home-based-monitor-for-gait-and-activity-analysis

Home-Based Monitor for Gait and Activity Analysis

Current outcomes in neuromuscular disorder clinical trials include motor function scales, timed tests, and strength measures performed by trained clinical ...

Institut de Myologie

We report on a 5-year-old girl who presented with an association of symptoms reminiscent of an Ullrich-like congenital muscular dystrophy including congenital hypotonia, proximal joint contractures, hyperlaxity of distal joints, normal cognitive development, and kyphoscoliosis. There was an excess of neuromuscular spindles on the skeletal muscle biopsy. This very peculiar feature on muscle biopsy has been reported only in patients with mutations in the HRAS gene. Sequence analysis of the subject's HRAS gene from blood leukocytes and skeletal muscle revealed a previously described heterozygous missense mutation (c.187G>A, p. Glu63Lys). The present report thus extends the differential diagnosis of congenital muscular dystrophy with major "retractile" phenotypes and adds congenital muscular dystrophy to the clinical spectrum of HRAS-related disorders. 

Congenital muscular dystrophy phenotype with neuromuscular spindles excess in a 5-year-old girl caused by HRAS mutation.

Measurement of muscle strength and activity of upper limbs of non-ambulant patients with neuromuscular diseases is a major challenge. ActiMyo® is an innovative device that uses magneto-inertial sensors to record angular velocities and linear accelerations that can be used over long periods of time in the home environment. The device was designed to insure long-term stability and good signal to noise ratio, even for very weak movements. In order to determine relevant and pertinent clinical variables with potential for use as outcome measures in clinical trials or to guide therapy decisions, we performed a pilot study in non-ambulant neuromuscular patients. We report here data from seven Duchenne Muscular Dystrophy (DMD) patients (mean age 18.5 ± 5.5 years) collected in a clinical setting. Patients were assessed while wearing the device during performance of validated tasks (MoviPlate, Box and Block test and Minnesota test) and tasks mimicking daily living. The ActiMyo® sensors were placed on the wrists during all the tests. Software designed for use with the device computed several variables to qualify and quantify muscular activity in the non-ambulant subjects. Four variables representative of upper limb activity were studied: the rotation rate, the ratio of the vertical component in the overall acceleration, the hand elevation rate, and an estimate of the power of the upper limb. The correlations between clinical data and physical activity and the ActiMyo® movement parameters were analyzed. The mean of the rotation rate and mean of the elevation rate appeared promising since these variables had the best reliability scores and correlations with task scores. Parameters could be computed even in a patient with a Brooke functional score of 6. The variables chosen are good candidates as potential outcome measures in non-ambulant patients with Duchenne Muscular Dystrophy and use of the ActiMyo® is currently being explored in home environment.

A Movement Monitor Based on Magneto-Inertial Sensors for Non-Ambulant Patients with Duchenne Muscular Dystrophy: A Pilot Study in Controlled Environment.

Nemaline myopathies are clinically and genetically heterogeneous muscle diseases characterized by the presence of nemaline bodies (rods) in muscle fibers. Mutations in the KLHL40 (kelch-like family member 40) gene (NEM 8) are common cause of severe/lethal nemaline myopathy. We report an 8-year-old girl born to consanguineous Moroccan parents, who presented with hypotonia and poor sucking at birth, delayed motor development, and further mild difficulties in walking and fatigability. A muscle biopsy revealed the presence of nemaline bodies. KLHL40 gene Sanger sequencing disclosed a never before reported pathogenic homozygous mutation which resulted in absent KLHL40 protein expression in the muscle. This further expands the phenotypical spectrum of KLHL40 related nemaline myopathy.

Mild clinical presentation in KLHL40-related nemaline myopathy (NEM 8).

Exon skipping therapy is an emerging approach in Duchenne Muscular Dystrophy (DMD). Antisense oligonucleotides that induce skipping of exon 51, 44, 45, or 53 are currently being evaluated in clinical trials. These trials were designed on the basis of data available in general DMD population.

Article	Year
Congenital muscular dystrophy phenotype with neuromuscular spindles excess in a 5-year-old girl caused by HRAS mutation. Neuromuscular disorders : NMD\| PubMed ID: 25070542	2014
A Movement Monitor Based on Magneto-Inertial Sensors for Non-Ambulant Patients with Duchenne Muscular Dystrophy: A Pilot Study in Controlled Environment. PloS one\| PubMed ID: 27271157	2016
Mild clinical presentation in KLHL40-related nemaline myopathy (NEM 8). Neuromuscular disorders : NMD\| PubMed ID: 27528495	2016
Non-Ambulant Duchenne Patients Theoretically Treatable by Exon 53 Skipping have Severe Phenotype. Journal of neuromuscular diseases\| PubMed ID: 27858743	2015

Andreea Seferian

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