The clinical diagnosis of Parkinson's disease rests on the identification of the characteristics related to dopamine deficiency that are a consequence of degeneration of the substantia nigra pars compacta. However, non-dopaminergic and non-motor symptoms are sometimes present before diagnosis and almost inevitably emerge with disease progression. Indeed, non-motor symptoms dominate the clinical picture of advanced Parkinson's disease and contribute to severe disability, impaired quality of life, and shortened life expectancy. By contrast with the dopaminergic symptoms of the disease, for which treatment is available, non-motor symptoms are often poorly recognised and inadequately treated. However, attention is now being focused on the recognition and quantitation of non-motor symptoms, which will form the basis of improved treatments. Some non-motor symptoms, including depression, constipation, pain, genitourinary problems, and sleep disorders, can be improved with available treatments. Other non-motor symptoms can be more refractory and need the introduction of novel non-dopaminergic drugs. Inevitably, the development of treatments that can slow or prevent the progression of Parkinson's disease and its multicentric neurodegeneration provides the best hope of curing non-motor symptoms.
"There is good evidence that patient priorities in symptomatology do not consistently match those of the treating physician's. Patients often put greater emphasis on "soft signs" rather than the more readily quantifiable and overt symptomatology . For instance, in a survey conducted by Parkinson's Movement (http://parkinsonsmovement.com), there was little correlation between patient-reported quality of life and motor symptoms, suggesting that motor symptoms, the most visible to a physician, are an inadequate measure upon which to base treatment decisions (figure 1). "
[Show abstract][Hide abstract] ABSTRACT: Parkinson's Disease (PD) involves well known motor symptoms such as tremor, rigidity, bradykinesia, and altered gait but there are also non-locomotory motor symptoms (e.g., changes in handwriting and speech) and even non-motor symptoms (e.g., disrupted sleep, depression) that can be measured, monitored, and possibly better managed through activity based monitoring technologies. This will enhance quality of life (QoL) in PD through improved self-monitoring, and also provide information which could be shared with a health care provider to help better manage treatment. Until recently, non-motor symptoms ("soft signs") had been generally overlooked in clinical management yet these are of primary importance to patients and their QoL. Day-to-day variability of the condition, the high variability in symptoms between patients, and the isolated snapshots of a patient in periodic clinic visits makes better monitoring essential to the proper management of PD. Continuously monitored patterns of activity, social interactions, and daily activities could provide a rich source of information on status changes, guiding self correction and clinical management. The same tools can be useful in earlier detection of PD and will improve clinical studies. Remote medical communications in the form of telemedicine, sophisticated tracking of medication use, and assistive technologies that directly compensate for disease related challenges are examples of other near term technology solutions to PD problems. Ultimately, a sensor technology is no good if it is not used. The Parkinson's community is a sophisticated early adopter of useful technologies and a group for which engineers can provide near term gratifying benefits.
"Alongside motor symptoms, people with PD also experience non-motor symptoms (NMS) such as: pain, drooling; choking/ swallowing difficulties; constipation; bladder dysfunction; cognitive impairment; hallucinations; depression/anxiety; sexual dysfunction; insomnia, which occur from disease onset . Nonmotor symptoms contribute to severe disability, impaired QoL, and institutionalization , and can be more troublesome and disabling for the patient than motor complications . Recent work suggests some NMS are treatable using device-aided therapies   since they are often dopaminergic in origin. "
"Thus, it may be important for clinicians to consider the complementary effects of dopaminergic and anti-anxiety medications on baseline trait anxiety levels in the management of PD and potentially other movement disorders, especially when considering the secondary influences on gait. Dopamine receptor agonists (such as pramipexole and ropinerole) may be an alternative therapeutic strategy, as dopamine agonists can increase dopamine levels within the limbic system (D3 receptors) and alleviate anxiety symptoms (Chaudhuri et al., 2006; Lemke, 2008; Coakeley et al., 2014), which might also reduce motor symptoms that are worsened by anxiety. Another advantage is that dopamine agonists are argued to reduce motor fluctuations that have been shown to amplify anxiety in PD (Henderson et al., 1992; Witjas et al., 2002; Richard, 2005; Leentjens et al., 2012), and possibly accelerate the 'wearing off' period. "
[Show abstract][Hide abstract] ABSTRACT: In order to understand how dopamine modulates the effect of anxiety on gait, the goal of this study was to use virtual reality to provoke anxiety in PD (in both ON and OFF states) and quantify its effect on gait. Seventeen PD and 20 HC were instructed to walk in a virtual environment in two anxiety-provoking conditions: (i) across a plank that was located on the GROUND; (ii) across an ELEVATED plank. All PD participants completed this in both the ON and OFF states, and then were striated into groups based on baseline trait anxiety scores for further analyses. Anxiety (skin conductance and self-report) and spatiotemporal aspects of gait were measured. Overall, the ELEVATED condition resulted in greater skin conductance levels and self-reported anxiety levels. Additionally, all participants demonstrated slower gait with increased step-to-step variability when crossing the ELEVATED plank compared to the plank on the GROUND. Results showed that dopaminergic treatment selectively improved gait in only the highly anxious PD group, by significantly improving velocity, step length, step time and step-to-step variability specifically when walking across the ELEVATED plank (ON versus OFF comparison). In conclusion, only highly trait anxious PD benefitted from dopaminergic treatment, specifically when walking in the anxiety-provoking environment. Improvements to gait during anxious walking might be a result of dopaminergic medication acting in two ways: 1) improving the basal ganglia's capacity to process information and 2) by reducing the load from anxiety and subsequently making more resources available to effectively process other competing inputs. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
European Journal of Neuroscience 04/2015; DOI:10.1111/ejn.12928 · 3.18 Impact Factor
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