Normal and pathological gait: what we learn from Parkinson's disease

Abstract

Gait and balance disorders represent a major therapeutic challenge in Parkinson's disease (PD). These symptoms respond poorly to dopaminergic treatments, except in the early phase of the disease. Currently, no other treatment is particularly efficient and rehabilitation appears to be the most effective approach. Since these gait and balance deficits are resistant to dopaminergic drugs, their occurrence could be related to the development of extradopaminergic lesions in PD patients. We provide a comprehensive description of the clinical features of gait and balance disorders in PD. We also highlight the brain networks involved in gait and balance control in animals and humans with a particular focus on the relevant structures in the context of PD, such as the mesencephalic locomotor region. We also review other neuronal systems that may be involved in the physiopathology of gait and balance disorders in PD (noradrenergic and serotoninergic systems, cerebellum and cortex). In addition, we review recent evidence regarding functional neurosurgery for gait disorders in PD and propose new directions for future therapeutic research.

Figure 1

A. Anatomy and connectivity of the pedunculopontine (PPN) and cuneiform nuclei (CN) in primates. Both nuclei have reciprocal connections with the basal ganglia (GP, globus pallidus; Pu, putamen; SN, substantia nigra; STN, subthalamic nucleus). They also receive inputs from the cerebellum and motor cortices. The existence of inputs from the spinal cord remains to be demonstrated in monkeys. The PPN and CN have major outputs to the descending reticulo-spinal pathway and the ascending thalamo-cortical pathway through the thalamic centromedian nucleus. Cholinergic neurons in the PPN visualized using NADPH-diaphorase histochemistry are also represented in a transverse brainstem section (lower right panel). B. Anterior view of surgical targets for Parkinson disease. Targets are defined in a three-dimensional histological atlas, with axial and coronal sections of the corresponding post-mortem T1-weighted MRI. The usual targets are visualized on the right hemisphere: GPi, internal globus pallidus; STN, subthalamic nucleus; Vim, ventral intermediate thalamic nucleus. New targets are visualized on the left hemisphere: CM, thalamic centromedian nucleus; CN, cuneiform nucleus; PPN, pedunculopontine nucleus; SNr, substantia nigra pars reticulata.