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

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.

In this proposal we will explore the feasibility and effectiveness of non-invasive cerebellar stimulation to enhance motor plasticity and swallowing recovery after stroke. Such an approach has mainly been examined in animals where direct cerebellar stimulation has showed enhancement of limb motor evoked potentials and enhanced motor recovery after focal cortical ischemia. By comparison, we have shown that the human cerebellum when stimulated with single magnetic pulses can strongly facilitate corticobulbar pharyngeal projections in humans. More recently we have identified the most relevant frequency of stimulation of the cerebellum (10Hz) that can produce longer term excitation in the human swallowing motor system.

Our objectives are to test the following hypotheses: Cerebellar stimulation will -
i. Reverse the brain inhibition and behavioural dysfunction following a virtual lesion model of disrupted swallowing in healthy brain;
ii. Reduce the degree of aspiration in acute dysphagia after brain damage (stroke).

The studies will utilise transcranial magnetic stimulation (TMS), motor evoked potentials and swallowing evaluations (i.e instrumental exams) in order to answer the questions below:
Question 1: Can cerebellar stimulation of either cerebellar hemisphere reverse swallowing dysruption following unilateral suppression of swallowing motor cortex?
We will use a virtual lesion approach in healthy participants in a randomised study of cerebellar stimulation to determine the optimal side of stimulation.
Question 2: Can cortical stimulation produce short term improvements in swallowing after acute stroke and what is the optimal stimulation regimen for longer term improvement?
This part of the proposal will include a short-term feasibility RCT of a single session of cerebellar stimulation on dysphagic stroke followed by a small dose ranging phase IIa RCT of 2 different regimens of treatment (vs. sham) with changes in aspiration as the primary outcome.

Swallowing therapy has yet to convincingly "prove" its benefits in regard to patients with dysphagia, facilitating removal of feeding tubes and return to oral intake. Dysphagia after stroke affects at least 40,000 patients annually in the UK alone and increases mortality (x2.7 relative risk of death) and prolongs hospital bed stay by >10 days. The consequence is that dysphagia in stroke has an estimated £400M cost burden to the UK NHS each year. Despite this, the treatment of swallowing problems remains difficult, with very few treatments being shown to have any major effect on swallowing disability (Geeganage C, et al. Interventions for dysphagia and nutritional support in acute and subacute stroke. Cochrane Database Syst Rev. 2012 Oct 17;10:CD000323).

The general goals in dysphagia therapy are to reduce the morbidity and mortality associated with aspiration and chest infections (6% of all strokes), improve nutritional status, and return patients to a normal diet with resultant reductions in complications and improvement of their quality of life. This is recognised in the UK National Stroke Strategy 2007 where the aim of "the life after stroke" strategy section is for patients to "achieve a good quality of life and maximise independence, well-being and choices." The report goes on to identify seven target outcomes that contribute to achieving this goal. Restoration of swallowing function has the highest impact in almost all of the seven outcomes identified.Beside these goals, rehabilitative strategies of dysphagia management have restoring of the swallowing function in their focus.

Thus the impact of an effective treatment for dysphagia after stroke and other neurological conditions would be significant and dramatic. The effects on clinical function, well being and quality of life are both substantial and immeasurable. Our proposal to develop a disruptive technology to treat this group of patients (in the form of cerebellar brain stimulation) has the potential to change the landscape of dysphagia and revolutionise the care pathway with major impact on the burden of management to the health service.