History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include preceding viral or bacterial infection.

muscle weakness

Progressive symmetrical muscle weakness usually affecting lower extremities before upper extremities and proximal muscles before distal muscles accompanied by paraesthesias in the feet and hands is typical.[21]​[90][91]​​ The paralysis is typically flaccid with areflexia and progresses acutely over days, with around 80% of patients reaching a nadir by 2 weeks and 97% by 4 weeks.[92] Weakness evolving over >4 to 8 weeks is more consistent with chronic inflammatory demyelinating polyradiculoneuropathy.[90][91]

paraesthesia

Paraesthesias in hands and feet occur in most Guillain-Barre syndrome (GBS) patients and frequently precede the onset of weakness.[21]​ Paresthesias may extend proximally in the extremities, but sensory abnormalities on examination are usually mild. If a distinct sensory level is noted on examination, this is unlikely to be GBS and is more likely a spinal cord process.

back/leg pain

Pain is a common feature of Guillain-Barre syndrome, and may precede muscle weakness; back and leg pain is typical.[15]​ The presence of back pain and paralysis is easily misinterpreted as cord compression.

Pain is a much more prominent symptom in children than in adults.[96][97]

respiratory distress

Typical signs may include dyspnoea on exertion and shortness of breath, but respiratory muscle weakness can often be asymptomatic. Approximately 20% to 30% of patients develop respiratory muscle weakness requiring mechanical ventilation.[21][100]

speech problems

Facial weakness and oropharyngeal weakness occurs in around two-thirds of patients.[141][142] Typical signs include slurred speech.

areflexia/hyporeflexia

The majority of patients are areflexic on admission, with ankle jerks and knee jerks being the most commonly affected. In some patients the areflexia/hyporeflexia may be present only in the weakest limbs. Plantar reflex should be downgoing or absent but never upgoing. Tone should be flaccid. However, all Guillain-Barre syndrome variants and subtypes can present with hyper-reflexia, although this is rare.[143]

facial weakness

Occurs in around two-thirds of patients.[141][142]

bulbar dysfunction causing oropharyngeal weakness

Together with bilateral facial weakness, bulbar dysfunction is associated with increased risk of progression to mechanical ventilation.[128] Oropharyngeal weakness occurs in around 50% of patients.[141] Typical signs include swallowing difficulty.

extra-ocular muscle weakness

Occurs in around 15% of patients.[141]

facial droop

Often occurs after trunk and limb involvement but occurs before in a small number of patients.

diplopia

Often occurs after trunk and limb involvement but occurs before in a small number of patients.

dysarthria

Often occurs after trunk and limb involvement but occurs before in a small number of patients.

dysphagia

Often occurs after trunk and limb involvement but occurs before in a small number of patients.

dysautonomia

Mild dysautonomia is common and results in sinus tachycardia, hypertension, and postural hypotension in approximately two-thirds of patients.[93] Other autonomic symptoms such as urinary retention and ileus can also occur.[99] Bladder disturbance is usually mild or absent early in the disease; if severe, cord compression should be excluded. Life-threatening cardiac arrhythmias are relatively rare.[21]

Autonomic dysfunction in children may be an independent risk factor for mechanical ventilation.[96]

uncommon

pupillary dysfunction

Guillain-Barre syndrome (GBS) may be associated with bilateral tonic pupils and may involve both parasympathetic and sympathetic post-ganglionic neurons.[14] Up to nearly half of patients with Miller-Fisher syndrome have sluggish pupils and mydriasis.[107]​[108]​​

Although uncommon, light-fixed dilated pupils in GBS have been described.[144][145] If pupils are fixed and dilated, the possibility of botulism needs to be considered.[146]

Anisocoria (unequal pupils) may occasionally be seen; tends to accompany severe ophthalmoparesis and ptosis.

ophthalmoplegia

Ataxia, areflexia, and ophthalmoplegia are the classic triad for Miller-Fisher syndrome (MFS), although not all patients with MFS have ophthalmoplegia.[104][105]​ Around 30% of patients with MFS develop extremity weakness manifesting as an overlapping syndrome with classic Guillain-Barre syndrome.[11]

Other diagnostic factors

uncommon

ataxia

Characteristic feature of Miller-Fisher syndrome (MFS). A few patients with MFS present with ataxia and hyporeflexia without ophthalmoplegia.[104]

ptosis

May occur in Miller-Fisher syndrome.

altered level of consciousness

Uncommon in Guillain-Barre syndrome, but encephalopathy and hyper-reflexia may be the presenting features of Bickerstaff's brainstem encephalitis.

Risk factors

strong

preceding viral illness

Two-thirds of patients with Guillain-Barre syndrome have a history of antecedent infection in the weeks before onset of neurological symptoms, most commonly an influenza-like illness, upper respiratory tract infection, or gastroenteritis.​[37][38]​​[39]​ The most commonly identified viruses are cytomegalovirus (4% to 15% of cases) and Epstein-Barr virus (1% to 8% of cases).[37][41]

preceding bacterial infection

Approximately 60% to 70% of acute motor axonal neuropathy and acute motor-sensory axonal neuropathy cases and up to 30% of acute inflammatory demyelinating polyradiculoneuropathy cases are preceded by Campylobacter jejuni infection.[42][43]Campylobacter-associated Guillain-Barre syndrome (GBS) appears to have a worse prognosis, manifested by slower recovery and greater residual neurological disability.[37][40]​​​ One study in Sweden estimated that the risk of developing GBS during the 2 months following C jejuni infection is approximately 100-fold higher than in the general population.[75]

preceding arthropod-borne viral infection

Cases of Guillain-Barre syndrome (GBS) were reported following the outbreak of Zika virus in 2013.[5][28]​​[55][56]​​​​​ One case control study from French Polynesia found that 98% of patients with GBS harboured anti-Zika virus IgG or IgM, and that the risk of GBS was 0.24 per 1000 Zika virus infections.[76] However, this risk is lower than that associated with Campylobacter jejuni (0.25 to 0.65 per 1000 cases) or cytomegalovirus infections (0.6 to 2.2 per 1000 cases).[11] Guidelines are available regarding the risk of GBS following Zika virus infection.[77][78]​ Several other mosquito-borne viral infections such as dengue, chikungunya, and Japanese encephalitis have been linked to GBS.[6][7][8][9]​ Oropouche fever, an arbovirus primarily transmitted by biting midges, has also been associated with GBS.[10][57]​​

hepatitis E infection

There is evidence that hepatitis E virus is a risk factor for the development of Guillain-Barre syndrome (GBS).[79][80]​ Of patients with GBS in the Netherlands, 5% had preceding acute hepatitis E infection; in Bangladesh (where hepatitis E is endemic), this figure was 11%.[81]

weak

immunisation

Immunisations have been proposed to trigger Guillain-Barre syndrome (GBS), but this suggestion is controversial, and was based primarily on data relating to the no longer used swine influenza vaccines (US in 1976) and the rabies vaccine containing brain material.[46][47]​ Overall, the benefits of immunisation outweigh any small risk of developing vaccine-induced GBS.[15][34]

Epidemiological evidence indicates that the relative risk of GBS after immunisation is far lower than that following an infectious disease, especially for influenza (<1 per million vaccinations vs. 17 per million infections).[16]​​[48][49]​​

Recombinant respiratory syncytial virus (RSV) vaccines have been associated with a small increased risk of GBS.[50][51]​ One case control study of older adults aged ≥60 years reported an excess risk of 18.2 cases of GBS syndrome per million doses of the recombinant RSV vaccine, and an excess risk of 5.2 cases of GBS per million doses of the recombinant adjuvanted RSV vaccine.[52]

Cohort studies found no risk of GBS following the meningococcal conjugate vaccine (MenACWY).[53]​

There is a comparatively higher risk for pandemic influenza vaccines than for seasonal influenza vaccines.[54] There have been rare reports of GBS associated with vaccination against coronavirus disease 2019 (COVID-19); the risk is much lower with mRNA-based vaccines compared with adenovirus-vectored vaccines (0.32 vs. 2.37 cases per million doses).[33][34]​​

cancer and lymphoma

Case reports link Guillain-Barre syndrome (GBS) with Hodgkin's lymphoma.[82][83]​​ Less commonly, other malignancies have been associated with GBS.​[84][85]

immune checkpoint inhibitor or chimeric antigen receptor (CAR) T-cell immunotherapy

A Guillain-Barre syndrome (GBS)-like acute neuropathy has been reported as a rare neurological complication in patients with cancer prescribed immune checkpoint inhibitors or CAR T-cell immunotherapy; clinicians should be aware of this risk when using these therapies.[58][59][60]​ The incidence is around 0.1% to 0.2% in patients receiving immune checkpoint inhibitors.[58]​ However, there is a growing consensus to consider this immune checkpoint inhibitor-related neuritis rather than GBS per se.[61]

Prompt recognition of immune checkpoint inhibitor-related neuritis is key as the treatment strategy differs from treatment of GBS.[61]​ Detailed discussion of the diagnosis and treatment of immune checkpoint inhibitor-related neuritis is beyond the scope of this topic.

older age

Incidence increases with age. For people age <30 years, the incidence is <1:100,000. For people age >75 years, incidence is 4:100,000.[39][86]​​ The mean age of onset is approximately 50 years.[22]​​​

HIV infection

There are several case reports of Guillain-Barre syndrome in people with HIV.​​[87]​​[88]

COVID-19 infection

Guillain-Barre syndrome (GBS) has been reported in patients with confirmed COVID-19 infection.[30][31]​ However, one large cohort study in the UK found no evidence of a significant causal link between COVID-19 infection and GBS, and the association remains controversial.[32]​

male sex

Guillain-Barre syndrome is slightly more common in males, with an estimated female-to-male ratio of 0.86 (95% CI: 0.84 to 0.89).​[20]​​

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