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.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Hughes RA, Cornblath DR (2005) Guillain-Barré syndrome. Lancet 366:1653–1666
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
Soliven B (2014) Animal models of autoimmune neuropathy. ILARJ 54:282–289
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
Vucic S, Cairns KD, Black KR, Chong PS, Cros D (2004) Neurophysiologic findings in early acute inflammatory demyelinating polyradiculoneuropathy. Clin Neurophysiol 115:2329–2335
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
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
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
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
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
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
Asbury AK, Arnason BG, Adams RD (1969) The inflammatory lesion in idiopathic polyneuritis. Its role in pathogenesis. Medicine 48:173–215
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
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. https://doi.org/10.1136/jnnp-2019-322479(Online ahead of print)
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
Berciano J, García A (2016) Sural-sparing in Guillain-Barré syndrome: does it mean lack of histopathological changes? Clin Neurophysiol 127:969–970
Hall SM, Hughes RAC, Atkinson PF, McColl I, Gale A (1992) Motor nerve biopsy in severe Guillain-Barré syndrome. Ann Neurol 31:441–444
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
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
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
Kanda T (2013) Biology of the blood-nerve barrier and its alteration in immune mediated neuropathies. J Neurol Neurosurg Psychiatry 84:208–212
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
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
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
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
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
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
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
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
Powell HC, Myers RR (1996) The axon in Guillain-Barré syndrome: immune target or innocent bystander? Ann Neurol 39:4–5
I thank Dr. José Gazulla (Service of Neurology, “Hospital Universitario Miguel Servet”, Saragossa) for his commentaries on the manuscript.
Conflict of interest
The author declares no conflict of interest.
This article does not contain studies with human participants or animals performed by the author.
Not applicable as this is a review manuscript.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Berciano, J. Inflammatory oedema of nerve trunks may be pathogenic in very early Guillain–Barré syndrome. Acta Neurol Belg (2020). https://doi.org/10.1007/s13760-020-01413-3
- Acute motor axonal neuropathy
- Axonal degeneration
- Blood–nerve barrier
- Endoneurial fluid pressure
- Experimental autoimmune neuritis
- Guillain–Barré syndrome
- Nerve inflammatory oedema
- Spinal nerve
- Endoneurial ischaemia
- Neurofilament light chain
- Very early Guillain–Barré syndrome