Design and implementation of a new treatment for dysphagia after stroke
Submitting InstitutionUniversity of Manchester
Unit of AssessmentClinical Medicine
Summary Impact TypeHealth
Research Subject Area(s)
Medical and Health Sciences: Neurosciences
Summary of the impact
Dysphagia affects >50% of stroke patients with increased risk of aspiration and pneumonia,
costing the NHS approximately £400m pa. Until recently there has been no effective treatment.
Over the last 15 years, Hamdy has identified the mechanisms underlying dysphagia after stroke
and demonstrated that electrostimulation delivered to the pharynx dramatically alters brain regions
controlling swallowing beneficially. This work has gone through extensive clinical evaluation and
forms the basis of a company, Phagenesis Ltd (~£10m VC funding), which has now commenced
implementation of the technology (PhagenyxTM), gained CE marking and has sold >£2.0m of
product in the UK, Europe and the Middle East.
See section 3 for references 1-6. UoM researchers are given in bold.
Research activity was carried out from 1996 to the present. Key researchers at UoM:
David Thompson (Professor of Gastroenterology, 1996-date)
Shaheen Hamdy (MRC Clinician Scientist, 2000-2005; Professor of
Qasim Aziz (Clinical Research Fellow, 1991-1994; Clinical Lecturer, 1994-1998; Clinical
Research Fellow, 2000-2002; Senior Lecturer, 2002-2006; Honorary Professor, 2006-2009)
Details of the research innovation
Swallowing problems (dysphagia) after stroke result in major morbidity and mortality yet the
treatments available are both disappointing in terms of efficacy and lacking in terms of scientific
evidence. The research was developed to revolutionise the management of swallowing after
dysphagic stroke. The initial phases of the research are described below:
- The cortical organisation of swallowing in health
This research demonstrated that the swallowing muscles are arranged in separate areas on
the motor strip, with the oral muscles most lateral and the pharynx and oesophagus more
medial. However, the most important finding was that in the majority of individuals, one or other
hemispheres tended have dominant swallowing representation, independent of handedness
- Mechanisms for dysphagia after stroke
This research showed that although activity in the stroke damaged hemisphere was reduced or
absent in most stroke victims, activity in the undamaged hemisphere was greater in the non-dysphagic
than in the dysphagic patients. Thus, the size of the hemispheric projection to
swallowing muscles could determine the presence or absence of dysphagia, supporting the
concept of cerebral dominance for swallowing (2).
- Mechanisms for swallowing recovery after brain injury
This research explored the mechanisms of recovery from dysphagia by mapping changes in
swallowing representation in a large series of dysphagic stroke patients over several months.
In those who recovered swallowing, the area of pharyngeal representation on the unaffected
hemisphere increased markedly, suggesting that the recovery depends on the increasing
activity in intact pathways in undamaged hemisphere (i.e. compensatory reorganisation) (3).
- Inducing reorganisation in swallowing motor cortex
This research examined the role of peripheral pharyngeal stimulation as a means of
accelerating swallowing reorganisation and recovery. The work was able to show that
prolonged electrical stimulation of the pharynx can induce immediate and sustained changes in
cortical swallowing excitability (4).
- Peripheral stimulation and plasticity associated with changes in swallowing behaviour
This research identified the parameters for optimal excitation of the cortical swallowing
pathways (i.e. 10 minutes of 5Hz of pharyngeal electrical stimulation at 75% of that maximally
tolerated). Critically, when applied to stroke patients, this was associated with an improvement
in swallowing using objective measures. The implication from these results was that input to
the human adult brain can be programmed to promote beneficial changes in plasticity that
result in an improvement of function after stroke (5, 6).
References to the research
Below is a list in sequence of the 6 key references that have led to the implementation of
pharyngeal stimulation in stroke patients.
1. Hamdy S, Aziz Q, Rothwell JC, Singh K, Barlow J, Hughes DG, Tallis RC, Thompson DG.
The Cortical Topography of Human Swallowing Musculature in Health and Disease. Nature
Medicine. 1996;2(11):1217-1224. DOI: 10.1038/nm1196-1217
2. Hamdy S, Aziz Q, Rothwell JC, Crone R, Hughes DG, Tallis RC, Thompson DG. Explaining
Oro-pharyngeal Dysphagia after Unilateral Hemispheric Stroke. Lancet. 1997;350:686-692.
3. Hamdy S, Aziz Q, Rothwell JC, Power M, Singh K, Nicholson DA, Tallis RC, Thompson DG.
Recovery of Swallowing after Dysphagic Stroke Relates to Functional Reorganisation in Intact
Motor Cortex. Gastroenterology. 1998;115:1104-1112. DOI: 10.1016/S0016-5085(98)70081-2
4. Hamdy S, Rothwell JC, Aziz Q, Singh K, Thompson DG. Long-Term Reorganisation of
Human Motor Cortex Driven by Short-Term Sensory Stimulation. Nature Neuroscience
1998;1(1):64-68. DOI: 10.1038/264
5. Fraser C, Hamdy S, Power M, Rothwell JC, Tyrell P, Hollander I, Hobday D, Williams S,
Jackson A, Thompson DG. Driving Plasticity in Adult Human Motor Cortex Improves
Functional Performance after Cerebral Injury. Neuron. 2002;34:831-840. DOI: 10.1016/S0896-6273(02)00705-5
6. Jayasekeran V, Singh S, Rothwell JC, Tyrrell P, Mistry S, Jefferson S, Michou E, Gamble
E, Thompson DG, Hamdy S. Adjunctive functional pharyngeal electrical stimulation reverses
swallowing disability following brain lesions. Gastroenterology. 2010;138:1737-1746. DOI:
1. Studies of dysphagia following hemispheric stroke using transcranial magnetic stimulation:
assessment of pathophysiology, mechanisms of recovery and outcome. Stroke Association.
1994-1996. £150k. Awarded to David Thompson, UoM.
2. Exploring mechanisms of dysphagia in brain injury. MRC. 1996-1999. £280k. Awarded to
David Thompson, UoM.
3. Characterisation, modulation and therapeutic application of neuroplasticity within human
cerebral cortex in health and after brain injury. MRC Clinician Scientist Fellowship. 2000-2004. £600k. Awarded to Shaheen Hamdy, UoM.
4. Exploring the functional, behavioural and neurochemical correlates of stimulus-induced
cortical plasticity in health and stroke. MRC. 2004-2006. £220k. Awarded to Shaheen
5. Imaging the neuroanatomical, functional and behavioural substrates of cortical swallowing
organization. Wellcome Trust. 2007-2010.£260k. Awarded to Shaheen Hamdy, UoM.
6. A randomised controlled trial of pharyngeal electrical stimulation in the treatment of dysphagia
after brain injury. NIHR Research for Patient Benefit Scheme. 2009-2013. £265k. Awarded to
Shaheen Hamdy, UoM.
7. Design and implementation of electrical pharyngeal stimulation in chronic dysphagic stroke.
Wellcome Trust. 2011-2014. £990k. Awarded to Daniel Green, CEO of Phagenesis.
Details of the impact
See section 5 for corroborating sources S1-S7.
Dysphagia after stroke affects at least 40,000 patients annually in the UK alone, 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 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 (S1).
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 quality of life. This is
recognised in the UK National Stroke Strategy (2007), in which 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' (S2). 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.
Pathways to impact
From these observations, the innovation was created and has progressed to an automated
bedside, patient-friendly, battery operated intra-luminal throat (pharyngeal) stimulator for use in
Two patent applications for the UK and Europe have been approved. Through a spin out company
(Phagenesis Ltd — see below), the innovation has started to lead to improved patient outcome,
shorter hospital stays, and significant financial savings for the NHS. An analysis of phase 2 study
data shows that pharyngeal stimulation produces a 25% reduction in aspiration compared with
standard therapy and that catheters are well tolerated by patients and are easily operated by
Reach and significance of the impact
Research at UoM funded by MRC and then NIHR RfPB has led to new evidence that pharyngeal
stimulation is an effective treatment in stroke. Over the last 7 years, in collaboration with the
University of Manchester Intellectual Property Ltd, Hamdy has become the clinical scientific officer
of a UMIP spin out company, Phagenesis Ltd (S3).
Funded initially by £220,000 of pump priming venture capital money from UMIP and The Liverpool
Seed Fund, Merseyside Investment Group, Phagenesis Limited is now managing and leading the
programme of work in the area. As industry lead, Phagenesis is now managing and delivering the
commercial business based on the technology. Indeed, the company entered into an exclusive
funding round arrangement with Angloscientific in 2010, a technology based investment company,
and has secured 2 tranches of finance.
Phagenesis Ltd, having successfully raised ~£10m in VC funding, has now commenced
implementation of the technology (PhagenyxTM), gained CE marking in 2012 (S4), has been
awarded the BioNow healthcare product of the year 2012 and is achieving sales in the UK, Europe
and the Middle East. The medical technologies panel of NICE and Health Horizons are currently
looking at the product with a view to providing the NHS with clinical recommendations (S5-7). Over
100 patients have now been treated. Sales are now estimated at £2m with orders from the Middle
East (£1.5m), UK Hospitals (£0.25m), RoI (£0.3m) and Germany (£0.1m).
Sources to corroborate the impact
S1.Geeganage C, Beavan J, Ellender S, Bath Philip MW. Interventions for dysphagia and
nutritional support in acute and subacute stroke. Cochrane Database of Systematic Reviews.
2012; (10). DOI: 10.1002/14651858.CD000323.pub2
S2.Department of Health. National Stroke Strategy. 2007 (p. 34) Available from:
S4.CE marking certificate, awarded July 2012.
S5.Reuters, Electric stimulation may help stroke victims swallow, 24 Feb 2010
S6.Letter from Professor of Stroke Medicine, King's College London.
S7.Letter from Professor of Stroke Medicine, University of Edinburgh.