(Stroke. 1996;27:1817-1820.)
© 1996 American Heart Association, Inc.
Articles |
the University Department of Medicine and Therapeutics, Western Infirmary, Glasgow (K.W.M., C.J.W., K.R.L.); Robertson Center for Biostatistics, University of Glasgow (C.J.W., G.D.M.); and Scottish Record Linkage, Information and Statistics Division, Edinburgh (C.P.) (UK).
Correspondence to Dr Kennedy R. Lees, University Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, UK.
| Abstract |
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Methods A single observer scored consecutive admissions to an acute stroke unit on the National Institutes of Health Stroke Scale (NIHSS), the Canadian Neurological Scale, and the Middle Cerebral Artery Neurological Score. Guy's prognostic score was determined from clinical data. Outcome at 2, 3, 6, and 12 months was categorized as good (alive at home) or poor (alive in care or dead). Predictive accuracy of the variables was compared by receiver operating characteristic curves and stepwise logistic regression.
Results Of the 408 patients studied, 373 had confirmed acute stroke and completed follow-up. The three stroke rating scales each predicted 3-month outcome with an accuracy of .79 or greater. The NIHSS provided the most prognostic information: sensitivity to poor outcome, .71 (95% confidence interval [CI], .64 to .79); specificity, .90 (95% CI, .86 to .94); and overall accuracy, .83 (95% CI, .79 to .87). Logistic regression showed that the NIHSS added significantly to the predictive value of all other scores. No score added useful information to the NIHSS. A cut point of 13 on the NIHSS best predicted 3-month outcome.
Conclusions Baseline NIHSS best predicts 3-month outcome. The Canadian Neurological Scale and Middle Cerebral Artery Neurological Score also perform well. Baseline assessments in clinical trials only need to include a single stroke rating scale.
Key Words: clinical trials prognosis stroke assessment
| Introduction |
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Several multivariate scoring systems have been developed with the sole aim of predicting outcome. A recent evaluation8 compared five multivariate prognostic scoring systems with simple univariate predictors of outcome, such as level of consciousness, and concluded that multivariate scoring systems, when applied outside the context of their development, fare no better than simple predictors.
We sought to determine the best statistical model for predicting outcome at 3 months after stroke using baseline measures on three stroke scales (the MCANS,9 10 CNS,3 and NIHSS4 ) and a specifically designed prognostic score (Guy's prognostic score11 ).
| Subjects and Methods |
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A single experienced observer (K.W.M.) assessed each of the patients within 72 hours of admission according to the NIHSS, CNS, and MCANS. The originally described version of the NIHSS was used for all patients. Guy's prognostic score was derived for each patient with information from the ASU clinical database.
Outcome follow-up was by record linkage13 to death records from the Registrar General of Scotland and to hospital discharge records to obtain information on medical events after stroke. This technique has been validated previously in an epidemiological study of hypertension14 and has also been used for end point monitoring in a large clinical trial.15 The method of record linkage is a reliable one; however, admissions to private hospitals or institutions outside Scotland are not detected. Outcome was categorized as alive at home, alive in care, or dead at 2, 3, 6, and 12 months after stroke. Outcome at 3 months was chosen as the outcome measure for the subsequent multivariate analysis. This practical outcome measure is a marker for 3-month functional outcome, an end point commonly used in trials of therapeutic agents in acute stroke.16
Throughout the analysis, nonparametric methods were used, since stroke scales provide ordinal level data that are not normally distributed. Correlations between the stroke scales and Guy's score were expressed with the use of Spearman's rank correlation coefficient. Kruskal-Wallis tests were used to investigate differences in median scores between patients in the alive at home, alive in care, and dead outcome groups. ROC curves17 were used to assess the usefulness of the individual scores in predicting whether outcome was poor (alive in care or dead) or good (alive at home).
Stepwise logistic regression18 was used to assess which subset of the variables best predicted good or poor outcome as defined above. This sequential procedure first includes the best predictor variable, then the next best predictor variable, and so on until no significant variables remain outside the model. Logistic regression estimates the probability of poor outcome for each patient, and by choosing a cutoff probability, we may then predict whether patients will have a good or poor outcome. These predictions may be compared with the true outcomes to obtain the sensitivity and specificity of the procedure for identifying patients who will have a poor outcome. A cutoff probability of .5 was chosen. We performed the statistical analysis using MINITAB and BMDP on a PC and Splus on a UNIX workstation. The logistic regression analysis was repeated after the exclusion of patients with clinical signs of posterior circulation stroke, since the CNS was designed for use in carotid territory stroke with motor signs and the MCANS for use in middle cerebral artery strokes. This avoids a biased comparison of the stroke assessment scales since the NIHSS is the only one to include signs indicative of vertebrobasilar stroke, such as ataxia.
| Results |
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Table 1
shows the placement of patients at 2, 3, 6, and 12 months after admission to the ASU. Table 2
shows pairwise Spearman rank correlation coefficients among the four scores being tested. Table 3
gives the median of each score according to the 3-month outcome grouping. For each score, a Kruskal-Wallis ANOVA showed highly significant differences in median baseline score between outcome groups (P<.001 in each case). The Figure
presents ROC curves for prediction of 3-month poor outcome for each of the numerical scores. A comparison of the predictive power of variables can be made by assessing which curve approaches the top left corner of the plot most closely. Guy's prognostic score appears to be a weaker predictor of outcome than the stroke scales, of which the NIHSS seems narrowly to be the best.
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In the stepwise logistic regression model, the NIHSS (P<.0001) was the first variable to be included. This model, in which only the NIHSS was used, gave a sensitivity to poor outcome of .71 (95% CI, .64 to .79), a specificity of .90 (95% CI, .86 to .94), a positive predictive value of .82 (95% CI, .75 to .89), and an overall predictive accuracy of .83 (95% CI, .79 to .87). Guy's prognostic score was the next variable to be added to the model. However, although this variable was statistically significant (P=.0016), the number of correct predictions decreased slightly (sensitivity, .70 [95% CI, .62 to .77]; specificity, .89 [95% CI, .85 to .93]; positive predictive value, .80 [95% CI, .73 to .87]; and overall predictive accuracy, .82 [95% CI, .78 to .86]). None of the other variables (CNS, MCANS) was significant. Prediction according to the model based on NIHSS score alone is equivalent to choosing a cutoff of 13 on the baseline NIHSS and predicting all patients scoring 13 or more as having a poor outcome. Despite its statistical significance, the model in which the NIHSS alone was used did not give substantially greater accuracy than those in which the CNS or MCANS alone was used.
To further investigate the apparent superiority of the NIHSS over the CNS, MCANS, and Guy's prognostic score, each variable in turn was forced into the model. Stepwise logistic regression was then used to test whether any of the other variables significantly improved the fit of the model. Table 4
shows the results of this additional modeling. In each case the NIHSS was found to add extra predictive information to the variable that was initially forced into the model. However, these more complex models did not result in better predictive accuracy than the model in which only the NIHSS was used.
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After the exclusion of patients with posterior circulation events, the results of the stepwise logistic regression modeling were identical to those in which all patients were considered. The NIHSS was the best predictor of outcome, providing extra predictive information over the other scores. Overall accuracy of the individual scales, except for Guy's score, was slightly lower than in the entire patient group (Table 5
).
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| Discussion |
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None of the acute impairment scales has sought to assess disability, and none was designed to provide any indication of prognosis. The use of stroke scales in clinical trials to measure either baseline severity or progress has therefore hitherto been based on the assumption that the features assessed by a scale are of relevance to disability. In contrast, scales designed to predict outcome have not been used widely in clinical trials.
Most impairment scales, including the MCANS, CNS, the Scandinavian Stroke Scale,19 and the European Stroke Scale,20 are weighted very heavily toward motor function in the hemiparetic limbs, with minor additional scores for language function, level of consciousness, or hemianopia. There has if anything been a tendency to increase the relative importance of the motor score and to specify more complex assessments with each new scale. The NIHSS is constructed differently, in that each test item is graded, but no significant weighting is given to limb function, and many additional items, such as ataxia, sensory loss, or visuospatial perception, are also included. However, scoring these additional aspects of neurological function may be a mixed blessing since they are often untestable in aphasic or comatose patients. Total scores cannot be reliably compared between the NIHSS and other scales,21 and in clinical use the NIHSS total score has a practical ceiling well below its theoretical upper limit because of nonscoring of untestable items. Patients with language disorders are particularly likely to produce scores of poor comparability between the NIHSS and MCANS or CNS.
Given these differences between stroke scales, why should the NIHSS provide a better prediction of 3-month outcome than either the MCANS or CNS? Unlike the MCANS or CNS, the NIHSS is not weighted in an arbitrary fashion toward motor function of limbs, but since all tested items are graded more or less equally, it rather reflects the overall degree of neurological deficit. While limb strength is certainly an important determinant of functional recovery from stroke, our results suggest that the MCANS and CNS perhaps place unnecessary emphasis on assessment of the degree of weakness over other neurological features. An even more heavily motor-weighted scale such as the European Stroke Scale is clearly open to similar criticism. These differences will also be determined by the chosen outcome measure since many of the disability scales in current use are similarly heavily weighted toward motor function (notably the Barthel Index22 ). Simple and robust outcome criteria were chosen for this study since these are of greater importance to patients and caregivers than minor differences in the abstract numbers of a rating scale. Our inclusion of patients "alive in care" in the poor outcome group reflects the situation in Scotland, where more severely disabled patients are cared for in the hospital rather than at home.
If several rating scales for prediction of outcome are available, sensitivity and specificity to poor outcome are only two criteria used to compare scales. If there is no substantial difference in the predictive accuracy of a number of rating scales, then simplicity of use becomes important. The NIHSS requires scoring of a greater number of aspects of neurological function than the CNS or MCANS. However, video training in the use of the NIHSS is available, which provides a standard for the use of the scale and improves interobserver reliability.23
Our results suggest that when baseline comparison of treatment groups in a clinical trial is required, the NIHSS is sufficiently accurate and for many trials should be routine. The CNS, MCANS, and Guy's prognostic score offer no useful additional information. The NIHSS remains accurate even when patients with vertebrobasilar stroke are not considered, a fact relevant to the many clinical trials that limit inclusions to patients with hemispheric strokes only.
| Selected Abbreviations and Acronyms |
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| Acknowledgments |
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Received March 28, 1996; revision received July 4, 1996; accepted July 5, 1996.
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M. Weih, K. Kallenberg, A. Bergk, U. Dirnagl, L. Harms, K. D. Wernecke, and K. M. Einhaupl Attenuated Stroke Severity After Prodromal TIA : A Role for Ischemic Tolerance in the Brain? Stroke, September 1, 1999; 30(9): 1851 - 1854. [Abstract] [Full Text] [PDF] |
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S. E. Kasner, J. A. Chalela, J. M. Luciano, B. L. Cucchiara, E. C. Raps, M. L. McGarvey, M. B. Conroy, and A. R. Localio Reliability and Validity of Estimating the NIH Stroke Scale Score from Medical Records Stroke, August 1, 1999; 30(8): 1534 - 1537. [Abstract] [Full Text] [PDF] |
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H. P. Adams Jr., P. H. Davis, E. C. Leira, K.-C. Chang, B. H. Bendixen, W. R. Clarke, R. F. Woolson, and M. D. Hansen Baseline NIH Stroke Scale score strongly predicts outcome after stroke: A report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST) Neurology, July 1, 1999; 53(1): 126 - 126. [Abstract] [Full Text] |
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S.-M. Lai, P. W. Duncan, and J. Keighley Prediction of Functional Outcome After Stroke : Comparison of the Orpington Prognostic Scale and the NIH Stroke Scale Stroke, September 1, 1998; 29(9): 1838 - 1842. [Abstract] [Full Text] [PDF] |
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M. O. McCarron, K. W. Muir, C. J. Weir, A. G. Dyker, I. Bone, J.A.R. Nicoll, and K.R. Lees The Apolipoprotein E {epsilon}4 Allele and Outcome in Cerebrovascular Disease Stroke, September 1, 1998; 29(9): 1882 - 1887. [Abstract] [Full Text] [PDF] |
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M. A. Meyer, J. Grotta, and A. Alexandrov Quantitative Brain SPECT and the NIH Stroke Scale • Response Stroke, July 1, 1998; 29(7): 1480 - 1480. [Full Text] |
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P. M. Kelly-Hayes, J. T. Robertson, J. P. Broderick, P. W. Duncan, L. A. Hershey, E. J. Roth, W. H. Thies, and C. A. Trombly The American Heart Association Stroke Outcome Classification Stroke, June 1, 1998; 29(6): 1274 - 1280. [Full Text] [PDF] |
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H. P. Adams Jr Treating Ischemic Stroke as an Emergency Arch Neurol, April 1, 1998; 55(4): 457 - 461. [Abstract] [Full Text] [PDF] |
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S. C. Cramer, G. Nelles, J. D. Schaechter, J. D. Kaplan, and S. P. Finklestein Computerized Measurement of Motor Performance After Stroke Stroke, November 1, 1997; 28(11): 2162 - 2168. [Abstract] [Full Text] |
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