Guillain–Barré Syndrome
   HOME

TheInfoList



OR:

Guillain–Barré syndrome (GBS) is a rapid-onset
muscle weakness Muscle weakness is a lack of muscle strength. Its causes are many and can be divided into conditions that have either true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, includ ...
caused by the
immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
damaging the
peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of Bilateria, bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside t ...
. Typically, both sides of the body are involved, and the initial symptoms are changes in sensation or pain often in the back along with muscle weakness, beginning in the feet and hands, often spreading to the arms and upper body. The symptoms may develop over hours to a few weeks. During the acute phase, the disorder can be life-threatening, with about 15% of people developing respiratory muscle weakness requiring
mechanical ventilation Mechanical ventilation or assisted ventilation is the Medicine, medical term for using a ventilator, ventilator machine to fully or partially provide artificial ventilation. Mechanical ventilation helps move air into and out of the lungs, wit ...
. Some are affected by changes in the function of the
autonomic nervous system The autonomic nervous system (ANS), sometimes called the visceral nervous system and formerly the vegetative nervous system, is a division of the nervous system that operates viscera, internal organs, smooth muscle and glands. The autonomic nervo ...
, which can lead to dangerous abnormalities in
heart rate Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the nee ...
and
blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...
. Although 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 Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...
insulation. Sometimes this immune dysfunction is triggered by an infection or, less commonly, by surgery, and by
vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...
. The diagnosis is usually 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 Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...
. There are several 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 Polyneuropathy () is damage or disease affecting peripheral nerves (peripheral neuropathy) in roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain. It usually begins in the hands and feet and may prog ...
. In those with severe weakness, prompt treatment with
intravenous immunoglobulin Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory demyelinat ...
s or
plasmapheresis Plasmapheresis (from the Greek language, Greek πλάσμα, ''plasma'', something molded, and ἀφαίρεσις ''aphairesis'', taking away) is the removal, treatment, and return or exchange of blood plasma or components thereof from and to the ...
, together with supportive care, will lead to good recovery in the majority of cases. Recovery may take weeks to years, with about a third having some permanent weakness. Globally, death occurs in approximately 7.5% of those affected. Guillain–Barré syndrome is rare, at 1 or 2 cases per 100,000 people every year. The
illness A disease is a particular abnormal condition that adversely affects the structure or function (biology), function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical condi ...
that afflicted US president
Franklin D. Roosevelt Franklin Delano Roosevelt (January 30, 1882April 12, 1945), also known as FDR, was the 32nd president of the United States, serving from 1933 until his death in 1945. He is the longest-serving U.S. president, and the only one to have served ...
, and left him paralysed from the waist down, which was believed at the time to be
polio Poliomyelitis ( ), commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 75% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe ...
, may have been Guillain–Barré syndrome, according to more recent research. The syndrome is named after the French
neurologist Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the ...
s
Georges Guillain Georges Charles Guillain () (3 March 1876 – 29 June 1961) was a French neurologist born in Rouen. He studied medicine in Rouen and Paris, where he learned clinical education at several hospitals. He developed an interest in neurology, and his f ...
and Jean Alexandre Barré, who, together with French physician
André Strohl André Strohl (20 March 1887 – 10 March 1977) was a French physiologist who was a native of Poitiers. He is remembered for his role in the diagnosis of Guillain–Barré syndrome (sometimes called Guillain–Barré–Strohl syndrome), a form of ...
, described the condition in 1916.


Signs and symptoms

The first symptoms of Guillain–Barré syndrome are numbness, tingling, and pain, alone or in combination. This is followed by weakness of the legs and arms that affects both sides equally and worsens over time. The weakness can take half a day to over two weeks to reach maximum severity, and then becomes steady. In one in five people, the weakness continues to progress for as long as four weeks. The muscles of the neck may also be affected, and about half experience involvement of the
cranial nerves Cranial nerves are the nerves that emerge directly from the brain (including the brainstem), of which there are conventionally considered twelve pairs. Cranial nerves relay information between the brain and parts of the body, primarily to and f ...
that supply the head and face; this may lead to weakness of the muscles of the face, swallowing difficulties and sometimes weakness of the eye muscles. In 8%, the weakness affects only the legs (paraplegia or paraparesis). Involvement of the muscles that control the bladder and anus is unusual. In total, about a third of people with Guillain–Barré syndrome continue to be able to walk. Once the weakness has stopped progressing, it persists at a stable level ("plateau phase") before improvement occurs. The plateau phase can take between two days and six months, but the most common duration is a week. Pain-related symptoms affect more than half, and include
back pain Back pain (Latin: ''dorsalgia'') is pain felt in the back. It may be classified as neck pain (cervical), middle back pain (thoracic), lower back pain (lumbar) or coccydynia (tailbone or sacral pain) based on the segment affected. The lumbar area ...
, parasthesia, muscle pain, and pain in the head and neck relating to irritation of the lining of the brain. Many people with Guillain–Barré syndrome have experienced the signs and symptoms of an infection in the 3–6 weeks before the onset of the neurological symptoms. The infection typically affects the upper respiratory tract (rhinitis, sore throat, cough) or
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...
(
diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...
, abdominal pain, bloating). 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 A neurological examination is the assessment of sensory neuron and motor responses, especially reflexes, to determine whether the nervous system is impaired. This typically includes a physical examination and a review of the patient's medical his ...
, characteristic features are the reduced strength of muscles and reduced or absent tendon reflexes ( hypo- or areflexia, respectively). However, a small proportion have normal reflexes in affected limbs before developing areflexia, and some may have exaggerated reflexes. In the Miller Fisher variant of Guillain–Barré syndrome , a triad of weakness of the eye muscles, abnormalities in coordination, as well as absent reflexes can be found. The level of consciousness is normally unaffected in Guillain–Barré syndrome, but the Bickerstaff brainstem encephalitis subtype may feature drowsiness, sleepiness, or coma.


Respiratory failure

A quarter of all people with Guillain–Barré syndrome develop weakness of the breathing muscles leading to
respiratory failure Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a r ...
, the inability to breathe adequately to maintain healthy levels of
oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...
, and/or
carbon dioxide Carbon dioxide is a chemical compound with the chemical formula . It is made up of molecules that each have one carbon atom covalent bond, covalently double bonded to two oxygen atoms. It is found in a gas state at room temperature and at norma ...
in the blood. This life-threatening scenario is complicated by other medical problems such as
pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...
, severe infections, blood clots in the lungs, and bleeding in the digestive tract in 60% of those who require artificial ventilation.


Autonomic dysfunction

The autonomic or involuntary nervous system, which is involved in the control of body functions such as
heart rate Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the nee ...
and
blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...
, 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 requires pacemaker-based treatment. Other associated problems are abnormalities in
perspiration Perspiration, also known as sweat, is the fluid secreted by sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and Apocrine sweat gland, apocrine glands. The eccrine sweat glands are distribu ...
and changes in the reactivity of the pupils. Autonomic nervous system involvement can affect even those who do not have severe muscle weakness.


Causes


Infection onset

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 Gastroenteritis, also known as infectious diarrhea, is an inflammation of the Human gastrointestinal tract, gastrointestinal tract including the stomach and intestine. Symptoms may include diarrhea, vomiting, and abdominal pain. Fever, lack of ...
or a
respiratory tract infection Respiratory tract infections (RTIs) are infectious diseases involving the lower or upper respiratory tract. An infection of this type usually is further classified as an upper respiratory tract infection (URI or URTI) or a lower respiratory tract ...
. In many cases, the exact nature of the infection can be confirmed. Approximately 30% of cases are provoked by ''
Campylobacter jejuni ''Campylobacter jejuni'' is a species of pathogenic bacteria that is commonly associated with poultry, and is also often found in animal feces. This species of microbe is one of the most common causes of food poisoning in Europe and in the US, w ...
'' bacteria, which cause diarrhea. A further 10% are attributable to
cytomegalovirus ''Cytomegalovirus'' (CMV) (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order '' Herpesvirales'', in the family '' Herpesviridae'', in the subfamily '' Betaherp ...
(CMV, HHV-5). Despite this, only very few people with ''Campylobacter'' or CMV infections develop Guillain–Barré syndrome (0.25–0.65 per 1000 and 0.6–2.2 per 1000 episodes, respectively). The strain of ''Campylobacter'' involved may determine the risk of GBS; different forms of the bacteria have different
lipopolysaccharide Lipopolysaccharide (LPS), now more commonly known as endotoxin, is a collective term for components of the outermost membrane of the cell envelope of gram-negative bacteria, such as '' E. coli'' and ''Salmonella'' with a common structural archit ...
s on their surface, and some may induce illness (see below) while others will not. Links between other infections and GBS are less certain. Two other herpes viruses (
Epstein–Barr virus The Epstein–Barr virus (EBV), also known as human herpesvirus 4 (HHV-4), is one of the nine known Herpesviridae#Human herpesvirus types, human herpesvirus types in the Herpesviridae, herpes family, and is one of the most common viruses in ...
/HHV-4 and
varicella zoster virus Varicella zoster virus (VZV), also known as human herpesvirus 3 (HHV-3, HHV3), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting children and young adults, and shingles (herpes zos ...
/HHV-3) and the bacterium '' Mycoplasma pneumoniae'' have been associated with GBS. GBS is known to occur after influenza and influenza vaccination has been demonstrated to be associated with a reduced risk. The tropical flaviviral infections
dengue fever Dengue fever is a mosquito-borne disease caused by dengue virus, prevalent in tropical and subtropical areas. Asymptomatic infections are uncommon, mild cases happen frequently; if symptoms appear, they typically begin 3 to 14 days after i ...
and
Zika virus Zika virus (ZIKV; pronounced or ) is a member of the virus family ''Flaviviridae''. It is spread by daytime-active ''Aedes'' mosquitoes, such as '' A. aegypti'' and '' A. albopictus''. Its name comes from the Ziika Forest of Uganda, where ...
have also been associated with episodes of GBS. Previous hepatitis E virus infection is more common in people with GBS.


Vaccine onset

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 (0.0088 per 1000) recipients developed it as a complication. GBS cases occurred in 362 patients during the 6 weeks after influenza vaccination of 45 million persons, an 8.8-fold increase over normal rates. The 1976 swine flu vaccination-induced GBS was an outlier; 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. In fact, "studies found a small increase of approximately 1 case per million vaccines above the baseline rate, which is similar to that observed after administration of seasonal influenza vaccines over the past several years." Natural influenza infection is a stronger risk factor for the development of GBS than is influenza vaccination and the vaccination reduced the risk of GBS overall by lowering the risk of catching influenza. In the United States, GBS after seasonal influenza vaccination is listed on the federal government's vaccine injury table. On March 24, 2021, after reviewing several post-marketing observational studies, where an increased risk of Guillain–Barré syndrome was observed after 42 days following vaccination with the Zoster vaccine Shingrix, the
FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
required safety label changes from the manufacturer
GlaxoSmithKline GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers an ...
to include warnings for risk of Guillain–Barré syndrome.


COVID-19 infection or vaccine related

GBS has been reported in association with
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...
, and may be a potential neurological complication of the disease. GBS has been reported as a very rare side effect of the Janssen and
Oxford–AstraZeneca COVID-19 vaccine The Oxford–AstraZeneca COVID19 vaccine, sold under the brand names Covishield and Vaxzevria among others, is a viral vector vaccine COVID-19 vaccine, for the prevention of COVID-19. It was developed in the United Kingdom by University of ...
s and the
European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...
issued a warning to the patients and healthcare providers. The incidence of GBS following the vaccination with the Oxford–AstraZeneca vaccine was originally reported as being lower than the incidence of GBS following a COVID-19 infection. More recent studies, however, found no measurable link between COVID-19 infection and GBS, while correlations with a first dose of AstraZeneca or Janssen vaccines were still positive. COVID-19 has been reported as causing peripheral neuropathy and more recently some evidence of aggravation of autoimmune disorders including GBS.


Drug induced

Zimelidine Zimelidine (International Nonproprietary Name, INN, British Approved Name, BAN; brand names Zimeldine, Normud, Zelmid) was one of the first selective serotonin reuptake inhibitor (SSRI) antidepressants to be marketed. It is a pyridylallylamine, a ...
, an antidepressant, had a very favorable safety profile but as a result of rare case reports of Guillain–Barré syndrome was withdrawn from the market.


Pathophysiology

The nerve dysfunction in Guillain–Barré 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) in the
spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...
and a long projection (the
axon An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...
) that carries electrical nerve impulses to the
neuromuscular junction A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to ...
, where the impulse is transferred to the muscle. Axons are wrapped in a sheath of
Schwann cell Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include Satellite glial cell, satellite ...
s that contain
myelin Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...
. Between Schwann cells are gaps (
nodes of Ranvier Nodes of Ranvier ( ), also known as myelin-sheath gaps, occur along a myelinated axon where the axolemma is exposed to the extracellular space. Nodes of Ranvier are uninsulated axonal domains that are high in sodium and potassium ion channels ...
) where the axon is exposed. Different types of Guillain–Barré syndrome feature different types of immune attacks. The demyelinating variant (AIDP, see below) features damage to the myelin sheath by
white blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
s (
T lymphocytes T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes A lymphocyte is a type of white blood cell (leukoc ...
and
macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
s); 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 the axon without direct lymphocyte involvement. 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
ganglioside A ganglioside is a molecule composed of a glycosphingolipid (ceramide and oligosaccharide) with one or more sialic acids (e.g. N-acetylneuraminic acid, ''N''-acetylneuraminic acid, NANA) linked on the sugar chain. NeuNAc, an acetylated derivative ...
s, a group of substances found in peripheral nerves. A ganglioside is a molecule consisting of
ceramide Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid joined by an amide bond. Ceramides are found in high concentrations within the cell membrane of Eukaryote, eukaryotic cells, since they are co ...
bound to a small group of
hexose In chemistry, a hexose is a monosaccharide (simple sugar) with six carbon atoms. The chemical formula for all hexoses is , and their molecular weight is 180.156 g/mol. Hexoses exist in two forms, open-chain or cyclic, that easily convert into ...
-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 antiganglioside 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 probably is 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 cross-react with human nerve cell gangliosides. It is not currently known how this process escapes
central tolerance In immunology, central tolerance (also known as negative selection) is the process of eliminating any ''developing'' T or B lymphocytes that are autoreactive, i.e. reactive to the body itself. Through elimination of autoreactive lymphocytes, t ...
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 An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although e ...
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. It has been suggested that a poor injection technique may also cause a direct injury to the axillary nerves adjacent to the injection site in the deltoid muscle which may lead to peripheral neuropathy. The consequent vaccine transfection and translation in the nerves may spur an immune response against nerve cells potentially causing an autoimmune nerve damage, leading to conditions like Guillain–Barré syndrome.


Diagnosis

The diagnosis of Guillain–Barré syndrome depends on findings such as rapid development of muscle paralysis, absent reflexes, absence of fever, and absence of a likely cause. Cerebrospinal fluid analysis (through a lumbar spinal puncture) and nerve conduction studies are supportive investigations commonly performed in the diagnosis of GBS. Testing for antiganglioside antibodies is often performed, but their contribution to diagnosis is usually limited. Blood tests are generally performed to exclude the possibility of another cause for weakness, such as a low level of potassium in the blood. An abnormally low level of sodium in the blood is often encountered in Guillain–Barré syndrome. This has been attributed to the inappropriate secretion of antidiuretic hormone, leading to relative retention of water. In many cases,
magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...
of the spinal cord is performed to distinguish between Guillain–Barré syndrome and other conditions causing limb weakness, such as spinal cord compression. If an MRI scan shows enhancement of the nerve roots, this may be indicative of GBS. In children, this feature is present in 95% of scans, but it is not specific to Guillain–Barré syndrome, so other confirmation is also needed.


Spinal fluid

Cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...
envelops the brain and the spine, and a lumbar puncture or spinal tap is the removal of a small amount of fluid using a needle inserted between the
lumbar vertebrae The lumbar vertebrae are located between the thoracic vertebrae and pelvis. They form the lower part of the back in humans, and the tail end of the back in quadrupeds. In humans, there are five lumbar vertebrae. The term is used to describe t ...
. Characteristic findings in Guillain–Barré syndrome are an elevated protein level, usually greater than 0.55 g/L, and fewer than 10 white blood cells per cubic millimeter of fluid ("albuminocytological dissociation"). This pattern distinguishes Guillain–Barré syndrome from other conditions (such as
lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...
and
poliomyelitis Poliomyelitis ( ), commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 75% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe ...
) in which both the protein and the cell count are elevated. Elevated CSF protein levels are found in approximately 50% of patients in the first 3 days after onset of weakness, which increases to 80% after the first week. Repeating the lumbar puncture during the disease course is not recommended. The protein levels may rise after treatment has been administered.


Neurophysiology

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 Electromyography (EMG) is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph to produce a record called an electromyogram. An electromyo ...
(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 Guillain–Barré syndrome (AIDP and AMAN/AMSAN, see below), but these may misclassify some cases (particularly where there is reversible conduction failure), and therefore changes to these criteria have been proposed. Sometimes, repeated testing may be helpful.


Clinical subtypes

Several subtypes of Guillain–Barré syndrome are recognized. Despite this, many people have overlapping symptoms that can make the classification difficult in individual cases. All types have partial forms. For instance, some people experience only isolated eye movement or coordination problems; these are thought to be a subtype of and have similar antiganglioside antibody patterns. Other diagnostic entities are often included in the spectrum of Guillain–Barré syndrome. Bickerstaff's brainstem encephalitis (BBE), for instance, is part of the group of conditions now regarded as forms of Miller Fisher syndrome (anti-GQ1b antibody syndrome), as well as a related condition labelled "acute ataxic hypersomnolence" where coordination problems and drowsiness are present but no muscle weakness can be detected. BBE is characterized by the rapid onset of ophthalmoplegia, ataxia, and disturbance of consciousness, and may be associated with absent or decreased tendon reflexes and as well as Babinski's sign. The course of the disease is usually monophasic, but recurrent episodes have been reported. MRI abnormalities in the brainstem have been reported in 11%. Whether isolated acute sensory loss can be regarded as a form of Guillain–Barré syndrome is a matter of dispute; this is a rare occurrence compared to GBS with muscle weakness but no sensory symptoms.


Treatment


Immunotherapy

Plasmapheresis Plasmapheresis (from the Greek language, Greek πλάσμα, ''plasma'', something molded, and ἀφαίρεσις ''aphairesis'', taking away) is the removal, treatment, and return or exchange of blood plasma or components thereof from and to the ...
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; the risks include occasionally causing liver inflammation, or in rare cases, kidney failure.
Glucocorticoids Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...
alone are not effective in speeding recovery and could potentially delay recovery.


Respiratory failure

Respiratory failure may require intubation of the trachea and breathing support through
mechanical ventilation Mechanical ventilation or assisted ventilation is the Medicine, medical term for using a ventilator, ventilator machine to fully or partially provide artificial ventilation. Mechanical ventilation helps move air into and out of the lungs, wit ...
, generally on an
intensive care unit An intensive care unit (ICU), also known as an intensive therapy unit or intensive treatment unit (ITU) or critical care unit (CCU), is a special department of a hospital or health care facility that provides intensive care medicine. An inten ...
. The need for ventilatory support can be anticipated by measurement of two
spirometry Spirometry (meaning ''the measuring of breath'') is the most common of the pulmonary function tests (PFTs). It measures lung function, specifically the amount (volume) and/or speed (flow) of air that can be inhaled and exhaled. Spirometry is h ...
-based breathing tests: the
forced vital capacity Spirometry (meaning ''the measuring of breath'') is the most common of the pulmonary function tests (PFTs). It measures lung function, specifically the amount (volume) and/or speed (flow) of air that can be inhaled and exhaled. Spirometry is he ...
(FVC) and the negative inspiratory force (NIF). An FVC of less than 15 mL per kilogram body weight or an NIF of less than 60  cmH2O are considered markers of severe respiratory failure.


Pain

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.


Rehabilitation

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 Activities of daily living (ADLs) is a term used in healthcare to refer to an individual's daily self-care activities. Health professionals often use a person's ability or inability to perform ADLs as a measure of their Performance status, functi ...
(ADLs). Studies into the subject have been limited, but it is likely that intensive rehabilitation improves long-term symptoms. Teams may include
physical therapists Physical therapy (PT), also known as physiotherapy, is a healthcare profession, as well as the care provided by physical therapists who promote, maintain, or restore health through patient education, physical intervention, disease prevention ...
, occupational therapists, speech language pathologists, social workers,
psychologist A psychologist is a professional who practices psychology and studies mental states, perceptual, cognitive, emotional, and social processes and behavior. Their work often involves the experimentation, observation, and explanation, interpretatio ...
s, 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. Occupational therapy aims to improve everyday function with domestic and community tasks as well as driving and work. Home modifications, gait aids,
orthotics Orthotics () is a medical specialty that focuses on the design and application of orthoses, sometimes known as braces, calipers, or splints. An is "an externally applied device used to influence the structural and functional characteristics of ...
, and splints may be provided. Speech-language pathology input may be required in those with speech and swallowing problems, as well as to support communication in those who require ongoing breathing support (often through a
tracheostomy Tracheotomy (, ), or tracheostomy, is a surgical airway management procedure which consists of making an incision on the front of the neck to open a direct airway to the trachea. The resulting stoma (hole) can serve independently as an airway ...
). Nutritional support may be provided by the team and by
dietitian A dietitian, medical dietitian, or dietician is an expert in identifying and treating disease-related malnutrition and in conducting medical nutrition therapy, for example designing an enteral tube feeding regimen or mitigating the effects of ...
s. Psychologists may provide counselling and support. Psychological interventions may also be required for anxiety, fear, and depression. Ongoing specialist community support, information, advice, and guidance is available from a range of
Charities A charitable organization or charity is an organization whose primary objectives are philanthropy and social well-being (e.g. educational, religious or other activities serving the public interest or common good). The legal definition of a cha ...
,
Non-Government Organisations A non-governmental organization (NGO) is an independent, typically nonprofit organization that operates outside government control, though it may get a significant percentage of its funding from government or corporate sources. NGOs often focus ...
(NGOs), and Patient Advisory Groups around the world. In the
United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Northwestern Europe, off the coast of European mainland, the continental mainland. It comprises England, Scotlan ...
this is provided by GAIN (Guillain–Barré and Associated Inflammatory Neuropathies), in the USA it is provided by GBS/CIDP Foundation International, and in The European Union by a range of organisations under the umbrella of EPODIN (European Patient Organization for Disimmune & Inflammatory Neuropathies).


Prognosis

Guillain–Barré syndrome can lead to death as a result of many complications: severe infections, blood clots, and cardiac arrest likely due to autonomic neuropathy. Despite optimum care, this occurs in about 5% of cases. There is a variation in the rate and extent of recovery. The prognosis of Guillain–Barré syndrome is determined mainly by age (those over 40 may have a poorer outcome), and by the severity of symptoms after two weeks. Furthermore, those who experienced diarrhea before the onset of the disease have a worse prognosis. In the nerve conduction study, the presence of conduction block predicts poorer outcomes at six months. In those who have received intravenous immunoglobulins, a smaller increase in IgG in the blood two weeks after administration is associated with poorer mobility outcomes at six months than those whose IgG level increased substantially. If the disease continues to progress beyond four weeks, or there are multiple fluctuations in the severity (more than two in eight weeks), the diagnosis may be
chronic inflammatory demyelinating polyneuropathy Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disease of the peripheral nervous system characterized by progressive weakness and impaired sensory function in the legs and arms. The disorder is sometimes calle ...
, which is treated differently. 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 Guillain–Barré syndrome can be significantly impaired. About a fifth are unable to walk unaided after six months, and many experience
chronic pain Chronic pain is pain that persists or recurs for longer than 3 months.https://icd.who.int/browse/2025-01/mms/en#1581976053 It is also known as gradual burning pain, electrical pain, throbbing pain, and nauseating pain. This type of pain is in cont ...
,
fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...
, and difficulty with work, education, hobbies, and social activities. HRQL improves significantly in the first year.


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 relative risk increases by 20% for every decade of life. Men are more likely to develop Guillain–Barré syndrome than women; the
relative risk The relative risk (RR) or risk ratio is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group. Together with risk difference and odds ratio, relative risk measures the association bet ...
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. The Miller Fisher variant is thought to be more common in Southeast Asia.


History

Jean-Baptiste Octave Landry first described the disorder in 1859. In 1916,
Georges Guillain Georges Charles Guillain () (3 March 1876 – 29 June 1961) was a French neurologist born in Rouen. He studied medicine in Rouen and Paris, where he learned clinical education at several hospitals. He developed an interest in neurology, and his f ...
, Jean Alexandre Barré, and
André Strohl André Strohl (20 March 1887 – 10 March 1977) was a French physiologist who was a native of Poitiers. He is remembered for his role in the diagnosis of Guillain–Barré syndrome (sometimes called Guillain–Barré–Strohl syndrome), a form of ...
diagnosed two soldiers with the illness and described the key diagnostic abnormality—albuminocytological dissociation—of increased spinal fluid protein concentration but a normal cell count. C. Miller Fisher described the variant that bears his name in 1956. British neurologist Edwin Bickerstaff described the
encephalitis Encephalitis is inflammation of the Human brain, brain. The severity can be variable with symptoms including reduction or alteration in consciousness, aphasia, headache, fever, confusion, a stiff neck, and vomiting. Complications may include se ...
type in 1951 and made further contributions with another paper in 1957. Guillain had reported on some of these features before 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 1986. 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 was confirmed in larger studies in 1985. Intravenous immunoglobulins were introduced in 1988, and studies in the early 1990s demonstrated that they were no less effective than plasma exchange.


Research directions

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 shown only a small increase. Studies of the immunosuppressive drugs mycophenolate mofetil,
brain-derived neurotrophic factor Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the can ...
and
interferon beta The type-I interferons (IFN) are cytokines which play essential roles in inflammation, immunoregulation, tumor cells recognition, and T cell, T-cell responses. In the human genome, a cluster of thirteen functional IFN genes is located at the 9p2 ...
(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 Glatiramer acetate, sold under the brand name Copaxone among others, is an immunomodulator medication used to treat multiple sclerosis. Glatiramer acetate is approved in the United States to reduce the frequency of relapses, but not for reduci ...
, quinupramine, 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. In animals, it is called acute polyradiculoneuritis or "coonhound paralysis", and may onset in the coonhound 7 to 10 days after transmission from raccoons. If the coonhound has not been around raccoons, the disease is called acute idiopathic polyradiculoneuritis.


See also

* List of neurological conditions and disorders * List of syndromes


References


Further reading

*


External links


Information on GBS from UK Charity GAIN (Guillain–Barré and Associated Inflammatory Neuropathies)

Information on GBS from NGO GBS/CIDP Foundation International

Information on GBS from NGO EPODIN (European Patient Organization for Disimmune & Inflammatory Neuropathies)
{{DEFAULTSORT:Guillain-Barre Syndrome 1976 health disasters Autoimmune diseases Cytomegalovirus-associated diseases Medical triads Myelin disorders Peripheral nervous system disorders Rare syndromes Syndromes affecting the nervous system Wikipedia medicine articles ready to translate Wikipedia neurology articles ready to translate Diseases named after discoverers