Abstract WP56: Improvement In Motor And Language Domains Mediates Most Of The Effect Of 24h NIHSS Improvement On Functional Independence

Abstract

Introduction: Improvement in NIH stroke scale scores on 24h follow-up is considered a key prognostic element after endovascular thrombectomy (EVT). We aimed to evaluate the proportion of effect of 24h NIHSS improvement on mRS 0-2 at 90d mediated through improvement in motor and language domains. Methods: From SELECT study, EVT patients with detailed NIHSS components on presentation and 24h follow-up as well as complete mRS on discharge and 90d were selected. Motor improvement was defined as ≥2 point in cumulative arms and legs score or 0 score at 24h and language improvement was defined as ≥1 point in cumulative aphasia and dysarthria scores at 24h. Mediation analysis framework using 4-step method (Figure 1a) was used to evaluate the effect of 24h NIHSS improvement mediated through improvement in motor and language scores. Results: Of 192 eligible EVT patients, 176 demonstrated motor deficits and 187 demonstrated language deficits. 24h NIHSS improvement was significantly associated with mRS 0-2 (aOR:1.15[1.07-1.23], p<0.001) - step 1. 24h NIHSS improvement was also significantly associated with motor (aOR:1.77[1.48-2.12],p<0.001) and speech improvement (aOR:1.25[1.16-1.36],p<0.001) - step 2. In the full model, motor (aOR:3.00[1.07-8.46],p=0.037) and speech improvement (aOR:3.15[1.37-7.27],p=0.007) were significantly associated with mRS 0-2, whereas 24h NIHSS improvement was no longer a significant predictor (aOR:1.05[0.96-1.15],p=0.33) - step 3 of figure 1a. Motor improvement mediated 68% and speech improvement mediated 27% of the association of 24h NIHSS improvement with mRS 0-2 (Figure 1b) - step 4. Conclusions: Almost all (~95%) of the effect of 24h NIHSS improvement on functional independence (mRS 0-2) was mediated through specific improvement in motor and language domains, suggesting a large role of improvement in motor and language domains in achieving better functional independence. Further studies are needed to confirm the findings.

Alberta Stroke Program Early Computed Tomography Score, Infarct Core Volume, and Endovascular Therapy Outcomes in Patients With Large Infarct

“…Currently, 4 RCTs have been published to compare the outcomes of EVT vs medical management in patients with large infarct. [3][4][5][6] The RESCUE-Japan LIMIT trial 5 was the first RCT conducted in Japan to demonstrate that in patients with large infarct, stroke defined as an ASPECTS score of 3 to 5 (assessed by MRI mostly) with symptom onset within 6 hours or between 6 and 24 hours, and no signal change on MR-fluidattenuated inversion recovery, EVT led to better functional outcomes but increased the risk of ICH. The SELECT2 trial 4 was an international RCT enrolling patients with anterior circulation LVO with ASPECTS of 3 to 5 on NCCT or infarct core volume greater than 50 mL and demonstrated that EVT resulted in better functional outcomes than medical management, with an increased risk of vascular complications.…”

“…[3][4][5][6] The RESCUE-Japan LIMIT trial 5 was the first RCT conducted in Japan to demonstrate that in patients with large infarct, stroke defined as an ASPECTS score of 3 to 5 (assessed by MRI mostly) with symptom onset within 6 hours or between 6 and 24 hours, and no signal change on MR-fluidattenuated inversion recovery, EVT led to better functional outcomes but increased the risk of ICH. The SELECT2 trial 4 was an international RCT enrolling patients with anterior circulation LVO with ASPECTS of 3 to 5 on NCCT or infarct core volume greater than 50 mL and demonstrated that EVT resulted in better functional outcomes than medical management, with an increased risk of vascular complications. The ANGEL-ASPECT RCT 3 involving Chinese patients with anterior circulation LVO who had ASPECTS of 3 to 5 on NCCT within 24 hours after symptom onset or ASPECTS of 0 to 2 on NCCT with in-farct core volume of 70 to 100 mL within 24 hours after symptom onset also found that EVT was associated with better clinical outcomes compared with medical management for such patients, with a higher ICH rate.…”

“…Results from the HERMES meta-analysis are consistent with our findings. 22 As the RESCUE-Japan LIMIT trial, 5 SELECT 2 trial, 4 and TENSION trial 6 excluded patients with LVO with baseline ASPECTS of 0 to 2, the ANGEL-ASPECT trial 3 was, to our knowledge, the first RCT to investigate the effect of EVT in patients with LVO with ASPECTS of 0 to 2. The findings of this secondary analysis are concordant with a subgroup analysis of the RESCUE-Japan LIMIT trial, which demonstrated that EVT was associated with improved 90-day functional outcomes in patients with LVO with baseline ASPECTS of 4 to 5 but not in those with ASPECTS of 3 or less.…”

“…Enrolled in the ANGEL-ASPECT trial ASPECTS indicates Alberta Stroke Program Early Computed Tomography Score; EVT, endovascular therapy; MM, medical management. Endovascular Therapy Outcomes by ASPECTS and Infarct Core Volume in Patients With Large Infarct Original Investigation Research Baseline Characteristics of Patients From the ANGEL-ASPECT Randomized Clinical Trial Across the 3 Imaging Threshold GroupsFor the primary outcome, in the group with ASPECTS of 3 to 5 and infarct core volume less than 70 mL, we found a shift in the distribution of the 90-day mRS score toward better outcomes in the EVT group than in the medical management group (median score, 3 [IQR, 2-5] vs 4 [IQR,[3][4][5]; generalized OR,1.40 …”

“…T he benefit of endovascular therapy (EVT) for patients with acute anterior circulation large vessel occlusion (LVO) with large infarct has been proven by 4 randomized clinical trials (RCTs). [1][2][3][4][5][6] The mechanical thrombectomy for large brain infarctions (MAGNA) individual patient-level data meta-analysis of 3 RCTs (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Large Ischemic Core Trial [RESCUE-Japan LIMIT], 5 Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke [SELECT2], 4 and Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core [ANGEL-ASPECT] 3 ) presented at the European Stroke Conference (ESOC) 2023 7 and 2 other study-level meta-analyses including RCTs and observational studies 8,9 also confirmed the efficacy of EVT for such patients. However, the Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke (TESLA) RCT presented at ESOC 2023 did not demonstrate that EVT was superior to medical management for such patients according to the utility-weighted modified Rankin Scale (mRS) at 90 days, falling just short of the prespecified primary outcome threshold to confirm efficacy.…”