ASSESSMENT OF DISTAL LOWER LIMB STRENGTH IN CHARCOT-MARIE-TOOTH DISEASE (CMT) TYPE 1A

A. Alangary^1,2, J. Morrow¹, M. Dudziec¹, A. Hiscock¹, G. Ramdharry¹, M. M Reilly¹, M. Laura¹

Background: Clinical trials in Charcot Marie Tooth disease (CMT) need highly responsive outcome measures that can detect changes in this slowly progressive disorder. The current management is symptomatic in order to correct or prevent deformities and improve patient mobility and quality of life. In the last decade, a number of clinical trials were performed to evaluate the safety and the efficacy of ascorbic acid on the progression of CMT1A. Although the trials proved the safety of high dose ascorbic acid, they failed to show its efficacy partly due to low responsiveness of the outcome measures used.

Purpose: This study provides an evaluation of four different muscle testing techniques to assess whether they have sufficient sensitivity to detect change in plantar flexor and dorsiflexor muscle strength over 12 months. Secondary aims were to assess correlation between measurements techniques, and to define inter-rate and intra-rate reliability of quantitative ankle strength measurement. Techniques used to measure muscle strength of lower limb distal muscles are: isometric and isokinetic muscle strength, MRC strength score, hand-held dynamometry.

Methods: Twenty participants with genetically confirmed CMT type 1A were assessed 3 times over 12 months using: isometric (ISOM) and isokinetic (ISOK) muscle strength, MRC strength score, hand-held dynamometry (IHHD) with immobilizer. The Wilcoxon Signed rank test was used to determine the level of change over 12 months. A Spearman test was used to determine the correlation between measurement techniques. Intraclass correlation (ICC) and Bland Altman plots were used to test inter-rater and intra-rater reliability of isometric and isokinetic dynamometry.

Results: No significant longitudinal changes over 12 months were detected for any of the measures (p > 0.05). Correlation among all techniques varied from very strong to moderate (0.50 ≥ R ≥ 1.00). A strong inter-rater and intra-rater reliability were detected for ISOK and ISOM measures of plantar flexion (0.75 ≥ ICC ≥ 0.95).

Conclusion(s): The findings did not indicate significant changes in the different measures from baseline to 12 months. This confirms previous results observed in the ascorbic acid trials where some of the techniques (manual muscle testing and IHHD) were applied. Correlation of a gold standard measure; isokinetic dynamometer; with more basic measures; manual muscle test and hand-held dynamometer; supports the use of these measures interchangeably particularly in clinical settings, while some techniques are more practical than others. The results presented also showed that intra-rater reliability was better than inter-rater reliability.  This means that results are consistent for specific raters. This would help provide greater reliability and reduce operator bias for studies where only one-rater is conducting the test. Limitations can be mainly noted in the small population measured for this study. This means that the results cannot be applied to a general population. Further studies analyzing a larger cohort of patients and more number of raters would be recommended, especially for reliability studies. Adding matching controls to define the values detected by each technique is also recommended.

Implications: The results of this study can serve as basis for improvements in the practice for testing muscle strength among individuals with CMT clinically and for research purposes.

Funding, acknowledgements: Alangary is funded by  SaudiArabian Cultural Bureau in UK. This research was supported by the NIHR UCLH Biomedical Research Centre.

Keywords: Charcot Marie Tooth disease, Muscle strength, Reliability

Topic: Neurology

Did this work require ethics approval? Yes

Institution: NHS

Committee: Research Ethics Committee

Ethics number: 11/LO/1230