Pro: Intravenous Tissue Plasminogen Activator in Stroke Patients With Rapid, Complete Recovery During Evaluation (Transient Ischemic Attack) and Evidence of Middle Cerebral Artery Occlusion
Carlos A. Molina MD, PhD Magdy H. Selim MD, PhD Section Editors: The Case:
A patient presents within 3 hours of acute onset of left-sided weakness. Symptoms rapidly resolve spontaneously. Vascular imaging reveals evidence of right middle cerebral artery (MCA) occlusion.
(1) Should treatment decision be based on clinical or vascular status?
(2) Would treatment with t-PA prevent clinical worsening or early stroke recurrence in this patient?
(3) Is increased collateral flow good enough to maintain perfusion?
Role of Thrombolysis in Patients with Rapid Recovery during Evaluation and Evidence of Arterial Occlusion on Vascular Imaging.
There are some points on which to agree at the beginning of this controversy. The middle cerebral artery (MCA) supplies a large and important proportion of the brain, which is not meant to be perfused through small collaterals. Acute occlusion of the MCA in most cases leads to devastating strokes. Thus, a patent MCA is probably better than an occluded one. Would we really consider a spontaneously recovering stroke patient with a proven, persistent occlusion of the MCA to have a “transient ischemic attack” (TIA) not necessitating thrombolysis? The key to guide the decision is to weigh the potential risk without treatment against the risk of treatment in such a patient.
First of all, the term TIA is in danger of extinction … and rightfully so. Not only do TIA and stroke share the same risk factors and pathophysiologic mechanisms, but also modern imaging techniques reveal a high prevalence of underlying cerebral infarctions in (clinical) TIA. Rates of recurrence or symptom worsening as well as early secondary stroke recurrence are comparable or even higher after TIA. As a consequence, modern guidelines call for the same rigorous and early diagnostic work-up and acute care for TIA as for stroke patients. In addition, clinicians face an unsolvable problem in the acute phase in a patient with an MCA occlusion and recovery at hospital admission: For the next 24 hours, they will not know whether they are actually dealing with a “real TIA” or the first warning symptoms of a potentially devastating stroke.
Deterioration after spontaneous improvement in the acute phase is a frequent problem. In fact, early improvement is the strongest predictor of subsequent deterioration. The rate of stroke after an initial TIA is 15% within 7 days and up to 30% within the first year. However, which patients will deteriorate, and what is the risk for a patient with an MCA occlusion? Several investigators have studied predictors of neurologic worsening in “TIA” patients.1,2 During the past several years, transcranial Doppler and advanced imaging have entered the equation. Alexandrov et al2 demonstrated an overall rate of secondary deterioration of 16% in patients with spontaneously resolving symptoms; among those with intra- or extracranial vessel occlusion on transcranial Doppler, the rate increased to 62%. Similar findings were reported in magnetic resonance imaging studies. Patients with vessel occlusion had an 18-fold higher risk for early deterioration (absolute risk of 38%) and a 7-fold higher risk for permanent disability (absolute risk of 50%).3 The Vision Study used magnetic resonance imaging to complement the clinical ABCD2 score to predict stroke and functional impairment after TIA and mild stroke. Again, patients with vessel occlusion had a 46% risk for progression of stroke (compared with 6% without vessel occlusion; P<0.001) and 38% for functional impairment after 90 days (compared with 7%; P<0.001).4 Another study identified patients with TIA or minor stroke and an intracranial vessel occlusion on computed tomography angiography to have a 3-fold higher risk for a poor outcome. Importantly, it is often the progression of ischemia rather than an early recurrence of stroke that leads to poor outcome,3,4 suggesting that recanalization therapies will be more effective than antithrombotic treatments for early secondary prevention.
What is the flip side of the coin? To begin with, the risk of thrombolysis-related symptomatic hemorrhage (sICH) even in unselected patients is low compared with the risk for early deterioration described earlier (overall 1.7% in SITS-MOST). In addition, the severity of stroke at baseline has been shown to be an important risk factor for sICH in many studies. Only 0.7% of patients with a National Institutes of Health Stroke Scale score of 0 to 7 experienced sICH in SITS-MOST. In the National Institute of Neurological Disorders and Stroke trial, only 1 hemorrhage was observed in the group with a National Institutes of Health Stroke Scale score of 0 to 5 (2% vs 6.4% in the whole trial, according to the National Institute of Neurological Disorders and Stroke definition for sICH), and a higher National Institutes of Health Stroke Scale score at baseline was a significant risk factor for sICH. Furthermore, and directly linked to stroke severity, lesion size on diffusion-weighted imaging was shown to predict sICH. Asymptomatic patients, however, are unlikely to display large lesions on diffusion-weighted imaging, again emphasizing the safety of such treatment in this patient group.
Of course, tissue plasminogen activator will not completely eliminate the risk of secondary deterioration. However, 1 additional and often-ignored convenience of asymptomatic patients is that the situation can and should be discussed with the patients themselves. A patient, after elaborate information, takes part in the decision-making process. Will the patient choose the ≥40% risk for deterioration and functional impairment over a <1% risk of significant bleeding? Likely not! Ignoring the high risk for deterioration based on the fear of the small risk of treatment complications reminds us of the situation in anticoagulation for atrial fibrillation in the elderly. In this case, a high-risk population is frequently not treated because of an irrational fear of less-likely complications. Let us not make the same mistakes over and over again.
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. This article is Part 1 in a 3-part series. Parts 2 and 3 appear on pages 3005 and 3007, respectively.
- Received July 25, 2010.
- Accepted July 26, 2010.
Alexandrov AV, Felberg RA, Demchuk AM, Christou I, Burgin WS, Malkoff M, Wojner AW, Grotta JC. Deterioration following spontaneous improvement: sonographic findings in patients with acutely resolving symptoms of cerebral ischemia. Stroke. 2000; 31: 915–919.
Rajajee V, Kidwell C, Starkman S, Ovbiagele B, Alger JR, Villablanca P, Vinuela F, Duckwiler G, Jahan R, Fredieu A, Suzuki S, Saver JL. Early MRI and outcomes of untreated patients with mild or improving ischemic stroke. Neurology. 2006; 67: 980–984.
Coutts SB, Hill MD, Campos CR, Choi YB, Subramaniam S, Kosior JC, Demchuk AM. Recurrent events in transient ischemic attack and minor stroke: what events are happening and to which patients? Stroke. 2008; 39: 2461–2466.