An exploration of the application of non-invasive cerebellar stimulation in the neurorehabilitation of dysphagia after stroke

中风后的吞咽问题(吞咽困难)是NHS的一个主要临床问题，每年有超过40,000名患者患有吞咽困难，从而导致吸入/肺炎。这导致住院时间更长，对食物资源的需求增加，疗养院的入院率更高，生存能力更差，估计NHS每年要花费4亿GB。传统上，言语和语言治疗师使用饮食调整和床边策略来恢复吞咽，尽管几乎没有证据表明有益。虽然管饲可以改善营养，但没有证据表明(食物)吸入的风险会降低。随着中风的发病率预计在未来20年内增加，吞咽困难的问题可能会增加，因此更好地了解吞咽康复是如何操作的将对人类健康和疾病有明显的好处。我们小组之前的工作着眼于可能有助于中风患者吞咽困难成功康复的因素，其中一些工作导致了通过吞咽导管进行咽部刺激疗法的开发，目前正在进行第三阶段临床试验。不幸的是，许多患者不能参加这样的试验，因为他们的中风导致口腔/喉咙感觉受损，或者因为他们不能遵守导管放置的要求。此外，大约三分之一的吞咽障碍中风患者似乎对这种感官干预没有反应。因此，有必要探索替代策略来改善这类患者的吞咽控制。在这项建议中，我们将探索一种新的、令人兴奋的方法--非侵入性小脑刺激--的有效性，以增强中风后吞咽皮质的运动可塑性。这种方法主要在动物身上进行检验，在这些动物中，直接小脑刺激显示出大鼠人工中风后肢体运动反应的增强和运动恢复的增强。通过比较，我们已经证明，人类小脑在吞咽行为中被强烈激活，当受到头后部磁脉冲的刺激时，可以强烈地改善人类皮质到吞咽肌肉的通路。最近，我们已经确定了小脑磁刺激的最相关频率(10赫兹)，它可以在人类吞咽运动系统中产生长期改善。因此，我们认为小脑刺激在改善吞咽方面的潜力比其他方法要大得多。我们的计划是通过三项各自建立在另一项研究之上的研究来研究这一新方法。首先，在对健康受试者实施小脑刺激之前，我们将使用一种“虚拟损伤”技术来抑制大脑的吞咽区域，看看刺激两侧小脑是否能使吞咽区域恢复正常。然后，我们将测试对吞咽困难中风患者的最佳小脑一侧/部位的刺激，看看是否可以在刺激后立即(1小时)改善吞咽情况。假设这种方法奏效，我们将对吞咽困难中风患者的小脑刺激进行一项小剂量范围的研究，看看哪种刺激配方(每天多少天和多少次)在吞咽方面产生最大的长期变化(超过1小时，到2周)。如果有一个最优/最好的配方，我们预计这将导致未来对吞咽困难中风的小脑刺激进行更大规模的研究，预计这最终将成为这些痛苦和虚弱的中风患者的治疗选择。

Swallowing problems (dysphagia) after stroke represent a major clinical problem for the NHS, with over 40,000 patients annually suffering from dysphagia with consequent aspiration/pneumonia. This leads to longer hospital stays, increased demands on feeding resources, higher admissions to care homes and poorer survival, costing the NHS an estimated £400 million a year. Traditionally, speech and language therapists have used dietary modifications and bedside strategies to rehabilitate swallowing albeit with little evidence base for benefit. And while tube feeding can improve nutrition, there is no evidence that the risk of (food) aspiration is reduced. With the incidence of stroke projected to increase over the next 20 years, the problem of dysphagia is likely to grow, so a better understanding of how swallowing recovery can be manipulated would of clear benefit to human health and disease. Previous work from our group has looked at the factors that might make for successful recovery from dysphagia in stroke patients, and some of this work led to development of a pharyngeal stimulation therapy via a swallowing catheter that is now undergoing phase III clinical trials. Unfortunately, many patients cannot participate in such trials because their stroke has resulted in either impaired sensation in the mouth/throat or because they cannot comply with catheter placement. Moreover, about a third of dysphagic stroke patients don't seem to respond to this sensory intervention. There is therefore a need to explore alternative strategies to improve control of swallowing in this group of patients.In this proposal we will explore the effectiveness of a new and exciting approach, non-invasive cerebellar stimulation, to enhance motor plasticity in the swallowing cortex after stroke. This approach has mainly been examined in animals where direct cerebellar stimulation has showed enhancement of limb motor responses and enhanced motor recovery after artificial stroke in rats. By comparison, we have shown that the human cerebellum is strongly activated during the act of swallowing and when stimulated with magnetic pulses over the back of the head can strongly improve the cortex to swallowing muscles pathway in humans. More recently we have identified the most relevant frequency of magnetic stimulation of the cerebellum (10Hz) that can produce longer term improvements in the human swallowing motor system. We therefore believe that the potential for cerebellar stimulation in improving swallowing is much greater than other methods.Our plans are to look at this new approach through three studies that each build on the other. First we will use a "virtual lesion" technique to suppress the swallowing areas of the brain before applying the cerebellar stimulation in health participants to see if stimulation either side of the cerebellum can restore the swallowing regions to normal. We will then test out stimulation of best cerebellar side/site in dysphagic stroke patients to see if we can improve swallowing in the period immediately after stimulation (1 hour). Assuming this works, we will then run a small dose ranging study of cerebellar stimulation in dysphagic stroke patients to see which recipe of stimulation (how many days and how many times per day) produces the greatest long term changes in swallowing (beyond 1 hour, to 2 weeks). If there is an optimal/best recipe for this, we expect this will then lead on to future larger scale studies of the cerebellar stimulation in dysphagic stroke with the anticipation that this will eventually become a treatment option for these distressed and debilitated victims of stroke.