Spinal cord stimulation for gait dysfunction in Parkinson's disease

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.

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.

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.