Environmental risk factors of young onset Parkinson`s disease: a case-control study

While the cause of Parkinson's disease (PD) remains unknown, recent evidence suggests certain environmental factors, such as well water drinking, herbicides and pesticides exposure, and neurotoxins, may trigger the chain of oxidative reactions culminating in the death of dopaminergic neurons in substantia nigra to cause parkinsonism. Most studies to date focused on PD with old age onset. However, there is a peculiar group of parkinsonian patients, the young onset Parkinson's disease (YOPD), in whom the age of onset is before 40. It is intriguing to know whether earlier exposure to the putative neurotoxin(s) may contribute to the earlier onset. We therefore conducted this case-control study in which 60 PD patients, 30 YOPD patients and the same number of age- and sex-matched young controls were included. Using logistic regression, we found well water drinking and head injury were risk factors for the development of YOPD. When YOPD patients were compared with PD, we found head injury and exercise were the significant predictors. Keeping all other variables constant, head injury was a risk factor and exercise appeared to be a protective factor. We conclude early exposure to well water drinking and head trauma may trigger and expedite the appearance of parkinsonian features, but such acceleration may be prevented through regular exercise.

Shake rattle and roll: a journey with Parkinson's

This is the journey of a man suffering from Parkinson's disease. Ross Collins tells of his past twelve years' experiences of living with Parkinson's. Before, he had a steady job with Victoria Police, with promising future prospects; and was happily married with two young children. The disease struck him at an early age, changing his life and setting him on a different course. His outlook on life has changed, and his decision-making influenced; as well, his relationships with his family affected. He feels normal only when he is shaking, rattling and rolling along on his Harley. His wish for a cure leads him to pin his hopes on faith healing by the 'miracle man', in Brazil. The first two visits did not seem to have done anything to improve his physical condition. Ross is returning to Brazil for the third time, hoping against hope that his condition could be improved by a miracle healing. This documentary gives an intimate look into the life of a Parkinson's disease sufferer and that of his family. Includes al.

Role of dopamine D3 and serotonin 5-HT1A receptors in l-DOPA-induced dyskinesias and effects of sarizotan in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease

Sarizotan, a 5-HT1A agonist with additional affinity for D3 and D4 receptors, has been demonstrated to have anti-dyskinetic effects. The mechanism by which these effects occur is not clear. Using unilateral 6-hydroxydopamine-lesioned rats that received chronic intraperitoneal (ip) administration of L-3,4-dihydroxyphenylalanine (L-DOPA) we investigated the involvement of D3 and 5-HT1A receptors in the effects of sarizotan on contraversive circling and abnormal involuntary movements (AIMs). Before sensitization by chronic L-DOPA treatment (12.5 with 3.25 mg/kg benserazide ip, twice daily for 21 days), no effect of the selective D3 agonist, PD128907 (1 or 3 mg/kg ip), or the selectiveD3 antagonist,GR103691 (0.5 or 1.5 mg/kg ip), was observed. Treatment with sarizotan (1 or 5 mg/kg ip) dosedependently inhibited the L-DOPA-induced contraversive turning and AIMs. In co-treatment with the 5-HT1A antagonist, WAY100635 (1 mg/kg ip), sarizotan failed to affect this behaviour, confirming the prominent 5-HT1A receptor-mediated mechanism of action. In the presence of PD128907 (3 mg/kg ip), the effects of sarizotan on contraversive turning, locomotive dyskinesia and axial dystonia, but not on orolingual and forelimb dyskinesia, were blocked. On its own, PD128907 had no effect on the behavioural effects of L-DOPA except that it tended to reduce orolingual and forelimb dyskinesia. GR103691 had no effect on its own or in combination with sarizotan. These data identify an involvement of D3 receptors in the action of sarizotan on some, but not all L-DOPA-induced motor side effects. This selective involvement is in contrast to the more general involvement of 5-HT1A receptors in the anti-dyskinetic effects of sarizotan.

Underlying neurobiology and clinical correlates of mania status after subthalamic nucleus deep brain stimulation in Parkinson's Disease : a review of the literature

Deep brain stimulation (DBS) is a novel and effective surgical intervention for refractory Parkinson's disease (PD). The authors review the current literature to identify the clinical correlates associated with subthalamic nucleus (STN) DBS-induced hypomania/mania in PD patients. Ventromedial electrode placement has been most consistently implicated in the induction of STN DBS-induced mania. There is some evidence of symptom amelioration when electrode placement is switched to a more dorsolateral contact. Additional clinical correlates may include unipolar stimulation, higher voltage (>3 V), male sex, and/or early-onset PD. STN DBS-induced psychiatric adverse events emphasize the need for comprehensive psychiatric presurgical evaluation and follow-up in PD patients. Animal studies and prospective clinical research, combined with advanced neuroimaging techniques, are needed to identify clinical correlates and underlying neurobiological mechanisms of STN DBS-induced mania. Such working models would serve to further our understanding of the neurobiological underpinnings of mania and contribute valuable new insight toward development of future DBS mood-stabilization therapies.

Rural living and health-related quality of life in Australians with Parkinson's disease

Introduction: The motor and non-motor symptoms associated with idiopathic Parkinson’s disease (PD) may compromise the health-related quality of life (HRQOL) of some individuals living with this debilitating condition. Although growing evidence suggests that PD may be more prevalent in rural communities, there is little information about the life quality of these individuals. This study examines whether HRQOL ratings vary in relation to rural and metropolitan life settings.
Methods: An analytic cross-sectional study was conducted to compare the HRQOL of two separate samples of people with PD living in metropolitan Melbourne and rural Victoria. The metropolitan sample consisted of 210 individuals who had participated in the baseline assessment for an existing clinical trial. The rural sample comprised 24 participants who attended community-based rehabilitation programs and support groups in rural Victoria. Health-related quality of life was quantified using the Parkinson’s Disease Questionnaire-39 (PDQ-39).
Results: The HRQOL of participants in rural Australia differed from individuals living in a large metropolitan city (p=0.025). Participants in rural Australia reported worse overall HRQOL, after controlling for differences in disease duration. Their overall HRQOL was lower than for city dwellers. Rural living was also found to be a significant negative predictor of HRQOL (β=0.14; 95% CI -1.27 to -0.08; _p=0.027).
Conclusion: The findings of this study suggest that some people with PD living in rural Victoria perceive their HRQOL to be relatively poor. In order to minimise the debilitating consequences of this disease, further studies examining the factors that may contribute to the HRQOL of individuals living in rural and remote areas are required.

Health-related quality of life of Australians with Parkinson disease : a comparison with international studies

Purpose: This study describes the health-related quality of life (HRQOL) of Australians living with Parkinson disease (PD) and compares the findings to international reports.
Methods: The Parkinson’s Disease Questionnaire-39 (PDQ-39) was used to measure HRQOL in 210 individuals with PD living in Australia. In parallel, a tailored literature search identified previous studies on HROQL in people with PD. A quantitative meta-analysis with a random-effects model was used to compare the HRQOL of individuals with PD living in Australia and other countries.
Results : The mean PDQ-39 summary index (SI) score for this sample of Australians with PD was 20.9 (SD 12.7). Ratings for the dimension of social support and stigma were significantly lower than ratings for bodily discomfort, mobility, activities of daily living, cognition, and emotional well-being. Comparing the Australian and international PD samples revealed a significant heterogeneity in overall HRQOL (I² = 97%). The mean PDQ-39 SI scores for Australians were lower, indicating better HRQOL relative
to samples from other countries.
Conclusions: This Australian sample with PD perceived their HRQOL as poor, although it was less severely compromised than that of international samples. While further research is required, these findings can inform the clinical decision-making processes of physiotherapists

Quantifying the profile and progression of impairments, activity, participation, and quality of life in people with Parkinson disease : protocol for a prospective cohort study

Background Despite the finding that Parkinson disease (PD) occurs in more than one in every 1000 people older than 60 years, there have been few attempts to quantify how deficits in impairments, activity, participation, and quality of life progress in this debilitating condition. It is unclear which tools are most appropriate for measuring change over time in PD.
Methods and design This protocol describes a prospective analysis of changes in impairments, activity, participation, and quality of life over a 12 month period together with an economic analysis of costs associated with PD. One-hundred participants will be included, provided they have idiopathic PD rated I-IV on the modified Hoehn & Yahr (1967) scale and fulfil the inclusion criteria. The study aims to determine which clinical and economic measures best quantify the natural history and progression of PD in a sample of people receiving services from the Victorian Comprehensive Parkinson's Program, Australia. When the data become available, the results will be expressed as baseline scores and changes over 3 months and 12 months for impairment, activity, participation, and quality of life together with a cost analysis.
Discussion This study has the potential to identify baseline characteristics of PD for different Hoehn & Yahr stages, to determine the influence of disease duration on performance, and to calculate the costs associated with idiopathic PD. Valid clinical and economic measures for quantifying the natural history and progression of PD will also be identified.

Cost effectiveness of preventing falls and improving mobility in people with Parkinson disease : protocol for an economic evaluation alongside a clinical trial

Background Cost of illness studies show that Parkinson disease (PD) is costly for individuals, the healthcare system and society. The costs of PD include both direct and indirect costs associated with falls and related injuries.
Methods This protocol describes a prospective economic analysis conducted alongside a randomised controlled trial (RCT). It evaluates whether physical therapy is more cost effective than usual care from the perspective of the health care system. Cost effectiveness will be evaluated using a three-way comparison of the cost per fall averted and the cost per quality adjusted life year saved across two physical therapy interventions and a control group.
Conclusion This study has the potential to determine whether targetted physical therapy as an adjunct to standard care can be cost effective in reducing falls in people with PD.

A randomized controlled trial to reduce falls in people with Parkinson's Disease

Background. Falls are common and disabling in people with Parkinson's disease (PD). There is a need to quantify the effects of movement rehabilitation on falls in PD. Objective. To evaluate 2 physical therapy interventions in reducing falls in PD. Methods. We randomized 210 people with PD to 3 groups: progressive resistance strength training coupled with falls prevention education, movement strategy training combined with falls prevention education, and life-skills information (control). All received 8 weeks of out-patient therapy once per week and a structured home program. The primary end point was the falls rate, recorded prospectively over a 12 month period, starting from the completion of the intervention. Secondary outcomes were walking speed, disability, and quality of life. Results. A total of 1547 falls were reported for the trial. The falls rate was higher in the control group compared with the groups that received strength training or strategy training. There were 193 falls for the progressive resistance strength training group, 441 for the movement strategy group and 913 for the control group. The strength training group had 84.9% fewer falls than controls (incidence rate ratio [IRR] = 0.151, 95% CI 0.071-0.322, P < .001). The movement strategy training group had 61.5% fewer falls than controls (IRR = 0.385, 95% CI 0.184-0.808, P = .012). Disability scores improved in the intervention groups following therapy while deteriorating in the control group. Conclusions. Rehabilitation combining falls prevention education with strength training or movement strategy training reduces the rate of falls in people with mild to moderately severe PD and is feasible.

Lower limb progressive resistance training improves leg strength but not gait speed or balance in Parkinson's disease: a systematic review and meta-analysis.

The use of progressive resistance training (PRT) to improve gait and balance in people with Parkinson's disease (PD) is an emerging area of interest. However, the main effects of PRT on lower limb functions such as gait, balance, and leg strength in people with PD remain unclear. Therefore, the aim of the meta-analysis is to evaluate the evidence surrounding the use of PRT to improve gait and balance in people with PD. Five electronic databases, from inception to December 2014, were searched to identify the relevant studies. Data extraction was performed by two independent reviewers and methodological quality was assessed using the PEDro scale. Standardized mean differences (SMD) and 95% confidence intervals (CIs) of fixed and random effects models were used to calculate the effect sizes between experimental and control groups and I (2) statistics were used to determine levels of heterogeneity. In total, seven studies were identified consisting of 172 participants (experimental n = 84; control n = 88). The pooled results showed a moderate but significant effect of PRT on leg strength (SMD 1.42, 95% CI 0.464-2.376); however, no significant effects were observed for gait speed (SMD 0.418, 95% CI -0.219 to 1.055). No significant effects were observed for balance measures included in this review. In conclusion, our results showed no discernable effect of PRT on gait and balance measures, although this is likely due to the lack of studies available. It may be suggested that PRT be performed in conjunction with balance or task-specific functional training to elicit greater lower limb functional benefits in people with PD.

Interactive effects of GPI stimulation and levodopa on postural control in Parkinson's disease.

INTRODUCTION: Postural instability is a major source of disability in idiopathic Parkinson's disease (IPD). Deep brain stimulation of the globus pallidus internus (GPI-DBS) improves clinician-rated balance control but there have been few quantitative studies of its interactive effects with levodopa (L-DOPA). The purpose of this study was to compare the short-term and interactive effects of GPI-DBS and L-DOPA on objective measures of postural stability in patients with longstanding IPD. METHODS: Static and dynamic posturography during a whole-body leaning task were performed in 10 IPD patients with bilateral GPI stimulators under the following conditions: untreated (OFF); L-DOPA alone; DBS alone; DBS+L-DOPA, and in 9 healthy Control subjects. Clinical status was assessed using the UPDRS and AIMS Dyskinesia Scale. RESULTS: Static sway was greater in IPD patients in the OFF state compared to the Control subjects and was further increased by L-DOPA and reduced by GPI-DBS. In the dynamic task, L-DOPA had a greater effect than GPI-DBS on improving Start Time, but reduced the spatial accuracy and directional control of the task. When the two therapies were combined, GPI-DBS prevented the L-DOPA induced increase in static sway and improved the accuracy of the dynamic task. CONCLUSION: The findings demonstrate GPI-DBS and L-DOPA have differential effects on temporal and spatial aspects of postural control in IPD and that GPI-DBS counteracts some of the adverse effects of L-DOPA. Further studies on larger numbers of patients with GPI stimulators are required to confirm these findings and to clarify the contribution of dyskinesias to impaired dynamic postural control.