Pathology of Initial Axon Segments in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Related Disorders

Abstract

The diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is based on a combination of clinical, electrodiagnostic and laboratory features. The different entities of the disease include chronic immune sensory polyradiculopathy (CISP) and autoimmune nodopathies. It is debatable whether CIDP occurring in the course of other conditions, i.e., monoclonal IgG or IgA gammopathy, should be treated as a separate disease entity from idiopathic CIDP. This study aims to evaluate the molecular differences of the nodes of Ranvier and the initial axon segment (AIS) and juxtaparanode region (JXP) as the potential cause of phenotypic variation of CIDP while also seeking new pathomechanisms since JXP is sequestered behind the paranode and autoantibodies may not access the site easily. The authors initially present the structure of the different parts of the neuron and its functional significance, then discuss the problem of whether damage to the juxtaparanodal region, Schwann cells and axons could cause CIDP or if these damages should be separated as separate disease entities. In particular, AIS’s importance for modulating neural excitability and carrying out transport along the axon is highlighted. The disclosure of specific pathomechanisms, including novel target antigens, in the heterogeneous CIDP syndrome is important for diagnosing and treating these patients.