Guillain-Barré syndrome: Pathogenesis
- Francine J Vriesendorp, MD
Francine J Vriesendorp, MD
- Professor of Neurology
- SUNY Upstate Medical University
- Section Editors
- Jeremy M Shefner, MD, PhD
Jeremy M Shefner, MD, PhD
- Section Editor — Neuromuscular Disease
- Professor and Chair of Neurology, Barrow Neurological Institute
- Professor of Neurology, University of Arizona, Phoenix
- Clinical Professor of Neurology, Creighton University
- Ira N Targoff, MD
Ira N Targoff, MD
- Section Editor — Muscle Disease
- Professor of Medicine, Section of Rheumatology
- University of Oklahoma Health Sciences Center
The acute immune-mediated polyneuropathies are classified under the eponym Guillain-Barré syndrome (GBS), after the authors of early descriptions of the disease. GBS is an acute monophasic paralyzing illness, usually provoked by a preceding infection. GBS occurs world-wide and all age groups are affected.
Historically, GBS was considered a single disorder. It now is recognized as a heterogeneous syndrome with several variant forms. The major forms are acute inflammatory demyelinating polyradiculoneuropathy (AIDP), the Miller Fisher syndrome (MFS), acute motor axonal neuropathy (AMAN), and acute sensorimotor axonal neuropathy (AMSAN). Each form of GBS has distinguishing clinical, pathophysiologic, and pathologic features. (See "Clinical features and diagnosis of Guillain-Barré syndrome in adults".)
The pathogenesis of GBS will be reviewed here. Other aspects of GBS are discussed separately. (See "Clinical features and diagnosis of Guillain-Barré syndrome in adults" and "Treatment and prognosis of Guillain-Barré syndrome in adults" and "Guillain-Barré syndrome in children: Epidemiology, clinical features, and diagnosis" and "Guillain-Barré syndrome in children: Treatment and prognosis".)
One proposed mechanism for GBS is that an antecedent infection evokes an immune response, which in turn cross-reacts with peripheral nerve components because of the sharing of cross-reactive epitopes (molecular mimicry) . The end result is an acute polyneuropathy. This immune response can be directed towards the myelin or the axon of peripheral nerve.
Immune reactions directed against epitopes in Schwann cell surface membrane or myelin can cause acute inflammatory demyelinating neuropathy (AIDP) . The pathology is that of multifocal inflammatory demyelination starting at the level of the nerve roots. The earliest changes are frequently seen at the nodes of Ranvier. Both the cellular and humoral immune responses participate in the process. Invasion by activated T-cells is followed by macrophage-mediated demyelination with evidence of complement and immunoglobulin deposition on myelin and Schwann cells [3-5]. No specific myelin antigen(s) have been identified.
- Yuki N, Hartung HP. Guillain-Barré syndrome. N Engl J Med 2012; 366:2294.
- Hahn AF. Guillain-Barré syndrome. Lancet 1998; 352:635.
- Asbury AK, Arnason BG, Adams RD. The inflammatory lesion in idiopathic polyneuritis. Its role in pathogenesis. Medicine (Baltimore) 1969; 48:173.
- Hafer-Macko CE, Sheikh KA, Li CY, et al. Immune attack on the Schwann cell surface in acute inflammatory demyelinating polyneuropathy. Ann Neurol 1996; 39:625.
- Kieseier BC, Kiefer R, Gold R, et al. Advances in understanding and treatment of immune-mediated disorders of the peripheral nervous system. Muscle Nerve 2004; 30:131.
- Yuki N, Yoshino H, Sato S, Miyatake T. Acute axonal polyneuropathy associated with anti-GM1 antibodies following Campylobacter enteritis. Neurology 1990; 40:1900.
- Rees JH, Gregson NA, Hughes RA. Anti-ganglioside GM1 antibodies in Guillain-Barré syndrome and their relationship to Campylobacter jejuni infection. Ann Neurol 1995; 38:809.
- Jacobs BC, van Doorn PA, Schmitz PI, et al. Campylobacter jejuni infections and anti-GM1 antibodies in Guillain-Barré syndrome. Ann Neurol 1996; 40:181.
- Hafer-Macko C, Hsieh ST, Li CY, et al. Acute motor axonal neuropathy: an antibody-mediated attack on axolemma. Ann Neurol 1996; 40:635.
- Ogawara K, Kuwabara S, Mori M, et al. Axonal Guillain-Barré syndrome: relation to anti-ganglioside antibodies and Campylobacter jejuni infection in Japan. Ann Neurol 2000; 48:624.
- Jacobs BC, Hazenberg MP, van Doorn PA, et al. Cross-reactive antibodies against gangliosides and Campylobacter jejuni lipopolysaccharides in patients with Guillain-Barré or Miller Fisher syndrome. J Infect Dis 1997; 175:729.
- Koga M, Takahashi M, Masuda M, et al. Campylobacter gene polymorphism as a determinant of clinical features of Guillain-Barré syndrome. Neurology 2005; 65:1376.
- Aspinall GO, Fujimoto S, McDonald AG, et al. Lipopolysaccharides from Campylobacter jejuni associated with Guillain-Barré syndrome patients mimic human gangliosides in structure. Infect Immun 1994; 62:2122.
- Yuki N, Susuki K, Koga M, et al. Carbohydrate mimicry between human ganglioside GM1 and Campylobacter jejuni lipooligosaccharide causes Guillain-Barre syndrome. Proc Natl Acad Sci U S A 2004; 101:11404.
- Yuki N, Yamada M, Koga M, et al. Animal model of axonal Guillain-Barré syndrome induced by sensitization with GM1 ganglioside. Ann Neurol 2001; 49:712.
- Yuki N, Kuwabara S. Axonal Guillain-Barré syndrome: carbohydrate mimicry and pathophysiology. J Peripher Nerv Syst 2007; 12:238.
- Halstead SK, Zitman FM, Humphreys PD, et al. Eculizumab prevents anti-ganglioside antibody-mediated neuropathy in a murine model. Brain 2008; 131:1197.
- Prineas JW. Pathology of the Guillain-Barré syndrome. Ann Neurol 1981; 9 Suppl:6.
- Griffin JW, Li CY, Macko C, et al. Early nodal changes in the acute motor axonal neuropathy pattern of the Guillain-Barré syndrome. J Neurocytol 1996; 25:33.
- Uncini A, Kuwabara S. Nodopathies of the peripheral nerve: an emerging concept. J Neurol Neurosurg Psychiatry 2015; 86:1186.
- Ho TW, Hsieh ST, Nachamkin I, et al. Motor nerve terminal degeneration provides a potential mechanism for rapid recovery in acute motor axonal neuropathy after Campylobacter infection. Neurology 1997; 48:717.
- Lu JL, Sheikh KA, Wu HS, et al. Physiologic-pathologic correlation in Guillain-Barré syndrome in children. Neurology 2000; 54:33.
- Rees JH, Soudain SE, Gregson NA, Hughes RA. Campylobacter jejuni infection and Guillain-Barré syndrome. N Engl J Med 1995; 333:1374.
- Visser LH, Van der Meché FG, Van Doorn PA, et al. Guillain-Barré syndrome without sensory loss (acute motor neuropathy). A subgroup with specific clinical, electrodiagnostic and laboratory features. Dutch Guillain-Barré Study Group. Brain 1995; 118 ( Pt 4):841.
- Griffin JW, Li CY, Ho TW, et al. Pathology of the motor-sensory axonal Guillain-Barré syndrome. Ann Neurol 1996; 39:17.
- McCarthy N, Giesecke J. Incidence of Guillain-Barré syndrome following infection with Campylobacter jejuni. Am J Epidemiol 2001; 153:610.
- Lastovica AJ, Goddard EA, Argent AC. Guillain-Barré syndrome in South Africa associated with Campylobacter jejuni O:41 strains. J Infect Dis 1997; 176 Suppl 2:S139.
- Nishimura M, Nukina M, Kuroki S, et al. Characterization of Campylobacter jejuni isolates from patients with Guillain-Barré syndrome. J Neurol Sci 1997; 153:91.
- Brannagan TH 3rd, Zhou Y. HIV-associated Guillain-Barré syndrome. J Neurol Sci 2003; 208:39.
- Piliero PJ, Fish DG, Preston S, et al. Guillain-Barré syndrome associated with immune reconstitution. Clin Infect Dis 2003; 36:e111.
- Tam CC, O'Brien SJ, Rodrigues LC. Influenza, Campylobacter and Mycoplasma infections, and hospital admissions for Guillain-Barré syndrome, England. Emerg Infect Dis 2006; 12:1880.
- Lehmann HC, Hartung HP, Kieseier BC, Hughes RA. Guillain-Barré syndrome after exposure to influenza virus. Lancet Infect Dis 2010; 10:643.
- Vellozzi C, Iqbal S, Broder K. Guillain-Barre syndrome, influenza, and influenza vaccination: the epidemiologic evidence. Clin Infect Dis 2014; 58:1149.
- Tam CC, O'Brien SJ, Petersen I, et al. Guillain-Barré syndrome and preceding infection with campylobacter, influenza and Epstein-Barr virus in the general practice research database. PLoS One 2007; 2:e344.
- Stowe J, Andrews N, Wise L, Miller E. Investigation of the temporal association of Guillain-Barre syndrome with influenza vaccine and influenzalike illness using the United Kingdom General Practice Research Database. Am J Epidemiol 2009; 169:382.
- Winer JB, Hughes RA, Anderson MJ, et al. A prospective study of acute idiopathic neuropathy. II. Antecedent events. J Neurol Neurosurg Psychiatry 1988; 51:613.
- Steininger C, Popow-Kraupp T, Seiser A, et al. Presence of cytomegalovirus in cerebrospinal fluid of patients with Guillain-Barre syndrome. J Infect Dis 2004; 189:984.
- Orlikowski D, Porcher R, Sivadon-Tardy V, et al. Guillain-Barré syndrome following primary cytomegalovirus infection: a prospective cohort study. Clin Infect Dis 2011; 52:837.
- Jacobs BC, Rothbarth PH, van der Meché FG, et al. The spectrum of antecedent infections in Guillain-Barré syndrome: a case-control study. Neurology 1998; 51:1110.
- Ropper AH. The Guillain-Barré syndrome. N Engl J Med 1992; 326:1130.
- Mori M, Kuwabara S, Miyake M, et al. Haemophilus influenzae infection and Guillain-Barré syndrome. Brain 2000; 123 ( Pt 10):2171.
- Kamar N, Bendall RP, Peron JM, et al. Hepatitis E virus and neurologic disorders. Emerg Infect Dis 2011; 17:173.
- Geurtsvankessel CH, Islam Z, Mohammad QD, et al. Hepatitis E and Guillain-Barre syndrome. Clin Infect Dis 2013; 57:1369.
- Meyer Sauteur PM, Huizinga R, Tio-Gillen AP, et al. Mycoplasma pneumoniae triggering the Guillain-Barré syndrome: A case-control study. Ann Neurol 2016; 80:566.
- Ropper AH, Wijdicks EFM, Truax BT. Guillain-Barré syndrome, FA Davis, Philadelphia 1991. p.57.
- Shin IS, Baer AN, Kwon HJ, et al. Guillain-Barré and Miller Fisher syndromes occurring with tumor necrosis factor alpha antagonist therapy. Arthritis Rheum 2006; 54:1429.
- Pritchard J, Appleton R, Howard R, Hughes RA. Guillain-Barré syndrome seen in users of isotretinoin. BMJ 2004; 328:1537.
- Baxter R, Bakshi N, Fireman B, et al. Lack of association of Guillain-Barré syndrome with vaccinations. Clin Infect Dis 2013; 57:197.
- Lasky T, Terracciano GJ, Magder L, et al. The Guillain-Barré syndrome and the 1992-1993 and 1993-1994 influenza vaccines. N Engl J Med 1998; 339:1797.
- Salmon DA, Proschan M, Forshee R, et al. Association between Guillain-Barré syndrome and influenza A (H1N1) 2009 monovalent inactivated vaccines in the USA: a meta-analysis. Lancet 2013; 381:1461.
- De Wals P, Deceuninck G, Toth E, et al. Risk of Guillain-Barré syndrome following H1N1 influenza vaccination in Quebec. JAMA 2012; 308:175.
- Baxter R, Lewis N, Bakshi N, et al. Recurrent Guillain-Barre syndrome following vaccination. Clin Infect Dis 2012; 54:800.
- Hughes RA, Charlton J, Latinovic R, Gulliford MC. No association between immunization and Guillain-Barré syndrome in the United Kingdom, 1992 to 2000. Arch Intern Med 2006; 166:1301.