GUILLAIN–BARRé SYNDROME (GBS) is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system . The initial symptoms are typically changes in sensation or pain along with muscle weakness, beginning in the feet and hands. This often spreads to the arms and upper body with both sides being involved. The symptoms develop over hours to a few weeks. During the acute phase, the disorder can be life-threatening with about 15% developing weakness of the breathing muscles requiring mechanical ventilation . Some are affected by changes in the function of the autonomic nervous system , which can lead to dangerous abnormalities in heart rate and blood pressure .
The cause is unknown. The underlying mechanism involves an autoimmune disorder in which the body's immune system mistakenly attacks the peripheral nerves and damages their myelin insulation. Sometimes this immune dysfunction is triggered by an infection or, less commonly, surgery or vaccination . The diagnosis is usually made based on the signs and symptoms, through the exclusion of alternative causes, and supported by tests such as nerve conduction studies and examination of the cerebrospinal fluid . There are a number of subtypes based on the areas of weakness, results of nerve conduction studies, and the presence of certain antibodies . It is classified as an acute polyneuropathy .
In those with severe weakness, prompt treatment with intravenous
immunoglobulins or plasmapheresis , together with supportive care,
will lead to good recovery in the majority. Recovery may take weeks to
years. About a third have some permanent weakness. Globally death
occurs in about 7.5% of those affected.
* 1 Signs and symptoms
* 2 Causes * 3 Mechanism
* 4 Diagnosis
* 4.1 Spinal fluid * 4.2 Neurophysiology * 4.3 Clinical subtypes
* 5 Treatment
* 5.1 Immunotherapy
* 6 Prognosis * 7 Epidemiology * 8 History * 9 Research directions * 10 References * 11 Further reading * 12 External links
SIGNS AND SYMPTOMS
The first symptoms of
Many people with
In children, particularly those younger than six years old, the diagnosis can be difficult and the condition is often initially mistaken (sometimes for up to two weeks) for other causes of pains and difficulty walking, such as viral infections, or bone and joint problems.
On neurological examination , characteristic features are the reduced
power and reduced or absent tendon reflexes (hypo- or areflexia ,
respectively). However, a small proportion has normal reflexes in
affected limbs before developing areflexia, and some may have
exaggerated reflexes. In the "
Miller Fisher variant" subtype of
A quarter of all people with
The autonomic or involuntary nervous system , which is involved in
the control of body functions such as heart rate and blood pressure ,
is affected in two thirds of people with Guillain–Barré syndrome,
but the impact is variable. Twenty percent may experience severe
blood-pressure fluctuations and irregularities in the heart beat ,
sometimes to the point that the heart beat stops and requiring
pacemaker-based treatment . Other associated problems are
abnormalities in perspiration and changes in the reactivity of the
Autonomic nervous system
A scanning electron microscope -derived image of Campylobacter jejuni, which triggers about 30% of cases of Guillain–Barré syndrome
Two thirds of people with
Links between other infections and GBS are less certain. 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 Guillain–Barré syndrome.
Some cases may be triggered by the influenza virus and potentially
influenza vaccine . An increased incidence of Guillain–Barré
syndrome followed influenza immunization that followed the 1976 swine
flu outbreak (H1N1 A/NJ/76); 8.8 cases per million recipients
developed the complication. Since then, close monitoring of cases
attributable to vaccination has demonstrated that influenza itself can
induce GBS. Small increases in incidence have been observed in
subsequent vaccination campaigns, but not to the same extent. The
2009 flu pandemic vaccine (against pandemic swine flu virus H1N1/PDM09
) did not cause a significant increase in cases. It is considered
that the benefits of vaccination in preventing influenza outweigh the
small risks of GBS after vaccination. Even those who have previously
Structure of a typical neuron NEURON
The nerve dysfunction in
Various antibodies directed at nerve cells have been reported in Guillain–Barré syndrome. In the axonal subtype, these antibodies have been shown to bind to gangliosides , a group of substances found in 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. 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. lipooligosaccharides ) that crossreact with human nerve cell gangliosides. It is not currently known how this process escapes central tolerance to gangliosides, which is meant to suppress the production of antibodies against the body's own substances. Not all antiganglioside antibodies cause disease, and it has recently been suggested that some antibodies bind to more than one type of epitope simultaneously (heterodimeric binding) and that this determines the response. Furthermore, the development of pathogenic antibodies may depend on the presence of other strains of bacteria in the bowel.
The diagnosis of
In many cases, magnetic resonance imaging of the spinal cord is
performed to distinguish between
Cerebrospinal fluid envelops the brain and the spine, and lumbar
puncture or spinal tap is the removal of a small amount of fluid using
a needle inserted between the lumbar vertebrae . Characteristic
Repeating the lumbar puncture during the disease course is not recommended. The protein levels may rise after treatment has been administered.
Directly assessing nerve conduction of electrical impulses can exclude other causes of acute muscle weakness, as well as distinguish the different types of Guillain–Barré syndrome. Needle electromyography (EMG) and nerve conduction studies may be performed. In the first two weeks, these investigations may not show any abnormality. Neurophysiology studies are not required for the diagnosis.
Formal criteria exist for each of the main subtypes of
A number of subtypes of
TYPE SYMPTOMS POPULATION AFFECTED NERVE CONDUCTION STUDIES ANTIGANGLIOSIDE ANTIBODIES
Acute inflammatory demyelinating polyneuropathy (AIDP) Sensory symptoms and muscle weakness, often with cranial nerve weakness and autonomic involvement Most common in Europe and North America Demyelinating polyneuropathy No clear association
Acute motor axonal neuropathy (AMAN) Isolated muscle weakness without sensory symptoms in less than 10%; cranial nerve involvement uncommon Rare in Europe and North America, substantial proportion (30-65%) in Asia and Central and South America; sometimes called "Chinese paralytic syndrome" Axonal polyneuropathy, normal sensory action potential GM1a/b, GD1a this is a rare occurrence compared to GBS with muscle weakness but no sensory symptoms.
Plasmapheresis and intravenous immunoglobulins (IVIG) are the two main immunotherapy treatments for GBS. Plasmapheresis attempts to reduce the body's attack on the nervous system by filtering antibodies out of the bloodstream. Similarly, administration of IVIG neutralizes harmful antibodies and inflammation. These two treatments are equally effective, but a combination of the two is not significantly better than either alone. Plasmapheresis speeds recovery when used within four weeks of the onset of symptoms. IVIG works as well as plasmapheresis when started within two weeks of the onset of symptoms, and has fewer complications. IVIG is usually used first because of its ease of administration and safety. Its use is not without risk; occasionally it causes liver inflammation , or in rare cases, kidney failure. Glucocorticoids alone have not been found to be effective in speeding recovery and could potentially delay recovery.
While pain is common in people with Guillain–Barré syndrome, studies comparing different types of pain medication are insufficient to make a recommendation as to which should be used.
Following the acute phase, around 40% of people require intensive rehabilitation with the help of a multidisciplinary team to focus on improving activities of daily living (ADLs). Studies into the subject have been limited, but it is likely that intensive rehabilitation improves long-term symptoms. Teams may include physical therapists , occupational therapists , speech language pathologists, social workers , psychologists , other allied health professionals and nurses . The team usually works under the supervision of a neurologist or rehabilitation physician directing treatment goals.
Physiotherapy interventions include strength, endurance and gait
training with graduated increases in mobility, maintenance of posture
and alignment as well as joint function.
There is a variation in the rate and extent of recovery. The
In research studies, the outcome from an episode of Guillain–Barré syndrome is recorded on a scale from 0 to 6, where 0 denotes completely healthy, 1 very minor symptoms but able to run, 2 able to walk but not to run, 3 requiring a stick or other support, 4 confined to bed or chair, 5 requiring long-term respiratory support, 6 death.
The health-related quality of life (HRQL) after an attack of
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
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.
Georges Guillain, together with Barré and Strohl, described two cases of self-limiting acute paralysis with peculiar changes in the cerebrospinal fluid. He succeeded his teacher Pierre Marie as professor of neurology at the Salpêtrière hospital in Paris in 1925.
French physician Jean-Baptiste Octave Landry first described the
disorder in 1859. In 1916,
Canadian neurologist C. Miller Fisher described the variant that bears his name in 1956. British neurologist Edwin Bickerstaff , based in Birmingham, described the brainstem encephalitis type in 1951 with Philip Cloake, and made further contributions with another paper in 1957. Guillain had reported on some of these features prior to their full description in 1938. Further subtypes have been described since then, such as the form featuring pure ataxia and the type causing pharyngeal-cervical-brachial weakness. The axonal subtype was first described in the 1990s.
Diagnostic criteria were developed in the late 1970s after the series of cases associated with swine flu vaccination. These were refined in 1990. The case definition was revised by the Brighton Collaboration for vaccine safety in 2009, but is mainly intended for research. Plasma exchange was first used in 1978 and its benefit confirmed in larger studies in 1985. Intravenous immunoglobulins were introduced in 1988, and its non-inferiority compared to plasma exchange was demonstrated in studies in the early 1990s.
The understanding of the disease mechanism of Guillain–Barré syndrome has evolved in recent years. Development of new treatments has been limited since immunotherapy was introduced in the 1980s and 1990s. Current research is aimed at demonstrating whether some people who have received IVIg might benefit from a second course if the antibody levels measured in blood after treatment have only shown a small increase. Studies of the immunosuppressive drug mycophenolate mofetil , brain-derived neurotrophic factor and interferon beta (IFN-β) have not demonstrated benefit to support their widespread use.
An animal model (experimental autoimmune neuritis in rats) is often used for studies, and some agents have shown promise: glatiramer acetate , quinpramine , fasudil (an inhibitor of the Rho-kinase enzyme), and the heart drug flecainide . An antibody targeted against the anti-GD3 antiganglioside antibody has shown benefit in laboratory research. Given the role of the complement system in GBS, it has been suggested that complement inhibitors (such as the drug eculizumab ) may be effective.
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CLASSIFICATION V · T · D
* ICD -10 : G61.0 * ICD -9-CM : 357.0 * OMIM : 139393 * MESH : D020275 * DISEASESDB : 5465
* MEDLINEPLUS : 000684 * EMEDICINE : emerg/222 neuro/7 pmr/48 neuro/598 * PATIENT UK : Guillain–Barré syndrome