GBS, also known as Guillain-Barré syndrome, is an extremely uncommon and possibly lethal autoimmune disorder that mainly affects people who were previously healthy and is characterized by progressive muscle weakness and demyelination of the peripheral nervous system1,2,3. Contrary to multiple sclerosis (MS), this disorder does not impact the central nervous system4.

Epidemeiology
Global Incidence
The incidence of common Guillain-Barré syndrome has been estimated to range between 0.6-4 instances per 100 000 people per year globally, although the most recent, meticulous population-based studies in Europe consistently report an incidence of 1.2-1.9 per 100 000 people5,6.
Atypical cases like Fisher’s syndrome are extremely uncommon, with an incidence of 0.1 per 100 000, according to Italian researchers. According to the researchers, men have a 1.5 times higher risk of being impacted than women7. Also, cohort research indicates that the risk for Guillain-Barré syndrome decreases during pregnancy and rises after delivery based on age-adjusted relative risks.
In addition, any age group can have this disorder1,7. It appears that the age-specific curve has a bimodal distribution. According to research, the incidence rises with age, especially among older age groups2,5,7. The incidence in Europe and North America increases gradually with age, from less than one per 100,000 patients under the age of 30 to approximately four per 100,000 patients over the age of 75. The estimated incidence in China is 0.66 per 100 000 for all ages8, which is about the same for children and significantly less for adults than for adults elsewhere.
The incidence on the Caribbean island of Curaçao increased significantly from 1.62 per 100,000 from 1987 to 1991 to 3.10 per 100,000 from 1992 to 1999 5. Studies of a similar nature from other locations indicate a steady incidence of Guillain-Barré syndrome throughout time. There are no significant regional differences. However, several series show minor seasonal fluctuations7.

*Upper Respiratory Tract Infection (URTI)
Aetiology
Antecedent Major Triggers
Infections
As antecedent events of the Guillain-Barré syndrome, infections are well-known9. The fast-progressing, monophasic illness of Guillain-Barré syndrome indicates that it is a typical post-infectious disorder. Within 4 weeks of the start of paralysis, 2/3 of adult patients report experiencing respiratory or gastrointestinal symptoms previously10,11. An earlier diarrheal disease is reported by 20% of patients on average9.
However, only a small number of microorganisms have a link with the disorder been demonstrated in case-control studies, despite the fact that patients with the disorder have been found to have a wide variety of prior infections. The most often identified pathogens are Campylobacter jejuni. In 25–50% of adult patients, C jejuni has a higher incidence in Asian countries10,11,12,13. Infection with Campylobacter jejuni is most likely the source of summer epidemics in northern China14.
Cytomegalovirus (CMV), Epstein-Barr virus, influenza A virus, Mycoplasma pneumoniae, and Haemophilus influenza are other infections linked to Guillain-Barré syndrome. The second most frequently reported infection is cytomegalovirus7. In a Japanese study15, 5% of patients with Guillain-Barré syndrome had signs of a prior CMV infection, while in European studies, 11–13% did. Initial clinical symptoms in affected people often include significant respiratory problems.
Hepatitis E has been linked to Guillain-Barré syndrome in both individuals from some countries. As the global epidemic expands, there is increasing interest in the potential link between acute arbovirus infections, such as Zika16 and chikungunya, and Guillain-Barré syndrome. It is not more frequent than in controls to have serological evidence of infections with Haemophilus influenzae, parainfluenza type 1 virus, influenza A and B viruses, adenovirus, varicella-zoster virus, and parvovirus B4. The actual incidence figures for Guillain-Barré syndrome will become obvious as more data from case-control studies and epidemiological surveillance are revealed. The clinical phenotype and prognosis are influenced by the type of the prior infection.

Vaccines
Numerous vaccines, including Semple rabies, oral polio, influenza, measles, measles/mumps/rubella (MMR)17, tetanus toxoid-containing vaccines, and hepatitis B, may be linked to Guillain-Barré syndrome, according to epidemiological research6. A temporal connection between two events does not, however, indicate a cause-and-effect relationship. In order to determine whether the putative link is statistically significant, one must assess the epidemiological data that are currently available6.
An increase in Guillain-Barré syndrome patients was observed in the USA during the A/New Jersey influenza vaccination program6. As a result, epidemiological research was carried out to establish the statistical significance of the association and nationwide surveillance for the illness was started. It was discovered that the six-week18 relative risks of Guillain-Barré syndrome increased after vaccination varied from 4 to 7.816. However, later research did not support such a high relative risk.
Other Possible Factors
Most often in the form of individual case reports1, several associations and triggering variables have been identified. Surgery, epidural anesthesia, kidney and bone marrow transplants, cancer, and snake bite are some of these 6. These relationships may simply be chance associations given the lack of clarity surrounding their statistical significance. Immunization, insect bites, and animal interaction were all similarly prevalent in both the index and control groups, according to a prospective study 2 looking at the antecedent events for the illness. Several medicines have also been mentioned as potential triggers. According to a case-control study, people with Guillain-Barré syndrome used penicillins and antimotility medications more frequently than oral contraceptives6.
Clinical Features and Mechanism
In Landry’s report on 10 patients with “ascending paralysis”6 in 1859, one of the earliest reports of what we now identify to as Guillain-Barré syndrome may be discovered. Two French soldiers were diagnosed in 1916 by Guillain, Barré, and Strohl with motor weakness, areflexia, and “albuminocytological dissociation” in the cerebral fluid 6. Later, after additional individuals with identical symptoms were identified, this clinical entity was given the names Guillain and Barré. Later, many variants of the syndrome with distinguishing clinical features were reported. Based on clinical features, aetiology, and electrophysiological traits, this separation is now attainable.
Symptoms
In almost two-thirds of patients, symptoms are preceded by an antecedent event. The most frequent illness is a respiratory infection, which occurs in around 40% of cases within a month before the condition manifests itself. Gastroenteritis is a significant contributing factor in about 20% of cases1,2,4,6. Limb weakness is the most typical symptom. The most frequent cranial nerve involvement is facial palsy (occurring in 53%), followed by tongue weakness, bulbar weakness, and ophthalmoplegia (eyelid drooping by optic nerve paralysis)10. The illness is indicated by sensory signs in around 50% of patients. About 80% of people experience sensory symptoms overall. Around 90% of people report having some form of pain, and it is frequently very severe6,10.

About two-thirds of cases have autonomic dysfunction, which shows up as either increased or decreased activity of the sympathetic or parasympathetic nervous systems. The most typical signs of dysautonomia are variations in blood pressure and pulse. Either acute or subacute symptoms may appear at first. After a phase of plateauing, recovery occurs gradually2,6,10.
GBS Subtypes
According to recent research, there are at least four main clinical and electrophysiological subtypes of GBS, including miller fisher syndrome (MSF), acute inflammatory demyelinating polyneuropathy (AIDP), acute motor and sensory axonal neuropathy (AMSAN), acute motor axonal neuropathy (AMAN)2,4,6.
AMAN is limited to pure motor involvement, AMSAN is a more severe disease with motor-sensory involvement, and AIDP is characterized by demyelination.

Acute Inflammatory Demyelinating Polyneuropathy (AIDP)
Most cases of acute inflammatory demyelinating polyneuropathy (AIDP)2,19, which is characterized pathologically by demyelination, lymphocytic infiltration, and macrophage-mediated removal of myelin, occur in this manner. Asymmetrical ascending motor weakness with hypo- or areflexia is the clinical sign. The underlying pathogenic process involves inflammation and the activation of macrophages to cause the myelin sheaths protecting the peripheral nerve axons to be destroyed2,6. This causes a slowing and blocking of conduction in peripheral nerves, which weakens muscles. In severe situations, there may be a subsequent axonal injury. Antibody binding and complement fixation occur after AIDP-induced injury to nerve terminal axons. With the breakdown of the terminal axonal cytoskeleton and mitochondrial damage2, activation of the complement system primarily results in membrane attack complex (MAC) production19.
Acute Motor Axonal Neuropathy (AMAN)
The term “acute motor axonal neuropathy” (AMAN) was coined when it was discovered that the majority of patients with Guillain-Barré syndrome during summer epidemics in northern China in 1991 and 1992 had a pure motor axonal form of neuropathy6. In comparison to 42 percent of AIDP cases, between 55 and 65 percent of the patients fell into this category, with 76 percent of them seropositive for C. jejuni. About 10–20 percent of sporadic instances of Guillain–Barré syndrome are of the AMAN type6.
Although tendon reflexes may still be present, the clinical characteristics of AIDP are identical. Acute motor axonal neuropathy is thought to be an IgG- and complement-mediated disease, similar to AIDP10. As specific motor nerve and axonal involvement are shown, electrophysiological testing may be able to distinguish from other types. In AMAN, the pathogenic process includes macrophage invasion10,20, inflammation, and axonal injury in addition to antibodies binding to ganglioside antigens on the axon cell membrane. Most likely the target of antibodies that bind to their Fc receptors and are directed towards ganglioside antigens on the axolemma. Invading macrophages leave the myelin sheath intact as they invade the nodes of Ranvier and insert between the axon and the surrounding Schwann cell axolemma10.
The feature of AMAN is quickly progressing weakness, frequently accompanied by respiratory failure, and has typically good recovery21.
Acute Motor Sensory Axonal Neuropathy (AMSAN)
Feasby et al. published observations on seven individuals who experienced a very acute and severe sickness with motor and sensory impairment in 19866. These patients’ symptoms included substantial muscular atrophy and slow healing. Motor nerves that were inactive and signs of sensory and motor axonal malfunction were visible through electrophysiology. In one of the cases, there was no demyelination or inflammation but there were signs of axonal degradation. They concluded that the traits pointed to a novel clinicopathological entity23. This group was diagnosed with acute motor sensory axonal neuropathy in later research from northern China (AMSAN). Additionally, reports from northern China suggested that AMSAN might occur after C. jejuni infection6.
Sensory and motor fiber degeneration that resembles Wallerian disease has been observed in studies, with little demyelination or lymphocytic infiltration.
The disease course in AMSAN is frequently fulminant (rapidly and fatal)2,6, with typically poor and incomplete recovery. The immune-mediated axonal damage in Guillain-Barré syndrome in this group is more likely to be severe10.
Millet-Fısher Syndrome (MFS)
Fisher first identified three patients in 1956 who had the characteristic Miller-Fisher syndrome triad of symptoms: ataxia, areflexia, and external and internal ophthalmoplegia24. Miller-Fisher syndrome can also cause mild facial palsy, bulbar palsy, ptosis, and limb weakness. About 5% of patients with Guillain-Barré syndrome have this condition.
Given that Miller-Fisher syndrome is a rare condition2,6, there are few neuropathological investigations on it. One examination revealed signs of demyelination and inflammation in the spinal ganglia, peripheral nerves25, and the third and sixth cranial nerves. These characteristics were not linked to any indications of neurogenic atrophy or axonal injury, and the central nervous system’s histology was also normal.
The electrophysiological evaluation’s most recurrent and obvious finding is the absence or reduction of sensory nerve action potentials6,10. Conduction speeds of the motor and sensory nerves are either normal or only slightly slowed. The conduction velocity increases with clinical recovery when slowed6.

Conclusion
Guillain-Barré Syndrome or GBS is a loose paralysis disease of the peripheral nervous system with acute onset and due to immune dysfunction2,6.

The incidence of GBS is rare worldwide10. Although it can be seen at any age from childhood to advanced age, its frequency increases in young adults and over the age of 55, and men are affected 1.5 times more than women2. Generally, there is a history of an infection such as upper respiratory tract infection, gastroenteritis, surgical intervention, vaccination, or birth 1 to 4 weeks before the onset of the disease. The most commonly detected agent is Campylobacter jejuni, other GBS-associated pathogens are cytomegalovirus (CMV), Epstein–Barr virus, Mycoplasma pneumonia, Haemophilus influenzae, and influenza A virus2,4,6,10. Cases have also been reported with the Covid 19 virus6. There are four different subtypes of GBS. AIDP is the most common subtype and has good recovery, while AMSAN is a rapidly developing fatal10 subtype. So, the prognosis varies according to these types6.
References:
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- Jacobs, B. C., Rothbarth, P. H., Van der Meché, F. G. A., Herbrink, P., Schmitz, P. I. M., De Klerk, M. A., & Van Doorn, P. A. (1998). The spectrum of antecedent infections in Guillain-Barré syndrome: a case-control study. Neurology, 51(4), 1110-1115.
- Hughes, R., & Cornblath, D. (2005, November 03). Guillain-Barré syndrome. Retrieved August 6, 2022, from https://www.sciencedirect.com/science/article/pii/S0140673605676659
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Figure References:
- https://propelphysiotherapy.com/neurological-injuries/guillain-barre-syndrome-treatment/#
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- (PDF) Guillain-Barré syndrome (GBS): A Review – Researchgate. (n.d.). Retrieved August 3, 2022, from https://www.researchgate.net/publication/309770980_Guillain-barre_syndrome_GBS_A_Review
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