Clot migration in patients treated with tenecteplase versus alteplase before mechanical thrombectomy.

INTRODUCTION: This study aimed to describe and analyze the rate of clot migration of vessel thrombosis to distal segments in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis (IVT) with tenecteplase (TNK) and alteplase (ALT) before mechanical thrombectomy (MT). In addition, we aimed to determine the relationship between thrombus migration and functional prognosis. METHODS: This study followed the STROBE reporting guidelines. We performed a retrospective analysis of a series of patients from November 2017 to April 2023 with an AIS with thrombosis on CT imaging, treated with IVT (TNK or ALT, split into two distinct groups) prior to mechanical thrombectomy. RESULTS: Two hundred and fifty-six patients with large vessel occlusion (LVO) were included. Ninety-six had received TNK. One hundred and sixty had received ALT. Of the 96 TNK patients, 25 experienced either complete recanalization (n = 3) or thrombus migration (n = 22). Of the 160 ALT patients, 20 experienced either complete recanalization (n = 6) or thrombus migration (n = 14). The difference being statistically substantial for the thrombus migration rate (OR = 3.61, 95% confidence interval: 1.63; 7.98). Migration to an irretrievable very distal segment occurred in four (4%) patients with TNK and in three patients (2%) with ALT (p > 0.05). Thrombus migration was not significantly associated to a different functional prognosis, measured through Rankin scale after 3 months (OR = 0.44, 95% confidence interval: 0.17; 1.12). CONCLUSION: The use of TNK over ALT as a fibrinolytic agent is associated with a higher thrombus migration rate. The migration of thrombi to distal segments, which are theoretically less accessible for mechanical thrombectomy, did not result in worse clinical outcomes.

Phosphorylation of Eukaryotic Initiation Factor 4G1 (eIF4G1) at Ser1147 Is Specific for eIF4G1 Bound to eIF4E in Delayed Neuronal Death after Ischemia.

Ischemic strokes are caused by a reduction in cerebral blood flow and both the ischemic period and subsequent reperfusion induce brain injury, with different tissue damage depending on the severity of the ischemic insult, its duration, and the particular areas of the brain affected. In those areas vulnerable to cerebral ischemia, the inhibition of protein translation is an essential process of the cellular response leading to delayed neuronal death. In particular, translation initiation is rate-limiting for protein synthesis and the eukaryotic initiation factor (eIF) 4F complex is indispensable for cap-dependent protein translation. In the eIF4F complex, eIF4G is a scaffolding protein that provides docking sites for the assembly of eIF4A and eIF4E, binding to the cap structure of the mRNA and stabilizing all proteins of the complex. The eIF4F complex constituents, eIF4A, eIF4E, and eIF4G, participate in translation regulation by their phosphorylation at specific sites under cellular stress conditions, modulating the activity of the cap-binding complex and protein translation. This work investigates the phosphorylation of eIF4G1 involved in the eIF4E/eIF4G1 association complex, and their regulation in ischemia-reperfusion (IR) as a stress-inducing condition. IR was induced in an animal model of transient cerebral ischemia and the results were studied in the resistant cortical region and in the vulnerable hippocampal CA1 region. The presented data demonstrate the phosphorylation of eIF4G1 at Ser1147, Ser1185, and Ser1231 in both brain regions and in control and ischemic conditions, being the phosphorylation of eIF4G1 at Ser1147 the only one found in the eIF4E/eIF4G association complex from the cap-containing matrix (m7GTP-Sepharose). In addition, our work reveals the specific modulation of the phosphorylation of eIF4G1 at Ser1147 in the vulnerable region, with increased levels and colocalization with eIF4E in response to IR. These findings contribute to elucidate the molecular mechanism of protein translation regulation that underlies in the balance of cell survival/death during pathophysiological stress, such as cerebral ischemia.

Malignant Left Atrial Appendage Morphology: Current Classification vs H-L System.

INTRODUCTION: In previous studies the risk of stroke recurrence has been associated with the left atrial appendage (LAA) morphology (non-chicken wing (NCW)), knowing those with a greater risk as malignant LAA. Recently, a simpler morphological classification has been suggested with two categories: Low-risk (LAA-L) and High-risk (LAA-H); which could be easier to apply and may correlate better with the risk of embolic stroke. METHODS: Retrospective analysis from a registry of patients with recurrent cardioembolic strokes despite appropriate anticoagulant therapy, in which LAA morphology was studied with cardiac CT scan. LAA morphology was classified according to the four current categories and H-L morphology by the same cardiologist. Other variables associated with a high risk of stroke were also assessed, such as CHA2DS2-VASc score and left atrial (LA) size. RESULTS: Twenty-six cases were included in the analysis. We identified 22 (84.6%) chicken wing (CW), 1 (3.8%) windsock and 3 (11.5%) cactus by the current classification system, while 15 (57.7%) were classified as LAA-H and 11 (42.3%) as LAA-L by the new system. Half of the 22 cases with CW morphology were considered LAA-H, whereas all NCW were also classified as LAA-H. LA diameter and area were significantly higher in cases with LAA-H morphology (p=0.03 and 0.014), and also in those CW and LAA-H, compared to those CW with LAA-L (p=0.035). CONCLUSIONS: With this new classification system more than half of the cases of our malignant LAAs were classified as high-risk morphology. This morphology was also associated with an increased LA size.

Use of the Cardiovascular Polypill in Secondary Prevention of Cerebrovascular Disease: A Real-Life Tertiary Hospital Cohort Study of 104 Patients.

BACKGROUND: The use of the cardiovascular polypill, a fixed-dose combination treatment, is conceived to improve adherence. However, randomized controlled trials (RCTs) may overestimate it. Studies focusing on cerebrovascular disease and real-life efficacy compared with conventional treatment are lacking. METHODS: This is a retrospective, hospital-based cohort study of acute ischaemic stroke patients who were prescribed a polypill (aspirin 100 mg, atorvastatin 20/40 mg, ramipril 2.5/5/10 mg) versus conventional treatment (aspirin 100 mg and other blood pressure/lipid-lowering agents) in secondary prevention (2017-2018). Clinical records were reviewed 90 days after discharge for stroke recurrence, vascular risk factor control, and safety. Adherence was assessed using the adapted Morisky-Green scale. RESULTS: A total of 104 patients were included (61% male; mean age 69.7 ± 13.9 years); 54 were treated with the polypill and 50 with conventional treatment. No baseline differences in clinical or demographic variables were detected. No recurrences were registered in the polypill group, compared to 1 recurrence in the conventional treatment group. A significant reduction of systolic blood pressure (SBP) was achieved in the polypill group (12.1 mm Hg) compared to the conventional treatment group (6.8 mm Hg) (p = 0.002). No significant differences were detected regarding the goal of LDL cholesterol ≤70 mg/dL (41 vs. 44%). The adverse events were mild and their frequency was similar in the two groups (9 vs. 2%, ns). Adherence was similarly good in the two groups (93 vs. 88%, ns). Polypill group adherence was similar to that reported in a previous meta-analysis of RCTs (93 vs. 84%, ns). CONCLUSION: In our experience, the cardiovascular polypill achieved a higher reduction in SBP levels and was well tolerated. Adherence was similar to that found in the previous literature, which is remarkable given the real-life setting of our study.