Premium
Conduction block in immune‐mediated neuropathy: paranodopathy versus axonopathy
Author(s) -
Garg N.,
Park S. B.,
Howells J.,
Vucic S.,
Yiannikas C.,
Mathey E. K.,
Nguyen T.,
Noto Y.,
Barnett M. H.,
Krishnan A. V.,
Spies J.,
Bostock H.,
Pollard J. D.,
Kiernan M. C.
Publication year - 2019
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.13953
Subject(s) - mismatch negativity , multifocal motor neuropathy , medicine , chronic inflammatory demyelinating polyneuropathy , polyradiculoneuropathy , pathophysiology , polyneuropathy , nerve conduction , node of ranvier , cardiology , neuroscience , antibody , central nervous system , immunology , guillain barre syndrome , myelin , electroencephalography , psychiatry , biology
Background and purpose Conduction block is a pathognomonic feature of immune‐mediated neuropathies. The aim of this study was to advance understanding of pathophysiology and conduction block in chronic inflammatory demyelinating polyneuropathy ( CIDP ) and multifocal motor neuropathy ( MMN ). Methods A multimodal approach was used, incorporating clinical phenotyping, neurophysiology, immunohistochemistry and structural assessments. Results Of 49 CIDP and 14 MMN patients, 25% and 79% had median nerve forearm block, respectively. Clinical scores were similar in CIDP patients with and without block. CIDP patients with median nerve block demonstrated markedly elevated thresholds and greater threshold changes in threshold electrotonus, whilst those without did not differ from healthy controls in electrotonus parameters. In contrast, MMN patients exhibited marked increases in superexcitability. Nerve size was similar in both CIDP groups at the site of axonal excitability. However, CIDP patients with block demonstrated more frequent paranodal serum binding to teased rat nerve fibres. In keeping with these findings, mathematical modelling of nerve excitability recordings in CIDP patients with block support the role of paranodal dysfunction and enhanced leakage of current between the node and internode. In contrast, changes in MMN probably resulted from a reduction in ion channel density along axons. Conclusions The underlying pathologies in CIDP and MMN are distinct. Conduction block in CIDP is associated with paranodal dysfunction which may be antibody‐mediated in a subset of patients. In contrast, MMN is characterized by channel dysfunction downstream from the site of block.