Leading opinions Is a prestroke modified Rankin Scale sensible? Askiel Bruno1, Jeffrey A. Switzer1, Valerie L. Durkalski2, and Fenwick T. Nichols1
Eligibility criteria are one of the crucial acute stroke clinical trial design issues. To enhance detection of favorable clinical outcomes related to acute stroke interventions, it seems reasonable to exclude patients with significant premorbid handicaps from acute treatment trials. The identification of such significantly impaired patients during screening in acute stroke trials has not been standardized. Many acute stroke trials estimated the modified Rankin Scale (1) score (mRS) (Table 1) before the stroke to determine patient eligibility (2–7). However, careful consideration of the mRS shows that applying it before stroke is problematic. The problem stems from the fact that the mRS was developed and is intended for use after a period of recovery from stroke to evaluate the residual effects, by comparing general function just before the stroke to that after some recovery period (8, 9, 1, 10). This is unlike the Barthel Index (11) for example, where activities of daily living can be evaluated any time without comparison to another time point. The guidelines for scoring the mRS do not apply before a stroke. Investigators attempting to assign a prestroke mRS must assume some reference point of ‘normal’ functioning for comparison. As such assumptions are not defined, they likely vary by rating, resulting in possible inclusion of some undesirable subjects, and exclusion of some desirable subjects in clinical stroke trials. Such incompletely defined eligibility criteria can retard recruitment, impede the detection of a treatment effect, hinder trial reproducibility, and limit the generalizability of clinical trial results. We offer further insight into this problem and a simple interim alternative.
The problem When distinguishing mRS scores 2, 1, and 0 comparison to the prestroke state is needed (Table 1); 2 5 ‘able to look after own affairs’ but ‘unable to carry out some of previous activities’ (‘previous’ implies just before the stroke), 1 5 ‘able to carry out all usual duties and activities’ (‘usual’ implies those just before the stroke), 0 5 ‘no symptoms at all’ (completely recovered Correspondence: Askiel Bruno, 1120 15th Street BI 3076, Department of Neurology, Georgia Health Sciences University, Augusta, GA 30912, USA. E-mail:
[email protected] 1 Department of Neurology, Georgia Health Sciences University 2 Department of Medicine, Division of Biostatistics and Epidemiology, Medical University of South Calrolina Conflict of interest: None declared. DOI: 10.1111/j.1747-4949.2011.00661.x
414
Table 1 The modified Rankin Scale. Reproduced from reference #1 Grade Description 0 1 2 3 4 5
No symptoms at all No significant disability despite symptoms: able to carry out all usual duties and activities Slight disability: unable to carry out all previous activities, but able to look after own affairs without assistance Moderate disability: requiring some help, but able to walk without assistance Moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance Severe disability: bedridden, incontinent, and requiring constant nursing care and attention
from the symptoms and deficits of the recent stroke) (8, 9, 1, 10). As there is no established reference point to compare the immediate prestroke state to, mRS categories 2, 1, and 0 cannot be reliably distinguished from one another before stroke. For example, if an acute stroke patient has limb dysfunction with symptoms and neurological deficits from a childhood nerve injury, does he have a prestroke mRS score of 1 because whatever he was doing right before his stroke could be considered his usual duties and activities? Or does he have a score of 2 because he also has a neurological deficit? Another example of this dilemma is a medical condition without neurological symptoms, such as congestive heart failure. Does such a patient have no symptoms at all (prestroke mRS 5 0) because the symptoms are not neurological? Or does he have a prestroke mRS 5 1 because he has symptoms (exertional dyspnea) and whatever he was doing right before the stroke could be considered his usual duties and activities? Or does he have a prestroke mRS 5 2 because due to the heart failure he is not able to do all the things that he was doing some time before, but still ‘able to look after own affairs?’ Furthermore, if a prestroke mRS is scored 1 or 2, this could result in an unreasonable situation after a period of recovery. As some of the patients with a prestroke mRS of 1 or 2 will recover fully from their most recent stroke, they should score 0 on their subsequent mRS according to the scale instructions (8, 9, 1, 10). This would thus be misleading, suggesting that some patients’ functioning is better after their stroke than it was before. Also, using the undefined and not validated prestroke mRS in statistical analysis further increases the risk of getting misleading results.
& 2011 The Authors. International Journal of Stroke & 2011 World Stroke Organization Vol 6, October 2011, 414–415
Leading opinions
A. Bruno et al.
One potential alternative The mRS is a popular and useful functional outcome measure after stroke, but it is unsuitable for prestroke assessment and defined and valid options exist. For example, ability to walk and live independently before a stroke could be rapidly ascertained during screening in acute stroke trials. Such patients have the potential to achieve any mRS score after rehabilitation. Welldefined eligibility criteria in acute stroke trials will optimize patient selection and consequently trial efficiency, trial reproducibility, and the detection of treatment effects.
References 1 van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1988; 19:604–7. 2 Ogawa A, Mori Efor the MELT Japan Study Group. et al. Randomized trial of intraarterial infusion of urokinase within 6 hours of middle cerebral artery stroke: the middle cerebral artery embolism local fibrinolytic intervention trial (MELT) Japan. Stroke 2007; 38:2633–9. 3 Mayer SA, Brun NC, Begtrup K. et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2008; 358:2127–37. 4 Hacke W, Furlan AJ, Al-Rawi Y et al. Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-
5
6
7
8
9
10
11
diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Lancet Neurol 2009; 8:141–50. Levy DE, del Zoppo GJ, Demaerschalk BM et al. Ancrod in acute ischemic stroke: results of 500 subjects beginning treatment within 6 hours of stroke onset in the ancrod stroke program. Stroke 2009; 40: 3796–803. Potter JF, Robinson TG, Ford GA et al. Controlling hypertension and hypotension immediately post-stroke (CHHIPS): a randomised, placebo-controlled, double-blind pilot trial. Lancet Neurology 2009; 8: 48–56. Meurer WJ, Scott PA, Caveney AF et al. Lack of association between hyperglycaemia at arrival and clinical outcomes in acute stroke patients treated with tissue plasminogen activator. Int J Stroke 2010; 5:163–6. Modified Rankin scale, English.. Available at http://trials-rankin.Trainingcampus.Net/uas/modules/trees/windex.Aspx (accessed March 29, 2011). Wilson L.. Structured interview for the modified Rankin scale: questionnaire and guidelines. Available at http://www.Psychology.Stir.Ac.Uk/ staff/lwilson/documents/mrs_structured_interview.Pdf (accessed March 29, 2011). Wilson JTL, Hareendran A, Grant M, Baird T, Schulz UGR, Muir KW, Bone I. Improving the assessment of outcomes in stroke: use of a structured interview to assign grades on the modified Rankin scale. Stroke 2002; 33:2243–6. The Barthel Index of activities of daily living.. Available at http:// www.healthcare.uiowa.edu/igec/tools/function/barthelADLs.pdf (accessed March 29, 2011).
& 2011 The Authors. International Journal of Stroke & 2011 World Stroke Organization Vol 6, October 2011, 414–415
415
