Abstract 112: When Cell Blood Count Matter, Hypereosinophilic Syndrome a Rare Cause of Ischemic Strokes

Introduction Hypereosinophilic syndrome (HES) is a rare hematological disorder defined by persistently elevated blood eosinophil count (>1500/μL), associated with evidence of organ damage. It can occasionally present primarily with neurological conditions such as ischemic strokes, encephalopathy, or sensory neuropathy. Driving hypothesized mechanisms are hypercoagulability owing to eosinophil‐related endothelial damage or cardioembolism. We present an unusual case of ischemic strokes due to HES in the setting of Fip1‐like 1‐platelet‐derived growth factor receptor alpha (FIP1L1‐PDGFRA) mutation. Methods The patient was identified in routine clinical practice. Results 38 year‐old‐male with no significant medical history who was transferred to our institution for blurred vision, and dizziness. His initial National Institutes of Health Stroke Scale was 3 for bilateral leg weakness. The neurological exam was pertinent for paresis in his left arm and legs. Magnetic resonance imaging (MRI) of the brain demonstrated multiple acute infarcts in bilateral cortical and subcortical structures as shown in Figure 1. Computed tomography angiography (CTA) of the brain and neck did not show significant stenosis or occlusion. During admission, transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) did not reveal any source for cardioembolism. Subsequently, he developed hyperactive delirium requiring anti‐psychotics. He was worked up for any infectious etiology because he continued to have a leukocytosis with an eosinophil count as high as 49%. Doppler of lower extremities showed deep vein thrombosis in the left femoral vein. Hematology evaluated the patient and, after performing a bone marrow biopsy, he was diagnosed with primary Hypereosinophilic syndrome (HES) in the setting of FIP1L1‐PDGFRA mutation. He was started on high‐dose methylprednisolone, hydroxyurea and later switched to Imatinib. A cardiac MRI was performed which was negative for eosinophilic myocarditis. The patient's mental status improved significantly after starting Imatinib and his anti‐psychotics were discontinued. In regards to secondary prevention, vascular neurology wanted antiplatelet monotherapy, however, the patient was started on Apixaban to treat his DVT. He was followed up in the stroke clinic 2 months after discharge, his modified Rankin score (mRS) was 1. Aspirin was recommended for secondary stroke prevention once hematology considers it safe to discontinue apixaban. Conclusion This case encourages the consideration of HES in patients with low cardiovascular risk factors who have infarcts following a cardioembolic or watershed pattern in brain imaging. Going back to the basics and reviewing simple laboratory tests like cell blood count can be the initial clue for diagnosis. Early recognition is crucial as immunosuppression is the most important treatment in the acute phase. While imatinib is the treatment of choice for FIP1L1‐PDGFRA mutation HES, patients continued to be at risk of stroke recurrence despite having normal eosinophil count as described by Rohmer et al

Protective effect of hydrogen sulfide in a murine model of acute lung injury induced by combined burn and smoke inhalation. Clin Sci 115:91–7

Acute lung injury results in a severe inflammatory response, which leads to priming and activation of leucocytes, release of reactive oxygen and reactive nitrogen species, destruction of pulmonary endothelium, extravasation of protein-rich fluid into the interstitium and formation of oedema. Recently, H 2 S (hydrogen sulfide) has been shown to decrease the synthesis of pro-inflammatory cytokines, reduce leucocyte adherence to the endothelium and subsequent diapedesis of these cells from the microvasculature in in vivo studies, and to protect cells in culture from oxidative injury. In the present study, we hypothesized that a parenteral formulation of H 2 S would reduce the lung injury induced by burn and smoke inhalation in a novel murine model. H 2 S post-treatment significantly decreased mortality and increased median survival in mice. H 2 S also inhibited IL (interleukin)-1β levels and significantly increased the concentration of the anti-inflammatory cytokine IL-10 in lung tissue. Additionally, H 2 S administration attenuated protein oxidation following injury and improved the histological condition of the lung. In conclusion, these results suggest that H 2 S exerts protective effects in acute lung injury, at least in part through the activation of anti-inflammatory and antioxidant pathways

Abstract 272: Effect of Level of Education on Outcomes of Mechanical Thrombectomy

Introduction Multiple epidemiological studies have investigated the association between stroke clinical outcomes and education level. However, the relationship between the level of education in patients who underwent mechanical thrombectomy (MT) is limited. We aim to assess if the level of education is associated with poor functional outcome, defined as a modified Rankin Scale (mRS) score of ≥3, in patients following MT. Methods We reviewed 257 patients with large vessel occlusion (LVO) who underwent MT between 2018 and June 2023, education levels were available on 106 patients. Education level was defined as “less than high school” (n=15, 14.2%), “high school” (n=54, 50.9%), and “college or higher” (n=36, 34%), 1 of these with “other” education level was excluded from the analysis. Chi‐square and Kruskal Wallis tests were used to examine potential differences in education level and outcomes. All analyses were conducted in IBM SPSS Statistics version 29. Results Compared to those with a college or higher education, those with a less than high school education were more likely to have a poor functional outcome (mRS ≥3) at 90 days. (p=0.03). Black patients were more likely to have a less than high school education than white patients (30.0% vs 4.8%) p<0.001. There were no significant differences in mortality, length of hospitalization, comorbid conditions, Alberta stroke program early CT score (ASPECTS), or initial National Institutes of Health Stroke Scale (NIHSS). Conclusion In our cohort, patients with less than a high school education are more likely to have poorer functional outcomes 90 days post‐MT compared with patients with a college education or higher. Interestingly, there was no significant statistical difference noted in initial NIHSS, ASPECTS, and length of hospitalization between these cohorts. Larger post‐thrombectomy cohorts should be used to further investigate these initial results. In addition, it is important to note that education and race are intertwined in this study, though our relatively small sample of post‐thrombectomy patients limited our analyses. Future research should evaluate this relationship further

Abstract 161: Repeated administration of thrombolytic therapy in the setting of stuttering lacunar infarct

Introduction Tissue plasminogen activator (tPA) is the standard of care for the treatment of acute ischemic stroke with symptom onset within 4.5 hours. One exclusion criterion for tPA administration is stroke within 3 months due to the presumed increased risk of hemorrhage. While the rate of early recurrent stroke (ERS) within 3 months is as high as 14.5‐18.3%, the safety and effectiveness of repeated tPA administration remain unclear. An increasing number of studies pose a challenge to this recommendation. One study identified 19 patients who received tPA for ERS and found no symptomatic intracranial hemorrhage. Fifteen other studies with a cohort of 57 patients (including one patient receiving repeated tPA within 90 minutes) reached the same conclusion that repeated tPA is safe in ERS. We present a patient with stuttering motor weakness who received intravenous (IV) tPA twice, 3 days apart with discharged modified Rankin scale (mRS) of 3. Methods The patient was identified in routine clinical practice. Results Our patient is a 61‐year‐old right‐handed Caucasian woman with a medical history of untreated hypertension presented with sudden onset of left arm and leg weakness. IV tPA was given at the local emergency department (ED) and she was then transferred to our comprehensive stroke center. Upon arrival, her National Institutes of Health Stroke Scale (NIHSS) was 0. Her symptoms were completely resolved. Computed tomography (CT) head was unremarkable and CT angiography (CTA) did not show significant stenosis or occlusion. Magnetic resonance imaging (MRI) of the brain was negative for an acute infarct. She was diagnosed with a transient ischemic attack and was discharged home with aspirin and a high‐intensity statin for secondary stroke prevention. She presented to the ED the next day with identical left‐sided weakness again. Her NIHSS was 5 this time and IV tPA was given again. MRI showed an acute infarct in the right posterior limb of the internal capsule. Transthoracic echo did not reveal an intracardiac shunting or thrombus. The stroke mechanism was small vessel disease, and anti‐hypertensive medications were added to the treatment. She was discharged to an acute rehabilitation center with an mRS of 3 and her 90‐day mRS was 1 on follow up. Conclusion Management of ERS is a challenging issue in stroke care. Our case adds value to the current limited literature demonstrating the safety and effectiveness of repeated tPA in ERS, especially in patients with MR negative stuttering lacunar infarct and subsequent improvement following tPA. Further research with larger registries is needed to identify appropriate selection criteria for repeated tPA use in this patient population

Abstract 222: Immediate post thrombectomy extubation is associated with improved clinical outcomes

Introduction Recent findings suggest that general anesthesia with endotracheal intubation (GA) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) who receive mechanical thrombectomy (MT) is associated with similar outcomes to conscious sedation (CS). [1][2] However, these trials involved stroke specific GA protocols in which immediate, post‐operative extubation was emphasized. In this study, we investigated outcomes of MT in AIS due to LVO as a function of the timing of extubation and explored variables that could delay extubation. Methods We performed a retrospective analysis of collected data gathered during a 5‐year period (2018‐2022) for all our patients with AIS due to LVO who received MT. We analyzed the stroke outcomes and complications between patients who had received GA and those who had received CS. We also investigated the relationships between associated pulmonary risk factors, timing of extubation, and tracheostomy, on the outcomes of stroke. Results A total of 242 patients were included in our study. 83 patients received GA and 159 patients received CS. Our study shows CS in MT had a 2.74 (95% CI = 1.21‐6.22) higher odds of having a final TICI rating of 0‐2a compared to those who had GA. A logistic regression model was fitted that included NIHSS prior to MT; in this analysis, patients who received GA had 2.71 times higher odds of reaching TICI 2b or higher (OR = 2.71, 95% CI = 1.19‐6.17). NIHSS was not a significant predictor of recanalization in our patients. Patients extubated in the IR suite vs. elsewhere (excluding patients who were not extubated in hospital) had 3.82 (95% CI = 1.03‐14.18) times higher odds of having an excellent mRS at 90 days (n=65). Those extubated late had higher odds of transitioning to comfort care (OR=4.50, 95% CI = 1.52‐13.31, p=0.004), and 90‐day mortality (OR=5.49, 95% CI = 1.71‐17.65, p=0.002). Those who were extubated early had a lower NIHSS post MT (mean = 10.89 vs 19.18), t=‐5.79, p<0.001), and a lower NIHSS at discharge (mean = 9.20 vs 17.11), t=‐5.79, p<0.001). There were no significant correlations between history of COPD or the BMI and the timing of extubation or the outcomes of MT. In addition, COPD was not associated with any significant changes in discharge or 90 days mRS. Conclusion Administration of GA to patients who receive MT for AIS was associated with better outcomes in our cohort. Immediate extubation was associated with better outcomes than delayed extubation in the GA group. A history of COPD or high BMI should not affect the decision to provide with GA for MT

Time course of nitric oxide synthases, nitrosative stress, and poly(ADP ribosylation) in an ovine sepsis model

Introduction: Different isoforms of nitric oxide synthases (NOS) and determinants of oxidative/nitrosative stress play important roles in the pathophysiology of pulmonary dysfunction induced by acute lung injury (ALI) and sepsis. However, the time changes of these pathogenic factors are largely undetermined. Methods: Twenty-four chronically instrumented sheep were subjected to inhalation of 48 breaths of cotton smoke and instillation of live Pseudomonas aeruginosa into both lungs and were euthanized at 4, 8, 12, 18, and 24 hours postinjury. Additional sheep received sham injury and were euthanized after 24 hrs (control). All animals were mechanically ventilated and fluid resuscitated. Lung tissue was obtained at the respective time points for the measurement of neuronal, endothelial, and inducible NOS (nNOS, eNOS, iNOS) mRNA and their protein expression, calcium-dependent and -independent NOS activity, 3-nitrotyrosine (3-NT), and poly(ADP-ribose) (PAR) protein expression. Results: The injury induced severe pulmonary dysfunction as indicated by a progressive decline in oxygenation index and concomitant increase in pulmonary shunt fraction. These changes were associated with an early and transient increase in eNOS and an early and profound increase in iNOS expression, while expression of nNOS remained unchanged. Both 3-NT, a marker of protein nitration, and PAR, an indicator of DNA damage, increased early but only transiently. Conclusions: Identification of the time course of the described pathogenetic factors provides important additional information on the pulmonary response to ALI and sepsis in the ovine model. This information may be crucial for future studies, especially when considering the timing of novel treatment strategies including selective inhibition of NOS isoforms, modulation of peroxynitrite, and PARP.Center for Electromechanic

Beneficial pulmonary effects of a metalloporphyrinic peroxynitrite decomposition catalyst in burn and smoke inhalation injury

During acute lung injury, nitric oxide (NO) exerts cytotoxic effects by reacting with superoxide radicals, yielding the reactive nitrogen species peroxynitrite (ONOO−). ONOO− exerts cytotoxic effects, among others, by nitrating/nitrosating proteins and lipids, by activating the nuclear repair enzyme poly(ADP-ribose) polymerase and inducing VEGF. Here we tested the effect of the ONOO− decomposition catalyst INO-4885 on the development of lung injury in chronically instrumented sheep with combined burn and smoke inhalation injury. The animals were randomized to a sham-injured group (n = 7), an injured control group [48 breaths of cotton smoke, 3rd-degree burn of 40% total body surface area (n = 7)], or an injured group treated with INO-4885 (n = 6). All sheep were mechanically ventilated and fluid-resuscitated according to the Parkland formula. The injury-related increases in the abundance of 3-nitrotyrosine, a marker of protein nitration by ONOO−, were prevented by INO-4885, providing evidence for the neutralization of ONOO− action by the compound. Burn and smoke injury induced a significant drop in arterial Po2-to-inspired O2 fraction ratio and significant increases in pulmonary shunt fraction, lung lymph flow, lung wet-to-dry weight ratio, and ventilatory pressures; all these changes were significantly attenuated by INO-4885 treatment. In addition, the increases in IL-8, VEGF, and poly(ADP-ribose) in lung tissue were significantly attenuated by the ONOO− decomposition catalyst. In conclusion, the current study suggests that ONOO− plays a crucial role in the pathogenesis of pulmonary microvascular hyperpermeability and pulmonary dysfunction following burn and smoke inhalation injury in sheep. Administration of an ONOO− decomposition catalyst may represent a potential treatment option for this injury