Risk of Retinal Vascular Occlusion among Patients with Covid-19 and Influenza A: A Multi-Centered Analysis

Purpose of Study: Severe COVID-19 infection has been associated with a hypercoagulable state, contributing to the formation of clots. Retinal vascular occlusion (RVO) is a common cause of vision impairment and is due to blockage of the retinal arteries and veins. There have been reported cases of patients with previous history of COVID-19 presenting with new RVO. Given the minimal research delving into this relationship, the purpose of this study was to investigate the short-term prevalence and risk for RVO following infection by COVID-19 compared to Influenza A. Methods Used: Two cohorts were created using TrinetX, a national federated electronic health record (EHR). The two cohorts consisted of patients with a history of COVID-19 (n=2,352,475) and patients with a history of Influenza A (n=67,065). Both cohorts were balanced using 1:1 propensity score matching (PSM) addressing demographics and medical comorbidities. Outcomes between the two cohorts were compared using adjusted risk ratios (aRR), with a confidence interval of 95%. Summary of Results: After PSM, two cohorts of 67,063 patients each were compared. Patients in the COVID-19 cohort had an average age of 41.4+/-23.0 years compared to 34.4+/-27.7 years in the Influenza cohort. Between the two cohorts, there was no significant difference in risk of developing retinal vascular occlusion (aRR [95% CI] = 0.72 [0.49,1.06];p=0.097) and patients with COVID-19 had a significantly lower risk for developing retinal vein occlusion (aRR [95% CI] = 0.45 [0.27,0.77];p=0.03). Incidence of retinal vascular occlusion was 0.1% between both cohorts. Retinal artery occlusion was excluded from analysis due to obfuscation of the data by the EHR. Conclusion(s): Between the two cohorts, there was no significant difference in risk for developing RVO within 120 days. However, while there was no significant difference, vascular occlusions were found at a relatively younger age than the general population. Although incidence of RVO was low between the two cohorts, both viruses could be considered a risk factor for development of RVO, particularly in younger patients lacking classic risk factors for the disease.

CRT-200.01 Impact of the COVID-19 Pandemic on STEMI Activation Incidence, Characteristics, and Outcomes

Background: ST-elevation myocardial infarction (STEMI) is characterized by acute coronary artery occlusion warranting emergent intervention. We aim to investigate the incidence, patient characteristics, hospital course and outcomes of STEMI patients as the pandemic continues to evolve. Method(s): STEMI alert data was obtained from an institutional database from 2009 to 2022. Patient characteristics, outcomes, and hospital course were obtained via chart review. True STEMI was determined by classic clinical presentation, ST elevation on EKG, troponin elevation, and acute vessel occlusion on coronary angiogram. We defined the pre-pandemic time frame as prior to 3/18/2020 (n=1002), and pandemic activations from 3/19/2020 - 10/2022 (n=113). Result(s): True STEMI incidence was significantly higher during the pandemic when compared to the pre-pandemic period (85.9% vs. 52.6%;p<0.05). 30- and 90-day mortality rate was significantly higher during the COVID-19 pandemic (12.1% vs. 6.8%;p<0.05 and 15.5 vs. 8.0%;p=0.01). There was a higher use of temporary mechanical support use in STEMI patients during the pandemic (19.5% vs. 10.3%;p=0.003). Interestingly, despite a higher percentage of true STEMIs and higher mortality rate during the pandemic, initial troponin (7.8 vs. 17.46;p=0.09) and peak troponin (18.1 vs. 52.8;p<0.001) were significantly lower. Conclusion(s): STEMI activations dipped during the pandemic and are still below pre-pandemic levels. During the pandemic, there were higher rates of true STEMIs, utilization of temporary mechanical support, and complicated hospitalizations with higher mortality. Despite poorer outcomes and complicated hospital course, patients presenting during the pandemic had lower initial and peak troponin levels, possibly indicating delayed presentation. [Formula presented]Copyright © 2023

A Series of Catastrophic Events

Case report - Introduction: Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening disease occurring in up to 1% of antiphospholipid syndrome (APS) cases. It was first defined in 1992 and remains a difficult to treat entity with a mortality rate of 37%. We describe a patient with systemic lupus erythematosus (SLE) and CAPS presenting with simultaneous multi-organ injuries who was successfully managed with 'triple' therapy including cyclophosphamide. Case report - Case description: A 42-year-old female presented to her local hospital with chest pain and worsening vision. She had a background of SLE, triple antibody-positive APS (previous DVT, pregnancy loss and strokes), hypertension, a metallic mitral valve, a previous myocardial infarction and pre-existing visual impairment due to a prior intra-cerebral bleed related to anticoagulation. Examination revealed a faint malar rash, cortical blindness and long tract neurological signs. Her ECG showed ischaemic changes and the admission troponin was significantly raised (3773ng/L). An echocardiogram showed new left ventricular dysfunction and a subsequent cardiac MRI was in keeping with coronary artery disease. Investigations showed an acute kidney injury, newly deranged liver function tests and a raised INR (>11, with no bleeding). Complement was normal with a low dsDNA titre. Urinalysis revealed proteinuria and a protein creatinine ratio measured 176mg/mmol. MRI diffusion weighted brain imaging showed acute bilateral occipital and left fronto-parietal infarcts. She had symptoms of a lupus flare with arthralgia and a butterfly facial rash. COVID-19 PCR tests were negative and she had not been recently vaccinated. She was diagnosed with CAPS and transferred to St Thomas' hospital intensive care. On arrival, she received 1mg intravenous vitamin K followed by triple therapy for CAPS: an unfractionated heparin infusion, oral prednisolone 40mg daily, 5 days of plasma exchange and, given her background of SLE, she was treated with intravenous cyclophosphamide (according to the EUROLUPUS regimen). Intravenous methylprednisolone was avoided due to a previous hypertensive encephalopathy reaction. She responded rapidly. Her troponin fell from a peak of 5054 to 294ng/ L, her creatinine settled at a new baseline (232umol/L) and her liver function normalised. She was switched back to warfarin due to her metallic valve and started on aspirin for cardiovascular secondary prevention. She required physical and occupational therapy due to her strokes but recovered well. Case report - Discussion: According to the 2003 criteria, CAPS can be classified as definite when there is evidence of: -3 organs involved, development of manifestations simultaneously or within a week, confirmation by imaging and/or histopathology of small vessel occlusion and positive antiphospholipid antibodies. Probable CAPS is when 3 out of the 4 criteria are present. In this case, three organs were confirmed to be involved with imaging showing cerebral and cardiac ischaemia. Her creatinine rose from a base of 190 to 289umol/L coupled with a high protein creatinine ratio confirming renal involvement. A Budd-Chiari syndrome was also suspected due to deranged liver function tests and INR, though imaging performed after therapy did not confirm this. A biopsy of any of these four organs was not feasible given the severity of her presentation and coagulopathy. There are no randomised controlled trials but data from the CAPS registry guides treatment and management follows a logical approach: anticoagulation to treat thrombosis, glucocorticoids for inflammation and plasma exchange (or IVIG) to remove the circulating autoantibodies. Triple therapy was associated with a reduced mortality compared to no treatment (28.6% versus 75%, respectively). Following analyses from the CAPS registry we also chose to treat with cyclophosphamide, which is associated with improved survival in patients with SLE. This decision was based on the clinical features of an SLE flare as opposed to serological grounds. There have b en reports of rituximab and eculizumab being used successfully in CAPS, though generally as a last resort. As complement activation is seen in animal models of antiphospholipid syndrome thrombosis and rituximab is often used in refractory SLE, they may prove to be promising agents for refractory CAPS. Case report - Key learning points: 1. Prompt recognition and early treatment is vital in managing CAPS 2. Triple therapy with anticoagulation, glucocorticoids and plasma exchange / IVIG is associated with better survival in CAPS 3. Cyclophosphamide is associated with better survival in patients with CAPS and concomitant SLE.

A Series of Catastrophic Events

Case report - Introduction: Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening disease occurring in up to 1% of antiphospholipid syndrome (APS) cases. It was first defined in 1992 and remains a difficult to treat entity with a mortality rate of 37%. We describe a patient with systemic lupus erythematosus (SLE) and CAPS presenting with simultaneous multi-organ injuries who was successfully managed with 'triple' therapy including cyclophosphamide. Case report - Case description: A 42-year-old female presented to her local hospital with chest pain and worsening vision. She had a background of SLE, triple antibody-positive APS (previous DVT, pregnancy loss and strokes), hypertension, a metallic mitral valve, a previous myocardial infarction and pre-existing visual impairment due to a prior intra-cerebral bleed related to anticoagulation. Examination revealed a faint malar rash, cortical blindness and long tract neurological signs. Her ECG showed ischaemic changes and the admission troponin was significantly raised (3773ng/L). An echocardiogram showed new left ventricular dysfunction and a subsequent cardiac MRI was in keeping with coronary artery disease. Investigations showed an acute kidney injury, newly deranged liver function tests and a raised INR (>11, with no bleeding). Complement was normal with a low dsDNA titre. Urinalysis revealed proteinuria and a protein creatinine ratio measured 176mg/mmol. MRI diffusion weighted brain imaging showed acute bilateral occipital and left fronto-parietal infarcts. She had symptoms of a lupus flare with arthralgia and a butterfly facial rash. COVID-19 PCR tests were negative and she had not been recently vaccinated. She was diagnosed with CAPS and transferred to St Thomas' hospital intensive care. On arrival, she received 1mg intravenous vitamin K followed by triple therapy for CAPS: an unfractionated heparin infusion, oral prednisolone 40mg daily, 5 days of plasma exchange and, given her background of SLE, she was treated with intravenous cyclophosphamide (according to the EUROLUPUS regimen). Intravenous methylprednisolone was avoided due to a previous hypertensive encephalopathy reaction. She responded rapidly. Her troponin fell from a peak of 5054 to 294ng/ L, her creatinine settled at a new baseline (232umol/L) and her liver function normalised. She was switched back to warfarin due to her metallic valve and started on aspirin for cardiovascular secondary prevention. She required physical and occupational therapy due to her strokes but recovered well. Case report - Discussion: According to the 2003 criteria, CAPS can be classified as definite when there is evidence of: -3 organs involved, development of manifestations simultaneously or within a week, confirmation by imaging and/or histopathology of small vessel occlusion and positive antiphospholipid antibodies. Probable CAPS is when 3 out of the 4 criteria are present. In this case, three organs were confirmed to be involved with imaging showing cerebral and cardiac ischaemia. Her creatinine rose from a base of 190 to 289umol/L coupled with a high protein creatinine ratio confirming renal involvement. A Budd-Chiari syndrome was also suspected due to deranged liver function tests and INR, though imaging performed after therapy did not confirm this. A biopsy of any of these four organs was not feasible given the severity of her presentation and coagulopathy. There are no randomised controlled trials but data from the CAPS registry guides treatment and management follows a logical approach: anticoagulation to treat thrombosis, glucocorticoids for inflammation and plasma exchange (or IVIG) to remove the circulating autoantibodies. Triple therapy was associated with a reduced mortality compared to no treatment (28.6% versus 75%, respectively). Following analyses from the CAPS registry we also chose to treat with cyclophosphamide, which is associated with improved survival in patients with SLE. This decision was based on the clinical features of an SLE flare as opposed to serological grounds. There have b en reports of rituximab and eculizumab being used successfully in CAPS, though generally as a last resort. As complement activation is seen in animal models of antiphospholipid syndrome thrombosis and rituximab is often used in refractory SLE, they may prove to be promising agents for refractory CAPS. Case report - Key learning points: 1. Prompt recognition and early treatment is vital in managing CAPS 2. Triple therapy with anticoagulation, glucocorticoids and plasma exchange / IVIG is associated with better survival in CAPS 3. Cyclophosphamide is associated with better survival in patients with CAPS and concomitant SLE.

Imaging of COVID-19 vasculopathy from head to toe: Egyptian collective experience after 2 years of the pandemic

Background: COVID-19 vasculopathy is a critical condition that impacts the disease prognosis including vasculitis and thromboembolic complications. This study aimed to provide the Egyptian experience about the COVID-19 vasculopathy during the past two years of the pandemic and to collectively include the different modalities and imaging techniques for the diagnosis of cerebrovascular, pulmonary, gastrointestinal, and peripheral arterial vascular complications. Result(s): This is a multi-center retrospective analysis of 3500 PCR-proved COVID-19 infection between March 2020 and December 2021. A cohort of 282 consecutive patients with COVID-19 vasculopathy was considered for inclusion. They included 204 males and 78 females (72:28%). The mean age was 68 years, and age ranged from 48 to 90 years. Five radiologists evaluated the different imaging examinations in consensus including computed tomography (CT), CT-angiography (CTA), CT-perfusion (CTP), magnetic resonance imaging (MRI), MR-arteriography (MRA), and MR-venography (MRV). 244/282 (86.5%) patients suffered from non-hemorrhagic cerebral ischemic infarctions. 13/282 (4.6%) patients suffered from hemorrhagic cerebral infarctions. 5/282 (1.8%) patients suffered from cerebral vasculitis. Pulmonary vascular angiopathy was detected in 10/282 (3.5%) patients, including pulmonary embolism in 10/10 patients, pulmonary infarctions in 8/10 patients, pulmonary vascular enlargement in 5/10 patients, and vascular "tree-in-bud" sign in 2/10 patients. Intestinal ischemia and small bowel obstruction were detected in 3/282 patients (1%) while GIT bleeding was encountered in 4/282 patients (1.4%). Lower limb arterial ischemia was found in 3/282 patients (1%). Additionally;39/282 (13.8%) patients developed peripheral deep venous thrombosis (DVT) due to prolonged ICU recumbence while 28/282 (10%) patients developed jugular vein thrombosis sequel to prolonged catheterization. A p value (0.002) and (r) = 0.8 statistically proved strong significant relation between COVID-19 vasculopathy and D-dimer levels. Conclusion(s): Multi-system vasculopathy was a serious complication of COVID-19 which impacted the patients' morbidity and mortality. An Egyptian experience about the COVID-19 vasculopathy during the past two years of the pandemic was provided. It encountered the different modalities and imaging techniques for the diagnosis of cerebrovascular, pulmonary, gastrointestinal, and peripheral arterial COVID-19 vascular complications. Copyright © 2022, The Author(s).

Effective mechanical thrombectomy in a patient with stroke and SARS-Cov-2 infection with fatal outcome

Ischemic stroke has been reported in patients with SARS-CoV-2 infection. It is not clear if COVID-19 is causal or simply coexists or triggers the onset of stroke. Stroke is relatively rare in the context of COVID-19 and mostly occurs in the elderly with vascular risk factors. The underlying mechanism of stroke is multiple. We present an 84-year-old male with a stroke due to large vessel occlusion coincident with severe COVID-19 infection, that despite an initial successful mechanical thrombectomy, had a fatal outcome due to respiratory complications and contralateral massive cerebral infarction due to early recurrence. Consequently, vigilance in this type of patients should be extreme since ischemic stroke with active SARS-CoV-2 infection may have a poor prognosis. Copyright © 2022 Fundacion para la difusion neurologica en Ecuador - FUNDINE. All rights reserved.

Evaluating the Risk of Retinal Vascular Occlusion among COVID-19 patients

Purpose : SARS-CoV-2, the viral infection that causes COVID-19, is known to induce a hypercoagulable state in patients. While there have been isolated reports of retinal vascular occlusion among patients with a pre-existing COVID-19 infection, research into this topic remains scant. Therefore, the purpose of this study is to investigate the shortterm prevalence and risk for retinal vascular occlusion between COVID-19 and influenza A patients. Methods : TrinetX is a national, federated database that was utilized in this retrospective cohort analysis. At the time of the study, electronic medical records from over 80 million patients across 57 healthcare organizations were analyzed to create two cohorts of patients. At the time of the analysis, 1,224,770 patients with a previous history for COVID19 were compared to 61,555 patients with a previous history for influenza A. Then, 1:1 propensity score matching (PSM) was utilized to balance each cohort by demographics and comorbidities (age, sex, BMI, history of hypertension, chronic lower respiratory disease, diabetes mellitus, nicotine dependence, heart failure, and alcohol related disorders). Adjusted risk ratios (aRR) using 95% confidence intervals (CI) were used to assess risk of retinal vascular occlusion 120 days after initial diagnosis for COVID-19 or influenza A. Results : Before PSM, COVID-19 patients were at significantly lesser risk for retinal vascular occlusion within 120 days of initial diagnosis than influenza A patients (aRR [95% CI] = 0.58 [0.42,0.8];p<0.001). However, the incidence for influenza patients to develop retinal vascular occlusion was very small (0.1%). After PSM, two balanced cohorts of 61,555 patients were compared to one another and revealed that there is no significant difference in developing a retinal vascular occlusion after a previous diagnosis of COVID19 or influenza A (0.92 [0.58,1.46];p=0.725). Likewise, the incidence for retinal vascular occlusion remained very small (0.1% between both cohorts) (Table 1). Conclusions : This is the first large-scale study investigating the risk of retinal vascular occlusion among COVID-19 and influenza A patients. We found that each cohort was at similar risk for developing retinal vascular occlusion within 120 days. Likewise, the incidence for retinal vascular occlusion was miniscule among patients in this study.

CHARACTERISTICS OF A COVID-19 COHORT WITH LARGE VESSEL OCCLUSION: A MULTICENTER INTERNATIONAL STUDY

Background The mechanisms and outcomes in COVID-19- associated stroke are unique from those of non-COVID-19 stroke. Objectives The purpose of this study is to describe the efficacy and outcomes of acute revascularization of large vessel occlusion (LVO) in the setting of COVID-19 in an international cohort. Methods We conducted an international multicenter retrospective study of consecutively admitted COVID-19 patients with concomitant acute large vessel occlusion (LVO) across 50 comprehensive stroke centers. Our control group constituted historical controls of patients presenting with LVO and receiving a MT between January 2018 to December 2020.Results: The total cohort was 575 patients with acute LVO, 194 had COVID-19 while 381 patients did not. Patients in the COVID-19 group were younger (62.5 vs. 71.2;p<0.001), and lacked vascular risk factors (49, 25.3% vs. 54, 14.2%;p =0.001). mTICI 3 revascularization was less common in the COVID-19 group (74, 39.2% vs. 252, 67.2%;p < 0.001). Poor functional outcome at discharge (defined as mRS 3-6) was more common in the COVID-19 group (150, 79.8% vs.132, 66.7%;p =0.004). COVID-19 was independently associated with a lower likelihood of achieving mTICI 3 (OR: 0.4, 95% CI: 0.2 -0.7;p<0.001), and unfavorable outcomes (OR: 2.5, 95% CI: 1.4 - 4.5;p=0.002). Conclusion COVID-19 was an independent predictor of incomplete revascularization and poor outcomes in patients with stroke due to LVO. COVID-19 patients with LVO patients were younger, had fewer cerebrovascular risk factors, and suffered from higher morbidity/mortality rates. (Figure Presented).

DON'T LOSE SIGHT OF GPA

CASE: A 48-year-old female with no medical history presented with 2 days of decreased vision in the right eye. She reported painless blurry vision that progressed to near complete vision loss. The vision loss was accompanied by one month of progressively worsening cough, body aches, and subjective fevers. She denied smoking and reported no sick contacts. Physical exam was notable for submandibular lymphadenopathy, bilateral conjunctival injection, and grossly decreased vision of the right eye. She also endorsed decreased sensation in bilateral lower extremities distally. Her initial labs showed leukocytosis (13), thrombocytosis (754), and elevated inflammatory markers (ESR 105 and CPR 359). A chest CT showed bilateral upper lobe consolidations and scattered mass like opacities bilaterally. Ophthalmic exam of the right eye revealed multiple small retinal infarctions consistent with paracentral acute middle maculopathy. A CT head was negative and TTE showed no vegetation. Additional testing revealed negative TB, COVID, and normal complements. Initial ANCA testing was negative, however a repeat test was strongly positive for ANCA with PR3 significantly elevated to 428. She was diagnosed with granulomatosis with polyangiitis (GPA) vasculitis and treated with prednisone and started induction therapy of Rituximab. IMPACT/DISCUSSION: GPA is a small-medium vessel necrotizing vasculitis and the most common anti-neutrophil- cytoplasmic-antibody (ANCA) associated vasculitis. GPA classically involves the upper respiratory tract, lungs, and kidneys referenced by the ELK criteria (ENT, Lung, Kidney) commonly used for diagnosis. ENT findings are present in 70-100% of cases with the nasal cavity and paranasal sinuses most commonly involved. Roughly 50% have pulmonary involvement on presentation, as in this patient, while only 10-20% have initial renal involvement. A prodrome of systemic symptoms including body aches and fevers is often present. GPA is closely associated with c-ANCA, with autoantibodies to proteinase 3 (PR3) positive in over 80% of cases. This patient did have prodromal symptoms yet her primary presenting symptom of vision loss was atypical. Eye involvement is not part of the diagnostic triad yet it can occur in GPA. When it does present, it usually manifests as scleritis, conjunctivitis, or uveitis. Retinal infarctions, as seen in this patient, are uncommon and make this case an atypical presentation of GPA. Additionally, ANCA positivity is related to disease activity and a negative ANCA should not exclude GPA from a differential. Not all patients will be ANCA positive on initial presentation and 10% of patients with GPA will remain ANCA negative. CONCLUSION: Providers should consider atypical presentations of GPA in addition to the classic triad of ENT, Lungs, and Kidneys. Renal manifestations are often missing initially and involvement of other systems, such as ocular, can take place. With a positive c-ANCA and high clinical suspicion, treatment should not be delayed.

THE IMPACT OF SARS-COV-2 INFECTION ON THE OUTCOME OF ACUTE ISCHEMIC STROKE - A RETROSPECTIVE COHORT STUDY

Background: Acute ischemic stroke (AIS) is a frequent complication of coronavirus disease (COVID-19), but the prognosis of these patients is poorly understood. Aim: To explore the impact of COVID-19 on neurological outcome in AIS patients. Methods: A comparative retrospective cohort study was conducted in 32 consecutive AIS patients with and 51 without COVID-19 between the 1st of March 2020 and 1st of May 2021. The evaluation was based on a detailed chart review for demographic data, medical history, stroke severity, cranial and vessel imaging results, laboratory parameters, COVID-19 severity, hospitalization time, in-hospital mortality, and functional deficits at discharge (modified Rankin Scale, mRS). Results: COVID-19 AIS patients had worse initial neurological deficit (NIHSS 9 (3-13) vs. 4 (2-10);p=0.06), showed tendency to higher rate of large vessel occlusion (LVO;13/32 vs. 14/51;p=0.21), had prolonged hospitalization (19.4 ± 17.7 vs. 9.7 ± 7 days;p=0.003), had lower chance of functional independence (mRS≤2) (12/32 vs. 32/51;p=0.02) and showed higher in-hospital mortality (10/32 vs. 6/51;p=0.02). In COVID-19 AIS patients, LVO was more common with COVID-19 pneumonia than without (55.6% vs. 23.1%;p=0.139). Conclusion: COVID-19-related AIS carries a worse prognosis. COVID- 19 with pneumonia seems to be associated with a higher rate of LVO.

SHARED GENETIC MECHANISMS AMONG STROKE POST-COVID-19 CASES AND ISCHEMIC STROKE SUBTYPES

Background and aims: SARS-CoV2 infection may increase stroke risk. The biological mechanisms underlying ischemic stroke occurrence during COVID-19 remains unclear. Methods: A Genome-Wide Association Study (GWAS) from MEGASTROKE was used to generate Polygenic risk scores (PRSs) across four p-value thresholds (p=0.05-p=5e-8) using PRSice-2. For all ischemic stroke (AIS) we used 34217 cases and 406111 controls, large-artery atherosclerosis (LAA) 4373 cases 297290 controls, cardioembolic (CE) 7193 cases 355468 controls and small-vessel occlusion (SVO) 5386 cases 343560 controls. For undetermined stroke etiology (UND) 984 cases and 5590 controls from a Spanish stroke cohort were used. PRSs were tested in 54 patients with an ischemic stroke that occurred after COVID-19 hospitalization (<8 days)(IS-COV). IS-COV cases were genotyped with Axiom Spain Biobank Array (11 UND, 6 CE, 6 LAA, 5 SVO, 2 infrequent cause and 24 unknown etiology). 726 population controls were also genotyped. Results: We found significant associations of IS-COV with PRSAIS (threshold= 5e-5, p= 0.04;R2= 0.01, number of SNPs= 60), PRSCE (threshold= 5e-8, p= 0.02, R2= 0.01, SNPs= 4;threshold= 0.05, p= 5.9e-4, R2= 0.03, SNPs=19308), PRSLAA (threshold= 5e-5, p= 6.5e-3, R2= 0.02, SNPs= 81;threshold= 1e-4, p= 0.02, R2= 0.01, SNPs= 146;threshold= 0.05, p =1.3e-3, R2= 0.03, SNPs= 20722) and PRSUND (threshold= 1e-4, p= 0.04, R2= 0.01, SNPs=10;threshold= 0.05, p =1.5e-6, R2= 0.06, SNPs= 3416). We did not find any association between PRSSVO and IS-COV. Conclusions: CE, LAA and UND shared genetic mechanisms with ischemic stroke cases due to COVID-19. We found no association between SVO and IS-COV.

LARGE VESSEL OCCLUSION STROKE IN A 17 YEAR OLD MALE WITH PAEDIATRIC INFLAMMATORY MULTI-SYSTEM SYNDROME ASSOCIATED WITH SARS-COV-2

Background: Paediatric Cov-2 infections have been less severe than in adults, however some have developed a newly defined syndrome, Paediatric Inflammatory Multisystem Syndrome associated with CoV-2 (PIMS -TS). Its presentation is variable and can cause multi-system involvement. It belongs to the common spectrum of pathogen-triggered hyperinflammatory states, including atypical Kawasaki disease. Case summary: 17 year old male of Ghanaian origin, with no significant past medical history, presented with a one-week history of general malaise, fevers and sore throat. He developed severe chest pain and cardiogenic shock, with a CRP of 200, raised troponin and global hypokinesia on echocardiogram with an ejection fraction of 20%. He was positive for SARS-CoV-2 antibodies (though PCR-antigen negative at admission) and fit the criteria for myocarditis secondary to PIMS-TS. He was treated for sepsis, commenced on IV methylprednisolone and needed intubation, sedation and cardiothoracic ICU level care. On weaning sedation after 3 days, he was found to have left middle cerebral artery syndrome with NIHSS 16. CT head and CT angiogram showed a left MCA ischaemic stroke, and a thrombus in the Sylvian MCA branch. This was treated with antiplatelets. His disease markers and motor deficits improved significantly, however he has cognitive impairment and low mood. Conclusion: PIMS-TS related LVO anterior circulation infarct is rare. It necessitates urgent recognition and multi-specialty involvement as currently management is not standardised. Axial DWI (A), ADC (B) MRI demonstrate large left MCA territory infarct. Axial MRA (C) shows occlusion of the left M2 branches, signal drop-out on SWI (D).

PREDICTING FACTORS OF PROLONGED MECHANICAL VENTILATION AFTER ENDOVASCULAR TREATMENT IN LARGE VESSEL OCCLUSION STROKE

Background and aims: Intensive Care Units(ICUs) are a necessary resource for many patients with large vessel occlusion stroke(LVOS) after endovascular treatment(EVT). However, ICUs have a limited availability of beds and ventilators, situation that has been worsened by the current Covid-19 pandemic. We analyze predicting factors for prolonged mechanical ventilation(PMV) after EVT in patients with LVOS. Methods: Retrospective study of patients admitted to our stroke center from 2012-2019 for LVOS who were treated with EVT. We identified patients that required PMV(defined as >24h intubation with admission in ICU) after EVT, and evaluated the association with clinical and radiological factors on admission. Results: N=438. 236(53.9%) women. Mean age 69(DE 14.6). 411(93.8%) anterior circulation stroke, 27(6.2%) posterior. 82(19%) required general anesthesia and intraprocedural intubation, and 47 of them(10.7%) required PMV. Median length of stay(LOS) in ICU: 3 days(1-7). 12/47(25.5%) had prolonged LOS for another reason (6 neurological worsening, 4 hemodynamic instability, 1 respiratory infection, 1 no available beds at Stroke Unit). 19/47(44%) died and 22/47(52.4%) were functionally dependent at three months. Factors associated to a higher risk of PMV after EVT were: basilar occlusion (OR=12.3, IC95%[5.3-28.4],p<0,001);ASPECTS ≤7 (OR=3, IC95%[1.4-6.1],p=0,003) and NIHSS ≥18 (OR=2.8, IC95%[1.3- 5.8],p=0,006). Patients with PMV had a higher risk of mortality (OR=6.5, IC95%[3.3-12.8],p<0,001) and functional dependence (OR=5.1, IC95%[2.4-1],p<0,001) at three months. Conclusions: In our study, patients with basilar occlusion, high NIHSS and lower ASPECTS had higher probability of requiring PMV after EVT, which also led to worse outcome. These are aspects to consider in scenarios with limited availability of ICU beds.

Pediatric Cerebral Infarction associated with recent SARS-CoV-2 mild infection treated with intravenous thrombolysis and endovascular thrombectomy

Objective: N/A Background: Acute ischemic stroke is a major cause of disability worldwide in adults and children. It is a common disease after middle age but uncommon in the pediatric population. Disabling arterial ischemic strokes due to acute intracranial large vessel occlusion within 3-4 weeks of SARS-CoV-2 (COVID-19) infection have been described. Design/Methods: N/A Results: A 15-year-old boy presented with sudden onset right-sided weakness and expressive aphasia witnessed by mother. He presented within 50 minutes of symptom onset to the regional ER facility. Around 4 weeks ago, patient had mild SARS-Cov-2 infection with flu-like symptoms and mild chest pain that worsened with exertion lasting 3-4 days. Neurological examination revealed diminished fluency, anomia, and right upper extremity drift. Initial non contrast computed tomography (CT) demonstrated hyperdense left middle cerebral artery (MCA) sign with subtle loss of gray/white matter differentiation in the left anterior insula. Aphasia and right-sided weakness worsened as he was coming back from CT 2 hours after symptom onset. Intravenous Tenecteplase was administered. CT angiography of head/neck confirmed left proximal M2 occlusion with no arterial dissection. Patient underwent successful mechanical thrombectomy. Three days later his deficits completely resolved. Transthoracic echocardiography with contrast bubble study was unremarkable. Laboratory workup demonstrated mildly low ATIII, positive Factor V Leiden screen with negative genetic testing, positive SARS coronavirus-2 IgG, mildly low PTT. Remaining coagulopathy workup was unremarkable. Conclusions: To our knowledge this is the first case of large vessel occlusion in a pediatric patient treated successfully with both intravenous thrombolysis and mechanical thrombectomy associated with recent SARS-Cov-2 infection. The AIS etiology in our case remains uncertain as abnormal laboratory findings do not explain this presentation. There is high clinical suspicion of an embolic event as possible explanation, possibly related to SARS-CoV-2 postinfectious stage.

Patterns of Seeking Emergent Stroke Care During the COVID-19 Pandemic: A Nebraska Stroke Center Perspective

Objective: To determine the influence of the COVID-19 pandemic on seeking timely stroke care in Nebraska. Background: Stroke is the 5th leading cause of mortality in the United States and a major contributor to disability. Timely stroke management has made a significant impact in reducing morbidity and mortality. Reduction in hospital visits for myocardial infarctions and strokes have been reported during current and prior pandemics. Studying changing patterns of seeking stroke care can identify vulnerable populations, increase awareness and improve systems to ensure timely hospital access during the pandemic. Design/Methods: This is a retrospective chart review of patients aged 19-89 years who presented within the acute stroke (24 hour) window at our institution's emergency departments (ED) from 1/1/2020 to 4/30/2020 and 1/1/2019 to 4/30/2019. Interrupted time-series design was used to identify differences between the two time periods in terms of ED acute stroke presentation, presentation within IV thrombolysis and mechanical thrombectomy time windows, stroke admissions, types of stroke, stroke severity, demographics, stroke risk factors and baseline disability. Statistical significance was defined as P-value of ≤ 0.05. Results: 608 eligible patients were identified (mean age 64.1±14.8 years;52% were females);out of which 330 (54%) presented within the stated 2020 time period. Time from last known well (LKW) to presentation was increased during the stated pandemic period (median 8.5 [2-24] hours vs. 6 [2-16] hours;p=0.010). Stroke admissions were higher (82.1 % vs. 70.5 %;p=<0.001). Large vessel occlusion was more common in ischemic stroke patients during the pandemic (10.6% vs 4.1%;p= 0.03). Presentation within the acute stroke window decreased significantly in April 2020 compared to April 2019 (17.9% vs 21.9%;p=0.05). Conclusions: Time from last LKW to ED presentation increased and presentation within the acute stroke window eventually decreased during the pandemic, especially as the pandemic spread within Nebraska.

Corpus Callosum in COVID-19 Cytokinopathy

Objective: Report a COVID-19 related encephalopathy from selective white matter involvement of corpus callosum. Background: A 26-year-old African American female tested positive for SARS - COV 2 in April 2020. Her medical morbidities included uncontrolled type 1 DM (on insulin), obesity, and CKD stage III (diabetic nephropathy). She presented with fever, headache, dyspnea, myalgia, nausea, and loss of appetite. She was tachypneic, tachycardic, hypertensive, had a temperature of 39.2deg;C and saturating 98% at room air. Pertinent lab values included a glucose of 212 mg/dl, creatinine of 2.7 mg/dl, BUN of 34 mg/dl, and lipase 771 IU/L. CRP was 66.9 mg/L, with a normocytic anemia of 7.9 gm/dl, ferritin 1784 ng/ml, fibrinogen of 651 mg/dl and a peak D-dimer of 10,180 ng/ml. CXR was hypoinflated with mild bibasilar airspace opacities. A NCCT head obtained for a stroke alert, revealed a hypodense corpus collosum. She was admitted to the ICU with worsening hypoxia, kidney injury, metabolic acidosis, and alteration of consciousness. She received tocilizumab, steroids, remdesivir and convalescent plasma exchange for a severe COVID-19 infection. After extubation she developed a dysexecutive syndrome. Design/Methods: Case report Results: A contrast enhanced MR brain confirmed an expansile T2 hyperintense signal along the complete length of corpus callosum associated with restriction of diffusion, and T1 prolongation. There was no superimposed susceptibility or pathologic enhancement. No large vessel occlusions were identifiable from gradient echo (GRE), turbo spin echo (TSE), susceptibility weighted imaging (SWI) and post contrast MR sequences. A repeat MRI brain post discharge demonstrated an improving leukoencephalopathy by virtue of normalizing ADC values. Conclusions: Like prior coronaviridae, severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) affects the brain over a spectrum of injury. Until we clarify direct neurotropism of SARS-CoV-2;this case is supportive of a cytokine mediated excitotoxic injury concomitant with the severity of disease.

A late diagnosis of eosinophilic granulomatosis with polyangiitis

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a medium and small vessel vasculitis. Discussion: A 58-years man was admitted to the Emergency Department in January 2022 for myalgia and weakness of lower limbs in recent COVID-19 infection. He had a clinical history of allergic asthma and eosinophilic pneumonia (ANCA negative) diagnosed as secondary to sensitization work-related in 2001. Blood test showed a severe hypereosinophilia (absolute eosinophil count: 9875/microL) and elevated creatine kinase (CK: 7555 U/L). He was hospitalized in HUB COVID. During hospitalization reported paraesthesia of upper and lower limbs and fever;blood test showed elevation of inflammation markers. Autoimmune screening showed a antineutrophil cytoplasmic antibodies positivity (ANCA anti-MPO 178UI/mL). A sinus CT showed nasal polyposis. A neurological evaluation and electromyography were performed with the evidence of polyneuropathy. Muscle biopsy showed eosinophil-associated vascular occlusion and eosinophilassociated tissue damage. The investigation excluded renal, cardiac, pulmonary and gastro-intestinal involvement. A steroid therapy (Prednisone 1 mg/kg/die) was started with clinical improvement. Conclusions: EGPA is a multisystemic disorder, typically suspected based on a combination of clinical findings, such as asthma, nasal and sinus symptoms, peripheral neuropathy, and eosinophilia ≥1500/microL. ANCA antibodies are positive in around 40% of patients and diagnosis can often be challenging and delayed.

ISCHEMIC STROKE IN COVID-19 PATIENTS: SINGLE CENTER, ONE YEAR EXPERIENCE

INTRODUCTION: The clinical presentation of COVID-19 varies greatly. Even though, disease cause predominantly respiratory manifestations, because of the inflammatory nature of the disease, it also triggers thromboembolic conditions. We aim to describe the features of COVID-19 positive ischemic stroke patients of 1-year experiences of a single center. METHODS: A total of 258 patients, diagnosed with ischemic cerebrovascular disease (25 patients of with strokes had respiratory symptoms at initial presentation and COVID-19 diagnosis), were evaluated retrospectively during the study period. RESULTS: A majority of these patients strokes were in anterior circulation territory and most of them were large vessel occlusion. Eighteen of the patients had positive COVID-19 RT-PCR results, while 7 of the patients had negative results but their thorax CTs made the diagnosis of COVID-19. Hypertension (56%), diabetes (44%), and atrial fibrillation (44%) were the most comorbidities. Thirteen patients stroke etiology was cardioembolism, 9 had atherosclerosis. Fourteen of the patients NIHSS were >10, and 13 of them died. Patients with high levels of CRP (13/25), D-Dimer (15/25) and Ferritin (14/25) had mRS>3 at admission. Most of the patients (19/25) had CO-RADS 5 scores at admission. Two patients had mRS 4-5, 9 patients had mRS 0-3 at the discharge period. Fourteen patients died at the hospital period. DISCUSSION AND CONCLUSION: The admission NIHSS scores determined significantly the prognosis. Moreover, higher age, women gender, LVO in neuroimagining, high CRP, Ferritin, D-dimer levels, COVID-19 RT-PCR positivity, presence of hypertension and atrial fibrillation comorbidities showed poor outcome.

Endovascular Thrombectomy for Large Vessel Occlusions in Covid-19 Patients: Technical Challenges and Lessons

INTRODUCTION: Covid 19 infections has been shown to be associated with a range of thromboembolic disease that has implications for the neuro-endovascular management of large vessel occlusions. METHODS: Five consecutive Covid-19 positive patients presented with large vessel occlusions to our institution. Covid-19 testing was performed using nasal swab. All thrombectomy cases was performed under general endotracheal anesthesia using a stent-aspiration combination as primary thrombectomy technique. The technical details of each case and the angiographic outcome are described. Routine labs including D-dimer, platelet count, coagulation panel (aPTT, INR), Interleukin 6 (IL-6), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) were evaluated in all patients. Rotational thrombelastography (ROTEM) was performed on the patients' blood samples to assess real-time clot formation/dissolution properties. RESULTS: Four patients had anterior circulation large vessel occlusions and one patient had both anterior and posterior circulation occlusions. Mean age was 52.8 years and 80% were males. TICI 3 revascularization was achieved in one patient, TICI 2B achieved in two patients and TICI 2A in two patients. In our cohort, patients were on average 52.8 years old and presented with a median NIHSS of 27. All our patients had very proximal occlusions. Three patients presented with intra-cranial ICA occlusions. Two patients presented with a tandem carotid bulb thrombus in conjunction with an intracranial vessel occlusion. One patient had an ICA terminus occlusion with a concomitant basilar occlusion. Second, the intravascular clots in all our patients were prone to fragment and migrate into both new vascular territories and into distal downstream vasculature. Distal emboli into a different territory (anterior cerebral artery occlusion) was seen in two two of our five patients (40%) and distal emboli into a downstream territory was seen in all five patients (100%). An average of 2.7 pstent-retriever passes was needed to achieve a final TICI revascularization of IIb or better. CONCLUSION: Covid-19 patients are predisposed to a hypercoagulable state. When presenting with large vessel occlusions, these patients present unique challenges that make successful revascularization difficult.