Quantitative Motion Measurements Based on Markerless 3D Full-Body Tracking in Children with SMA Highly Correlate with Standardized Motor Assessments

Background: Spinal Muscular Atrophy (SMA) is the most common neurodegenerative disease in childhood. New therapeutic interventions have been developed to interrupt rapid motor deterioration. The current standard of clinical evaluation for severely weak infants is the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), originally developed for SMA type 1. This test however, remains subjective and requires extensive training to be performed reliably. Objective: Proof of principle of the motion tracking method for capturing complex movement patterns in ten children with SMA. Methods: We have developed a system for tracking full-body motion in infants (KineMAT) using a commercially available, low-cost RGB-depth sensor. Ten patients with SMA (2–46 months of age; CHOP INTEND score 10–50) were recorded for 2 minutes during unperturbed spontaneous whole-body activity. Five predefined motion parameters representing 56 degrees of freedom of upper, lower extremities and trunk joints were correlated with CHOP INTEND scores using Pearson product momentum correlation (r). Test-retest analysis in two patients used descriptive statistics. Results: 4/5 preselected motion parameters highly correlated with CHOP INTEND: 1. Standard deviation of joint angles (r = 0.959, test-retest range 1.3–1.9%), 2. Standard deviation of joint position (r = 0.933, test-retest range 2.9%), 3. Absolute distance of hand/foot travelled (r = 0.937, test-retest range 6–10.5%), 4. Absolute distance of hand/foot travelled against gravity (r = 0.923; test-retest range 4.8–8.5%). Conclusions: Markerless whole-body motion capture using the KineMAT proved to objectively capture motor performance in infants and children with SMA across different severity and ages.

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Of rAAV and Men: From Genetic Neuromuscular Disorder Efficacy and Toxicity Preclinical Studies to Clinical Trials and Back

Journal of Personalized Medicine ◽

10.3390/jpm10040258 ◽

2020 ◽

Vol 10 (4) ◽

pp. 258

Author(s):

Laurine Buscara ◽

David-Alexandre Gross ◽

Nathalie Daniele

Keyword(s):

Clinical Trials ◽

Muscular Atrophy ◽

Neuromuscular Disorders ◽

Neuromuscular Disorder ◽

Whole Body ◽

Skeletal Muscle Atrophy ◽

General Strategy ◽

Serious Adverse Events ◽

Worst Case ◽

Organ Failures

Neuromuscular disorders are a large group of rare pathologies characterised by skeletal muscle atrophy and weakness, with the common involvement of respiratory and/or cardiac muscles. These diseases lead to life-long motor deficiencies and specific organ failures, and are, in their worst-case scenarios, life threatening. Amongst other causes, they can be genetically inherited through mutations in more than 500 different genes. In the last 20 years, specific pharmacological treatments have been approved for human usage. However, these “à-la-carte” therapies cover only a very small portion of the clinical needs and are often partially efficient in alleviating the symptoms of the disease, even less so in curing it. Recombinant adeno-associated virus vector-mediated gene transfer is a more general strategy that could be adapted for a large majority of these diseases and has proved very efficient in rescuing the symptoms in many neuropathological animal models. On this solid ground, several clinical trials are currently being conducted with the whole-body delivery of the therapeutic vectors. This review recapitulates the state-of-the-art tools for neuron and muscle-targeted gene therapy, and summarises the main findings of the spinal muscular atrophy (SMA), Duchenne muscular dystrophy (DMD) and X-linked myotubular myopathy (XLMTM) trials. Despite promising efficacy results, serious adverse events of various severities were observed in these trials. Possible leads for second-generation products are also discussed.

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A Hybrid Tracking System of Full-Body Motion Inside Crowds

Sensors ◽

10.3390/s21062108 ◽

2021 ◽

Vol 21 (6) ◽

pp. 2108

Author(s):

Maik Boltes ◽

Juliane Adrian ◽

Anna-Katharina Raytarowski

Keyword(s):

Motion Tracking ◽

Inertial Sensors ◽

Tracking System ◽

Body Motion ◽

Whole Body ◽

Body Parts ◽

Movement Velocity ◽

Camera System ◽

Pedestrian Dynamics ◽

Full Body

For our understanding of the dynamics inside crowds, reliable empirical data are needed, which could enable increases in safety and comfort for pedestrians and the design of models reflecting the real dynamics. A well-calibrated camera system can extract absolute head position with high accuracy. The inclusion of inertial sensors or even self-contained full-body motion capturing systems allows the relative tracking of invisible people or body parts or capturing the locomotion of the whole body even in dense crowds. The newly introduced hybrid system maps the trajectory of the top of the head coming from a full-body motion tracking system to the head trajectory of a camera system in global space. The fused data enable the analysis of possible correlations of all observables. In this paper we present an experiment of people passing though a bottleneck and show by example the influences of bottleneck width and motivation on the overall movement, velocity, stepping locomotion and rotation of the pelvis. The hybrid tracking system opens up new possibilities for analyzing pedestrian dynamics inside crowds, such as the space requirement while passing through a bottleneck. The system allows linking any body motion to characteristics describing the situation of a person inside a crowd, such as the density or movements of other participants nearby.

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Integrating pediatric palliative care across the spectrum of life threatening pediatric neuromuscular disorders focused on Spinal muscular atrophy type I and Duchenne muscular dystrophy

Neuropediatrics ◽

10.1055/s-0031-1274094 ◽

2011 ◽

Vol 42 (S 01) ◽

Author(s):

M von der Hagen ◽

M Smitka ◽

A Pyper ◽

M Breiting ◽

A Müller ◽

...

Keyword(s):

Palliative Care ◽

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Spinal Muscular Atrophy ◽

Muscular Atrophy ◽

Neuromuscular Disorders ◽

Pediatric Palliative Care ◽

Type I ◽

Spinal Muscular Atrophy Type ◽

Life Threatening

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A novel case of concurrent occurrence of demyelinating-polyneuropathy-causing PMP22 duplication and SOX10 gene mutation producing severe hypertrophic neuropathy

BMC Neurology ◽

10.1186/s12883-021-02256-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Nozomu Matsuda ◽

Koushi Ootsuki ◽

Shunsuke Kobayashi ◽

Ayaka Nemoto ◽

Hitoshi Kubo ◽

...

Keyword(s):

Hearing Loss ◽

Neuromuscular Disorders ◽

Whole Body ◽

Congenital Hearing Loss ◽

Severe Phenotype ◽

Demyelinating Neuropathy ◽

Magnetic Resonance Neurography ◽

Peripheral Myelin Protein 22 ◽

Hypertrophic Neuropathy

Abstract Background Hereditary motor and sensory neuropathy, also referred to as Charcot–Marie–Tooth disease (CMT), is most often caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. This duplication causes CMT type 1A (CMT1A). CMT1A rarely occurs in combination with other hereditary neuromuscular disorders. However, such rare genetic coincidences produce a severe phenotype and have been reported in terms of “double trouble” overlapping syndrome. Waardenburg syndrome (WS) is the most common form of a hereditary syndromic deafness. It is primarily characterized by pigmentation anomalies and classified into four major phenotypes. A mutation in the SRY sex determining region Y-box 10 (SOX10) gene causes WS type 2 or 4 and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, WS, and Hirschsprung disease. We describe a 11-year-old boy with extreme hypertrophic neuropathy because of a combination of CMT1A and WS type 2. This is the first published case on the co-occurrence of CMT1A and WS type 2. Case presentation The 11-year-old boy presented with motor developmental delay and a deterioration in unstable walking at 6 years of age. In addition, he had congenital hearing loss and heterochromia iridis. The neurological examination revealed weakness in the distal limbs with pes cavus. He was diagnosed with CMT1A by the fluorescence in situ hybridization method. His paternal pedigree had a history of CMT1A. However, no family member had congenital hearing loss. His clinical manifestation was apparently severe than those of his relatives with CMT1A. In addition, a whole-body magnetic resonance neurography revealed an extreme enlargement of his systemic cranial and spinal nerves. Subsequently, a genetic analysis revealed a heterozygous frameshift mutation c.876delT (p.F292Lfs*19) in the SOX10 gene. He was eventually diagnosed with WS type 2. Conclusions We described a patient with a genetically confirmed overlapping diagnoses of CMT1A and WS type 2. The double trouble with the genes created a significant impact on the peripheral nerves system. Severe phenotype in the proband can be attributed to the cumulative effect of mutations in both PMP22 and SOX10 genes, responsible for demyelinating neuropathy.

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Using Biofeedback to Reduce Step Length Asymmetry Impairs Dynamic Balance in People Poststroke

Neurorehabilitation and Neural Repair ◽

10.1177/15459683211019346 ◽

2021 ◽

pp. 154596832110193

Author(s):

Sungwoo Park ◽

Chang Liu ◽

Natalia Sánchez ◽

Julie K. Tilson ◽

Sara J. Mulroy ◽

...

Keyword(s):

Angular Momentum ◽

Sagittal Plane ◽

Dynamic Balance ◽

Objective Measure ◽

Frontal Plane ◽

Step Length ◽

Berg Balance Scale ◽

Whole Body ◽

Functional Gait ◽

Full Body

Background People poststroke often walk with a spatiotemporally asymmetric gait, due in part to sensorimotor impairments in the paretic lower extremity. Although reducing asymmetry is a common objective of rehabilitation, the effects of improving symmetry on balance are yet to be determined. Objective We established the concurrent validity of whole-body angular momentum as a measure of balance, and we determined if reducing step length asymmetry would improve balance by decreasing whole-body angular momentum. Methods We performed clinical balance assessments and measured whole-body angular momentum during walking using a full-body marker set in a sample of 36 people with chronic stroke. We then used a biofeedback-based approach to modify step length asymmetry in a subset of 15 of these individuals who had marked asymmetry and we measured the resulting changes in whole-body angular momentum. Results When participants walked without biofeedback, whole-body angular momentum in the sagittal and frontal plane was negatively correlated with scores on the Berg Balance Scale and Functional Gait Assessment supporting the validity of whole-body angular momentum as an objective measure of dynamic balance. We also observed that when participants walked more symmetrically, their whole-body angular momentum in the sagittal plane increased rather than decreased. Conclusions Voluntary reductions of step length asymmetry in people poststroke resulted in reduced measures of dynamic balance. This is consistent with the idea that after stroke, individuals might have an implicit preference not to deviate from their natural asymmetry while walking because it could compromise their balance. Clinical Trials Number: NCT03916562.

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