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Abstract: Background: Motor response complications that arise with repeated L-dopa administration for the treatment of Parkinson’s disease are well understood but the relationship between motor response complications and affect are not. We proposed that patients with dyskinesias would report rebound worsening in affect during wearing-off of L-dopa effect. Methods: Fifty Parkinson’s disease patients with were assessed with the Purdue Pegboard test and rated Positive Affect and Negative Affect after overnight withdrawal of dopaminergic medications and half hourly for 6 h after a standard L-dopa challenge. Patients were carefully classified into stable responder (n = 12), fluctuator (n = 15), and dyskinetic (n = 23) groups. Results: Positive Affect was improved by L-dopa in dyskinetics and to a lesser degree in fluctuators but not in stable responders. At T = 4–6 h, Positive Affect rebounded below baseline in dyskinetics only. On regression analysis, rebound worsening positively correlated with ratings of dyskinesia severity. Negative Affect improved with L-dopa in all groups and tended to remain below baseline for 6 h after L-dopa challenge. Peak effects of L-dopa on Positive Affect and Negative Affect occurred significantly earlier than effects on Purdue Pegboard test and were positively correlated with L-dopa equivalent daily dose. Conclusion: There is a clinical dissociation between L-dopa effects on motor function, Positive Affect and Negative Affect. Rebound worsening in Positive Affect occurred only in dyskinetic patients and the onset of rebound worsening occurred before the end of the motor benefit phase. These observations could explain why some Parkinson patients report wearing-off symptoms despite the external impression of good motor control. [Copyright &y& Elsevier]

Abstract: Data regarding the effect of deep brain stimulation (DBS) surgery on the dopamine dysregulation syndrome (DDS), impulse control disorders (ICDs) and punding in Parkinson’s disease (PD) are limited. We present a case series of 21 operated PD patients who had exhibited DDS, ICDs or punding at some stage during the disease. DDS remained unimproved or worsened post-operatively in 12/17 patients with pre-operative DDS (71%) (nine bilateral subthalamic nucleus [STN], one right-sided STN, two bilateral globus pallidus internus [GPi] DBS). DDS improved or resolved after bilateral STN DBS in 5/17 patients with pre-operative DDS. DDS apparently developed for the first time after bilateral STN DBS in two patients, although only after a latency of eight years in one case. One patient without reported pre-operative DDS or ICDs developed pathological gambling post-STN DBS. One patient had pathological gambling which resolved pre-operatively, and did not recur post-DBS. Thus, DDS, ICDs and punding may persist, worsen or develop for the first time after DBS surgery, although a minority of patients improved dramatically. Predictive factors may include physician vigilance, motor outcome and patient compliance. [Copyright &y& Elsevier]

Dopamine replacement therapy (DRT) is the most effective treatment for Parkinson''s disease (PD); it provides substantial benefit for most patients, extends independence, and increases survival. A few patients with PD, however, take increasing quantities of medication far beyond those required to treat their motor disabilities. These patients demand rapid drug escalation and continue to request more DRT despite the emergence of increasingly severe drug-induced motor complications and harmful behavioural consequences. In this article we detail the features of compulsive DRT-seeking and intake in PD, in relation to theories of compulsive drug use. [Copyright &y& Elsevier]

1·8 billion people of diverse ethnicities and cultures live in the Western Pacific Region. The increasing longevity of populations in this region is a major contributor to the exponential increase in Parkinson's disease prevalence worldwide. Differences exist between Parkinson's disease in the Western Pacific Region and in Europe and North America that might provide important insights into our understanding of the disease and approaches to management. For example, some genetic factors (such as LRRK2 mutations or variants) differ, environmental exposures might play differential roles in modulating the risk of Parkinson's disease, and fewer dyskinesias are reported, with some differences in the profile of non-motor symptoms and comorbidities. Gaps in awareness of the disease and inequitable access to treatments pose challenges. Further improvements in infrastructure, clinical governance, and services, and concerted collaborative efforts in training and research, including greater representation of the Western Pacific Region in clinical trials, will improve care of patients with Parkinson's disease in this region and beyond. [ABSTRACT FROM AUTHOR]

Introduction: Pain is a common and disabling non-motor symptom of Idiopathic Parkinson's disease (PD) but its underlying pathophysiological mechanisms are not well understood. There is evidence to suggest that altered pain sensitivity may contribute to the experience of pain in PD patients, but clinical studies investigating this have yielded inconsistent results.Objectives: To examine whether pain thresholds are altered in PD patients compared to normal healthy controls (HC), via the use of systematic review and meta-analysis.Data Sources: A systematic search of the MEDLINE and EMBASE library from 1966 to April 2015.Study Selection: Studies that compared pain thresholds in PD patients versus HC were included in the systematic review. Additionally, data comparing PD patients off dopaminergic medications (PDMoff) to HC off medications (HCMoff) were pooled for meta-analysis by pain modality.Main Outcomes: Heat pain threshold, cold pain threshold, electrical pain threshold, nociceptive withdrawal reflex threshold, pressure pain threshold, and pain ratings.Results: 22 studies were reviewed, comprising of 616 PD and 451 HC. In the comparison of PDMoff versus HCMoff, a large majority of trials (15/19) found reduced pain thresholds (increased pain sensitivity) in PD patients. Meta-analysis of these trials revealed significantly reduced pain thresholds, of moderate to large effect size, in PD patients across all pain modalities. Results were much more heterogenous when PD patients on medications were compared with HC off medications, with most trials reporting no significant difference in pain thresholds between groups. No significant differences were found in pain thresholds for trials that compared PD patients on medications and HC on medications.Conclusion: PD patients are more sensitive to noxious stimuli compared to HC when tested in the off medication state. This increase in pain sensitivity is observed across all modalities, but is not as apparent when PD patients are administered Levodopa, suggesting that dopamine deficient states may contribute to hyperalgesia. However, it remains to be seen whether or not increased pain sensitivity translates clinically into increased prevalence of pain. Similarly, it is unclear if dopaminergic medications influence pain sensitivity. Performing a meta-analysis on studies comparing pain thresholds in PD patients with and without pain, and on and off dopaminergic medications, may draw more definitive conclusions in this regard. [ABSTRACT FROM AUTHOR]