Way to Accurately Measure Changes in Ankle Muscles in Myotonic Dystrophy Type 1 May Aid Clinical Trials

A quantitative method that can detect changes in ankle muscle strength in patients with myotonic dystrophy type 1 (MD1) was found to be highly accurate, and may work as an accurate and consistent way of assessing patients in clinical trials.

The study, “Ankle Strength Impairments in Myotonic Dystrophy Type 1: A Five-Year Follow-up,” appeared in the Journal of Neuromuscular Diseases.

The availability of standardized methods of measuring response in patients is particularly relevant for investigating rare diseases, as they require consistent and accurate data reported from multiple trial sites.  Assessments of muscle strength in MD1 is typically performed by manual (MMT) or quantitative (QMT) muscle testing.

However, MMT has raised concerns regarding its reproducibility and sensitivity, and it is of limited use in clinical follow-up.

Progression of muscle weakness in the lower limbs of MD1 patients is often worse in distal muscles, such as the ankle dorsiflexors (DF) and evertors (EV). Both are affected early in disease course.

Prior studies showed that measuring ankle DF muscle strength and walking speed is important for identifying risk of falls in MD1 patients. In turn, scientists have shown that EV muscles act in synergy with DF to stabilize the foot and ankle during weight bearing activities.

Determination of weaknesses in ankle muscles would help to assess the efficacy of therapies intended to ease patients’ loss of independence and physical limitations, the researchers said.

They previously used a QMT approach with a device called a hand-held dynamometer (HHD) to measure DF and EV force in MD1 patients, a technique which showed excellent reliability, the team wrote.

The scientists now used their standardized HHD protocol in a five-year multi-center characterization of changes in maximal muscle strength of the ankle’s DF and EV in MD1 patients. Assessments were made at baseline (study’s start), and at 18, 36, and 60 months.

The research also evaluated differences in muscle strength results across the different study sites, as well as the agreement between the HHD protocol and a system called MyoAnkle. This system was developed to assess problems in ankle joint strength in people with neurodegenerative conditions.

Researchers also further explored the relationship between muscle strength and gait.

The trial was conducted in Quebec, Canada, and in Lyon, France. A total of 26 patients (16 from Quebec and 10 from Lyon) completed the study.

Results revealed progressive decline in the strength of the DF/EV muscles of patients in Quebec (a 36.0%/31.3% decline, respectively) and those in Lyon (27.7%/35.5%, respectively). Although not linear over the five years, this loss of strength reflected a true clinical change in patients’ condition, the researchers said. They also noted the similarity in results between the groups in Quebec and in Lyon, suggests this HDD approach is appropriate for multicenter studies.

Data also revealed that DF force measured using by HHD and MyoAnkle highly correlated.

The researchers noted that HHD requires specific training, but is relatively “simple to use, fairly inexpensive, and since it is commercially available, all sites can acquire the same device and receive the same training.”

They added: “Results obtained with this method highlight the relevance to also use it in clinical trials, where the capacity of instruments to detect small changes is crucial for the success of these studies.”