Miller Fisher Syndrome (MFS) is an acute peripheral neuropathy that can develop after exposure to a viral or bacterial infection. It includes triad of ophthalmoplegia, areflexia and ataxia. In COVID-19 pandemic period, while COVID-19 typically presents with fever, shortness of breath (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.

• The first reported case of MFS with a history of COVID-19 was detected in January 2020 in Shanghai, who was a middle-aged 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. ^[1]

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

• Miller Fisher Syndrome (MFS) is related to dysfunction of third, fourth, 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 ophthalmoparesis 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.^[2]

• Although Miller Fisher Syndrome (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

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

• 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.

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

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

• 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

• Although the diagnosis of COVID-19 is based on respiratory symptoms, it can be associated with neurological symptoms, which overlap the diagnosis of MFS.
• Consequently, inpatient 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, a nasal swab test and neurological examination should be considered.
• MRI may be performed as a part of the diagnostic workup. Although in majority of cases no abnormality is detected, enlargement and prominent enhancement in orbits and retro-orbital region has been reported in some cases.^[3]. ^[4]

• Common symptoms of covid-19 associated with MFS include:
  • Shortness of breath
  • Cough
  • Fever
  • Ophthalmoplegia
  • Areflexia
  • Ataxia

• Less common symptoms of covid-19 associated with MFS include:
  • Headache^[5]
  • Diplopia
  • Blurred vision
  • Ptosis
  • Facial droop

• 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:

Abnormal signs associated with covid-19:

• Tachycardia
• Tachypnea
• Fever

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

• Laboratory findings consistent with the diagnosis of COVID-19 include positive PCR nasal swab.
• Laboratory tests for neurological signs are not diagnostic and should be used with other clinical parameters. They include:
  • Ganglioside (GM1) Antibodies, IgG and IgM
  • GD1b Antibody, IgM
  • GQ1b Antibody, IgG

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

• Chest X-ray 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.^[6]

• Lung ultrasound may be helpful in the 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

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

• Bilateral ground glass opacities
• Air space consolidation
• Bronchovascular thickening
• Traction bronchiectasis

• 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.

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

• No specific treatment and vaccine exists for covid-19 yet.
• However, patients with moderate to severe ARDS and respiratory manifestations can benefit from Mechanical ventilation and extracorporeal membrane oxygenation (ECMO).
• In some patients the combination of antiviral therapies like protease inhibitors, ritonavir, and lopinavir (100-400mg/day)^[7] indicated partial success in treatment of COVID-19.
• Remdesivir (100-200mg/day)^[8], a drug originally developed to treat Ebola virus, showed positive results against SARS-CoV-2.
• Dexamethasone (6mg/day)^{_Coronavirus_Disease_COVID-19-9|[9]} has been announced as an effective treatment in patients with systematic manifestations.

• Surgical intervention is not recommended for the management of covid-19.

• Effective measures for the primary prevention of covid-19 include hand-washing, wearing of face masks, social distancing, avoidance of large gathering and self-isolation for patients who have mild symptoms.

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