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Axonal degeneration in Guillain–Barré syndrome: a reappraisal

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Abstract

The aim of this review was to analyse the pathophysiology of axonal degeneration in Guillain–Barré syndrome (GBS) with emphasis on early stages (≤ 10 days after onset). An overview of experimental autoimmune neuritis (EAN) models is provided. Originally GBS and acute inflammatory demyelinating polyneuropathy were equated, presence of axonal degeneration being attributed to a “bystander” effect. Afterwards, primary axonal GBS forms were reported, designated as acute motor axonal neuropathy/acute motor–sensory axonal neuropathy. Revision of the first pathological description of axonal GBS indicates the coexistence of active axonal degeneration and demyelination in spinal roots, and pure Wallerian-like degeneration in peripheral nerve trunks. Nerve conduction studies are essential for syndrome subtyping, though their sensitivity is scanty in early GBS. Serum markers of axonal degeneration include increased levels of neurofilament light chain and presence of anti-ganglioside reactivity. According to nerve ultrasonographic features and autopsy studies, ventral rami of spinal nerves are a hotspot in early GBS. In P2-induced EAN models, the initial pathogenic change is inflammatory oedema of spinal roots and sciatic nerve, which is followed by demyelination, and Wallerian-like degeneration in nerve trunks possessing epi-perineurium; a critical elevation of endoneurial fluid pressure is a pre-requisite for inducing ischemic axonal degeneration. Similar lesion topography may occur in GBS. The repairing role of adaxonal Schwann cytoplasm in axonal degeneration is analysed. A novel pathophysiological mechanism for nerve trunk pain in GBS, including pure motor forms, is provided. The potential therapeutic role of intravenous boluses of methylprednisolone for early severe GBS and intractable pain is argued.

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Acknowledgements

I thank my colleagues of the Service of Neurology, Drs Antonio García y Pedro Orizaola (Service of Clinical Neurophysiology), Dr. Elena Gallardo (Service of Radiology), Dr. Nuria Terán-Villagrá (Service of Pathology), and Professors Miguel Lafarga and María T. Berciano (Department of Anatomy and Cell Biology, UC) for their help in clinical, electrophysiological, imaging and pathological studies. I wish also to thank Dr José Gazulla (Service of Neurology, University Hospital Miguel Servet, Saragosse) for his comments on the manuscript, and Mr Mario Corral (Director of “Marquesa de Pelayo” Library) for his technical support.

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  1. Professor Emeritus of Neurology, Service of Neurology, University Hospital “Marqués de Valdecilla (IDIVAL)”, “Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED)”, University of Cantabria, Santander, Spain

    José Berciano

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Berciano, J. Axonal degeneration in Guillain–Barré syndrome: a reappraisal. J Neurol 268, 3728–3743 (2021). https://doi.org/10.1007/s00415-020-10034-y

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  • DOI: https://doi.org/10.1007/s00415-020-10034-y

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