Influence of age on outcome from thrombolysis in acute stroke: a controlled comparison in patients from the Virtual International Stroke Trials Archive (VISTA)

<p><b>Background and Purpose:</b> Thrombolysis for acute ischemic stroke in patients aged >80 years is not approved in some countries due to limited trial data in the very elderly. We compared outcomes between thrombolysed and nonthrombolysed (control) patients from neuroprotection trials to assess any influence of age on response.</p> <p><b>Method:</b>Among patients with ischemic stroke of known age, pretreatment severity (baseline National Institutes of Health Scale Score), and 90-day outcome (modified Rankin Scale score; National Institutes of Health Scale score), we compared the distribution of modified Rankin score in thrombolysed patients with control subjects by Cochran-Mantel-Haenszel test and then logistic regression after adjustment for age and baseline National Institutes of Health Scale score. We examined patients ≤80 and ≥ 81 years separately and then each age decile.</p> <p><b>Results:</b> Rankin data were available for 5817 patients, 1585 thrombolysed and 4232 control subjects; 20.5% were aged >80 years (mean ± SD, 85.1 ± 3.4 years). Baseline severity was higher among thrombolysed than control subjects (median National Institutes of Health Scale score 14 versus 13, P<0.05). The distribution of modified Rankin Scale scores was better among thrombolysed patients (P<0.0001; OR, 1.39; 95% CI, 1.26 to 1.54). The association occurred independently with similar magnitude among young (P<0.0001; OR, 1.42; 95% CI, 1.26 to 1.59) and elderly (P=0.002; OR, 1.34; 95% CI, 1.05 to 1.70) patients. ORs were consistent across all age deciles >30 years; outcomes assessed by National Institutes of Health Scale score gave supporting significant findings, and dichotomized modified Rankin Scale score outcomes were also consistent.</p> <p><b>Conclusions:</b> Outcome after thrombolysis for acute ischemic stroke was significantly better than in control subjects. Despite the expected poorer outcomes among elderly compared with young patients that is independent of any treatment effect, the association between thrombolysis treatment and improved outcome is maintained in the very elderly. Age alone should not be a barrier to treatment.</p&gt

Safety and tolerability of NXY-059 for acute intracerebral hemorrhage: the CHANT trial

<p><b>Background and Purpose:</b> NXY-059 is a free radical-trapping neuroprotectant developed for use in acute ischemic stroke. To facilitate prompt administration of treatment, potentially before neuroimaging, we investigated the safety of NXY-059 in patients with intracerebral hemorrhage (ICH).</p> <p><b>Methods:</b> We randomized 607 patients within 6 hours of acute ICH to receive 2270 mg intravenous NXY-059 over 1 hour and then up to 960 mg/h over 71 hours, or matching placebo, in addition to standard care. The primary outcome was safety: the mortality and the frequency of adverse events, and the change from baseline for a variety of serum, imaging, and electrophysiological measurements. We also studied the overall distribution of disability scores on the modified Rankin Scale (mRS) and the Barthel index.</p> <p><b>Results:</b> We treated 300 patients with NXY-059 and 303 with placebo. Treatment groups were well matched for prognostic variables including Glasgow Coma Scale, risk factors, and age. The mean National Institute of Health Stroke Scale score on admission was 14 in both groups. The baseline hemorrhage volume was 22.4±20.1 mL in the NXY-059 group and 23.3±22.8 mL in the placebo group (mean±SD). Most hemorrhages were related to hypertension or anticoagulant use. Mortality was similar in both groups: 20.3% for NXY-059 and 19.8% for placebo-treated patients. The proportion of patients who experienced an adverse event was the same for both groups, whereas for serious adverse events the proportion was slightly higher in the NXY-059 group. However, no pattern emerged to indicate a safety concern. Serum potassium fell transiently in both groups, lower in the NXY-059 group. There were no differences in 3-month function, disability, or neurological deficit scores. The odds ratio for an improved outcome in 3-month mRS scores in the NXY-059 group was 1.01 (95% CI 0.75, 1.35).</p> <p><b>Conclusions:</b> NXY-059 given within 6 hours of acute ICH has a good safety and tolerability profile, with no adverse effect on important clinical outcomes.</p&gt

Correlations among impairment, daily activities and thinking operations after stroke

OBJECTIVES: We investigated the hypothesis that ADL tests dependent on cortical functions could be used to assess outcome in stroke patients. MATERIALS AND METHOD: 27 right-handed stroke patients were evaluated on National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), Instrumental Activities of Daily Living (IADL) Scale and thinking process items of Lowenstein Occupational Therapy Cognitive Assessment (LOTCA). RESULTS: Correlations between thinking process subtests of LOTCA and different items of NIHSS such as consciousness, arm movement, aphasia, ataxia and inattention was significant. Spearman correlation of thinking process and BI tasks showed no relationship, although Structured Riska of thinking process evaluation was correlated to both self-care and mobility areas of the BI. Thinking process was strongly related to IADL total score (p = 0.004). The total NIHSS correlated significantly with BI and IADL total scores. CONCLUSION: Higher-order functions, such as categorization, sorting and reasoning, are related to IADL performance which depends on complicated cognitive abilities. In contrast, the BI depends heavily on motoric function, and does not correlate with higher-order functions. Further confirmation is needed, but our data suggest that commonly used IADL tests could serve to as valid, reliable tests of cognitive impairment and recovery in stroke victims. © 2013 - IOS Press and the authors. All rights reserved

Prostaglandin concentrations in cerebrospinal fluid of rabbits under normal and ischemic conditions

Clinical studies have demonstrated elevated levels of both arachidonic acid and prostaglandins in the cerebrospinal fluid of humans after ischemic stroke and subarachnoid hemorrhage. Such increases in free fatty acid, arachidonic acid, and prostaglandin concentrations suggest excessive production and accumulation of these substances in the ischemic brain. We used a rabbit model of ischemic infarction to examine the relation between controlled central nervous system ischemia and cerebrospinal fluid prostaglandin levels. We found that following stroke PGF(2α) and not PGD2 was the predominant prostaglandin present in the cerebrospinal fluid. PGF(2α) also underwent the largest percent increase over control prostaglandin concentations. This is similar to human and dog cerebrospinal fluid studies, which demonstrate PGF(2α) as the predominant prostaglandin following ischemic injury. The lack of PGD2 elevation under ischemic conditions may suggest that the rabbit model is more like stroke in humans than the rat or gerbil models. Our preliminary work demonstrates that it is practical to study postischemic prostaglandin changes in cerebrospinal fluid rather than in brain tissue in a rabbit model of central nervous system ischemia

Low body temperature does not compromise the treatment effect of alteplase

<p>Background and Purpose: Hypothermia is neuroprotective in ischemic stroke models. The influence of baseline body temperature on outcomes after thrombolytic therapy is unclear. We examined outcomes after alteplase treatment across baseline body temperature for patients with ischemic stroke in data held within the Virtual International Stroke Trials Archive (VISTA; 1998 to 2007).</p> <p>Methods: We collated data on age, baseline severity (National Institutes of Health Stroke Scale), and 90-day modified Rankin Scale score on patients presenting with acute ischemic stroke. We compared 90-day modified Rankin Scale score between thrombolyzed and nonthrombolyzed comparators across baseline body temperature. We report age and baseline National Institutes of Health Stroke Scale-adjusted Cochran-Mantel-Haenszel probability value and proportional OR with 95% CI for improved modified Rankin Scale distribution. We report temperature profiles over 72 hours after stroke by treatment group.</p> <p>Results: Rankin data were available for 5586 patients with acute ischemic stroke in VISTA (1980 received alteplase). Age and baseline severity were similar (age 68.0±13.0 years versus 69.9±12.3 years, National Institutes of Health Stroke Scale 14.2±5.2 versus 13.0±5.6). Alteplase was associated with improved outcome (OR, 1.49; 95% CI, 1.35 to 1.65, P<0.0001). Alteplase treatment effect was not associated with baseline temperature (P=0.14). Point estimates showed benefit of alteplase treatment across 35.5°C to 37.5°C but showed a negative trend >37.5°C. Alteplase did not influence temperature profiles over 72 hours after stroke.</p> <p>Conclusions: There is no evidence of influence of body temperature on alteplase treatment response. These results are reassuring that low temperatures across a physiological range do not compromise therapeutic effect of alteplase.</p&gt

The correlation of independency in activities of daily living performance with cognitive status and the intensity of neurological impairment in right-handed stroke patients

Purpose: We aimed to investigate whether test performance in neurological and cognitive areas is able to predict daily task performance in stroke patients and if the two selected measures of stroke severity and cognitive function could be used as valid tools to predict functional outcomes after stroke. Method: We assessed 27 stroke patients (hemorrhagic and infarct) through Barthel Index (BI), Lowenstein Occupational Therapy Cognitive Assessment (LOTCA) and National Institute of Health Stroke Scale (NIHSS) in the first 6 months after stroke. Results: The correlation of intensity of neurological impairment (NIHSS score) and ADL performance (BI score) was significant (P < 0/05), but we found no relation between general cognitive function (the total score of LOTCA) and individual independence (total score of BI). Although ADL performance areas associated with some cognitive components. Conclusion: The dependency after stroke is more affected by physical symptoms of stroke than by cognitive disorders. Moreover, the intensity of neurological impairment could be a better explanation for a patient's inability to perform basic ADL independently. Low direct relations in total scores of NIHS scale and BI was found, but LOTCA is not appropriate for prediction of independency in basic ADL performance after stroke. Nevertheless, further studies and confirmation are needed. © 2011-IOS Press and the authors. All rights reserved

Delayed detection of atrial fibrillation after ischemic stroke

&lt;b&gt;Background&lt;/b&gt;: Detection of atrial fibrillation (AF) after ischemic stroke is important because anticoagulation is indicated to reduce the risk of recurrent stroke. However, no consensus exists about the optimum method for detecting underlying paroxysmal AF not apparent on presentation with stroke. The aim of this study was to characterize the rate, timing, and predictors of delayed detection of AF after stroke. &lt;b&gt;Methods&lt;/b&gt;: The Virtual International Stroke Trials Archive provided data from 3464 patients in the placebo arms of 4 clinical trials of therapies for acute ischemic stroke. Patients who had AF by history or on the baseline electrocardiogram were excluded. Electrocardiograms were obtained routinely and as clinically indicated. The time to detection of AF was evaluated using Kaplan-Meier survival statistics. Cox proportional hazards analysis was used to evaluate risk factors for AF. &lt;b&gt;Results&lt;/b&gt;: Among 2504 qualifying patients, AF was detected in 174 (6.9%; 95% confidence interval [CI] 6.0%-8.0%). In 68% of patients, AF was detected more than 48 hours after presentation. Detection of AF was associated with increasing age (hazard ratio [HR] 1.6/decade; 95% CI 1.4-1.9; P &#60; .005), female sex (HR 1.7; CI 1.2-2.4; P &#60; .005), congestive heart failure (HR 1.9; CI 1.1-3.4; P = .02), and the absence of hypertension (HR 1.6; CI 1.1-2.2; P = .01). &lt;b&gt;Conclusions&lt;/b&gt;: Delayed detection of AF was common in this large cohort of patients carefully monitored after ischemic stroke. Current methods of screening may fail to detect underlying paroxysmal AF in a substantial proportion of patients

Protective Effect of Melatonin upon Neuropathology, Striatal Function, and Memory Ability after Intracerebral Hemorrhage in Rats

Since free radicals play a role in the mechanisms of brain injury after hemorrhagic stroke, the effect of melatonin (a potent antioxidant and free-radical scavenger) on outcomes was investigated after intracerebral hemorrhage (ICH) in rats. ICH was induced by clostridial collagenase infusion into the right caudate putamen, and several time points and doses of melatonin were studied. Brain edema and neurological function at 24 h were unchanged in comparison with vehicle-treated groups, in spite of oxidative stress reductions. Repeated treatment with the lower dose of melatonin (5 mg/kg) given at 1 h and every 24 h thereafter for 3 days after ICH, led to normalization of striatal function and memory ability over the course of 8 weeks, and less brain atrophy 2 weeks later. These results suggest that melatonin is safe for use after ICH, reduces oxidative stress, provides brain protection, and could be used for future investigations of free radical mechanisms after cerebral hemorrhage