Neurophysiological mechanisms of gait disturbance in advanced Parkinson's disease patients

Abstract This review considers pathophysiological mechanisms of posture‐gait disturbances in Parkinson's disease (PD). Clinical studies have shown that posture‐gait disturbance attributes to the dysfunction of the whole neuraxis in addition to the musculoskeletal system. The cerebral cortex, basal ganglia (BG), cerebellum, brainstem, and spinal cord temporally and spatially integrate and coordinate multisensory feedback and efferent copies of the motor command. Therefore, the extensive repertoire of voluntary movements can be coupled with anticipatory and reactive postural adjustments to provide the framework for supporting and stabilizing the goal‐directed gait activity. Redundancies in the system allow adaptation and compensation through reward‐oriented and error‐based learning processes implemented through the BG and cerebellar pathways, respectively. However, the impairment of these systems in PD may considerably compromise the capacity to adapt and lead to maladaptive changes impairing posture‐gait control. When these impairments occur, the risk of falls can significantly increase, and interventions are required to reduce morbidity. The damage in dopamine (DA) neurons is the primary cause of PD. Insufficient DA supply in the striatum disturbs the operation of intrinsic networks in the BG. This also pathologically increases GABAergic BG output to the cerebral cortex and brainstem, resulting in functional disconnection of other structures from the BG. The disconnection makes PD patients disable to achieve habitually acquired automatized gait control. Moreover, Lewy body degeneration in most brain areas, particularly in cholinergic and other monoaminergic systems vulnerable to neurodegeneration, further disturbs posture‐gait control and alters non‐motor symptoms of PD.