[Axonal involvement in dysimmune neuropathies]

Abstract

Dysimmune neuropathies, in common with other neuropathies, comprise an axonal impairment that it is primary or secondary to a demyelinating process. We consider here axonal impairment in the course of certain dysimmune neuropathies, such as the Guillain Barré syndrome, chronic inflammatory demyelinating polyradiculoneuritis and multiple conduction block neuropathy. We mention the fact that it is not always easy to evidence the axonal impairment, its severity and its potential for regeneration. The mechanisms of the axonal lesions stem essentially from the special and tight bonds between the axon and the Schwann cell, which in the central central nervous system are mirrored by the bonds between axons and oligodendrocytes. Indeed, myelinating Schwann cells modify the properties of the axon in the normal peripheral nervous system, and abnormal Schwann cells induce pathological modifications. The periods of appearance of the axonal impairment are nevertheless quite variable depending on the type of the dysimmune neuropathy: acute or chronic. Some Guillain-Barré syndromes may be distinguished by a severe axonal impairment, now well documented and referred to as AMSAN and AMAN. Various mechanisms of axonal impairment are discussed. The bond between axon and myelin means that any pathological process in Schwann cells leads to axonal impairment, with inflammatory processes having a direct impact on the axon: mechanism of typical 'by-stander effect', repressive role of endoneurial edema, direct dysimmune attack on axonal epitopes on the corresponding axolemma, especially on the GM1 gangliosides, intra-axonal accumulation of sodium and calcium due to disruption the voltage-dependent sodium/potassium ion channels, slow retrograde progression to anterior horn neurons and possibly also to posterior spinal cords. The treatment of the axonal impairment is not straightforward; it is based, in a first instance, on the direct relation between the severity of the demyelinating lesions and the axonal impairment. For the acute forms of typical Guillain-Barré syndrome, the value of plasma exchanges and intravenous immunoglobulins has demonstrated in double blind, randomized trials. For the chronic demyelinating inflammatory polyradiculoneuritis, corticotherapy, along with plasma exchange and the immunoglobulins, have also been shown to be effective. Immunosuppressor treatment has benefits, but it is hard to prove objectively. It is generally recognized that it is only useful if applied for a period of weeks, although this is currently a matter of debate. Other therapeutic options have been discussed and proposed, although to date there is a lack of proven efficiency: such treatments include neuroprotective agents and drugs which block sodium/potassium ion channels. It is increasingly difficult to propose new treatments with validated efficiency, due to the small number of patients presenting dysimmune neuropathies of the type discussed here that are both typical and suitable for inclusion in medium to long term studies.