To Treat or Not to Treat?
Pilot Survey for Minor and Rapidly Improving Stroke
Background and Purpose—Minor strokes and rapidly improving stroke symptoms are frequent exclusions for intravenous tissue-type plasminogen activator. We explored factors influencing tissue-type plasminogen activator treatment decision for minor strokes/rapidly improving stroke symptoms.
Methods—A pilot survey, including 110 case scenarios, was completed by 17 clinicians from 2 academic medical centers. Respondents were asked whether they would treat each case with tissue-type plasminogen activator at 60 minutes after emergency department admission. Cases varied by (1) National Institutes of Health Stroke Scale score at treatment decision time, (2) symptom pattern over time (improvement or worsening and then improving), (3) type of neurological deficit (3 main domains: motor, visual/sensory/ataxia, and language/neglect), and (4) age/occupation (4 profiles). Logistic regression was used to predict probability of omission (pO). A binomial regression model was used to predict probability of treatment decision.
Results—Predicted probability of treatment decision was affected by National Institutes of Health Stroke Scale score (P<0.001) and age/occupation profiles (P<0.001) but not by symptom patterns (P=0.334). There were significant, albeit modest, main effects on probability of treatment decision for neurological domains. Responses were most likely omitted (P=0.027) for cases improvement pattern and language/neglect domain (pO=0.74; 95% confidence interval, 0.52–0.89) and with visual/sensory/ataxia domain (pO=0.74; confidence interval, 0.37–0.93) when compared with improvement pattern and motor domain (pO=0.17; confidence interval, 0.06–0.42) and to any worsening and then improving patterns (0.37<pO<0.56).
Conclusions—This pilot survey provides the first quantitative evidence that National Institutes of Health Stroke Scale score is not the only determinant of treatment decision. A National Institutes of Health Stroke Scale score of 2 is the potential equipoise point, with the least consensus on treatment decision. These preliminary findings require validation in larger population surveys.
Minor strokes and rapidly improving stroke symptoms are the most frequently cited exclusion criteria for intravenous tissue-type plasminogen activator (tPA).1 Approximately half of all ischemic stroke cases have mild symptom severity at presentation (ie, median National Institutes of Health Stroke Scale [NIHSS] score ≤3; 25–75 interquartile range, 1–7)2 with not always favorable outcomes when left untreated.1,3–7
These exclusion criteria are left to clinical judgments without standard or accepted guidelines.8 The most appropriate diagnostic and management approach to minor strokes or rapidly improving stroke symptoms remains debatable.5 A post hoc analysis of outcomes of minor strokes included in the National Institute of Neurological Disorders and Stroke trials revealed too small a sample for definitive conclusions.9 A currently ongoing randomized clinical trial, A Study of the Efficacy and Safety of Activase (Alteplase) in Patients With Mild Stroke (PRISMS),10 is evaluating the safety and efficacy of tPA for minor strokes.
Factors influencing treatment of minor strokes or rapidly improving stroke symptoms have not been systematically studied.
Our pilot study explored factors influencing the tPA treatment decision for minor strokes and rapidly improving stroke symptoms among neurologists treating acute stroke. We hypothesized that different ages and occupations, symptom patterns over time, types of neurological deficits, and stroke severity at treatment decision time affect a clinician’s decision to use tPA.
This study was approved by the Institutional Review Board. A pilot survey, including 110 case scenarios, was provided to 40 physicians, 36 attendings (vascular and general neurologists), and 4 stroke fellows from 2 urban academic medical centers (The State University of New York, Downstate Medical Center, Brooklyn, NY and Tufts University Medical Center, Boston, MA). Answers were collected anonymously.
Each scenario provided an individual patient with acute stroke with graphical representation of the patient’s stroke symptoms defined by the NIHSS score at presentation to the emergency department and again at 30 minutes and 60 minutes after emergency department admission (Figure 1). For each scenario, respondents were asked whether they would treat with tPA at 60 minutes after emergency department admission provided that there were no other contraindications for tPA. Cases varied on the following factors: (1) NIHSS score (range, 1–5), at treatment decision time; (2) symptom pattern measured by NIHSS over 3 time points (continuous improvement [IMP] or worsening and then improving [WI]); (3) type of neurological deficit grouped into 3 domains (motor [M], visual/sensory/ataxia [VSA], and language/neglect [LN]); and (4) age/occupation (4 profiles: 35 year old violinists, 65 year old lawyers, 52 year old taxi drivers, and 80 year old retired cases).
The M domain included the following NIHSS items: facial palsy (4), motor arm (5), motor leg (6), and dysarthria (10). The VSA domain included the following NIHSS items: visual (3), limb ataxia (7), and sensory (8). The LN domain included the following NIHSS items: best language (9), level of consciousness questions (1b), level of consciousness commands (1c), and extinction and inattention (formerly neglect; 11). Survey samples are provided in Figure 1.
The unit of analysis was the individual case scenario (n=110). Each scenario was dichotomized into those having ≥1 missing response or no missing response from any respondent. A logistic regression model was fitted to predict the probability of omitted responses to scenarios. After excluding omissions, a binomial regression model was fitted predicting the probability of tPA treatment recommendation. Predictors for the model were NHSS score (linear, varying from 1–5), the specific neurological domain (M, VSA, or LN), symptom pattern over time (IMP or WI), and any potential interactions. Subsequent analyses included factor age/occupation included in 80 scenarios.
Seventeen of 40 (43%) physicians completed the survey.
Predicted Probability of Treatment Recommendation
Predicted probability of treatment recommendation (p[tPA]) was significantly affected by the NIHSS score (P<0.001), decreasing with decreasing scores (p[tPA]=0.98, 0.97, 0.83, 0.57, and 0.36 for NIHSS scores of 5, 4, 3, 2, and 1, respectively).
The closest p(tPA) to equipoise was at an NIHSS score of 2 (0.57; 95% confidence interval [CI], 0.51–0.62; Figure 2).
Treatment decision was also affected by age/occupation profiles (P<0.001). Treatment was less likely recommended for the 80 year old retired cases. Model-estimated probabilities of treatment recommendation by age/occupation were as 35 year old violinists 0.888 (95% CI, 0.836–0.925), 65 year old lawyers 0.865 (95% CI, 0.807–0.908), 52 year old taxi drivers 0.885 (95% CI, 0.836–0.921), and 80 year old retired cases 0.744 (95% CI, 0.660–0.812). There were no significant interactions between NIHSS and age/occupation.
There were significant, albeit modest, main effects on p(tPA) for neurological domains (LN, 0.873 [95% CI, 0.841–0.900]; M, 0.825 [95% CI, 0.782–0.860]; and VSA 0.850 [95% CI, 0.800–0.889]; P=0.032) but not for symptom patterns (IMP or WI; P=0.334).
Predicted Probability of Omissions
The frequency of omitted responses was 2.8% of the total of 1870 responses analyzed. Fifty-two of the 110 scenarios analyzed had exactly 1 missing response each. Model-estimated probabilities of omission by any respondent for any individual factor ranged from the IMP pattern associated with LN 0.74 (95% CI, 0.523–0.885) and VSD domain 0.74 (95% CI, 0.367–0.934) to IMP pattern combined with the M domain 0.17 (95% CI, 0.059–0.416) and to any WI patterns (0.37<probability of omission<0.56). There was a significant 2-way interaction between symptom pattern over time and domains of neurological deficits (P=0.027). There was no significant effect involving NIHSS scores (P=0.785).
This pilot survey provides, to our knowledge, the first quantitative evidence that the NIHSS score at treatment time is not the only determinant of a clinician’s tPA treatment decision. The type of neurological deficits at treatment decision time influenced the clinician’s recommendation: the LN domain deficits were more likely to be recommended for treatment than M domain deficits. We recognize that the LN domain included both language and neglect, and therefore, we cannot ascertain their individual importance. This is also true for the other domains where NIHSS items were combined. Our findings suggest the need to further explore, in a larger survey, specific individual NIHSS items and to analyze their role in the clinician’s treatment decision.
An NIHSS score of 2 was identified as a potential equipoise point, with the least consensus on tPA decision. To our knowledge, a specific NIHSS score reflecting the greatest level of uncertainty for a tPA treatment decision has not been previously reported. We found that the lower the NIHSS score within the range of 1 to 5, the less likely the clinician would treat with tPA. Even though the symptom pattern over time did not significantly affect the probability of treatment, in conjunction with the domains of neurological deficits, it was the strongest predictor of the clinician’s response omission, suggesting a greater level of uncertainty for giving tPA when symptoms are fluctuating and not stable. It is also possible that answers were inadvertently skipped rather than omitted because of uncertainty.
Our study has several limitations. The response rate was 43%. We could not test the effect of each NIHSS item, age/occupation, and symptom pattern over time on p(tPA) because the number of clinical scenarios requiring testing would be burdensome in this preliminary study. As we only piloted 2 urban academic medical centers, we may not be able to generalize these results to all academic stroke centers and to nonacademic institutions. Further, we did not explore how training level may influence physicians’ treatment decision.
Our study provides objective evidence that there are various factors affecting clinician’s treatment decision and that an NIHSS score of 2 seems the equipoise point with the least consensus on treatment decision. These findings require to be validated in a larger population survey.
Sources of Funding
Dr Levine was supported by the National Institutes of Health grants 1RO1HL96944, 1U0NS1080377, and 1U01NS077378. Dr Balucani was supported by the American Heart Association/American Stroke Association/Founders Affiliate and the American Brain Foundation Lawrence M. Brass, MD, Stroke Research Postdoctoral Fellowship Award.
Dr Levine is a member of Scientific Advisory Committee for PRISMS (An Ongoing Genentech, Inc–funded study—modest honorarium and travel expenses). The other authors report no conflicts.
- Received November 26, 2014.
- Revision received December 24, 2014.
- Accepted December 26, 2014.
- © 2015 American Heart Association, Inc.
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