COVID-19-associated Miller-Fischer syndrome

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Template:ArashMoosavi

Synonyms and keywords:

Overview

Miller Fisher Syndrome (MFS) is an acute peripheral neuropathy which can develop after exposure to a viral or bacterial infection. It includes triad of ophtalmoplegia, areflexia and ataxia. In covid-19 pandemic period, while covid-19 typically presents with fever, SOB and respiratory symptoms, MFS with prior history of covid-19 has been seen in several cases all around the world.
One retrospective study in 214 patients has shown that 8.9 % of covid-19 patients have reported peripheral neurological symptoms.

Historical Perspective

The first reported case of MFS with history of covid-19 was detected on January 2020 in Shanghai, who was a middle-age woman diagnosed with MFS presented with areflexia, acute weakness in both legs and severe fatigue. Further reports were announced by medical groups in Spain and the USA which presented neuro-ophtalmological symptoms.

Classification

MFS is a rare variant of Guillain-Barre syndrome, characterized by ophtalmoplegia, areflexia and ataxia.

Pathophysiology

MFS is related to dysfunction of third, forth and sixth cranial nerves. A typical serological finding in patients with MFS and prior history of covid-19 is antibodies against GQ1b ganglioside, though negative test for antibodies does not rule out the diagnosis. The presence of ophtalmoparesis in MFS is related to a action of anti-GQ1b antibodies on the neuromuscular junction between the cranial nerves and ocular muscle. ELISA test is positive in 70% to 90% of patients.

Causes

Although MFS has been detected in some patients with covid-19, other viral and bacterial infections can also cause MFS

• Influenza virus
• Cytomegalovirus
• Zika virus
• Mycoplasma
• Campylobacter

Differentiating COVID-19-associated Miller-Fischer syndrome from other Diseases

MFS must be differentiated from other diseases that cause ophthalmoplegia, areflexia, and ataxia, such as myasthenia gravis, botulism, diphtheria, brain stem stroke, brain stem encephalitis and basal meningitis. It is essential to rule out emergent neurological disorders like stroke or brain injury in patients with MFS symptoms.

Epidemiology and Demographics

While the incidence of MFS is one or two person per million each year, the prevalence of MFS associated with covid-19 is still unknown.

Risk Factors

There are no established risk factors for MFS associated with covid-19.

Screening

There is insufficient evidence to recommend routine screening for patients with MFS caused by covid-19.

Natural History, Complications, and Prognosis

There is an increased risk of death in patients over the age of 60 year-old. Hence, the mortality rate is estimated to be 3.6%.
Risk factors for severe illness and poor prognosis include:

• Old age
• Male gender
• Patients with
  • Diabetes Mellitus
  • Hypertension
  • COPD
  • CKD

Diagnosis

Diagnostic Study of Choice

Although the diagnosis of covid-19 is based on respiratory symptoms, it can be associated with neurological symptoms, of which overlap the diagnosis of MFS. Consequently, in patient with prior history of covid-19, other neurologic diseases should be ruled out and anti-GQ1b antibody test should be considered. Also, in new patients with suspicious symptoms for covid-19 and neurological symptoms, nasal swab test and neurological examination should be considered.
MRI may be performed as a part of diagnostic work up. Although in majority of cases no abnormality is detected, enlargement and prominent enhacement in orbits and retro-orbital region has been reported in some cases..

History and Symptoms

Symptoms of covid-19 associated with MFS include:

• Respiratory system symptoms
  • shortness of breath
  • cough
• Neurological symptoms
  • headache
  • ataxia
  • ophthalmoplegia
  • areflexia

Physical Examination

Patients with covid-19 associated with MFS present various signs and symptoms related to systematic and neurological presentation. Hence physical examination should be performed based on signs and symptoms include:

Vitals

Abnormal signs associated with covid-19:

• Tachycardia
• Tachypnea
• Fever

neurological

• Eye dropping
• Blurry vision
• Paresthesia
• Decreased sensation
• Myalgia
• Weakness of breathing muscle

Laboratory Findings

Laboratory findings consistent with the diagnosis of covid-19 include positive PCR nasal swab.
Laboratory test for neurological signs are not diagnostic and should be used with other clinical parameters. They are include:

• Ganglioside (GM1) Antibodies, IgG and IgM
• GD1b Antibody, IgM
• GQ1b Antibody, IgG

Electrocardiogram

There are no ECG findings associated with covid-19.

X-ray

CXR is less sensitive in detection of covid-19 in comparison with CT. However, in some cases lung consolidation and patchy peripheral opacities corresponding to ground glass opacities has been reported.

Echocardiography or Ultrasound

There are no echocardiography/ultrasound findings associated with covid-19.
Lung Ultrasound may be helpful in evaluation of patients with covid-19. It indicates :

• Multiple B-lines
  • Ranging from focal to diffuse with spared areas
• Irregular and thickened pleural lines
• Subpleural consolidations
• Alveolar consolidations
• Bilateral A-lines

CT scan

The preliminary findings of CT in COVID-19 associated with MFS include:

• Bilateral Ground Glass Opacities
• Air space consolidation
• Bronchovascular thickening
• Traction bronchiectasis

MRI

Brain MRI may be helpful in the diagnosis of MFS in patients with prior history of covid-19 and neurological manifestations. Although there can be no abnormalities, multiple cranial nerve enhancement has been reported in some patients.

Other Diagnostic Studies

There are no other diagnostic studies associated with covid-19 with MFS manifestations.

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

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