A therapeutic approach to 'freezing' in Parkinson's disease

Freezing of gait has been described as one of the most disturbing and least understood symptoms of Parkinson?s disease. In its severest form it can stop patients in their tracks and render them completely immobile for 10 s or so as they urge themselves to walk. It is profoundly detrimental to patients? independence, quality of life, and health. It can often be a cause of falls leading to fractures, hospitalisation and social isolation. Freezing of gait is a common problem and difficult to treat. Conventional treatments for Parkinson?s disease, such as levodopa or deep brain stimulation, can abolish freezing in some patients. However, there are many other patients for whom freezing episodes persist after treatment. The present proposal targets this latter category of patient and suggests an alternative therapeutic approach based on non-invasive electrical stimulation techniques. Our hypothesis is that freezing results from a failure of the postural adjustment that has to occur before a foot can be lifted from the ground to take a step. Our plan is to evoke the postural adjustment by activating a reflex that is intact in Parkinson?s disease. This will be done by passing a small electrical current through the skin behind the ears, which stimulates nerves from balance organs in the inner ear and causes a reflex body sway. The body sway will act as a surrogate postural adjustment and free the leg for stepping. In addition, we shall electrically stimulate leg muscles to assist the subsequent stepping movement. We suggest that this sequence of stimulation will break the freezing episode and allow the gait cycle to continue. The results we obtain in our planned laboratory-based experiments will provide a starting point for designing a simple prosthetic device that can be used outside the laboratory.

Freezing of gait is a disturbing and poorly understood symptom of Parkinson‘s disease. It is a common symptom that is difficult to treat and detrimental to patients‘ independence, quality of life, and health. Conventional treatments for Parkinson‘s disease, such as levodopa or deep brain stimulation, can abolish freezing in some patients. However, there is a class of patients in whom freezing episodes persist after treatment (on-freezing). We plan to build a laboratory obstacle course that is designed to promote freezing of gait so that freezing can be measured and quantified in a controlled experimental environment. Non-contact 3-D motion capture systems and floor-mounted force places will be used to measure motor behaviour as subjects walk the obstacle course. With this we shall study a cohort of selected PD patients who suffer from freezing of gait. They will be studied both ‘on‘ and ‘off‘ levodopa. These data will enable us to classify freezing behaviour, to correlate it with clinical state, and to identify a sub-group of patients with on-freezing. We shall target this group and investigate the efficacy of an alternative therapeutic approach based on non-invasive electrical stimulation techniques. Our hypothesis is that freezing results from a failure of the postural adjustment that has to occur before a foot can be lifted from the ground to take a step. Our plan is to evoke an equivalent postural adjustment artificially by activating a vestibulospinal reflex that is intact in Parkinson‘s disease. This will be achieved using galvanic vestibular stimulation (GVS) in which a small direct current is applied via surface electrodes placed behind the ears to produce a reflex body sway. We shall first study GVS in a group of healthy subjects to determine the stimulation parameters required to produce an appropriately directed body sway. This will be applied to our sub-group of PD patients in an attempt to evoke body sway that will act as a surrogate postural adjustment and free the leg for stepping. In addition, we shall use functional electrical stimulation (FES) of leg muscles to assist the subsequent stepping movement. We shall test patients on the obstacle course to establish whether this sequence of stimuli can interrupt the freezing episode and allow the gait cycle to continue. If successful, these results will provide a starting point for designing a simple prosthetic device that can be used outside the laboratory.