A Double-blind, Cross-over Comparison of Closed Loop Versus Conventional Deep Brain Stimulation of the Subthalamic Nucleus in the Treatment of Parkinson's Disease

Parkinson's disease (PD) is the major neurological movement disorder in terms of both prevalence and morbidity, and in associated health care and social care costs. In the United Kingdom about 120,000 people are affected and associated costs are estimated at £ 2 billion per year. The current gold standard treatment for PD is levodopa therapy, however its use is limited by the development of motor complications in up to 80% of patients over a 5-10 year period. This has led to a resurgence in functional neurosurgery for PD over the last three decades.

Deep brain stimulation (DBS) is now accepted treatment for patients with severe PD and is supported by the Food and Drug Administration in the USA and National Institute of Clinical Excellence in the UK with trials providing evidence that it improves quality of life over best medical treatment. However, due to partial efficacy and side effects its potential is relatively limited and it has so far generally been restricted to patients with severe disease and uncontrollable motor complications with medical therapy.

Currently DBS provides continuous and fixed stimulation, but this constant stimulation promotes side-effects like speech disturbance. Research by the investigators has shown that by controlling the stimulation and only delivering it when needed side-effects can be reduced. To show this the investigators developed a form of adaptive DBS in which they controlled how much stimulation is delivered by directly recording the brain's activity from the electrode used for brain stimulation. This provides a feedback signal.

However, although adaptive DBS works in an acute research setting, there are still several questions to be answered before it can be translated in to a durable therapy option. The main remaining questions are whether the amelioration of Parkinsonian symptoms is maintained over periods longer than an hour or so, and whether it is triggered when arousals occur during sleep. The latter is important to ensure that mobility is maintained when turning in bed and during bathroom visits.

The Investigators would like to contrast conventional (continuous) DBS with adaptive DBS when the same patients with Parkinsons are treated while both awake and asleep. Thus they can follow treatment effects during the day and at night, in sleep. Patients will receive the two types of stimulation in randomised order. Patients will not be told which form of stimulation is being applied and the main measures used to evaluate the outcome of the study will be video-taped performance on a number of motor tasks and the video-taping of mobility during arousals and awakenings from sleep. Assessment of video-tapes is desirable as assessors can then be blind to the treatment being applied. Thus assessments should not be biased.