Motor fluctuations and dyskinesias in advanced/end stage Parkinson's disease: A study from a population of brain donors

Treatment-related motor fluctuations (MFs) and dyskinesias are considered one of the most important problems in the long-term management of Parkinson's disease (PD). However, only a few studies have focused on their characteristics during advanced and end stages of the disease. We therefore assessed MFs and dyskinesias in a cohort of 61 late/end stage patients with a clinical and pathological diagnosis of PD and investigated the influence of disease- and treatment-related variables on their occurrence. A total of 62.3% of our patients experienced "wearing-off" phenomena, 68.9% "on-off" motor fluctuations and 60.7% dyskinesias at advanced/end stage disease. Age at disease onset and disease duration were significantly associated with dyskinesias. A substantial number of patients experienced spontaneous resolution of their motor complications during the last two years of their disease without treatment modifications. The clinical heterogeneity of treatment-related motor complications in PD points towards a complex mechanism for their etiopathogenesis. Although advanced disease and L-dopa administration are closely tied to their development, other mechanisms involving synaptic aging, altered neuronal plasticity and post-synaptic degeneration may be involved.