A Case of Ocular Myasthenia Gravis Seen by Rheumatology as Suspected Mononeuritis Multiplex in an Adult Male Shortly after Pfizerbiontech Sars-Cov-2 Vaccination

Background/Aims Myasthenia gravis (MG) is an antibody-mediated autoimmune disease targeting proteins at the postsynaptic membrane of the neuromuscular junction. MG is thought to occur in genetically susceptible individuals following an environmental trigger. SARS-CoV-2 infection has been associated with new-onset autoimmune disease, new-onset MG, and exacerbations of pre-existing MG, with molecular mimicry between SARS-CoV-2 epitopes and autoantigen-induced autoreactivity thought to be part of the underlying mechanism. We report a case of newonset ocular MG following first dose Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination which was referred to rheumatology as suspected mononeuritis multiplex. Methods A 53-year-old man of East Asian ethnicity presented to the emergency department (ED) with sudden onset diplopia and left lateral gaze restriction 7 days after receiving his first dose of the Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination. He had longstanding myopia and dry eyes but no other medical history, no regular medications or significant family history. He was a current smoker, with a 50-pack year history. He did not drink alcohol or use any recreational drugs. He was found to have an isolated left VI cranial nerve (CN) palsy with an otherwise normal ocular and physical examination. Blood tests were unremarkable apart from raised cholesterol, and he was discharged with a suspected self-limiting microvascular CN lesion. Three weeks later he presented to ED with worsening diplopia, increasingly restricted eye movements, headache, nausea, vomiting and blurred vision. Ophthalmology assessment noted new right sided CN III and VI palsy, persistent left CN VI palsy, and vertical diplopia in all fields of gaze. Neurological and physical examination were normal. Bloods including an autoimmune screen were unremarkable. SARS-CoV-2 Spike antibodies were positive consistent with SARS-CoV-2 vaccination but not infection. Intracranial and thoracic imaging were unremarkable. He was referred to and seen by both rheumatology and neurology as a case of suspected mononeuritis multiplex. Results A diagnosis of ocular MG was confirmed with positive serum acetylcholine receptor antibodies, and he was started on prednisolone, and pyridostigmine to good effect. Daily forced vital capacity (FVC) showed no respiratory muscle involvement, and nerve conduction studies and electromyography were normal, excluding secondary generalisation. Conclusion A review of the literature found 14 reported cases of new-onset MG all within 4 weeks following SARS-CoV-2 vaccine. Whilst these cases provide interesting insights into the pathogenesis of autoimmune conditions such as MG, they are not epidemiological studies to inform vaccine safety. Ultimately, current evidence suggests that the risks of SARS-COV-2 infection outweigh the risk of vaccine-related adverse events, therefore we suggest clinicians should be aware of potential new-onset autoimmune conditions, but support the safety of SARSCOV2 vaccination. Further, research into possible immunological mechanisms behind this phenomenon, including identifying potential epitopes inducing molecular mimicry, could help establish the likelihood of a causative link.

The CRISIS Approach When Autonomy and Beneficence Are in Conflict (CS358)

Outcomes: 1. Utilizing CRISIS approach, participants can employ a unique strategy to holistically support patients with poor coping in an acute life-threatening situation. 2. Utilizing the CRISIS approach, participants will apply an ethical tool to mitigate the incongruence that sometimes happens between two ethical principles-autonomy versus beneficence. Autonomy is not always in harmony with beneficence. We present a patient with decisional capacity hospitalized with acute reversible neuromuscular paralysis who refused treatment despite expected recovery. Her decision created moral distress for the clinicians. An improvised palliative strategy resolved the above dilemma. Case presentation: 68-year-old female admitted with new-onset unsteady gait, diplopia, and speech impairment on waking up. She was healthy until 3 weeks before admission, when she developed upper extremity numbness progressing to both legs after a COVID-19 infection. She had bulbar and axial muscle weakness and right oculomotor nerve palsy with ptosis. Positive ice pack and pyridostigmine test indicated myasthenia gravis (MG). During hospitalization, she required mechanical ventilation secondary to acute respiratory failure from progressive paralysis. Serum-negative MG diagnosed, given the response to IVIG and pyridostigmine. The patient, amid acute crisis, refused therapies and wanted to transition to DNR-comfort care despite understanding the reversibility of her illness. Her family members supported comfort care option. Neurology was conflicted with the patient's choice because MG was treatable. Palliative care, ethics, and neuropsychology consulted to establish decision-making capacity, goals-of-care, and holistic support. Intervention(s): Palliative team utilized the CRISIS approach to address the impasse between the patient and the clinicians: 1. Continue care, collaborate with the teams 2. Respond empathetically 3. Integrate patient's autonomy 4. Support holistically 5. Improvise a care plan 6. Sustain quality of life We validated patient's autonomy. We recommended allowing time for the patient/family to process her illness. We continued holistic support and symptom management and created an improvised multidisciplinary plan to help her cope with the acute illness. The above approach enabled her to opt for therapies instead of comfort care only, and she gradually recovered. Respecting patients' autonomy and incorporating beneficence via our intervention led to positive outcomes. The CRISIS approach could help other clinicians in the situation when conflict arises between autonomy and beneficence.Copyright © 2023

SARS-CoV- 2 vaccine-induced Eosinophilic Granulomatosis with PolyAngiitis (EGPA)

Case report: A 63 y.o. man with known allergic rhinoconjunctivitis and mild asthma, sensitized to house dust mites, cat dander and grass and pellitory pollens, presented at the Emergency Department (ED) of our Hospital for diplopia, left temporo-parietal headache, fleeting knurled scotoma, and impaired color vision, associated with dry cough, occurring the day after the booster dose of the anti-SARS- CoV- 2 vaccine (mRNA-1273). Collecting clinical history, it emerged that 6 months before, just after the first vaccine dose (BNT162b2), he developed a progressive worsening of asthma, becoming severe and uncontrolled despite high dose inhaled corticosteroids plus long-acting beta2-agonists, montelukast and tiotropium bromide, and requiring maintenance oral corticosteroid treatment: any attempt to withdraw systemic corticosteroid was associated with exacerbations of asthma. During the access to the emergency room and the subsequent hospitalization, the following emerged: severe hypereosinophilia (12400 cells/mcl), left third cranial nerve palsy, elevated serum troponin, echocardiographic signs of acute myopericarditis with interventricular septal thickening, MRI signs of cardiac interventricular septal hypokinesia, and multiple pulmonary consolidations on CT scan. Serum ANCA was negative. The clinical presentation (asthma, third cranial nerve mononeuropathy, myopericarditis with signs of interventricular septal distress, typical lung involvement) associated with the finding of severe hypereosinophilia was suggestive of eosinophilic granulomatosis with polyagioitis (EGPA). Already in the emergency room, the patient was promptly treated with 3 boluses of methylprednisolone 1 g i.v. (1 bolus per dey). During the hospitalization he underwent the first cycle (out of 6 planned) of i.v. cyclophosphamide 1000 mg and initiated therapy with oral prednisone 75 mg/day (1 mg/kg/day). After the initiation of systemic corticosteroid therapy there was depletion of blood eosinophils, progressive reduction of serum troponin, resolution of cough and almost complete regression of 3rd cranial nerve palsy. At the time of submission, the patient was discharged and taken on an outpatient basis to continue therapy with cyclophosphamide and possibly associate mepolizumab as a steroid-sparing strategy. In conclusion, this is a case of EGPA arising after SARS-CoV- 2 vaccination. It has been described that vasculitis can be triggered by infectious episodes or vaccinations: to date only two other EGPA cases likely induced by anti-SARS- CoV- 2 mRNA vaccines have been described in the literature.

COVID-19 and isolated oculomotor nerve palsy: Clinical features and outcomes.

AIM: This study aims to describe the clinical characteristics of patients with isolated oculomotor nerve palsy from COVID-19 infection, and provide guidance on their treatment and management. METHODS: We performed a systematic review and retrospective analysis on the clinical features and outcomes of patients with isolated oculomotor nerve palsy from COVID-19 reported in literature over the past three years. RESULTS: We analyzed a total of 11 cases; 9 identified in literature from January 2020 to September 2022, together with our two patients. Their median age was 46 years (range 2-65), and three were children. More than half (6/11, 55 %) were without medical history. Oculomotor nerve palsies tended to occur early (longest interval of 16 days), but they can also occur concurrently (2/11, 18 %) or before the appearance of COVID-19 symptoms (1/11, 9 %). COVID-19 symptoms tended to be mild (8/11, 73 %). Oculomotor nerve palsies, however, displayed neither a clear gender predilection, nor consistent clinical features in terms of the severity of extraocular weakness and the involvement of pupillary light responses. Nearly two-thirds (7/11, 64 %) received no pharmacological treatment. Regardless, recovery was complete in nearly all (9/10, 90 %), with most occurring within a month (8/9, 89 %) CONCLUSION: Isolated oculomotor nerve palsies are early but uncommon complications of COVID-19. They affect patients with mild infections, and can be the first symptom. Prognosis is excellent, with recovery being often complete and early. Early discharge and outpatient clinical review, with or without short courses of oral steroids, are reasonable treatment measures.

Acute Angle Closure Glaucoma Following COVID-19 Vaccination: An International Journal of Medical Toxicology and Drug Experience

Introduction: Although vaccines against COVID-19 are strongly recommended as safe and effective at alleviating the morbidity and mortality, different types of ocular complications have been reported after COVID-19 vaccination, including oculomotor nerve palsy, episcleritis, anterior uveitis, multifocal choroiditis, reactivation of Vogt-Koyanagi-Harada disease, acute macular neuroretinopathy and central serous retinopathy(1).Acute angle closure glaucoma (AACG) is an ophthalmic emergency that can be drug induced. If not promptly identified and treated, it can cause irreversible blindness.

OCULOMOTOR NERVE PALSY FOLLOWING COVID-19 INFECTION

CASE: Patient is a 60-year-old woman who works at a local hospital in billing department. She has a history of rheumatic fever, non ST elevation MI, osteoarthritis, Crohn's disease. Her husband was diagnosed with COVID-19 infection in November 2020. A Week later, patient developed myalgias, diarrhea and subsequent testing confirmed COVID-19 infection. Overall, her symptoms were mild and required no treatment or hospitalization. Six weeks following the infection she woke up one morning with diplopia and a large left pupil. She tried to manage this by covering one eye initially, but later visited with a neurologist, ophthalmologist, neuro-ophthalmologist. She was found to have fixed, dilated left pupil and horizontal diplopia with some diagonal component. There were no other neurological signs or meningismus. Laboratory tests showed hemoglobin of 12.5, White cell count 5.7, platelets 405. Electrolytes, kidney function, liver function tests were normal. ACH receptor antibodies were negative. Imaging studies included a negative CTA head, negative brain MRI, face, orbits and optic nerves. She was diagnosed with left third cranial nerve palsy possibly as a complication of COVID-19 infection. She was prescribed oral prednisone 60 mg with a slow taper. Her pupil size and vision gradually improved over the ensuing weeks and the recovery of the third cranial nerve was nearly complete. IMPACT/DISCUSSION: The third cranial nerve supplies the levator muscle of the eyelid, medial rectus, superior rectus, inferior rectus, and inferior oblique;constricts the pupil through its parasympathetic fibers. Patients with oculomotor cranial nerve palsy develop diplopia and droopy eyelid. Etiology for third cranial nerve palsy include many pathologies such as a structural lesion, infectious or inflammatory conditions, cerebrovascular disease and trauma. Our patient developed acute 3rd cranial nerve palsy 6 weeks following the COVID-19 infection. The workup was negative for any structural lesions, CVA or other known causes. This raised the possibility that her symptoms are possibly complications of COVID-19 infection. Neurological complications of COVID-19 infection have been well documented. These include encephalopathy, stroke, dysgeusia and anosmia. There were two case reports of oculomotor nerve palsy that occurred during the acute phase of COVID-19 infection. These were thought to be from direct invasion of the virus. Our patient however, had developed symptoms 6 weeks following the infection raising the possibility of immune mediated complication. She made near complete recovery with oral glucocorticoid treatment. However, it is not known whether the improvement is the result of the treatment. CONCLUSION: 1. Oculomotor cranial nerve palsy is potentially associated with COVID-19 infection. 2. Oculomotor cranial nerve palsy could present several weeks after the acute COVID-19 infection. 3. In patients presenting with 3rd cranial nerve palsy, it is important to obtain the history of past COVID-19 infection.

Distant Ocular Manifestations after New Coronavirus Infection

Purpose. Theoretically substantiate and practically identify ocular manifestations after the transferred SARS-CoV-2 virus. Patients and methods. For the study we were invited patients who had recovered from SARS-CoV-2 at the hospital of V.M. Buyanova, the age from 20 to 65 years old in period from 2020 to 2021. The total number of patients was 68 people. The patients had with them the results of PCR tests or ELISA tests, or an extract from the hospital confirmed COVID-19 case and also a clinical blood test and CT scan of the chest organs for the period of illness. Before the start of the study, the patients were asked to fill out a questionnaire “Questionnaire for patients who have had a new coronavirus infection” (Appendix 1). For a detailed study of this group of people, each underwent visometry, pneumotonometry, B-scan, a slit lamp study and also a slit lamp study with a 60D lens using 0.5 % Mydriacyl eye drops in the absence of contraindications and pupillography. Results. As a result of the work carried out, we concluded that the virus is capable of causing inflammation of the choroid of the eyeball, uveitis. Moreover, in our study, we identified patients with acquired intermittent divergent strabismus, anisocoria, ptosis, and accommodation disorder. And, in this regard, we came to the conclusion that the coronavirus belongs to the group of neurotropic, as it is able to affect the nervous tissue and cause the above clinical picture. In other words, the virus negatively affects the somatic and autonomic innervation of the oculomotor nerve. As a result of these lesions, we get the corresponding tetrad of symptoms: heterotropy, mydriasis, ptosis, accommodation paralysis. Conclusions. One of the extraordinary complications of coronavirus infection is damage effect to the fibers of the oculomotor nerve, the signs include: strabismus, mydriasis, ptosis and accommodation paralysis. Thus, this clinical picture is associated with the affinity of the virus to the nervous tissue. And as a result, this ability of the virus can probably infect various areas of the brain, which will lead to corresponding complications, not only from the oculomotor nerve, but also from other cranial nerves with the manifestation of the corresponding symptoms, which in theory can aggravate the patient's condition, causing deep disturbances of motor and sensory innervation.

Presumed oculomotor nerve palsy following COVID-19 vaccination.

We herein report the case of an 84-year-old female who presented to the outpatient clinic one day following her first dose of the Pfizer-BioNTech COVID-19 vaccine with mydriasis, ptosis, and a "down and out" gaze. She was subsequently diagnosed with oculomotor nerve palsy, and treated with corticosteroids and valacyclovir for a total of 7 days, with no clear improvement. On subsequent visits, ophthalmic examination improved steadily and showed complete resolution after 8 weeks. This article aims to report this unusual incidence that occurred following vaccination with the Pfizer-BioNTech COVID-19 vaccine. It is important for physicians to identify and report abnormal occurrences which may potentially be related to the COVID-19 vaccines, in order to reach a complete understanding of their possible side effects.

Superior Divisional Palsy of the Oculomotor Nerve as a Presenting Sign of SARS-CoV-2 (COVID-19).

Although COVID is a predominantly respiratory disease, recent studies demonstrate variable and atypical presentations with multiorgan involvement. Neurological manifestations involving cranial nerves and the peripheral nervous system are more frequently being described. Although mechanisms are still under investigation, several studies demonstrate the neuroinvasive potential of COVID via angiotensin-converting enzyme 2 (ACE2) receptor interactions and postulate this mechanism to be the route of COVID central nervous system (CNS) infection. We present the rare case of a purely superior divisional palsy of the left oculomotor nerve in a 46-year-old woman with no medical history in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, confirmed by magnetic resonance imaging (MRI) findings of asymmetrical thickening and enhancement of the left oculomotor nerve. With this report, we hope to increase clinical suspicion for oculomotor nerve palsies as a manifestation of SARS-CoV-2 infection and also to inspire further studies investigating neurological manifestations of COVID.

Third Cranial Nerve Palsy Due to COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) is known to be primarily a viral infection affecting the pulmonary system leading to severe pneumonia and acute respiratory distress syndrome. COVID-19 has also been found to affect the neurological system causing various nerve palsies. While some studies have suggested these neurological manifestations may indicate severe disease, cranial nerve palsies in the setting of COVID-19 infection have been linked to improved patient outcomes and mild viral symptoms. We present a case of a 55-year-old male with confirmed COVID-19 infection presenting with third cranial nerve palsy. Since his hospital course remained unremarkable, he was treated supportively for his COVID-19 infection and remained stable on room air during his hospitalization. No causative factors other than COVID-19 were identified as a cause for his cranial three nerve palsy which resolved spontaneously during outpatient follow-up. Although different cranial nerve palsies associated with COVID-19 infection have been identified in the literature, the pathogenesis and prognosis of cranial nerve palsy is still unclear. This case emphasizes the need for continued symptom monitoring and identification in patients diagnosed with COVID-19.