Available online 10 November 2022

Abstract

Neuropathy with anti-myelin-associated glycoprotein (MAG) antibodies commonly demonstrates distal-dominant prolongation of nerve conduction. However, recent electrophysiological studies have shown that distal motor demyelination is not always a distinct feature. We aimed to elucidate whether the longitudinal progression of nerve impairment occurs in a distal-dominant manner. Seven patients with neuropathy with anti-MAG antibodies were enrolled. Sequential nerve conduction studies revealed nerve conduction reduction only at the wrist segment in the median nerve of the patients, but not in the ulnar nerve. Median nerve entrapment at the wrist may play a role in longitudinal disease progression in neuropathy with anti-MAG antibodies.

Introduction

Neuropathy with anti-myelin-associated glycoprotein (MAG) antibodies is the most common form of immunoglobulin M (IgM) neuropathy and is typically characterized by slowly progressive distal paresthesia [1]. Most nerve conduction studies (NCSs) have demonstrated prolonged distal motor and sensory latencies, indicative of distal demyelination [2]. Recent cross-sectional NCSs revealed that distal-dominant motor demyelination is not necessarily a distinctive feature of neuropathy with anti-MAG antibodies [3]. A more recent study evaluating longitudinal NCSs showed that terminal latency index (TLI, used to demonstrate distal predominant nerve conduction slows) was decreased only in the median nerve and rather increased in the ulnar nerve over the disease progression [4]. Although these results may be interpreted as the presence of progressive disproportionate distal conduction slowing only in the median nerve, statistical analysis was not performed in this regard.

In the present study, we aimed to elucidate whether there is a distal-dominant presence of disease progression in NCSs of patients with the neuropathy. The longitudinal change in nerve conduction time (NCT) or motor conduction velocity (MCV) was analyzed. To exclude any treatment effects on the NCSs, we first evaluated NCSs performed during observation periods with stable serum IgM levels, as anti-MAG IgM is a direct pathogen to the peripheral nerves [5], [6], and a decrease in its levels is associated with clinical improvement in the disease [7]. We also evaluated the association between longitudinal changes in serum IgM levels and TL or MCV in both nerve segments.

Section snippetsMaterials and methods

The study subjects were patients admitted to the Department of Neurology at Tokyo Medical and Dental University Hospital from 2011 to 2019. Ninety-five inpatients with neuropathy were analyzed by chart review; of these, 11 patients had IgM monoclonal gammopathy of undetermined significance. The anti-MAG antibody in these 11 patients was evaluated by both ELISA and western blotting (WB) (Athena Diagnostics, Marlborough, MA, USA) and seven of the 11 patients were diagnosed with neuropathy with

Results

Participants’ clinical data are presented in Table 1. Median TLI in the median nerve was 0.21 while median TLI in the ulnar nerve was 0.33. NCS finding during period of stable serum IgM levels in each patient was described in Online material Table S1. Longitudinal NCSs conducted during periods of stable serum IgM levels revealed that TL in the median nerve was significantly worse than conduction in the forearm segment (Fig. 1A; P = 0.047). Contrarily, ΔTLs of the ulnar nerve were not

Discussion

Our study demonstrated that the longitudinal progression of nerve impairment varied between nerves: a distal-predominant progression was noted in the median nerve while such trend was not observed in the ulnar nerve. Disproportionate prolongation of the median TL has been reported in cross-sectional studies [3], [4], [11], in which entrapment of the nerves was speculated to be associated with such neuropathic conduction impairment. However, in our study, we first confirmed distinct progression

Data availability statement

The data are not publicly available due to privacy or ethical restrictions.

Funding

This work was partly supported by the Ministry of Health, Labour, and Welfare of Japan [grant numbers H29-Nanchitou (Nan)-Ippan-043; TY].

Author contributions

MO designed the study, acquired and analyzed the data, and wrote the draft. NS designed the study, revised and finalized the manuscript, and supervised the research. TK acquired and interpretated the data, as well as revised the manuscript. TY supervised the study and revised the manuscript.

Disclosure of interest

The authors declare that they have no competing interest.

Acknowledgments

The authors would like to thank the members of the Department of Neurology and Neurological Science at Tokyo Medical and Dental University Hospital. The authors are grateful to the patients with anti-MAG neuropathy and their family members for providing important clinical information.

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