated with the device (Solitaire, Trevo): 66 with anterior circulation stroke and 6 with posterior circulation stroke. Thirty two (44 %) patients received previously rtPA. Six patients had an occlusion of the basilar artery, forty had a middle cerebral artery occlusion, twenty had terminal carotid artery occlusions and six extracranial carotid occlusion. Successful recanalization results were assessed by follow-up angiography immediately after the procedure (TIMI II-III). We divided them in two groups, good (90 days mRankin score ≤3) or bad neurological outcome and find out variables associated with it. RESULTS: The mean age was 66.5 years (range, 32-86 years; 53% men). The median NIHSS score at presentation was 18 (range, 6-26). Recanalization (TIMI 2-3) was achieved in (67%). Symptomatic hemorrhage occurred in 8%. Procedural complications occurred in 2 patients, vessel perforation without clinical consequences. Ninety-day mortality was 23%; good 90-day functional outcome (mRS, ≤ 2) was achieved by 39%. Good neurologic outcomes (mRankin ≤3 at 90 days) were more frequent (83% versus 18%), and mortality rates were lower (5 % versus 18 %) with successful compared with unsuccessful recanalization . Besides good or bad prognosis of patients aren’t associated with severe carotid stenosis or occlusion (carotid T or tandem occlusion) . Neither sex nor other epidemiologic datas were indicator of bad prognosis. CONCLUSIONS: Efficacy and safety of thrombectomy and translation to improved patient outcome is sufficiently established. New thrombectomy devices might be used in case of unsuccessful recanalization as failure of complete recanalization is associated with poor outcome.

Oxidative markers in spontaneous intracerebral hemorrhage: leukocyte 8-hydroxy-2'-deoxyguanosine as an independent predictor of the 30-day outcome.

Oxidative stress may play a role in spontaneous intracerebral hemorrhage (ICH), but data on oxidative burden in cerebral hemorrhage are limited, and it is not clear whether oxidative markers add predictive power regarding ICH outcome beyond that of traditional factors. The authors therefore examined redox status and traditional factors in ICH patients within 3 days of hemorrhage onset to delineate redox status in ICH and investigate the predictive value with respect to 30-day functional outcome. Sixty-four patients with ICH and 114 controls were prospectively enrolled in this study. Blood samples were collected within 3 days of ICH onset and processed for isolation of plasma, erythrocytes, and leukocytes. The authors evaluated levels or activities of leukocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG), erythrocyte glucose-6-phosphate dehydrogenase (G6PD), erythrocyte glutathione peroxidase (GPx), plasma malondialdehyde (MDA), vitamin E, and vitamin A, as well as traditional factors including the presence of hypertension or diabetes mellitus, total cholesterol level, and measures of liver function. A general linear model and multivariable logistic regression were used for analyses where appropriate. After adjustment for age and sex and traditional risk factors, ICH was significantly associated with an increased level of 8-OHdG (p < 0.0001), decreased GPx activity (p = 0.0002), and a decreased level of vitamin E (p = 0.003). There was no association of ICH risk with G6PD activity or MDA or vitamin A level. Considering all the oxidative markers and traditional risk factors together, logistic regression showed an independent association of ICH with 8-OHdG (OR 2.7, 95% CI 1.7-4.2, p < 0.0001). The association between increased 8-OHdG level and lower 30-day Barthel Index was also independent of the effects of age, sex, hemorrhage location and size, and traditional factors (p = 0.026). Unfavorable outcome (modified Rankin Scale score ≥ 3) at 30 days after ICH onset was not significantly associated with any of the examined oxidative markers. Increased leukocyte 8-OHdG levels, as well as decreased GPx activity and vitamin E levels, were found during acute ICH. Only 8-OHdG was associated with ICH and the 30-day outcome independently from the other oxidative markers and traditional factors. Leukocyte 8-OHdG may add power beyond the traditional factors in predicting ICH outcome and thus may be used as an independent surrogate for clinical ICH study.

Growth hormone and outcome in patients with intracerebral hemorrhage: a pilot study

Background: Endocrine alterations of the hypothalamic-pituitary-axis are one of the first measurable physiological changes in cerebral insults. During acute stress, human growth hormone (GH) is stimulated and has shown to have a prognostic value in various diseases. Within this pilot study, we evaluated the prognostic value of GH in patients with acute intracerebral hemorrhage (ICH).Methods: In a prospective observational study in 40 consecutive patients with ICH, GH was measured on admission. The prognostic value of GH to predict 30-day mortality and 90-day functional outcome was assessed. Favorable functional outcome was defined as Barthel Index score >85 points and Modified Rankin Scale <3 points.Results: GH levels were increased in patients who died within 30 days as compared to survivors (0.45 (IQR 0.20–1.51) vs. 1.51 (IQR 0.91–4.08) p = 0.03), and in patients with an unfavorable functional outcome as compared to patients with a favorable functional outcome after 90 days 0.28 (IQR 0.16–0.61) vs. 0.78 (IQR 0.31–1.99) p = 0.03). For mortality prediction, receiver-operating-characteristics revealed an area under the curve (AUC) on admission for GH of 0.78 (95% CI 0.60–0.96), which was in the range of the Glasgow Coma Score (GCS) (AUC 0.82 (95% CI 0.59–1.00) p = 0.80). For functional outcome prediction, GH had an AUC of 0.71 (95% CI 0.54–0.87), which was statistically not different from the GCS (AUC 0.81 (95% CI 0.68–0.94) p = 0.36).Conclusions: In our small cohort of patients with acute ICH, elevated GH level were associated with increased mortality and worse outcome. If confirmed in a larger study, GH levels may be used as an additional prognostic factor in ICH patients. (ClincalTrials.gov number NCT00390962).

Mechanical Thrombectomy in Acute Ischemic Stroke: Catch Device

Mechanical thrombectomy presents today a promising alternative to traditional stroke therapies. Our aim with this study was to evaluate the safety and efficacy of the Catch mechanical thrombectomy device in the treatment of acute stroke and report the angiographic results and clinical outcomes. We performed an analysis of 40 consecutive patients with ischemic stroke treated with the Catch device at our academic center. Forty patients were treated with the device: 25 with anterior circulation stroke and 15 with posterior circulation stroke. Thirty seven (92.5%) patients received an additional treatment to aid revascularization, including 36 patients treated with rtPA (mean dose of 35 mg). The mean age was 63.5 years (range, 31-82 years; 55% men). The median NIHSS score at presentation was 18 (range, 3-38). The mean symptom-to-procedure start time was 440 minutes (range, 150-2637 minutes). Recanalization (TIMI 2-3) was achieved in 26/40 (65%). Symptomatic hemorrhage occurred in 18%. Procedural complications occurred in 6 patients without clinical consequences: 4 clot fragmentations and 2 vasospasms. Data were missing for 4 patients at 90 days. Ninety-day mortality was 41%; good 90-day functional outcome (mRS, ≤ 2) was achieved by 39% (14/36). Good neurologic outcomes at 90 days were more frequent (56.5% versus 7.7%), and mortality rates were lower (30% versus 61.5%) with successful compared with unsuccessful recanalization. In our retrospective case series, the Catch device appears effective in achieving recanalization and improving 90-day outcome in patients with acute ischemic stroke.

C-Reactive Protein Level Measurement Improves Mortality Prediction When Added to the Spontaneous Intracerebral Hemorrhage Score

Hyperglycemia and inflammation are involved in the progression of spontaneous intracerebral hemorrhage (sICH)-induced brain injury, but their role in predicting clinical outcome is not clear. We sought to determine whether elevation of white blood cell count (WBC), C-reactive protein (CRP), and blood glucose (BG) concentration at presentation prognosticate poor outcome in sICH patients. Between November 1, 2005 and October 31, 2009, 210 patients admitted to 2 intensive care units were prospectively consecutively evaluated after exclusion of patients with underlying inflammatory conditions. WBC, CRP, and BG were measured and ICH scores were calculated on first evaluation. Primary outcome was 30-day mortality. Secondary outcome was 30-day functional outcome using the Glasgow Outcome scale. The median CRP concentration was 7.85 mg/L (interquartile range, 4.0-12.0 mg/L), median WBC count was 8.05×10(9)/L (interquartile range, 6.45-9.9×10(9)/L) and median glucose concentration was 7.66 mmol/L (interquartile range, 6.11-10.83 mmol/L). At 30 days, 63 patients (30%) were dead and 101 (48.1%) had poor outcome (Glasgow Outcome scale score, 1-3). Higher WBC (P<0.001), CRP (P<0.05), and BG (P<0.001) were associated with mortality on univariate analyses, but only CRP remained associated with mortality (P<0.005) after adjustment for multiple confounders. CRP improved mortality prediction when added to the ICH score. None of the markers tested had significant associations with functional outcome. Higher WBC, CRP, and BG are associated with increased mortality in sICH patients. Only CRP elevation portends higher risk of death independently of other indicators of sICH severity.

Statin use and outcome after intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is a highly lethal disease of the elderly. Use of statins is increasingly widespread among the elderly, and therefore common in patients who develop ICH. Accumulating data suggests that statins have neuroprotective effects, but their association with ICH outcome has been inconsistent. We therefore performed a meta-analysis of all available evidence, including unpublished data from our own institution, to determine whether statin exposure is protective for patients who develop ICH. In our prospectively ascertained cohort, we compared 90-day functional outcome in 238 pre-ICH statin cases and 461 statin-free ICH cases. We then meta-analyzed results from our cohort along with previously published studies using a random effects model, for a total of 698 ICH statin cases and 1,823 non-statin-exposed subjects. Data from our center demonstrated an association between statin use before ICH and increased probability of favorable outcome (odds ratio [OR] = 2.08, 95% confidence interval [CI] 1.37-3.17) and reduced mortality (OR = 0.47, 95% CI 0.32-0.70) at 90 days. No compound-specific statin effect was identified. Meta-analysis of all published evidence confirmed the effect of statin use on good outcome (OR = 1.91, 95% CI 1.38-2.65) and mortality (OR = 0.55, 95% CI 0.42-0.72) after ICH. Antecedent use of statins prior to ICH is associated with favorable outcome and reduced mortality after ICH. This phenomenon appears to be a class effect of statins. Further studies are required to clarify the biological mechanisms underlying these observations.

Functional outcome after convulsive status epilepticus

Few outcome data are available about convulsive status epilepticus managed in the intensive care unit. We studied 90-day functional outcomes and their determinants in patients with convulsive status epilepticus. Two hundred forty-eight convulsive status epilepticus patients admitted to 18 intensive care units in 2005-2007 were included in a prospective observational cohort study. The main outcome measure was a Glasgow Outcome Scale score of 5 (good recovery) on day 90. Convulsive status epilepticus occurred out of hospital in 177 (67%) patients, and all but 15 patients were still seizing at medical team arrival. The median time from convulsive status epilepticus onset to anticonvulsant drug initiation was 40 mins (interquartile range, 5-80). Total seizure duration was 85 mins (interquartile range, 46.5-180). Convulsive status epilepticus was refractory in 49 (20%) patients. The most common causes of convulsive status epilepticus were anticonvulsive agent withdrawal (36.4%) in patients with previous epilepsy and stroke (27.7%) in inaugural convulsive status epilepticus. Mechanical ventilation was needed in 210 (85%) patients. On day 90, 42 (18.8%) patients were dead, 87 (38.8%) had marked functional impairments (Glasgow Outcome Scale score, 2-4), and 95 (42.4%) had a good recovery (Glasgow Outcome Scale score, 5). Factors showing independent positive associations with poor outcome (Glasgow Outcome Scale score, <5) were older age (odds ratio, 1.04/year; 95% confidence interval, 1.02-1.05; p=.0005), cerebral insult (odds ratio, 2.70; 95% confidence interval, 1.37-5.26; p=.007), longer seizure duration (odds ratio, 1.72/120 min; 95% confidence interval, 1.05-2.86; p=.03), on-scene focal neurologic signs (odds ratio, 2.08; 95% confidence interval, 1.03-4.16; p=.04), and refractory convulsive status epilepticus (odds ratio, 2.70; 95% confidence interval, 1.02-7.14; p=.045). Ninety days after intensive care unit admission for convulsive status epilepticus, half the survivors had severe functional impairments. Longer seizure duration, cerebral insult, and refractory convulsive status epilepticus were strongly associated with poor outcomes, suggesting a role for early neuroprotective strategies.

Outcomes of Thrombolysis for Acute Ischemic Stroke in Octogenarians Versus Nonagenarians

Little is reported on the outcomes of nonagenarians who are treated with intravenous tissue plasminogen activator for acute ischemic stroke. It is uncertain whether nonagenarians have higher mortality and worse functional outcomes than octogenarians. All patients who were >or=80 years of age were extracted from the Canadian Activase for Stroke Effectiveness Study national registry, a 60-center Canadian acute ischemic stroke treatment network. Patients were divided into 2 groups: those who were 80 to 89 years of age (octogenarians) and those who were 90 to 99 years of age (nonagenarians), and compared by baseline clinical, demographic, treatment, and outcome-related measures. Twenty-eight nonagenarians and 242 octogenarians were treated with intravenous tissue plasminogen activator for acute ischemic stroke over the 2.5-year observation period. Nonagenarians and octogenarians did not differ on any of the baseline clinical or demographic variables. Both groups were predominantly female (77% nonagenarians and 61% octogenarians), hypertensive (54% and 60%), and predominantly had severe strokes (National Institutes of Health Stroke Scale score >15; 58% and 52%). The rate of symptomatic intracerebral hemorrhage (7% nonagenarians versus 4% octogenarians; P=0.359), 90-day mortality (52% versus 33%; P=0.087), and 30-day favorable functional outcomes ([modified Rankin score <or=1] 30% versus 26%; P=0.647) showed no statistically significant difference when comparing the 2 age groups. There is no significant difference in 90-day mortality, 30-day functional outcome, or rate of symptomatic intracerebral hemorrhage between nonagenarians and octogenarians treated with intravenous tissue plasminogen activator when comparing populations of similar baseline risk.

Stroke Team Remote Evaluation Using a Digital Observation Camera in Arizona

Background and Purpose— Telemedicine techniques can be used to address the rural–metropolitan disparity in acute stroke care. The Stroke Team Remote Evaluation Using a Digital Observation Camera (STRokE DOC) trial reported more accurate decision making for telemedicine consultations compared with telephone-only and that the California-based research network facilitated a high rate of thrombolysis use, improved data collection, low risk of complications, low technical complications, and favorable assessment times. The main objective of the STRokE DOC Arizona TIME (The Initial Mayo Clinic Experience) trial was to determine the feasibility of establishing, de novo, a single-hub, multirural spoke hospital telestroke research network across a large geographical area in Arizona by replicating the STRokE DOC protocol. Methods— Methods included prospective, single-hub, 2-spoke, randomized, blinded, controlled trial of a 2-way, site-independent, audiovisual telemedicine system designed for remote examination of adult patients with acute stroke versus telephone consultation to assess eligibility for treatment with intravenous thrombolysis. The primary outcome measure was whether the decision to give thrombolysis was correct. Secondary outcomes were rate of thrombolytic use, 90-day functional outcomes, incidence of intracerebral hemorrhages, and technical observations. Results— From December 2007 to October 2008, 54 patients were assessed, 27 of whom were randomized to each arm. Mean National Institutes of Health Stroke Scale score at presentation was 7.3 (SD 6.2) points. No consultations were aborted; however, technical problems (74%) were prevalent in the telemedicine arm. Overall, the correct treatment decision was established in 87% of the consultations. Both modalities, telephone (89% correct) and telemedicine (85% correct), performed well. Intravenous thrombolytic treatment was used in 30% of the telemedicine and telephone consultations. Good functional outcomes at 90 days were not significantly different. There were no statistically significant differences in mortality (4% in telemedicine and 11% in telephone) or rates of intracerebral hemorrhage (4% in telemedicine and 0% in telephone). Conclusions— It is feasible to extend the original STRokE DOC trial protocol to a new state and establish an operational single-hub, multispoke rural hospital telestroke research network in Arizona. The trial was not designed to have sufficient power to detect a difference between the 2 consultative modes: telemedicine and telephone-only. Whether by telemedicine or telephone consultative modalities, there were appropriate treatment decisions, high rates of thrombolysis use, improved data collection, low rates of intracerebral hemorrhage, and equally favorable time requirements. The learning curve was steep for the hub and spoke personnel of the new telestroke network, as reflected by frequent technical problems. Overall, the results support the effectiveness of highly organized and structured stroke telemedicine networks for extending expert stroke care into rural remote communities lacking sufficient neurological expertise.

A Pilot Trial of Low-Dose Intravenous Abciximab and Unfractionated Heparin for Acute Ischemic Stroke: Translating GP IIb/IIIa Receptor Inhibition to Clinical Practice

Thrombolysis remains a mainstay in the treatment of ischemic stroke. While not usually considered in the spectrum of clot lysis, experimental data show that inhibition of the platelet glycoprotein (GP) IIb/IIIa receptor can reduce as well as reverse thrombus formation and improve microvascular flow in stroke models. However, a recent clinical trial of GP IIb/IIIa inhibition in stroke did not demonstrate clinical benefit and was associated with increased hemorrhage. Based on an understanding of the relationship between GP IIb/IIIa receptor inhibition, efficacy and hemorrhage, we hypothesized that a lower dose of abciximab would achieve a favorable range of platelet inhibition and potentially good clinical outcomes. Forty-four patients with suspected large vessel occlusion, who were not eligible for rt-PA were offered treatment with approximately 30% lower total dose of intravenous abciximab if within 6h for anterior circulation or 24h for posterior circulation stroke (later modified to 12h). Concomitant anticoagulation, usually with unfractionated heparin was employed. The extent of platelet inhibition was measured in 21 patients. Hemorrhage rate and 90-day functional outcomes and mortality were obtained. A matching algorithm involving finding the nearest neighbor from individual subjects in the control arm of the NINDS rt-PA database was used to compare outcomes at similar baseline characteristics and gender. Mean platelet inhibition was 92.1 ± 6.7% vs inhibition reported with percutaneous coronary intervention (PCI) of 96 ± 10; p = 0.08. Successful matching to NINDS controls was accomplished: after outlier elimination, median and mean NIHSS of the abciximab subjects compared to NINDS controls was 16.5 vs 15.5 (p = 0.92) and 16.3 vs 16.0 (p = 0.86). Mean age was 67.2 vs 67.1 (p = 0.97). Mean glucose was 141 vs 142 (p = 0.92). There was one symptomatic hemorrhage; minor hemorrhages occurred in 9%. The percent of patients who achieved an mRS 0-2 or died in the treated vs matched NINDS control patients was 63 vs 38 (p = .02) and 23 vs 23 (p = 1.0). Our pilot results indicated that a lower dose of abciximab results in platelet inhibition similar to that achieved in the coronary vascular bed during PCI. Comparison to matched historical controls suggests that this lower dose in combination therapy may be safe and effective therapy for thrombotic stroke and a randomized trial is warranted.

Impact of COX-2 rs5275 and rs20417 and GPIIIa rs5918 Polymorphisms on 90-Day Ischemic Stroke Functional Outcome: A Novel Finding

We hypothesized that polymorphisms in 5 genes related to thrombolytic and inflammation pathways will independently influence occurrence, severity, and 3-month functional outcome in patients with ischemic stroke. This was a case-control design with ischemic stroke patients recruited from 4 public hospitals (n = 640) and community controls (n = 627). Baseline clinical data were collected, and follow-up telephone interviews were conducted with 520 patients at 90 days postevent to determine stroke outcome using the Barthel Index (BI), Modified Rankin Scale (mRS) and Glasgow Outcome Scale (GOS). Blood samples were collected and genotyped for polymorphisms in platelet glycoprotein Ibα (GPIbα) rs224309 and rs6065, glycoprotein IIIa (GPIIIa) rs5918, tissue plasminogen activator (tPA) rs63020761, plasminogen activating inhibitor (PAI-1) rs72578597, and cyclooxygenase-2 (COX-2) rs5275 and rs20417. COX-2 polymorphism rs5275 demonstrated a significant association with poststroke mRS, with a dominant genetic model demonstrating the best fit (CC + TC) (adjusted odds ratio [aOR] = 1.61; P = .026). The COX-2 rs20417 C allele showed an association with GOS (aOR = 1.95; P = .012), and again a dominant genetic model demonstrated the best fit (CC + GC). GPIIIa rs5918 (A1A2) was associated with poststroke BI, with a dominant model demonstrating the best fit (A1A2 + A2A2) (aOR = 0.56; P = .014). There was a significant association between stroke severity and tPA rs63020761 TT allele (aOR = 1.96; 95% CI = 1.03-3.72; P = .040). This is the first study to demonstrate associations between stroke functional outcome and 2 COX-2 variants (rs20417 and rs5275) and a GPIIIa variant (rs5918).