Early nodal changes in the acute motor axonal neuropathy pattern of the Guillain-Barré syndrome

Abstract

The axonal patterns of Guillain-Barré syndrome, associated in many cases with antecedent Campylobacter jejuni infection, are now recognized as frequent causes of acute flaccid paralysis in some regions of the world. This study examined ultrastructurally the PNS of seven cases of the acute motor axonal neuropathy form of Guillain-Barré syndrome. In this disorder previous studies of advanced cases have found Wallerian-like degeneration of motor fibres in the spinal roots and peripheral nerves, with little lymphocytic inflammation or demyelination. The present study was focused on identifying early changes and establishing the sequence of changes. By electron microscopy the earliest and mildest changes consisted of lengthening of the node of Ranvier with distortion of the paranodal myelin, and in some instances with breakdown of the outermost myelin terminal loops. At this stage many nodes had overlying macrophages which extended their processes through the Schwann cell basal lamina covering the node and apposed the axolemma. Macrophage processes then extended beneath the myelin terminal loops, and the whole macrophage entered the periaxonal space at the paranode. Macrophage processes dissected the axon from the adaxonal Schwann cell plasmalemma and the macrophages advanced into the internodal periaxonal space, where they typically surrounded a condensed-appearing axon. At this stage the adaxonal Schwann cell cytoplasm regularly degenerated and disappeared, so that the periaxonal space was bounded by the innermost myelin lamella, and the axolemma of many fibres could not be seen. The internodal myelin sheath and the abaxonal Schwann cell cytoplasm remained normal. This arrangement appeared to be stable for some time, but in many fibres the axon subsequently underwent Wallerian-like degeneration. By interfering with impulse conduction, these nodal and periaxonal changes may explain paralysis in some pathologically mild cases. In addition, at early stages, these changes may be reversible, thus explaining the rapid recovery of some patients who become paralysed with acute motor axonal neuropathy. These observations, taken together with previous studies, suggest that acute motor axonal neuropathy is an antibody- and complement-mediated disorder in which the relevant epitopes are present on the nodal and internodal axolemma.

Carbohydrate mimicry between human ganglioside GM1 and Campylobacter jejuni lipooligosaccharide causes Guillain–Barré syndrome

“…This characteristic seems to occur because the blood-brain barrier that protects the brain and spinal cord is much tighter than the blood-nerve barrier. Electrophysiological, immunohistochemical, and pathological study findings show that the initial lesion in axonal GBS may be localized in the spinal nerve roots (23,24). The reason may be that nerve roots are vulnerable because they lack a blood-nerve barrier.…”

Electron tomographic analysis of cytoskeletal cross-bridges in the paranodal region of the node of Ranvier in peripheral nerves

“…Equally compelling support for an axo-glial integration of function is provided by the disruption of the myelin structure or maintenance of the glial cell in Charcot-Marie-Tooth disease, a set of human hereditary neuropathies (Bergoffen et al, 1993;Martini, 2001), causing changes in axonal morphology and nerve impulse conduction. Pathological conditions in peripheral neuropathies are also found when constituent proteins of the node of Ranvier malfunction (Bergoffen et al, 1993;Griffin et al, 1996;Rasband et al, 2003;Sima, 1993), are deficiently expressed (Bhat et al, 2001;Boyle et al, 2001;Sherman et al, 2005;Weber et al, 1999) or after axonal ischemic injury (Waxman et al, 1992) and trauma (Maxwell et al, 1991).…”

“…The continued work to identify the proteins that constitute these bridges, how they link with each other to form filaments or rods, and how they attach to membranes and cytoskeleton is anticipated to enhance discovery of functional interactions. The combination of high-resolution 3D structures of the paranodal region with the localization of specific macromolecules that populate this region is essential for subsequent modeling studies (Sosinsky et al, 2005) and for a better understanding of the structural and molecular bases for diseases affecting the node and paranode (Bergoffen et al, 1993;Bhat et al, 2001;Boyle et al, 2001;Griffin et al, 1996;Martini, 2001;Rasband et al, 2003;Sherman et al, 2005;Sima, 1993;Weber et al, 1999). The cytoskeletal filaments with their various crossbridges, including those that are transcellular, are assumed to play an important role in maintaining the electrophysiological properties required for functioning of the node of Ranvier by establishing a mechanical link between the glial and neuronal cytoskeletons, thereby stabilizing the relationship between these cells.…”

Guillain-Barré Syndrome

“…The two early changes are the lengthening of the node of Ranvier followed by complement-mediated recruitment of macrophages to the nodal region [30]. Macrophages distort paranodal axons and myelin sheaths, separate myelin from the axolemma and induce condensation of axoplasm in a reversible fashion.…”