Fridman, Vera;
Sillau, Stefan;
Bockhorst, Jacob;
Smith, Kaitlin;
Moroni, Isabella;
Pagliano, Emanuela;
Pisciotta, Chiara;
... Inherited Neuropathies Consortium-Rare Diseases Clinical Researc; + view all
(2023)
Disease Progression in CMT related to MPZ Mutations: A Longitudinal Study.
Annals of Neurology
, 93
(3)
pp. 563-576.
10.1002/ana.26518.
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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 2 years (p=0.008)]. Subgroup analysis revealed greater change in CMTES at 2 years 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.
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