COVID-19-associated Miller-Fischer syndrome
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Synonyms and keywords: MFS, fisher syndrome
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. 
- 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.
- Although Miller Fisher Syndrome (MFS) has been detected in some patients with COVID-19, other viral and bacterial infections can also cause MFS:
Differentiating COVID-19-associated Miller-Fischer syndrome from other Diseases
- For further information about the differential diagnosis, click here.
- To view the differential diagnosis of COVID-19, click here.
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.
- 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:
Diagnostic Study of Choice
- 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.. 
History and Symptoms
- Common symptoms of covid-19 associated with MFS include:
Less common symptoms
- Less common symptoms of covid-19 associated with MFS include:
- 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:
- 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:
- 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.
Echocardiography or Ultrasound
- 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.
Other Diagnostic Studies
- 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) indicated partial success in treatment of COVID-19.
- Remdesivir (100-200mg/day), a drug originally developed to treat Ebola virus, showed positive results against SARS-CoV-2.
- Dexamethasone (6mg/day) 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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