Associate Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Chin reports no financial relationships relevant to this field of study.

SYNOPSIS: Most patients with anti-MAG neuropathy complain of painful paresthesias or dysesthesias, but unlike diabetic neuropathy, these symptoms are not severe and do not affect quality of life as much as motor weakness.

SOURCE: Rajabally YA, Delmont E, Hiew FL, et al. Prevalence, correlates and impact of pain and cramps in anti-MAG neuropathy: A multicenter European study. Eur J Neurol 2018;25:135-141.

Anti-MAG neuropathy is associated with an IgM monoclonal gammopathy and manifests typically as a slowly progressive, symmetric, predominantly sensory neuropathy affecting distal lower more than upper extremities. Sensory loss, involving all modalities, typically occurs earlier than weakness, which eventually develops in most patients in the distal extremities. Unlike chronic inflammatory demyelinating polyneuropathy, proximal strength typically is spared. Hand tremor may develop later in the disease course. Demyelinating features are noted by electromyography/nerve conduction studies in more than 90% of patients, particularly severely prolonged distal motor latencies and severe conduction velocity slowing, while conduction block is uncommon. Widening of myelin lamellae can be noted on ultrastructural examination of the nerve. No significant benefit from plasmapheresis, steroids, intravenous immunoglobulin, chlorambucil, or other immunosuppressive agents has been found. Rituximab has been reported to be beneficial¹; however, clinical trials have been negative. Longer duration studies with adequate outcome measures may be necessary.²

In this study, pain of any type was reported in 80% of clinically stable patients with anti-MAG neuropathy. Paresthesiae/dysesthesiae were the most common pain subtypes. Cramps involving the lower extremities were reported in 64% (35/55) of patients, with concomitant upper extremity involvement in 29% (10/35). Correlation analyses showed multiple positive associations between pain severity and cramp severity, location, and frequency with various measures of quality of life and disability.

COMMENTARY

Pain typically is associated more with diabetic and amyloid neuropathies because of small fiber sensory involvement. It also is reported with demyelinating neuropathy, such as Guillain-Barré syndrome, presumably because of direct inflammation of nerve roots. Rajabally et al highlighted the fact that pain also may be a prominent but under-recognized feature of inflammatory, immune-mediated neuropathies such as anti-MAG neuropathy, in particular.³

In this study, dysesthesias/paresthesias were present in more than 70% of patients. Although these symptoms generally are not considered painful by physicians or patients, they were associated independently with some measures of fatigue and a poorer quality of life. As would be expected, other types of pain (such as burning, pressing, or paroxysmal pain) also correlated positively with other quality-of-life metrics.

Cramps were described in the lower extremities more frequently, but hand involvement (specifically the severity and frequency of cramps) was most relevant to disability and quality of life. A beneficial role for physiotherapy was suggested by the finding of inverse correlations between: 1) cramp severity and level of physiotherapy, and 2) cramps interfering with sleep and level of physiotherapy.

This article raises awareness of the high frequency of pain and cramps that might affect quality of life in anti-MAG neuropathy. Non-drug treatments, such as physiotherapy for cramps, may be helpful and should not be neglected. Any treatment interventions will need to affect quality of life measures positively to be meaningful for the patient.

REFERENCES

1. Svahn J, Petiot P, Antoine JC, et al. Anti-MAG antibodies in 202 patients: Clinicopathological and therapeutic features. J Neurol Neurosurg Psychiatry 2017; Oct. 25. doi: 10.1136/jnnp-2017-316715. [Epub ahead of print].
2. Pruppers MH, Merkies IS, Notermans NC. Recent advances in outcome measures in IgM-anti-MAG+ neuropathies. Curr Opin Neurol 2015;28:486-493.
3. Pazzaglia C, Briani C, Nobile-Orazio E, et al. Occurrence and characterization of pain in immune-mediated neuropathies: A multicenter prospective study. Eur J Neurol 2011;18:177-183.