Beecher, G and Shelly, S and Dyck, PJB and Mauermann, ML and Martinez-Thompson, JM and Berini, SE and Naddaf, E and Shouman, K and Taylor, BVM and Dyck, PJB and Engelstad, J and Howe, Benjamin M and Mills, JR and Dubey, D and Spinner, RJ and Klein, CJ, Pure motor onset and IgM-Gammopathy occurrence in multifocal acquired demyelinating sensory and motor neuropathy, Neurology, 97, (14) pp. 1-12. ISSN 0028-3878 (2021) [Refereed Article]
Objectives: To longitudinally investigate patients with multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, quantifying timing and location of sensory involvements in motor-onset patients, along with clinico-histopathological and electrophysiological findings to ascertain differences in patients with and without monoclonal gammopathy of uncertain significance (MGUS).
Methods: Patients with MADSAM neuropathy seen at Mayo Clinic and tested for monoclonal gammopathy and ganglioside antibodies, were retrospectively reviewed (January 1st, 2007-December 31st, 2018).
Results: Of 76 patients with MADSAM, 53% had pure motor, 16% pure sensory, 30% sensorimotor and 1% cranial nerve onsets. Motor-onset patients were initially diagnosed as multifocal motor neuropathy (MMN). MGUS occurred in 25% (89% IgM subtype), associating with ganglioside autoantibodies (p<0.001) and higher IgM titers (p<0.04). Median time to sensory involvements (confirmed by electrophysiology) in motor-onset patients was 18 months (range: 6-180). Compared to initial motor nerve involvements, subsequent sensory findings were within the same territory 35% (14/40), outside 20% (8/40), or both 45% (18/40). Brachial and lumbosacral plexus MRI was abnormal in 87% (34/39) and 84% (21/25), respectively, identifying hypertrophy and increased T2 signal predominantly in brachial plexus trunks (64%), divisions (69%), and cords (69%), and intrapelvic sciatic (64%) and femoral (44%) nerves. Proximal fascicular nerve biopsies (n=9) more frequently demonstrated onion-bulb pathology (p=0.001) and endoneurial inflammation (p=0.01) than distal biopsies (n=17). MRI and biopsy findings were similar amongst patient subgroups. Initial Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores were higher in patients with MGUS relative to without (p=0.02). Long-term treatment responsiveness by INCAT score reduction ≥1 or motor Neuropathy Impairment Score (mNIS) >8 point reduction occurred in 75% (49/65) irrespective of MGUS or motor-onsets. Most required ongoing immunotherapy (86%). Patients with MGUS more commonly required dual-agent immunotherapy for stability (p=0.02).
Discussion: Pure motor-onsets are the most common MADSAM presentation. Long-term follow-up, repeat electrophysiology and nerve pathology help distinguish motor-onset MADSAM from MMN. Better long-term immunotherapy responsiveness occurs in motor-onset MADSAM compared to MMN reports. Patients having MGUS commonly require dual immunotherapy.
|Item Type:||Refereed Article|
|Keywords:||intravenous immunoglobulin, controlled trial, follow up, IVIG, Polyneuropathy, Rituximab, criteria, term|
|Research Division:||Health Sciences|
|Research Group:||Sports science and exercise|
|Research Field:||Motor control|
|Objective Group:||Clinical health|
|Objective Field:||Treatment of human diseases and conditions|
|UTAS Author:||Taylor, BVM (Professor Bruce Taylor)|
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