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

Abstract

Objective: To 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).

Methods: Patients 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.

Results: Baseline 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).

Conclusion: The 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.

Clinicaltrialsgov identifier: NCT01193075.

Figure 1. Change in CMTES-R score over 6 years

Change in Rasch analysis-adjusted Charcot-Marie-Tooth Examination Scores (CMTES-R) from baseline over a 6-year period. CMTES-R scores increase gradually over subsequent years with relatively linear progression. Linear model estimates a change in mean CMTES-R score of 0.59 (95% confidence interval [CI] 0.44–0.74, p < 0.0001) over 2 years.

Figure 2. Change in CMTES score over 6 years

Change in Charcot-Marie-Tooth Examination Score (CMTES) from baseline over a 6-year period. CMTES scores increase gradually over subsequent years with relatively linear progression. CI = confidence interval.

Figure 3. Influence of baseline disease severity on change in CMTES-R score (mixed model regression)

Categorical model showing change in Rasch-modified Charcot-Marie-Tooth Examination Score (CMTES-R) based on disease severity at baseline over a 6-year period. Red indicates mild (CMTES-R score 0–9); green, moderate (CMTES-R score 10–18); and blue, severe (CMTES-R score >19). Bars are 95% confidence intervals (CIs). Mildly and moderately affected patients show more disease progression than severely affected patients. SRM = standardized response mean.

Figure 4. Change in CMTNS-R score over 4 years

Categorical model showing change in Rasch-modified Charcot-Marie-Tooth Examination Scores (CMTNS-R) from baseline over a 4-year period. CMTNS-R scores increase over subsequent years.

Figure 5. Responsiveness to change of individual CMTES items at 2 years

Change in individual Charcot-Marie-Tooth Examination Score (CMTES) items over a 2-year period. Pinprick sensibility and arm strength were least responsive.