COVID-19-associated Miller-Fischer syndrome

COVID-19 Microchapters
Home
Long COVID
Frequently Asked Outpatient Questions
Frequently Asked Inpatient Questions
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating COVID-19 from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X-ray
Echocardiography and Ultrasound
CT scan
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Interventions
Surgery
Primary Prevention
Vaccines
Secondary Prevention
Future or Investigational Therapies Ongoing Clinical Trials
Case Studies
Case #1
COVID-19-associated Miller-Fischer syndrome On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of COVID-19-associated Miller-Fischer syndrome All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on COVID-19-associated Miller-Fischer syndrome
CDC on COVID-19-associated Miller-Fischer syndrome
COVID-19-associated Miller-Fischer syndrome in the news
Blogs on COVID-19-associated Miller-Fischer syndrome
Directions to Hospitals Treating Psoriasis
Risk calculators and risk factors for COVID-19-associated Miller-Fischer syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Seyed Arash Javadmoosavi, MD[2]

Synonyms and keywords: MFS, fisher syndrome

Overview

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.

Historical Perspective

• 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.

Classification

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

Pathophysiology

• 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.

Causes

• 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

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:

Diseases	History and Physical								Diagnostic tests		Other Findings
	Motor Deficit	Sensory deficit	Cranial nerve Involvement	Autonomic dysfunction	Proximal/Distal/Generalized	Ascending/Descending/Systemic	Unilateral (UL) or Bilateral (BL) or No Lateralization (NL)	Onset	Lab or Imaging Findings	Specific test
Guillian-Barre syndrome	+	-	-	-	Generalized	Ascending	BL	Insidious	CSF: ↑Protein ↓Cells	Clinical & Lumbar Puncture	Progressive ascending paralysis following infection, possible respiratory paralysis
Acute Flaccid Myelitis	+	+	+	-	Proximal > Distal	Ascending	UL/BL	Sudden	MRI (Longitudinal hyperintense lesions)	MRI and CSF PCR for viral etiology	Drooping eyelids Difficulty swallowing Respiratory failure
Adult Botulism	+	-	+	+	Generalized	Descending	BL	Sudden	Toxin test	Blood, Wound, or Stool culture	Diplopia, Hyporeflexia, Hypotonia, possible respiratory paralysis
Infant Botulism	+	-	+	+	Generalized	Descending	BL	Sudden	Toxin test	Blood, Wound, or Stool culture	Flaccid paralysis (Floppy baby syndrome), possible respiratory paralysis
Eaton Lambert syndrome	+	-	+	+	Generalized	Systemic	BL	Intermittent	EMG, repetitive nerve stimulation test (RNS)	Voltage gated calcium channel (VGCC) antibody	Diplopia, ptosis, improves with movement (as the day progresses)
Myasthenia gravis	+	-	+	+	Generalized	Systemic	BL	Intermittent	EMG, Edrophonium test	Ach receptor antibody	Diplopia, ptosis, worsening with movement (as the day progresses)
Electrolyte disturbance	+	+	-	-	Generalized	Systemic	BL	Insidious	Electrolyte panel	↓Ca++, ↓Mg++, ↓K+	Possible arrhythmia
Organophosphate toxicity	+	+	-	+	Generalized	Ascending	BL	Sudden	Clinical diagnosis: physical exam & history	Clinical suspicion confirmed with RBC AchE activity	History of exposure to insecticide or living in farming environment. with : Diarrhea, Urination, Miosis, Bradycardia, Lacrimation, Emesis, Salivation, Sweating
Tick paralysis (Dermacentor tick)	+	-	-	-	Generalized	Ascending	BL	Insidious	Clinical diagnosis: physical exam & history	-	History of outdoor activity in Northeastern United States. The tick is often still latched to the patient at presentation (often in head and neck area)
Tetrodotoxin poisoning	+	-	+	+	Generalized	Systemic	BL	Sudden	Clinical diagnosis: physical exam & dietary history	-	History of consumption of puffer fish species.
Stroke	+/-	+/-	+/-	+/-	Generalized	Systemic	UL	Sudden	MRI +ve for ischemia or hemorrhage	MRI	Sudden unilateral motor and sensory deficit in a patient with a history of atherosclerotic risk factors (diabetes, hypertension, smoking) or atrial fibrillation.
Poliomyelitis	+	+	+	+/-	Proximal > Distal	Systemic	BL or UL	Sudden		PCR of CSF	Asymmetric paralysis following a flu-like syndrome.
Transverse myelitis	+	+	+	+	Proximal > Distal	Systemic	BL or UL	Sudden	MRI & Lumbar puncture	MRI	History of chronic viral or autoimmune disease (e.g. HIV)
Neurosyphilis	+	+	-	+/-	Generalized	Systemic	BL	Insidious	MRI & Lumbar puncture	CSF VDRL-specifc CSF FTA-Ab -sensitive	History of unprotected sex or multiple sexual partners. History of genital ulcer (chancre), diffuse maculopapular rash.
Muscular dystrophy	+	-	-	-	Proximal > Distal	Systemic	BL	Insidious	Genetic testing	Muscle biopsy	Progressive proximal lower limb weakness with calf pseudohypertrophy in early childhood. Gower sign positive.
Multiple sclerosis exacerbation	+	+	+	+	Generalized	Systemic	NL	Sudden	↑CSF IgG levels (monoclonal)	Clinical assessment and MRI	Blurry vision, urinary incontinence, fatigue
Amyotrophic lateral sclerosis	+	-	-	-	Generalized	Systemic	BL	Insidious	Normal LP (to rule out DDx)	MRI & LP	Patient initially presents with upper motor neuron deficit (spasticity) followed by lower motor neuron deficit (flaccidity).
Inflammatory myopathy	+	-	-	-	Proximal > Distal	Systemic	UL or BL	Insidious	Elevated CK & Aldolase	Muscle biopsy	Progressive proximal muscle weakness in 3rd to 5th decade of life. With or without skin manifestations.

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, 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

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 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

Electrocardiogram

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

X-ray

• 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

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

• 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.

Surgery

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

Primary Prevention

• 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.

References

Template:WikiDoc Sources