Guillain–Barré syndrome

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. On neurological examination, 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. Respiratory failure A quarter of all people with Guillain–Barré syndrome develop weakness of the breathing muscles leading to respiratory failure, the inability to breathe adequately to maintain healthy levels of oxygen, and/or carbon dioxide in the blood. This life-threatening scenario is complicated by other medical problems such as pneumonia, 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 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 requires pacemaker-based treatment. Other associated problems are abnormalities in perspiration 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 -derived image of Campylobacter jejuni, which triggers about 30% of cases of Guillain–Barré syndrome 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. The tropical flaviviral infections dengue fever and Zika virus have also been associated with episodes of GBS. Previous hepatitis E virus infection is more common in people with GBS. 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." 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 required safety label changes from the manufacturer GlaxoSmithKline to include warnings for risk of Guillain–Barré syndrome. COVID-19 infection or vaccine related GBS has been reported in association with COVID-19, 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 vaccines and the European Medicines Agency 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, 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 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 (nodes of Ranvier) where the axon is exposed. 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 to gangliosides, which is meant to suppress the production of antibodies against the body's own substances. 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. In many cases, magnetic resonance imaging of the spinal cord is performed to distinguish between Guillain–Barré syndrome and other conditions causing limb weakness, such as spinal cord compression. This pattern distinguishes Guillain–Barré syndrome from other conditions (such as lymphoma and poliomyelitis) 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. Neurophysiology studies are not required for the diagnosis. Sometimes, repeated testing may be helpful. 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. 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, 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 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. Glucocorticoids 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, generally on an intensive care unit. The need for ventilatory support can be anticipated by measurement of two spirometry-based breathing tests: the forced vital capacity (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 (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. 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 Dysimmune & 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 optimal care, this occurs in about 5% of cases. 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, fatigue, 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 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==

, 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. Jean-Baptiste Octave Landry first described the disorder in 1859. In 1916, Georges Guillain, Jean Alexandre Barré, and André Strohl 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 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. 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. 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. == See also ==