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 clinical. Treatment includes IV immune globulin, plasma exchange, and, for severe cases, mechanical ventilation.
(See also Overview of Peripheral Nervous System Disorders.)
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 banal 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 later shown to be spurious, due to ascertainment bias. In some patients, Guillain-Barré syndrome has developed after a Zika virus infection or after COVID-19.
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 Epub 2022 Aug 18.
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 it occasionally begins in the arms or head. In 90% of patients, weakness is usually maximal at 3 to 4 weeks (1). Deep tendon reflexes are lost. Sphincters are usually spared. Weakness remains the same for a variable period of time, typically for 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 20% (2).
A few patients (possibly with a variant form) have significant, life-threatening autonomic dysfunction 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 Epub 2013 Oct 26.
2. Shahrizaila N, Lehmann HC , Kuwabara S: Guillain-Barré syndrome. Lancet 397 (10280):1214–1228, 2021. doi: 10.1016/S0140-6736(21)00517-1 Epub 2021 Feb 26.
Diagnosis of Guillain-Barré Syndrome
Clinical evaluation
Electrodiagnostic testing
Cerebrospinal fluid (CSF) analysis
Diagnosis of Guillain-Barré syndrome is primarily clinical.
Differential diagnosis
Similar acute weakness can result from myasthenia gravis, botulism, poliomyelitis (mainly outside the United States), 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.
If 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.
Rarely, cervical spinal cord compression—particularly when polyneuropathy coexists (causing or contributing to hyporeflexia) and bulbar involvement is not prominent—may mimic Guillain-Barré syndrome; in such cases, MRI should be done.
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 frequently 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.
Given early, IVIG is the treatment of choice (1, 2, 3). It can be given in one the following ways:
IVIG given more slowly, as 400 mg/kg IV once a day for 5 consecutive days
IVIG has some benefit up to 1 month from disease onset.
Plasma exchange helps when done early; it is used if IVIG is ineffective. Plasma exchange shortens the disease course and hospital stay, and reduces mortality risk and incidence of permanent paralysis (4). However, it may cause hypotension due to large fluid shifts, and IV access may be difficult or cause complications. Plasma exchange removes any previously administered IVIG, negating its benefits, and so should never be done during or soon after use of IVIG. Waiting at least 2 to 3 days after stopping IVIG is recommended.
Pearls & Pitfalls
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Treatment references
1. Tavee J, Brannagan 3rd TH, Lenihan MW, et al: Updated consensus statement: Intravenous immunoglobulin in the treatment of neuromuscular disorders report of the AANEM [American Association of Neuromuscular and Electrodiagnosic Medicine] ad hoc committee. Muscle Nerve 68 (4):356–374, 2023. doi: 10.1002/mus.27922 Epub 2023 Jul 11.
2. Hughes RAC, Swan AV, van Doorn PA: Intravenous immunoglobulin for Guillain-Barré syndrome. Cochrane Database Syst Rev 2014 (9): CD002063 2014. doi: 10.1002/14651858.CD002063.pub6 Published online 2014 Sep 19.
3.Tavee J, Brannagan, TH III, Lenihan MW, et al: Updated consensus statement: Intravenous immunoglobulin in the treatment of neuromuscular disorders report of the AANEM ad hoc committee. Muscle Nerve 68 (4):356–374, 2023. doi: 10.1002/mus.27922 Epub 2023 Jul 11.
4 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
5. Misawa S, Kuwabara S, Sato Y, et alLancet Neurol 17 (6):519–529, 2018. doi: 10.1016/S1474-4422(18)30114-5 Epub 2018 Apr 21.
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, orthopedic appliances, or surgery.
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. Neurology 80 (18):1650–1654, 2013. doi: 10.1212/WNL.0b013e3182904fcc Epub 2013 Apr 10.
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 Published online 2019 Sep 20.
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 clinical.
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 2 to 5% develop chronic inflammatory demyelinating polyneuropathy.
Intensive supportive care is key to recovery.
Try IVIG first, then if it is ineffective, plasma exchange.
