Comparison of the National Institutes of Health Stroke Scale with disability outcome measures in acute stroke trials

<p><b>Background and Purpose:</b> Acute stroke trials typically use disability scales as their primary end point. Neurologic impairment scales such as the National Institutes of Health Stroke Scale (NIHSS) are possibly more sensitive to change in patient status. We aimed to compare a range of potential NIHSS end points with modified Rankin Scale (mRS) and Barthel Index (BI) end points.</p> <p><b>Methods:</b> We simulated a total of 6000 clinical trials, each with 1400 patients. We estimated statistical power for a range of NIHSS end points, including prognosis-adjusted and fixed dichotomized end points. These end points were compared with the BI and mRS dichotomized at 95 and 1, respectively.</p> <p><b>Results:</b> The most powerful fixed end point was the NIHSS dichotomized at 1. For prognosis-adjusted outcome, we found greatest power if we defined success as achieving a score of ≤1 or improvement by at least 11 points from baseline. We are more likely to achieve a statistically significant result by using this prognosis-adjusted end point instead of NIHSS ≤1 (odds ratio, 2.8; 95% confidence interval [CI], 2.5 to 3.2). Use of the optimal NIHSS prognosis-adjusted end point rather than BI ≥95 could justify a reduction in sample size of approximately 68% (95% CI, 67% to 69%) without loss of statistical power.</p> <p><b>Conclusions:</b> The NIHSS neurologic scale appears more sensitive than the BI or mRS, allowing smaller sample sizes or greater statistical power. The use of an NIHSS prognosis-adjusted end point could allow therapeutic effects from drugs to be more easily identified.</p&gt

Categorizing stroke prognosis using different stroke scales

<p><b>Background and Purpose</b>: Stroke severity and dependency are often categorized to allow stratification for randomization or analysis. However, there is uncertainty whether the categorizations used for different stroke scales are equivalent. We investigated the amount of information retained by categorizing severity and dependency, and whether the currently used cut-offs are equivalent across different stroke scales.</p> <p><b>Methods</b>: Stroke severity and dependency have been categorized as mild, moderate, or severe. We studied 2 acute stroke unit cohorts, measuring Scandinavian Stroke Scale (SSS), modified Rankin Scale (mRS), Barthel Index (BI), and modified National Institutes of Health Stroke Scale (mNIHSS). Receiver operating characteristic (ROC) curves were examined to determine the ability of full and categorized scales to predict death and dependency. A weighted kappa analysis assessed agreement between the categorized scales.</p> <p><b>Results</b>: When scales are categorized, the area under the ROC curve is significantly reduced; however, the differences are small and may not be practically important. BI, mRS, and SSS all have excellent agreement with each other when categorized, whereas mNIHSS has substantial agreement with mRS and BI.</p> <p><b>Conclusions</b>: Little predictive information is lost when stroke scales are categorized. There is substantial to almost perfect agreement among categorized scales. Therefore the use and categorization of a variety of stroke severity or dependency scales is acceptable in analyses.</p&gt

The evidence-base for stroke education in care homes

<b>Summary.</b> <b>Research questions:</b> 1. What are registered care home nurses’ educational priorities regarding stroke care? 2. What are senior care home assistants’ educational priorities regarding stroke care? 3. How do care home nurses conceive stroke care will be delivered in 2010? <b>Study design:</b> This was a 2-year study using focus groups, stroke guidelines, professional recommendations and stroke literature for the development of a questionnaire survey for data collection. Workshops provided study feedback to participants. Data were collected in 2005–2006. <b>Study site:</b> Greater Glasgow NHS Health Board. <b>Population and sample:</b> A stratified random selection of 16 private, 3 voluntary and 6 NHS continuing care homes from which a sample of 115 trained nurses and 19 senior care assistants was drawn. <b>Results:</b> The overall response rate for care home nurses was 64.3% and for senior care assistants, 73.6%. Both care home nurses and senior care assistants preferred accredited stroke education. Care home nurses wanted more training in stroke assessment, rehabilitation and acute interventions whereas senior care assistants wanted more in managing depression, general stroke information and communicating with dysphasic residents. Senior care assistants needed more information on multidisciplinary team working while care home nurses were more concerned with ethical decision-making, accountability and goal setting. <b>Conclusions:</b> Care home staff need and want more stroke training. They are clear that stroke education should be to the benefit of their resident population. Guidelines on stroke care should be developed for care homes and these should incorporate support for continuing professional learning in relation to the resident who has had a stroke

Stroke education for healthcare professionals: making it fit for purpose

<b>Research questions:</b> 1. What are healthcare professionals’ (HCPs) educational priorities regarding stroke care? 2. Do stroke care priorities vary across the primary and secondary sectors? 3. How do HCPs conceive stroke care will be delivered in 2010? <b>Study design:</b> This was a two-year study using focus groups and interviews for instrument development, questionnaires for data collection and workshops to provide study feedback. Data were collected in 2005–06. <b>Study site:</b> One Scottish health board. <b>Inclusion criteria:</b> All National Health Service healthcare professionals working wherever stroke care occurred. <b>Population and sample:</b> Participants were drawn from 4 university teaching hospitals, 2 community hospitals, 1 geriatric medicine day hospital, 48 general practices (GPs), 12 care homes and 15 community teams. The sample comprised 155 doctors, 313 nurses, 133 therapists (physiotherapists, occupational therapists, speech and language therapists), and 29 ‘other HCPs’ (14 dieticians, 7 pharmacists, 2 podiatrists and 6 psychologists). <b>Results:</b> HCPs prefer face-to-face, accredited education but blended approaches are required that accommodate uni- and multidisciplinary demands. Doctors and nurses are more inclined towards discipline-specific training compared to therapists and other healthcare professionals (HCPs). HCPs in primary care and stroke units want more information on the social impact of stroke while those working in stroke units in particular are concerned with leadership in the multidisciplinary team. Nurses are the most interested in teaching patients and carers. <b>Conclusions</b> Stroke requires more specialist stroke staff, the upskilling of current staff and a national education pathway given that stroke care is most effectively managed by specialists with specific clinical skills. The current government push towards a flexible workforce is welcome but should be educationally-sound and recognise the career aspirations of healthcare professionals

Allopurinol use yields potentially beneficial effects on inflammatory indices in those with recent ischemic stroke: a randomized, double-blind, placebo-controlled trial

<p><b>Background and Purpose</b>: Elevated serum uric acid level is associated with poor outcome and increased risk of recurrent events after stroke. The xanthine oxidase inhibitor allopurinol lowers uric acid but also attenuates expression of inflammatory adhesion molecules in murine models, reduces oxidative stress in the vasculature, and improves endothelial function. We sought to investigate whether allopurinol alters expression of inflammatory markers after acute ischemic stroke.</p> <p><b>Methods</b>: We performed a randomized, double-blind, placebo-controlled trial to investigate the safety, tolerability, and effect of 6 weeks’ treatment with high- (300 mg once a day) or low- (100 mg once a day) dose allopurinol on levels of uric acid and circulating inflammatory markers after ischemic stroke.</p> <p><b>Results</b>: We enrolled 50 patients with acute ischemic stroke (17, 17, and 16 in the high, low, and placebo groups, respectively). Mean (±SD) age was 70 (±13) years. Groups had similar characteristics at baseline. There were no serious adverse events. Uric acid levels were significantly reduced at both 7 days and 6 weeks in the high-dose group (by 0.14 mmol/L at 6 weeks, P=0.002). Intercellular adhesion molecule-1 concentration (ng/mL) rose by 51.2 in the placebo group, rose slightly (by 10.6) in the low-dose allopurinol group, but fell in the high-dose group (by 2.6; difference between groups P=0.012, Kruskal-Wallis test).</p> <p><b>Conclusion</b>: Allopurinol treatment is well tolerated and attenuates the rise in intercellular adhesion molecule-1 levels seen after stroke. Uric acid levels were lowered with high doses. These findings support further evaluation of allopurinol as a preventive measure after stroke.</p&gt

Poststroke neurological improvement within 7 days is associated with subsequent deterioration

Background and Purpose: Improvement in the National Institutes of Health Stroke Scale (NIHSS) 24 hours after stroke has been associated with subsequent neurological deterioration. We hypothesized that a similar association would be apparent for events occurring after 7 days, when acute changes from edema and herniation are less common. We evaluated the degree of NIHSS improvement at 7 days (recovery) as a predictor of subsequent neurological deterioration from day 7 to day 90. Methods: We studied all patients of the Glycine Antagonist (gavestinel) In Neuroprotection (GAIN) International Trial with ischemic stroke alive at day 7, excluding patients with hemorrhagic events and deaths from nonstroke-related causes. The GAIN International Trial was a randomized, double-blind, placebo-controlled, and parallel-group trial; because the study drug had no effect on stroke outcome, treatment groups were combined for this analysis. Neurological deterioration was assessed by the combined measure, including: (1) stroke-related events recorded as “serious adverse events,” (2) recurrent stroke recorded on a separate case report form, and (3) any NIHSS worsening. Results: Among 1187 patients included, 25% had >65% recovery. Deterioration was more prevalent in the group with &#62;65% early recovery (15.5% versus 10.3%; P=0.01). Logistic regression modeling indicated that recovery was associated with subsequent neurological deterioration (odds ratio, 1.2; 95% CI, 1.1 to 1.3, per 10% recovery) after adjusting for age, NIHSS at 7 days, and stroke subtype. Conclusions: Substantial neurological recovery at 7 days is associated with subsequent neurological deterioration.</p

Magnesium for treatment of acute lacunar stroke syndromes: further analysis of the IMAGES trial

&lt;p&gt;&lt;b&gt;Background and Purpose:&lt;/b&gt; A prespecified interaction analysis of the neutral Intravenous Magnesium Efficacy in Stroke (IMAGES) trial revealed significant benefit from magnesium (Mg) in patients with noncortical stroke. Post hoc analysis indicated that this effect was seen in lacunar clinical syndromes (LACS), interaction P=0.005. We have now examined whether this interaction could be explained by confounding baseline factors.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; LACS was defined on the basis of neurological signs and did not include imaging. We investigated the interaction between baseline variables and Mg treatment on global outcome. We used logistic-regression models to test whether the Mg-LACS interaction remained significant after adjusting for stratification variables, sex, a novel stroke severity score, and baseline variables that had an interaction with treatment (P&#60;0.1).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; The Mg (n=383) and placebo (n=382) groups of LACS patients were well matched on baseline factors. In addition to LACS, we found an interaction between beneficial Mg treatment effect and younger age (P=0.003), higher baseline diastolic blood pressure (P=0.02), higher mean blood pressure (P=0.02), and absence of ischemic heart disease (P=0.07). Even so, the adjusted Mg-LACS interaction remained significant (odds ratio [OR] 0.57; 95% CI, 0.39 to 0.83; P=0.003). In the LACS subgroup, Mg improved Barthel Index &#60;95 (OR 0.73; 95% CI, 0.55 to 0.98), modified Rankin Scale &#62;1 (OR 0.67; 95% CI, 0.50 to 0.91), and global outcome (OR 0.70; 95% CI, 0.53 to 0.92) but not Barthel Index &#60;60 or mortality.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; The positive treatment effect of Mg in LACS cannot be ascribed to general issues of severity, time to treatment, blood pressure, or other baseline factors; equally, this finding may be due to chance. A large trial of Mg treatment in LACS appears justified.&lt;/p&gt

Effects of magnesium treatment in a model of internal capsule lesion in spontaneously hypertensive rats

&lt;p&gt;&lt;b&gt;Background and Purpose:&lt;/b&gt; The study aim was to assess the effects of magnesium sulfate (MgSO4) administration on white matter damage in vivo in spontaneously hypertensive rats.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; The left internal capsule was lesioned by a local injection of endothelin-1 (ET-1; 200 pmol) in adult spontaneously hypertensive rats. MgSO4 was administered (300 mg/kg SC) 30 minutes before injection of ET-1, plus 200 mg/kg every hour thereafter for 4 hours. Infarct size was measured by T2-weighted magnetic resonance imaging (day 2) and histology (day 11), and functional recovery was assessed on days 3 and 10 by the cylinder and walking-ladder tests.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; ET-1 application induced a small, localized lesion within the internal capsule. Despite reducing blood pressure, MgSO4 did not significantly influence infarct volume (by magnetic resonance imaging: median, 2.1 mm3; interquartile range, 1.3 to 3.8, vs 1.6 mm3 and 1.2 to 2.1, for the vehicle-treated group; by histology: 0.3 mm3 and 0.2 to 0.9 vs 0.3 mm3 and 0.2 to 0.5, respectively). Significant forelimb and hindlimb motor deficits were evident in the vehicle-treated group as late as day 10. These impairments were significantly ameliorated by MgSO4 in both cylinder (left forelimb use, P&#60;0.01 and both-forelimb use, P&#60;0.03 vs vehicle) and walking-ladder (right hindlimb score, P&#60;0.02 vs vehicle) tests.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; ET-1–induced internal capsule ischemia in spontaneously hypertensive rats represents a good model of lacunar infarct with small lesion size, minimal adverse effects, and a measurable motor deficit. Despite inducing mild hypotension, MgSO4 did not significantly influence infarct size but reduced motor deficits, supporting its potential utility for the treatment of lacunar infarct.&lt;/p&gt

Results of the MRI substudy of the intravenous magnesium efficacy in stroke trial

&lt;p&gt;&lt;b&gt;Background and Purpose:&lt;/b&gt;Although magnesium is neuroprotective in animal stroke models, no clinical benefit was confirmed in the Intravenous Magnesium Efficacy in Stroke (IMAGES) trial of acute stroke patients. The Magnetic Resonance in IMAGES (MR IMAGES) substudy investigated the effects of magnesium on the imaging surrogate outcome of infarct growth.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; IMAGES trial patients in participating centers were randomized to receive either intravenous magnesium or placebo within 12 hours of stroke onset. Infarct growth was defined as volume difference between baseline diffusion-weighted imaging and day 90 fluid-attenuated inversion recovery image lesions. Patients who died were imputed the largest infarct growth observed.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Among the 90 patients included in the primary analysis, there was no difference in infarct growth (median absolute growth, P=0.639; median percentage growth, P=0.616; proportion with any growth, P=0.212) between the 46 treated with magnesium and 44 with placebo. Infarct growth correlated with NIHSS score change from baseline to day 90. There was a trend showing baseline serum glucose correlated with infarct growth with magnesium treatment, but not in the placebo group. The mismatch frequency was reduced from 73% to 47% by increasing the mismatch threshold from &#62;20% to &#62;100% of core volume.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Infarct growth, confirmed here as a surrogate for clinical progression, was similar between magnesium and placebo treatment, paralleling the main IMAGES trial clinical outcomes. Glucose was a covariate for infarct growth with magnesium treatment. A more stringent mismatch threshold to define penumbra more appropriately would have excluded half of the patients in this 12-hour time window stroke study.&lt;/p&gt