Bahar M. Beaver, MD

Schlemm L, Endres M, Werring DJ, Nolte CH. Benefit of Intravenous Thrombolysis in Acute Ischemic Stroke Patients With High Cerebral Microbleed Burden. Stroke. 2020;51:232–239.

Cerebral microbleeds (CMB) have long presented a clinical challenge in the treatment of acute ischemic stroke. Patients with a high burden of CBMs are at a higher risk of intraparenchymal hemorrhage; however, thoroughly evaluating this burden in each treatment-eligible patient is time-intensive and can delay otherwise life-saving therapy. The authors in this article, led by Dr. Ludwig Schlemm, MD, of Berlin, dove into this dilemma and evaluated risk/benefit profiles of treatment with intravenous thrombolysis (IVT) in patients with both high (> 10) and low (<10) CMB burden presenting with acute ischemic stroke. Their attention was mainly on outcomes in these patients. 

The authors used existing data from recent meta-analyses and prospective cohort studies in their statistical analysis. In total, they used data from seven studies. The primary outcome measure was the effect of IVT in patients with high CMB burden and low CMB burden. This was measured using a weighted modified Rankin Score (mRS). In a complicated, yet thorough, 13-step algorithm, results were divided into multiple categories and compared against several pathways. This breakdown is nicely depicted in Figure 1 of the article. Briefly, the authors used estimated 90-day mRS of patients with acute ischemic stroke and presumed average CMB burden who did not receive IVT and those who did. They also included treatment delay as a factor in this model. Then, they analyzed the mRS outcomes of patients who received IVT with high CMB burden and low CMB burden. They further compared the outcomes of patients with both high and low CMB burden who did not receive IVT.

Schematic diagram of the algorithm.

Figure 1. Schematic diagram of the algorithm.

Ultimately, the authors found that favorable outcomes were more likely in patients with low CMB burden who were treated with IVT than those with high CMB burden. This discrepancy of benefit in outcomes was time-dependent, however. They found that delaying tPA between 120-210 minutes resulted in a “no benefit” result when comparing the two groups. Furthermore, the authors concluded that the overall net benefit of IVT was higher in patients with a low CMB burden and lower age, lower NIHSS score, and minimal delay in treatment. Additionally, they found that the risk of mortality is higher in patients with high CMB burden who received IVT than those with low CMB burden. Finally, the authors touched on the feasibility of obtaining an MRI to evaluate CMB burden in patients who were otherwise eligible for IVT. They found that a delay of greater than 10 minutes would negatively impact outcomes. Specifically, the authors concluded that patients with older age and higher NIHSS had even less time to delay treatment before the net benefit of IVT on outcomes diminished. 

There is a significant amount of stroke literature on the risks of hemorrhage in patients with CMB who receive thrombolysis. In this article, Dr. Schlemm and colleagues evaluate the overall benefit of IVT and how it relates to CMB burden, age, NIHSS, and time to treatment. Their conclusions highlight that there is perhaps a need for rapid determination of CMB burden in patients who present with acute ischemic stroke, but that currently, this is not a feasible option in most institutions. Some emergency rooms currently have an MRI protocol in place for their acute ischemic stroke patients, in lieu of a CT. These protocols involve not only well-trained clinical staff, but also a very limited number of MRI sequences to help expedite the process. Perhaps over time, incorporating a universal MRI protocol which includes only DWI, ADC, T2 FLAIR, and GRE/SWI would replace a non-contrast CT head. For this to happen, we would also need advancement in the technology of rapidly obtained MRIs. Until that time, review of prior images, if available, could help guide the physician in determining the overall risk/benefit of the individual patient eligible for IVT.