Milestones in the Course of Parkinson's Disease

Parkinson's disease is a progressive neurodegenerative disorder. There are various ways to describe the severity and progresion of the disease. For clincal purposes the Hoehn and Yahr staging is still the mostly used, whereas the Braak staging is the best neuropathological staging. Using neuroanatomic analyses, clinical follow-up and technical investigations with SPEC and PET some typical milestones of Parkinson's disease have been established. At onset the cell death of dopaminergic neurons is high which is not noted by the patients due to the fact that motor symptoms do not occur until the patients have lost more than 60% of their nigral dopaminergic cells. In this prodromal phase non-motor symptoms such as hyposmia, REM sleep behaviour disorder, constipation and depression occur. This implies that the disease does not start in the substantia nigra which is supported by the findings of Braak and colleagues who detected Lewy pathology first in the olfactory bulb and medulla oblongata. Thereafter, Lewy bodies spread out to the cortex which explains dementia. Milestones such as visual hallucinations, dementia, admittance to a nursing home and frequent falls indicate that death will occur within the next 3-5 years independent of the age of the patient at the onset of Parkinson's disease. This suggests that the end stage is related to an exponential cell death.