James Parkinson accurately described the motor problems of patients with Parkinson’s disease but also noted several non-motor features. While most people associate Parkinson’s disease (PD) with tremors and other abnormal body movements, PD also affects other areas of the nervous system. The increasing improvement of PD therapy improved the control of motor symptoms and unmasked non-motor and nondopaminergic symptoms. Moreover, several studies have shown that the non-motor symptoms of PD, such as depression, psychosis, falls, and sleep disturbance, have greater signifi cance when assessed by quality-of-life measures, institutionalization rates, or health economics.
Non-motor symptoms correlate with advancing age and disease severity, although some non-motor symptoms, such as olfactory problems, constipation, and depression, can occur early in the disease. As the average age and life expectancy of the population increases, the non-motor features of PD are becoming increasingly important. In the advanced stages non-levodopa responsive non-motor symptoms, such as diffi culties with balance, sleep disturbance, memory failure or confusional episodes, and dribbling of saliva, are the most disabling features of the disease.
Our understanding of the sequence and distribution of pathological changes in PD continues to evolve with non-dopaminergic cell dysfunction being thought to play a major part in the development of the non-motor symptom complex. A substantial part of the discussion in relation to the pathophysiology of non-motor symptoms, therefore, remains speculative. The traditional view that the pathological process in PD starts with degeneration of dopaminergic neurons in the substantia nigra has been challenged by Braak and colleagues who introduced the concept of a six-stage pathological process.
Some non-motor symptoms may emerge during the “off” periods and characterize the non-motor “off”. These phenomena are underestimated and can be the first sign of the wearing-off phenomenon. Non-motor symptoms, such as anxiety, pain, tingling, coldness of limbs, restless legs, and unclear thinking, can occur at the onset of wearing-off and a specific wearing-off patient questionnaire has been validated to aid clarification and better definition of motor and non-motor symptoms in PD related to wearing-off.
These pieces of evidence should lead us to think that PD is a systemic disorder and not only a movement disorder. Dopaminergic drugs improve motor symptoms but non-motor symptoms remained an unsolved problem and require attention. Poor recognition of non-motor symptoms affects cost of care of patients with the disease. The research for new drugs or other therapeutic approaches should seriously consider non-motor symptoms. A therapeutic approach able to improve at least some of the non-motor symptoms will be a real step forward in the management of PD.