Fig. 3

Biotherapeutic disease-modifying treatment. The specific PD-NMS treatment outcome evaluation is included in the 2011 and 2019 guidelines of the International Parkinson’s Disease and Movement Disorders Society (www.movementdisorders.org), providing their optimized, recommended, and standardized treatment strategic issues. It has been performed based on the clinical significance, the effectiveness, and the safety, for any random trials on large cohort of PD-NMS intervention candidates only. By number, PD becomes the second most common progressive neurodegenerative disease, demonstrated by a variety of pathological features with the progressive cellular loss for substantia nigra dopaminergic neurons and by an appearance of neurotoxic Lewy bodies. To our knowledge, whether precise neuronal cell replacement strategies may halt the disease progress/delay the PD symptoms remains unproved. In addition to the typical manifestations with PD motor symptoms, there is, more devastating if untreated, a wider range of NMS to be managed [83]. Since that occurrence usually lasts over years, all together, PD and related symptoms can bring huge costs and problems. There are major impacts on patient families, hospitalization/nursing cost, and challenge to the clinical management [84]. It is critical for identifying an early PD/pre-PD stage with PD-NMS considering diagnosis/treatment. PD-NMS with/without symptomatic comorbidities usually involve larger individual differences and wider spectrum from lack of specificity. Those symptoms are potentially driven by underlying disease processes rather than coping with PD. Fundamental to PD-NMS, many of which begin prior to motor deficits, the pathological feature distinctly involves non-dopaminergic processes. Current PD treatments against both its motor symptoms and PD-NMS as well as considerations for an effective recognition of PD-NMS management are referenced in the “Chinese Parkinson's Disease Treatment Guidelines,” [85] recently updated with the fourth edition