Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke
Yuanjun Shan,
Jie Pu,
Yang Ni
et al.
Abstract:ImportanceIt is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy.ObjectiveTo assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO.Design, Setting, and ParticipantsThis investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospita… Show more
With recent advances in endovascular devices and techniques for the treatment of large-vessel occlusion (LVO) stroke, rates of successful recanalization are as high as 90%. 1 While technologies may continue to improve, it would be unreasonable to anticipate significant gains in this measure of macroperfusion. Instead, efforts are increasingly turned toward neuroprotection and augmenting the microcirculation to promote tissue viability during acute cerebral ischemia. Adjunctive intra-arterial thrombolysis 2 and the recombinant variant of human activated protein C (3K3A-APC) 3 have shown promising preliminary results, but warrant additional validation. Inflammatory mechanisms following acute cerebral infarction are also the subject of much clinical research. Following acute ischemic stroke, there is robust activation of peripherally circulating and central immune cells that contribute to cytotoxic and vasogenic edema, leading to progressive tissue injury, hemorrhagic transformation, and ultimately poorer clinical outcomes. 4 The evidence that heightened acute inflammation mediates poor outcomes following infarction is also supported by evidence suggesting potential benefit of anti-inflammatory treatments including the toll-like receptor 4 antagonist ApTOLL, 5 and the combination antioxidant/anti-inflammatory compound edaravone dexborneol 6 in acute cerebral infarction; however, more research is needed.In this issue of JAMA, the MARVEL Investigators explore the potential benefits of acute anti-inflammatory treatment in patients with acute stroke treated with endovascular thrombectomy by randomizing patients with acute LVO of the internal carotid or proximal middle cerebral artery to intravenous methylprednisolone or placebo. 7 Patients were eligible for inclusion if they had severe stroke-related deficits as defined by a National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater and early evidence of ischemic injury on the baseline computed tomography (CT) scan, as measured by the Alberta Stroke Program Early CT Score (ASPECTS) of 3 or greater (where 3 indicates as much as 70% of the middle cerebral artery territory showing ischemic changes). The primary efficacy outcome was the distribution in functional disability at 90 days using the modified Rankin Scale (mRS), with scores ranging from 0 to 6, where 0 represents no symptoms, 2 represents the inability to carry out all activities of daily living but remaining independent, and 6 indicates death.Among the 1687 included patients treated across the 82 sites in China, the stroke severity according to the NIHSS score was expectedly high (median, 19 [IQR,(16)(17)(18)(19)(20)(21)), with a median ASPECTS of 6 (IQR, 4-7). Regarding the primary outcome of a shift in the distribution of the mRS score 90 days after stroke,
With recent advances in endovascular devices and techniques for the treatment of large-vessel occlusion (LVO) stroke, rates of successful recanalization are as high as 90%. 1 While technologies may continue to improve, it would be unreasonable to anticipate significant gains in this measure of macroperfusion. Instead, efforts are increasingly turned toward neuroprotection and augmenting the microcirculation to promote tissue viability during acute cerebral ischemia. Adjunctive intra-arterial thrombolysis 2 and the recombinant variant of human activated protein C (3K3A-APC) 3 have shown promising preliminary results, but warrant additional validation. Inflammatory mechanisms following acute cerebral infarction are also the subject of much clinical research. Following acute ischemic stroke, there is robust activation of peripherally circulating and central immune cells that contribute to cytotoxic and vasogenic edema, leading to progressive tissue injury, hemorrhagic transformation, and ultimately poorer clinical outcomes. 4 The evidence that heightened acute inflammation mediates poor outcomes following infarction is also supported by evidence suggesting potential benefit of anti-inflammatory treatments including the toll-like receptor 4 antagonist ApTOLL, 5 and the combination antioxidant/anti-inflammatory compound edaravone dexborneol 6 in acute cerebral infarction; however, more research is needed.In this issue of JAMA, the MARVEL Investigators explore the potential benefits of acute anti-inflammatory treatment in patients with acute stroke treated with endovascular thrombectomy by randomizing patients with acute LVO of the internal carotid or proximal middle cerebral artery to intravenous methylprednisolone or placebo. 7 Patients were eligible for inclusion if they had severe stroke-related deficits as defined by a National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater and early evidence of ischemic injury on the baseline computed tomography (CT) scan, as measured by the Alberta Stroke Program Early CT Score (ASPECTS) of 3 or greater (where 3 indicates as much as 70% of the middle cerebral artery territory showing ischemic changes). The primary efficacy outcome was the distribution in functional disability at 90 days using the modified Rankin Scale (mRS), with scores ranging from 0 to 6, where 0 represents no symptoms, 2 represents the inability to carry out all activities of daily living but remaining independent, and 6 indicates death.Among the 1687 included patients treated across the 82 sites in China, the stroke severity according to the NIHSS score was expectedly high (median, 19 [IQR,(16)(17)(18)(19)(20)(21)), with a median ASPECTS of 6 (IQR, 4-7). Regarding the primary outcome of a shift in the distribution of the mRS score 90 days after stroke,
This study aims to compare the incidences of ND and poor outcome (a modified Ranking scale > 2 points at discharge) among patients with different atherosclerotic stroke patterns. A total of 688 participants were categorized into 4 groups according to atherosclerotic stroke pattern: multiple small infarcts (MSI), single subcortical infarction (SSI), borderzone infarct (BZI) and large infarct groups. Among the 4 groups, MSI group had the lowest incidences of ND and poor outcome (13.5% and 16.2%, respectively). In multivariable analyses, for BZI patients, the risks of ND [odds ratio (OR) = 4.33, 95% confidence interval (CI) = 2.37–7.94, p< 0.001] and poor outcome (OR = 4.16, 95% CI = 2.04–8.50, p < 0.001) both increased approximately 3-fold than MSI, both of which were the highest among the 4 stroke patterns. The neutrophil to lymphocyte ratio in BZI and large infarct groups were higher than in MSI and SSI groups [3.35 (2.28, 5.04) and 3.36 (2.53, 4.94) vs. 2.64 (1.89, 4.06) and 2.71 (1.93, 3.91), p< 0.001]. BZI group had the highest risks of ND and poor outcome among atherosclerotic stroke patients. BZI and large infarct patients had stronger poststroke inflammation than MSI and SSI patients.
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