COVID-19-associated myelitis

In the current pandemic state, COVID-19 should be considered as a differential diagnosis in a patient presenting with acute myelitis. Acute Transverse Myelitis is a neurological condition characterized by inflammation and injury of the spinal cord. In a confirmed or newly diagnosed patient of COVID-19, it is thought to be either a direct consequence of viral infection or a sequalae of autoimmune-mediated response. COVID-19-associated myelitis is diagnosed based on the hallmark symptoms of acute myelitis and confirmed with changes on spinal MRI, after ruling out other possible etiologies of myelitis. The symptoms show marked improvement after treatment with steroids and plasma exchange.

• First case of acute myelitis as a COVID-19 complication was reported in February 2020 in Wuhan by Kang Zhao et al, in a 66 year old male patient. ^[1]
• The second case was reported in Boston by Sarma et al in a 28 year old female patient who developed acute myelitis 7 days after symptoms of upper respiratory tract infection. ^[2]
• As of now, only few case reports have been published in literature showing an association of COVID-19 with acute myelitis as a neurological complication.

• There is no established system for the classification of COVID-19-associated myelitis.

• The pathogenesis of the disease behind this manifestation is not fully understood yet.
• There is a strong evidence suggesting that COVID-19 virus uses angiotensin-converting enzyme2 (ACE2) as its receptor to interact with host cells.
• This evidence is based on the previous extensive SARS-CoV structural analyses that showed interactions between the SARS-CoV virus and ACE2 receptors and because of the marked sequence similarities between Covid-19 and the SARS-CoV virus it is hypothesized that COVID 19 virus pathogenesis is comparable.
• The ACE2 receptors are expressed on alveolar epithelial cells, intestinal enterocytes and arterial and venous endothelial cells.
• In the brain, only the vascular cells expressed ACE2 cell receptors, not the neurons; yet attachment of the virus to the vascular endothelium this could be a potential mechanism for dissemination of the virus into the brain by the blood circulation^[3].
• It is also hypothesized that the virus can disseminate into the nervous system through the olfactory bulb in which sensory neurons connect the nasal cavity to the central nervous system by the axons, which terminate in the olfactory bulb and passes through the cribriform plate^[4].
• Early‐phase COVID‐19‐affected patients may exhibit loss of smell and taste as a result of this ^[5].
• In advanced stages of the disease the neurological signs and symptoms observed with COVID‐19 could also be due to the effects of hypoxia, respiratory, and metabolic acidosis^[6].

Apart from COVID-19 other causes of viral myelitis include^[7]:

• Herpes viruses, including the one that causes shingles and chickenpox (zoster)
• Cytomegalovirus
• Epstein-Barr
• HIV
• Enteroviruses such as poliovirus and coxsackievirus
• West Nile
• Echovirus
• Zika
• Influenza
• Hepatitis B
• Mumps, measles and rubella

Other causes of myelitis are:

• Bacterial myelitis
• Fungal myelitis
• Parasitic myelitis
• Multiple Sclerosis
• Transverse Myelitis
• Autoimmune disorders like SLE and Sjogren’s Syndrome
• Sarcoidosis
• Vaccinations

• For further information about the differential diagnosis, click here.
• To view the differential diagnosis of COVID-19, click here.

• As of now, the incidence of acute myelitis associated with Covid-19 infection in unknown. ^[8][9]
• To view epidemiology and demographics for COVID-19, click here.
  

• There are no established risk factors for COVID-19-associated myelitis. However, since this condition is a direct consequence of infection by the novel coronavirus, risk factors for COVID-19 should be considered.
• To view the risk factors of COVID-19, click here.

• Screening for COVID-19-associated myelitis is not currently done.
• To view screening for COVID-19, click here.
  

Natural History

• Myelitis associated with COVID-19 is an acute condition. The first case of COVID-19 associated myelitis developed the symptoms 5 days after the onset of fever. ^[1]
• The second case developed symptoms of myelitis 7 days after the upper respiratory symptoms. ^[2]

Complications

• Lack of prompt recognition and management may result in lasting neurological complications (such as residual loss of sensation in lower extremities) after novel corona virus infection. ^[2]

Prognosis

• Exact prognosis of COVID-19-associated myelitis is not known.
• Marked improvement in symptoms is seen with steroids and plasma exchange.

• Diagnosis of COVID-19-associated myelitis is based on the hallmark symptoms of acute myelitis in a known case of COVID-19 or a positive PCR nasal swab for COVID-19 in a new patient. And classic contrast-enhancing lesions on MRI spine.
• Hallmark symptoms of acute myelitis include bilateral symmetric weakness and sensory changes in extremities, urinary retention and lower back pain.
• Absence of visual symptoms such as eye pain or vision loss ( classically seen in Multiple Sclerosis or Neuromyelitis optica), negative immunoglobulin G auto-antibodies or oligoclonal bands, negative anti-nuclear antibody (ANA) test (very sensitive test for autoimmune diseases such as lupus), absence of other system involvement (such as skin rash, nodules, cardiac arrhythmias or arthritis seen in lupus or sarcoidosis) rule out other possible etiologies. ^[8]

Common symptoms

• Paraplegia ^[8]

• Urinary retention ^[8]
• Lower back pain ^[2]
• Weakness in lower extremities ^[8]

Less common symptoms

• Paresthesias in lower extremities with possible ascension to upper extremities ^[2]
• Numbness in lower extremities with possible ascension to upper extremities^[2]
• Numbness in tip of tongue ^[2]

Vitals:

Abnormal vitals can be seen due to COVID-19 association. These include:

• Decreased O2 saturation
• Tachycardia
• Tachypnea

Abdominal exam:

• Palpable distended bladder

Neurological exam:

Neurological findings are symmetric and more severe in lower extremities. ^{[1] [2] [8]}

• Wide based gait
• Decreased muscle strength
• Decreased sensation
• Decreased proprioception
• Hyporeflexia
• Paresthesias
• Positive Lhermitte’s sign
• Positive Babinski’s sign bilaterally.

Nasal swab:

• PCR nasal swab may give positive result for COVID-19.

Other Viral Screening:

• Viral PCR screening including Adenovirus, Herpes Simplex Virus (Type 1&2), Epstein Barr Virus, Cytomegalovirus, Human Immunodeficiency Virus (HIV) will yield negative results.
• Viral serology for Influenza Virus A and B, Parainfluenza 1-4, Respiratory Syncytial virus, Enterovirus and Rhinovirus with negative results.
• Negative antibody results for bacteria such as Chlamydia Pneumoniae, Bordetella Pertussis, Mycoplasma Pneumoniae and Borrelia.

MRI spine:

• MRI findings consistent with Acute Transverse Myelitis (involving more than three spinal cord segments) are seen. This includes widespread elongated signal changes throughout the gray matter of spinal cord, with no disc pathology or spinal canal narrowing. ^[2]

Urinary retention:

• Foley catheter insertion will show and relieve retained urine.

Lumbar Puncture (LP):

• CSF analysis may show lymphocytic pleocytosis and elevated protein level. ^[10]

To view the laboratory findings on COVID-19, click here

• There are no ECG findings associated with COVID-19-associated myelitis.
• To view the electrocardiogram findings on COVID-19, click here.
  

• Chest X-ray may or may not show opacities in lungs depending on the degree of lung damage caused by COVID-19.
• To view the x-ray finidings on COVID-19, click here.
  

• There are no echocardiography findings associated with COVID-19-associated myelitis.
• Abdominal ultrasound may show bladder distension due to urinary retention.
• To view the echocardiographic findings on COVID-19, click here.
  

• CT scan exclude other causes that can cause myelitis.
• To view the CT scan findings on COVID-19, click here.

• MRI may be used to exclude other causes.
• MRI findings consistent with Acute Transverse Myelitis (involving more than three spinal cord segments) are seen.
• This includes widespread elongated signal changes throughout the gray matter of spinal cord, with no disc pathology or spinal canal narrowing.
• T2-weighted fast spin-echo and short-tau inversion recovery (STIR) are the best sequences to view the spinal cord lesions^[11].
• To view other imaging findings on COVID-19, click here.
  

• Oxygen inhalation treatment with high-flow nasal catheters.
• Ganciclovir ( 0.5g once daily) for 14 days, Lopinavir/ritonavir (500mg twice daily) for 5 days. “Coronavirus Disease 2019 (COVID-19) Treatment Guidelines”.
• Moxifloxacin (400mg once daily) for 6 days.(Treatment with arbidol and moxifloxacin could be helpful in reducing viral load and inflammation during SARS-CoV2 infection, especially for negatively regulating fatal inflammation in severe COVID-19 patients)^[12].
• Glutathione (1.8g once daily) for 14 days. (Glutathione inhibits replication of various viruses at different stages of the viral life cycle and decreasing viral load. It also prevents the massive release of inflammatory cells into the lung “cytokine storm”)^[13].
• Dexamethasone (10mg once daily) for 10 days^[14]. (NIH COVID-19 Treatment Guidelines Panel recommends using dexamethasone (at a dose of 6 mg per day for up to 10 days) in patients with COVID-19 who are mechanically ventilated and in patients with COVID-19 who require supplemental oxygen but who are not mechanically ventilated. And recommends against using dexamethasone in patients with COVID-19 who do not require supplemental oxygen.
• Human immunoglobulin (15g once daily) for 7 days.
• Pantoprazole (80mg once daily) for 10 days.
• Mecobalamin (1000ug once daily) for 14days.^[15] (Vitamin B12 may inhibit RNA-dependent-RNA polymerase activity of nsp12 protein from the COVID-19 Virus).
• Plasma exchange.
• Foley’s catheter to relieve urinary retention

• Surgical intervention is not recommended for the management of COVID-19-associated myelitis.

• Effective measures for the primary prevention of COVID-19-associated myelitis are the same as of COVID-19.

• Effective measures for the secondary prevention of COVID-19-associated myelitis are the same as of COVID-19.

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