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

英国每年有1200人被诊断患有运动神经元疾病（MND）。它导致进行性瘫痪和平均在症状出现三年内死亡，目前只有一种获得许可的药物（利鲁唑），只有适度的生存益处。MND的药物试验对患者来说很耗时，对资助者来说也很昂贵。迫切需要一种疾病活性的生物标志物来加快药物发现的步伐。MND是由运动神经元的进行性功能障碍和死亡引起的。脊髓中生病的运动神经元在电上不稳定，会自发地释放电脉冲，导致一小群肌肉纤维抽搐（称为束动）。当运动神经元变得无电反应时，这些束动停止，运动神经元随后死亡。也有一些实验证据表明，束动可能引起化学紊乱，加速运动神经元的死亡。这些肌束可以在皮肤下看到，是MND的标志性临床症状之一。因此，随着时间的推移，记录束动的位置和频率可以很好地衡量运动神经元的健康状况。传统的电测试（针肌电图，NEMG）需要将细针插入肌肉深处来记录束状运动，这只能在医院里完成。NEMG只能检测到一分钟内的电活动，记录的数据只有几分钟，而且非常痛苦，所以很少有病人能忍受重复的测试。高密度表面肌电图（HDSEMG）使用一种贴在皮肤上的非侵入式传感器，可以记录比针头大100倍的区域内的束状结构。这项测试是无痛的，因此可以记录数小时的抽搐，并经常重复。在运动神经元疾病和神经生理学领域的杰出教授Chris Shaw和Kerry Mills的指导下，我作为一名临床医生和神经学实习生，目前正在伦敦国王学院进行为期六个月的预备可行性研究。在这项研究中，我们正在使用市售的HDSEMG传感器来记录MND患者休息时的肌束。我们招募了8名患者，同时对四肢进行代表性录音。本研究的目的是确保这种方法对患者来说是舒适和方便的，并且这些初步数据可以按照我们期望的方式进行解释。我们预测，肌束的位置、频率和形状可能为个体疾病进展提供更敏感的衡量标准。一旦校准，这种方法就可以用来评估一种新药的积极影响，如果它减少了区域扩散和收缩的频率。为了校准这项技术，我们将进行一项为期12个月的纵向研究，从国王学院医院运动神经诊所招募24名患者，包括MND患者和良性束状综合征患者。后一组患者有抽搐，但不出现虚弱，寿命正常。因此，他们是最佳控制组。在每次就诊时，我们将采集所有四肢的静息HDSEMG记录，并对疾病进展进行标准的临床测量。除了生存之外，这些是我们用来检验药物在临床试验中是否有效的标准测试。最终，通过与伦敦帝国理工学院生物工程的同事合作，我们希望设计出一种可穿戴的人体工程学服装，该服装具有嵌入式高清肌电信号和远程数据传输功能。我们设想对这种新设备进行测试和校准，以对照我们经过验证的完善的系统。这种强大工具的便携性将允许在患者家中对其进行评估，从而可能增加客观监测的强度。这将被证明是对未来临床药物试验的宝贵补充。

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.