Pathophysiology of the Different Clinical Phenotypes of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

Abstract

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common form of autoimmune polyneuropathy. It is a chronic disease and may be monophasic, progressive or recurrent with exacerbations and incomplete remissions, causing accumulating disability. In recent years, there has been rapid progress in understanding the background of CIDP, which allowed us to distinguish specific phenotypes of this disease. This in turn allowed us to better understand the mechanism of response or non-response to various forms of therapy. On the basis of a review of the relevant literature, the authors present the current state of knowledge concerning the pathophysiology of the different clinical phenotypes of CIDP as well as ongoing research in this field, with reference to key points of immune-mediated processes involved in the background of CIDP.

Neurophysiological Hallmarks of Axonal Degeneration in CIDP Patients: A Pilot Analysis

“…Although CIDP is an acquired demyelinating disease, secondary axonal degeneration is commonly observed [ 8 ] and mainly related to therapeutic unresponsiveness [ 29 , 30 ]. Mechanisms of axonal damage are largely unknown; in the acute phase of the disease, demyelination and node/paranodal dysfunction may lead to Wallerian degeneration phenomena, while in the chronic phase the persistence of inflammatory and immune attack may lead to progressive degeneration of nerve fibers [ 31 ].…”

“…Fourth, we included in the analysis the extensor digitorum brevis muscle that may present para-physiological abnormalities even in HCs; however, we needed to apply the same electrophysiological protocol for both upper and lower limbs. Finally, we are aware of the different clinical response and pathophysiological mechanisms (inflammatory, demyelinating or dysimmune) in CIDP variants and after other therapeutic strategies than IVIg or ScIg, such as corticosteroids, plasma exchange or rituximab [ 31 ], that might have a different impact on axonal degeneration and produce different results.…”

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

“…For the action potential initiation, the axon initial segment (AIS) plays a crucial role, with several factors modulating excitability, such as localization, anatomy and channels. Due to the postulated importance of dysfunction in this area for the pathophysiology of atypical forms of CIDP, the structure of the AIS is presented [ 7 , 8 ].…”

“…A detailed review of current findings on myelin sheath structure in NOR and PNJ has been presented in another study [ 8 ]; now, the authors intend to discuss JXP in detail, which could be essential for the development of atypical forms of peripheral nervous system pathologies.…”

“…The AIS is a dynamic structure, with changing geometry, usually located just after the neuron hillock ( Figure 3 ). It has several microscopic morphological features: bundles of 3–10 microtubules called fascicles, a dense layer of finely granular material undercoating the plasma membrane, and dispersed ribosomes [ 8 , 9 , 10 ]. It is characterized by the lowest threshold for action potentials within neurons due to the high density of voltage-gated Na+ (Nav) channels (for review, Debanne et al, 2011 [ 11 ]).…”