MRI of tibialis anterior skeletal muscle in myotonic dystrophy type 1.

OBJECTIVE: The aim of this study was to evaluate whether magnetic resonance imaging (MRI) can be used as a noninvasive approach to assessment of disease severity and muscle damage in Myotonic Dystrophy type 1 (DM1). METHODS: The MRI findings in legs of 41 patients with DM1 were evaluated with respect to the tibialis anterior (TA) skeletal muscle impairment. Magnetic resonance imaging findings were compared with TA strength measurements obtained by quantitative manual testing, duration of the disease and with the length of the CTG repeats. RESULTS: Muscle MRI abnormalities were observed in 80% of DM1 patients, ranging from edema-like abnormalities alone to severe atrophy/fatty replacement. Edema-like abnormalities seem to be an earlier MRI marker of the disease. Fatty infiltration/atrophy correlated with the TA muscle force (r = 0.95), the severity (P = 0.00001) of the disease but not with the duration of the disease (P = 0.3) or the length of the CTG repeats (P > 0.10), measured in peripheral leukocytes. Evaluation of other muscles of the legs revealed that the medial gastrocnemius and soleus muscles were the most frequently and severely affected muscles, while tibialis posterior muscles were relatively spared. Edema-like abnormalities are most frequently observed in the skeletal muscles of the anterior compartment. CONCLUSION: Muscle MRI is helpful to depict muscle abnormalities but does not seem to be a reliable indicator of skeletal muscle involvement in DM1 since the decrease in TAmuscle force is not correlated with MRI abnormalities in some patients.

The use of muscle strength assessed with handheld dynamometers as a non-invasive biological marker in myotonic dystrophy type 1 patients: a multicenter study.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a multisystem disorder that demonstrates variable symptoms and rates of progression. Muscle weakness is considered one of the main problems with a clinical picture that is characterized by distal weakness of the limbs progressing to proximal weakness. The main objective of this study was to characterize the maximal strength of ankle eversion and dorsiflexion in DM1 patients. Manual and handheld dynamometer (HHD) muscle testing were also compared. METHODS: The maximal strength of 22 patients from Quebec (mean age = 41,1 +/- 13,8) and 24 from Lyon (mean age = 41,6 +/- 10,2) were compared to 16 matched controls. RESULTS: With the use of HHD, an excellent reproducibility of the torque measurements was obtained for both centers in eversion (R2 = 0,94/Quebec; 0,89/Lyon) and dorsiflexion (R2 = 0,96/Quebec; 0,90/Lyon). The differences between 3 groups of DM1 (mild, moderate, severe) and between them and controls were all statistically significant (p < 0,001). No statistical differences between sites were observed (p > 0.05). The degree of muscle strength decline in dorsiflexion (eversion) were 60% (47%), 77% (71%), and 87% (83%) for DM1 with mild, moderate, and severe impairments, respectively. The smallest mean difference between all DM1 patients taking together was 2.3 Nm, a difference about twice than the standard error of measurement. There was a strong relationship between eversion and dorsiflexion strength profiles (R2 = 0,87;Quebec/0,80;Lyon). Using a 10-point scale, manual muscle testing could not discriminate between the 3 groups of DM1 patients. CONCLUSIONS: The HHD protocol showed discriminative properties suitable for multicentre therapeutic trial. The present results confirmed the capacity of quantitative muscle testing to discriminate between healthy and DM1 patients with different levels of impairments. This study is a preliminary step for the implementation of a valid, reliable and responsive clinical outcome for the measurement of muscle impairments with this population.

Effect of ascorbic acid in patients with Charcot-Marie-Tooth disease type 1A: a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Charcot-Marie-Tooth disease type 1A (CMT1A) is a hereditary peripheral neuropathy that affects roughly one in 5000 births. No specific therapy currently exists for this degenerative disorder, which is characterised by distal progressive muscle atrophy and sensory loss, although ascorbic acid has been shown to reduce demyelination and improve muscle function in a transgenic mouse model of CMT1A. We tested the safety and efficacy of ascorbic acid in adults with CMT1A. METHODS: This 12-month, randomised, double-blind, placebo-controlled study was undertaken between September, 2005, and October, 2008. Patients diagnosed with CMT1A according to clinical examination and confirmation by genotyping were randomly assigned in a 1:1:1 ratio to receive 1 g ascorbic acid per day, 3 g ascorbic acid per day, or placebo. Treatment allocation was based on a computer-generated list of random numbers in blocks of 12, with stratification according to study site and sex; all investigators and participants were unaware of treatment allocation. The primary outcome was the Charcot-Marie-Tooth disease neuropathy score (CMTNS) at 12 months. Analysis was by intention to treat. This study is registered with the Orphanet Database, number ORPHA60779. FINDINGS: The median change in CMTNS from baseline to 12 months was 0.5 points (95% CI -0.3 to 1.4) for the placebo group (n=62), 0.7 points (0.0 to 1.4) for the 1 g ascorbic acid group (n=56), and -0.4 points (-1.2 to 0.4) for the 3 g ascorbic acid group (n=61). We did not find any significant difference in these changes between the groups (p=0.14). The occurrence of adverse events did not differ between the groups (p=0.74). INTERPRETATION: Ascorbic acid at both doses was safe and well tolerated in adults with CMT1A over 12 months. However, there were no significant differences between the groups and the efficacy of ascorbic acid was not shown.