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Coronavirus and Neuromuscular Disorders PowerPoint Presentation

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Description : In this presentation, you will find recent studies about the effects of coronavirus from the neuromuscular disorders aspect.

Tags : coronavirus neurology neuromuscular

Published on : Mar 30, 2021 | Views : 2122 | Downloads : 8

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Neuromuscular Disorders COVID-19
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newer coronavirus infections Severe Acute respiratory syndrome (SARS) Middle East respiratory syndrome (MERS) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – (COVID-19) Headache Seizures Stroke Neuromuscular complications?
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Assessment of overall risk from COVID-19 in patients with NMD Risks will depend upon the specific NMD, other comorbidities, age, and what immunotherapies the patients may be receiving. We do not expect the majority of patients, even in the higher risk categories, to have severe complications of COVID-19. We also can reassure patients that NMDs that spare swallowing and breathing muscles and where treatment does not involve immunosuppression are not considered to be high risk in COVID-19.
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COVID-19–associated GBS GBS has been described in association with SARS-CoV-22-7 and other coronaviruses. molecular mimicry between viral epitopes and peripheral nerves, stimulates an autoimmune driven bystander attack against myelin or axons Although there are multiple case reports, the frequency of GBS in association with SARS-CoV-2 infection is unclear
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COVID-19–associated GBS The latency between the onset of COVID-19 symptoms and time to onset of GBS ranges from 2 days to 4 weeks, cases in which weakness preceded typical COVID-19 symptoms have been described The frequency of respiratory failure is slightly higher in COVID-19-associated GBS compared with more commonly described GBS, likely a reflection of the concurrent pulmonary disease.
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COVID-19–associated GBS (CSF) analysis: typical albumin-cytological dissociation Sensorimotor axonal, mixed axonal and demyelinating and demyelinating findings Miller-Fisher syndrome has also been reported.
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COVID-19–associated GBS COVID-19–associated GBS have been treated with IVIG IVIG - a potential treatment of COVID-19 Thromboembolic side effects! Hemodynamic status in critically ill patients - a limiting factor to the use of PLEX
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Muscle Complications Muscle complications have been commonly associated with coronavirus infections. Postmortem pathology (8 people died from SARS) myofiber necrosis (50%) myofiber atrophy (50%) Immune-mediated myopathy and superimposed steroid myopathy were postulated as the causes.
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Muscle Complications Coronavirus infections may be associated with muscle complications. Myalgia or fatigue (36-70%) CK ↑ (>200) + myalgia (11%) – Wuhan, China CK ↑ (9%) – evidence of myopathy (3%) – Spain (814 pts) Flaccid quadriplegia, intact facial strength and ocular movements Normal – mildly elevated CK Evidence of myopathic abnormalities on electrophysiologic testing 6 individuals Italy
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Muscle Complications These are likely finding of critical illness myopathy. A direct effect of SARS-CoV-2 on muscle fibers? Supported by finding of angiotensin converting enzyme (ACE) 2 receptors on myofibers Myositis - MRI in a person with interstitial pneumonitis / auto-immune mechanism Rhabdomyolysis (0.2% - 1.1%) - more prevalent in patients with severe disease
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Mononeuropathies In a cohort of 83 patients admitted to hospital with ARDS and COVID-19, 14.5% - mononeuropathies Ulnar Radial Sciatic Nerves Could be related to the use of prone positioning for management However, whether this finding is directly associated with the prone position, the viral infection, or the multiple comorbidities seen in this patient group is unknown
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Neuromuscular Junction Disorders In a series of 3 cases of new onset acetylcholine receptor antibody-positive (antiAChR+) myasthenia gravis (MG) after COVID-19 diplopia, ptosis, dysphagia, generalized weakness 5 to 7 days after the onset of febrile illness
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Neuromuscular Junction Disorders A decrement in repetitive nerve stimulation Elevated titers of antiAChR were found in all 3 individuals. The authors concluded these are cases of new-onset MG and proposed a molecular mimicry mechanism. The direct relationship between COVID-19 and the development of MG, however, is debatable.
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Neuromuscular Junction Disorders It is possible these patients had subclinical MG that was unmasked by viral illness or the use of antibiotics or antimalarials There are no other cases described in the literature Further studies are needed to determine if there is a true association between SARS-CoV-2 infection and the development of neuromuscular junction disorders.
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Critical Illness Acquired Weakness In those who are critically ill with COVID-19, determining if weakness is a manifestation of the critical illness itself or the complications associated with SARS-CoV-2 can be challenging. In a large case series, neurologic complications were more common in severe COVID-19, suggesting that neuromuscular manifestations could be related, at least in part, to the critical illness.
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Critical Illness Acquired Weakness A single-center study: people with COVID‑19 who required mechanical ventilation had ICUAW upon awakening (72%), at ICU discharge (52%), at the time of hospital discharge (27%). Those who developed ICUAW had longer times on ventilation and in the ICU, higher morning glucose levels, and received more dialysis, corticosteroids, sedatives, analgesics, and neuromuscular blockade.
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Neuromuscular complications
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Risk of infection causing a new NMD No current evidence of direct viral invasion with inflammation and degeneration of motor neurons and peripheral nerves as seen in some viral infections 1 report of a 3-year-old child with acute flaccid paralysis who was coinfected with 2 coronaviruses (HCoV 229E and OC43) It is possible that the virus may be neurotropic and directly infect and damage motor neurons and peripheral nerves.
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Risk of infection causing a new NMD Critical illness myopathy  use of nondepolarizing neuromuscular blocking agents This has not been reported in patients with other coronavirus receiving short courses of these medications. Weakness related to type 2 muscle fiber atrophy from disuse - after 1 week in ill patients who are bedridden
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Risk of COVID-19 infection exacerbating NMDs There are no data regarding magnitude of risk of exacerbation due to COVID-19 or prior coronaviruses for rare NMDs. We expect that we will observe both increased rates of disease worsening and an increased incidence of new presentations during the COVID-19 pandemic. Considerations for exacerbation in acquired and inherited disorders are related to: degree of baseline cardiac and respiratory dysfunction, bulbar weakness, underlying pathophysiology of disease related comorbid conditions
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Risk of COVID-19 infection exacerbating NMDs Motor neuron disease  hereditary neuropathies with ventilatory muscle involvement may be particularly susceptible to infection. Those with metabolic myopathies  ↑risk of rhabdomyolysis with fever, infection, or fasting (lipid storage diseases, mitochondrial disorders) Various muscular dystrophies  increased risk for severe COVID-19 (myotonic dystrophy and metabolic diseases + resp weakness/cardiomyopathy) Patients who develop COVID-19 may not return to their prior baseline.
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Risks of immunosuppressant therapies in patients with autoimmune NMDs Patients with NMDs who use immunosuppressive therapies  ↑risk of contracting COVID-19 or having a more severe course of the virus. This risk is variable even among patients on ISTs and with the same disease. Most outpatients without infection should continue to take their medications, Instructions to call their neurologist and temporarily hold the medication if they develop symptoms of infection.
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Risks of immunosuppressant therapies in patients with autoimmune NMDs Efficient prescribing - minimizing trips to pharmacies: refilling prescriptions for 90 days and encouraging delivery through mail order pharmacies Weighing benefits of transitioning from infusion centers to home infusions will depend on patients’ overall COVID-19 risk, transportation needs, geography/local resources, insurance coverage.
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Risks of immunosuppressant therapies in patients with autoimmune NMDs Some patients may be treated with a different, less immunosuppressive option after discussion of risk and benefit between the patient and provider: age, comorbid medical problems, geographic location, household or occupational risk factors, underlying neuromuscular disease severity
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Risks of immunosuppressant therapies in patients with autoimmune NMDs Holding or suspending prednisone is not recommended. Some therapies are not expected to increase the risk of COVID-19 or severe disease: Immunoglobulin therapy (intravenous or subcutaneous), Complement inhibitor therapy (e.g., eculizumab), Therapeutic plasma exchange, Neonatal Fc receptor (FcRn) antagonists
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COVID-19 vaccine efficacy and access in NMDs Immunocompromised patients including those with autoimmune disorders or on immunosuppressive medications were excluded from vaccine trials. In addition to the unknown efficacy of the COVID-19 vaccine in these patients, there are several other unanswered questions about vaccinations in patients on immunosuppressive agents. The data so far has not revealed an increased risk of COVID-19 complications in immunocompromised patients except those on moderate or high doses of corticosteroids.
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Management of patients with NMD who develop COVID-19 There are no neuromuscular-specific recommendations for patients who contract COVID-19. Monitoring moderate to high risk patients with NMDs closely for the possibility of more rapid decline in respiratory function or for worsening of their underlying neuromuscular disease is recommended. Corticosteroids are not routinely given for treatment of COVID-19 but are sometimes used in sepsis. A discussion of the potential pros and cons of additional corticosteroids is available. Patients with NMD already on corticosteroids may require stress doses. Typically, other immunosuppression is held or continued based on the patient’s clinical status from COVID-19 and the severity of their underlying NMD.
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Management of patients with NMD who develop COVID-19 Several organizations, such as the association of British neurologists in association with subspecialist advisory groups and the World Muscle Society have proposed guidance for people with specific neurologic diseases during the COVID‑19 pandemic. In general, physicians caring for patients with neuromuscular disorders should reinforce public health recommendations including practicing social distancing, wearing facemasks, and handwashing. Hospitalization should be avoided if possible but not be delayed when necessary
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Risks of treatments for COVID-19 Antiviral drugs Lopinavir/ Ritonavir - protease inhibitors / HIV infection Remdesivir - inhibits viral RNA polymerases ( Potent activity in vitro against filoviruses (e.g., Ebola virus) and coronaviruses (e.g., ARSCoV, MERS-CoV) ) Both, however, failed to show clinical improvement for COVID‑19 Associated with toxic myopathy and rhabdomyolysis
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Risks of treatments for COVID-19 Chloroquine and hydroxychloroquine (in vitro studies) New-onset or worsening MG slowly progressive, painless, proximal weakness and atrophy in the legs sensory loss and reduced muscle stretch reflexes Cardiomyopathy CK levels are usually slightly elevated
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Risks of treatments for COVID-19 Motor and sensory nerve conductions: reduced amplitudes with slightly slow conduction velocities Needle EMG: positive sharp waves, fibrillation potentials, and myotonic discharges, particularly in proximal muscles Muscle biopsy: autophagic vacuoles in skeletal and cardiac muscle fibers Toxic Neuromyopathy - high dosages for a year or more
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Risks of treatments for COVID-19 Azithromycin  worsening of MG was not associated with reduced 90-day mortality, no improvement in CoV RNA clearance
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NEUROMUSCULAR DISEASES AND COVID-19
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Changes in neuromuscular systems of care Triage system to allocate scheduled outpatients in-person encounters, telemedicine encounters, to delay the visit or procedure if medically appropriate. Most outpatient electrodiagnostic studies and muscle and nerve biopsies postponed Outpatient pulmonary function tests could not be performed due to increased risks Speech therapy – swallow assessment
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Rapid integration of telemedicine Many institutions have transitioned heavily to telemedicine due to necessity and relaxation of prior regulatory limitations Neurologists are quickly discovering the strengths and limitations of telemedicine, and new tools and skills required. Limitations in the physical examination - strength, sensation, and reflex examination Coordinating local laboratory or imaging evaluation and pulmonary function testing
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Rapid integration of telemedicine
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COVID-19’s effect on neuromuscular training
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PowerPoint-Presentation COVID-19