Sequential surface EMG recordings in motor neurone disease. Fasciculations as a biomarker of motor neurone health.

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Motor neurone disease (MND) is diagnosed in 1,200 people in the UK every year. It causes progressive paralysis and death on average within three years of symptom onset and there is currently only one licensed drug (riluzole) with only modest survival benefit. Drug trials in MND are time-consuming for patients and expensive for funders. A biomarker of disease activity is urgently needed to accelerate the pace of drug discovery. MND is caused by the progressive dysfunction and death of motor neurons. Ailing motor neurons in the spinal cord are electrically unstable and spontaneously discharge electrical impulses that cause small groups of muscle fibres to twitch (known as fasciculations). When the motor neuron becomes electrically unresponsive these fasciculations stop and the motor neuron subsequently dies. There is also some experimental evidence that the fasciculations may cause chemical disturbances that hasten the death of motor neurons. These muscle fasciculations can be seen under the skin and are one of the hallmark clinical signs of MND. Thus, recording the site and frequency of fasciculations over time may provide a good measure of motor neuron health. Conventional electrical testing (needle electromyography, NEMG) involves putting a fine needle deep into muscles to record fasciculations and this can only be done in a hospital. NEMG only detects electrical activity within a minute field, records data for only a few minutes and is quite painful so few patients would tolerate repeated testing. High-density surface EMG (HDSEMG), using a non-invasive sensor that sticks to the skin, can record fasciculations over a field that is 100 times larger than the needle. The test is painless so fasciculations can be recorded over many hours and repeated frequently.Under the guidance of Professors Chris Shaw and Kerry Mills, eminent in their respective fields of motor neurone disease and neurophysiology, I, as a clinician and neurology trainee, am currently undertaking a six-month preparatory feasibility study at King's College London. In this study, we are making use of commercially available HDSEMG sensors to record fasciculations at rest in patients with MND. We have recruited eight patients and are taking representative recordings from all four limbs simultaneously. The purpose of this study is to ensure this method is comfortable and convenient for patients, and that these preliminary data can be interpreted in the way we expect. We predict that the site, frequency and shape of fasciculations might provide a more sensitive measure of disease progression in an individual. Once calibrated, this method may then be used to assess the positive impact of a new drug if it reduces the regional spread and frequency of fasciculations. In order to calibrate this technique, we will conduct a 12-month longitudinal study, recruiting 24 patients from the King's College Hospital Motor Nerve Clinic, comprising a mixture of patients with MND and those with benign fasciculation syndrome. Patients in this latter group have fasciculations but do not develop weakness and have normal lifespans. They are therefore an optimal control group. At each visit, we will take resting HDSEMG recordings from all four limbs and perform standard clinical measures of disease progression. In addition to survival, these are the standard tests we use to see whether a drug is working in clinical trials.Ultimately, through collaboration with Bioengineering colleagues at Imperial College London, we hope to design a wearable ergonomic garment with embedded HDSEMG and remote data transfer capabilities. We envisage testing and calibrating this new equipment against our validated, well-established system. The portability of such a powerful tool will allow the assessment of patients in their own homes, potentially increasing the intensity of objective monitoring. This will prove an invaluable addition to future clinical drug trials.