Freezing of Gait and its Associations in the Early and Advanced Clinical Motor Stages of Parkinson's Disease: A Cross-Sectional Study

Background: Freezing of gait is a common disabling symptom of Parkinson's disease (PD) with limited treatment options. The pathophysiological mechanisms of freezing behaviour are still contentious. Objective: To investigate the prevalence of freezing of gait and its associations with increasing disease severity to gain a better understanding of the underlying pathophysiology. Methods: This exploratory study included 389 idiopathic PD patients, divided into four groups; early and advanced PD with freezing of gait, and early and advanced PD without freezing of gait. Motor, cognitive and affective symptoms, REM sleep behaviour disorder and autonomic function were assessed. Results: Regardless of disease stage, patients with freezing of gait had more severe motor symptoms and a predominant non-tremor phenotype. In the early stages, freezers had a selective impairment in executive function and had more marked REM sleep behaviour disorder. Autonomic disturbances were not associated with freezing of gait across early or advanced disease stages. Conclusion: These findings support the notion that impairments across the frontostriatal pathways are intricately linked to the pathophysiology underlying freezing of gait across all stages of PD. Features of REM sleep behaviour disorder suggest a contribution to freezing from brainstem pathology but this does not extend to more general autonomic dysfunction.