Guillain–Barré Syndrome including variants (GBS)

Version: 3.2
Published: 29 February 2024
Condition for which Ig has an established therapeutic role.

View Superseded Version  Print
Specific Conditions
  • Guillain–Barré Syndrome (GBS)
  • Guillain–Barré Syndrome (GBS) variants
Indication for Ig Use
  • Initial therapy for GBS with significant disability and progression
  • Relapse in GBS - treatment related fluctuation with initial improvement and subsequent deterioration post IVIg treatment
Level of Evidence Clear evidence of benefit (Category 1)
Description and Diagnostic Criteria Guillain–Barré Syndrome (GBS) is the commonest cause of acute flaccid paralysis in the West. The syndrome typically presents with rapidly progressive, relatively symmetrical ascending limb weakness consistent with a polyradiculoneuropathy and often with associated cranial nerve involvement.
 
Motor signs and symptoms usually predominate over sensory signs and symptoms. Loss of tendon reflexes occurs in most cases. Major complications include respiratory failure and autonomic dysfunction.
 
The disease is monophasic, reaching its nadir usually within two weeks, although arbitrary definition accepts a limit of four weeks. A plateau phase of variable duration follows the nadir before gradual recovery. Although recovery is generally good or complete in the majority of patients, persistent disability has been reported to occur in about 20 percent and death in four to 15 percent of patients.

Treatment related fluctuations within 8 (eight) weeks of treatment occur in about 10% of patients and typically exhibit as improvement or stabilisation of the patient after completing treatment followed by deterioration. Improvement/ stabilisation and subsequent deterioration is evident using GBS disability score or Medical Research Council (MRC) sum score assessment.

Chronic inflammatory demyelinating polyneuropathy (CIDP) may present acutely (A-CIDP) after initially being diagnosed as GBS. A-CIDP is defined by worsening clinical features such as weakness more than 4 weeks after onset. The CIDP criteria should be considered in that context, but should not be applied in the context of GBS where recovery is slow or incomplete (Walgaard et al., 2021).

Intravenous immunoglobulin (IVIg) has been shown to have the same efficacy as plasma exchange. While the Asia-Pacific IVIg Advisory Group suggests that the choice between Ig and plasma exchange is based on availability, practicality, convenience, cost, and ease or safety of administration, Australia’s National Ig Governance program has a policy to preference alternative therapies where available and appropriate.
 
Investigations 
There is no biological marker for GBS. It is diagnosed by clinical recognition of rapidly evolving paralysis with areflexia. Investigations include the following:
  • Cerebrospinal fluid (CSF) protein elevation, although the level may be normal in the first two weeks of illness. The CSF white cell count may rise transiently, but a sustained pleocytosis suggests an alternative diagnosis or association with an underlying illness (e.g. HIV).
  • Electrophysiological studies may show changes after the first or second week of the illness, including conduction block, conduction slowing or abnormalities in F waves.
Justification for Evidence Category One systematic review of nine randomised controlled trials (RCTs) of moderate quality found intravenous immunoglobulin (IVIg) hastened recovery in adults with GBS to the same degree as plasma exchange (Biotext 2004).
 
This conclusion was confirmed in a 2014 Cochrane review. In severe disease, IVIg started within two weeks from onset hastens recovery as much as plasma exchange. Three studies, including a total of 75 children, suggested that IVIg significantly hastens recovery compared with supportive care. One low-quality RCT with 21 mildly affected children showed earlier signs of improvement and lower disability grades after four weeks with IVIg than supportive treatment alone (Frommer and Madronio 2006).

Persistent weakness or failure to recover with persistent weakness does not qualify for a second dose of IVIg. A randomised controlled trial investigating the effectiveness of a second dose of IVIg (Walgaard et al., 2021) showed no benefit and increased adverse events associated with the administration of a second dose. 
Diagnosis Requirements

A diagnosis must be made by a Neurologist, Paediatrician, General Medicine Physician or an Intensivist.
Qualifying Criteria for Ig Therapy
Initial therapy for GBS with significant disability and progression
This indication must be used for initial GBS therapy only.

The failure to improve from GBS with persistent weakness or failure to recover with persistent weakness does not qualify for a second IVIg dose, except where treatment-related fluctuations occur within 8 (eight) weeks of treatment and there is evidence of initial improvement followed by deterioration. A second dose is available under the indication for Relapse in Guillain–Barré syndrome (GBS) treatment-related fluctuation with initial improvement and subsequent deterioration post IVIg treatment but must only be on the advice of, and after assessment by, a neurologist.
 
AND
  • Weakness is progressive and indicates a trajectory to significant disability
Postscript
Relapse in GBS (treatment-related fluctuation) within 8 weeks with recurrent weakness after initial improvement may require a second treatment with IVIg. A second dose is available under the ‘Relapse’ indication but must only be on the advice of, and after assessment by, a neurologist.

Treatment-related fluctuations (TRFs) are defined as: 

1) improvement in GBS disability score of at least 1 grade or improvement in MRC sum score of more than 5 points after completion of therapy, followed by a worsening in GBS disability score of at least 1 grade or a decrease in MRC sum score of more than 5 points within the first months after onset of disease; OR
2) stabilization of the clinical course for more than 1 week after completion of therapy, followed by a worsening of at least 1 grade of the GBS disability score or more than 5 points on the MRC sum score.

Note an application can be made for either a second course under GBS-TRF or a switch to A-CIDP in the 4-8 week window after onset.
Relapse in GBS - treatment related fluctuation with initial improvement and subsequent deterioration post IVIg treatment
Relapse in GBS (treatment-related fluctuation) within 8 (eight) weeks with recurrent weakness after initial improvement may require a second treatment with IVIg. After qualifying for intial treatment under the indication Initial therapy for Guillain–Barré Syndrome (GBS) with significant disability and progression a second dose is available under this relapse indication but must only be on the advice of, and after assessment by, a neurologist.

Treatment-related fluctuations (TRFs) are defined as: 

1) improvement in GBS disability score of at least 1 grade or improvement in MRC sum score of more than 5 points after completion of therapy, followed by a worsening in GBS disability score of at least 1 grade or a decrease in MRC sum score of more than 5 points within the first months after onset of disease; OR
2) stabilisation of the clinical course for more than 1 week after completion of therapy, followed by a worsening of at least 1 grade of the GBS disability score or more than 5 points on the MRC sum score.

Note an application can be made for either a second course under GBS-TRF or a switch to A-CIDP in the 4-8 week window after onset.
 
  • Initial response to Ig therapy was followed by recurrent weakness within 8 (eight) weeks with no alternative explanation and deterioration in a recent Medical Research Council (MRC) sum score (Kleyweg et al 1991)
  • OR
  • Initial response to Ig therapy was followed by recurrent weakness within 8 (eight) weeks with no alternative explanation and deterioration in a recent GBS outcome score (van Koningsveld et al 2007)
Exclusion Criteria Chronic inflammatory demyelinating polyneuropathy (CIDP)
Acute - Chronic inflammatory demyelinating polyneuropathy (CIDP)
Review Criteria for Assessing the Effectiveness of Ig Use
Initial therapy for GBS with significant disability and progression
Review is not mandated for this indication however the following criteria may be useful in assessing the effectiveness of Ig therapy.
 
AND
  • Patient survival and symptom improvement
Relapse in GBS (treatment-related fluctuation) with recurrent weakness after initial improvement may require a second treatment with IVIg. A second dose is available under the ‘Relapse’ indication but must only be on the advice of, and after assessment by, a neurologist.
 
Relapse in GBS - treatment related fluctuation with initial improvement and subsequent deterioration post IVIg treatment
Review is not mandated for this indication however the following criteria may be useful in assessing the effectiveness of therapy.
 
AND
  • Patient survival and symptom improvement
Dose
Initial therapy for GBS with significant disability and progression
  • Initial Dose (IVIg) - 2 g/kg in 2 to 5 divided doses.
Relapse in GBS (treatment-related fluctuation) within 8 weeks with recurrent weakness after initial improvement may require a second treatment with IVIg. A second dose is available under the ‘Relapse’ indication but must only be on the advice of, and after assessment by, a neurologist.

Treatment-related fluctuations (TRFs) are defined as

1) improvement in GBS disability score of at least 1 grade or improvement in MRC sum score of more than 5 points after completion of therapy, followed by a worsening in GBS disability score of at least 1 grade or a decrease in MRC sum score of more than 5 points within the first months after onset of disease; OR
2) stabilization of the clinical course for more than 1 week after completion of therapy, followed by a worsening of at least 1 grade of the GBS disability score or more than 5 points on the MRC sum score.

Note an application can be made for either a second course under GBS-TRF or a switch to A-CIDP in the 4-8 week window after onset.

Refer to the current product information sheet for further information on dose, administration and contraindications.
 Dose Calculator
Relapse in GBS - treatment related fluctuation with initial improvement and subsequent deterioration post IVIg treatment
  • Second Dose (IVIg) - 2g/kg in 2 to 5 divided doses
Refer to the current product information sheet for further information on dose, administration and contraindications.
 Dose Calculator
Bibliography
Association of British Neurologists 2005, Guidelines for the use of intravenous immunoglobulin in neurological diseases, The Association, London. Available from: http://www.theabn.org/media/docs/ABN%20publications/IVIg-guidelines-final-July05.pdf

Biotext 2004, ‘Summary data on conditions and papers’, in A systematic literature review and report on the efficacy of intravenous immunoglobulin therapy and its risks, commissioned by the National Blood Authority on behalf of all Australian Governments, pp.149–50. Available from:
https://www.blood.gov.au/system/files/A-systematic-literature-review-and-report-on-the-efficacy-of-IVIg-therapy-and-its-risks.pdf

Frommer, M & Madronio, C 2006, The use of intravenous immunoglobulin in Australia. A report for the National Blood Authority, Part B: systematic literature review, Sydney Health Projects Group, University of Sydney, Sydney, pp. 32–4.

Hughes, RA, Newsom-Davis, JM, Perkin, GD, et al 1978, ‘Controlled trial of prednisolone in acute polyneuropathy’, Lancet, vol. 2, no. 8093, pp. 750-3.

Hughes, RAC, Raphaël, J-C, Swan, AV, et al 2006, ‘Intravenous immunoglobulin for Guillain– Barré syndrome (Cochrane Review)’, in The Cochrane Library, Issue 1, John Wiley & Sons, Ltd, Chichester, United Kingdom.

Hughes, RAC, Swan, AV & van Doorn, PA 2014, ‘Intravenous immunoglobulin for Guillain Barré syndrome’,  The Cochrane database of systematic reviews, vol. 19, no. 9, pp. CD002063.

Kleyweg, RP, van der Meché, FG, Schmitz, PI 1991, ‘Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain-Barré syndrome’, Muscle Nerve, vol. 14, no. 11. pp. 1103–9.

Korinthenberg, R, Schessl, J, Kirschner, J, et al 2005, 'Intravenously administered immunoglobulin in the treatment of childhood Guillain–Barré syndrome: a randomized trial’, Paediatrics, vol. 116, no. 1, pp. 8–14.

Kornberg, AJ, for the Asia–Pacific IVIg Advisory Board 2004, Bringing consensus to the use of IVIg in neurology. Expert consensus statements on the use of IVIg in neurology, 1st edn, Asia–Pacific IVIg Advisory Board, Melbourne, pp. 14–20.

Medical Research Council. Aids to the examination of the peripheral nervous system, Memorandum no. 45, Her Majesty's Stationery Office, London, 1981. Available from: https://mrc.ukri.org/research/facilities-and-resources-for-researchers/mrc-scales/mrc-muscle-scale/

Ruts L, Drenthen J, Jacobs BC, et al., 2010. ‘Distinguishing acute-onset CIDP from fluctuating Guillain-Barré syndrome’, Neurology, vol 74, pp 1680-1686

van Koningsveld, R, Steyerberg, EW, Hughes, RAC, et al 2007, ‘A clinical prognostic scoring system for Guillain-Barré syndrome’, The Lancet. Neurology, vol. 6, no. 7, pp.589-94.

Verboon, C, van Doorn, PA, & Jacobs, BC 2017, ‘Treatment dilemmas in Guillain-Barré syndrome’, Journal of neurology, neurosurgery, and psychiatry,  vol. 88, no. 4, pp. 346-352.

Walgaard C, Jacobs BC, Lingsma HF, et al 2021.´ Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial.´ Lancet Neurol; 20: 275–83