Guillain-Barré syndrome is an acute, usually rapidly progressive but self-limited, inflammatory polyneuropathy characterized by muscular weakness and mild distal sensory loss. Cause is thought to be autoimmune. Diagnosis is based on history and physical examination. Treatment includes IV immune globulin, plasma exchange, and, for severe cases, mechanical ventilation.
Guillain-Barré syndrome is the most common acquired inflammatory neuropathy. There are several variants. In some variants, demyelination predominates; other variants affect the axon.
Etiology of Guillain-Barré Syndrome
Although the cause of Guillain-Barré syndrome is not fully understood, it is thought to be autoimmune.
In about two-thirds of patients, Guillain-Barré syndrome begins 5 days to 3 weeks after a minor or common infectious disorder, surgery, or vaccination. Infection is the trigger in > 50% of patients (1). Common pathogens include:
Enteric viruses
Herpesviruses (including cytomegalovirus and Epstein-Barr virus)
Mycoplasma species (2)
A cluster of cases followed the swine flu vaccination program in 1976, but the association was shown to be spurious, due to ascertainment bias. In some patients, Guillain-Barré syndrome has developed after a Zika virus or COVID-19 infection.
Adverse effects of immune checkpoint inhibitors include a syndrome that resembles Guillain-Barré syndrome.
If weakness progresses for > 2 months, chronic inflammatory demyelinating polyneuropathy is diagnosed.
Etiology references
1. Leonhard SE , van der Eijk AA, Andersen H, et al. An international perspective on preceding infections in Guillain-Barré syndrome: The IGOS-1000 Cohort. Neurology. 99 (12):e1299-e1313, 2022. doi: 10.1212/WNL.0000000000200885
2. Tam CC, O’Brien SJ, Rodrigues LC. Influenza, Campylobacter and Mycoplasma infections, and hospital admissions for Guillain-Barré syndrome, England. Emerg Infect Dis. 12 (12):1880–1887, 2006. doi: 10.3201/eid1212.051032
Symptoms and Signs of Guillain-Barré Syndrome
Flaccid weakness predominates in most patients with Guillain-Barré syndrome; it is always more prominent than sensory abnormalities and may be most prominent proximally. Relatively symmetric weakness with paresthesias usually begins in the legs and progresses to the arms, but occasionally it begins in the arms or head. In 90% of patients, weakness is maximal at 3 to 4 weeks (1). Deep tendon reflexes are lost. Sphincters are usually spared. Weakness persists at the same intensity for a variable period of time, typically a few weeks, then resolves.
Facial and oropharyngeal muscles are weak in > 50% of patients with severe disease. Dehydration and undernutrition may result. Respiratory paralysis severe enough to require endotracheal intubation and mechanical ventilation occurs in 20% of patients (2).
Although symptoms primarily involve motor function, pain may also occur in the acute stage of disease (3).
Life-threatening autonomic dysfunction (possibly due to a variant form of Guillain-Barre syndrome) occurs infrequently, causing blood pressure fluctuations, inappropriate antidiuretic hormone secretion, cardiac arrhythmias, gastrointestinal stasis, urinary retention, and pupillary changes.
An unusual variant (Fisher variant, or Miller-Fisher syndrome) may cause only ophthalmoparesis, ataxia, and areflexia.
Symptoms and signs references
1. Fokke C, van den Berg B, Drenthen J, et al. Diagnosis of Guillain-Barré syndrome and validation of Brighton criteria. Brain. 137 (Pt 1):33–43, 2014. doi: 10.1093/brain/awt285
2. Shahrizaila N, Lehmann HC , Kuwabara S. Guillain-Barré syndrome. Lancet. 397 (10280):1214–1228, 2021. doi: 10.1016/S0140-6736(21)00517-1
3. Zhao F, Wang J, Zhang J, et al. Pain in acute motor axonal neuropathy. Muscle Nerve. 2021;64(6):739-743. doi:10.1002/mus.27414
Diagnosis of Guillain-Barré Syndrome
History and physical examination
Electrodiagnostic testing
Cerebrospinal fluid (CSF) analysis
Diagnosis of Guillain-Barré syndrome is primarily clinical, based on findings from history and physical examination.
Differential diagnosis
Similar acute weakness can result from myasthenia gravis, botulism, poliomyelitis, tick paralysis, West Nile virus infection, metabolic neuropathies, and transverse myelitis, but these disorders can usually be distinguished as follows:
Myasthenia gravis is intermittent and worsened by exertion.
Botulism may cause fixed dilated pupils (in 50%) and prominent cranial nerve dysfunction, with normal sensation.
Poliomyelitis usually occurs in epidemics.
Tick paralysis causes ascending paralysis but spares sensation.
West Nile virus causes headache, fever, and asymmetric flaccid paralysis but spares sensation.
Metabolic neuropathies occur with a chronic metabolic disorder.
Transverse myelitis causes pain, weakness, abnormal sensation, and urinary dysfunction.
Testing
Tests for infectious disorders and immune dysfunction, including tests for hepatitis and HIV and serum protein electrophoresis, are done.
When Guillain-Barré syndrome is suspected, patients should be admitted to a hospital for electrodiagnostic testing (nerve conduction studies and electromyography), CSF analysis, and monitoring by measuring forced vital capacity every 6 to 8 hours. Initial electrodiagnostic testing detects slow nerve conduction velocities and evidence of segmental demyelination in two-thirds of patients; however, normal results, particularly within the first 5 to 7 days, do not exclude the diagnosis and should not delay treatment.
CSF analysis may detect albuminocytologic dissociation (increased protein but normal white blood cell count), but it may not appear for up to 1 week and does not develop in 10% of patients.
Cervical spinal cord compression—particularly when polyneuropathy coexists (causing or contributing to hyporeflexia) and bulbar involvement is not prominent—may rarely mimic Guillain-Barré syndrome. In atypical cases, MRI can be used to exclude alternative pathology and look for supportive features such as nerve root enhancement.
Treatment of Guillain-Barré Syndrome
Intensive supportive care
IV immune globulin (IVIG) or plasma exchange
Guillain-Barré syndrome is a medical emergency, requiring constant monitoring and support of vital functions, typically in an intensive care unit. Forced vital capacity should be measured every 6 to 8 hours so that respiration can be assisted if necessary; if vital capacity is < 15 mL/kg, endotracheal intubation is indicated. Inability to lift the head off the pillow by flexing the neck is another danger sign; it frequently develops simultaneously with phrenic nerve (diaphragm) weakness.
If oral fluid intake is difficult, IV fluids are given as needed to maintain a urine volume of at least 1 to 1.5 L/day. Extremities should be protected from trauma and from the pressure of bed rest.
GBS can present with lower back pain. Heat therapy helps relieve pain, making early physical therapy possible. Immobilization, which may cause ankylosis and contractures, should be avoided. Passive full-range joint movement should be started immediately, and active exercises should be initiated when acute symptoms subside. Low molecular weight heparin (LMWH) helps prevent deep venous thrombosis in bedbound patients.GBS can present with lower back pain. Heat therapy helps relieve pain, making early physical therapy possible. Immobilization, which may cause ankylosis and contractures, should be avoided. Passive full-range joint movement should be started immediately, and active exercises should be initiated when acute symptoms subside. Low molecular weight heparin (LMWH) helps prevent deep venous thrombosis in bedbound patients.
Plasma exchange (PLEX) and IVIG are the treatments of choice (1). IVIG may be administered in higher dosing over 1 to 2 days, given either with pretreatment with acetaminophen and diphenhydramine or more slowly over 5 days. It has some benefit up to 1 month from disease onset. Repeating a second course of IVIG for refractory cases is not beneficial (). IVIG may be administered in higher dosing over 1 to 2 days, given either with pretreatment with acetaminophen and diphenhydramine or more slowly over 5 days. It has some benefit up to 1 month from disease onset. Repeating a second course of IVIG for refractory cases is not beneficial (2).
Plasma exchange shortens the disease course and hospital stay, and reduces mortality risk and incidence of permanent paralysis (3). However, it may cause hypotension due to large fluid shifts, and IV access may be difficult or cause complications. Plasma exchange theoretically removes any previously administered IVIG, negating its benefits, and should not be performed after IVIG. There is no evidence that repeating a second course of IVIG or a course of IVIG after PLEX is beneficial and may lead to adverse outcomes (2–5).
Glucocorticoids are not indicated for treatment of Guillain-Barre syndrome; they do not hasten recovery and there is some evidence that they may delay recovery. Eculizumab may be beneficial, but further study is needed before it can be recommended (Glucocorticoids are not indicated for treatment of Guillain-Barre syndrome; they do not hasten recovery and there is some evidence that they may delay recovery. Eculizumab may be beneficial, but further study is needed before it can be recommended (6).
Pearls & Pitfalls
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Treatment references
1. Lin J, Gao Q, Xiao K, Tian D, Hu W, Han Z. Efficacy of therapies in the treatment of Guillain-Barre syndrome: A network meta-analysis. Medicine (Baltimore). 2021;100(41):e27351. doi:10.1097/MD.0000000000027351
2. Walgaard C, Jacobs BC, Lingsma HF, et al. Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2021;20(4):275-283. doi:10.1016/S1474-4422(20)30494-4
3. Chevret S, Hughes RAC,Annane D. Plasma exchange for Guillain‐Barré syndrome. Cochrane Database Syst Rev. 2 (2):CD001798, 2017. doi: 10.1002/14651858.CD001798.pub3
4. Shahrizaila N, Lehmann HC, Kuwabara S. Guillain-Barré syndrome. Lancet. 2021;397(10280):1214-1228. doi:10.1016/S0140-6736(21)00517-1
5. Zhao F, Wang J, Zhang J, et al. Pain in acute motor axonal neuropathy. Muscle Nerve. 2021;64(6):739-743. doi:10.1002/mus.27414
6. Misawa S, Kuwabara S, Sato Y, et al. Safety and efficacy of eculizumab in Guillain-Barré syndrome: A multicentre, double-blind, randomised phase 2 trial. . Safety and efficacy of eculizumab in Guillain-Barré syndrome: A multicentre, double-blind, randomised phase 2 trial.Lancet Neurol. 17 (6):519–529, 2018. doi: 10.1016/S1474-4422(18)30114-5
Prognosis for Guillain-Barré Syndrome
Guillain-Barré syndrome is fatal in < 4% (1). Most patients improve considerably over a period of months, but a substantial number of adults and even more children have some residual weakness at 3 years. Patients with residual defects may require retraining and orthopedic appliances.
After initial improvement, approximately 5% of patients develop chronic inflammatory demyelinating polyneuropathy (2).
Prognosis references
1. van den Berg B, Bunschoten C, van Doorn PA, Jacobs BC. Mortality in Guillain-Barré syndrome. Nuerology. 80 (18):1650–1654, 2013. doi: 10.1212/WNL.0b013e3182904fcc
2. Leonhard SE, Mandaraka MR, Gondim FAA, et al. Diagnosis and management of Guillain–Barré syndrome in ten steps. Nat Rev Neurol. 1 5(11): 671–683, 2019. doi: 10.1038/s41582-019-0250-9
Key Points
Guillain-Barré syndrome typically begins with an ascending, relatively symmetric flaccid weakness.
Initially, distinguish other disorders that cause similar symptoms (eg, myasthenia gravis, botulism, tick paralysis, West Nile virus infection, metabolic neuropathies, transverse myelitis; outside the United States, poliomyelitis) based on history and examination results.
Do electrodiagnostic testing and CSF analysis, even though diagnosis is primarily based on history and physical examination.
Most patients improve considerably over a period of months, but a substantial number of adults and even more children have some residual weakness at 3 year, and up to 5% develop chronic inflammatory demyelinating polyneuropathy.
Intensive supportive care is key to recovery.
Treat with IVIG initially; if it is ineffective, do plasma exchange.
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