CIDP – the relevance of recent advances in Schwann cell/axonal neurobiology

Abstract

Early pathological studies in patients with acute and chronic inflammatory demyelinating neuropathies, and the animal model experimental autoimmune neuritis (EAN) showed similarities in the process of demyelination. These studies focused on compact myelin proteins and peptides as targets of immune attack in Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and EAN. However, serological studies in patients with subsets of GBS highlighted the importance of gangliosides -glycolipids enriched in non-compact Schwann cell regions and the node, paranodal, and internodal axolemma. In the acute motor axonal neuropathy (AMAN) rabbit model, antibodies to the ganglioside GM1 bind in the nodal region, impair Na channel clustering and disturb Schwann cell/axon organisation. Schwann cell neurobiological studies now highlight the importance of adhesion molecules, including neurofascins, gliomedin, contactins, and NrCAM to Schwann cell/axon integrity. Changes to nodal fine structure by immune responses against such molecules may provide a mechanism for reversible conduction failure or block. Recovery of patients with CIDP or multifocal motor neuropathy (MMN) following treatment may sometimes be better explained by reversal of conduction failure than remyelination or regeneration. This review considers the importance of the intricate molecular arrangements at the nodal and paranodal regions in inflammatory neuropathies such as CIDP. Early images of compact myelin stripping and phagocytosis, may have diverted the research focus away from these vital non-compact myelin Schwann cell areas.

Two years’ long-term follow up in chronic inflammatory demyelinating polyradiculoneuropathy: efficacy of intravenous immunoglobulin treatment

“…In line with further studies these effects are suspected to act on humoral and cellular levels and directly at myelin sheath levels [van Doorn et al 1990;Frank et al 1992;van Engelen et al 1994;Miyagi et al 1997;Vucic et al 2007]. Other studies suggest that the main target for immunomodulatory effects might be within the nodal or paranodal regions because clinical improvement within days after IVIg treatment could otherwise not be explained by rapid remyelination [Dalakas and Medscape, 2011;Pollard and Armati, 2011;Dalakas, 2015]. INCAT disability score was evaluated for the upper extremity.…”

Epidemiology of Chronic Inflammatory Demyelinating Polyneuropathy Abroad and in Russia

“…ХВДП -аутоиммунное заболевание, характеризу-ющееся поражением миелиновой оболочки перифе-рических нервов [2][3][4][5][6][7][8][9][10]. На долю ХВДП приходится примерно 20-50 % недиагностированных полиневро-патий [11,12].…”

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Нервно-мышечные Б О Л Е З Н ИЛекции и обзоры 10 Введение Хронические иммуноопосредованные демиели-низирующие полиневропатии включают в себя клас-сическую хроническую воспалительную демиели-низирующую полиневропатию (ХВДП), дистальную сен сорную полиневропатию, приобретенную мульти-фокальную демиелинизирующую сенсорно-моторную невропатию (синдром Льюиса-Самнера) и мультифо-кальную моторную нейропатию [1].ХВДП -аутоиммунное заболевание, характеризу-ющееся поражением миелиновой оболочки перифе-рических нервов [2][3][4][5][6][7][8][9][10]. На долю ХВДП приходится примерно 20-50 % недиагностированных полиневро-патий [11,12].

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“…На долю ХВДП приходится примерно 20-50 % недиагностированных полиневро-патий [11,12]. ХВДП является приобретенной невро-патией, в развитии которой большое значение имеют изменения иммунологической реактивности организ-ма и возникновение аутоиммунного процесса [3,8,[13][14][15][16][17][18][19][20]. До сих пор специфические антигены, прово-цирующие процесс демиелинизации, не идентифици-рованы.…”

Subcutaneous immunoglobulins in the treatment of chronic immune-mediated neuropathies

“…The heterogeneous antibody profiles in the different inflammatory conditions target different functional components of peripheral nerves such as Schwann cells, myelin, nodes of Ranvier and axons, which lead to alterations of nodal structure and alterations in the distribution of ion channels, and culminates in impaired conduction or disturbed axonal function [Berger et al 2013;Boerio et al 2010;Dyck et al 2015;Franssen and Straver, 2013;Kiernan et al 2000;Lin et al 2011;Pollard and Armati, 2011;Yuki and Hartung, 2012]. In this context, well known pathologic changes such as demyelination or destruction of axons, as well as autoantibody-induced alterations of nodal, paranodal and juxtaparanodal regions lead to a functional impairment [Dalakas, 2015;Peltier and Donofrio, 2012].…”