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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.
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The management of patients with cognitive impairment (CI) is one of the urgent problems of modern medicine. Issues of diagnostics and therapy of patients with CI and their high mortality during the period of coronavirus infection are discussed. A wide prevalence of patients with mild CI (MCI), an important role of neuropsychological research in establishing CI, and frequent diagnosis of CI only at the stage of dementia were noted. In our country, CI is poorly diagnosed, the most common cause of CI in the elderly - Alzheimer's disease (AD) - is rarely established, patients are observed for a long time with a diagnosis of cerebrovascular disease (CVD). Some non-drug and drug methods can reduce the manifestations of CI, improve the quality of life of both the patients themselves and those around them. In severe CI, socio-psychological methods, stimulating patients to feasible household and social, physical and mental activity, and avoiding prolonged hospitalization are of primary importance. In addition to lifestyle changes, much attention in CI is given to the prevention of stroke, the treatment of arterial hypertension and diabetes mellitus. At the stage of dementia, cholinomimetic drugs (acetylcholinesterase inhibitors, donepezil, rivastigmine, galantamine) and the glutamate receptor blocker memantine are used. The use of choline alfoscerate in CI and the results of the multicenter, placebo-controlled ASCOMALVA study are discussed, in which, in patients with AD and CVD, the addition of choline alfoscerate to donepezil reduced the severity of CI, manifestations of depression, anxiety, and apathy. A new oral form of choline alfoscerate (Cerpechol) is reported that may improve patient compliance and be used in patients with swallowing disorders.Copyright © 2023 Ima-Press Publishing House. All rights reserved.
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The management of patients with cognitive impairment (CI) is one of the urgent problems of modern medicine. Issues of diagnostics and therapy of patients with CI and their high mortality during the period of coronavirus infection are discussed. A wide prevalence of patients with mild CI (MCI), an important role of neuropsychological research in establishing CI, and frequent diagnosis of CI only at the stage of dementia were noted. In our country, CI is poorly diagnosed, the most common cause of CI in the elderly - Alzheimer's disease (AD) - is rarely established, patients are observed for a long time with a diagnosis of cerebrovascular disease (CVD). Some non-drug and drug methods can reduce the manifestations of CI, improve the quality of life of both the patients themselves and those around them. In severe CI, socio-psychological methods, stimulating patients to feasible household and social, physical and mental activity, and avoiding prolonged hospitalization are of primary importance. In addition to lifestyle changes, much attention in CI is given to the prevention of stroke, the treatment of arterial hypertension and diabetes mellitus. At the stage of dementia, cholinomimetic drugs (acetylcholinesterase inhibitors, donepezil, rivastigmine, galantamine) and the glutamate receptor blocker memantine are used. The use of choline alfoscerate in CI and the results of the multicenter, placebo-controlled ASCOMALVA study are discussed, in which, in patients with AD and CVD, the addition of choline alfoscerate to donepezil reduced the severity of CI, manifestations of depression, anxiety, and apathy. A new oral form of choline alfoscerate (Cerpechol) is reported that may improve patient compliance and be used in patients with swallowing disorders.Copyright © 2023 Ima-Press Publishing House. All rights reserved.
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Virus entry into animal cells is initiated by attachment to target macromolecules located on host cells. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) trimeric spike glycoprotein targets host angiotensin converting enzyme 2 to gain cellular access. The SARS-CoV-2 glycoprotein contains a neurotoxin-like region that has sequence similarities to the rabies virus and the HIV glycoproteins, as well as to snake neurotoxins, which interact with nicotinic acetylcholine receptor (nAChR) subtypes via this region. Using a peptide of the neurotoxin-like region of SARS-CoV-2 (SARS-CoV-2 glycoprotein peptide [SCoV2P]), we identified that this area moderately inhibits α3ß2, α3ß4, and α4ß2 subtypes, while potentiating and inhibiting α7 nAChRs. These nAChR subtypes are found in target tissues including the nose, lung, central nervous system, and immune cells. Importantly, SCoV2P potentiates and inhibits ACh-induced α7 nAChR responses by an allosteric mechanism, with nicotine enhancing these effects. Live-cell confocal microscopy was used to confirm that SCoV2P interacts with α7 nAChRs in transfected neuronal-like N2a and human embryonic kidney 293 cells. The SARS-CoV-2 ectodomain functionally potentiates and inhibits the α7 subtype with nanomolar potency. Our functional findings identify that the α7 nAChR is a target for the SARS-CoV-2 glycoprotein, providing a new aspect to our understanding of SARS-CoV-2 and host cell interactions, in addition to disease pathogenesis.
Subject(s)
Receptors, Nicotinic , SARS-CoV-2 , alpha7 Nicotinic Acetylcholine Receptor , Humans , alpha7 Nicotinic Acetylcholine Receptor/genetics , COVID-19 , Neurotoxins , Receptors, Nicotinic/genetics , Spike Glycoprotein, Coronavirus/geneticsABSTRACT
Background: Myasthenia gravis (MG) is an autoimmune disease of unknown etiology. Infections are known as a major cause of MG exacerbations. A few studies have shown an association between new onset MG and SARS-CoV-2 infection. Case presentation: We have reported a case of new onset myasthenia gravis in a 68-year-old man presented with bulbar symptoms a few days after receiving COVID-19 vaccine (Sinopharm vaccine). The disease was confirmed by high titer of antibody against acetylcholine receptor and electrophysiological examinations. Conclusion(s): Among the adverse effects reported with the COVID-19 vaccine, new onset myasthenia gravis is very rare. The underlying mechanism is unknown but the immune response after vaccination and molecular mimicry theory has been proposed.Copyright © 2022
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Background: Unexpectedly, COVID-19 was less prevalent in Chronic Respiratory Disease(CRD) than in the general population (Gupta N et al. Lung India. 2021;38(5):454-9). The vaccine and infection-related immune status of CRD patients is unknown. Aims and Objectives: Our primary objective was to study the cross sectional seroprevalence among chronic respiratory disease patients attending the Pulmonary medicine outpatients service and comparing it with the national seroprevalence data. Method(s): Consecutive subjects with CRD were recruited. History of past COVID 19 infection and other relevant information was obtained. Blood sample was taken for Roche Elecsys SARS-CoV-2 assay to detect anti-N and anti-S antibodies. Result(s): We recruited 364 patients(Asthma & COPD-100 each, Bronchiectasis, ILD & PTB-sequelae- 50 each and other restrictive diseases-14). The overall seroprevalence in CRD(Anti-S) was 85.16%, which was significantly higher than the 4th national serosurvey seroprevalence of 67.60%(p=0.001) (ICMR, Ministry of Health and Family Welfare;2021). Asthma had the highest seroprevalence, which was higher than COPD [93% vs 78%, p=0.027] and bronchiectasis [93% vs 80%, p=0.018]. Seroprevalence dropped with increasing age: <40 yrs: 93%, 41-60 yrs: 87% and >= 61 yrs: 77% (p=0.004). Patients on inhaled-steroids had higher seroprevalence than those without (89% vs 80%;p=0.026) and those on inhaled-anticholinergics (89% VS 79%;p=0.013). Conclusion(s): COVID-19 seroprevalence is higher in CRD than in the general population. Asthmatics had the highest prevalence and the seroprevalence dropped with increasing age.
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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;
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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: Myasthenia gravis (MG) occurs sporadically with no known causes. We present a rare case of new onset MG s/p COVID-19 vaccination. CASE PRESENTATION: A healthy 46-year-old female presented with progressing LE weakness for 3 months. Symptoms started 5 days after her initial Pfizer COVID-19 vaccine. Her workup showed negative neuroimaging, bland basic CSF studies from LP, with negative MS profile and AChR Ab. She presented again in 1 month with difficulty rising from a seated position, raising her arms above her head with blurry vision. Exam showed bilateral ptosis that improved with an ice pack test, weakness is worst in proximal muscles, but normal reflexes. Workup was again negative. Pyridostigmine was added after discharge (DC). 2 months after, she was admitted to the ICU for acute progressive fatiguability and dyspnea. EMG/NCS of the ulnar nerve showed 60-70% electrical decrement. She underwent therapeutic PLEX. Prednisone was added at DC followed by mycophenolate. 2 weeks later, she was again admitted with myasthenic crisis. She again underwent PLEX with improvement and intubation was avoided. Biweekly PLEX was started at DC. Testing for AChR, MuSK, and LRP4 Abs were initially negative, but AChR Abs were present 6 months later. She then underwent thymectomy showing hyperplasia. DISCUSSION: MG exacerbations have been attributable to infections (50%) and medications (30%). This has worsened during the COVID-19 pandemic especially when medications such as azithromycin were used to treat acute infections. While vaccine-induced flares or onset of autoimmune diseases have been described in literatures, new onset MG following vaccines is rare, limited to 1 to 3 case reports. No case, to our knowledge, correlated to the 1st dose like our patient. The temporal relationship between the COVID-19 vaccination and onset of MG symptoms in our patient could represent a correlation, but does not prove causality. Perhaps a more plausible theory is that the vaccine may have unmasked a previously unrecognized disease in high-risk patient. We ask if the COVID vaccine induces a similar cytokine storm, which hyperstimulates the immune system to a point that breaks immunologic self-tolerance. Interestingly, our patient was initially seronegative, but the presence of AChR Ab was confirmed after sensitive cell-based assays testing. Our patient may have had pre-existing self-antigens to the AChR that were released after receiving the Pfizer COVID-19 vaccine. CONCLUSIONS: The rate of COVID-19 vaccinations will soon surpass that of infections placing vulnerable individuals at risk for MG onset. Recognizing this risk will open discussions about vaccine safety. In doing so, we can begin to formulate new parameters for post-vaccination monitoring. The risks of and complications from acute COVID-19 still outweigh the rare adverse events from vaccines;thus, eligible patients should be offered the COVID-19 vaccine. Reference #1: Guidon AC, Amato AA. COVID-19 and neuromuscular disorders. Neurology. 2020 Jun 2;94(22):959-969. doi: 10.1212/WNL.0000000000009566. Epub 2020 Apr 13. PMID: 32284362. Reference #2: Tagliaferri AR, Narvaneni S, Azzam MH, Grist W. A Case of COVID-19 Vaccine Causing a Myasthenia Gravis Crisis. Cureus. 2021;13(6):e15581. Published 2021 Jun 10. doi:10.7759/cureus.15581 Reference #3: Chavez A, Pougnier C. A Case of COVID-19 Vaccine Associated New Diagnosis Myasthenia Gravis. Journal of Primary Care & Community Health. January 2021. doi:10.1177/21501327211051933 DISCLOSURES: No relevant relationships by andrew bui No relevant relationships by Sharonya Shrivastava
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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: SARS-CoV-2 has demonstrated an impact on the lungs, leads to hypercoagulable states, and has caused immune-mediated reactions. Myasthenia Gravis (MG) represents a neuromuscular junction autoimmune disorder, with only a few case reports associated with new-onset MG following COVID-19 vaccination. Very rarely, MG has been reported in coexistence with Primary Sjogren's Syndrome (PSS). Here we present a case of new-onset MG in a patient with a positive COVID-19 a nasopharyngeal RT-PCR swab test, who received 3 doses of the Moderna COVID-19 vaccine with the latest dose 2 weeks prior to presentation and demonstrated positive PSS antibodies (Abs). CASE PRESENTATION: A 67-year-old male with no known past medical history presented with complaints of progressive weakness for 2 weeks, which began as diffuse malaise, and progressed to upper and lower extremity weakness with associated neck weakness, and dysphagia. Physical exam was remarkable for bilateral ptosis and difficulty ambulating. The patient was admitted to the ICU for suspected new-onset neuromuscular junction disorder and for close monitoring of his respiratory function. COVID-19 PCR was positive. MG and autoimmune disease workup was sent along with COVID-19 antibody testing. Chest X-Ray, CT head, and CT thorax were unremarkable. The patient was started on Pyridostigmine and IVIG, with low dose prednisone initiated on day 3 of admission. On the fifth day, symptoms improved significantly. Antibodies (Ab) against Acetylcholine (Ach) receptors were elevated and the diagnosis of MG was made. PSS Abs were also detected. Lyme, HIV, RPR, thyroid, and B12 levels were within the normal range which may mimic NMJ dysfunction. DISCUSSION: MG represents an autoimmune disorder due to autoantibodies against nicotinic AChR at the neuromuscular junction;however, these Abs can also target non-AChR muscle-specific receptor tyrosine kinase (MUSK). The exact mechanism of the autoimmune response with MG is not fully understood;however, there have been associations found with thymus gland hyperplasia and neoplasm when anti-AChR Abs are involved. Genetic predisposition is also likely to play a role. Viral and bacterial infections are established triggers for a myasthenic crisis in patients with pre-existing MG;however, there is yet to be a clear consensus regarding infections causing MG in otherwise healthy patients. As our pt did receive the COVID-19 vaccine, we have to consider an autoimmune reaction secondary to his administration. CONCLUSIONS: COVID-19 vaccines have demonstrated autoimmune responses such as myocarditis and myasthenic crisis in individuals. There have also been documented cases of MG in symptomatic COVID-19 infections. Given these findings, this patient may have experienced an environmental insult on top of a genetic predisposition and may warrant further investigation in patients with similar presentations. Reference #1: Sriwastava S, Tandon M, Kataria S, Daimee M, Sultan S. New onset of ocular myasthenia gravis in a patient with COVID-19: a novel case report and literature review. J Neurol. 2021 Aug;268(8):2690-2696. doi: 10.1007/s00415-020-10263-1. Epub 2020 Oct 12. PMID: 33047223;PMCID: PMC7549728. Reference #2: Chavez A, Pougnier C. A Case of COVID-19 Vaccine Associated New Diagnosis Myasthenia Gravis. J Prim Care Community Health. 2021 Jan-Dec;12:21501327211051933. doi: 10.1177/21501327211051933. PMID: 34709075;PMCID: PMC8559213. Reference #3: Witberg G, Barda N, Hoss S, Richter I, Wiessman M, Aviv Y, Grinberg T, Auster O, Dagan N, Balicer RD, Kornowski R. Myocarditis after Covid-19 Vaccination in a Large Health Care Organization. N Engl J Med. 2021 Dec 2;385(23):2132-2139. doi: 10.1056/NEJMoa2110737. Epub 2021 Oct 6. PMID: 34614329;PMCID: PMC8531986. DISCLOSURES: No relevant relationships by Brooke Kania No relevant relationships by Anas Mahmoud No relevant relationships by Ahmed Salem No relevant elationships by Jessimar Sanchez No relevant relationships by Shivanck Upadhyay No relevant relationships by Deniz Yucel
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Introduction: Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction that causes muscle weakness and fatigability. Majority of MG patients request a long-term immune suppression. Aim: To analyze frequency and severity of COVID- 19 infection in MG patients, as well as frequency of patients vaccinated against SARS-CoV-2. Patients and Methods: 125 MG patients from the central Belgrade municipalities were included - 60.0% females, age at MG onset 50.1 (19.7) years, age at testing 61.7 (16.8) years, AChR positive 78.4% and MuSK positive 8.6%. Results: One third of MG patients have had a COVID- 19 and they were younger compared to those who did not suffer from a COVID-19. Severe COVID- 19 was registered in 27.9% of MG patients, mostly in elder subjects with comorbidities such as cardiac diseases and history of malignancies. Two patients had a lethal outcome. MG worsening was noticed in 21.4% of patients after COVID-19 and 41.8% had COVID-19 sequalae. Majority of our MG patients were vaccinated against SARS-CoV-2 (68.8%). Vaccination was more common among MG patients with diabetes and in those with a milder form of MG. Main reasons not to accept a vaccine were: Do not wish to be vaccinated (12 patients), afraid of MG worsening (10), advise of a neurologist (8), and advise of a general practitioner (6). The most common types of vaccine were Sinopharm (42.2%) and Pfizer-BioNTech (25.6%). Adverse events were noticed in 36.0% of vaccinated patients, with mild infection (77.4%) and local reactions (12.9%) being the most common. MG worsening was noticed in 5 (5.8%) vaccinated patients. Conclusion: COVID-19 has placed a significant burden for MG patients, with severe COVID-19 forms and MG worsening being common. Percentage of vaccinated MG patients was higher than in general Serbian population.
ABSTRACT
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.
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Donepezil hydrochloride is an acetylcholine esterase inhibitor studied and approved to treat Alzheimer’s disease (AD). However, this drug can have positive therapeutic potential in treating different conditions, including various neurodegenerative disorders such as other types of dementia, multiple sclerosis, Parkinson’s disease, psychiatric and mood disorders, and even infectious diseases. Hence, this study reviewed the therapeutic potential of this drug in treating Alzheimer’s and other diseases by reviewing the articles from databases including Web of Science, Scopus, PubMed, Cochrane, and Science Direct. It was shown that donepezil could affect the pathophysiology of these diseases via mechanisms such as increasing the concentration of acetylcholine, modulating local and systemic inflammatory processes, affecting acetylcholine receptors like nicotinic and muscarinic receptors, and activating various cellular signaling via receptors like sigma-1 receptors. Despite many therapeutic potentials, this drug has not yet been approved for treating non-Alzheimer’s diseases, and more comprehensive studies are needed.
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Introduction: While an estimated 50% of adult women experience urinary incontinence (UI), the majority will never receive treatment. Most studies of incontinence care delivery have been limited to administrative (billing) data following treatment. Much less is known about earlier steps in evaluation, including primary care intentions to refer to specialty care. Objective: To better understand the gaps and barriers to receiving care, we examined referral patterns from primary care providers for patients with new diagnoses of urinary incontinence between 2018-2020 and the extent to which such referrals changed during the COVID-19 pandemic. Methods: Electronic health records (EHR) from 24 primary care practices within a single academic medical system were queried to identify a cohort of adult (18 - 90-year-old) female patients first diagnosed with urinary incontinence during primary care (family or general internal medicine) outpatient visits between January 2018 and December 2020. Demographics were determined from appropriate EHR fields, and diagnoses pulled from problem lists, past medical histories, and office visit diagnosis fields. EHR referral fields were utilized to ascertain referral dates, types, and associated diagnoses. Electronic prescription fields were used to record treatment information including medication class, name, and prescription dates. Subjects were excluded if there was EHR evidence of urinary tract infection at diagnosis, UI in the prior year based on diagnosis or medication usage (anticholinergic, B3 agonists), or presence of conditions for which incontinence management might differ substantially in the prior year (pregnancy, spinal cord injury). Referrals to specialty physicians (urology/urogynecology) and pelvic floor physical therapy (PFPT) were examined for the year after UI diagnosis. Logistic regression was then used to assess for associations between referrals and patient demographics, comorbidity, and diagnosis dates (pre-vs during-COVID-19). Results: The study identified 514 women with a newly diagnosed urinary incontinence diagnosis (Table 1). In the year following UI diagnosis, 31.91% were referred to specialty care for management -29.0% to urology/urogynecology and 3.5% to pelvic floor physical therapists. Women diagnosed with UI during the COVID-19 pandemic, starting January 2020, were less likely to be referred with an odds ratio of 0.29 (95% CI 0.19, 0.45) compared to those diagnosed before (Table 2). There was no association of referrals with patient age, race, or number of comorbidities (Elixhauser Comorbidity Index), but confidence intervals were wide. Patterns were similar for models that examined specialty physician or PFPT referral separately. Conclusions: Less than 1 in 3 women were referred to specialty care for UI by their primary care provider with less than 1 in 25 referred to PFPT. There was a significant decrease in likelihood of referrals during 2020 suggesting that the COVID-19 pandemic interfered with UI patients receiving quality care. Future studies aiming to improve incontinence care should examine other aspects of nonsurgical UI care delivery, including barriers to behavioral self-management, medication use, and completion of specialty referrals.
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CASE: 74 year old woman with history of anxiety, depression, and nonsecretory adrenal adenoma presented with two months of progressive night sweats. Initially, she described waking up damp all over, but without needing to change her sheets. Her weight had been stable, and she denied recent travel. Her recent health changes included starting sertraline and receiving the Moderna COVID vaccines. Her other medications included atorvastatin and lisinopril. Her vital signs were all within normal range and her physical exam was unremarkable. Night sweats described were mild, so work up began with checking a CBC with differential and a TSH level. Initial labs were normal. However, the patient called a week later with night sweats that were worsening. She also recalled being treated for tuberculosis at age fifteen. This prompted additional bloodwork including Quantiferon, ACTH, androstenedione, estradiol, testosterone, progesterone, and DHEAS levels, as well as urine catecholamines and metanephrines. Additionally, it was noted sertraline could be a potential cause of night sweats. The dose was halved with the goal to taper off and discontinue the medication. All lab results came back within normal limits, so CT scans of the chest/ abdomen/ pelvis were ordered, and blood cultures collected. Imaging showed an unchanged adrenal adenoma and blood cultures had no growth. Ultimately, after five months of symptoms, her night sweats completely resolved five weeks after stopping sertraline. IMPACT/DISCUSSION: When working up night sweats, first, the severity of symptoms should be determined and medications reviewed. Mild night sweats with no associated red flag symptoms (weight loss, lymphadenopathy, and fever) do not need immediate or extensive work up. Further work up is essential in the setting of any red flag symptoms. Without a clear etiology, the work up includes the following items: chest radiography along with bloodwork including Quantiferon test, CBC, TSH, HIV serology, and CRP. If these results are normal then a CT of the chest, abdomen, and pelvis could be obtained as well as a bone marrow biopsy. Little evidence exists to guide an exact order of workup for night sweats, so it remains the clinician's responsibility to determine which tests to prioritize. Classes of medications that tend to cause night sweats are cholinergics and anti-depressants. Anti-depressants most associated with night sweats include TCAs and SNRIs. Sertraline has been implicated as a cause of night sweats, but little data exists as to how often this occurs and how often severe presentations like the one described occur. Given that selective serotonin reuptake inhibitors are a first line treatment in depression, recognizing this adverse effect is important in primary care and could prevent unnecessary extensive work ups for night sweats. CONCLUSION: -An initial step in evaluating persistent night sweats should be medication review -Many antidepressants including sertraline can have night sweats as an adverse effect.
ABSTRACT
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.
ABSTRACT
Introduction: Reports of vestibular syndrome have been associated with COVID vaccination in the recent literature. In this study, we aimed to evaluate the association between COVID-19 vaccines and vestibular disorders using Vigibase®, the WHO pharmacovigilance database. Material and methods: On January 5th, 2022, we extracted in a deduplicated dataset of VigiBase® reports of vestibular disorders for tozinameran (Pfizer®), elasomeran (Moderna®), Ad26.COV2.S (Janssen®) and ChadOx1nCov-19 (Astra-Zeneca®), using MedDRA preferred terms neuronitis vestibular, acute vestibular syndrome, vestibular disorder and the low level term vestibular vertigo. Seriousness was analyzed and reported odds ratio (ROR) were calculated. We also reviewed the management of COVID-vaccine associated vestibular disorders reported in Caen Regional Pharmacovigilance Center. Results: In Vigibase®, 226 reports of vestibular disorders were found for ChadOx1nCov-19, 40 for Ad26.COV2.S, 254 for elasomeran and 1,050 for tozinameran. The ROR were respectively 2.5 (2.2-2.8), 2.5 (1.8-3.2), 3.6 (3.2-4.0) and 7.0 (6.6-7.4). Reports were considered serious in 74.3% for ChadOx1nCov-19, 70.0% for Ad26.COV2.S, 60.6% for elasomeran and 56.01% for tozinameran. Finally, we collected 13 reports of COVID-19 vaccines associated vestibular disorders in our pharmacovigilance center. Concerning the management of those vestibular disorders, 4 patients received antiemetics, 1 received betahistine, 7 received acetylleucine, 2 received corticoids and 6 had vestibular physiotherapy sessions. After 1 month of follow-up, only one patient had recovered. Discussion/Conclusion: The Vigibase® analysis showed a statistically significant association between the 4 COVID-19 vaccines under study and vestibular disorders. Short-term anticholinergics, antiemetics, antihistamines or benzodiazepines, and a corticosteroid burst with rapid taper as well as vestibular rehabilitation are usually recommended treatments. In our case series we noticed the long duration of the symptoms despite the treatments received and the heterogeneity of the adopted therapeutic strategy. Physicians should be aware and careful of the potential association of COVID-19 vaccines and vestibular disorders. Management guidelines are needed given the wide exposure to COVID-19 vaccines.
ABSTRACT
Background: Delirium, a syndrome characterized by impairment in attention and consciousness, commonly occurs in hospital setting and is associated with higher mortality and poor long-term outcomes. With precise etiology of delirium yet to be elucidated, our current understanding describes delirium as a state of multifactorial global brain dysfunction occurring in susceptible elderly and critically ill patients. (Maldonado, 2008) To treat such a multimodal disorder, we propose investigating two novel multimodal pharmacological approaches: Granulocyte-macrophage colony stimulating factor (GM-CSF) inhibitors and pro-cholinergic muscarinic-receptor agonists. Discussion: Neuroinflammation is a focus of inquiry in a number of neuropsychiatric diseases. Unlike individual cytokine (TNF, IL-6) inhibitors, GM-CSF inhibitors combat the entire inflammatory cascade implicated in delirium: blunting the cytokine response (IL-1, IL-6, TNF) to reduce inflammation, limiting chemotaxis (IL-8 inhibition), reducing cell degradation (H2O2, MMPs), and dulling the T- and B-cell response. (Patel, 2021) GC-CSF inhibitors (otilimab and TMJ2) have already been shown to be effective in and approved for the treatment of inflammatory conditions, such as Rheumatoid Arthritis, and have been effective in treatment of inflammatory processes of COVID-19. (Patel, 2021) Given the role of the neuroinflammatory cascade in delirium, we propose investigating the GM-CSF inhibitors to treat delirium. Acetylcholine dysregulation (‘anticholinergic surge’), on the other hand, has long been implicated in delirium and studies suggest some efficacy of acetylcholinesterase inhibitors in treatment of delirium. Novel schizophrenia treatment studies combine xanomeline, a M-receptor agonist, with trospium, a peripheral anticholinergic, to create a net-positive pro-cholinergic state in the brain while minimizing systemic side-effects. (Brannan, 2020) In addition to treating schizophrenia and cognitive impairment, this combination (KarXT), may be useful in reversing the anti-cholinergic state of the delirious brain. Currently in Phase III clinical trials, KarXT should be considered a viable candidate for delirium treatment, once FDA-approved. Conclusions: Pharmacological approaches to delirium have been limited to managing behavioral dysregulation and sleep-wake cycle disturbances. Presently, we are looking at two potential additional approaches to delirium treatment. One is limited to cholinergic circuitry and aims to restore AcH balance via direct M-receptor agonism. The other, based on Systems Integration Failure Hypothesis, addresses the entire inflammatory cascade via GM-CSF inhibition. As agents from both classes are either approved or are close to FDA-approval, we should consider them as candidates for delirium management. References: 1. Maldonado, J, Kapinos, G. (2008). Pathoetiological Model of Delirium, Critical care clinics. 24. 789-856, ix. 10.1016/j.ccc.2008.06.004. 2. Brannan, S, Sawchak, S, et al.(2020). Efficacy and Safety of Xanomeline, a M1/M4 Receptor Preferencing Agonist, Plus Trospium, a Peripheral Muscarinic Antagonist, in Schizophrenia. Biological Psychiatry, 87(9), S169. doi: 10.1016/j.biopsych.2020.02.446 3. Patel, S, Saxena, B., Mehta, P. (2021). Recent updates in the clinical trials of therapeutic monoclonal antibodies targeting cytokine storm for the management of COVID-19. Heliyon, 7(2), e06158. doi: 10.1016/j.heliyon.2021.e06158
ABSTRACT
Objective: To report a patient presenting with bulbar symptoms in the setting of COVID-19 infection leading to a new diagnosis of Myasthenia Gravis. Background: There have been many reports of neurological complications in patients with COVID-19 infection including Guillain Barre syndrome, Bell's palsy and transverse myelitis. There are limited case series describing the effects of COVID-19 in patients with known Myasthenia Gravis, but there have only been rare reports of new onset Myasthenia Gravis in the setting of COVID-19 infection. Design/Methods: Electronic medical records of the patient were reviewed. Results: 78 year old man presented to the hospital with new onset of dysphagia, dysarthria, bilateral ptosis and left facial droop. The patient was given intravenous alteplase for possible stroke. On admission the patient also tested positive for COVID-19. His symptoms persisted post-alteplase. On exam he was noted to have fatigable ptosis, weakness of brow elevation, eye closure, horizontal movements of the tongue and intermittent dysarthria, raising the concern for myasthenia gravis. A trial of Mestinon led to improved symptoms. Serum acetylcholine receptor antibodies were positive, confirming the Myasthenia Gravis diagnosis. He received 5 sessions of intravenous immunoglobulin (IVIG) due to persistent bulbar symptoms. He initially responded well to treatment but later decompensated with respiratory failure requiring intubation. He was then treated with plasmapheresis for 5 days with symptom improvement and was successfully extubated. Conclusions: Our patient with a new diagnosis of myasthenia gravis with simultaneous COVID-19 infection eventually progressed into myasthenic crisis. This case raises the possibility of myasthenia and/or myasthenic crisis being a neurological complication of COVID-19 infection. Mechanisms behind this have been postulated to include molecular mimicry, the inflammatory cascade of COVID-19 leading to immune dysregulation, or viral illness triggering previously asymptomatic patients. Awareness of new onset myasthenia associated with COVID-19 infection can lead to earlier diagnosis and treatment.