COVID-19-associated myelitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Musadiq Ali M.B.B.S.[2] Tayebah Chaudhry[3]

Synonyms and keywords:

Overview

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/or plasma exchange.

Historical Perspective

  • 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, few case reports have been published in literature showing an association of COVID-19 with acute myelitis as a neurological complication.

Classification

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

Pathophysiology

  • 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.
  • The brain only the vascular cells were expressing ACE2 as a cell receptor not the neurons; yet this could be a potential mechanism for dissemination of the virus into the brain by the blood circulation.
  • 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.
  • This route must be taken into consideration in cases of early‐phase COVID‐19‐affected patients who exhibit loss of smell and taste.
  • Furthermore, in advanced stages of the disease the neurological signs and symptoms observed in the COVID‐19 cases could be due to the effects of hypoxia, respiratory, and metabolic acidosis

Causes

  • Apart from Covid associated Myelitis other Viruses associated with myelitis are:
  • 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

Differentiating COVID-19-associated myelitis from other Diseases

  • There are a number of conditions that appear to cause myelitis and hence should be differentiated from COVID-19-associated myelitis:

Multiple sclerosis

  • The immune system destroys myelin surrounding nerves in your spinal cord and brain. Transverse myelitis can be the first sign of multiple sclerosis or represent a relapse. Transverse myelitis as a sign of multiple sclerosis usually causes symptoms on only one side of your body. Neuromyelitis optica (Devic's disease) is a condition that causes inflammation and myelin loss around the spinal cord and the nerve in your eye that transmits information to your brain. Transverse myelitis associated with neuromyelitis optica usually affects both sides of your body.

Transverse myelitis

  • Transverse myelitis experience symptoms of damage to myelin of the optic nerve, including pain in the eye with movement and temporary vision loss. This can happen with or separately from transverse myelitis symptoms. However, some people with neuromyelitis optica don't experience eye-related problems and might have only recurrent episodes of transverse myelitis.

Autoimmune disorders

  • These disorders include lupus, which can affect multiple body systems, and Sjogren's syndrome, which causes severe dryness of the mouth and eyes.

Vaccinations

  • Vaccination for infectious diseases have occasionally been associated as a possible trigger. However, at this time the association is not strong enough to warrant limiting any vaccine.

Sarcoidosis

  • Sarcoidosis is a condition that leads to inflammation in many areas of the body, including the spinal cord and optic nerve. It may mimic neuromyelitis optica, but typically sarcoidosis symptoms develop more slowly. The cause of sarcoidosis isn't understood.

Epidemiology and Demographics

As of now, the incidence of acute myelitis associated with Covid-19 infection in unknown. [3]

Risk Factors

There are no established risk factors for COVID-19-associated myelitis.

Screening

Screening for COVID-19-associated myelitis is not currently done.

Natural History, Complications, and Prognosis

  • Exact prognosis of COVID-19-associated myelitis is not known.
  • Marked improvement in symptoms is seen with steroids and plasma exchange. However, lack of prompt recognition and management may result in lasting neurological effects (such as residual loss of sensation in lower extremities) after novel corona virus infection. [2]

Diagnosis

Diagnostic Study of Choice

  • 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. [3]

History and Symptoms

Symptoms of COVID-19-associated myelitis include:

Physical Examination

Vitals:

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

Abdominal exam:

  • Palpable distended urinary bladder

Neurological exam:

Neurological findings are symmetric and more severe in lower extremities. [1] [2] [3]

Laboratory Findings

Nasal swab:

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

Other Viral Screening:

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. [4]

Electrocardiogram

There are no ECG findings associated with COVID-19-associated myelitis.

X-ray

Chest X-ray may or may not show opacities in lungs depending on the degree of lung damage caused by COVID-19.

Echocardiography or Ultrasound

  • There are no echocardiography findings associated with COVID-19-associated myelitis.
  • Abdominal ultrasound may show bladder distention due to urinary retention.

CT scan

CT chest may show patchy changes in the lung fields due to COVID-19-associated lung damage.

MRI

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.

Treatment

Medical Therapy

There is no treatment for [disease name]; the mainstay of therapy is supportive care.

OR

Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].

OR

The majority of cases of [disease name] are self-limited and require only supportive care.

OR

[Disease name] is a medical emergency and requires prompt treatment.

OR

The mainstay of treatment for [disease name] is [therapy].

OR

The optimal therapy for [malignancy name] depends on the stage at diagnosis.

OR

[Therapy] is recommended among all patients who develop [disease name].

OR

Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].

OR

Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].

OR

Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].

OR

Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].

Surgery

Surgical intervention is not recommended for the management of [disease name].

OR

Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]

OR

The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].

OR

The feasibility of surgery depends on the stage of [malignancy] at diagnosis.

OR

Surgery is the mainstay of treatment for [disease or malignancy].

Primary Prevention

There are no established measures for the primary prevention of [disease name].

OR

There are no available vaccines against [disease name].

OR

Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

OR

[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].

Secondary Prevention

There are no established measures for the secondary prevention of [disease name].

OR

Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].

References

  1. 1.0 1.1 "www.medrxiv.org" (PDF).
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "A Case Report of Acute Transverse Myelitis Following Novel Coronavirus Infection".
  3. 3.0 3.1 3.2 3.3 3.4 3.5 AlKetbi, Reem; AlNuaimi, Dana; AlMulla, Muna; AlTalai, Nouf; Samir, Mohammed; Kumar, Navin (2020). "Acute Myelitis as a Neurological Complication ofCovid-19:A Case Report and MRI Findings". Radiology Case Reports. doi:10.1016/j.radcr.2020.06.001. ISSN 1930-0433.
  4. "Acute transverse myelitis after COVID-19 pneumonia".


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