Background and Purpose Recognizing that early spontaneous neurological improvement not uncommonly follows acute ischemic stroke, we conducted this study to determine the incidence of such improvement and its potential relation to stroke etiology.
Methods We prospectively evaluated 68 patients who presented within 12 hours after ischemic stroke, exhibited moderate or severe new functional neurological deficit acutely, and received either no stroke-specific therapy or only antiplatelet therapy over the ensuing week. We reexamined all patients 1 week after stroke onset.
Results Sixteen (24%) of the 68 patients improved to the point of having no or mild functional neurological deficit at 1 week. Patients with lacunar stroke were more likely to enjoy early spontaneous improvement (8/22=36% versus 8/46=17%), but this difference did not reach statistical significance (P=.15).
Conclusions Early spontaneous improvement after ischemic stroke may occur in a substantial proportion of patients and more commonly after lacunar stroke. Even so, the majority of patients with acutely disabling stroke will remain significantly impaired 1 week after stroke onset.
Early spontaneous neurological improvement after ischemic stroke is not uncommon.1 Given the growing interest in acute interventional therapy for stroke, along with the expense and potential risk often associated with such therapy, there may be benefit in distinguishing patients destined for spontaneous improvement from those unlikely to improve without treatment.
We conducted this study to determine the incidence of spontaneous early improvement in patients presenting with functionally disabling acute ischemic stroke and to evaluate whether stroke etiology may influence early prognosis.
Subjects and Methods
Over a period of 4 years (1985-1989) we prospectively and consecutively evaluated all patients presenting to the combined services of the University of California at San Diego Stroke Center with acute ischemic stroke. We rated acute stroke-associated neurological deficits according to the validated Rankin Scale, which we “collapsed” in an effort to further reduce interobserver variability (Table 1⇓).2 We excluded patients with primary hemorrhagic stroke and those with preexisting moderate or severe functional neurological deficit. Our primary study group was composed of patients who were evaluated within 12 hours of ischemic stroke onset, who exhibited moderate or severe deficit at the initial evaluation, and who received either no stroke-specific therapy or only antiplatelet therapy over the ensuing week.
At several points during the course of this investigation we participated in multicenter trials involving experimental therapy for acute stroke. At such times all patients eligible for such treatment were randomized to receive either active study drug or placebo; none are included here in the primary study group.
We attempted to determine stroke etiology at the completion of the patient’s diagnostic evaluation and according to University of California at San Diego Stroke Data Bank criteria published elsewhere.3 All patients underwent at least one brain imaging study. We again examined the patients under study 1 week after stroke onset, and we again rated their neurological deficits according to our functional disability scale. Significant improvement was defined as an improvement from “moderate” or “severe” at the time of the initial examination to “normal” or “mild” at 1 week.
We prospectively evaluated 415 consecutive patients with acute ischemic stroke. Of these, 228 (55%) presented within 12 hours of stroke onset, and 139 patients (61%) in this group had moderate or severe new functional neurological deficit at the time of the initial examination; 89 patients with acute ischemic stroke who presented within 12 hours of stroke onset exhibited no or only mild functional neurological deficit at the time of initial examination. Sixty-eight (68/139, 49%) patients received either no stroke-specific therapy (39) or antiplatelet therapy only (29) over the ensuing week. These 68 patients comprised the primary study group.
Sixteen (24%) of the 68 patients improved to the point of having no or mild functional neurological deficit on repeated examination 1 week after stroke onset. Relative incidences of stroke etiologies and spontaneous early improvement are listed in Table 2⇓. Compared with all other etiologies combined, patients with lacunar stroke appeared more likely to enjoy spontaneous early improvement (8/22=36% versus 8/46=17%), but this difference did not reach significance (P=.15).
Another 71 patients presented within 12 hours of stroke onset, exhibited moderate or severe new functional deficit acutely, and received specific treatment other than antiplatelet therapy. Of these, 34 (48%) were treated acutely and exclusively with intravenous heparin, oral warfarin, or both. Thirty-two patients (45%) were randomized within acute interventional treatment trials involving either nimodipine (12), hypervolemic hemodilution (12), or tissue plasminogen activator (8) versus placebo; 9 of these patients also received anticoagulant therapy within the first week after stroke. Two additional patients were treated with dexamethasone, and 1 of them also received mannitol. One patient was treated with intravenous antibiotics for infectious endocarditis, and 2 patients improved to the point where carotid endarterectomy was performed within the week after stroke.
The relative incidences of stroke etiologies and significant early improvement for the patients who received specific treatment other than antiplatelet therapy within the first week are listed in Table 3⇓. Overall, the incidence of early improvement was the same (24%) in this group as in the group that received no specific treatment or antiplatelet therapy only.
While there have been a number of studies dealing with spontaneous neurological worsening in the setting of acute ischemic stroke,1 4 5 6 7 relatively little has been reported regarding early spontaneous improvement. Levy8 investigated 1343 patients hospitalized for transient ischemic attack, reversible ischemic neurological deficit, or ischemic stroke. In the group with transient ischemic attack or reversible ischemic neurological deficit, neurological recovery occurred within 30 minutes of symptom onset in half and within 60 minutes of onset in two thirds; in only 2.5% did recovery occur after 24 hours and within 1 week, suggesting that early and complete recovery after stroke is rare in patients whose stroke-induced deficits outlast the time period traditionally defined for transient ischemic attack.
In the study by Biller et al,9 29 patients with symptoms and signs of acute ischemic stroke were prospectively evaluated and followed up with serial neurological examinations. Over half (52%) were judged to be improved within 6 hours of stroke onset, with improvement defined as a gain of two or more points on a modified National Institutes of Health stroke scale. This “spontaneous improvement” group included some individuals who would appear to have been either minimally impaired at the time of baseline examination or insignificantly improved in terms of true functional recovery. Although the authors reported having observed no obvious relationship between stroke etiology and incidence of spontaneous improvement in their patients, specific data regarding this point and the diagnostic criteria used for identification of stroke etiologies were not provided.
In their randomized, double-blind, placebo-controlled study involving intravenous administration of tissue plasminogen activator versus placebo to patients presenting within 6 hours of ischemic stroke onset, Mori et al10 reported that “significant improvement was not observed until day 30 in the placebo group.” Even in the placebo group, treatment with antiplatelet or anticoagulant agents was allowed less than 24 hours after stroke onset, and no attempt to subtype patients specifically according to etiology was reported.
Wishing to exclude minimally impaired patients and believing that a functional scale might provide outcome data more clinically relevant than that obtained from point system scales, we restricted our study to patients with moderate or severe functional neurological deficit. In an effort to reduce interobserver variability, we used predetermined and largely objective criteria for identification of stroke etiology. On the negative side, selective treatment with anticoagulants and frequent use of antiplatelet therapy within the week after stroke may have influenced our findings.
Minematsu et al11 recently reported that a small percentage of their patients who presented with major hemispheral stroke syndromes dramatically improved within 24 hours of stroke onset; such dramatic recovery typically occurred in patients with probable cardioembolic stroke, and angiographic correlation suggested early distal migration of the embolus as the mechanism for recovery. In our series, 6 untreated patients suffered cardioembolic stroke, and only 1 (17%) exhibited significant early spontaneous improvement; serial angiography was not performed in any of these cases. Of the stroke etiologies recorded in our patients, lacunar stroke was the one most likely to be associated with early spontaneous recovery; even so, over half (64%) of our lacunar stroke patients were still significantly impaired 1 week after stroke onset.
Our data suggest that the attempt to clinically “subtype” stroke by etiology will be insufficient to reliably identify patients destined for early spontaneous improvement. Further investigation in this area may allow us to select from the acute stroke population at large those patients who are most in need of therapeutic intervention and most likely to respond to such intervention. Until then, inclusion of patients destined for early spontaneous improvement in treatment trials conducted to evaluate these new therapies may be expected to confound analyses of efficacy.
- Received March 31, 1995.
- Revision received May 15, 1995.
- Accepted May 15, 1995.
- Copyright © 1995 by American Heart Association
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