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Disease Progression in CMT related to MPZ Mutations: A Longitudinal Study. Annals of neurology Fridman, V., Sillau, S., Bockhorst, J., Smith, K., Moroni, I., Pagliano, E., Pisciotta, C., Piscosquito, G., Laura, M., Muntoni, F., Bacon, C., Feely, S., Grider, T., Gutmann, L., Shy, R., Wilcox, J., Herrmann, D. N., Li, J., Ramchandren, S., Sumner, C. J., Lloyd, T. E., Day, J., Siskind, C. E., Yum, S. W., Sadjadi, R., Finkel, R. S., Scherer, S. S., Pareyson, D., Reilly, M. M., Shy, M. E., Inherited Neuropathies Consortium-Rare Diseases Clinical Research Network (INC-RDCRN), Fridman, V., Sillau, S., Acsadi, G., Bacon, C., Dooley, K., Burns, J., Day, J., Feely, S., Finkel, R. S., Grider, T., Gutmann, L., Herrmann, D. N., Volpenhein, C., Bockhorst, J., Laura, M., Lewis, R. A., Li, J., Lloyd, T. E., Moroni, I., Muntoni, F., Pagliano, E., Pareyson, D., Pisciotta, C., Piscosquito, G., Ramchandren, S., Saporta, M., Sadjadi, R., Shy, R. R., Siskind, C. E., Sumner, C. J., Walk, D., Yum, S. W., Zuchner, S., Scherer, S. S., Reilly, M. M., Shy, M. E. 2022

Abstract

OBJECTIVE: The paucity of longitudinal natural history studies in MPZ-neuropathy remains a barrier to clinical trials. We have completed a longitudinal natural history study in patients with MPZ-neuropathies across 13 sites of the Inherited Neuropathy Consortium.METHODS: Change in Charcot Marie Tooth Examination scores (CMTES) and Rasch modified CMTES (CMTES-R) scores were evaluated using longitudinal regression over a 5-year period in subjects with MPZ-neuropathy. Data from 139 patients with MPZ-neuropathy were examined.RESULTS: The average baseline CMTES and CMTES-R scores were 10.84 (SD 6.0, range 0 - 28) and 14.60 (SD=7.56, range 0 - 32), respectively. A mixed regression model showed significant change in CMTES at years 2-5 [mean change from baseline of 0.87 points at 2years (p=0.008)]. Subgroup analysis revealed greater change in CMTES at 2years in subjects with axonal as compared to demyelinating neuropathy [mean change of 1.30 points, (p=0.016) versus 0.06 points, (p=0.889)]. Patients with a moderate baseline neuropathy severity also showed more notable change, by estimate, than those with mild or severe neuropathy [mean 2 year change of 1.14 for baseline CMTES 8-14 (p=0.025), versus -0.03 for baseline CMTES 0-7 (p=0.958) and 0.25 for baseline CMTES =15 (p=0.6897)]. The progression in patients harboring specific MPZ mutations was highly variable.INTERPRETATION: CMTES scores are sensitive to change over time in adult patients with axonal but not demyelinating forms of MPZ-neuropathy. Change in CMTES was greatest in patients with moderate baseline disease severity. These findings will inform future clinical trials of MPZ-neuropathies. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/ana.26518

View details for PubMedID 36203352