HISTOPATHOLOGY OF GUILLAIN BARRE SYNDROME ......Guillain-Barre syndrome often begins with tingling and weakness starting in your feet and legs and spreading to your upper body and

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812

Sourav et al. World Journal of Pharmacy and Pharmaceutical Sciences

HISTOPATHOLOGY OF GUILLAIN – BARRE SYNDROME (GBS)

AND ITS PREVENTION

Sourav Santra*, Sudeshna Santra, Amit Kumar Das, Aakash Chatterjee, Dr. Dhrubo

Jyoti Sen

Department of Pharmaceutical Chemistry, School of Pharmacy, Techno India

University, Salt Lake City, Sector-5, EM-4, Kolkata -700091, West Bengal, India.

ABSTRACT

Guillain-Barre syndrome (GBS) is clinically defined as an acute

peripheral neuropathy causing limb weakness that progresses over a

time period of days or, at the most, up to 4 weeks. GBS occurs

throughout the world with a median annual incidence of 1.3 cases per

population of 100 000, with men being more frequently affected than

women. GBS is considered to be an autoimmune disease triggered by a

preceding bacterial or viral infection. Campylobacter jejuni,

cytomegalovirus, Epstein-Barr virus and Mycoplasma pneumoniae are

commonly identified antecedent pathogens. In the acute motor axonal

neuropathy (AMAN) form of GBS, the infecting organisms probably

share homologous epitopes to a component of the peripheral nerves

(molecular mimicry) and, therefore, the immune responses cross-react

with the nerves causing axonal degeneration. The target molecules in

AMAN are likely to be gangliosides GM1, GM1b, GD1a and GalNAc-GD1a expressed on the

motor axolemma. In the acute inflammatory demyelinating polyneuropathy (AIDP) form,

immune system reactions against target epitopes in Schwann cells or myelin result in

demyelination. However, the exact target molecules in the case of AIDP have not yet been

identified. AIDP is by far the most common form of GBS in Europe and North America,

whereas AMAN occurs more frequently in east Asia (China and Japan). The prognosis of

GBS is generally favourable, but it is a serious disease with a mortality of approximately

10% and approximately 20% of patients are left with severe disability. Treatment of GBS is

subdivided into: (i) the management of severely paralysed patients with intensive care and

ventilatory support; and (ii) specific immunomodulating treatments that shorten the

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.632

Volume 9, Issue 6, 812-826 Review Article ISSN 2278 – 4357

*Corresponding Author

Sourav Santra

Department of

Pharmaceutical Chemistry,

School of Pharmacy,

Techno India University,

Salt Lake City, Sector-5,

EM-4, Kolkata -700091,

West Bengal, India.

Article Received on

08 April 2020,

Revised on 28 April 2020,

Accepted on 18 May 2020

DOI: 10.20959/wjpps20206-16377


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progressive course of GBS, presumably by limiting nerve damage. High-dose intravenous

immunoglobulin (IVIg) therapy and plasma exchange aid more rapid resolution of the

disease. The predominant mechanisms by which IVIg therapy exerts its action appear to be a

combined effect of complement inactivation, neutralisation of idiotypic antibodies, cytokine

inhibition and saturation of Fc receptors on macrophages. Corticosteroids alone do not alter

the outcome of GBS.

KEYWORDS: Guillain-barre syndrom (GBS), Acute inflammatory demyelinating

polyradiculoneuropathy (AIDP), Acute motor axonal neuropathy (AMAN), acute motor-

sensory axonal neuropathy (AMSAN), Link between zika virus and GBS, Pathophysiology of

GBS, Link with COVID-19.

INTRODUCTION

Guillain-Barre syndrome is an uncommon disorder that causes damage to the peripheral

nerves. These nerves send messages from the brain to the muscles, instructing the muscles to

move. They also carry sensations such as pain from the body to the brain. The nerve damage

often causes muscle weakness, often to the point of paralysis, and can cause problems with

sensation, including pain, tingling, "crawling skin" or a certain amount of numbness.

GBS is an autoimmune disorder in which the body's immune system attacks and destroys the

myelin sheath, which wraps around long nerve cell bodies much like insulation around a

water pipe. Myelin protects the nerve and helps to speed the transmission of electrical

impulses down the nerve. If the myelin is destroyed, nerve impulses travel very slowly and

can become disrupted. If muscles don't get proper stimulation through the nerves, they will

not function properly.[1]

Figure-1: Guillain-Barre syndrome.


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GBS is uncommon, affecting fewer than 4,000 people in the United States each year. Why

the disorder strikes some people is a mystery. In more than two-thirds of patients, Guillain-

Barre syndrome occurs one to three weeks after a viral disease, including the common cold,

flu, or infection with human immunodeficiency virus (HIV), Epstein-Barr virus or

cytomegalovirus. The most common infectious trigger seems to be a bacterial infection with

Campylobacter jejuni, which causes intestinal infections. Occasionally, Guillain-Barre

syndrome seems to follow immunization, surgery or bone marrow transplantation. The causes

of the syndrome are unknown, but many experts think that the immune system is trying to

fight an infectious organism (bacteria or virus) and accidentally injures nerve tissue in the

process. It is a rare condition, and while it is more common in adults and in males, people of

all ages can be affected.[2]

Figure-2: Time course of GUILLAIN BARRE SYNDROME.

SYMPTOMS

Guillain-Barre syndrome often begins with tingling and weakness starting in your feet and

legs and spreading to your upper body and arms. In about 10% of people with the disorder,

symptoms begin in the arms or face. As Guillain-Barre syndrome progresses, muscle

weakness can evolve into paralysis.

Signs and symptoms of Guillain-Barre syndrome may include:

Prickling, pins and needles sensations in your fingers, toes, ankles or wrists

Weakness in your legs that spreads to your upper body

Unsteady walking or inability to walk or climb stairs

Difficulty with facial movements, including speaking, chewing or swallowing

Double vision or inability to move eyes


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Severe pain that may feel achy, shooting or cramp like and may be worse at night

Difficulty with bladder control or bowel function

Rapid heart rate

Low or high blood pressure

Difficulty breathing

People with Guillain-Barre syndrome usually experience their most significant weakness

within two weeks after symptoms begin.[3]

TYPES

Once thought to be a single disorder, Guillain-Barre syndrome is now known to occur in

several forms. The main types are:

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP), the most

common form in North America and Europe. The most common sign of AIDP is muscle

weakness that starts in the lower part of your body and spreads upward.

Miller Fisher syndrome (MFS), in which paralysis starts in the eyes. MFS is also

associated with unsteady gait. MFS is less common in the U.S. but more common in Asia.

Acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal

neuropathy (AMSAN) are less common in the U.S. But AMAN and AMSAN are more

frequent in China, Japan and Mexico.

Figure: Types Of GBS.

Figure-3: Neuron disorder in Guillain–Barré syndrome.


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CAUSES

Two thirds of people with Guillain–Barré syndrome have experienced an infection before the

onset of the condition. Most commonly these are episodes of gastroenteritis or a respiratory

tract infection. In many cases, the exact nature of the infection can be confirmed.

Approximately 30% of cases are provoked by Campylobacter jejuni bacteria, which cause

diarrhea. A further 10% are attributable to cytomegalovirus (CMV, HHV-5). Despite this,

only very few people with Campylobacter or CMV infections develop Guillain–Barre

syndrome. The strain of Campylobacter involved may determine the risk of GBS. Two other

herpesviruses (Epstein–Barr virus/HHV-4 and varicella zoster virus/HHV-3) and the

bacterium Mycoplasma pneumoniae have been associated with GBS. The tropical viral

infection dengue fever and zika virus have also been associated with episodes of GBS.

Previous hepatitis E virus infection has been found to be more common in people with GBS.

Some cases may be triggered by the influenza virus and potentially influenza vaccine. In fact,

natural influenza infection is a stronger risk factor for the development of GBS than is

influenza vaccination and getting the vaccination actually reduces the risk of GBS overall by

lowering the risk of catching influenza. Even those who have previously experienced

Guillain–Barré syndrome are considered safe to receive the vaccine in the future.[4]

Figure-4: A. Campylobacter jejuni bacteria B. Zika virus.

There are some known risk factors, including

Sex: Males are slightly more likely to contract GBS.

Age: Risk increases with age.

Campylobacter jejuni bacterial infection: A common cause of food poisoning, this

infection sometimes occurs before GBS.

https://en.m.wikipedia.org/wiki/Epstein%E2%80%93Barr_virus

https://en.m.wikipedia.org/wiki/Varicella_zoster_virus

https://en.m.wikipedia.org/wiki/Mycoplasma_pneumoniae

https://en.m.wikipedia.org/wiki/Hepatitis_E_virus

https://en.m.wikipedia.org/wiki/Campylobacter_jejuni

https://en.m.wikipedia.org/wiki/Zika_virus


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Influenza virus, HIV, or Epstein-Barr virus (EBV): These have occurred in association

with cases of GBS.

Mycoplasma pneumonia: This is a bacterial infection of the lungs.

Surgery: Some surgeries can trigger GBS.

Hodgkin’s lymphoma: Cancer of the lymphatic system can lead to GBS.

Influenza vaccination or childhood vaccinations: These have also been linked to GBS

in rare cases.

Figure-5: Scanning Electron Micrograph of organism and Graphical plot of Guillain-

Barre syndrome.

MECHANISM

Guillain–Barre syndrome is caused by an immune attack on the nerve cells of the peripheral

nervous system and their support structures. The nerve cells have their body (the soma) and a

long projection (the axon) that carries electrical nerve impulses to the neuromuscular junction

where the impulse is transferred to the muscle. Axons are wrapped in a sheath of Schwann

cells that contain myelin. Between Schwann cells are gaps called nodes of Ranvier where the

axon is exposed. Different types of GBS feature different types of immune attack. The

demyelinating variant (AIDP) features damage to the myelin sheath by white blood cells (T

lymphocytes and macrophages), this process is preceded by activation of a group of blood

proteins known as complement. In contrast, the axonal variant is mediated by IgG antibodies

and complement against the cell membrane covering axon without direct lymphocyte

involvement.

Various antibodies directed at nerve cells have been reported in GBS. In the axonal subtype,

these antibodies have been shown to bind to gangliosides, a group of substances found in

https://en.m.wikipedia.org/wiki/T_cell

https://en.m.wikipedia.org/wiki/T_cell

https://en.m.wikipedia.org/wiki/Macrophage


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peripheral nerves. A ganglioside is a molecule consisting of ceramide bound to a small group

of hexose-type sugars and containing various numbers of N-acetylneuraminic acid groups.

The key four gangliosides against which antibodies have been described are GM1, GD1a,

GT1a, and GQ1b, with different anti-ganglioside antibodies being associated with particular

features; for instance, GQ1b antibodies have been linked with Miller Fisher variant GBS and

related forms including Bickerstaff encephalitis. The production of these antibodies after an

infection is probably the result of molecular mimicry, where the immune system is reacting to

microbial substances, but the resultant antibodies also react with substances occurring

naturally in the body.[5]

After a Campylobacter infection, the body produces antibodies of the IgA class, only a small

proportion of people also produce IgG antibodies against bacterial substance cell wall

substances (e.g. lipopolysaccharides). Molecular mimicry between lipo-oligosaccharides

structure on the cell envelop of these bacteria and glycoside epitode on the human nerve that

generates cross-reactive immune response result in autoimmune -driven nerve damage.

Figure-6: mechanism used by GBS to evade the immune system.

LINK BETWEEN ZIKA VIRUS AND GBS

There is a growing evidence that zika virus may also an trigger Guillain Barre Syndrome the

thought is that the body creates antibodies to marshal an assault on the zika infection, and

after the illness subsides, these antibodies then start attacking the peripheral nerves that

connect the brain and spinal cord to the rest of the body.

Zika virus has previously been associated with GBS. The link was first described in 2013 and

2014 when the incidence of GBS showed a significant increase over 4 to 5 years during a

https://en.m.wikipedia.org/wiki/Hexose

https://en.m.wikipedia.org/wiki/N-Acetylneuraminic_acid

https://en.m.wikipedia.org/wiki/Antiganglioside_antibodies

https://en.m.wikipedia.org/wiki/GM1

https://en.m.wikipedia.org/wiki/Immunoglobulin_A

https://en.m.wikipedia.org/wiki/Lipopolysaccharide


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Zika outbreak in the French Polynesian islands. This was the first evidence of such a link, and

more research is required. However, there have been a few studies looking at the in the

incidence of GBS in French Polynesia and Latin America after recent Zika outbreaks.

Zika has been associated with mild flu-like symptoms in most people that contract the

disease, similar to many of the infections that appear before GBS.[6]

Figure-7: Effect of zika virus on neuron.

PATHOPHYSIOLOGY

Infections with pathogens, such as Campylobacter jejuni, can trigger humoral immune and

autoimmune responses that result in nerve dysfunction and the symptoms of GBS. Lipo-

oligosaccharides on the C. jejuni outer membrane may elicit the production of antibodies that

cross react with gangliosides, such as GM1 and GD1a on peripheral nerves. The antigens

targeted in AMAN are located at or near the node of Ranvier. The anti-GM1 and anti-GD1a

antibodies bind to the nodal axolemma, leading to complement activation followed by MAC

formation and disappearance of voltage-gated sodium channels. This damage can lead to

detachment of paranodal myelin, and nerve conduction failure. Macrophages then invade

from the nodes into the periaxonal space, scavenging the injured axons. The antigens targeted

in AIDP are, presumably, located on the myelin sheath. The antibodies can activate

complement, which leads to formation of the MAC on the outer surface of Schwann cells,

initiation of vesicular degeneration, and invasion of myelin by macrophages. Some antibody

specificities are associated with particular GBS subtypes and related neurological deficits,


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reflecting the distribution of different gangliosides in human peripheral nerves C. jejuni

infections are predominantly, but not exclusively, related to the AMAN or pure motor

subtype of GBS. Patients with AMAN frequently have serum antibodies against GM1a,

GM1b, GD1a and GalNAc-GD1a gangliosides. Patients with MFS or MFS–GBS overlap

syndrome frequently have antibodies against GD1b, GD3, GT1a and GQ1b gangliosides,

which are related to ataxia and ophthalmoplegia. In a study from the Netherlands, 20% of

patients with AIDP related to cytomegalovirus infection had anti-GM2 antibodies, although

these antibodies are also found in patients with uncomplicated cytomegalovirus infections.

Interestingly, as well as antibodies against single gangliosides, patients can also have

antibodies against combinations of epitopes from ganglioside complexes. Such complexes are

located in specialized microdomains, or 'lipid rafts', in the cell membrane. Antibodies that

target ganglioside complexes also cross react with C. jejuni lipo-oligosaccharides, and are

probably induced by a preceding infection with C. jejuni. Antibodies against various

combinations or complexes of glycolipids have also been reported in patients with AIDP,

although the role of these antibodies in its pathogenesis remains to be determined.[7]

In conjunction with the presence of antiganglioside antibodies, complement activation seems

to contribute to nerve degeneration in GBS a phenomenon that has been studied at the nodes

of Ranvier and at the motor nerve terminal in a mouse model of AMAN. Sodium channel

clusters, as well as paranodal axoglial junctions, the nodal cytoskeleton, and Schwann cell

microvilli, all of which stabilize the sodium channel clusters, were disrupted by complement

activation in a GBS disease model. Additional studies in a GBS mouse model provided

evidence that blockade of complement activation prevents emergence of the clinical signs of

antiganglioside-mediated neuropathy.

The development of GBS after a C. jejuni infection may also depend on patient-related

factors that influence the susceptibility to produce cross reactive, carbohydrate-targeted

antibodies. This hypothesis is supported by the fact that GBS has a relapse rate of 5%, which

is clearly higher than would be expected by chance. The initial pathogen–host interaction has

a key role in the development of GBS. C. jejuni lipo-oligosaccharides bind to siglec-7 (sialic

acid-binding immunoglobulin-like lectin 7) and activate dendritic cells via Toll-like receptor

4 and CD14. These dendritic cells produce type 1 interferon and tumour necrosis factor

(TNF), which induce proliferation of B cells. This immune activation could be influenced by

genetic polymorphisms but, to date, genetic factors have only been studied in small cohorts of


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patients. Interestingly, a meta-analysis identified a moderate association between GBS and a

particular TNF polymorphism. In addition, an association between polymorphisms in the

MBL2 gene (encoding mannose-binding protein C) and the severity and outcome of GBS has

been confirmed. Future genome-wide association studies in large, well-described and

adequately controlled cohorts are required to establish the role of host factors in the

pathogenesis of GBS.[8]

DIAGNOSIS

Guillain-Barre syndrome can be difficult to diagnose in its earliest stages. Its signs and

symptoms are similar to those of other neurological disorders and may vary from person to

person.

Doctors are likely to start with a medical history and thorough physical examination.

• Spinal tap (lumbar puncture). A small amount of fluid is withdrawn from the spinal canal in

your lower back. The fluid is tested for a type of change that commonly occurs in people who

have Guillain-Barre syndrome.

• Electromyography. Thin-needle electrodes are inserted into the muscles your doctor wants

to study. The electrodes measure nerve activity in the muscles.

• Nerve conduction studies. Electrodes are taped to the skin above your nerves. A small shock

is passed through the nerve to measure the speed of nerve signals.

TREATMENT

There's no cure for Guillain-Barre syndrome. But two types of treatments can speed recovery

and reduce the severity of the illness:

Plasma exchange (plasmapheresis). The liquid portion of part of your blood (plasma) is

removed and separated from your blood cells. The blood cells are then put back into your

body, which manufactures more plasma to make up for what was removed.

Plasmapheresis may work by ridding plasma of certain antibodies that contribute to the

immune system's attack on the peripheral nerves.

Immunoglobulin therapy. Immunoglobulin containing healthy antibodies from blood

donors is given through a vein (intravenously). High doses of immunoglobulin can block

the damaging antibodies that may contribute to Guillain-Barre syndrome.

These treatments are equally effective. Mixing them or administering one after the other is no

more effective than using either method alone.[9]


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Figure-8: Pathogenesis of GBS: molecular mimicry and antiganglioside antibodies.

Doctors are also likely to be given medication to:

Relieve pain, which can be severe.

Prevent blood clots, which can develop while you're immobile.

People with Guillain-Barre syndrome need physical help and therapy before and during

recovery. They may include:

Movement of your arms and legs by caregivers before recovery, to help keep your

muscles flexible and strong.

Physical therapy during recovery to help you cope with fatigue and regain strength and

proper movement.

Training with adaptive devices, such as a wheelchair or braces, to give you mobility and

self-care skills.[10]

RECOVERY

Although some people can take months and even years to recover, most people with Guillain-

Barre syndrome experience this general timeline:


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After the first signs and symptoms, the condition tends to progressively worse for about

two weeks.

Symptoms reach a plateau within four weeks.

Recovery begins, usually lasting six to 12 months, though for some people it could take

as long as three years.

Among adults recovering from Guillain-Barre syndrome:

About 80% can walk independently six months after diagnosis.

About 60% fully recover motor strength one year after diagnosis.

About 5% to 10% have very delayed and incomplete recovery.

Children, who rarely develop Guillain-Barre syndrome, generally recover more completely

than adults.[11]

EPIDEMIOLOGY

In Western countries, the number of new episodes per year has been estimated to be between

0.89 and 1.89 cases per 100,000 people. Children and young adults are less likely to be

affected than the elderly: the risk increases by 20% for every decade of life. Men are more

likely to develop Guillain–Barre syndrome than women; the relative risk for men is 1.78

compared to women.

The distribution of subtypes varies between countries. In Europe and the United States, 60–

80% of people with Guillain–Barré syndrome have the demyelinating subtype (AIDP), and

AMAN affects only a small number (6–7%). In Asia and Central and South America, that

proportion is significantly higher (30–65%). This may be related to the exposure to different

kinds of infection, but also the genetic characteristics of that population. Miller Fisher variant

is thought to be more common in Southeast Asia.[12]

LINK BETWEEN COVID-19 AND GBS

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), originating from Wuhan, is

spreading around the world and the outbreak continues to escalate. Patients with coronavirus

disease 2019 (COVID-19) typically present with fever and respiratory illness. However, little

information is available on the neurological manifestations of COVID-19. Here, we report the

first case of COVID-19 initially presenting with acute Guillain-Barré syndrome. On Jan 23,

2020, a woman aged 61 years presented with acute weakness in both legs and severe fatigue,

https://en.m.wikipedia.org/wiki/Relative_risk


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progressing within 1 day. She returned from Wuhan on Jan 19, but denied fever, cough, chest

pain, or diarrhoea. Her body temperature was 36·5°C, oxygen saturation was 99% on room

air, and respiratory rate was 16 breaths per min. Lung auscultation showed no abnormalities.

Neurological examination disclosed symmetric weakness (Medical Research Council grade

4/5) and areflexia in both legs and feet. 3 days after admission, her symptoms progressed.

Muscle strength was grade 4/5 in both arms and hands and 3/5 in both legs and feet.

Sensation to light touch and pinprick was decreased distally.[13]

Figure-9: Distribution of GBS between countries.

CONCLUSION

In conclusion, a diagnosis of Guillain-Barre syndrome may still be considered in a patient

with clinical findings and EMG studies consistent with GBS but with a CSF profile that does

not show the typical albuminocytologic dissociation. The long-term outlook for Guillain-

Barre syndrome is generally good. Most patients recover fully, although it can take months or

years to regain pre-illness strength and movement. About 30% of patients still have some

weakness three years after the illness strikes. Some keywords are Guillain Barré syndrome,

Campylobacter jejuni, antiganglioside antibodies, intravenous immunoglobulin treatment,

plasma exchange.

Investigators of large, worldwide, collaborative studies of the spectrum of Guillain-Barré

syndrome are accruing data for clinical and biological databases to inform the development

of outcome predictors and disease biomarkers. Such studies are transforming the clinical and

scientific landscape of acute autoimmune neuropathies. Treatments have been developed and


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proved effective, but these are not sufficient in many patients. Although there have been

major steps forward, this is no time for complacency as the research area continues to face

deep, unsolved issues around pathogenesis of Guillain-Barré syndrome, especially for the

acute inflammatory demyelinating polyneuropathy form of the disorder. Newly emerging

post-infectious forms of Guillain-Barré syndrome, such as those associated with arboviruses

including Zika, need to be closely monitored as global epidemics spread. Biomarkers,

prognostic models, and better therapies are needed. Many of these issues are being addressed

through multicentre, collaborative efforts such as IGOS. Prevention of severe axonal injury

early in the course of the disease remains a major focus, because it is an important limiting

factor in achieving a good, long-term outcome.

REFERENCES

1. Watanabe T, Matsuura O, Natsume J, et al. Dramatic improvement with

immunoabsorption therapy in a 7-year-old girl with severe Guillain-Barré syndrome after

unsuccessful gammaglobulin therapy. No To Hattatsu, 1998; 30: 255–60.

2. Guillain G, Barre J, Strohl A. Sur un syndrome de radiculo-nevrite avec hyperalbuminose

du liquide cephalorachidien sans reaction cellulaire. Remarques sur les characteres

clinique et graphique des reflexes tendinaux. Bulletins et Memories de la Societe

Medicale des Hopitaux de Paris, 1916; 40: 1462–70.

3. Kaplan JE, Katona P, Hurwitz ES, et al. Guillain-Barré syndrome in the United States,

1979–1980 and 1980–1981. Lack of an association with influenza vaccination. JAMA,

1982; 248: 698–700.

4. Carpo M, Pedotti R, Allaria S, et al. Clinical presentation and outcome of Guillain-Barré

and related syndromes in relation to anti-ganglioside antibodies. J Neurol Sci., 1999; 168:

78–84.

5. Prof. Dr. Dhrubo Jyoti Sen; Zika virus outbreak: the global endemic to pandemic:

European Journal of Pharmaceutical and Medical Research, 2017; 4(3): 01-07.

6. Vriesendorp FJ, Mishu B, Blaser MJ, et al. Serum antibodies to GM1, GD1b, peripheral

nerve myelin, and Campylobacter jejuni in patients with Guillain-Barré syndrome and

controls: correlation and prognosis. Ann Neurol, 1993; 34: 130–5.

7. Van den Berg, B., Walgaard, C., Drenthen, J. et al. Guillain–Barré syndrome:

pathogenesis, diagnosis, treatment and prognosis. Nat Rev Neurol, 2014; 10: 469–482.


826


8. Heikema, A. P. et al. Siglec-7 specifically recognizes Campylobacter jejuni strains

associated with oculomotor weakness in Guillain–Barré syndrome and Miller Fisher

syndrome. Clin. Microbiol. Infect, 2013; 19: E106–E112.

9. Kuijf, M. L. et al. Origin of ganglioside complex antibodies in Guillain–Barré syndrome.

J. Neuroimmunol, 2007; 188: 69–73.

10. Cao-Lormeau, V., Blake, A., Mons, S., Lastère, S., Roche, C., Vanhomwegen, J., … &

Ghawché, F. Guillain-Barré syndrome outbreak associated with Zika virus infection in

French Polynesia: A case-control study. The Lancet, 2016; 387(10027): 1531-1539.

11. Dimachkie, M. M. & Barohn, R. J. Guillain-Barré Syndrome and variants. Neurology

Clinics, 2014; 31(2): 491-510.

12. Cao-Lormeau VM, Blake A, Mons S, Lastère S, Roche C, Vanhomwegen J, Ghawché F.

Guillain-Barré syndrome outbreak associated with Zika virus infection in French

Polynesia: a case-control study. Lancet, 2016; 387(10027): 1531–1539.

13. Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain-Barré syndrome associated with SARS-

CoV-2 infection: Causality or coincidence? Lancet Neurol, 2020; S1474-4422(20):

30109–30105.

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HISTOPATHOLOGY OF GUILLAIN BARRE SYNDROME ......Guillain-Barre syndrome often begins with tingling and weakness starting in your feet and legs and spreading to your upper body and