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Introduction Severe loss of muscle strength is common following stroke, and rehabilitation in the form of targeted physical therapy is often needed to recover partial muscular function. Although lower limb weakness is typical in stroke patients, upper body complications presenting as decreased grip strength and hand motor coordination can also occur. The biceps brachii, one of the most frequently used upper body muscles, often shows weakness post‐stroke. Although recent literature has touched on various techniques to help regain biceps brachii function, studies looking at quantifiable recovery of muscular strength are limited.In this review, we summarize strength recordings of the biceps brachii from stroke patients collected over the past 20 years to better characterize upper extremity functional recovery after stroke. Methods Using PRISMA guidelines, we queried 3 databases to identify all studies reporting findings of stroke recovery including isolated strength measurement of the bicep brachii muscle in newtons (N). Results 15 studies describing 384 patients (mean age range: 55.7‐73.6 years) were included for formal analysis. Baseline biceps strength range following stroke was 12.1‐91.23 N. At 4 weeks, strength ranged from 16.3‐85.8N, and this range improved to 85.31‐97.38N and 29–125.04N at 5 and 8 weeks, respectively. Additionally,Folkerts et al. found a significant improvement in biceps function from the 5 week value (97.38N) to the 10 week final follow‐up (108.46N). Over 12 weeks post‐stroke, Donaldson and colleagues observed a significant improvement in bicep strength range (27.1‐61.0N vs. 59.5‐76.1N). Conclusions Our study is the first systematic review assessing the recovery of biceps function with time following stroke in the current literature. Singular timepoint studies showed a significant loss of bicep function post‐stroke. Multiple timepoint studies showed semi‐linear relationships between biceps strength recovery and time within studies but no patterns when comparing between studies. Further research is required to quantify biceps strength recovery in a sex‐specific manner.

Introduction EXCELLENT (NCT03685578; Cerenovus) is a large, prospective, international, real‐world registry of endovascular clot removal in acute ischemic stroke (AIS) with EmboTrap as the first line mechanical thrombectomy (MT) device, which included collection and analysis of the retrieved thrombus material. Methods Between September 2018 and March 2021, 1000 “all‐comer” patients were enrolled at 34 global sites (27 US, 5 EU, 1 UK, 1 Israel) and treated according to standard of care at each center (with Embrotrap as first line). The study employed blind endpoint evaluation, including a core imaging lab and an independent 90‐day mRS assessment. Retrieved clot was collected per each MT maneuver from 538 subjects across 26 sites and clot analysis was performed by independent central labs blinded to clinical data. Results mITT population included 998 subjects. Mean age was 69.9±14.18 years (range 18–102), 51.8% (517/998) subjects were female and 9.9% (97/997) had a pre‐stroke mRS 3–5. Baseline NIHSS was 15.6±6.87 (range 0–36); 10.1% (82/815) subjects had a large core (ASPECTS 0–5); 5.8% (57/990) had posterior stroke; 56.3% (523/929) underwent MT ≤ 6hrs of onset and 38.1% (380/998) received IV‐tPA prior to MT. First pass eTICI 2c‐3 was achieved in 38.3% (377/984) and final 2b‐3 in 94.5 % (930/984; median number of passes = 1) of subjects. 90‐day mRS≤2 or ≤pre‐stroke was 46.9% (429/915) and 90‐day all‐cause mortality was 19.0% (175/921). The univariate analysis of clot components showed high red blood cell and low platelet content were significant predictors of good mRS outcome (p < 0.001 and 0.009) and negative predictors of 90‐day mortality (p < 0.001 and 0.017, respectively). Conclusions This large multi‐center, all‐comer cohort reflects the population undergoing thrombectomy today in a real world‐setting. Final angiographic, clinical and thrombus composition results, along with multivariate analysis of predictors of clinical outcomes, will be presented at the time of the conference.

Abstract Cellular senescence has been identified as a pathological mechanism linked to tau and amyloid beta (Aβ) accumulation in mouse models of Alzheimer's disease (AD). Clearance of senescent cells using the senolytic compounds dasatinib (D) and quercetin (Q) reduced neuropathological burden and improved clinically relevant outcomes in the mice. Herein, we conducted a vanguard open-label clinical trial of senolytic therapy for AD with the primary aim of evaluating central nervous system (CNS) penetrance, as well as exploratory data collection relevant to safety, feasibility, and efficacy. Participants with early-stage symptomatic AD were enrolled in an open-label, 12-week pilot study of intermittent orally-delivered D+Q. CNS penetrance was assessed by evaluating drug levels in cerebrospinal fluid (CSF) using high performance liquid chromatography with tandem mass spectrometry. Safety was continuously monitored with adverse event reporting, vitals, and laboratory work. Cognition, neuroimaging, and plasma and CSF biomarkers were assessed at baseline and post-treatment. Five participants (mean age: 76±5 years; 40% female) completed the trial. The treatment increased D and Q levels in the blood of all participants ranging from 12.7 to 73.5 ng/ml for D and 3.29-26.30 ng/ml for Q. D levels were detected in the CSF of four participants ranging from 0.281 to 0.536 ng/ml (t(4)=3.123, p=0.035); Q was not detected. Treatment was well-tolerated with no early discontinuation and six mild to moderate adverse events occurring across the study. Cognitive and neuroimaging endpoints did not significantly differ from baseline to post-treatment. CNS levels of IL-6 and GFAP increased from baseline to post-treatment (t(4)=3.913, p=008 and t(4)=3.354, p=0.028, respectively) concomitant with decreased levels of several cytokines and chemokines associated with senescence, and a trend toward higher levels of Aβ42 (t(4)=-2.338, p=0.079). Collectively the data indicate the CNS penetrance of D and provide preliminary support for the safety, tolerability, and feasibility of the intervention and suggest that astrocytes and Aβ may be particularly responsive to the treatment. While early results are promising, fully powered, placebo-controlled studies are needed to evaluate the potential of AD modification with the novel approach of targeting cellular senescence.

VEXAS is caused by somatic mutations in UBA1 (UBA1mut) and characterized by heterogenous systemic auto-inflammation and progressive hematologic manifestations, meeting criteria for myelodysplastic syndrome (MDS) and plasma cell dyscrasias. The landscape of myeloid-related gene mutations leading to typical clonal hematopoiesis (CH) in these patients is unknown. Retrospectively, we screened 80 VEXAS patients for CH in their peripheral blood (PB) and correlated findings with clinical outcomes in 77. UBA1mutwere most common at hotspot p.M41 (median variant allele frequency/VAF = 75%). Typical CH mutations co-occurred with UBA1mut in 60% of patients, mostly in DNMT3A and TET2, and were not associated with inflammatory or hematologic manifestations. In prospective single-cell proteogenomic sequencing (scDNA), UBA1mutwas the dominant clone, present mostly in branched clonal trajectories. Based on integrated bulk and scDNA analyses, clonality in VEXAS followed two major patterns: with either typical CH preceding UBA1mutselection in a clone (Pattern 1), or occurring as an UBA1mutsubclone or in independent clones (Pattern 2). VAF in PB differed markedly between DNMT3A and TET2 clones (median VAF of 25% vs 1%). DNMT3A and TET2 clones associated with hierarchies representing patterns 1 and 2, respectively. Overall survival for all patients was 60% at 10 years. Transfusion-dependent anemia, moderate thrombocytopenia, and typical CH mutations, each correlated with poor outcome. In VEXAS, UBA1mut cells are the primary cause of systemic inflammation and marrow failure, being a new molecularly defined somatic entity associated with MDS. VEXAS-associated MDS is distinct from classical MDS in its presentation and clinical course.

AbstractIntroductionLumbar puncture (LP) to collect and examine cerebrospinal fluid (CSF) is an important option for the evaluation of Alzheimer's disease (AD) biomarkers but it is not routinely performed due to its invasiveness and link to adverse effects (AE).MethodsWe include all participants who received at least one LP in the Alzheimer's Disease Neuroimaging Initiative (ADNI) Study. For comparison between groups, two‐sample t‐tests for continuous, and Pearson's chi‐square test for categorical variables were performed.ResultsTwo hundred twenty‐seven LP‐related AEs were reported by 172 participants after 1702 LPs (13.3%). The mean age of participants who reported at least one AE was 69.79 (standard deviation (SD) 6.3) versus none 72.44 (7.17) years (p < 0.001) with female predominance (115/172 = 67.4% vs 435/913 = 48%), and had greater entorhinal cortical thickness and hippocampal volume (3.903 (0.782) vs 3.684 (0.775) mm, p = 0.002; 7.38 (1.06) vs 7.05 (1.15) mm3, p < 0.001), respectively.DiscussionWe found that younger age, female sex, and greater thickness of the entorhinal cortex were associated with a higher rate of LP‐related AE reports.