(See also Overview of Peripheral Nervous System Disorders Overview of Peripheral Nervous System Disorders The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. It includes the cranial nerves and spinal nerves from their origin to their end. The anterior... read more .)
Guillain-Barré syndrome is the most common acquired inflammatory neuropathy. There are several variants. In some variants, demyelination Overview of Demyelinating Disorders Myelin sheaths cover many nerve fibers in the central and peripheral nervous system; they accelerate axonal transmission of neural impulses. Disorders that affect myelin interrupt nerve transmission... read more 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 Etiology references 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... read more ); common pathogens include
Enteric viruses
Herpesviruses Overview of Herpesvirus Infections Eight types of herpesviruses infect humans (see table ). After initial infection, all herpesviruses remain latent within specific host cells and may subsequently reactivate. Clinical syndromes... read more (including cytomegalovirus and Epstein-Barr virus)
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 Zika Virus (ZV) Infections The Zika virus is a mosquito-borne flavivirus that is antigenically and structurally similar to the viruses that cause dengue, yellow fever, and West Nile virus. Zika virus infection is typically... read more or after COVID-19 COVID-19 COVID-19 is a respiratory illness caused by the novel coronavirus SARS-CoV-2. Infection may be asymptomatic or have symptoms ranging from mild upper respiratory symptoms to acute respiratory... read more .
Adverse effects of immune checkpoint inhibitors include a syndrome that resembles Guillain-Barré syndrome.
If weakness progresses for > 2 months, chronic inflammatory demyelinating polyneuropathy Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Chronic inflammatory demyelinating polyneuropathy is an immune-mediated polyneuropathy characterized by symmetric weakness of proximal and distal muscles and by progression continuing > 2 months... read more 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 Symptoms and signs references 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... read more ). 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 Symptoms and signs references 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... read more ).
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 Weakness Weakness is one of the most common reasons patients present to primary care clinicians. Weakness is loss of muscle strength, although many patients also use the term when they feel generally... read more 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:
Botulism Botulism Botulism is poisoning that is due to Clostridium botulinum toxin and that affects the peripheral nerves. Botulism may occur without infection if toxin is ingested, injected, or inhaled... read more may cause fixed dilated pupils (in 50%) and prominent cranial nerve dysfunction with normal sensation.
West Nile virus West Nile Virus West Nile virus is a flavivirus that is now the primary cause of arbovirus encephalitis in the United States. Most patients have mild or no symptoms. About 1 out of 150 patients develop a severe... read more causes headache, fever, and asymmetric flaccid paralysis but spares sensation.
Metabolic neuropathies occur with a chronic metabolic disorder.
Transverse myelitis Acute Transverse Myelitis Acute transverse myelitis is acute inflammation of gray and white matter in one or more adjacent spinal cord segments, usually thoracic. Causes include multiple sclerosis, neuromyelitis optica... read more 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.
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.
Given early, IVIG is the treatment of choice (1 Treatment references 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... read more , 2, Treatment references 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... read more 3 Treatment references 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... read more ). It can be given in one the following ways:
IVIG 2 g/kg over 1 to 2 days, with acetaminophen 650 mg and diphenhydramine 25 mg given orally 30 minutes before
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 Plasma exchange Apheresis refers to the process of separating the cellular and soluble components of blood using a machine. Apheresis is often done on donors where whole blood is centrifuged to obtain individual... read more 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 Treatment references 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... read more ). 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.
Corticosteroids do not improve and may worsen the outcome. Eculizumab may be beneficial, but further study is needed before it can be recommended (5 Treatment references 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... read more ).
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 al: 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 Epub 2018 Apr 21.
Prognosis for Guillain-Barré Syndrome
Guillain-Barré syndrome is fatal in < 4% (1 Prognosis references 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... read more ). 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 Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Chronic inflammatory demyelinating polyneuropathy is an immune-mediated polyneuropathy characterized by symmetric weakness of proximal and distal muscles and by progression continuing > 2 months... read more (2 Prognosis references 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... read more ).
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.