Inflammatory oedema of nerve trunks may be pathogenic in very early Guillain–Barré syndrome


The aim of this paper is to analyse the pathological background of very early Guillain-Barré (VEGBS) (≤ 4 days after onset) comparing it with initial stages of experimental autoimmune neuritis (EAN). The pathological hallmark of VEGBS is inflammatory oedema predominating in proximal nerve trunks. In EAN inflammatory oedema precedes the development of demyelination or axonal degeneration; such oedema may increase endoneurial fluid pressure (EFP) stretching the perineurium and constricting the transperineurial microcirculation. Centrofascicular or wedge-shaped areas of nerve ischemia have been reported in GBS and EAN. Additional support for proximal VEGBS pathology comes from electrophysiology showing alterations in late responses as the most frequent features, and ultrasonography illustrating that main changes rely on ventral rami of spinal nerves. Selective inefficiency of the blood-nerve barrier would explain the topography of changes in VEGBS. Increased serum neurofilament light chain concentration has recently been reported in VEGBS, with no difference between demyelinating and axonal subtypes. This is a marker of axonal damage, which could be correlated with endoneurial ischemia caused by increased EFP. Inflammatory oedema of proximal nerve trunks may be pathogenic in VEGBS, and consequently there is a pressing need for therapeutic strategies to stop its rapid impact on the axons.

This is a preview of subscription content, log in to check access.

Fig. 1


  1. 1.

    Hughes RA, Cornblath DR (2005) Guillain-Barré syndrome. Lancet 366:1653–1666

    CAS  Article  Google Scholar 

  2. 2.

    Griffin JW, Li CY, Ho TW, Tian M, Gao CY, Xue P, Mishu B, Cornblath DR, Macko C, McKhann GM, Asbury AK (1996) Pathology of the motor-sensory axonal Guillain-Barré syndrome. Ann Neurol 39:17–28

    CAS  Article  Google Scholar 

  3. 3.

    Soliven B (2014) Animal models of autoimmune neuropathy. ILARJ 54:282–289

    CAS  Article  Google Scholar 

  4. 4.

    Hadden RD, Cornblath DR, Hughes RA, Zielasek J, Hartung HP, Toyka KV, Swan AV (1998) Electrophysiological classification of Guillain-Barré syndrome: clinical associations and outcome. Plasma Exchange/Sandoglobulin Guillain-Barré syndrome trial group. Ann Neurol 44:780–788

    CAS  Article  Google Scholar 

  5. 5.

    Vucic S, Cairns KD, Black KR, Chong PS, Cros D (2004) Neurophysiologic findings in early acute inflammatory demyelinating polyradiculoneuropathy. Clin Neurophysiol 115:2329–2335

    Article  Google Scholar 

  6. 6.

    Albertí MA, Alentorn A, Martínez-Yelamos S, Martínez-Matos JA, Povedano M, Montero J, Casasnovas C (2011) Very early electrodiagnostic findings in Guillain-Barré syndrome. J Peripher Nerv Syst 16:136–142

    Article  Google Scholar 

  7. 7.

    Berciano J, Orizaola P, Gallardo E, Pelayo-Negro AL, Sánchez-Juan P, Infante J, Sedano MJ (2020) Very early Guillain-Barré syndrome: a clinical-electrophysiological and ultrasonographic study. Clin Neurophysiol Pract 5:1–9

    Article  Google Scholar 

  8. 8.

    Haymaker WE, Kernohan JW (1949) The Landry-Guillain-Barré syndrome; a clinicopathologic report of 50 fatal cases and a critique of the literature. Medicine 28:59–141

    CAS  Article  Google Scholar 

  9. 9.

    Krücke W (1955) Die primär-entzündliche Polyneuritis unbekannter Ursache. In: Lubarsch O, et al. (eds) Handbuch der speziellen pathologischen Anatomie und Histologie, Erkrankungen des peripheren und des vegetativen Nerven, vol XIII/5. Springer-Verlag, Berlin, pp 164–182

    Google Scholar 

  10. 10.

    Berciano J, Sedano MJ, Pelayo-Negro AL, García A, Orizaola P, Gallardo E, Lafarga M, Berciano MT, Jacobs BC (2017) Proximal nerve lesions in early Guillain-Barré syndrome: implications for pathogenesis and disease classification. J Neurol 264:221–236

    Article  Google Scholar 

  11. 11.

    McKhann GM, Cornblath DR, Griffin JW, Ho TW, Li CY, Jiang Z, Wu HS, Zhaori G, Liu Y, Jou LP et al (1993) Acute motor axonal neuropathy: a frequent cause of acute flaccid paralysis in China. Ann Neurol 33:333–342

    CAS  Article  Google Scholar 

  12. 12.

    Asbury AK, Arnason BG, Adams RD (1969) The inflammatory lesion in idiopathic polyneuritis. Its role in pathogenesis. Medicine 48:173–215

    CAS  Article  Google Scholar 

  13. 13.

    Üçeyler N, Necula G, Wagemann E, Toyka KV, Sommer C (2016) Endoneurial edema in sural nerve may indicate recent onset inflammatory neuropathy. Muscle Nerve 53:705–710

    Article  Google Scholar 

  14. 14.

    Koike H, Fukami Y, Nishi R, Kawagashira Y, Iijima M, Katsuno M, Sobue GJ (2020) Ultrastructural mechanisms of macrophage-induced demyelination in Guillain-Barré syndrome. J Neurol Neurosurg Psychiatry. ahead of print)

    Article  PubMed  Google Scholar 

  15. 15.

    Umapathi U, Li Z, Verma K, Yuki N (2015) Sural-sparing is seen in axonal as well as demyelinating forms of Guillain-Barré syndrome. Clin Neurophysiol 126:2376–2380

    Article  Google Scholar 

  16. 16.

    Berciano J, García A (2016) Sural-sparing in Guillain-Barré syndrome: does it mean lack of histopathological changes? Clin Neurophysiol 127:969–970

    Article  Google Scholar 

  17. 17.

    Hall SM, Hughes RAC, Atkinson PF, McColl I, Gale A (1992) Motor nerve biopsy in severe Guillain-Barré syndrome. Ann Neurol 31:441–444

    CAS  Article  Google Scholar 

  18. 18.

    Gallardo E, Sedano MJ, Orizaola P, Sánchez-Juan P, González-Suárez A, García A (2015) Spinal nerve involvement in early Guillain-Barré syndrome: a clinico-electrophysiological, ultrasonographic and pathological study. Clin Neurophysiol 126:810–819

    Article  Google Scholar 

  19. 19.

    Kurt Incesu T, Secil Y, Tokucoglu F, Gurgor N, Özdemirkiran T, Akhan G, Ertekin C (2013) Diagnostic value of lumbar root stimulation at the early stage of Guillain-Barré syndrome. Clin Neurophysiol 124:197–203

    Article  Google Scholar 

  20. 20.

    Sevy A, Grapperon AM, Salort Campana E, Delmont E, Attarian S (2018) Detection of proximal conduction blocks using a triple stimulation technique improves the early diagnosis of Guillain-Barré syndrome. Clin Neurophysiol 129:127–132

    Article  Google Scholar 

  21. 21.

    Kanda T (2013) Biology of the blood-nerve barrier and its alteration in immune mediated neuropathies. J Neurol Neurosurg Psychiatry 84:208–212

    Article  Google Scholar 

  22. 22.

    Izumo S, Linington C, Wekerle H, Meyermann R (1985) Morphologic study on experimental allergic neuritis mediated by T cell line specific for bovine P2 protein in Lewis rat. Lab Invest 53:209–218

    CAS  PubMed  Google Scholar 

  23. 23.

    Hadden RD, Gregson A, Gold R, Smith J, Hughes RA (2002) Accumulation of immunoglobulin across the ‘blood-nerve barrier’ in spinal roots in adoptive transfer experimental autoimmune neuritis. Neuropathol Appl Neurobiol 28:489–497

    CAS  Article  Google Scholar 

  24. 24.

    Powell HC, Myers RR, Mizisin AP, Olee T, Brotoff SW (1991) Response of the axon and barrier endothelium to experimental allergic neuritis induced by autoreactive T cell lines. Acta Neuropathol 82:364–377

    CAS  Article  Google Scholar 

  25. 25.

    Hahn AF, Feasby TE, Steele A, Lovgren DS, Berry J (1988) Demyelination and axonal degeneration in Lewis rat experimental allergic neuritis depend on the myelin dosage. Lab Invest 59:115–125

    CAS  PubMed  Google Scholar 

  26. 26.

    Berciano J, García A, Figols J, Muñoz R, Berciano MT, Lafarga M (2000) Perineurium contributes to axonal damage in acute inflammatory demyelinating polyneuropathy. Neurology 55:552–559

    CAS  Article  Google Scholar 

  27. 27.

    Berthold CH, Fraher JP, King RHM, Rydmark M (2005) Microscopical anatomy of the peripheral nervous system. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy. WB Saunders, Philadelphia, pp 35–91

    Google Scholar 

  28. 28.

    Gaetani L, Blennow K, Calabresi P, FilippO Di, Parnetti L, Zetterberg HJ (2019) Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry 90:870–881

    Article  Google Scholar 

  29. 29.

    Altmann P, De Simoni D, Kaider A, Ludwig B, Rath J, Leutmezer F, Zimprich F, Hoeftberger R, Lunn MP, Heslegrave A, Berger T, Zetterberg H, Rommer PS (2020) Increased serum neurofilament light chain concentration indicates poor outcome in Guillain-Barré syndrome. J Neuroinflammation 17(1):86

    CAS  Article  Google Scholar 

  30. 30.

    Powell HC, Myers RR (1996) The axon in Guillain-Barré syndrome: immune target or innocent bystander? Ann Neurol 39:4–5

    CAS  Article  Google Scholar 

Download references


I thank Dr. José Gazulla (Service of Neurology, “Hospital Universitario Miguel Servet”, Saragossa) for his commentaries on the manuscript.

Author information



Corresponding author

Correspondence to José Berciano.

Ethics declarations

Conflict of interest

The author declares no conflict of interest.

Ethical approval

This article does not contain studies with human participants or animals performed by the author.

Informed consent

Not applicable as this is a review manuscript.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Berciano, J. Inflammatory oedema of nerve trunks may be pathogenic in very early Guillain–Barré syndrome. Acta Neurol Belg (2020).

Download citation


  • Acute motor axonal neuropathy
  • Axonal degeneration
  • Blood–nerve barrier
  • Demyelination
  • Electrophysiology
  • Endoneurial fluid pressure
  • Experimental autoimmune neuritis
  • Guillain–Barré syndrome
  • Nerve inflammatory oedema
  • Spinal nerve
  • Endoneurial ischaemia
  • Neurofilament light chain
  • Ultrasonography
  • Very early Guillain–Barré syndrome