A longitudinal study of CMT1A using Rasch analysis based CMT neuropathy and examination scores

Abstract

ObjectiveTo evaluate the sensitivity of Rasch analysis-based, weighted Charcot-Marie-Tooth Neuropathy and Examination Scores (CMTNS-R and CMTES-R) to clinical progression in patients with Charcot-Marie-Tooth disease type 1A (CMT1A).MethodsPatients with CMT1A from 18 sites of the Inherited Neuropathies Consortium were evaluated between 2009 and 2018. Weighted CMTNS and CMTES modified category responses were developed with Rasch analysis of the standard scores. Change from baseline for CMTNS-R and CMTES-R was estimated with longitudinal regression models.ResultsBaseline CMTNS-R and CMTES-R scores were available for 517 and 1,177 participants, respectively. Mean ± SD age of participants with available CMTES-R scores was 41 ± 18 (range 4–87) years, and 56% were female. Follow-up CMTES-R assessments at 1, 2, and 3 years were available for 377, 321, and 244 patients. A mixed regression model showed significant change in CMTES-R score at years 2 through 6 compared to baseline (mean change from baseline 0.59 points at 2 years, p = 0.0004, n = 321). Compared to the original CMTES, the CMTES-R revealed a 55% improvement in the standardized response mean (mean change/SD change) at 2 years (0.17 vs 0.11). Change in CMTES-R at 2 years was greatest in mildly to moderately affected patients (1.48-point mean change, 95% confidence interval 0.99–1.97, p < 0.0001, for baseline CMTES-R score 0–9).ConclusionThe CMTES-R demonstrates change over time in patients with CMT1A and is more sensitive than the original CMTES. The CMTES-R was most sensitive to change in patients with mild to moderate baseline disease severity and failed to capture progression in patients with severe CMT1A.ClinicalTrials.gov identifierNCT01193075.

Rate of Changes in CMT Neuropathy and Examination Scores in Japanese Adult CMT1A Patients

“…The mean observational period did not differ between the two groups (younger group: 4.7 ± 1.9 years, and older group: 5.2 ± 1.9 years, p = 0.74). Because Fridman et al showed that CMTES-R was sensitive to change in patients diagnosed as mild to moderate but not severe ( 15 ), we examined the rate of change between the two groups after excluding patients whose initial CMTES-R was over 19. As a result, a total of 31 patients were evaluated (11 patients were in the younger group, and 20 patients were in the older group), and there was no significant difference in the annual change of CMTES-R between the two groups (younger group: 1.1 ± 1.0, and older group: 0.9 ± 1.1, p = 0.68).…”

“…Clinical outcome measures for CMT including the CMT Neuropathy Score (CMTNS, version 2), Rasch-modified CMTNS (CMTNS-R), CMT Examination Score (CMTES), and Rasch-modified CMTES (CMTES-R) were evaluated by trained investigators ( 13 – 15 ). The most recent data were used for analysis of the current status.…”

“…The most recent data were used for analysis of the current status. The disease severity based on CMTES-R was classified into three groups: mild 0-9, moderate 10-18, and severe = or >19 (15). Considering that a previous report suggested that motor decline in CMT1A patients accelerated after 50 years of age (12), patients were divided into three groups according to their current age and age at diagnosis of CMT: (1) patients under 50 years of age, (2) patients over 50 years of age but diagnosed before 50, and (3) patients diagnosed after 50 years of age.…”

“…The distribution of CMTNS-R and CMTES-R were shown in Figure 1. When the patients were classified into three subgroups based on CMTES-R (15), eight patients (17%) were classified as mild (CMTES-R, 0-9), 26 patients (57%) as moderate (10)(11)(12)(13)(14)(15)(16)(17)(18), and 11 patients (24%) as severe (> or = 19). Regarding the family history, 10 patients (22%) had relatives already diagnosed with CMT by genetic testing and visited the hospital based on their recommendation, and 9 patients (20%) had relatives who were secondarily suspected of having CMT.…”

Humans: the ultimate animal models

“…7 In recent years the term CMT is increasingly used to include classical CMT with motor and sensory involvement but also the related disorders, hereditary motor neuropathy (HMN), a pure motor or motor predominant form, and hereditary sensory neuropathy (HSN), a pure sensory or sensory predominant form (figure 1). 2 8 The frequency of subtypes varies in different populations especially in populations with a high rate of consanguinity where AR forms are more common.…”