A different kind of extended window for stroke treatment

To fanfare at International Stroke Conference 2018, the results of the DEFUSE 31 extended window thrombectomy study were announced. The American Heart Association/American Stroke Association acute ischemic stroke guidelines were immediately updated to reflect the practice-changing findings. 

A few months later, Lee Schwamm and colleagues published their findings from MR WITNESS.2 In this study, patients with unwitnessed stroke onset between 4.5 and 24 hours underwent advanced magnetic resonance imaging to identify those individuals with radiographic evidence of hyperacute stroke. Based on prior work, it was known that evolution of imaging characteristic with respect to the fluid-attenuated inversion recovery (FLAIR) sequence correlates with time from onset. Patients who met imaging criteria based on the mismatch between FLAIR signal change and diffusion restriction were given tPA.

The researchers enrolled 80 individuals at multiple centers. Patients were treated at a median of 11 hours from their last known well. The rates of adverse events were very low and within the range of adverse event rates observed in prior stroke treatment trials. 

The standard stroke treatment paradigm allows patients to be treated within 4.5 hours of symptom onset. In general, patients treated beyond this window are at greater risk of brain hemorrhage and poor outcomes. The results of this Phase 2a study challenge the 4.5 hour time window. Like DEFUSE 3, this study uses advanced imaging to personalize acute stroke treatment. A frequent reason for patients to not receive tPA for stroke treatment has been that patients often present to hospitals too late. Expanding the time window for non-large vessel occlusion strokes, which are the vast majority of strokes but nonetheless disabling, has great public health implications. With the rest of the stroke community, I look forward to results of an efficacy trial.

References

  1. Albers GW, Marks MP, Kemp SK, Christensen S, Tsai JP, Santiago O, et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. NEJM 2018; 378:708-718.
  2. Schwamm LH, Wu O, Song SS, Ford AL, Hsia AW, Muzikansky A, Betensky RA, et al. Intravenous thrombolysis in unwitnessed stroke onset: MR WITNESS trial results. Ann Neurol 2018 Apr 24 [Epub ahead of print].

Neal Parikh Headshot

Neal S. Parikh, MD, earned his MD from Weill Cornell Medical College and completed residency training in neurology at the same institution. He is now an NIH T32 neuro-epidemiology and vascular neurology fellow at New York-Presbyterian Hospital/Columbia University Medical Center. He tweets @NealSParikhMD and contributes to Blogging Stroke as a blogger.

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