Spinal cord stimulation for gait dysfunction in Parkinson's disease
Lead Research Organisation:
Imperial College London
Department Name: Brain Sciences
Abstract
Parkinson's is the second most common brain degenerative disorder, affecting over 127,000 people in the UK alone. Parkinson's can result in loss of balance and falls, which then lead to a number of complications including fractures, nursing home admissions and premature death. Balance problems and falls in Parkinson's often do not respond to currently available Parkinson's medications, and treatment options are limited.
In this pilot study, I aim to recruit 5 patients with Parkinson's disease and gait dysfunction which is resistant to conventional Parkinson's treatments such as dopamine replacement therapy, and to offer them a new treatment by inserting a stimulator on the spinal cord. Spinal cord stimulator has been used to treat chronic pain for many years, and is a relatively safe procedure. Previous studies have shown that Parkinson's patients who have had spinal cord stimulator for back pain experienced an improvement in their walking and balance after the procedure. Since then, a small number of Parkinson's patients with balance problem but without back pain has also received spinal cord stimulation, and a beneficial effect has been seen in some of them. However, the number of patients studied was small and it is unclear who would benefit most from this treatment and whether the treatment effects are sustained. It is also unclear exactly how spinal cord stimulators improve balance in Parkinson's patients.
In my proposed study, the patients will be examined methodically using a range of stimulator settings over a 12-month period, in a blinded fashion (the patients would not know if they receive real stimulation or placebo/sham stimulation) to minimise the placebo effects. They will also undergo detailed testing using clinical scales and patient-reported outcomes, but also a new way of using computer modelling and remote monitoring (using wearable monitors) to more objectively measure balance problems and the effects of spinal cord stimulators. I will also apply transcranial magnetic stimulation and measure brain wave activities to find out how spinal cord stimulation changes the brain functions. Understanding how spinal cord stimulators work will enable us to refine the treatment, and to select the appropriate patients who are likely to benefit from the treatment.
In this pilot study, I aim to recruit 5 patients with Parkinson's disease and gait dysfunction which is resistant to conventional Parkinson's treatments such as dopamine replacement therapy, and to offer them a new treatment by inserting a stimulator on the spinal cord. Spinal cord stimulator has been used to treat chronic pain for many years, and is a relatively safe procedure. Previous studies have shown that Parkinson's patients who have had spinal cord stimulator for back pain experienced an improvement in their walking and balance after the procedure. Since then, a small number of Parkinson's patients with balance problem but without back pain has also received spinal cord stimulation, and a beneficial effect has been seen in some of them. However, the number of patients studied was small and it is unclear who would benefit most from this treatment and whether the treatment effects are sustained. It is also unclear exactly how spinal cord stimulators improve balance in Parkinson's patients.
In my proposed study, the patients will be examined methodically using a range of stimulator settings over a 12-month period, in a blinded fashion (the patients would not know if they receive real stimulation or placebo/sham stimulation) to minimise the placebo effects. They will also undergo detailed testing using clinical scales and patient-reported outcomes, but also a new way of using computer modelling and remote monitoring (using wearable monitors) to more objectively measure balance problems and the effects of spinal cord stimulators. I will also apply transcranial magnetic stimulation and measure brain wave activities to find out how spinal cord stimulation changes the brain functions. Understanding how spinal cord stimulators work will enable us to refine the treatment, and to select the appropriate patients who are likely to benefit from the treatment.
Technical Summary
Gait dysfunction and postural instability are one of the main causes of morbidity and mortality in Parkinson's disease (PD). They lead to falls and loss of independence, and are a major milestone of disease progression in PD. They are often unresponsive to dopamine replacement therapy and treatment options are limited. It is thought that degeneration of cholinergic brainstem nuclei may be responsible for PD gait dysfunction, but attempts to enhance brainstem cholinergic pathway using cholinesterase inhibitors or pedunculopontine nucleus deep brain stimulation have produced mixed outcome.
Spinal cord stimulation (SCS) is an established treatment for chronic back/neuropathic pain. It has been noted that PD patients with back pain experienced an improvement in their gait after SCS. A small number of PD patients without back pain have since received SCS, and beneficial effects were reported in some of them. However, these studies were small and unblinded, and there were many unanswered questions including optimal stimulation parameters, appropriate outcome measures, mechanisms of actions, and potential placebo effects.
In this pilot study, I aim to study 5 PD patients with treatment resistant gait dysfunction and offer them SCS. These patients will receive either sham stimulation or a range of stimulation parameters over a 12-month period. The patients and assessors will both be blinded to this. These patients will undergo detailed multi-modal quantitative gait analysis to study the effects of intervention. They will also receive transcranial magnetic stimulation and electroencephalogram (EEG) to study the neural effects of spinal cord stimulation, including cortical excitability and brain oscillations.
Spinal cord stimulation (SCS) is an established treatment for chronic back/neuropathic pain. It has been noted that PD patients with back pain experienced an improvement in their gait after SCS. A small number of PD patients without back pain have since received SCS, and beneficial effects were reported in some of them. However, these studies were small and unblinded, and there were many unanswered questions including optimal stimulation parameters, appropriate outcome measures, mechanisms of actions, and potential placebo effects.
In this pilot study, I aim to study 5 PD patients with treatment resistant gait dysfunction and offer them SCS. These patients will receive either sham stimulation or a range of stimulation parameters over a 12-month period. The patients and assessors will both be blinded to this. These patients will undergo detailed multi-modal quantitative gait analysis to study the effects of intervention. They will also receive transcranial magnetic stimulation and electroencephalogram (EEG) to study the neural effects of spinal cord stimulation, including cortical excitability and brain oscillations.
Planned Impact
Gait dysfunction is a major cause of hospitalisation and subsequent demise among Parkinson's patients. If spinal cord stimulation demonstrates promising results from this pilot study, it will need to be replicated in a larger scale study. The outcome from this study could potentially benefit most, if not all, patients with Parkinson's disease (of which there are 127,000 suffers in the UK alone) and related disorders, since gait and balance problems affect many of patients with this condition.
Falls and balance problems are difficult to measure and detect, as they often occur away from clinics/hospitals. The knowledge acquired from the detailed balance analysis in this study will allow clinicians and medical researchers to better understand and characterise patients with neurodegenerative disorders who might be at high risks of falls, and to allow targeted treatments to be offered to such patients. This method of balance analysis can potentially be applied to many other neurological conditions where balance is affected.
Falls and balance problems are difficult to measure and detect, as they often occur away from clinics/hospitals. The knowledge acquired from the detailed balance analysis in this study will allow clinicians and medical researchers to better understand and characterise patients with neurodegenerative disorders who might be at high risks of falls, and to allow targeted treatments to be offered to such patients. This method of balance analysis can potentially be applied to many other neurological conditions where balance is affected.
Publications
Smith Rebecca M
(2020)
A mixed methods randomised feasibility trial investigating the management of benign paroxysmal positional vertigo in acute traumatic brain injury.
in Pilot and Feasibility Studies
Smith RM
(2020)
A mixed methods randomised feasibility trial investigating the management of benign paroxysmal positional vertigo in acute traumatic brain injury.
in Pilot and feasibility studies
Murdin L
(2020)
Assessment of dizziness in neurology
in Medicine
Murdin L
(2023)
Assessment of dizziness in neurology
in Medicine
Shaikh AG
(2021)
Consensus on Virtual Management of Vestibular Disorders: Urgent Versus Expedited Care.
in Cerebellum (London, England)
Rust HM
(2022)
Force dependency of benign paroxysmal positional vertigo in acute traumatic brain injury: a prospective study.
in Journal of neurology, neurosurgery, and psychiatry
Cury RG
(2022)
Gaps and roadmap of novel neuromodulation targets for treatment of gait in Parkinson's disease.
in NPJ Parkinson's disease
Rajesh S
(2023)
Head injury: assessment and early management-summary of updated NICE guidance.
in BMJ (Clinical research ed.)
Lempert T
(2020)
How to define migraine with brainstem aura?
in Brain : a journal of neurology
Harris L
(2020)
Impact of anti-epileptic drug choice on discharge in acute traumatic brain injury patients.
in Journal of neurology
Davies H
(2023)
In-Ear SpO2 for Classification of Cognitive Workload
in IEEE Transactions on Cognitive and Developmental Systems
Hvingelby VS
(2022)
Interventions to improve gait in Parkinson's disease: a systematic review of randomized controlled trials and network meta-analysis.
in Journal of neurology
Mahmud M
(2022)
Prevalence of stroke in acute vertigo presentations: A UK tertiary stroke centre perspective
in Journal of the Neurological Sciences
Ciocca M
(2023)
Spinal Cord Stimulation for Gait Disorders in Parkinson's Disease and Atypical Parkinsonism: A Systematic Review of Preclinical and Clinical Data.
in Neuromodulation : journal of the International Neuromodulation Society
Seemungal BM
(2022)
The Bárány Society position on 'Cervical Dizziness'.
in Journal of vestibular research : equilibrium & orientation
Mahmud M
(2022)
The effect of galvanic vestibular stimulation on postural balance in Parkinson's disease: A systematic review and meta-analysis.
in Journal of the neurological sciences
Hadi Z
(2022)
The human brain networks mediating the vestibular sensation of self-motion.
in Journal of the neurological sciences
Hadi Z
(2022)
The human brain networks mediating the vestibular sensation of self-motion.
in Journal of the neurological sciences
Calzolari E
(2021)
Vestibular agnosia in traumatic brain injury and its link to imbalance.
in Brain : a journal of neurology
Lempert T
(2022)
Vestibular migraine: Diagnostic criteria1.
in Journal of vestibular research : equilibrium & orientation
Ciocca M
(2024)
Vestibular prepulse inhibition of the human blink reflex
Description | Association of British Neurologists Acute Neurology Advisory Board |
Geographic Reach | National |
Policy Influence Type | Membership of a guideline committee |
Impact | We are engaged in facilitating the current re-organisation of acute neurology services (and linking it to community services) in the UK. |
Description | Chair of trial steering committee |
Geographic Reach | National |
Policy Influence Type | Membership of a guideline committee |
Impact | I am chair of the steering committee for the VeRMiS trial which is a multi-centre study to assess the effectiveness of vestibular rehabilitation in people with Multiple Sclerosis. The trial outcomes will have imoplications for MS patients in the UK and beyond. Trial registry: https://doi.org/10.1186/ISRCTN27374299 |
URL | https://www.plymouth.ac.uk/research/vermis |
Description | GP referral guidelines for dizziness and imbalance for the North West region of London (population 2 million) |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
Impact | The online document also has teaching links, including videos I have made, showing GPs how to treat certain conditions. See: https://www.healthiernorthwestlondon.nhs.uk/sites/nhsnwlondon/files/documents/dizziness_guidelines_v0_6.pdf |
Description | Member of Neuromodulation and Gait Disorder Task Force of International Parkinson and Movement Disorder Society |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Membership of a guideline committee |
Impact | As a member of the taskforce, I have contributed to a position paper (in press) recommending new approaches to study and treat gait disorders in Parkinson's disease |
Description | NICE committee for head injury guidelines |
Geographic Reach | National |
Policy Influence Type | Membership of a guideline committee |
URL | https://www.nice.org.uk/Guidance/CG176 |
Description | Royal College of Physicians - Joint Clinical Neurosciences Committee - Acute Neurology Representative. |
Geographic Reach | National |
Policy Influence Type | Membership of a guideline committee |
Description | Remote assessment of Acute Stroke with Vertigo - (The ReActiVe study) |
Amount | £85,000 (GBP) |
Funding ID | II2021_17 |
Organisation | Imperial Health Charity |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2021 |
End | 12/2022 |
Description | Trial of spinal cord stimulation to reduce imbalance and falls in Parkinson's disease |
Amount | £542,526 (GBP) |
Funding ID | Imperial college reference P85312 |
Organisation | J P Moulton Charitable Foundation |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 04/2020 |
End | 04/2023 |
Description | mTBI-Predict study |
Amount | £2,000,000 (GBP) |
Funding ID | 1844551 |
Organisation | Ministry of Defence (MOD) |
Sector | Public |
Country | United Kingdom |
Start | 03/2022 |
End | 02/2023 |
Description | Spinal Cord Stimulation therapy for Parkinson's disease patients with gait problems |
Organisation | Aarhus University |
Country | Denmark |
Sector | Academic/University |
PI Contribution | My input has helped the Aarhus team win a grant of £700,000 from Denmark Independent Research Fund to study the effect of Spinal Cord Stimulation in Parkinson's disease in Denmark. I am also the co-supervisor of a PhD student who will undertake the research project in Aarhus. He/she will also be able to spend one year in our laboratory at Imperial to learn more about gait analysis. I have also started a collaboration with Dr Shlomi Haar from the Dementia Research Institute, Imperial College London, to look at the effects of neural stimulation on EEG. |
Collaborator Contribution | The Danish study will incorporate a Positron Emission Tomography (PET) component. Our Imperial College study participants will fly to Aarhus for pre- and 1-year post-implantation study PET to evaluate the effects of Spinal Cord Stimulation on brain glucose metabolism and cholinergic transmission. The costs of travel and PET scans are covered by the Danish grant. The DRI collaboration will bring in an Centre for Doctoral Training (CDT) AI PhD student to carry out the neurophysiological studies of these patients. |
Impact | Spinal cord stimulator implantation has commenced at Aarhus, and we have co-written a paper on study protocol and a meta-analysis on gait dysfunction in Parkinson which is about to be accepted for publication. |
Start Year | 2020 |
Description | Spinal Cord Stimulation therapy for Parkinson's disease patients with gait problems |
Organisation | Imperial College London |
Department | Dementia Research Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | My input has helped the Aarhus team win a grant of £700,000 from Denmark Independent Research Fund to study the effect of Spinal Cord Stimulation in Parkinson's disease in Denmark. I am also the co-supervisor of a PhD student who will undertake the research project in Aarhus. He/she will also be able to spend one year in our laboratory at Imperial to learn more about gait analysis. I have also started a collaboration with Dr Shlomi Haar from the Dementia Research Institute, Imperial College London, to look at the effects of neural stimulation on EEG. |
Collaborator Contribution | The Danish study will incorporate a Positron Emission Tomography (PET) component. Our Imperial College study participants will fly to Aarhus for pre- and 1-year post-implantation study PET to evaluate the effects of Spinal Cord Stimulation on brain glucose metabolism and cholinergic transmission. The costs of travel and PET scans are covered by the Danish grant. The DRI collaboration will bring in an Centre for Doctoral Training (CDT) AI PhD student to carry out the neurophysiological studies of these patients. |
Impact | Spinal cord stimulator implantation has commenced at Aarhus, and we have co-written a paper on study protocol and a meta-analysis on gait dysfunction in Parkinson which is about to be accepted for publication. |
Start Year | 2020 |
Description | Meeting with local Parkinson's patient support group |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Meeting with Parkinson's patients and carers to discuss the proposed Spinal Cord stimulation study, and to gather patient feedback on the proposed protocol |
Year(s) Of Engagement Activity | 2020 |
Description | News bulletin and social media output on the proposed Spinal Cord Stimulation study in Parkinson's |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | The planned study on Spinal Cord Stimulation in Parkinson's was reported on Imperial college website (available to the public) with subsequent news release in Imperial social media channels (including Facebook and Twitter). There were follow-up queries sent in by patients' families/carers. |
Year(s) Of Engagement Activity | 2020 |
URL | https://www.imperial.ac.uk/news/193546/trial-will-look-parkinsons-treatment-frequent/ |
Description | Plenary speaker at Parkinson's academy meeting "Cutting Edge Science for Parkinson's Clinicians" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | I was the invited plenary speaker for the Parkinson's academy's meeting entitled "Cutting Edge Science for Parkinson's Clinicians", talking about Spinal Cord stimulation for gait dysfunction in Parkinson's. The event was attended by Parkinson's practitioners and researchers. |
Year(s) Of Engagement Activity | 2022 |
URL | https://neurologyacademy.org/parkinsons-academy/cutting-edge-science-for-parkinsons-clinicians |
Description | Presentation on proposed Spinal Cord Stimulation study in Parkinson's at the UK National Deep Brain Stimulation Network meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Presented our planned study including preliminary protocol about the Spinal Cord Stimulation study in Parkinson's in the annual UK Deep Brain Stimulation (DBS) network meeting, attended by DBS clinicians/nurses and researchers in the UK |
Year(s) Of Engagement Activity | 2020 |
Description | Research featured on Humans of Health Research public exhibition hosted by Imperial College Academic Health Science Centre |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | This research was featured on Humans of Health Research public exhibition hosted by Imperial College Academic Health Science Centre, an exhibition which was open to the general public who can learn about the impact of medical research on patients. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.imperial.ac.uk/stories/humans-of-health-research-9/ |
Description | South West England Regional Neuroscience Meeting presentation on Neuromodulation in Gait dysfunction in Parkinson's |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Presented a talk on Neuromodulation in Gait Dysfunction in Parkinson's at the Southwest England Regional Neuroscience academic meeting, attended by neuroscience researchers, neurologists and trainees, and undergraduate/postgraduate students in neurology and neuroscience |
Year(s) Of Engagement Activity | 2020 |