Guillain-Barré syndrome
Synonyms
2
Overview
Guillain–Barré syndrome ( Landry's paralysis, acute idiopathic polyneuritis) is a rapid-onset muscle weakness as a result of damage to the peripheral nervous system. Many experience changes in sensation or develop pain, followed by muscle weakness beginning in the feet and hands. The symptoms develop over half a day to two weeks. During the acute phase, the disorder can be life-threatening with about a quarter developing weakness of the breathing muscles and 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.
This autoimmune disease is caused by the body's immune system mistakenly attacking the peripheral nerves and damaging their myelin insulation. Sometimes this immune dysfunction is triggered by an infection. The diagnosis is usually made on 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. Various classifications exist, depending on the areas of weakness, results of nerve conduction studies, and the presence of antiganglioside antibodies. It is classified as an acute polyneuropathy.
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 worsening 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, which 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, painful tingling, 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 prior to the onset of the neurological symptoms. This may consist of upper respiratory tract infection (rhinitis, sore throat) or diarrhea.
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 Guillain–Barré syndrome (see below), weakness of the eye muscles (ophthalmoplegia) is more pronounced and may occur together with abnormalities in coordination (ataxia). The level of consciousness is normally unaffected in Guillain–Barré syndrome, but the Bickerstaff brainstem encephalitis subtype may feature drowsiness, sleepiness, or coma.
Respiratory failur
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 requiring 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
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% cases are attributable to cytomegalovirus (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 lipopolysaccharides 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 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 has 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. The benefits from vaccination to prevent influenza outweigh the small risks of GBS after vaccination. Even those who have previously experienced Guillain–Barré syndrome are considered safe to receive the vaccine in the future. Other vaccines, such as those against poliomyelitis, tetanus or measles, have not been associated with a risk of GBS.
Prevention
Guillan-Barré syndrome cannot be prevented.
Diagnosis
The diagnosis of Guillain–Barré syndrome depends on findings such as rapid development of muscle paralysis, absent reflexes, absence of fever, and 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 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 (CSF) envelops the brain and the spine, and lumbar puncture is the removal of a small amount of fluid using a needle inserted between the lumbar vertebrae. A characteristic finding in Guillain–Barré syndrome is an elevated protein level with low numbers of white blood cells ("albuminocytological dissociation"); this distinguishes it from a number of other conditions (such as lymphoma and poliomyelitis) where both the protein and the cell count are elevated. Despite this, the CSF is unremarkable in 50% of people with Guillain–Barré syndrome in the first few days of symptoms, and 80% after the first week; therefore, normal results do not exclude the condition.
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 (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, repeat testing may be helpful.
Prognosis
Guillain–Barré syndrome can lead to death as a result of a number of 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 disease have a worse prognosis. On the nerve conduction study, the presence of conduction block predicts poorer outcome at 6 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 which is treated differently.
In research studies, the outcome from an episode of Guillain–Barré syndrome is recorded on a scale from 0-6, 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, fatigue and difficulty with work, education, hobbies and social activities. HRQL improves significantly in the first year
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 and 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.
Respiratory failure
Respiratory failure may require intubation of the windpipe 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, 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. Occupational therapy aims to improve everyday function with domestic and community tasks as well as driving and work. Psychologists may provide counseling and support. Home modifications, gait aids, orthotics 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). Nutritional support may be provided by the team and by dietitians. Psychological interventions may be required for anxiety, fear and depression.