Mild Acute Ischemic Stroke With Large Vessel Occlusion (MIST WAVE)

Patients who present with mild stroke symptoms (mAIS), and are also found to have an intracranial large vessel occlusion (LVO) pose an exceptionally difficult therapeutic dilemma. The need for any acute treatment is often debated since these patients "only" have mild deficits, and any therapy has associated risks. However, it has been shown that acute ischemic stroke (AIS) can lead to considerable morbidity and mortality even in patients presenting with mild symptoms (mAIS) in the presence of LVO. Despite reports that such patients have less favorable outcomes, these patients are often excluded from acute stroke therapy. Recent studies demonstrated that, despite mild and rapidly improving symptoms, many patients end up with unfavorable outcome. While the most recent AHA/ASA guidelines no longer recommend excluding patients with milder improving symptoms from intravenous tissue plasminogen activator administration, the role of endovascular intervention has not been clarified for these patients.

Prior data has shown high morbidity and mortality in mAIS patients (without specified large vessel status), who did not receive IV tPA, demonstrating that as high as 32% of patients was dependent during discharge or died in one study. A common reason for foregoing treatment in this patient group was that mild symptoms or rapid improvement were a contraindication to IV-tPA administration according to previous ASA/AHA guidelines. Higher morbidity was specifically noted in patients with concurrent large vessel occlusion as a cause of the symptom in another study. Mokin et al showed that for LVO patients excluded from thrombolysis, only 2/3rd could walk independently at discharge.

When assessing predictors of poor outcome, LVO seems to correlate with poor outcome despite mild symptoms. Nedeltchev et al published a study with 162 patients with either mild stroke symptoms (NIHSS of 3 or less) or rapidly improving symptoms (NIHSS improvement of 4 points or more), in which 25% of the patients had an unfavorable outcome. NIHSS of 10 or more and proximal vessel occlusion were independent predictors of poor outcome. LVO in patients with rapidly improving /mild symptoms conferred an 18-fold increased risk of early neurological deficit with infarct expansion. Patients with LVO were also more likely to have increased modified ranking scale (mRS), and LVO was an independent predictor of decline in functional status and a borderline significant predictor of poor outcome when adjusting for age, gender and presenting NIHSS.

NIH Stroke Scale Score Threshold The ideal NIHSS cutoff value for "mild" stroke remains unclear, and varies across studies. The investigators specifically chose the NIHSS 5 cut-off value for the cohort after careful consideration of the results of several earlier reports, which were available at the initiation of our research project. These studies, albeit with limited sensitivity and specificity, have concluded that an NIHSS cut-off of 7-10 and higher might be a reliable predictor of LVO. Since the investigators were trying to capture a controversial stroke population that was unlikely to have LVO because of mild symptoms, the investigators decided to include patients with NIHSS 5 or less.

Currently approved treatment and limitations At present, the American Heart Association and American Stroke Association guidelines recommend that eligible ischemic strokes be treated with IV tissue plasminogen activator (tPA) and/or mechanical thrombectomy. Severity of the stroke is based on the National institute of health stroke scale (NIHSS), and the guidelines do not specify any thrombolysis treatment for mild strokes.