COVID-19-associated Miller-Fischer syndrome: Difference between revisions
Line 12: | Line 12: | ||
==Historical Perspective== | ==Historical Perspective== | ||
The first reported case of MFS with history of | * 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. <ref><nowiki>{{</nowiki>https://n.neurology.org/content/early/2020/04/17/WNL.0000000000009619<nowiki>}}</nowiki></ref> | |||
==Classification== | ==Classification== | ||
MFS is a rare variant of [[Guillain-Barre syndrome]], characterized by [[ophtalmoplegia]], [[areflexia]] and [[ataxia]]. | * MFS is a rare variant of [[Guillain-Barre syndrome]], characterized by [[ophtalmoplegia]], [[areflexia]] and [[ataxia]]. | ||
==Pathophysiology== | ==Pathophysiology== | ||
MFS is related to dysfunction of third, | * [[Miller Fisher Syndrome]] (MFS) is related to dysfunction of third, fourth, and sixth [[cranial nerves]]. | ||
* A typical [[Serology|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 muscles|ocular muscle]]. [[ELISA test]] is positive in 70% to 90% of patients.<ref><nowiki>{{</nowiki>https://pubmed.ncbi.nlm.nih.gov/10695710<nowiki>}}</nowiki></ref> | |||
==Causes== | ==Causes== | ||
Although MFS has been detected in some patients with | |||
*[[Influenza | * Although [[Miller Fisher Syndrome]] (MFS) has been detected in some patients with [[COVID-19]], other viral and [[bacterial]] infections can also cause MFS: | ||
*[[Cytomegalovirus]] | **[[Influenza Virus]] | ||
*[[Zika virus]] | **[[Cytomegalovirus]] | ||
*[[Mycoplasma]] | **[[Zika virus]] | ||
*[[Campylobacter]] | **[[Mycoplasma]] | ||
**[[Campylobacter]] | |||
==Differentiating COVID-19-associated Miller-Fischer syndrome from other Diseases== | ==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:<ref><nowiki>{{</nowiki>https://rarediseases.org/rare-diseases/miller-fisher-syndrome/<nowiki>}}</nowiki></ref><ref name="pmid29433111">{{cite journal |vauthors=Kira R |title=[Acute Flaccid Myelitis] |language=Japanese |journal=Brain Nerve |volume=70 |issue=2 |pages=99–112 |date=February 2018 |pmid=29433111 |doi=10.11477/mf.1416200962 |url=}}</ref><ref name="pmid29433111">{{cite journal |vauthors=Kira R |title=[Acute Flaccid Myelitis] |language=Japanese |journal=Brain Nerve |volume=70 |issue=2 |pages=99–112 |date=February 2018 |pmid=29433111 |doi=10.11477/mf.1416200962 |url=}}</ref><ref name="pmid29181601">{{cite journal |vauthors=Hopkins SE |title=Acute Flaccid Myelitis: Etiologic Challenges, Diagnostic and Management Considerations |journal=Curr Treat Options Neurol |volume=19 |issue=12 |pages=48 |date=November 2017 |pmid=29181601 |doi=10.1007/s11940-017-0480-3 |url=}}</ref><ref name="pmid27422805">{{cite journal |vauthors=Messacar K, Schreiner TL, Van Haren K, Yang M, Glaser CA, Tyler KL, Dominguez SR |title=Acute flaccid myelitis: A clinical review of US cases 2012-2015 |journal=Ann. Neurol. |volume=80 |issue=3 |pages=326–38 |date=September 2016 |pmid=27422805 |pmc=5098271 |doi=10.1002/ana.24730 |url=}}</ref><ref name="pmid29028962">{{cite journal |vauthors=Chong PF, Kira R, Mori H, Okumura A, Torisu H, Yasumoto S, Shimizu H, Fujimoto T, Hanaoka N, Kusunoki S, Takahashi T, Oishi K, Tanaka-Taya K |title=Clinical Features of Acute Flaccid Myelitis Temporally Associated With an Enterovirus D68 Outbreak: Results of a Nationwide Survey of Acute Flaccid Paralysis in Japan, August-December 2015 |journal=Clin. Infect. Dis. |volume=66 |issue=5 |pages=653–664 |date=February 2018 |pmid=29028962 |pmc=5850449 |doi=10.1093/cid/cix860 |url=}}</ref><ref name="pmid29482893">{{cite journal |vauthors=Messacar K, Asturias EJ, Hixon AM, Van Leer-Buter C, Niesters HGM, Tyler KL, Abzug MJ, Dominguez SR |title=Enterovirus D68 and acute flaccid myelitis-evaluating the evidence for causality |journal=Lancet Infect Dis |volume=18 |issue=8 |pages=e239–e247 |date=August 2018 |pmid=29482893 |doi=10.1016/S1473-3099(18)30094-X |url=}}</ref><ref name="pmid30200066">{{cite journal |vauthors=Chen IJ, Hu SC, Hung KL, Lo CW |title=Acute flaccid myelitis associated with enterovirus D68 infection: A case report |journal=Medicine (Baltimore) |volume=97 |issue=36 |pages=e11831 |date=September 2018 |pmid=30200066 |pmc=6133480 |doi=10.1097/MD.0000000000011831 |url=}}</ref><ref name="urlBotulism | Botulism | CDC">{{cite web |url=https://www.cdc.gov/botulism/index.html |title=Botulism | Botulism | CDC |format= |work= |accessdate=}}</ref><ref name="pmid3290234">{{cite journal |vauthors=McCroskey LM, Hatheway CL |title=Laboratory findings in four cases of adult botulism suggest colonization of the intestinal tract |journal=J. Clin. Microbiol. |volume=26 |issue=5 |pages=1052–4 |date=May 1988 |pmid=3290234 |pmc=266519 |doi= |url=}}</ref><ref name="pmid16614251">{{cite journal |vauthors=Lindström M, Korkeala H |title=Laboratory diagnostics of botulism |journal=Clin. Microbiol. Rev. |volume=19 |issue=2 |pages=298–314 |date=April 2006 |pmid=16614251 |pmc=1471988 |doi=10.1128/CMR.19.2.298-314.2006 |url=}}</ref><ref name="pmid17224901">{{cite journal |vauthors=Brook I |title=Botulism: the challenge of diagnosis and treatment |journal=Rev Neurol Dis |volume=3 |issue=4 |pages=182–9 |date=2006 |pmid=17224901 |doi= |url=}}</ref><ref name="pmid23642721">{{cite journal |vauthors=Dimachkie MM, Barohn RJ |title=Guillain-Barré syndrome and variants |journal=Neurol Clin |volume=31 |issue=2 |pages=491–510 |date=May 2013 |pmid=23642721 |pmc=3939842 |doi=10.1016/j.ncl.2013.01.005 |url=}}</ref><ref name="pmid23418763">{{cite journal |vauthors=Walling AD, Dickson G |title=Guillain-Barré syndrome |journal=Am Fam Physician |volume=87 |issue=3 |pages=191–7 |date=February 2013 |pmid=23418763 |doi= |url=}}</ref><ref name="pmid21969911">{{cite journal |vauthors=Gilhus NE |title=Lambert-eaton myasthenic syndrome; pathogenesis, diagnosis, and therapy |journal=Autoimmune Dis |volume=2011 |issue= |pages=973808 |date=2011 |pmid=21969911 |pmc=3182560 |doi=10.4061/2011/973808 |url=}}</ref><ref name="pmid14977560">{{cite journal |vauthors=Krishnan C, Kaplin AI, Deshpande DM, Pardo CA, Kerr DA |title=Transverse Myelitis: pathogenesis, diagnosis and treatment |journal=Front. Biosci. |volume=9 |issue= |pages=1483–99 |date=May 2004 |pmid=14977560 |doi= |url=}}</ref><ref name="pmid24305450">{{cite journal |vauthors=Amato AA, Greenberg SA |title=Inflammatory myopathies |journal=Continuum (Minneap Minn) |volume=19 |issue=6 Muscle Disease |pages=1615–33 |date=December 2013 |pmid=24305450 |doi=10.1212/01.CON.0000440662.26427.bd |url=}}</ref><ref name="pmid24365430">{{cite journal |vauthors=Berger JR, Dean D |title=Neurosyphilis |journal=Handb Clin Neurol |volume=121 |issue= |pages=1461–72 |date=2014 |pmid=24365430 |doi=10.1016/B978-0-7020-4088-7.00098-5 |url=}}</ref> | MFS must be differentiated from other diseases that cause [[ophthalmoplegia]], [[areflexia]], and [[ataxia]], such as:<ref><nowiki>{{</nowiki>https://rarediseases.org/rare-diseases/miller-fisher-syndrome/<nowiki>}}</nowiki></ref><ref name="pmid29433111">{{cite journal |vauthors=Kira R |title=[Acute Flaccid Myelitis] |language=Japanese |journal=Brain Nerve |volume=70 |issue=2 |pages=99–112 |date=February 2018 |pmid=29433111 |doi=10.11477/mf.1416200962 |url=}}</ref><ref name="pmid29433111">{{cite journal |vauthors=Kira R |title=[Acute Flaccid Myelitis] |language=Japanese |journal=Brain Nerve |volume=70 |issue=2 |pages=99–112 |date=February 2018 |pmid=29433111 |doi=10.11477/mf.1416200962 |url=}}</ref><ref name="pmid29181601">{{cite journal |vauthors=Hopkins SE |title=Acute Flaccid Myelitis: Etiologic Challenges, Diagnostic and Management Considerations |journal=Curr Treat Options Neurol |volume=19 |issue=12 |pages=48 |date=November 2017 |pmid=29181601 |doi=10.1007/s11940-017-0480-3 |url=}}</ref><ref name="pmid27422805">{{cite journal |vauthors=Messacar K, Schreiner TL, Van Haren K, Yang M, Glaser CA, Tyler KL, Dominguez SR |title=Acute flaccid myelitis: A clinical review of US cases 2012-2015 |journal=Ann. Neurol. |volume=80 |issue=3 |pages=326–38 |date=September 2016 |pmid=27422805 |pmc=5098271 |doi=10.1002/ana.24730 |url=}}</ref><ref name="pmid29028962">{{cite journal |vauthors=Chong PF, Kira R, Mori H, Okumura A, Torisu H, Yasumoto S, Shimizu H, Fujimoto T, Hanaoka N, Kusunoki S, Takahashi T, Oishi K, Tanaka-Taya K |title=Clinical Features of Acute Flaccid Myelitis Temporally Associated With an Enterovirus D68 Outbreak: Results of a Nationwide Survey of Acute Flaccid Paralysis in Japan, August-December 2015 |journal=Clin. Infect. Dis. |volume=66 |issue=5 |pages=653–664 |date=February 2018 |pmid=29028962 |pmc=5850449 |doi=10.1093/cid/cix860 |url=}}</ref><ref name="pmid29482893">{{cite journal |vauthors=Messacar K, Asturias EJ, Hixon AM, Van Leer-Buter C, Niesters HGM, Tyler KL, Abzug MJ, Dominguez SR |title=Enterovirus D68 and acute flaccid myelitis-evaluating the evidence for causality |journal=Lancet Infect Dis |volume=18 |issue=8 |pages=e239–e247 |date=August 2018 |pmid=29482893 |doi=10.1016/S1473-3099(18)30094-X |url=}}</ref><ref name="pmid30200066">{{cite journal |vauthors=Chen IJ, Hu SC, Hung KL, Lo CW |title=Acute flaccid myelitis associated with enterovirus D68 infection: A case report |journal=Medicine (Baltimore) |volume=97 |issue=36 |pages=e11831 |date=September 2018 |pmid=30200066 |pmc=6133480 |doi=10.1097/MD.0000000000011831 |url=}}</ref><ref name="urlBotulism | Botulism | CDC">{{cite web |url=https://www.cdc.gov/botulism/index.html |title=Botulism | Botulism | CDC |format= |work= |accessdate=}}</ref><ref name="pmid3290234">{{cite journal |vauthors=McCroskey LM, Hatheway CL |title=Laboratory findings in four cases of adult botulism suggest colonization of the intestinal tract |journal=J. Clin. Microbiol. |volume=26 |issue=5 |pages=1052–4 |date=May 1988 |pmid=3290234 |pmc=266519 |doi= |url=}}</ref><ref name="pmid16614251">{{cite journal |vauthors=Lindström M, Korkeala H |title=Laboratory diagnostics of botulism |journal=Clin. Microbiol. Rev. |volume=19 |issue=2 |pages=298–314 |date=April 2006 |pmid=16614251 |pmc=1471988 |doi=10.1128/CMR.19.2.298-314.2006 |url=}}</ref><ref name="pmid17224901">{{cite journal |vauthors=Brook I |title=Botulism: the challenge of diagnosis and treatment |journal=Rev Neurol Dis |volume=3 |issue=4 |pages=182–9 |date=2006 |pmid=17224901 |doi= |url=}}</ref><ref name="pmid23642721">{{cite journal |vauthors=Dimachkie MM, Barohn RJ |title=Guillain-Barré syndrome and variants |journal=Neurol Clin |volume=31 |issue=2 |pages=491–510 |date=May 2013 |pmid=23642721 |pmc=3939842 |doi=10.1016/j.ncl.2013.01.005 |url=}}</ref><ref name="pmid23418763">{{cite journal |vauthors=Walling AD, Dickson G |title=Guillain-Barré syndrome |journal=Am Fam Physician |volume=87 |issue=3 |pages=191–7 |date=February 2013 |pmid=23418763 |doi= |url=}}</ref><ref name="pmid21969911">{{cite journal |vauthors=Gilhus NE |title=Lambert-eaton myasthenic syndrome; pathogenesis, diagnosis, and therapy |journal=Autoimmune Dis |volume=2011 |issue= |pages=973808 |date=2011 |pmid=21969911 |pmc=3182560 |doi=10.4061/2011/973808 |url=}}</ref><ref name="pmid14977560">{{cite journal |vauthors=Krishnan C, Kaplin AI, Deshpande DM, Pardo CA, Kerr DA |title=Transverse Myelitis: pathogenesis, diagnosis and treatment |journal=Front. Biosci. |volume=9 |issue= |pages=1483–99 |date=May 2004 |pmid=14977560 |doi= |url=}}</ref><ref name="pmid24305450">{{cite journal |vauthors=Amato AA, Greenberg SA |title=Inflammatory myopathies |journal=Continuum (Minneap Minn) |volume=19 |issue=6 Muscle Disease |pages=1615–33 |date=December 2013 |pmid=24305450 |doi=10.1212/01.CON.0000440662.26427.bd |url=}}</ref><ref name="pmid24365430">{{cite journal |vauthors=Berger JR, Dean D |title=Neurosyphilis |journal=Handb Clin Neurol |volume=121 |issue= |pages=1461–72 |date=2014 |pmid=24365430 |doi=10.1016/B978-0-7020-4088-7.00098-5 |url=}}</ref> | ||
{| | {| | ||
|- style="background: #4479BA; color: #FFFFFF; text-align: center;" | |- style="background: #4479BA; color: #FFFFFF; text-align: center;" | ||
Line 303: | Line 307: | ||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
While the incidence of MFS is one or two person per million each year, the prevalence of MFS associated with | |||
* 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== | ==Risk Factors== | ||
There are no established risk factors for MFS associated with | |||
* There are no established [[Risk factor|risk factors]] for MFS associated with [[COVID-19]]. | |||
==Screening== | ==Screening== | ||
There is insufficient evidence to recommend routine screening for patients with MFS caused by | |||
* There is insufficient evidence to recommend routine [[Screening (medicine)|screening]] for patients with MFS caused by [[COVID-19]]. | |||
==Natural History, Complications, and Prognosis== | ==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%. | |||
* 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%. | |||
* Old age | * Risk factors for severe illness and poor [[prognosis]] include: | ||
* Male gender | **[[Old age]] | ||
* Patients with | ** Male gender | ||
** [[Diabetes Mellitus]] | ** Patients with | ||
** [[Hypertension]] | ***[[Diabetes Mellitus]] | ||
** [[COPD]] | ***[[Hypertension]] | ||
** [[CKD]] | ***[[COPD]] | ||
***[[CKD]] | |||
==Diagnosis== | ==Diagnosis== | ||
===Diagnostic Study of Choice=== | ===Diagnostic Study of Choice=== | ||
Although the diagnosis of [[ | |||
* 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 [[Neurological|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. | |||
* [[Magnetic resonance imaging|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.<ref><nowiki>{{</nowiki>http://www.ajnr.org/content/early/2020/05/28/ajnr.A6609<nowiki>}}</nowiki></ref>. <ref><nowiki>{{</nowiki>https://rarediseases.org/rare-diseases/miller-fisher-syndrome/<nowiki>}}</nowiki></ref> | |||
===History and Symptoms=== | ===History and Symptoms=== | ||
Line 333: | Line 344: | ||
** [[cough]] | ** [[cough]] | ||
* Neurological symptoms | * Neurological symptoms | ||
** [[headache]] | **[[headache]]<ref><nowiki>{{</nowiki>http://www.ajnr.org/content/early/2020/05/28/ajnr.A6609<nowiki>}}</nowiki></ref> | ||
** [[ataxia]] | ** [[ataxia]] | ||
** [[ophthalmoplegia]] | ** [[ophthalmoplegia]] | ||
** [[areflexia]] | ** [[areflexia]] | ||
< | <br /> | ||
===Physical Examination=== | ===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: | |||
* 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==== | ====Vitals==== | ||
Abnormal signs associated with covid-19: | Abnormal signs associated with covid-19: | ||
* [[Tachycardia]] | * [[Tachycardia]] | ||
* [[Tachypnea]] | * [[Tachypnea]] | ||
* Fever | *[[Fever]] | ||
==== | |||
====Neurological==== | |||
* [[Eye dropping]] | * [[Eye dropping]] | ||
* [[Blurry vision]] | * [[Blurry vision]] | ||
Line 356: | Line 369: | ||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
Laboratory findings consistent with the diagnosis of | |||
* Laboratory findings consistent with the diagnosis of COVID-19 include positive [[PCR]] nasal swab. | |||
* Ganglioside (GM1) Antibodies, IgG and IgM | * Laboratory tests for neurological signs are not diagnostic and should be used with other clinical parameters. They include: | ||
* GD1b Antibody, IgM | **[[Ganglioside]] (GM1) [[Antibodies]], [[IgG]] and [[IgM]] | ||
* GQ1b Antibody, IgG | ** GD1b [[Antibody]], [[IgM]] | ||
** GQ1b Antibody, [[IgG]] | |||
===Electrocardiogram=== | ===Electrocardiogram=== | ||
There are no ECG findings associated with | |||
* There are no [[The electrocardiogram|ECG]] findings associated with [[COVID-19]]. | |||
===X-ray=== | ===X-ray=== | ||
* [[Chest X-ray]] is less sensitive in detection of [[COVID-19]] in comparison with [[Computed tomography|CT]]. | |||
* However, in some cases [[lung consolidation]] and patchy peripheral opacities corresponding to [[ground glass opacities]] has been reported.<ref><nowiki>{{</nowiki>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141645/<nowiki>}}</nowiki></ref> | |||
===Echocardiography or Ultrasound=== | ===Echocardiography or Ultrasound=== | ||
* Lung [[ultrasound]] may be helpful in the evaluation of patients with COVID-19. It indicates : | |||
* Multiple | |||
** Ranging from focal to diffuse with spared areas | * Multiple B-lines | ||
* Irregular and thickened pleural lines | ** Ranging from focal to diffuse with spared areas | ||
* Irregular and thickened [[pleural]] lines | |||
* Subpleural consolidations | * Subpleural consolidations | ||
* Alveolar consolidations | *[[Alveolar]] [[Consolidation (medicine)|consolidations]] | ||
* Bilateral [[A-lines]] | * Bilateral [[A-lines]] | ||
===CT scan=== | ===CT scan=== | ||
The preliminary findings of CT in COVID-19 associated with MFS include: | The preliminary findings of [[Computed tomography|CT]] in COVID-19 associated with MFS include: | ||
* Bilateral | * Bilateral ground glass opacities | ||
* Air space consolidation | * Air space [[Consolidation (medicine)|consolidation]] | ||
* Bronchovascular thickening | * Bronchovascular thickening | ||
* Traction bronchiectasis | * Traction [[bronchiectasis]] | ||
===MRI=== | ===MRI=== | ||
Brain MRI may be helpful in the diagnosis of MFS in patients with prior history of | |||
* Brain [[Magnetic resonance imaging|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 nerves|cranial nerve]] enhancement has been reported in some patients. | |||
===Other Diagnostic Studies=== | ===Other Diagnostic Studies=== | ||
There are no other diagnostic studies associated with | |||
* There are no other diagnostic studies associated with COVID-19 with MFS manifestations. | |||
==Treatment== | ==Treatment== | ||
===Medical Therapy=== | ===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 indicated partial success in treatment of covid-19. | |||
* 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 indicated partial success in treatment of covid-19. | |||
* [[Remdesivir]], a drug originally developed to treat [[Ebola virus]], showed positive results against [[SARS-CoV-2]]. | |||
* [[Dexamethasone]] has been announced as an effective treatment in patients with systematic manifestations. | |||
===Surgery=== | ===Surgery=== | ||
Surgical intervention is not recommended for the management of covid-19. | |||
* Surgical intervention is not recommended for the management of covid-19. | |||
===Primary Prevention=== | ===Primary Prevention=== | ||
Effective measures for the primary prevention of [[covid-19]] include | |||
* 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== | ==References== |
Revision as of 15:00, 14 July 2020
COVID-19 Microchapters |
Diagnosis |
---|
Treatment |
Case Studies |
COVID-19-associated Miller-Fischer syndrome On the Web |
American Roentgen Ray Society Images of COVID-19-associated Miller-Fischer syndrome |
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. [1]
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.[2]
Causes
- 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
MFS must be differentiated from other diseases that cause ophthalmoplegia, areflexia, and ataxia, such as:[3][4][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]
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
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.[20]. [21]
History and Symptoms
Symptoms of covid-19 associated with MFS include:
- Respiratory system symptoms
- Neurological symptoms
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:
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
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.[23]
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 indicated partial success in treatment of covid-19.
- Remdesivir, a drug originally developed to treat Ebola virus, showed positive results against SARS-CoV-2.
- Dexamethasone 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
- ↑ {{https://n.neurology.org/content/early/2020/04/17/WNL.0000000000009619}}
- ↑ {{https://pubmed.ncbi.nlm.nih.gov/10695710}}
- ↑ {{https://rarediseases.org/rare-diseases/miller-fisher-syndrome/}}
- ↑ 4.0 4.1 Kira R (February 2018). "[Acute Flaccid Myelitis]". Brain Nerve (in Japanese). 70 (2): 99–112. doi:10.11477/mf.1416200962. PMID 29433111.
- ↑ Hopkins SE (November 2017). "Acute Flaccid Myelitis: Etiologic Challenges, Diagnostic and Management Considerations". Curr Treat Options Neurol. 19 (12): 48. doi:10.1007/s11940-017-0480-3. PMID 29181601.
- ↑ Messacar K, Schreiner TL, Van Haren K, Yang M, Glaser CA, Tyler KL, Dominguez SR (September 2016). "Acute flaccid myelitis: A clinical review of US cases 2012-2015". Ann. Neurol. 80 (3): 326–38. doi:10.1002/ana.24730. PMC 5098271. PMID 27422805.
- ↑ Chong PF, Kira R, Mori H, Okumura A, Torisu H, Yasumoto S, Shimizu H, Fujimoto T, Hanaoka N, Kusunoki S, Takahashi T, Oishi K, Tanaka-Taya K (February 2018). "Clinical Features of Acute Flaccid Myelitis Temporally Associated With an Enterovirus D68 Outbreak: Results of a Nationwide Survey of Acute Flaccid Paralysis in Japan, August-December 2015". Clin. Infect. Dis. 66 (5): 653–664. doi:10.1093/cid/cix860. PMC 5850449. PMID 29028962.
- ↑ Messacar K, Asturias EJ, Hixon AM, Van Leer-Buter C, Niesters H, Tyler KL, Abzug MJ, Dominguez SR (August 2018). "Enterovirus D68 and acute flaccid myelitis-evaluating the evidence for causality". Lancet Infect Dis. 18 (8): e239–e247. doi:10.1016/S1473-3099(18)30094-X. PMID 29482893. Vancouver style error: initials (help)
- ↑ Chen IJ, Hu SC, Hung KL, Lo CW (September 2018). "Acute flaccid myelitis associated with enterovirus D68 infection: A case report". Medicine (Baltimore). 97 (36): e11831. doi:10.1097/MD.0000000000011831. PMC 6133480. PMID 30200066.
- ↑ "Botulism | Botulism | CDC".
- ↑ McCroskey LM, Hatheway CL (May 1988). "Laboratory findings in four cases of adult botulism suggest colonization of the intestinal tract". J. Clin. Microbiol. 26 (5): 1052–4. PMC 266519. PMID 3290234.
- ↑ Lindström M, Korkeala H (April 2006). "Laboratory diagnostics of botulism". Clin. Microbiol. Rev. 19 (2): 298–314. doi:10.1128/CMR.19.2.298-314.2006. PMC 1471988. PMID 16614251.
- ↑ Brook I (2006). "Botulism: the challenge of diagnosis and treatment". Rev Neurol Dis. 3 (4): 182–9. PMID 17224901.
- ↑ Dimachkie MM, Barohn RJ (May 2013). "Guillain-Barré syndrome and variants". Neurol Clin. 31 (2): 491–510. doi:10.1016/j.ncl.2013.01.005. PMC 3939842. PMID 23642721.
- ↑ Walling AD, Dickson G (February 2013). "Guillain-Barré syndrome". Am Fam Physician. 87 (3): 191–7. PMID 23418763.
- ↑ Gilhus NE (2011). "Lambert-eaton myasthenic syndrome; pathogenesis, diagnosis, and therapy". Autoimmune Dis. 2011: 973808. doi:10.4061/2011/973808. PMC 3182560. PMID 21969911.
- ↑ Krishnan C, Kaplin AI, Deshpande DM, Pardo CA, Kerr DA (May 2004). "Transverse Myelitis: pathogenesis, diagnosis and treatment". Front. Biosci. 9: 1483–99. PMID 14977560.
- ↑ Amato AA, Greenberg SA (December 2013). "Inflammatory myopathies". Continuum (Minneap Minn). 19 (6 Muscle Disease): 1615–33. doi:10.1212/01.CON.0000440662.26427.bd. PMID 24305450.
- ↑ Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.
- ↑ {{http://www.ajnr.org/content/early/2020/05/28/ajnr.A6609}}
- ↑ {{https://rarediseases.org/rare-diseases/miller-fisher-syndrome/}}
- ↑ {{http://www.ajnr.org/content/early/2020/05/28/ajnr.A6609}}
- ↑ {{https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141645/}}