Immune-Mediated Neuropathies: Pathophysiology and Management

Abstract

Dysfunction of the immune system can result in damage of the peripheral nervous system. The immunological mechanisms, which include macrophage infiltration, inflammation and proliferation of Schwann cells, result in variable degrees of demyelination and axonal degeneration. Aetiology is diverse and, in some cases, may be precipitated by infection. Various animal models have contributed and helped to elucidate the pathophysiological mechanisms in acute and chronic inflammatory polyradiculoneuropathies (Guillain-Barre Syndrome and chronic inflammatory demyelinating polyradiculoneuropathy, respectively). The presence of specific anti-glycoconjugate antibodies indicates an underlying process of molecular mimicry and sometimes assists in the classification of these disorders, which often merely supports the clinical diagnosis. Now, the electrophysiological presence of conduction blocks is another important factor in characterizing another subgroup of treatable motor neuropathies (multifocal motor neuropathy with conduction block), which is distinct from Lewis-Sumner syndrome (multifocal acquired demyelinating sensory and motor neuropathy) in its response to treatment modalities as well as electrophysiological features. Furthermore, paraneoplastic neuropathies are also immune-mediated and are the result of an immune reaction to tumour cells that express onconeural antigens and mimic molecules expressed on the surface of neurons. The detection of specific paraneoplastic antibodies often assists the clinician in the investigation of an underlying, sometimes specific, malignancy. This review aims to discuss the immunological and pathophysiological mechanisms that are thought to be crucial in the aetiology of dysimmune neuropathies as well as their individual electrophysiological characteristics, their laboratory features and existing treatment options. Here, we aim to present a balance of discussion from these diverse angles that may be helpful in categorizing disease and establishing prognosis.

Keywords: autoantibodies; demyelination; immunity; inflammation; neuropathy.

Figure 1

(A) A typical motor nerve is shown here. The nerve axon is covered by Schwann cells, which form the myelin sheath. This myelin sheath is discontinuous and contains gaps called as the node of Ranvier. The action potential travels from node to node. (B) In AIDP, the myelin sheath is affected; in AMAN and AMSAN, the axon is affected, while in MFS, the neuromuscular junction area is affected. Abbreviations: APC: antigen-presenting cell; MFS: Miller–Fisher syndrome.

Figure 2

Immunopathological mechanisms involved in Guillain–Barre syndrome. A schematic diagram shows the various immunopathological mechanisms observed in Guillain–Barre syndrome. Preceding infection is usually observed, and this can involve various bacterial, viral and fungal pathogens. The subsequent activation of plasma cells and the molecular mimicry involving gangliosides, leading to destruction of myelin and axons, are shown. Proinflammatory cytokines too play a role in disease pathogenesis. The complement system is activated and is significantly involved in disease pathogenesis. Abbreviations: HIV: Human immunodeficiency virus; VZ: Varicella Zoster virus; MAC: Membrane attack complex.