Matthew Edwardson, MD

Kim BJ, Kim H, Lee DH, KwonSU, Kim SJ, Kim JS, et al. Diffusion-Weighted Image and Fluid-Attenuated Inversion Recovery Image Mismatch: Unclear-Onset Versus Clear-Onset Stroke. Stroke. 2013

Around 1/4th of stroke patients first notice symptoms upon awakening and are therefore ineligible for thrombolytic therapy. However, many of these patients probably had their strokes close to the time of awakening and would be good candidates for thrombolytics. FLAIR positivity on MRI may provide this “tissue clock”, as FLAIR changes appear gradually over the first several hours after stroke as a result of ischemia related neuronal edema. Indeed, two ongoing trials – MR-WITNESS in the U.S. and WAKE-UP in Europe – hope to address the safety and efficacy of thrombolysis in patients with wake-up stroke using FLAIR as a surrogate for symptom onset time. One aspect of wake-up stroke that has never been addressed is how the time from symptom discovery correlates with the progression of these FLAIR changes.

Kim and colleagues retrospectively compared DWI-FLAIR mismatch in 114 patients with wake-up stroke and 145 patients with stroke of known symptom onset time, all presenting within 6 hrs of symptom discovery. The authors found that when MRI was performed within 2 hrs of symptom discovery the two groups had the same proportion of patients with DWI-FLAIR mismatch (50% vs. 51.5%, p = 0.92), but this proportion plummeted in the wake-up stroke group at 2-3 hrs (16.1% vs. 44%, p = 0.02), 3-4 hrs (13.8% vs. 36.4%, p = 0.04), and 4–5 h (5.6% vs. 29.6%, p = 0.05) (wake-up vs. non-wake-up respectively).

The results of this study imply that a large percentage of patients with wake-up stroke presenting rapidly after symptom discovery have infarcts that are still early in their time course – early enough to benefit from thrombolytic therapy. The authors suggest using 2 hrs from symptom discovery time as a potential selection criterion for multimodal MRI-based thrombolysis in wake-up stroke. However, if FLAIR positivity is truly an accurate gauge of infarct age this time cutoff seems unnecessary and would cause you to withhold treatment from the small percentage of patients with stroke onset just prior to awakening. I find the implications of this study much more interesting for CT-based thrombolysis in wake-up stroke. A minority of stroke neurologists currently treat wake-up strokes with off-label TPA in the setting of a pristine head CT. In settings where MRI is not readily available, using this 2 hr cutoff from symptom discovery time may dramatically increase the proportion of patients truly in the time window for thrombolytics. Perhaps 2 hrs from symptom discovery will become an important inclusion criterion for a future trial of CT-based thrombolysis for wake-up stroke.