Brain Advance Access published online on November 11, 2008
Brain, doi:10.1093/brain/awn294
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Effects of nigral stimulation on locomotion and postural stability in patients with Parkinson's disease
1Centre d’Investigation Clinique, Fédération des Maladies du Système Nerveux, Assistance Publique- Hôpitaux de Paris, 2Institut National de la Santé et de la Recherche Médicale, Unité 679, Université Pierre et Marie Curie-Paris 6, Groupe Hospitalier Pitié-Salpêtrière, Paris F-75013, 3Service de Neurophysiologie, Centre Hospitalier Universitaire de Rouen, Rouen F-76000, 4Groupe AVENIR-IFR 70, Institut National de la Santé et de la Recherche Médicale, Groupe Hospitalier Pitié-Salpêtrière, 5Centre National de la Recherche Scientifique, UPR 640, Université Pierre et Marie Curie-Paris 6, Paris F-75013, 6Centre de Neuro-Imagerie de Recherche CENIR, Université Pierre et Marie Curie-Paris 6, Paris F-75013, 7Centre National de la Recherche Scientifique, FRE 2507, Université Pierre et Marie Curie-Paris 6, Institut des Systèmes Intelligents et de Robotique, Paris F-75005 and 8LCMP/UFR STAPS-Orsay, Université Paris-Sud 11, Orsay F-91000, France
Correspondence to:
Marie-Laure Welter, MD, PhD, Fédération des Maladies du Système Nerveux, Centre d’Investigation Clinique, Groupe Hospitalier Pitié-Salpêtrière, 47-83 Boulevard de l’Hôpital, 75651 Paris CEDEX 13, France E-mail: marie-laure.welter{at}psl.aphp.fr
The physiopathology of gait and balance disorders in Parkinson's disease patients is still poorly understood. Levodopa treatment and subthalamic nucleus (STN) stimulation improve step length and walking speed, with less effect on postural instability. These disorders have been linked to dysfunction of the descending basal ganglia outputs to brainstem structures. In this study, we evaluated the effects of stimulation of the substantia nigra pars reticulata (SNr), on locomotion and balance in Parkinson's disease patients. Biomechanical parameters and leg muscle activity were recorded during gait initiation in seven selected patients operated for bilateral STN stimulation, out of 204 stimulated patients, with one contact of each electrode located within the SNr. Step length, anteroposterior and vertical velocities of the centre of gravity were studied, with special reference to the subjects’ ability to brake the centre of gravity fall before foot-contact, and compared to seven controls. In Parkinson's disease patients, five treatment conditions were tested: (i) no treatment, (ii) levodopa treatment, (iii) STN stimulation, (iv) SNr stimulation and (v) combined levodopa treatment and STN stimulation. The effects of these treatments on motor parkinsonian disability were assessed with the UPDRS III scale, separated into ‘axial’ (rising from chair, posture, postural stability and gait) and ‘distal’ scores. Whereas levodopa and/or STN stimulation improved ‘axial’ and ‘distal’ motor symptoms, SNr stimulation improved only the ‘axial’ symptoms. Compared to controls, untreated Parkinson's disease patients showed reduced step length and velocity, and poor braking just prior to foot-contact, with a decrease in both soleus (S) and anterior tibialis (AT) muscle activity. Step length and velocity significantly increased with levodopa treatment alone or in combination with STN stimulation in both natural and fast gait conditions, and with STN stimulation alone in the fast gait condition. Conversely, SNr stimulation had no significant effect on these measures in either condition. In the natural gait condition, no fall in the centre of gravity occurred as step length was low and active braking was unnecessary. In the fast gait condition, braking was improved with STN or SNr stimulation but not with levodopa treatment, with an increase in the stance leg S muscle activity. These results suggest that anteroposterior (length and velocity) and vertical (braking capacity) gait parameters are controlled by two distinct systems within the basal ganglia circuitry, representing respectively locomotion and balance. The SNr, a major basal ganglia output known to project to pontomesencephalic structures, is postulated as being particularly involved in balance control during gait.
Key Words: Gait and balance; Parkinson's disease; deep brain stimulation; substantia nigra; subthalamic nucleus
Abbreviations: AT, Anterior Tibialis; CG, Centre of Gravity; CP, Centre of Foot Pressure; GPi, Internal Part of the Globus Pallidus; L, Step Length; MRI, Magnetic Resonance Images; PD, Parkinson's Disease; PPN, Pedunculopontine Nucleus; PSP, Progressive Supranuclear Palsy; S, Soleus; STN, Subthalamic Nucleus; SNr, Substantia Nigra Pars Reticulata; V1, Minimum Vertical Velocity of the CG; V2, CG Vertical Velocity at Time of Foot-Contact; Vm, Maximum Anteroposterior Velocity of the CG.
Received May 21, 2008. Revised October 7, 2008. Accepted October 10, 2008.