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Background: Parkinson's disease (PD) patients develop levodopa induced dyskinesia with disease progression from sensitization of central pathways. Pain pathways are also impacted with suggestions dyskinetic patients may process pain differently., Objective: Establish if centrally sensitized nociceptive pathways are altered and dopaminergically driven in dyskinetic patients., Methods: Clinical characteristics, affect, pain thresholds and sensitivity to pressure stimulation in the ON and OFF medication states as well as distribution of pain related activation of cortical regions on BOLD fMRI were assessed and compared between groups of patients suffering from dyskinesia and not., Results: Dyskinetic PD participants experienced increased pressure pain sensitivity. This was associated with increased pressure induced pain>innocuous BOLD activity in areas associated with encoding pain intensity, pain spatial orientation, descending pain mediation, sensorimotor integration, and motor control. Levodopa reduced pressure pain ratings and improved negative affect, though did not impact BOLD activity differently between the groups., Conclusion: Dyskinetic PD patients experience increased pain sensitivity and centrally sensitized nociceptive pathways resembling levodopa induced sensitization though this is not directly influenced by dopamine., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: The increasing global burden of Parkinson's disease (PD) poses a particular challenge for developing countries, such as Thailand, when delivering care to a geographically diverse populace with limited resources, often compounded by a lack of expertise in the use of certain PD medications, such as device-aided therapies (DAT)., Areas Covered: A panel of local, regional, and international PD experts convened to review the unmet needs of PD in Thailand and share insights into effective delivery of DAT, focusing on experience with apomorphine infusion. Despite its proven efficacy and safety, implementation of apomorphine infusion as a new option was not straightforward. This has prompted a range of health-care professional and patient-focused initiatives, led by the Chulalongkorn Center of Excellence for Parkinson's Disease and Related Disorders in Bangkok, to help establish a more coordinated approach to PD management throughout the country and ensure patients have access to suitable treatments., Expert Opinion: Overcoming the challenges of education, proficiency, resource capacity and standard of care for PD patients in developing countries requires a coordinated effort both nationally and beyond. The best practices identified in Thailand following the introduction of apomorphine infusion might be helpful for other countries when implementing similar programs.

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Impulse control disorders (ICDs) and related impulsive and compulsive behaviors (together called ICBs) have been increasingly recognized in the context of Parkinson's disease (PD) and treatment. The International Parkinson's and Movement Disorder Society commissioned a task force to assess available clinical screening instruments and rating scales, including their clinimetric properties, make recommendations regarding their utility, and suggest future directions in scale development and validation. The literature was systematically searched for scales measuring a range of reported ICBs in PD. A scale was designated "recommended" if the scale had been employed in PD studies, been used beyond the group that developed it, and had adequate clinimetric data published for PD. Numerous diagnostic screening tools and severity rating scales were identified for a range of ICBs, including compulsive medication use, punding/hobbyism, walkabout, pathological gambling, hypersexuality, compulsive or binge eating, compulsive buying, reckless driving, compulsive exercise, pyromania, trichotillomania, hoarding, kleptomania, intermittent explosive disorder, and internet addiction. For screening across the range of ICBs (except compulsive medication use), the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP) and QUIP-Rating Scale (QUIP-RS) are recommended, and for severity rating across the range of ICBs the QUIP-RS and the Ardouin Scale of Behavior in Parkinson's Disease are recommended. The Scale for Outcomes in Parkinson's Disease-Psychiatric Complications is recommended for rating of hypersexuality and the compulsive behaviors gambling/shopping. Further testing of established scales against gold standard diagnostic criteria is urgently required for all other individual ICBs in PD. © 2019 International Parkinson and Movement Disorder Society © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)

Patients with Parkinson disease (PD) experience hyperalgesia on evoked pain sensitivity testing, although the relationship of this with persistent pain in PD is less certain. Studies examining this have generated contradictory findings. Further, the role of dopaminergic deficiency as an underlying substrate for hyperalgesia is controversial. We report the results of meta-analyses of the PD pain sensitivity literature in an attempt to answer these questions. We identified 429 records, of which ten articles compared pain sensitivity between PD patients that experienced clinical pain (PDP) to those who did not (PDNP), and twenty studies that examined the effect of dopaminergic medications on pain sensitivity in PD patients. PDP patients experienced a moderate increase in pain sensitivity, had more severe disease, required higher dosages of medication, and were more likely to be female when compared to those PDNP patients. PD patients also had reduced pain sensitivity when tested on dopaminergic medications compared to when they were not on medications. Overall, the results of this systematic review and meta-analysis supports the hypothesis that hyperalgesia contributes to clinical pain in PD, and that the underlying mechanism may be dopaminergically driven., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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 (PD Moff ) to HC off medications (HC Moff ) 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 PD Moff versus HC Moff , 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., (Copyright © 2017. Published by Elsevier Ltd.)

In Australia 1% of individuals aged over 50 years have Parkinson disease (PD). Guidance for commencing device-assisted therapies (DAT) for PD in Australia was developed based on a review of European recommendations and their relevance to the local clinical setting. An online survey and teleconference discussions were held by a group of eight local movement disorder experts to develop consensus. Referral to a movement disorder specialist and consideration of DAT is appropriate when motor fluctuations cause disability or reduced quality of life, response to treatment is inconsistent or motor fluctuations and dyskinesias require frequent treatment adjustment without apparent benefit and levodopa is required four or more times daily. Three types of DAT are available in Australia for patients with PD: continuous subcutaneous apomorphine; continuous levodopa-carbidopa intestinal gel infusion; and deep brain stimulation. All improve consistency of motor response. The most important aspects when considering which DAT to use are the preferences of the patient and their carers, patient comorbidities, age, cognitive function and neuropsychiatric status. Patients and their families need to be provided with treatment options that are suitable to them, with adequate explanations regarding the recommendations and comparison of potential device-related complications. DAT are best managed, where possible, in a specialist centre with experience in all three types of therapy. Proactive and early management of symptoms during disease progression is essential to maintain optimally motor responses and quality of life in patients with PD., (© 2017 Royal Australasian College of Physicians.)

Parkinson's disease (PD) is a complex motor and non-motor disorder and management is often challenging. In this review, we explore emerging approaches to improve the care of patients, drawing from the literature regarding patient-centred care, patient and caregiver perspectives and priorities, gaps in knowledge among patients and caregivers and the need for accurate information, individual variability in disease manifestations, prognostication of disease course, new developments in health technologies and personalized medicine, specialty care, pharmacological and non-pharmacological management, financial burden, lifestyle and work-related issues, support groups and palliative care.

Objective: This clinical update review focuses on treatment approaches of neuropsychiatric manifestations in Parkinson's disease., Methods: We conducted a systematic search of the literature using Pubmed and selected recent and relevant papers for this review., Results: Neuropsychiatric symptoms in Parkinson's disease usually require optimization of levodopa therapy as a first step. Most psychotropic drugs can be used in Parkinson's disease, however there is still lack of an evidence base due to limited studies and difficulties in diagnosis of neuropsychiatric disorders. Non-pharmacological treatments have also proved effective in Parkinson's disease. Cognitive impairment requires special consideration., Conclusions: Management of neuropsychiatric manifestations in Parkinson's disease is complicated by the lack of evidence. Treatment should be individualized and benefits and risks must be balanced., (© The Royal Australian and New Zealand College of Psychiatrists 2016.)

Objective: This clinical update review focuses on the classification and description of common neuropsychiatric manifestations in Parkinson's disease (PD)., Method: We conducted a systematic search of the literature using Pubmed and selected the most recent and relevant papers for this review., Results: Neuropsychiatric manifestations in PD are are very frequent and may arise from an abnormal psychopathological response to the disease, neurobiological changes related to the disease itself, complications of treatments or a combination of all of these., Conclusions: Neuropsychiatric symptoms may precede the motor clinical presentation of PD. Early recognition is essential., (© The Royal Australian and New Zealand College of Psychiatrists 2016.)

Background: In spite of the recognized physical and psychosocial effects of caring for patients with Parkinson's disease (PD), caregiver burden (CB) in this setting is poorly understood. The objective of this research was to identify factors that were associated with CB in an Australian population of PD caregivers using a novel instrument - the Parkinson's Disease Caregiver Burden (PDCB) questionnaire., Methods: Fifty patient-caregiver couples were recruited from three movement disorders clinics in Melbourne, Australia. Burden on caregivers was rated using the PDCB questionnaire. Burden scores were correlated with patient factors, including motor symptom severity (Unified Parkinson's Disease Ratings Scale and Hoehn & Yahr (H&Y) scale), patient cognition (Neuropsychiatry Unit Cognitive Assessment Tool; NUCOG), presence of impulsive and compulsive behaviors (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease), and patient olfaction. Caregiver and patient demographics, as well as results for depression and anxiety (Hospital Anxiety and Depression Scale; HADS), were also examined for their relationship with CB., Results: H&Y stage, depression or anxiety in either caregiver or patient, and decreased patient NUCOG score were significantly associated with higher PDCB score. Multiple linear regression analysis identified caregiver and patient depression score and patient score for the visuoconstructional subscale of NUCOG to predict burden score. In addition, disease duration, duration of caregiving, and increased hours per day spent in giving care were significantly associated with increased burden., Conclusions: We found psychiatric and cognitive factors to be the most relevant factors in the perception of burden in PD caregivers. On top of this, we found deficits in the domain of visuoconstruction predicted burden - a relationship not yet described in literature. Targeting depression and anxiety in this setting as well as identifying caregivers at high risk of burden may give clinicians the chance to optimize care of patients with PD through the caregiver.

Impulse control disorders (ICDs), including compulsive gambling, buying, sexual behavior, and eating, are a serious and increasingly recognized psychiatric complication in Parkinson's disease (PD). Other impulsive-compulsive behaviors (ICBs) have been described in PD, including punding (stereotyped, repetitive, purposeless behaviors) and dopamine dysregulation syndrome (DDS; compulsive PD medication overuse). ICDs have been most closely related to the use of dopamine agonists (DAs), perhaps more so at higher doses; in contrast, DDS is primarily associated with shorter-acting, higher-potency dopaminergic medications, such as apomorphine and levodopa. Possible risk factors for ICDs include male sex, younger age and younger age at PD onset, a pre-PD history of ICDs, and a personal or family history of substance abuse, bipolar disorder, or gambling problems. Given the paucity of treatment options and potentially serious consequences, it is critical for PD patients to be monitored closely for development of ICDs as part of routine clinical care., (© 2014 International Parkinson and Movement Disorder Society.)

Objectives: Parkinson's Disease patients wore a device on the wrist that gave reminders to take levodopa and also measured bradykinesia and dyskinesia. Consumption of medications was acknowledged by placing the thumb on the device. Some patients performed this acknowledgement repeatedly and unconsciously. This study examines whether this behaviour reflected increased impulsivity., Methods and Results: Twenty five participants were selected because they had i) excess acknowledgements described above or ii) Impulsive-Compulsive Behaviours or iii) neither of these. A blinded assessor applied clinical scales to measure Impulsive-Compulsive Behaviours, cognition, depression, anxiety and apathy. A Response Ratio, representing the number of acknowledgements/number of doses (expressed as a percentage) was tightly correlated with ratings of Impulsive-Compulsive Behaviours (r² = 0.79) in 19/25 subjects. Some of these patients had dyskinesia, which was higher with extraneous responses than with response indicating medication consumption. Six of the 25 subjects had high Impulsive-Compulsive Behaviour Scores, higher apathy scores, low levels of dyskinesia and normal Response Ratios. Patients without ICB (low RR) also had low dyskinesia levels regardless of the relevance of the response., Conclusion: An elevated Response Ratio is a specific measure of a type of ICB where increased incentive salience is attributed to cues by the presence of high striatal dopamine levels, manifested by high levels of dyskinesia. This study also points to a second form of ICBs which occur in the absence of dyskinesia, has normal Response Ratios and higher apathy scores, and may represent prefrontal pathology.

Background: The high incidence of falls associated with Parkinson's disease (PD) increases the risk of injuries and immobility and compromises quality of life. Although falls education and strengthening programs have shown some benefit in healthy older people, the ability of physical therapy interventions in home settings to reduce falls and improve mobility in people with Parkinson's has not been convincingly demonstrated., Methods/design: 180 community living people with PD will be randomly allocated to receive either a home-based integrated rehabilitation program (progressive resistance strength training, movement strategy training and falls education) or a home-based life skills program (control intervention). Both programs comprise one hour of treatment and one hour of structured homework per week over six weeks of home therapy. Blinded assessments occurring before therapy commences, the week after completion of therapy and 12 months following intervention will establish both the immediate and long-term benefits of home-based rehabilitation. The number of falls, number of repeat falls, falls rate and time to first fall will be the primary measures used to quantify outcome. The economic costs associated with injurious falls, and the costs of running the integrated rehabilitation program from a health system perspective will be established. The effects of intervention on motor and global disability and on quality of life will also be examined., Discussion: This study will provide new evidence on the outcomes and cost effectiveness of home-based movement rehabilitation programs for people living with PD., Trial Registration: The trial is registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12608000390381).

Objectives: Impulsive-compulsive behaviours (ICBs) in Parkinson's disease (PD) have been anecdotally linked with impaired sleep. The authors investigate measures of sleep in PD patients with and without ICBs, and in healthy controls., Methods: The authors compare Parkinsonian features, measures of depression, anxiety and mania, and sleep disturbance in 30 PD patients with ICBs (PD+ICB), 62 PD patients without ICBs (PD-ICB) and 48 healthy controls., Results: PD+ICB patients had a younger age of PD onset, took more dopamine replacement therapy (DRT) and had worse sleep, and elevated anxiety, depression and mania scores. Using multiple linear regression analyses, the total anxiety and depression scores, and presence of ICBs were the only variables associated with poorer sleep in PD., Conclusions: PD+ICB patients may show enhanced psychomotor effects of DRT that may in turn contribute to poor sleep quality. Sleep disturbance should be specifically queried in PD+ICB patients.

Impulsive-compulsive behaviours are a significant source of morbidity for patients with Parkinson's disease receiving dopaminergic therapy. The development of these behaviours may reflect sensitization of the neural response to non-drug rewards, similar to that proposed for sensitization to drug rewards in addiction. Here, by using (11)C-raclopride positron emission tomography imaging, we investigated the effects of reward-related cues and L-dopa challenge in patients with Parkinson's disease with and without impulsive-compulsive behaviours on striatal levels of synaptic dopamine. Eighteen patients (11 with and seven without impulsive-compulsive behaviours) underwent three (11)C-raclopride positron emission tomography scans. The impulsive-compulsive behaviours included hypersexuality, binge eating, punding, compulsive use of dopamine replacement therapy, compulsive buying and pathological gambling, with eight patients exhibiting more than one impulsive-compulsive behaviour. There were no significant differences in baseline dopamine D2 receptor availability between the Parkinson's disease groups. No differences were found when comparing the percentage change of raclopride binding potential between the two Parkinson's disease groups following L-dopa challenge with neutral cues. The group with Parkinson's disease with impulsive-compulsive behaviours had a greater reduction of ventral striatum (11)C-raclopride binding potential following reward-related cue exposure, relative to neutral cue exposure, following L-dopa challenge (16.3% compared with 5.8% in Parkinson's disease controls, P = 0.016). The heightened response of striatal reward circuitry to heterogeneous reward-related visual cues among a group of patients with different impulsive-compulsive behaviours is consistent with a global sensitization to appetitive behaviours with dopaminergic therapy in vulnerable individuals. Our findings are relevant for the broader debate on the relation between impulsive-compulsive behaviours and addictions and may have important implications with regards to advertisement legislation in an effort to prevent the onset of behavioural addictions.

Hoarding is seen in several psychiatric conditions, but has not been specifically assessed in Parkinson's disease (PD). This study investigates hoarding tendency amongst patients with PD, and its association with impulsive-compulsive spectrum behaviors (ICBs). We compare clinical features, measures of hoarding, impulse buying, self-control, obsessive-compulsive symptoms, depression, and anxiety in 39 patients with PD with ICBs (PD + ICB), 61 patients with PD without ICBs (PD - ICB), and 50 healthy controls. A much higher proportion of PD + ICB (27.8%) than PD - ICB (3.5%) were hoarders (P = 0.001). 6% of healthy controls were hoarders. Compulsive shoppers scored higher than other varieties of ICB on excessive acquisition measures. Hoarding correlated positively with impulsive buying, obsessive-compulsive symptoms, PD duration, and negatively with self-control measures. Using multivariate regression analyzes, the presence of ICBs and measures of impulsive buying were the only variables independently associated with hoarding in PD. The association of hoarding with other ICBs and low trait impulse control suggests that excessive hoarding is related to the spectrum of impulsive behaviors in PD., ((c) 2010 Movement Disorder Society.)

A few Parkinson patients develop a disabling pattern of compulsive dopaminergic drug use ("dopamine dysregulation syndrome"-DDS). DDS patients commonly identify aversive dysphoric "OFF" mood-states as a primary motivation to compulsively use their drugs. We compared motoric, affective, non-motor symptoms and incentive arousal after overnight medication withdrawal and after levodopa in DDS and control PD patients. Twenty DDS patients were matched to 20 control PD patients for age, gender, and disease duration and underwent a standard levodopa challenge. Somatic symptomatology, positive and negative affective states, drug effects, reward responsivity, motor disability, and dyskinesias were tested in the "OFF"-state after overnight withdrawal of medications, and then after a challenge with a standard dose of levodopa, after a full "ON"-state was achieved. In the "OFF"-state, DDS patients reported lower positive affect, and more motor and non-motor disability. In the "ON"-state, DDS patients had higher expressions of drug "wanting," reward responsivity, and dyskinesias. Positive and negative affect, non-motor symptomatology, and motor disability were comparable. These findings suggest that affective, motivational, and motoric disturbances in PD are associated with the transition to compulsive drug use in individuals who inappropriately overuse their dopaminergic medication., ((c) 2010 Movement Disorder Society.)

There is an increasing awareness of impulsive-compulsive phenomena in patients treated for Parkinson's disease (PD). We describe another, potentially related phenomenon putatively associated with the use of dopamine agonists in 3 patients with PD, characterized by excessive and inappropriate philanthropy., ((c) 2010 Movement Disorder Society.)

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.

Antiparkinson therapy can be the primary cause of a range of nonmotor symptoms that include a set of complex disinhibitory psychomotor pathologies and are linked by their repetitive, reward or incentive-based natures. These behaviors relate to aberrant or excessive dopamine receptor stimulation and encompass impulse control disorders (ICDs), punding, and the dopamine dysregulation syndrome (DDS). Common ICDs include pathological gambling, hypersexuality, compulsive eating, and compulsive buying. This review focuses on the phenomenology, epidemiology, and methods to identify and rate these disorders. The management of dopaminergic drug-related compulsive behaviors is discussed in the light of the current understanding of the neurobiological substrate of these disorders., (2009 Movement Disorder Society.)

Dopamine dysregulation syndrome (DDS) is a relatively recently described iatrogenic disturbance that may complicate long-term symptomatic therapy of Parkinson's disease. Patients with DDS develop an addictive pattern of dopamine replacement therapy (DRT) use, administering doses in excess of those required to control their motor symptoms. The prevalence of DDS in patients attending specialist Parkinson's disease centres is 3-4%. Amongst the behavioural disturbances associated with DDS are punding, which is a complex stereotyped behaviour, and impulse control disorders (ICDs), such as pathological gambling, hypersexuality, compulsive shopping and compulsive eating. We review the risk factors and potential mechanisms for the development of DDS, including personality traits, potential genetic influences and Parkinson's disease-related cognitive deficits. Impulsive personality traits are prominent in patients developing DDS, and have been previously associated with the development of substance dependence. Candidate genes affecting the dopamine 'D(2)-like' receptor family have been associated with impulsive personality traits in addition to drug and nondrug addictions. Impaired decision making is implicated in addictive behaviours, and decision-making abilities can be influenced by dopaminergic medications. In Parkinson's disease, disruption of the reciprocal loops between the striatum and structures in the prefrontal cortex following dopamine depletion may predispose to DDS. The role of DRT in DDS is discussed, with particular reference to models of addiction, suggesting that compulsive drug use is due to progressive neuroadaptations in dopamine projections to the accumbens-related circuitry. Evidence for neuroadaptations and sensitization occurring in DDS include enhanced levodopa-induced ventral striatal dopamine release. Levodopa is still considered the most potent trigger for DDS in Parkinson's disease, but subcutaneous apomorphine and oral dopamine agonists may also be responsible. In the management of DDS, further research is needed to identify at-risk groups, thereby facilitating more effective early intervention. Therefore, an increased awareness of the syndrome amongst treating physicians is vital. Medication reduction strategies are employed, particularly with regard to avoiding rapidly acting 'booster' DRT formulations. Psychosocial treatments, including cognitive-behavioural therapy, have been beneficial in treating substance use disorders and ICDs in non-Parkinson's disease patients, but there are currently no published trials of psychological interventions in DDS. Further studies are also required to identify factors that can predict those patients with DDS or ICDs who will derive benefit from surgical interventions such as deep brain stimulation.

In the past decade, impulse control disorders, punding, and dopamine dysregulation syndrome (which we refer to collectively as disinhibitory psychopathologies) have been increasingly recognized in treated patients with Parkinson's disease. Practicing neurologists must understand these problems to limit potential harm. In this article, we summarize current knowledge regarding these behavioral disorders, including phenomenology, epidemiology, pathophysiology, and treatment.

Pathological gambling (PG) has been reported as a complication of the treatment of Parkinson's disease (PD). We examined all published cases of PG for prevalence and risk factors of this complication, the relationship of PG and use of dopamine agonists (DA), and the relationship of PG to the dopamine dysregulation syndrome (DDS). The prevalence of PG in prospective studies of PD patients using DA has been reported between 2.3 and 8%, compared to approximately 1% in the general population. As in the general population, PD patients with this complication are often young, male and have psychiatric co-morbidity. The vast majority are on DA, often at maximum dose or above. Differences between oral DA failed to reach significance. PG associated with levodopa monotherapy is uncommon, but in the majority of cases levodopa is co-prescribed, suggesting possible cross-sensitization of brain systems mediating reward. PG can occur with DDS but often occurs in isolation. In contrast to DDS, escalation and self regulation of anti-parkinsonian medication are not usually seen. PG in patients with PD using DA is higher than PG reported in the general population, but shares similar characteristics and risk factors. PG is predominantly associated with oral DA. It often occurs in isolation and may not be associated with DDS, which typically occurs on treatment with levodopa or subcutaneous apomorphine., ((c) 2007 Movement Disorder Society.)

Reports of parkinsonism in phenylketonuria are exceedingly rare. We report on a patient who had received a delayed diagnosis of phenylketonuria as an infant and subsequently developed levodopa-responsive parkinsonism at the age of 33. Single-photon emission computed tomography (SPECT) using (123)I-FP-CIT ([(123))I]-2 beta-carbomethoxy-3beta-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane) used to measure dopamine transporter levels on two occasions, 7 and 9 years after the onset of neurological symptoms, were normal. Iodine-123-iodo-lisuride SPECT (IBZM) imaging, however, showed reduced caudate over putamen binding. This combination of imaging findings indicates a possible upregulation of postsynaptic D2 receptors in the context of intact presynaptic dopamine nerve terminal density., ((c) 2004 Movement Disorder Society.)

Punding is a term that was coined originally to describe complex prolonged, purposeless, and stereotyped behaviour in chronic amphetamine users. A structured interview of 50 patients with higher dopamine replacement therapy requirements (>800 levodopa equivalent units/day) from 123 unselected patients with Parkinson's disease (PD) from a PD clinic identified 17 (14%) patients with punding. Punding was acknowledged as disruptive and unproductive by the patients themselves, but forcible attempts by family to interrupt the behaviour led to irritability and dysphoria. Punding was associated with very high doses of dopamine replacement therapy often related to a pattern of chronic inappropriate overuse of dopaminergic medication. We believe that this is an underreported, socially disabling phenomenon that is commonly associated with the syndrome of dopamine dysregulation and is phenomenologically distinct from both obsessive-compulsive disorder and mania., (Copyright 2004 Movement Disorder Society)

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.