Management of Acute Stroke Patients With Rapidly Resolving Deficits and Persistent Vascular Occlusion
A Real Clinical Equipoise
An estimated 8% to 10% of stroke patients arriving at the emergency department within the time window for thrombolysis and with minor or rapidly resolving deficits (RRDs) are found to have proximal arterial occlusions (PAOs).1,2 The management of these patients, particularly when they are neurologically asymptomatic or have only minimal deficits of perceived negligible functional consequence, is challenging because their outcome is unpredictable. Supporters of thrombolysis argue that modern acute ischemic stroke therapy is based on the premise that recanalization and subsequent reperfusion are essential for the preservation of brain tissue and favorable outcomes and that timely thrombolysis is a better option than waiting for clinical deterioration to occur beyond the therapeutic window. Opponents argue that it is impossible to make asymptomatic patients better and cite “Primum non nocere.”
Drs Köhrmann and Schellinger provide convincing numbers showing that the risk of neurologic deterioration in patients with minor deficits or RRDs far exceeds that of hemorrhagic complications from thrombolysis and urge us not to hesitate in using it, even if the patient is completely asymptomatic. Dr Liebeskind advocates a conservative wait-and-monitor approach while implementing medical strategies to improve the cerebral hemodynamics and collateral flow.
Is it as straightforward as depicted by these skillful debaters? We initially held opposing viewpoints in support of our proponents but rapidly realized that there is an unquestionable clinical equipoise regarding the role of thrombolysis in these patients. Let us closely look at the data.
First, various studies have reported poor outcome rates (25% to 64%) in patients with minor deficits or RRDs at presentation, and patients with PAOs were the most likely to deteriorate.1,2 However, most of those studies were retrospective and included few patients with PAOs. They did not firmly establish the link between minor deficits or RRDs and poor outcome, nor did they ascertain that the reported poor outcome was not the direct result of the presenting deficits. Most of those studies also lumped all “minor strokes” into 1 category based on the National Institutes of Health Stroke Scale score on presentation, which varied from 0 to 10. Studies that categorized “minor stroke” on the basis of clinical and imaging information indicate that patients with a National Institutes of Health Stroke Scale score ≤3 and those with no neurologic deficits on initial assessment have a low risk for stroke recurrence and good outcomes3,4; yet again, only few patients with PAOs were included in these studies. Second, the benefit of thrombolysis in the treatment of minor deficits or RRDs is unclear, because previous randomized, controlled trials of thrombolysis in stroke did not use vascular imaging and excluded patients with minor deficits or RRDs. Third, the recanalization rate after intravenous thrombolysis is relatively low; therefore, thrombolysis may or may not successfully prevent clinical worsening or stroke recurrence. Fourth, the reported risk of symptomatic intracranial hemorrhage after thrombolysis in patients with minor deficits or RRDs is low. However, these estimates are based on very small numbers of patients, and the risk of symptomatic intracranial hemorrhage in those with PAOs is unknown, especially when delayed recanalization occurs. Also, the added risk of endovascular interventions, if required, is unclear, but is likely not negligible.
Overall, the data suggest that the risk of neurologic deterioration and subsequent poor outcome in patients with minor deficits or RRDs who have PAOs is not negligible; RRDs may herald a potentially devastating clinical deterioration. Apart from intuitive reasoning, there are no prospective or randomized data to indicate whether these patients might benefit from thrombolysis or not. We also note the paucity of prospective data on the natural history of minor stroke symptoms or RRDs based on the nature of the presenting symptoms, the presence versus absence of vascular occlusions, the location of the vascular occlusion (proximal versus distal middle cerebral artery, internal carotid artery, or basilar artery), perfusion imaging parameters, and the usefulness of short-term anticoagulation to prevent clot propagation or blood pressure and fluid-permissive therapies to improve cerebral hemodynamics and collateral flow.
Such studies are desperately needed to guide us on how best to treat these patients on an individual basis. We hope that the ongoing Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial and the planned Potential of rt-PA for Ischemic Strokes with Mild Symptoms Trial will help to answer the preceding questions.
At present, we agree that it is not unreasonable to consider thrombolysis in patients with mild deficits of significant functional importance, such as aphasia or motor weakness, in the hope that it could restore function, but we remain divided over its use in completely asymptomatic patients. So, the controversy continues …
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. This article is Part 3 in a 3-part series. Parts 1 and 2 appear on pages 3003 and 3005, respectively.
- Received July 20, 2010.
- Accepted July 20, 2010.
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