Mark N Rubin, MD

Coutts SB, Dubuc V, Mandzia J, Kenney C, Demchuk AM, Smith EE, et al. Tenecteplase–Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion. Stroke. 2015

As we recently discussed, there is a fair amount of heterogeneity in the evaluation and treatment of “minor strokes,” which actually represents the most common reason to not provide IV tPA. This is based on the assumption that the natural history of minor stroke is benign and the deficits amenable to rehabilitation. Even those of us firmly committed to syndromic neurology, however, have to admit that minor strokes can fool us with early and/or severe recrudescence. This is particularly the case in the presence of a cervical or intracranial arterial occlusion, which is probably an under-recognized phenomenon due to the fact that many stroke providers do not perform angiography of any kind in the setting of acute but minor stroke.

This study was a multicenter Phase I dose-escalation trial of tenecteplase for minor stroke (NIHSS < or = 5) within 12 hours of symptom onset. Fifty patients were enrolled, the first 25 getting 0.1mg/kg and the subsequent 25 received 0.25mg/kg (half the approved dose for coronary occlusion, as a frame of reference). The primary endpoint was safety, namely symptomatic ICH (defined idiosyncratically alongside SITS-MOST, ECASS, NINDS, etc.), extracranial hemorrhage or allergic reaction. Secondary endpoints included vessel recanalization (repeat CTA 8-12h after bolus) and 90 day mRS. Patients were followed in-person in a standardized format. The details are in the manuscript, but the basic idea is that 66% of the patients achieved an excellent outcome (mRS 0-1) and 90% good outcome (mRS 0-2) in this cohort, and the only adverse event was a single temporal hematoma in the distribution of a symptomatic occlusion and this was in the larger dose group.

The nebulous clinical phenomenon of “minor stroke” is difficult for patients and providers, and this is highlighted by the upwards of 34% of patients deemed to have a minor stroke that end up disabled or dead within 90 days of their supposedly minor stroke. Since the majority of these patients seem to have a relatively benign course, the level of risk tolerance in this setting is appropriately low, which is probably why tPA is so infrequently given in this population, possibly to their detriment and also to those with a wolf in sheep’s clothing: an intracranial occlusion with minor symptomatology. That being the case, these data are exciting but, as the authors suggest, a carefully designed Phase II trial is warranted to see if we might be able to provide safe and effective therapy for this not-so-uncommon cohort of minor stroke with intracranial occlusion.