Pre-motor and Non-motor Symptoms of Parkinson's Disease - Taxonomy, Clinical Manifestation and Neuropatholocical Correlates

Parkinson's disease (PD) is a multiple-system neurodegenerative disorder associated with typical alpha-synucleinopathy of Lewy type. It manifests clinically not only with the typical motor symptoms but also with the so-called non-motor symptoms (NMS). Recent data indicate that the non-motor symptoms occur in up to 100% of patients suffering from PD, they frequently determine the degree of disability and quality of life of patients much more than the motor symptoms. Since non-motor symptoms may even precede development of the "motor" disease by several decades, the term "pre-motor symptoms" has recently emerged. Non-motor symptoms also occur in late stages of the disease and form an integral part of the "advanced" PD clinical picture. NMS in PD are caused by impairment of central as well as peripheral extranigral structures by the Lewy's neurodegenerative process. Despite the increasing number of clinical-pathological and imaging studies published over the last decade, precise pathological and pathophysiological mechanisms of a number of these symptoms remain unclear.