Burton J. Tabaac, MD
@burtontabaac

Ma H, Campbell BCV, Parsons MW, Churilov L, Levi CR, Hsu C, et al. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke. N Engl J Med. 2019; 380:1795-1803.

The following discussion is documented via “LIVE Blogging,” a Journal Club held at Johns Hopkins Hospital in Baltimore, Maryland, on May 14, 2019. The journal article presented is “Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke,” published in The New England Journal of Medicine on May 9, 2019. The Journal Club presentation and discussion was led by Dr. Rebecca Gottesman, a neurology professor, cerebrovascular specialist, and International Stroke Conference 2019 award recipient.

Current American Heart Association/American Stroke Association guidelines for ischemic stroke limit the time to initiate intravenous thrombolytic therapy to within 4.5 hours after the onset of stroke. Representatives from the EXTEND trial and collaborators from the University of Melbourne, Royal Melbourne Hospital, in Australia published an article that challenges this limit. By carefully selecting the appropriate patient population using advanced imaging, patients who have salvageable brain tissue beyond 4.5 hours may benefit from treatment via IV thrombolysis! The authors tested the hypothesis that “intravenous thrombolysis with alteplase initiated between 4.5 and 9.0 hours after stroke onset or on awakening with stroke symptoms (for which the time of onset was not known) would provide a benefit in patients who had a small core volume of cerebral infarction that was disproportionate to a larger area of hypoperfusion.”

This paradigm change to carefully select the appropriate patients who may benefit from therapy outside current guidelines parallels a similar historical trajectory to that of endovascular intervention in treating large vessel occlusion. For an epoch, the standard of care in approaching embolectomies relied on the patient presenting to clinical attention within 6 hours of onset and a favorable ASPECTS score on “dry” CT brain imaging. This limit was breached via conclusions drawn from the DAWN and DEFUSE 3 trials. By carefully selecting the appropriate patient population in concordance with advanced imaging (e.g., CTP, hyperacute MRI), offerable treatment was readily introduced to a much larger eligible patient population.

Philip Chang, MD

Berberich A, Schneider C, Reiff T, Gumbinger C, Ringleb PA. Dual Antiplatelet Therapy Improves Functional Outcome in Patients With Progressive Lacunar Strokes. Stroke. 2019;50:1007–1009.

As neurologists, we have all encountered patients with mild lacunar stroke, confirmed on MRI to be a small subcortical lesion, especially if caught early on. However, some patients, despite a small stroke seen on early MRI having waxing and waning symptoms, for example going from complete plegia to a mild hemiparesis within the same hour. Why would this be the case? CHANCE and POINT enrolled patients of minor non-cardioembolic strokes, and proved that dual antiplatelet therapy was superior in reducing recurrent strokes in minor strokes with NIHSS<3. If one thinks about the enrollment criteria, this would likely leave small vessel disease, large vessel disease, and other/cryptogenic by TOAST criteria.

In my blog entries’ ongoing discussion on dual antiplatelet data, there has been a long story about likely success of dual antiplatelet therapy in stabilizing large artery atherosclerosis, both by transcranial doppler studies as well as a newly published study in Stroke, “Dual Versus Mono Antiplatelet Therapy in Large Atherosclerotic Stroke: A Retrospective Analysis of the Nationwide Multicenter Stroke Registry.” In my opinion, this likely drives a large portion of the effect size in CHANCE/POINT. However, early neurologic deterioration was not differentiated from early recurrent stroke in these trials, and a portion of the effect size may have been from dual antiplatelet treatment of lacunar strokes with early neurological deterioration, which likely includes entities such as “stuttering lacunar syndrome” or “capsular warning syndrome.”

Elena Zapata-Arriaza, MD
@ElenaZaps

Venema E, Lingsma HF, Chalos V, Mulder MJHL, Lahr MMH, van der Lugt A, et al. Personalized Prehospital Triage in Acute Ischemic Stroke: A Decision-Analytic Model. Stroke. 2019;50:313–320.

Delay in the administration of required treatment in ischemic stroke can worsen the patient’s functional prognosis. Which patient needs direct transfer to a primary stroke center or to an intervention center is still a challenge in decision making.

To determine optimal prehospital transportation strategy, the authors performed a decision – analytic model. As described in Figure 1, this model starts with the initial decision of transportation to the primary stroke center or to the nearest endovascular-capable intervention center. The benefit of direct transportation to the intervention center was defined as the average amount of quality-adjusted life years (QALYs) gained by this strategy (difference of >0.02 QALYs (=1 week in full health) was considered clinically relevant). The short-run model calculates the probability of every possible pathway and the associated distribution of the modified Rankin Scale (mRS) score after 3 months. It takes into account driving times, in-hospital workflow characteristics, and time-dependent treatment effects. In each annual cycle of the following Markov model, patients can remain in the same health state or die. These probabilities are based on the age and sex-dependent annual mortality rates, adjusted for previously reported death hazard rate ratios of stroke patients.

Figure 1. Schematic overview of the model structure. The decision node is represented with a square. The circles represent chance nodes, the circles marked with an M represent Markov models and the triangles represent terminal nodes. EVT indicates endovascular treatment; IVT, treatment with intravenous thrombolytics; and LVO, large vessel occlusion.