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Revision as of 17:13, 20 July 2020

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

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.^[3]. ^[4]

History and Symptoms

Symptoms of covid-19 associated with MFS include:

Respiratory system symptoms
- shortness of breath
- cough
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

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.^[6]

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)^[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)^[9] 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}}
↑ {{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/}}
↑ Cao, Bin; Wang, Yeming; Wen, Danning; Liu, Wen; Wang, Jingli; Fan, Guohui; Ruan, Lianguo; Song, Bin; Cai, Yanping; Wei, Ming; Li, Xingwang; Xia, Jiaan; Chen, Nanshan; Xiang, Jie; Yu, Ting; Bai, Tao; Xie, Xuelei; Zhang, Li; Li, Caihong; Yuan, Ye; Chen, Hua; Li, Huadong; Huang, Hanping; Tu, Shengjing; Gong, Fengyun; Liu, Ying; Wei, Yuan; Dong, Chongya; Zhou, Fei; Gu, Xiaoying; Xu, Jiuyang; Liu, Zhibo; Zhang, Yi; Li, Hui; Shang, Lianhan; Wang, Ke; Li, Kunxia; Zhou, Xia; Dong, Xuan; Qu, Zhaohui; Lu, Sixia; Hu, Xujuan; Ruan, Shunan; Luo, Shanshan; Wu, Jing; Peng, Lu; Cheng, Fang; Pan, Lihong; Zou, Jun; Jia, Chunmin; Wang, Juan; Liu, Xia; Wang, Shuzhen; Wu, Xudong; Ge, Qin; He, Jing; Zhan, Haiyan; Qiu, Fang; Guo, Li; Huang, Chaolin; Jaki, Thomas; Hayden, Frederick G.; Horby, Peter W.; Zhang, Dingyu; Wang, Chen (2020). "A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19". New England Journal of Medicine. 382 (19): 1787–1799. doi:10.1056/NEJMoa2001282. ISSN 0028-4793.
↑ "Coronavirus disease 2019 (COVID-19) investigational drug information for remdesivir".
↑ "Corticosteroids | Coronavirus Disease COVID-19".

Template:WikiDoc Sources

[1] {{https://n.neurology.org/content/early/2020/04/17/WNL.0000000000009619}}

[2] {{https://pubmed.ncbi.nlm.nih.gov/10695710}}

[3] {{http://www.ajnr.org/content/early/2020/05/28/ajnr.A6609}}

[4] {{https://rarediseases.org/rare-diseases/miller-fisher-syndrome/}}

[5] {{http://www.ajnr.org/content/early/2020/05/28/ajnr.A6609}}

[6] {{https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141645/}}

[CaoWang2020-7] Cao, Bin; Wang, Yeming; Wen, Danning; Liu, Wen; Wang, Jingli; Fan, Guohui; Ruan, Lianguo; Song, Bin; Cai, Yanping; Wei, Ming; Li, Xingwang; Xia, Jiaan; Chen, Nanshan; Xiang, Jie; Yu, Ting; Bai, Tao; Xie, Xuelei; Zhang, Li; Li, Caihong; Yuan, Ye; Chen, Hua; Li, Huadong; Huang, Hanping; Tu, Shengjing; Gong, Fengyun; Liu, Ying; Wei, Yuan; Dong, Chongya; Zhou, Fei; Gu, Xiaoying; Xu, Jiuyang; Liu, Zhibo; Zhang, Yi; Li, Hui; Shang, Lianhan; Wang, Ke; Li, Kunxia; Zhou, Xia; Dong, Xuan; Qu, Zhaohui; Lu, Sixia; Hu, Xujuan; Ruan, Shunan; Luo, Shanshan; Wu, Jing; Peng, Lu; Cheng, Fang; Pan, Lihong; Zou, Jun; Jia, Chunmin; Wang, Juan; Liu, Xia; Wang, Shuzhen; Wu, Xudong; Ge, Qin; He, Jing; Zhan, Haiyan; Qiu, Fang; Guo, Li; Huang, Chaolin; Jaki, Thomas; Hayden, Frederick G.; Horby, Peter W.; Zhang, Dingyu; Wang, Chen (2020). "A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19". New England Journal of Medicine. 382 (19): 1787–1799. doi:10.1056/NEJMoa2001282. ISSN 0028-4793.

[urlCoronavirus_disease_2019_(COVID-19)_investigational_drug_information_for_remdesivir-8] "Coronavirus disease 2019 (COVID-19) investigational drug information for remdesivir".

[urlCorticosteroids_|_Coronavirus_Disease_COVID-19-9] "Corticosteroids | Coronavirus Disease COVID-19".

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@@ Line 35: / Line 35: @@
 ==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 &#124; Botulism &#124; 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;"
-! rowspan="2" |<small>Diseases</small>
-! colspan="8" |<small>History and Physical
-! colspan="2" |<small>Diagnostic tests</small>
-! rowspan="2" |<small>Other Findings</small>
-|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
-!<small>Motor Deficit</small>
-!<small>Sensory deficit</small>
-!<small>Cranial nerve Involvement</small>
-!<small>Autonomic dysfunction</small>
-!<small>Proximal/Distal/Generalized</small>
-!<small>Ascending/Descending/Systemic</small>
-!<small>Unilateral (UL)
-or Bilateral (BL)
-or
-No Lateralization (NL)</small>
-!<small>Onset</small>
-!<small>Lab or Imaging Findings</small>
-!<small>Specific  test</small>
-|-
-| style="background: #DCDCDC; padding: 5px; text-align:center" |[[Guillian-Barre syndrome]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" |  +
-| style="background: #F5F5F5; padding: 5px; text-align:center" |  -
-| style="background: #F5F5F5; padding: 5px; text-align:center" |  -
-| style="background: #F5F5F5; padding: 5px; text-align:center" |<nowiki>-</nowiki>
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Generalized
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Ascending
-| style="background: #F5F5F5; padding: 5px; text-align:center" |BL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Insidious
-| style="background: #F5F5F5; padding: 5px; text-align:center" |CSF: ↑Protein
-↓Cells
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Clinical & Lumbar Puncture
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Progressive [[ascending paralysis]] following infection, possible respiratory paralysis
-|-
-| style="background: #DCDCDC; padding: 5px; text-align:center" |Acute Flaccid Myelitis
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Proximal > Distal
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Ascending
-| style="background: #F5F5F5; padding: 5px; text-align:center" |UL/BL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Sudden
-| style="background: #F5F5F5; padding: 5px; text-align:center" |MRI (Longitudinal hyperintense lesions)
-| style="background: #F5F5F5; padding: 5px; text-align:center" |MRI and CSF PCR for viral etiology
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Drooping eyelids
-Difficulty swallowing
-Respiratory failure
-|-
-| style="background: #DCDCDC; padding: 5px; text-align: center;" | Adult Botulism
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" |<nowiki>+</nowiki>
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Generalized
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Descending
-| style="background: #F5F5F5; padding: 5px; text-align:center" |BL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Sudden
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Toxin test
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Blood, Wound, or Stool culture
-| style="background: #F5F5F5; padding: 5px; text-align:center" |[[Diplopia]], [[Hyporeflexia|Hyporeflexia,]] [[Hypotonia]], possible respiratory paralysis
-|-
-| style="background: #DCDCDC; padding: 5px; text-align: center;" |Infant Botulism
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" |<nowiki>+</nowiki>
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Generalized
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Descending
-| style="background: #F5F5F5; padding: 5px; text-align:center" |BL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Sudden
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Toxin test
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Blood, Wound, or Stool culture
-| style="background: #F5F5F5; padding: 5px; text-align:center" |[[Flaccid paralysis]] ([[Floppy baby syndrome]]), possible respiratory paralysis
-|-
-| style="background: #DCDCDC; padding: 5px; text-align: center;" | [[Eaton lambert syndrome|Eaton Lambert syndrome]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" |<nowiki>+</nowiki>
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Generalized
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Systemic
-| style="background: #F5F5F5; padding: 5px; text-align:center" |BL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Intermittent
-| style="background: #F5F5F5; padding: 5px; text-align:center" | [[EMG]], repetitive nerve stimulation test (RNS)
-| style="background: #F5F5F5; padding: 5px; text-align:center" |[[Voltage gated calcium channel|Voltage gated calcium channe]]<nowiki/>l<nowiki/> (VGCC) antibody
-| style="background: #F5F5F5; padding: 5px; text-align:center" |[[Diplopia]], [[ptosis]], improves with movement (as the day progresses)
-|-
-| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Myasthenia gravis]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" |<nowiki>+</nowiki>
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Generalized
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Systemic
-| style="background: #F5F5F5; padding: 5px; text-align:center" |BL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Intermittent
-| style="background: #F5F5F5; padding: 5px; text-align:center" | [[Electromyography|EMG]], [[Edrophonium|Edrophonium test]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" |[[Acetylcholine receptor|Ach receptor]] antibody
-| style="background: #F5F5F5; padding: 5px; text-align:center" |[[Diplopia]], [[ptosis]], worsening with movement (as the day progresses)
-|-
-| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Electrolyte disturbance]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" |<nowiki>-</nowiki>
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Generalized
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Systemic
-| style="background: #F5F5F5; padding: 5px; text-align:center" |BL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Insidious
-| style="background: #F5F5F5; padding: 5px; text-align:center" | Electrolyte panel
-| style="background: #F5F5F5; padding: 5px; text-align:center" |↓Ca++, ↓Mg++, ↓K+
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Possible [[arrhythmia]]
-|-
-| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Organophosphate poisoning|Organophosphate toxicity]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" |<nowiki>+</nowiki>
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Generalized
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Ascending
-| style="background: #F5F5F5; padding: 5px; text-align:center" |BL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Sudden
-| style="background: #F5F5F5; padding: 5px; text-align:center" | Clinical diagnosis: physical exam & history
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Clinical suspicion confirmed with RBC AchE activity
-| style="background: #F5F5F5; padding: 5px; text-align:center" |History of exposure to i[[Insecticide|nsecticide]] or living in farming environment. with : [[Diarrhea]], [[Urination]], [[Miosis]], [[Bradycardia]], [[Lacrimation]], [[Emesis]], [[Salivation]], [[Sweating]]
-|-
-| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Tick paralysis]] ([[Dermacentor andersoni|Dermacentor tick]])
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" |<nowiki>-</nowiki>
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Generalized
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Ascending
-| style="background: #F5F5F5; padding: 5px; text-align:center" |BL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Insidious
-| style="background: #F5F5F5; padding: 5px; text-align:center" | Clinical diagnosis: physical exam & history
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" |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)
-|-
-| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Tetrodotoxin]] poisoning
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" |<nowiki>+</nowiki>
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Generalized
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Systemic
-| style="background: #F5F5F5; padding: 5px; text-align:center" |BL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Sudden
-| style="background: #F5F5F5; padding: 5px; text-align:center" | Clinical diagnosis: physical exam & dietary history
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" | History of consumption of puffer fish species.
-|-
-| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Stroke]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +/-
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +/-
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +/-
-| style="background: #F5F5F5; padding: 5px; text-align:center" |<nowiki>+/-</nowiki>
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Generalized
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Systemic
-| style="background: #F5F5F5; padding: 5px; text-align:center" |UL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Sudden
-| style="background: #F5F5F5; padding: 5px; text-align:center" | MRI +ve for ischemia or hemorrhage
-| style="background: #F5F5F5; padding: 5px; text-align:center" |MRI
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Sudden unilateral motor and sensory deficit in a patient with a history of [[Atherosclerosis|atherosclero]]<nowiki/>tic risk factors (diabetes, hypertension, smoking) or [[Atrial fibrillation|atrial fibrillation.]]
-|-
-| style="background: #DCDCDC; padding: 5px; text-align:center;" | [[Poliomyelitis]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +/-
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Proximal > Distal
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Systemic
-| style="background: #F5F5F5; padding: 5px; text-align:center" |BL or UL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Sudden
-| style="background: #F5F5F5; padding: 5px; text-align:center" |
-| style="background: #F5F5F5; padding: 5px; text-align:center" |PCR of CSF
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Asymmetric paralysis following a flu-like syndrome.
-|-
-| style="background: #DCDCDC; padding: 5px; text-align:center;" | [[Transverse myelitis]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" |<nowiki>+</nowiki>
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Proximal > Distal
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Systemic
-| style="background: #F5F5F5; padding: 5px; text-align:center" |BL or UL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Sudden
-| style="background: #F5F5F5; padding: 5px; text-align:center" |MRI & [[Lumbar puncture]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" |MRI
-| style="background: #F5F5F5; padding: 5px; text-align:center" |History of chronic viral or autoimmune disease (e.g. [[HIV]])
-|-
-| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Neurosyphilis]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +/-
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Generalized
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Systemic
-| style="background: #F5F5F5; padding: 5px; text-align:center" |BL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Insidious<nowiki/>
-| style="background: #F5F5F5; padding: 5px; text-align:center" |MRI & [[Lumbar puncture]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" |CSF [[VDRL]]-specifc
-CSF [[FTA-ABS|FTA-Ab]] -sensitive
-| style="background: #F5F5F5; padding: 5px; text-align:center" |History of unprotected sex or multiple sexual partners.
-History of [[genital ulcer]] ([[chancre]]), diffuse [[Maculopapular rash|maculopapular ras]]<nowiki/>h.
-|-
-| style="background: #DCDCDC; padding: 5px; text-align:center;" |[[Muscular dystrophy]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" |<nowiki>-</nowiki>
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Proximal > Distal
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Systemic
-| style="background: #F5F5F5; padding: 5px; text-align:center" |BL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Insidious
-| style="background: #F5F5F5; padding: 5px; text-align:center" | Genetic testing
-| style="background: #F5F5F5; padding: 5px; text-align:center" |[[Muscle biopsy]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Progressive proximal lower limb weakness with calf pseudohypertrophy in early childhood. [[Gowers' sign|Gower sign]] positive.
-|-
-| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Multiple sclerosis]] exacerbation
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" |<nowiki>+</nowiki>
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Generalized
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Systemic
-| style="background: #F5F5F5; padding: 5px; text-align:center" |NL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Sudden
-| style="background: #F5F5F5; padding: 5px; text-align:center" |'''[[CSF|↑]]'''[[CSF]] [[IgG]] levels
-(monoclonal)
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Clinical assessment and [[MRI]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" |[[Blurred vision|Blurry vision]], [[urinary incontinence]], [[fatigue]]
-|-
-| style="background: #DCDCDC; padding: 5px; text-align:center" |[[Amyotrophic lateral sclerosis]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" |<nowiki>-</nowiki>
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Generalized
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Systemic
-| style="background: #F5F5F5; padding: 5px; text-align:center" |BL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Insidious
-| style="background: #F5F5F5; padding: 5px; text-align:center" | Normal [[Lumbar puncture|LP]] (to rule out DDx)
-| style="background: #F5F5F5; padding: 5px; text-align:center" |MRI & [[Lumbar puncture|LP]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Patient initially presents with [[upper motor neuron]] deficit ([[spasticity]]) followed by [[lower motor neuron]] deficit ([[flaccidity]]).
-|-
-| style="background: #DCDCDC; padding: 5px; text-align:center;" | [[Myositis|Inflammatory myopathy]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" | +
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" | -
-| style="background: #F5F5F5; padding: 5px; text-align:center" |<nowiki>-</nowiki>
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Proximal > Distal
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Systemic
-| style="background: #F5F5F5; padding: 5px; text-align:center" |UL or BL
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Insidious
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Elevated [[Creatine kinase|CK]] & [[Aldolase]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" |[[Muscle biopsy]]
-| style="background: #F5F5F5; padding: 5px; text-align:center" |Progressive proximal muscle weakness in 3rd to 5th decade of life. With or without skin manifestations.
-|-
-|}
 ==Epidemiology and Demographics==