Pathogenic mechanisms in inflammatory and paraproteinaemic peripheral neuropathies

This review summarizes the major recent developments in understanding of pathogenic mechanisms in inflammatory and paraproteinaemic neuropathies.

In the inflammatory neuropathies, there has been a particular focus on antibody-mediated disease affecting the nodal/paranodal regions. Disruption of electrical integrity at these sites on the axonal membrane can cause conduction block without other electrophysiological features of demyelination, which has led to calls for a revision in the classification of axonal versus demyelinating neuropathies to include the new category of 'nodo-paranodopathies'. There has likewise been an expansion in knowledge regarding the diverse disease mechanisms of the paraproteinaemic neuropathies. These also include disease mediated by antibodies binding to peripheral nerve antigens, but additionally encompass immune complex deposition, cellular infiltration, and cytokine production.

An increasing range of laboratory tests for antibodies, growth factors, and cytokines are proposed as useful in the management of inflammatory and paraproteinaemic neuropathies. Furthermore, the traditional electrodiagnostic classification into axonal and demyelinating neuropathy may not always accurately reflect the underlying disease process. Understanding how these paraclinical tests aid in identifying the underlying disease has relevance to the practising clinician both in terms of diagnosis and for the selection of rational treatments.