Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial).

RATIONALE: In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. AIMS: To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. SAMPLE SIZE ESTIMATES: Two hundred forty patients will be enrolled, 120 in every treatment arm. METHODS AND DESIGN: A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. STUDY OUTCOMES: Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. DISCUSSION: This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. TRIAL REGISTRATION: The trial is registered as NCT05225961. February, 7th, 2022.

Comparing data from thrombectomy in m2 occlusion and proximal middle cerebral artery.

INTRODUCTION: Mechanical thrombectomy for large vessel occlusion in the anterior circulation has been shown to be beneficial. The question of whether this technique is safe and effective in the distal vasculature remains unanswered. We wanted to compare outcome data from mechanical thrombectomy of M2 branches of the middle cerebral artery (MCA) with those of the M1 segment, and better understand the clinical predictors of these M2 occlusions. METHODS: A retrospective analysis was performed of data prospectively collected between January 2017 and July 2021 from patients with acute ischemic stroke undergoing mechanical thrombectomy of isolated M1 or M2 branches of the MCA. RESULTS: 350 patients were identified, 287 with M1 and 63 with M2 occlusions. Mean age was 70.71 ± 12.55 and 75.21 ± 10.21 years, respectively (p = 0.0083). Baseline Alberta Stroke Program Computed Tomography (ASPECT) score was worse in the M1 cohort (7.68 ± 1.73 vs. 8.32 ± 1.54; p = 0.0079), while there was no significant difference in National Institutes of Health Stroke Scale (NIHSS) scores. No statistical disparity existed in mean procedure duration for each cohort; fewer thrombectomy attempts were required in the M2 cohort (2.01 vs. 1.63; p = 0.0478). There was no statistical difference in total time to recanalization (559.19 vs. 629.97, p = 0.2506). Similar rates of successful reperfusion were observed (Thrombolysis in Ischaemic Stroke score [TICI] ≥ 2b 80.84% vs. 71.43% p = 0.1221). Good outcome (modified Rankin scale ≤ 2) was 56.10 in M1 occlusions and 63.49% on M2 groups. Intracranial haemorrhage rates were similar. CONCLUSIONS: M2 thrombectomy is safe and a significant proportion of patients achieve a good clinical outcome. Advanced age, atrial fibrillation and previous treatment with anticoagulants were predictors for poor outcome. Good outcome was achieved when effective recanalization was obtained.

Effectiveness and safety of PCSK9 inhibitors in real-world clinical practice. An observational multicentre study. The IRIS-PCSK9I study.

Background and aims: The benefits of the PCSK9 inhibitors, alirocumab and evolocumab, in lowering LDL-cholesterol and preventing major adverse cardiac events (MACE) have been demonstrated in pivotal clinical trials. However, few studies of routine clinical practice have been conducted to analyse and compare the efficacy and safety of the two drugs. Methods: Retrospective observational study of patients treated with a PCSK9 inhibitor in five hospitals in Andalusia (southern Spain). Baseline demographic and clinical data, LDL-cholesterol levels and the occurrence of MACEs during the follow-up period were recorded. Results: A total of 141 patients were included in the study: 90 were treated with alirocumab and 51 with evolocumab. The patients' mean age (IQR) was 58 (11) years and 58 (41%) were women. The most frequent concomitant medications were statins, 94 (66.7%), followed by antiplatelet therapy (66%) and ezetimibe (65.2%). The median (IQR) follow-up period was 18 (18) months, with 18 (24) for alirocumab and 11 (18) for evolocumab. At the six-month follow-up visit, LDL-cholesterol values had decreased to pre-treatment levels and remained significantly decreased (p < 0.05) over time, for both drugs, and a greater reduction was achieved in patients with established cardiovascular disease and concomitant treatment with statins. With respect to adverse effects, there were nine MACEs (6.4%), of which seven were with alirocumab (7.8%) and two with evolocumab (3.9%) (p NS). Other adverse effects (9.2%) included local erythema (3.5%), muscle cramps (2.1%), respiratory symptoms (2.1%) and asthaenia (1.4%). Conclusions: The efficacy and safety of alirocumab and evolocumab in routine clinical practice are consistent with the findings of the pivotal clinical trials.

Endovascular stroke treatment after 6-24 hours only needs non-contrast CT.

OBJECTIVES: Imaging selected patients with proximal anterior circulation stroke who demonstrate limited infarct may benefit from endovascular treatment beyond conventional time limits. Our aim was to evaluate the results of the EVT group series arriving between 6 and 24 hours from the onset of symptoms with (ASPECTS) ≥7 to our hospital (with 24/7 interventional neuroradiology) comparing them with those obtained in our prospectively registered series arriving between 0 and 6 hours. MATERIALS AND METHODS: The inclusion criteria were ≥18 years, an interval between stroke and endovascular treatment of 6-24 hours, prestroke score mRS 0-2, no intracranial haemorrhage, (NIHSS) scale 8-22 and infarct evaluated by CT scan ≥7 in ASPECTS scale. Data, including patient demographics, neuroimaging findings, procedural details, recanalization rates and 90-day mRS, were collected. RESULTS: Twelve of the 14 (85.71%) endovascular group patients who came to our centre between 6 and 24 hours had good outcomes at 90 days. To confirm our findings, we evaluated patients treated at our centre who met the selection criteria from January 2017 to September 2019. In this period, 382 patients with large vessel occlusion were treated endovascularly. 56 patients met all the criteria for inclusion and exclusion for our study. 31 of these 56 patients (56.36%) obtained a (mRS) scale ≤2 at three months. There was no significant difference (P = 0.063). CONCLUSION: In circumstances of difficult access to MRI or CT perfusion, a computed tomography of ASPECTS ≥7 is sufficient to indicate endovascular treatment in a stroke of known onset between 6 and 24 hours.

Contrast-induced nephropathy: A dilemma between loss of neurons or nephrons in the setting of endovascular treatment of acute ischemic stroke.

PURPOSE: The aim is to report the incidence and risk factors of contrast-induced nephropathy after the use of iodine-based contrast for the endovascular treatment of acute ischemic stroke. METHODS: Data from patients who underwent neuroendovascular procedures in a center over a period of 22 months were analysed retrospectively. Contrast-induced nephropathy was determined by an increase in serum creatinine level of >25% of baseline or an absolute increase in serum creatinine level of at least 44 µmol/L (0.50 mg/dL) occurring after intravascular administration of contrast media without alternative explanation. The primary outcome measure of this study was the presence of contrast-induced nephropathy in these treated patients. Continuous data were presented as mean ± standard deviation, and categorical data as frequencies or percentages. The comparison was made using Student's t-test or Fisher's test. Logistic regression was performed to find independent contrast-induced nephropathy predictors. All statistical analyses were performed using Microsoft Excel. A p value of less than 0.05 was considered statistically significant. RESULTS: One hundred and eighty-nine patients undergoing endovascular treatment for acute ischemic stroke. Twenty cases of the total cohort (n = 189) presented contrast-induced nephropathy (10.58%). Only diabetes and creatinine levels between 1.3 and 2.5 mg/dL were associated with contrast-induced nephropathy. No patient was treated with dialysis. CONCLUSION: Contrast-induced nephropathy is a relatively common complication after endovascular treatment of acute ischemic stroke and is associated with worse outcome in patients with this condition. However, there is no increase in the frequency of hemodialysis after the use of iodinated contrast medium.

The effect of prioritization over cognitive-motor interference in people with relapsing-remitting multiple sclerosis and healthy controls.

The cognitive-motor interference (CMI) produced by simultaneous performance of a cognitive and a motor task has been proposed as a marker of real-life impairment of people with Multiple Sclerosis (pwMS), yet there is no consensus on the dual task (DT) procedure. This study aimed to compare DT performance of pwMS and healthy controls (HC) under different instructions and to examine its association with neuropsychological and clinical variables. PwMS (N = 23; relapsing-remitting course) and HC (N = 24) completed the cognitive (Verbal Fluency) and motor (walking) tasks under three conditions: independently or as single task (ST), both tasks simultaneously at best capacity or double prioritization (DT-DP), and only the cognitive task at best capacity while walking at preferred speed or cognitive prioritization (DT-CP). Compared to HC, pwMS walked significantly slower and produced less correct words under all conditions. The distance walked by pwMS and HC significantly differed between conditions (DT-CP< DT-DP< ST). PwMS produced more words during ST respective to DT-DP and DT-CP, with no difference between both DT conditions. HC showed no differences in cognitive performance between conditions. Motor and cognitive dual-task costs (DTC) were similar between groups. Only in pwMS, the cognitive DTC of DT-DP was different from zero. CMI measures correlated with neuropsychological, symptomatic, physiological (cognitive event-related potentials) and clinical variables. These results suggest that cognitive performance while walking is impaired in pwMS, but not in HC. CMI over cognitive performance might be a potential early marker of cognitive decline in pwMS, which may be enhanced by the instruction to prioritize both tasks in DT.

Half bolus dose of intravenous abciximab is safe and effective in the setting of acute stroke endovascular treatment.

BACKGROUND: A stent is often necessary for the treatment of stroke. In such cases,it is essential for the patient to have antiplatelet therapy. There are several methods of antiaggregation, such as oral loading doses of aspirin and clopidogrel, intravenous aspirin, or intravenous glycoprotein IIb/IIIa receptor antagonists, such as abciximab. The aim of this study was to evaluate the incidence of symptomatic intracerebral hematoma (sICH) associated with our antiplatelet protocol: intravenous abciximab bolus at half the dose (0125 mg/kg) at the time of the stenting procedure; oral aspirin (150 mg) and clopidogrel (75 mg) daily added the next day after CT shows no significant hematoma. MATERIALS AND METHODS: Retrospective review of our database of endovascular management of large acute vessel occlusion treated with intravenous abciximab between January 2015 and March 2018. Demographics data, material, drugs, and complications were registered. Fisher tests were used to compare the incidence of sICH in the literature where abciximab 0.25 mg/kg plus maintenance doses are often administrated. RESULTS: Intravenous abciximab was administered to 99 patients. No sICH was observed. According to the European Cooperative Acute Stroke Study Scale, there were 8 cases of hemorrhagic infarction 1, 5 cases of hemorrhagic infarction 2, 4 cases of parenchymal hemorrhage 1, and no cases of parenchymal hemorrhage 2. A comparison between sICH with conventional antiplatelet doses based on the literature showed a statistically significant difference favoring our protocol. CONCLUSION: In the endovascular treatment of acute ischemic stroke, a bolus dose of 0125 mg/kg of abciximab with no maintenance doses, followed by 150 mg of aspirin and 75 mg of clopidogrel orally the next day, is safe and effective.

Inhibition of neurogenesis in a case of Marburg variant multiple sclerosis.

INTRODUCTION: Neural stem cells (NSC) are located essentially in the subventricular zone (SVZ), subgranular zone (SGZ), and along the central canal of the spinal cord. These cells can proliferate in vitro and differentiate into neurons, oligodendrocytes, and astroglia, thus contributing to repair in multiple sclerosis (MS). We conducted a pathological study to analyse neurogenic response in a patient with Marburg variant MS. METHODS: We present the case of a 27-year-old immunocompetent patient with Marburg variant MS, a fulminant form of the disease. The condition lasted 20 days. Diagnosis was based on clinical symptoms and MRI showed demyelinating lesions located in subependymal areas and histopathological findings. Neurogenic niches (SVZ and dentate gyrus) were analysed by confocal microscopy using markers of proliferation (Ki-67, PCNA), neuroblasts (PSA-NCAM, DCX, Tuj1), stem cells (Nestin, GFAPδ, SOX2, PAX6, Musashi), astrocytes (GFAP, AQ4), oligodendrocytes (NG2, Olig), microglia and cell infiltrates (IBA-1, CD68, MHCII), and cell death (TUNEL). RESULTS: Expression of the markers GFAPδ, SOX2, and PAX6 in NSC was found to be very low. Likewise, markers of proliferation (Ki-67) and intermediate precursors (NG2) were also reduced. This lack of markers of the first stages of cell differentiation means that neurogenesis is inhibited even in very early stages of the disease. CONCLUSION: Inhibition of neurogenesis in our patient, which cannot be explained by the fulminant nature of his symptoms, may be related to inflammation and immune response. This finding may further our knowledge of repair mechanisms in MS.