Anaesthetic Management for A Patient Presenting for Caesarean Delivery with A giant Thymoma - A Case Report

Presentation of a thymoma during pregnancy means that safe delivery becomes more challenging. We present a 33-year-old pregnant woman who was diagnosed with a large thymoma causing marked compression of the tracheobronchial tree and right atrium. After various multidisciplinary meetings she presented for elective caesarean section delivery at 31 weeks of gestation. A combined spinal-epidural anaesthesia was performed, along with colloid pre-and co-loading, and vasopressor support. The delivery was uneventful. The possibility of catastrophic complications was foreseen. Therefore, all requirements for the possibility of airway or haemodynamic collapse were planned carefully, including the possibility of emergent cardiopulmonary bypass.Copyright © 2023, College of Anaesthesiologists of Sri Lanka. All rights reserved.

Myasthenia gravis with achalasia secondary to thymoma: a case report and literature review.

Background: Myasthenia gravis is an autoimmune neuromuscular junction disorder characterized by fatigable muscle weakness and autoantibodies. Frequent associations exist between myasthenia gravis and thymic abnormalities, including hyperplasia and thymoma. Several autoimmune illnesses have been identified to be associated with thymoma; however, a few case reports have linked thymoma and achalasia, and the underlying mechanism is unknown. Case report: A 43-year-old man with thymoma-associated myasthenia gravis presented with dysphagia that was refractory to conventional treatment of myasthenia gravis. This dysphagia was challenging to diagnose even after multiple gastroenterology consults and upper endoscopy. The diagnosis of achalasia type II was established after a comprehensive evaluation, including upper endoscopy, barium swallow, and high-resolution esophageal manometry. The patient underwent elective pneumatic balloon dilatation, which successfully alleviated his dysphagia. Conclusion: This case confirmed the association between myasthenia gravis secondary to thymoma and achalasia and showed how the diagnosis of achalasia was challenging. Awareness of this association is crucial for early diagnosis and treatment, improving affected patients' quality of life.

Ndegree35 - Neurophysiology solving the vomiting dilemma

Objectives: Post Covid severe vomiting together with proximal muscle weakness is a misleading combination, this describes a rare but definite clinical association between myasthenia gravis and autonomic failure and strengthen the concept that subacute autonomic neuropathy is an autoimmune disorder. Content: A 39 ys old adult female presented with postCovid severe vomiting for one year with 40 kgs loss Upper gastrointestinal endoscopy revealed gastric dilatation associated with eosophageal and gastric stasis and hypertrophic pyloric stenosis. the gastroenterologist sought neurological consultation for the coexisting unexplained limb weakness before operation EMG & NCV was all normal except instability of the MUAPs Slow rate Repetitive supramaximal stimulation (RNS) revealed significant decremental response with no significant high rate stimulation incrementation Chest CT revealed an anterior mediastinal mass Surprisingly, She had an old CT during the covid infection that showed the same mass. Thoracoscopic resection revealed type B1 thymoma Following tumor resection, the patient improved gradually, Few months later endoscopy revealed a normal stomach with strong peristaltic waves and the patient was symptom free Infections are recognized to trigger exacerbations and crisis in MG Dysautonomia is not a commonly recognized feature of myasthenia gravis, but there have been rare reports of myasthenia gravis coexisting with autonomic failure, usually in association with thymoma. The autonomic dysfunction can present as isolated gastroparesis these observations support a rare but definite clinical association between myasthenia gravis and autonomic failure Neurophysiology could reveal undiagnosed MG with thymoma causing autonomic dysfunction in the form of gastroparesis and agonizing vomiting. Keywords: Myasthenia gravis;Gastroparesis;Autonomic failure;Thymoma;PostCovid vomiting. French language not detected for EMBFRA articles source xmlCopyright © 2023

An unexpected diagnosis: Good's syndrome

Case report Introduction: Good's syndrome (GS) represents an acquired adult-onset immunodeficiency associated with thymoma. GS affects patients over 40 yrs in form of recurrent infections especially with encapsulated bacteria, opportunistic viral and fungal invasions as a result of combined T/B cell deficiency. The imbalanced immunity may also provoke autoimmune phenomena and tumorigenesis. Case report: We present a 40-year- old male with a newly onset of dull thoracic pain and with no history of previous diseases. Chest CT revealed an anterior mediastinal mass in 2021, without lympadenopathy. A CT-guided core biopsy was suggestive for malignant thymoma, so the patient underwent total thymectomy. Histology indicated a thymoma of the AB type (WHO), and stage I. (Masaoka-Koga);(pT1a pNo). After surgery he was readmitted due to recurrent febrile respiratory tract infections, caused by Gram (-) bacteria or fungi;combination therapy of antibiotics and antifungal drugs was used. With suspicion of GS we determined immunoglobulin levels and the distribution of peripheral lymphocyte subsets. Hypogammaglobulinemia (IgG/A/M), and by flow cytometry markedly reduced peripheral B cells, and an inverse ratio of CD4+/CD8+ T cells were detected, confirming the diagnosis. Blast transformation assay indicated decreased T cell proliferation. Thus, following thymectomy, the patient exhibited severe T/B cell alterations with subsequent recurrent infections. Detailed autoantibody and complement analyses indicated no autoimmune laboratory abnormalities so far. There are still no effective protocols for GS therapy, except of antibiotic prophylaxis, preventive vaccination, and regular immunoglobulin replacement, so IVIG was introduced. As part of the follow-up repeated CT indicated no thymoma recurrence or metastasis. In December 2021 the vaccination refusing patient survived a severe bilateral organizing pneumonia secondary to SARS-CoV2. Conclusion(s): Incidence of the thymic epithelial tumor, thymoma is 0.15-0.33 cases/100.000/year. Depending on histology it could be linked to various immunological abnormalities. Appr. 0.2%-6% of thymomas corresponds to GS. GS, with a still elusive pathogenesis is considered as an uncommon combined immunodeficiency of adults with a variable phenotype and certain similarities to CVID. The prevalence is estimated appr. as 1/500.000. Combination of the high infection susceptibility and concomitant autoimmune diseases could make the diagnosis a challenging task.

Covid-19 vaccines elicit effective IgG responses in an elderly thymus cancer patient with chemotherapy.

The rising need for repeated booster vaccinations against SARS-CoV-2 infections raises the question of whether chronic immunosuppressive chemotherapies influence the efficacy of vaccination. Here, we present the case of a 70-year-old post-thymoma surgery patient who received Vepesid (etoposide, Xediton Pharmaceuticals Inc) chemotherapy for six months before vaccination with Comirnaty (Pfizer-BioNTech COVID-19 mRNA Vaccine). The first two vaccinations elicited only minimal increases of IgG antibodies specific against the receptor-binding domain (RBD) on the spike protein (S1), while the third vaccination was effective in providing high, slowly subsiding antibody titers over a 7-month period. The patient also developed a cellular immune response after the third vaccination. Also, measuring of anti-polyethylene glycol (PEG) IgM titers before and after vaccinations showed no immunogenicity for PEG. Later, a single dose of Sinopharm (China National Pharmaceutical Group) inactivated virus-type vaccine was administered, which also modestly increased the level of IgG. A symptomless COVID-19 infection, however, greatly increased the serum level of anti-RBD IgG, which later subsided. This case confirms that an effective immune response can be achieved with a series of COVID-19 vaccinations despite cytostatic treatment in an old thymus cancer surviving patient in the absence of adverse reactions.

Diagnosis and management of thymomas in the Covid-19era

Introduction and Aims: Thymoma is a rare but the commonest primary malignancy of the anterior mediastinum(35%), with an annual incidence around 3 per million population (Girard et al. Annals of Oncology 2015;26:v40-55).Standard first line imaging is CT thorax with contrast. During the Covid-19 era more CTs were performed. Weevaluated whether this affected the diagnosis and management of thymomas in a UK district general hospital. Method(s): We included CT scan reports from 1 January 2019 to 31 December 2021 with the terms 'thymoma','thymic' and 'thymus' (n=171). Non-diagnoses and existing diagnoses of thymomas were excluded. Data wascollected on patient demographics, presenting symptoms, scan circumstances, size of mass, further investigationsand staging. Result(s): We identified 21 potential diagnoses of thymoma, ages ranging from 14 to 89 years. Half were male and71% Caucasian. Commonest presenting symptoms were shortness of breath and cough (33%). 3 scans wereperformed as part of Covid management. 7 patients underwent a biopsy, of whom 4 had histology-confirmedthymoma (Table 1). Discussion(s): Results highlight that despite frequent mentions of mediastinal abnormalities in CT reports, few are investigated. Only 57% of those biopsied were diagnosed with thymoma, likely representing underdiagnosis. In addition, the increased number of CTs performed during the Covid pandemic did not result in more diagnoses of thymoma.

Landscape Analysis of Quercetin: A Potential Candidate Against SARS-CoV-2

Fruit, vegetables, and green tea contain quercetin (a flavonoid). Some of the diet's most signifi-cant sources of quercetin are apples, onions, tomatoes, broccoli, and green tea. Antioxidant, anticancer, anti-inflammatory, antimicrobial, antibacterial, and anti-viral effects have been studied of quercetin. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, ribonucleic acid (RNA) polymer-ase, and other essential viral life-cycle enzymes are all prevented from entering the body by quercetin. Despite extensive in vitro and in vivo investigations on the immune-modulating effects of quercetin and vitamin C treatment. 3-methyl-quercetin has been shown to bind to essential proteins necessary to convert minus-strand RNA into positive-strand RNAs, preventing the replication of viral RNA in the cytoplasm. Quercetin has been identified as a potential SARS-CoV-2 3C-like protease (3CLpro) suppressor in recent molecular docking studies and in silico assessment of herbal medicines. It has been demonstrated that quercetin increases the expression of heme oxygenase-1 through the nuclear factor erythroid-related factor 2 (Nrf2) signal network. Inhibition of heme oxygenase-1 may increase bilirubin synthesis, an endoge-nous antioxidant that defends cells. When human gingival fibroblast (HGF) cells were exposed to lipo-polysaccharide (LPS), inflammatory cytokine production was inhibited. The magnesium (Mg+2) cation complexation improves quercetin free radical scavenging capacity, preventing oxidant loss and cell death. The main objective of this paper is to provide an overview of the pharmacological effects of quercetin, its protective role against SARS-CoV-2 infection, and any potential molecular processes.Copyright © 2022 Bentham Science Publishers.

COVID-19-associated AMPA-R and CRMP-5 autoimmune encephalitis in a patient with thymoma and myasthenia gravis.

Thymomas are associated with autoimmune disease, most commonly myasthenia gravis, and rarely with autoimmune encephalitis. More recently, viral triggers including COVID-19 have also been implicated in autoimmunity. We present a case of antibody-positive autoimmune encephalitis that developed in the setting of COVID-19 in a patient with thymomatous myasthenia gravis.

Incidental giant thymoma-a reminder of the importance of a global look of the imaging scans.

A 49-year-old female patient, without previous medical history, underwent a thoracic CT due to SARS-CoV2 infection. This exam revealed a heterogeneous mass in the anterior mediastinum with 11 × 8.8 cm in close contact with main thoracic vessels and pericardium. Surgical biopsy documented a B2 thymoma. This clinical case reminds the importance of a systematic and global look of the imaging scans. Years before the thymoma diagnosis, the patient underwent a shoulder X-ray due to musculoskeletal pain, where an irregular shape of the aortic arch was visible, probably related to the growing mediastinal mass. An earlier diagnosis would allow a complete mass resection without such extensive surgery and less morbidity.

Good's syndrome and COVID-19: case report and literature review.

Background: Good's syndrome (GS) is an adult-onset acquired immunodeficiency, in which patients present with thymoma and hypogammaglobulinemia (HGG). GS is characterized by low to absent peripheral B cells and impaired T-cell mediated immunity, often resulting in various (opportunistic) infections and concurrent autoimmune disorders. In this case report, we present a case of a patient with GS and coronavirus disease 2019 (COVID-19) infection after surgical removal of a thymoma. The simultaneous occurence of these two entities is extremely rare. Case Description: A 55-year-old man presented with oral lichen planus and cutaneous lesions. Additional symptoms included a weight loss of 5 kilograms in the last six months. Computed tomography (CT) and positron emission tomography (PET) of the chest showed a large anterior mediastinal mass with a maximum diameter of 10 centimetres. A core needle biopsy was performed, which led to a pathological diagnosis of thymoma type AB. In addition to these earlier findings, laboratory analysis revealed HGG. The combination of a thymoma and HGG led to a diagnosis of GS. Induction chemotherapy with cisplatin-etoposide was started, however, the patient developed COVID-19 after 2 cycles. Treatment with remdesivir was initiated and, subsequently, a thymectomy via sternotomy was performed. Final pathology confirmed a thymoma type AB of 14 centimetres, fully encapsulated, and without invasion. Resection margins were negative and the tumour was classified as pT1aN0, R0 resection. The patient has received immunoglobulin treatments every 4 weeks for his GS and has not developed any new infections since the start of this therapy. Conclusions: Patients with GS are prone to developing (pulmonary) infections. Clinicians should be aware of the possible clinical effects of COVID-19 infections in this patient population.

Thymoma and Myasthenia Gravis: An Examination of a Paraneoplastic Manifestation.

Thymoma is a rare type of malignancy but is considered one of the most common neoplasms that occur in the anterior mediastinum. A large proportion of thymomas are associated with paraneoplastic syndromes, such as myasthenia gravis. Whenever feasible, the standard of care for the treatment of thymoma should focus on the control of paraneoplastic syndromes, surgical resection, and adjuvant therapy if appropriate. A 36-year-old female patient with a significant past medical history of obesity and iron deficiency anemia who underwenten bloc resection of thymoma three months prior now presented to the benign hematology clinic to establish care for the management of anemia. Upon review of systems, the patient incidentally reported fatigue, weakness with repetitive motion, occasional blurred vision, headaches, and exertional dyspnea. Physical examination was positive for horizontal nystagmus. Given the patient's history and clinical findings, suspicion of myasthenia gravis was high. Further work-up demonstrated anti-acetylcholine receptor titers of 5.70 nmol/L (normal < 0.21 nmol/L), supporting a diagnosis of myasthenia gravis in this patient. She was subsequently started on pyridostigmine. Often, patients with thymoma experience paraneoplastic syndrome-related symptoms prior to thymectomy, and in many cases thymectomy is curative. However, in the case presented, we examine a patient that was asymptomatic prior to surgery and subsequently reported the onset of symptoms following what we suspect was an exacerbation due to general anesthesia and pain control medications. We argue that all patients with thymoma should undergo systematic evaluation and treatment of paraneoplastic syndromes, regardless of clinical symptoms and prior to surgery, in order to improve patient quality of life and hospital outcomes.

Autoimmune hemolytic anemia following SARS-COV- 2 vaccine in SLE nephritis with coexistent thymoma, complicated by severe COVID-19 infection

Background: We report a 40-year- old female with co-existent lupus nephritis and thymoma who developed severe lupus flare (worsening nephritis, new onset hemolytic anemia) following SARS-CoV- 2 vaccine. Case: This 40 year old female has had stable lupus nephritis (LN) while maintained on mycophenolate mofetil and hydroxychloroquine for several years. A co-existent thymoma was likewise stable and did not require any added therapy apart from the management of the LN. She received the first dose of inactivated vaccine for SARS-CoV- 2 without event. Two weeks following the second dose, she developed Coombs positive hemolytic anemia (hemoglobin 64 g/L) with leukopenia (WBC 2.3 x 109/L), worsening nephritis (3+ proteinuria with uPCR 1.0, active urine sediments), hypocomplementemia, and elevated anti-dsDNA. She received methylprednisolone pulse therapy then maintained on prednisone 40mg/day with clinical improvement. Two weeks thereafter, she was admitted due to severe COVID-19 pneumonia accompanied by severe anemia requiring blood transfusion;she received a regimen of bevacizumab, dexamethasone, and remdesivir and was discharged recovered, without overt sequelae at the time of this report. Discussion(s): Vaccines are highly effective in reducing hospitalization and death attributable to SARS-CoV- 2 infection. There are concerns however regarding autoimmune disease flares following SARS-CoV- 2 vaccine, reported to occur in about 4% patients with autoimmune disorders. It is also possible that this patient's reaction may have been further aggravated by the co-existent thymoma. While there was apparent sub-optimal protection of the vaccine against moderate to severe COVID-19 infection in this patient, it may be conjectured that her significant recovery and response to the anti-viral combined with immunosuppressive regimen may be due to the high dose steroid treatment given for the post-vaccine autoimmune reaction.

Cardiac tamponade as the first presentation of thymoma: A case report during COVID-19 pandemic

We report a case of neoplastic cardiac tamponade, a life-threatening condition, as the initial presentation of an anterior mediastinal malignancy. A 69-year-old gentleman with no known history of malignancy presented to the emergency department with shortness of breath, reduced effort tolerance and chronic cough. Clinically, he was not in distress but tachycardic. He was subjected to echocardiography which revealed large pericardial effusion with tamponade effect. Pericardiocentesis drained 1.5 L of haemoserous fluid. CECT thorax, abdomen and pelvis revealed an anterior mediastinal mass with intrathoracic extension complicated with mass effect onto the right atrium and mediastinal vessels. Ultrasound-guided biopsy histopathology examination revealed thymoma. Due to locally advanced disease, tumour resection was not possible, and patient was referred to oncology team for chemoradiotherapy. We report this case study not only due to the rarity of the case but also to highlight its diagnostic challenge due to the COVID-19 pandemic. Copyright © The Author(s) 2022.

Antibody Responses to the SARS-CoV-2 Vaccine in Individuals With Inborn Errors of Immunity

PURPOSE OF THE STUDY: To evaluate the impact of genetic diagnosis and treatment on antibody response to coronavirus disease 2019 (COVID-19) vaccine and related adverse effects in patients with inborn errors of immunity (IEI). STUDY POPULATION: Eighty-one patients with IEI (ages 13–71), 2 adults with thymoma and a control group consisting of 22 health care workers (HCWs) without histories of COVID-19 infection. METHODS: This was a longitudinal study of SARS-CoV-2 specific antispike (anti-S) and antinucleocapsid (anti-N) antibody levels in study subjects as compared with the control group. All subjects received SARS-CoV-2 immunizations between December 2020 and May 2021. Preimmunization anti-S and anti-N IgG levels were obtained in all the HCWs and 32 of 83 patients. For the study group, information on diagnosis, demographic data, history of COVID infection, type of vaccine received, interval between vaccine schedule completion (2 doses of messenger RNA [mRNA] vaccine or 1 dose of adenovirus vector vaccine) and sample collection, immunoglobulin replacement therapy, and use of immunomodulatory or immunosuppressive drugs were collected. RESULTS: Serology was obtained after completion of the recommended vaccine schedules for all the HCWs and 74 of 83 patients with immunodeficiency. Nine with IEI received just 1 dose of an mRNA vaccine and has serology obtained. All HCWs developed anti-S IgG after the first dose of vaccine with a broad range of response and 21 of 22 (95%, 95% confidence interval = 81.5% to 100%) had high levels after the second dose. The 1 exception was a HCW who 6 months earlier had received steroids and rituximab (a B-cell depleting monoclonal antibody) for antineutrophil cytoplasmic antibodies–positive granulomatous vasculitis. Of the immune deficient patients, 27 of 46 (58.7%) had positive anti-S IgG after 1 dose and 63 of 74 (85.4%, 95% confidence interval = 74.5% to 92%) after 2 doses of mRNA vaccines, a rate comparable to the HCWs. After 1 dose, the levels of anti-S IgG between groups approached but did not quite reach statistical significance (P = .06). In contrast, after 2 doses patients with IEI had lower levels than the HCWs (geometric mean = 611 938 light units vs 2 403 642 LU;P = .004). Some subgroups of patients IEI were less likely to have robust anti-S IgG response to immunization. Patients on rituximab, those with CD3+ (T lymphocyte) counts <1000/mL, and CD19+ (B lymphocyte) counts <100/mL had lower responses than those who did not meet those criteria. Most patients on immunoglobulin replacement therapy developed protective anti-S IgG levels after immunization. Adverse events of injection site redness, pain, and swelling and systemic symptoms were reported more commonly in patients with IEI than HCWs and more often after the second dose (local reactions: 66.7% vs 27.3%;systemic reactions: 52.9 vs 36.4% after the second dose). None of the systemic reactions were severe. CONCLUSIONS: COVID-19 immunization is safe and effective in patients with IEI. Some subsets of patients with IEI may not develop anti-S IgG levels after immunization.

CHEST-WALL CASTLEMAN DISEASE MIMICKING THYMOMA DROP METASTASIS

SESSION TITLE: Amazing Chest Imaging Findings SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm INTRODUCTION: Thoracic Castleman disease is challenging to diagnose and can mimic various lymphoproliferative disorders. Herein we present a case of unicentric thoracic castleman disease co-existing with thymoma, mimicking a thymoma drop metastasis. CASE PRESENTATION: A 50-year-old previously healthy Caucasian female presented to the emergency room with COVID-19 related respiratory symptoms. CTA was consistent with COVID-19 pneumonia and incidentally showed a 4.2 x 3.1 cm mass in the right anterosuperior mediastinum abutting the ascending aorta and superior right atrium, and a 3.3 x 2.1 cm mass in right posterior costophrenic sulcus abutting the right 11th rib raising suspicion for thymoma with a "drop metastases.” CT abdomen/pelvis was unrevealing. For proper staging, US guided biopsy of chest wall mass was performed which showed reactive lymphoid tissue. CT guided biopsy of the mediastinal mass revealed a thymoma. Due to ongoing concern for pleural metastases and possible sampling error with prior biopsy of the costophrenic lesion, she underwent surgical resection of the anterior mediastinal mass and chest wall lesion including part of 11th rib. The chest wall lesion was noted to be extrapleural. Surgical biopsy confirmed WHO grade B1 Thymoma and the chest wall lesion showed hyaline vascular Castleman disease. DISCUSSION: Pleural "Drop” metastasis from a thymoma or thymic carcinoma should be considered in patients with an anterior mediastinal mass and pleural based lesions. Imaging shows one or more pleural nodules or masses, which can be smooth, nodular, or diffuse. [1]. In our case, a basilar, discrete, nodular mass was suspicious for a drop metastasis. At the time of surgery, the lesion was noted to be extrapleural. Unicentric Castleman disease is a benign lymphoproliferative disorder which presents as a homogeneous, well-marginated, highly vascularized enhancing mass commonly involving the mediastinum. These lesions can mimic thymoma, lymphoma, sarcoma, hemangiopericytoma, and neural crest derived neoplasms. Pleural Castleman disease can arise from visceral and parietal pleura with extension into the chest wall or lung fissures and can cause pleural effusion. Intercostal disease can resemble other chest wall masses and cause rib erosions [2]. Chest-wall localization is a rare manifestation of Castleman disease often diagnosed due to non-specific thoracic symptoms such as dyspnea, cough, chest-wall pain or generalized malaise.[3] Complete excision of the lesion is generally curative with cure rate of 95-100%, with recurrence reported with partially resected lesions. CONCLUSIONS: Castleman disease located in the chest wall can present diagnostic and management challenges particularly when present in the context of other lesion with metastatic potential. Reference #1: 1.Benveniste, M.F.K., Rosado-de-Christenson, M.L., Sabloff, B.S., Moran, C.A., Swisher, S.G. and Marom, E.M. (2011). Role of Imaging in the Diagnosis, Staging, and Treatment of Thymoma. RadioGraphics, 31(7), pp.1847–1861. Reference #2: 2.Ko, S.-F., Hsieh, M.-J., Ng, S.-H., Lin, J.-W., Wan, Y.-L., Lee, T.-Y., Chen, W.-J. and Chen, M.-C. (2004). Imaging Spectrum of Castleman's Disease. American Journal of Roentgenology, 182(3), pp.769–775 Reference #3: 3. Rena, O., Casadio, C. and Maggi, G. (2001). Castleman's disease: unusual intrathoracic localization. European Journal of Cardio-Thoracic Surgery, 19(4), pp.519–521. DISCLOSURES: No relevant relationships by Peter LaCamera, value=Consulting fee Removed 04/06/2022 by Peter LaCamera No relevant relationships by Peter LaCamera, value=Consulting fee Removed 04/06/2022 by Peter LaCamera No relevant relationships by Alina Wasim

SEROPOSITIVE MYASTHENIA GRAVIS AS THE CAUSE OF MULTIPLE FAILED EXTUBATIONS AND A PROLONGED ICU STAY FOR COVID-19 PNEUMONIA: A CASE REPORT AND BRIEF LITERATURE REVIEW

SESSION TITLE: Autoimmune Disorders: Both Primary and Secondary SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Neurologic sequelae of COVID infection appear to be common. The infection may present with neurologic symptoms, unmask neurologic disease, or worsen established disease. Myasthenia gravis (MG) is an autoimmune neuromuscular disease (NMD) that does not appear to be a usual COVID sequela. We present an elderly veteran with COVID pneumonia who struggled to wean from mechanical ventilation (MV) secondary to neuromuscular weakness. He was ultimately diagnosed with seropositive MG. CASE PRESENTATION: A 79 year old male with a history of prior COVID infection complicated by need for mechanical ventilation (MV) complained of progressive cough and shortness of breath. He was admitted for treatment of community-acquired pneumonia. On hospital day 8, he developed respiratory failure, was intubated, and was transferred to the intensive care unit (ICU). He was diagnosed with COVID a second time. After antibiotics and supportive treatment, he successfully completed a spontaneous breathing trial and was extubated. Within 24 hours, he developed hypercapnia, necessitating reintubation. Given his need for repeat intubations, we ordered myositis titers and MG autoantibodies. After a fourth failed extubation, a tracheostomy was placed. On hospital day 32, his acetylcholine receptor binding antibody returned positive at 30.0, suggesting seropositive MG. His MG composite score was 11 (for ptosis and ventilator dependence). For further work-up, a CT chest excluded thymoma;a focused neurological exam was limited by sedation, and inpatient electrodiagnostics were not feasible. He received 5 days of intravenous immune globulin (40 mg), a Prednisone taper, and Rivastigmine 60 mg thrice daily. His symptoms improved and he was transferred to the floor. DISCUSSION: It is well established that coronaviruses exhibit neurotropism. However, it is unclear whether the novel coronavirus SARS-CoV-2 unmasks underlying neurologic illness or creates de novo disease. Critical care physicians are often tasked with making an initial diagnosis of neuromuscular disease (NMD). NMD is a known cause of complicated extubations. When the diaphragm and accessory respiratory muscles fatigue, respiratory decompensation ensues as full MV support is removed. In many cases, underlying illness is unmasked during this process of extubation. In our case, it is unknown whether infectious insult led to molecular mimicry and development of autoantibodies or unmasked latent neuromuscular disease. If the infection did cause his disease, it would be one of the first cases of COVID-associated MG to be published. Our case is a reminder that NMD is a secondary cause of extubation failure and may suggest MG as a cause of MV weaning failure secondary to COVID. CONCLUSIONS: Critical care physicians should be aware of this potential neuromuscular complication of COVID infection as it may complicate MV weaning, increase vent days, and prolong ICU stays. Reference #1: Collantes MEV, Espiritu AI, Sy MCC, Anlacan VMM, Jamora RDG. Neurological manifestations in covid-19 infection: A systematic review and meta-analysis. Can J Neurol Sci. 2021 Jan;48(1):66-76. Doi: 10.1017/cjn.2020.146. Epub 2020 Jul 15. PMID: 32665054. Reference #2: Huber M, Rogozinski S, Puppe W, Framme C, Hoglinger G, Hufendiek K, Wegner F. Postinfectious onset of myasthenia gravis in a COVID-19 patient. Front Neurol. 2020 Oct 6;11:576153. Doi: 10.3389/fneur.2020.576153. eCollection 2020. PMID: 33123081. Reference #3: Muralidhar Reddy Y, B SK, Osman S, Murthy JMK. Temporal association between SARS-CoV-2 and new-onset myasthenia gravis: Is it causal or coincidental? BMJ Case Rep. 2021 Jul 21;14(7):e244146. Doi: 10.1136/bcr-2021-244146. PMID: 34290032. DISCLOSURES: No relevant relationships by Jeffrey Li No relevant relationships by Anupa Nadkarni No relevant relationships by Justin Owens No relevant relationships by Jennifer Perry no disclosure on file for Hayley Sp res;

COMMON PRESENTATION WITH AN UNCOMMON ETIOLOGY: THYMOMA-ASSOCIATED AUTOIMMUNE ENCEPHALITIS INDUCED BY COVID-19 BOOSTER VACCINE

SESSION TITLE: Issues After COVID-19 Vaccination Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Thymoma-associated autoimmune encephalitis (TAAE) is an understudied and overlooked diagnosis in patients presenting with abrupt altered mental status. Described as inflammation of brain tissue, autoimmune encephalitis is seen in 5-10 cases per 100,000 across all age groups per year. A rare subtype involves neuronal surface antibodies to alpha-amino-3-hydroxyl-5-methyl-4isoxazolepropionic acid receptors (AMPA-R) encephalitis is seen even less commonly. Given the "unicorn” nature of presenting cases and difficulty of diagnosis, prompt identification and treatment are critical as prolonged courses without treatment are irreversible and deadly. CASE PRESENTATION: A 47-year-old male with no past medical history presented 3 days after a Johnson & Johnson coronavirus-2019 (COVID-19) booster vaccine due to worsening acute altered mental status over the past week. He complained of episodes of fever & chills prior to this. The patient's wife reported abrupt changes in memory and personality. Upon admission, the patient had a Glasgow Coma Scale of 4. The patient was intubated and transferred to the intensive care unit. Intravenous (IV) vancomycin, ceftriaxone and acyclovir was initiated for meningitis. Computed tomography (CT) scan of the head without contrast was unremarkable. Magnetic resonance imaging (MRI) showed enhancements of the right anterior and medial temporal lobe suggesting encephalitis. Cerebrospinal fluid analysis (CSF) revealed lymphocytic pleocytosis. A CT scan of the chest, abdomen and pelvis showed an anterior mediastinal mass measured 1.8 x 2.3 cm (Figure 1). FilmArray Meningitis polymerase chain reaction was negative as well as Herpes Simplex Virus (HSV) 1 and 2. Autoimmune encephalitis antibody was positive for Anti-AMPAR. Pulse dose steroids and intravenous immunoglobulin were initiated but failed. Rituximab was initiated and cardiothoracic surgery completed a thymectomy. DISCUSSION: TAAE is a rare disease, permanently debilitating, and deadly if unrecognized or treatment is delayed. Autoimmune encephalitis is an umbrella disease process seen in 0.00005% of patients per year. AMPA-R positive encephalitis is even less commonly seen with only 22 cases reported between the years 2009 and 2014 [1]. A rapidly progressive cognitive decline or psychiatric disorders are early features of this disease.Our patient had prodromal symptoms of fever and cognitive decline days after receiving his COVID-19 booster vaccine. CONCLUSIONS: Post-vaccine encephalomyelitis has been described in other settings[2]. This patient was free of symptoms prior to the COVID-19 vaccine booster, and demonstrated altered mental status hours after receiving it. This furthers the possibility of an association of the COVID-19 booster vaccine, development of encephalitis, and in this case a thymoma. Despite this, conclusions can not be made on the account of one report, but introduces a new area of focus to study. Reference #1: Höftberger, R., van Sonderen, A., Leypoldt, F., Houghton, D., Geschwind, M., Gelfand, J., Paredes, M., Sabater, L., Saiz, A., Titulaer, M. J., Graus, F., & Dalmau, J. (2015). Encephalitis and AMPA receptor antibodies: Novel findings in a case series of 22 patients. Neurology, 84(24), 2403–2412. https://doi.org/10.1212/WNL.0000000000001682 Reference #2: Huynh, W., Cordato, D. J., Kehdi, E., Masters, L. T., & Dedousis, C. (2008). Post-vaccination encephalomyelitis: literature review and illustrative case. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 15(12), 1315–1322. https://doi.org/10.1016/j.jocn.2008.05.002 DISCLOSURES: No relevant relationships by Matthew Frank No relevant relationships by Justin Ilagan No relevant relationships by Danielle Mahon No relevant relationships by Danielle Mahon No relevant relationships by Harshini Sahani No relevant relationships by Kameron Tavakolian No relevant relationship by Ndausung Udongwo

Myasthenic Crisis

Myasthenia gravis (MG) is an acquired autoimmune disorder of the neuromuscular junction, caused by antibodies that target the post-synaptic membrane. These antibodies most commonly bind to the nicotinic acetylcholine receptor (AChR), but in a smaller proportion of cases, antibodies to muscle specific tyrosine kinase (MuSK)(1-10%) or to lipoprotein receptor-related protein 4 (Lrp-4)(1-3%) can be present instead. These antibodies act on the receptors, prevent neuromuscular transmission and induce weakness of skeletal muscles. In 10-15% of MG patients, no antibodies are detected and these patients are designated as seronegative. Weakness can be generalized or localized, is usually more proximal than distal, and nearly always includes eye muscles, causing diplopia and/or ptosis. The pattern of involvement is usually symmetric, except for the eye involvement, which is mostly markedly asymmetric. The muscle weakness typically increases with exercise and repetitive muscle use (fatigue) and varies over the course of a day and from day to day. Patients commonly present first with ocular manifestations, however, the majority develop generalized muscle weakness, involving the facial and bulbar muscles (dysarthria, dysphagia), the limbs, the neck and axial muscles (dropped head, bent spine), and in severe cases the diaphragmatic and intercostal muscles. MuSK-MG predominantly appears in women, who show weakness in mostly cranial and bulbar muscles, commonly with an acute onset and a tendency to rapid progression in comparison to AchRMG. Myasthenic crisis (MC), the severe end of the disease spectrum, can occur at any age and is potentially life-threatening. This is a clinical emergency that requires management in an intensive care setting. MC is mostly provoked by infections or inadequate treatment. In 15-40% of the reported patients with COVID-19 infection a MC occurred. MC appears in around 15-20% of MG patients in the first 2 years after diagnosis. MC can be the first manifestation of MG. Up to a half of MuSK-MG patients develop a MC in their disease course and it is also common in patients with thymoma-associated disease, or AChR-positive late-onset disease;after surgery (including thymectomy);during or after childbirth;in patients taking a contraindicated medication;at the start of corticosteroid treatment or during the tapering of immunosuppression. In approximately 20% the cause of an exacerbation remains unknown. Characteristic symptoms for the impending MC include rapidly progressive muscle weakness, 'inverse aspiration', dysphagia with choking, and dyspnoea associated with orthopnoea and/or tachypnoea which can result in respiratory insufficiency. The clinical management of MC with mechanical ventilation, extended intensive care management and intravenous immunoglobulins (IVIg) or plasmapheresis (PLEX) or in case of persistent MC escalation with rituximab has led to a significant decline in mortality from around 40% in the early 1960s to 5-22% in recent studies with negative prognostic factors including older age at onset, prolonged intubation, and associated comorbidities. At present IVIg and PLEX are considered the gold standard treating MC. However, it may be conceiv- able that newly developed monoclonal antibody therapy (eculizumab, efgartigimod), could be used as rescue therapy to achieve a significant and rapid clinical improvement.

Surgery for Stage IVA Metastatic Thymoma Found Incidentally Post-COVID-19

Background: Thymic epithelial tumours (TET) are rare thoracic cancers with reported annual incidence of 1.3-3.2 per million. TETs are histologically classified as thymomas or thymic carcinomas. Thymomas are slow-growing tumours that comprise the majority of lesions found in the anterior mediastinum. They can be associated with autoimmune disorders such as Myasthenia Gravis. Contrast CT is the standard for diagnosis. Surgery is treatment of choice depending on resectability of the tumour. The Masaoka-Koga staging system is correlated with overall survival and is utilised post-surgical resection to guide adjuvant treatment. Case Presentation: A 50-year-old male presented with cough, shortness of breath, myalgia, sore throat, and reduced sense of smell that was diagnosed as COVID-19. CT chest and abdomen showed a large heterogeneous mediastinal mass (11cm) invading the innominate vein and left upper lobe with two left pleural deposits, and diaphragmatic disease. CT biopsy confirmed thymoma. MDT recommended surgery due to patient age and resectability of tumour with post-operative chemotherapy. The sites of disease necessitated a left thoracotomy and median sternotomy. The pleural and diaphragmatic deposits were resected, followed by left upper lobe anatomical dissection enbloc with invaded pericardium, phrenic and vagus nerve, followed by median sternotomy to resect the thymic mass along with the innominate vein. Final staging was stage IVA thymoma (B2 and B3) (T3N0M1aR0). A CT scan at 1 year showed no recurrence despite patient declining adjuvant chemotherapy. Conclusion: Surgical resection is a viable treatment option for patients with stage IVA thymoma who present with resectable primary and metastatic disease.

Impaired seroconversion after SARS-COV-2 mRNA vaccine in patients with thymic epithelial tumors

Background: Thymic epithelial tumors (TET) are rare malignancies associated with dysregulation of the immune system and humoral and cell mediated immunity abnormalities. Anti-syndrome coronavirus type 2 (SARS-CoV-2) vaccine is effective at preventing COVID-19 morbidity and mortality. No published data are available regarding the immunization in TET patients (pts). The aim of this study was to evaluate the immunization in TET pts who received two doses of mRNA vaccine, by longitudinal serological detection of SARS-COV-2 spike-binding IgG antibody. Methods: Starting from April 2021 to October 2021, consecutive TET pts referred to the Rare Tumors Coordinating Center of Campania Region (CRCTR - Naples, Italy) were enrolled. All study subjects received two doses of COVID-19 mRNA vaccine (BNT162b2 by Pfizer-BioNTech). SARS-CoV-2 spike-binding IgG antibody (Ab) serological levels were analyzed by centralized chemiluminescent immunoassay (CLIA) at different time-points, including before 1st vaccine dose (T0) and 1 month after 2nd dose (T2). Cut-off for Ab titers positivity was > 25 AU/mL. Results: Forty pts were enrolled;23 (57.5%) were female and 17 (42.5%) male. Eleven pts (27.5%) suffered from thymic carcinoma, 28 (70%) thymoma, and 1 (2.5%) thymic hyperplasia. At the time of study enrollment, 20 pts (50%) had no evidence of disease (NED) and were in followup;the remaining 20 pts had evidence of disease (ED) by imaging and were receiving systemic treatment (55% oral low-dose etoposide-based therapy, 40% somatostatin analogs + prednisone, 5% supportive care). Immune system disorders were diagnosed in 29 TET pts (72.5%): 19 pts (47.5%) had Good's Syndrome (GS) and 10 (25%) other immune disorders. At T0, all enrolled pts had negative Ab titers and no prior SARS-CoV-2 infection. At T2, Ab data were available for 37 pts (92.5%): 18 pts (48.7%) had positive Ab titers, whereas 19 (51.3%) did not achieve seroconversion. Among pts with ED, seroconversion was achieved only in 2 cases (11.8%). Lack of seroconversion at T2 was significantly associated with ED (Fisher's exact test p: 0.0001) and with the presence of GS (Fisher's exact test p: 0.0489). No significant association of seroconversion with other immune disorders and disease features was found. Conclusions: Our data showed that TET pts with ED had substantially higher probability of impaired seroconversion after SARS-COV-2 vaccine as compared with NED pts. We warrant further studies to evaluate the role of disease status, anti-tumor treatments and immune disorders in post-vaccine immunization of TET pts.