Bridging Therapy Versus Direct Mechanical Thrombectomy in Patients with Acute Ischemic Stroke due to Middle Cerebral Artery Occlusion: A Clinical- Histological Analysis of Retrieved Thrombi

Abstract

Mechanical thrombectomy (MT) is effective in managing patients with acute ischemic stroke (AIS) caused by large-vessel occlusions and allows for valuable histological analysis of thrombi. However, whether bridging therapy (pretreatment with intravenous thrombolysis before MT) provides additional benefits in patients with middle cerebral artery (MCA) occlusion remains unclear. Therefore, this study aimed to compare the effects of direct MT and bridging therapy, and to elucidate the correlation between thrombus composition and stroke subtypes. Seventy-three patients with acute ischemic stroke who received MT, were eligible for intravenous thrombolysis, and had MCA occlusion were included. We matched 21 direct MT patients with 21 bridging therapy patients using propensity score matching and compared their 3rd-month clinical outcomes. All MCA thrombi (n = 45) were histologically analyzed, and the red blood cell (RBC) and fibrin percentages were quantified. We compared the clot composition according to stroke etiology (large-artery atherosclerosis and cardioembolism) and intravenous thrombolysis application. The baseline characteristics showed no difference between groups except for a higher atrial fibrillation rate and NIHSS score on admission in the direct MT group. We performed a supportive analysis using propensity score matching but could not find any differences in the functional outcome, mortality, and intracerebral hemorrhage. In the histological clot analysis, the cardioembolic clots without intravenous thrombolysis pretreatment had higher RBC (P = 0.042) and lower fibrin (P = 0.042) percentages than the large-artery atherosclerosis thrombi. Similar findings were observed in the thrombi treated with recombinant tissue plasminogen activator (P = 0.012). In conclusion, there was no difference in the functional outcomes between the direct MT and bridging therapy groups. However, randomized trials are needed to elucidate the high ratio of cardioembolism subtype in our group of patients. The histological MCA thrombus composition differed between cardioembolism and large-artery atherosclerosis, and this finding provides valuable information on the underlying pathogenesis and thrombus origin.

Nomogram to Predict Poor Outcome after Mechanical Thrombectomy at Older Age and Histological Analysis of Thrombus Composition

“…Demographic and clinical data and procedural characteristics were collected at admission, as in our previous study [ 3 ]. Stroke subtypes were determined in accordance with the Trial of ORG10172 in Acute Stroke Treatment classification [ 12 ], and successful reperfusion was defined as a thrombolysis in cerebral infarction (TICI) score of 2b-3.…”

“…As described in our previous study, all formalin-fixed, paraffin-embedded thrombi were sectioned and stained with hematoxylin-eosin [ 3 ]. The percentages of red blood cells (RBCs), white blood cells (WBCs), and fibrin in retrieved thrombi were analyzed by two experienced pathologists (LJ.F and WZ) who were blinded to the clinical data and imaging findings.…”

“…Advanced age is particularly related to poor poststroke functional outcomes. Mechanical thrombectomy is an effective therapy for patients with acute ischemic stroke (AIS) due to large vessel occlusions [ 2 , 3 ]. Although the latest guidelines do not recommend an upper age limit for mechanical thrombectomy, there are increasing challenges with endovascular thrombectomy in the elderly, as well as the need to consider comorbidities in clinical decision-making [ 4 , 5 ].…”

“…A high neutrophil-to-lymphocyte ratio (NLR) indicates high neutrophil counts and/or low lymphocyte counts and is considered to accurately reflect the negative effects of neutrophils, as well as the positive roles of lymphocytes in patients with stroke [ 6 – 8 ]. Our previous findings have suggested that histological thrombus composition might provide valuable information on stroke etiology [ 3 ], but its relation to outcomes after mechanical thrombectomy in older patients is less well established.…”

First approach to distinguish between cardiac and arteriosclerotic emboli of individual stroke patients applying the histological THROMBEX-classification rule

“…Contrasting results showing higher red cell proportions 13 , 15 and lower fibrin percentages in cardiac emboli 13 were also obtained. Fitzgerald et al found significantly higher proportions of platelets for large artery atherosclerosis etiology 12 .…”