Minor Stroke and Transient Ischemic Attack: Research and Practice

Have you identified why some stroke patients are too good to treat? What are you doing to get rid of this asinine idea?

VIDEO: "Too good to treat" stroke patients may benefit from tPA  Feb. 2015

Outcomes mostly favorable for ‘too good to treat’ stroke patients  Dec, 2011

 

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Minor Stroke and Transient Ischemic Attack: Research and Practice

Aleksandra Yakhkind¹, Ryan A. McTaggart², Mahesh V. Jayaraman^1,2,3, Matthew S. Siket⁴, Brian Silver¹* and Shadi Yaghi¹

• ¹Department of Neurology, The Warren Alpert Medical School of Brown University, Providence, RI, USA
• ²Department of Diagnostic Imaging, The Warren Alpert Medical School of Brown University, Providence, RI, USA
• ³Department of Neurosurgery, The Warren Alpert Medical School of Brown University, Providence, RI, USA
• ⁴Department of Emergency Medicine, The Warren Alpert Medical School of Brown University, Providence, RI, USA

A majority of patients with ischemic stroke present with mild deficits for which aggressive management is not often pursued. Comprehensive work-up and appropriate intervention for minor strokes and transient ischemic attacks (TIAs) point toward better patient outcomes, lower costs, and fewer cases of disability. Imaging is a key modality to guide treatment and predict stroke recurrence. Patients with large vessel occlusions have been found to suffer worse outcomes and could benefit from intervention. Whether intravenous thrombolytic therapy decreases disability in minor stroke patients and whether acute endovascular intervention improves functional outcomes in patients with minor stroke and known large vessel occlusion remain controversial. Studies are ongoing to determine ideal antiplatelet therapy for stroke and TIA, while ongoing statin therapy, surgical management for patients with carotid stenosis, and anticoagulation for patients with atrial fibrillation have all been proven to decrease the rate of stroke recurrence and improve outcomes. This review summarizes the current evidence and discusses the standard of care for patients with minor stroke and TIA.

Background

In population-based studies, approximately two-thirds of ischemic stroke patients have mild deficits (1, 2). Minor stroke is generally defined as an National Institute of Health Stroke Scale (NIHSS) of 5 or less, which takes into account certain deficits but not the fact that some can have a more profound impact on quality of life than others. Hence, the scale does not linearly correlate deficit and disability. While studies suggest using an NIHSS of 3 or less to define minor stroke (3, 4), real-world definitions of non-disabling deficits are largely dependent on clinical judgment, which has been shown to vary widely among physicians (5). Transient ischemic attack (TIA) has a more widely accepted definition that includes focal neurological symptoms lasting for <24 h without the presence of infarction on diffusion-weighted imaging (6).

In clinical practice, both minor stroke and TIA patients undergo similar diagnostic evaluations. Due to the relatively high early risk of stroke recurrence in both groups and disability in minor stroke patients, key decisions in the management of minor strokes and TIA can have significant impacts on clinical outcomes, quality of life, and cost of care. In this review, we summarize the current research on minor stroke and TIA, and highlight key points in acute treatment and secondary stroke prevention strategies.

Acute Treatment

Thrombolytic Therapy

Thrombolytic therapy with intravenous recombinant tissue plasminogen activator (IV rtPA) is an important treatment for patients with acute ischemic stroke (7). Patients with minor deficits are often excluded from such treatment even though they demonstrate a high rate of suboptimal functional outcome. While retrospective studies show no benefit in 3-month outcome between thrombolysed and non-thrombolysed patients with mild deficits (8, 9), these studies are subject to selection bias in favor of treating patients with disabling versus non-disabling deficits. Recent evidence from a stroke registry supports the use of IV rtPA compared with routine medical management in patients with mild deficits (10). In addition, a post hoc analysis of the International Stroke Trial-3 (IST-3) found that patients with mild deficits who were treated IV rtPA compared to placebo had a favorable shift in the Oxford Handicap Scale distribution (adjusted odds ratio, 2.38; 95% confidence interval, 1.17–4.85). The most feared complication of IV rtPA is symptomatic intracerebral hemorrhage (sICH), which is seen in up to 2% of patients with minor stroke (11–13). Due to the fear of hemorrhagic complications, physicians tend to offer IV rtPA to patients who they consider to have a disabling deficit, a highly subjective clinical judgment. The subjectivity of this approach highlights the need for prospective cohorts to better understand the natural history and predictors of long-term functional and cognitive outcomes in patients with minor stroke, taking into account the type of deficit, the patient, and potential for stroke recovery. Two randomized clinical trials comparing IV rtPA versus placebo in patients with minor non-disabling deficits are underway (14, 15).

Acute Endovascular Therapy

Several clinical trials recently showed that the addition of mechanical thrombectomy to best medical treatment in patients with acute ischemic stroke and evidence of a large artery occlusion resulted in significant improvement in long-term functional outcomes (16). Most of these studies excluded patients with minor stroke leading to variability in the use of mechanical thrombectomy for patients with acute large vessel occlusion and transient or minor deficits. Large vessel occlusion is an important and consistent predictor of neurological deterioration and disability in patients with minor stroke (17, 18). Excluding these patients from endovascular treatment may lead to a sevenfold increased risk of long-term disabling deficits and up to 50% of patients being functionally disabled at 3 months (17, 18). Recent AHA/ASA guidelines suggest that it is reasonable to consider endovascular treatment for patients with an NIHSS score <6 and evidence of large vessel occlusion. However, clinical trials are needed to prove the efficacy of endovascular treatment in this patient population (19).

Risk of Recurrent Stroke

The risk of recurrent stroke in patients with minor stroke and TIA is 10–13% at 90 days, with approximately half of events occurring in the first 2 days (20, 21). Multiple scores have been used to predict the early risk of stroke after a TIA or minor stroke, including the ABCD2 score (22, 23) and the ABCD3-I (24) score that include neurovascular and MR imaging (Table 1). Studies have shown imaging-supplemented scores to be superior to clinical scores alone in predicting stroke recurrence in patients with minor stroke or TIA (25, 26). In a meta-analysis of 29 studies and over 130,000 patients, the ABCD2 score lacked reliability in predicting early recurrent stroke risk and in identifying patients with symptomatic large artery atherosclerosis (27), an important prognosticator of early stroke recurrence (25, 28, 29). In fact, a recent multi-center study showed that in patients with minor stroke or TIA, the risk of early stroke recurrence or neurological deterioration was only up to 2% in the absence an infarction on neuroimaging or large artery disease stroke subtype and approximately 30% in those with large artery disease stroke subtype who have an infarction on neuroimaging. In this study, the ABCD2 score was not a predictor of stroke recurrence (30). Another study showed that the addition of perfusion imaging to parenchymal and vascular imaging in patients with minor stroke TIA improved prediction of recurrent cerebrovascular events (31).

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