Conduction block in immune‐mediated neuropathy: paranodopathy versus axonopathy

European Journal of Neurology - Tập 26 Số 8 - Trang 1121-1129 - 2019
Nidhi Garg1,2, SB Park1, James Howells1, Steve Vucic3, Con Yiannikas4, E. K. Mathey1, Tuan Nghia Nguyen1, Yu‐ichi Noto1, Michael Barnett1,2, Arun V. Krishnan5, Judith Spies1,2, Hugh Bostock6,7, J. Pollard1,2, Matthew C. Kiernan1,2
1Brain and Mind Centre, Sydney Medical School, University of Sydney, Sydney, NSW, Australia
2Department of Neurology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
3Departments of Neurology and Neurophysiology, Westmead Hospital, University of Sydney, Sydney, NSW, Australia
4Department of Neurology, Concord and Royal North Shore Hospitals, University of Sydney, Sydney, NSW, Australia
5Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia
6Institute of Neurology, University College London, London, UK
7MRC Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, UK

Tóm tắt

Background and purposeConduction 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).MethodsA multimodal approach was used, incorporating clinical phenotyping, neurophysiology, immunohistochemistry and structural assessments.ResultsOf 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.ConclusionsThe 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.

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European Journal of Neurology

Tập 26 Số 8

1121-1129

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