MRI of motor units in spinal muscular atrophy - version 1.0
Research type
Research Study
Full title
Magnetic Resonance Imaging (MRI) of motor unit dynamics as a non-invasive disease biomarker in Spinal Muscular Atrophy (SMA).
IRAS ID
326920
Contact name
Andrew M Blamire
Contact email
Sponsor organisation
Newcastle Hospitals NHS Foundation Trust
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Summary of Research
Patients with spinal muscular atrophy (SMA) suffer muscle wasting and loss of function caused by damage to the motor nerves which connect the brain, via the spinal cord, to the muscles. Each motor nerve connects with many separate fibres within the same muscle which allows the brain to cause the muscle to contract and move. The collections of fibres connected to each nerve are known as motor units (MU). Damage to the motor nerves in SMA causes spontaneous MU activity called fasciculation and changes in the MUs which prevent the muscle from working normally. Therefore, measuring the spontaneous activity and size of MUs is an important diagnostic test for some patients with SMA. This assessment is normally made using electromyography (EMG) which uses either electrodes placed on the skin or a needle electrode inserted into the muscle. EMG cannot show where the MU actually are, can be insensitive and needle measurements can be painful.
This project will evaluate a new type of magnetic resonance imaging (MRI) scan called “Motor Unit MRI” (MUMRI) which takes pictures of the MUs. Preliminary investigations in patients with motor neuron disease suggest that MUMRI is very sensitive to motor neuron damage, but we need to conduct more research studies to fully evaluate and understand the potential of MUMRI to aid diagnosis of other motor neuron conditions.The research will conduct MUMRI imaging in the legs, back, arms and tongue in patients with SMA. The MUMRI scans will be compared with the standard EMG tests to determine how well MRI performs. Patients will be studied on one occasion with data compared to scans and EMG in healthy volunteers.
The research will help to define whether MUMRI is a useful test to measure disease activity and body distribution in SMA patients.Summary of Results
Our muscles are controlled by motor units. A motor unit is a structure which goes from the spinal cord to our muscles and controls the contraction and relaxation of hundreds of muscle fibres. We have thousands of motor units in our bodies. Spinal muscular atrophy (SMA) is a rare genetic condition, in which the motor units do not function correctly. This causes the muscle fibres to die off and they are replaced by fat. One of the earliest signs that somebody might have SMA is the spontaneous activity of the muscle fibres, which is caused by sick motor units, this spontaneous activity is called fasciculation. Fasciculation can be detected by using a recording pad on the surface of the skin, this is called surface electromyography, although painless this method can only detect fasciculation about 1 cm under the skin surface and so can possibly miss activity deeper within the muscles. This study aimed to test a new, non-invasive imaging technique which we have developed which uses magnetic resonance imaging (MRI) to detect fasciculation across all muscles in the body region studied. The imaging method is called MUMRI and our aim is to improve how much fasciculation we can detect.SMA is a rare disease and so we involved patients from across the UK. We studied ten people diagnosed with SMA and compared them with ten matched healthy people. We measured the amount of fasciculation in different muscles of the body: tongue, arm, back and lower limbs using both MUMRI and surface electromyography. We also collected routine MRI scans to look at how SMA affects loss of muscle.
We found that our MUMRI technique is highly sensitive to detect fasciculation and showed that people with SMA had significantly higher amounts of fasciculation than their healthy counterparts. We found these differences in the lower limbs, arm and back but not in the tongue. People with SMA also had significantly less remaining muscle than the healthy volunteers. These observations show that MRI can both measure the abnormal activity in the muscle and the loss of muscle which happen at different points as SMA progresses.
REC name
Wales REC 2
REC reference
23/WA/0295
Date of REC Opinion
16 Oct 2023
REC opinion
Favourable Opinion