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The early diagnosis of amyotrophic lateral sclerosis (ALS) is often difficult as not all patients meet clinical and electrophysiological criteria.1 Additionally a small per cent of patients have a divergent diagnosis, most commonly multifocal motor neuropathy (MMN) or motor-predominant multifocal acquired demyelinating sensory and motor neuropathy (MADSAM).2 Although motor conduction blocks distinguish MMN and MADSAM from ALS, it is often difficult to find these conduction abnormalities when present at the roots or plexus. Currently biomarkers to assist in the diagnosis of ALS versus MMN and MADSAM are inadequate. Specifically, GM1 (ganglioside monosialo-asialo) autoantibodies can be present in all these disorders, although typically of lower values in ALS. Recently, IgM-gammopathy was suggested to be more common in MMN (7%) compared with healthy (2%) and ALS (1%) controls.3 If true, IgM-gammopathy may forebode for an immune treatment refractory disorder as described in other IgM-gammopathy neuropathies.4
Herein, we address: (1) the occurrence of an IgM-gammopathy in MMN and MADSAM compared with ALS and (2) evaluate the immune treatment response of MMN and MADSAM IgM-monoclonal-gammopathy.
We identified 78 MADSAM, 65 MMN cases and 412 ALS patients matched in gender and age. ALS was considered in the differential diagnosis of 51% (40/78) of MADSAM and 64% (42/65) of MMN patients due to motor predominant progressive symptoms. IgM-gammopathy was significantly (p<0.001; OR estimate of 33, 95% CI) more common in MADSAM 23% (18/78) and MMN 17% (11/65) compared with ALS<1% (2/412) (figure 1). IgM-Kappa was the most …
Contributors SS, JM, CJK: study design. SS, CJK: writing the manuscript. SS, JRM, JMM-T, MMR, JM, JDT, MM, DD, SP, CJK: data collection. All co-authors: manuscript revision.
Funding The Mayo Clinic Foundation and its Center for Individualized Medicine have provided time to allow the authors to complete this work.
Disclaimer All the views expressed are those of the authors and not necessarily those of the Mayo Clinic Foundation.
Competing interests SJP: reports affiliation with Grifols, Alexion and Medimmune pharmaceuticals. He receives no personal compensation as all moneys are paid directly to Mayo Clinic; MM: reports receiving honorarium from Ackea related to TTR amyloidosis; DD Has received research support from Center of Multiple Sclerosis and Autoimmune Neurology, and Grifols pharmaceuticals. DD has consulted for UCB pharmaceuticals. All compensation for consulting activities is paid directly to Mayo Clinic; CJK reports receiving honorarium from Ackea related to TTR amyloidosis and Fabry disease. He has also been a consultant at Pfizer but received no personal compensation.
Patient consent for publication Not required.
Ethics approval Approval for this study was obtained by the Institutional Review Board at the Mayo Clinic and all patients provided written consent to participate.
Provenance and peer review Not commissioned; externally peer reviewed.
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