Nodopathies of the peripheral nerve: an emerging concept

Abstract

Peripheral nerve diseases are traditionally classified as demyelinating or axonal. It has been recently proposed that microstructural changes restricted to the nodal/ paranodal region may be the key to understanding the pathophysiology of antiganglioside antibody mediated neuropathies. We reviewed neuropathies with different aetiologies (dysimmune, inflammatory, ischaemic, nutritional, toxic) in which evidence from nerve conductions, excitability studies, pathology and animal models, indicate the involvement of the nodal region in the pathogenesis. For these neuropathies, the classification in demyelinating and axonal is inadequate or even misleading, we therefore propose a new category of nodopathy that has the following features:(1) it is characterised by a pathophysiological continuum from transitory nerve conduction block to axonal degeneration; (2) the conduction block may be due to paranodal myelin detachment, node lengthening, dysfunction or disruption of Na + channels, altered homeostasis of water and ions, or abnormal polarisation of the axolemma; (3) the conduction block may be promptly reversible without development of excessive temporal dispersion; (4) axonal degeneration, depending on the specific disorder and its severity, eventually follows the conduction block. The term nodopathy focuses to the site of primary nerve injury, avoids confusion with segmental demyelinating neuropathies and circumvents the apparent paradox that something axonal may be reversible and have a good prognosis.

Motor unit remodelling in multifocal motor neuropathy: The importance of axonal loss

“…Axonal degeneration has been shown to be strongly associated with conduction block supporting the notion that the same pathophysiology may account for both processes (Vucic et al, 2007;Van Asseldonk et al, 2006) and the continuum from conduction block to axonal degeneration with disease processes affecting the nodal/paranodal regions has recently become better recognised as a distinct entity (Uncini and Kuwabara, 2015).…”

“…GM 1 is enriched in the nodal and paranodal regions (Willison and Yuki, 2002) and gangliosides play an important role in the maintenance and stabilisation of the paranode and ion channel clustering (Susuki et al, 2007). Conduction block may result from a variety of processes such as lengthening of the node, detachment of myelin from the paranode, sodium channel dysfunction and/or abnormalities in axolemma polarisation (Barnett et al, 2016;Uncini and Kuwabara, 2015) and in theory, pathology at either the node and/or the paranode could lead to conduction failure and axonal degeneration.…”

“…Anti-GM 1 IgM is present in approximately 50% of patients with MMN with GM 1 enriched in the nodal and paranodal regions (Vlam et al, 2011;Willison and Yuki, 2002). It has recently been suggested that disease processes targeting these regions represent a distinct group of neuropathies characterised by a continuum from conduction block to axonal degeneration, a concept which may be pivotal in understanding the pathophysiology of conditions such as MMN (Uncini and Kuwabara, 2015).…”

Zika virus infection and Guillain-Barré syndrome: a review focused on clinical and electrophysiological subtypes

“…In the absence of abnormal temporal dispersion, these findings were referred to as RCF to distinguish them from classical demyelinating features 19 24. The concept of AMAN with RCF is supported by evidence from human pathological studies and animal models which indicates that AMAN is characterised by antibody-mediated and complement-mediated dysfunction/disruption due to microstructural changes in the axolemma at the nodes of Ranvier, termed ‘nodopathy’ 25. This results in a pathophysiological continuum in AMAN from transient nerve conduction failure to axonal degeneration 25.…”

Electrically Evoked Compound Action Potential Recording in Peripheral Nerves

“…The study of peripheral nerve compound muscle action potentials and sensory nerve action potentials has lead the development of the concept of Node-opathys [45], which could be directly assessed with fitting of detailed models to ECAP recordings. The various attempts to model the peripheral nerve ECAP from a peripheral nerve future science group www.futuremedicine.com rely on different simplifying assumptions, for instance that the form of the single fiber potential is consistent across the entire population or that the biological tissue can be considered a homogeneous conductor.…”