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Funded Studies

Freezing in Parkinson’s Disease: Clinical, Electrophysiological and Therapeutic Studies

Gait disorders and Freezing of Gait (FOG) are among the very common, disabling and poorly understood symptoms of Parkinson's disease. FOG is a debilitating phenomenon in which the person is suddenly unable to initiate gait or to continue moving forward. It affects up to 53% of the patients after 5 years of illness, and up to 85% in more advanced stages of the disease. In addition to restricting the patients' mobility, autonomy and independence, gait disorders and FOG are often responsible for falls, which can have severe consequences and diminish the quality of life of the patients. In advanced stages of the disease, these symptoms are little improved, if at all, by current therapeutic approaches, be it medication or brain surgery. This is largely so because of a lack of understanding of the basis of gait disturbances and FOG. The aim of this project is to evaluate the effects of electrical stimulation of a particularly promising brain region, the Peduncolo-Pontine Nucleus. This small area of the brain stem has been shown to play an important role in the control of gait, and we believe that stimulating the neurons in this region will alleviate gait disturbances and FOG. The feasibility of the surgical procedure has recently been demonstrated. We now want to precisely and objectively evaluate the benefits of this procedure in terms of relief from freezing, improvement of gait and improvement of patients' quality of life. Based on previous research, we expect a great improvement of the gait disorders. This study will enable us to determine the best site and the best electrical settings for stimulation, in order to propose a new procedure for the treatment of these severely disabling symptoms.

Final Outcome

Our aim was to assess the efficacy of deep brain stimulation of the pedunculopontine nucleus (PPN), which is believed to be involved in the control of gait, on freezing of gait (FOG), a sudden inability to walk that can lead to falls.

Eleven patients were operated on and received electrodes bilaterally in the PPN area. They were followed for two to four years.

The results showed an improvement of FOG and a reduction of the risk of fall in eight patients, the benefit being major in four. There was no serious adverse event; however, in one patient, postural instability was aggravated. Most patients also noticed an improvement of alertness, with a decrease in daytime sleepiness.

Quality of life was improved, but only in the mobility domain. There was no major effect on the other parkinsonian symptoms, but about half of the patients could decrease their daily dopaminergic medication.

It has been very difficult to determine the best stimulation parameters. We confirmed that a stimulation frequency of about 20 Hz was preferable to higher frequencies. We also observed that intermittent stimulation, with night arrests, efficiently limited the waning of the benefits observed after several weeks of continuous stimulation.

The reasons of the large variability in the outcome are not yet understood. The patients who had the best effects had a fully or partially dopa-resistant FOG. More studies will be needed to precisely define the factors predicting the best outcome of this new surgery.


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