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Background and Aims: Neurodegeneration underpins the pathological processes of younger‐onset dementia (YOD) and has been implicated in primary psychiatric disorders (PSYs). Cerebrospinal fluid (CSF) neurofilament light (NfL) has been used to investigate neurodegeneration severity through correlation with structural brain changes in various conditions, but has seldom been evaluated in YOD and PSYs. Methods: This retrospective study included patients with YOD or PSYs with magnetic resonance imaging (MRI) of the brain and CSF NfL analysis. Findings from brain MRI were analysed using automated volumetry (volBrain) to measure white matter (WM), grey matter (GM) and whole brain (WB) volumes expressed as percentages of total intracranial volume. Correlations between NfL and brain volume measurements were computed whilst adjusting for age. Results: Seventy patients (47 with YOD and 23 with PSY) were identified. YOD types included Alzheimer disease and behavioural variant frontotemporal dementia. PSY included schizophrenia and major depressive disorder. MRI brain sequences were either fast spoiler gradient‐echo (FSPGR) or magnetization‐prepared rapid acquisition gradient‐echo (MPRAGE). In the total cohort, higher NfL was associated with reduced WB in the FSPGR and MPRAGE sequences (r = −0.402 [95% confidence interval (CI), −0.593 to −0.147], P = 0.008 and r = −0.625 [95% CI, −0.828 to −0.395], P < 0.001, respectively). Higher NfL was related to reduced GM in FSPGR (r = 0.385 [95% CI, −0.649 to −0.014], P = 0.017) and reduced WM in MPRAGE (r = −0.650 [95% CI, −0.777 to −0.307], P < 0.001). Similar relationships were seen in YOD, but not in PSY. Conclusion: Higher CSF NfL is related to brain atrophy in YOD, further supporting its use as a nonspecific marker of neurodegeneration severity. [ABSTRACT FROM AUTHOR]

The article focuses on the clinical assessment of tremor for diagnosing and treating patients. It discusses the revised guidelines for tremor classification and provides recommendations for history-taking and examination. The article also highlights different causes of tremor and management options, emphasizing the importance of accurate diagnosis and individualized treatment.

Since the initial reports of COVID-19 in December 2019, the world has been gripped by the disastrous acute respiratory disease caused by the SARS-CoV-2 virus. There are an ever-increasing number of reports of neurological symptoms in patients, from severe (encephalitis), to mild (hyposmia), suggesting the potential for neurotropism of SARS-CoV-2. This Perspective investigates the hypothesis that the reliance on self-reporting of hyposmia has resulted in an underestimation of neurological symptoms in COVID-19 patients. While the acute effect of the virus on the nervous system function is vastly overshadowed by the respiratory effects, we propose that it will be important to monitor convalescent individuals for potential long-term implications that may include neurodegenerative sequelae such as viral-associated parkinsonism. As it is possible to identify premorbid harbingers of Parkinson's disease, we propose long-term screening of SARS-CoV-2 cases post-recovery for these expressions of neurodegenerative disease. An accurate understanding of the incidence of neurological complications in COVID-19 requires long-term monitoring for sequelae after remission and a strategized health policy to ensure healthcare systems all over the world are prepared for a third wave of the virus in the form of parkinsonism. [ABSTRACT FROM AUTHOR]

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). 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. 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. [ABSTRACT FROM AUTHOR]

Background: Although the COVID‐19 pandemic is affecting a relatively small proportion of the global population, its effects have already reached everyone. The pandemic has the potential to differentially disadvantage chronically ill patients, including those with Parkinson's disease (PD). The first health care reaction has been to limit access to clinics and neurology wards to preserve fragile patients with PD from being infected. In some regions, the shortage of medical staff has also forced movement disorders neurologists to provide care for patients with COVID‐19. Objective: To share the experience of various movement disorder neurologists operating in different world regions and provide a common approach to patients with PD, with a focus on those already on advanced therapies, which may serve as guidance in the current pandemic and for emergency situations that we may face in the future. Conclusion: Most of us were unprepared to deal with this condition given that in many health care systems, telemedicine has been only marginally available or only limited to email or telephone contacts. In addition, to ensure sufficient access to intensive care unit beds, most elective procedures (including deep brain stimulation or the initiation of infusion therapies) have been postponed. We all hope there will soon be a time when we will return to more regular hospital schedules. However, we should consider this crisis as an opportunity to change our approach and encourage our hospitals and health care systems to facilitate the remote management of chronic neurological patients, including those with advanced PD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Tremor of the upper limbs is a disabling symptom that is present during several neurological disorders and is currently without treatment. Functional MRI (fMRI) is an essential tool to investigate the pathophysiology of tremor and aid the development of treatment options. However, no adequately or standardized protocols for fMRI exists at present. Here we present a novel, online available fMRI task that could be used to assess the in vivo pathology of tremor. Objective: This study aims to validate the tremor-evoking potential of the fMRI task in a small group of tremor patients outside the scanner and assess the reproducibility of the fMRI task related activation in healthy controls. Methods: Twelve HCs were scanned at two time points (baseline and after 6-weeks). There were two runs of multi-band fMRI and the tasks included a “brick-breaker” joystick game. The game consisted of three conditions designed to control for most of the activation related to performing the task by contrasting the conditions: WATCH (look at the game without moving joystick), MOVE (rhythmic left/right movement of joystick without game), and PLAY (playing the game). Task fMRI was analyzed using FSL FEAT to determine clusters of activation during the different conditions. Maximum activation within the clusters was used to assess the ability to control for task related activation and reproducibility. Four tremor patients have been included to test ecological and construct validity of the joystick task by assessing tremor frequencies captured by the joystick. Results: In HCs the game activated areas corresponding to motor, attention and visual areas. Most areas of activation by our game showed moderate to good reproducibility (intraclass correlation coefficient (ICC) 0.531–0.906) with only inferior parietal lobe activation showing poor reproducibility (ICC 0.446). Furthermore, the joystick captured significantly more tremulous movement in tremor patients compared to HCs (p = 0.01) during PLAY, but not during MOVE. Conclusion: Validation of our novel task confirmed tremor-evoking potential and reproducibility analyses yielded acceptable results to continue further investigations into the pathophysiology of tremor. The use of this technique in studies with tremor patient will no doubt provide significant insights into the treatment options. [ABSTRACT FROM AUTHOR]

Objective: Deep brain stimulation can be of benefit in carefully selected patients with severe intractable obsessive-compulsive disorder. The aim of this paper is to describe the outcomes of the first seven deep brain stimulation procedures for obsessive-compulsive disorder undertaken at the Neuropsychiatry Unit, Royal Melbourne Hospital. The primary objective was to assess the response to deep brain stimulation treatment utilising the Yale-Brown Obsessive Compulsive Scale as a measure of symptom severity. Secondary objectives include assessment of depression and anxiety, as well as socio-occupational functioning. Methods: Patients with severe obsessive-compulsive disorder were referred by their treating psychiatrist for assessment of their suitability for deep brain stimulation. Following successful application to the Psychosurgery Review Board, patients proceeded to have deep brain stimulation electrodes implanted in either bilateral nucleus accumbens or bed nucleus of stria terminalis. Clinical assessment and symptom rating scales were undertaken pre- and post-operatively at 6- to 8-week intervals. Rating scales used included the Yale-Brown Obsessive Compulsive Scale, Obsessive Compulsive Inventory, Depression Anxiety Stress Scale and Social and Occupational Functioning Assessment Scale. Results: Seven patients referred from four states across Australia underwent deep brain stimulation surgery and were followed for a mean of 31 months (range, 8–54 months). The sample included four females and three males, with a mean age of 46 years (range, 37–59 years) and mean duration of obsessive-compulsive disorder of 25 years (range, 15–38 years) at the time of surgery. The time from first assessment to surgery was on average 18 months. All patients showed improvement on symptom severity rating scales. Three patients showed a full response, defined as greater than 35% improvement in Yale-Brown Obsessive Compulsive Scale score, with the remaining showing responses between 7% and 20%. Conclusion: Deep brain stimulation was an effective treatment for obsessive-compulsive disorder in these highly selected patients. The extent of the response to deep brain stimulation varied between patients, as well as during the course of treatment for each patient. The results of this series are comparable with the literature, as well as having similar efficacy to ablative psychosurgery techniques such as capsulotomy and cingulotomy. Deep brain stimulation provides advantages over lesional psychosurgery but is more expensive and requires significant multidisciplinary input at all stages, pre- and post-operatively, ideally within a specialised tertiary clinical and/or academic centre. Ongoing research is required to better understand the neurobiological basis for obsessive-compulsive disorder and how this can be manipulated with deep brain stimulation to further improve the efficacy of this emerging treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Sleep benefit ( SB) in Parkinson's disease refers to improved motor symptoms upon waking despite an entire night without medications. Although it was first proposed 30 years ago, this phenomenon proved difficult to investigate, and its true prevalence and underlying mechanisms remain unclear. Objective This study aimed to identify and quantify SB through measurement of motor function using a validated smartphone application and to identify disease characteristics that predicted SB. Methods Ninety-two patients recruited from 2 Movement Disorder Services were clinically assessed at home using a validated smartphone application. Each patient was tested in the on-state, at the end of dose, and on waking (before medications) 3 times. Differences between the 3 states were used to determine the impact of sleep and levodopa on motor function. SB was considered to be a 'measurable improvement in parkinsonism from the end of dose.' Results The morning waking motor function of 20 patients (22%) improved compared with the end-of-dose function, with 9 patients demonstrating superior function compared with their on-state. No clinical features predicted SB. Although all participants subjectively reported motor fluctuations, only 35 patients (38%) demonstrated an objective improvement with levodopa. Patients who had SB more often demonstrated objective motor fluctuations compared with those who did not (65% vs. 31%; P = 0.008). Conclusions SB is a genuine motor phenomenon: 1 in 5 patients have a measurable improvement in motor function on waking. It remains questionable whether this improvement is a direct effect of sleep. Until its underlying mechanism is better understood, it is more appropriate to refer to this phenomenon as simply morning improvement or diurnal fluctuation of motor symptoms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background. Nonmotor symptoms particularly olfactory dysfunction, RBD, depression, hallucinations, and constipation are currently not included in the typical clinical criteria for diagnosing Lewy body Parkinsonian disorders (LBPD). The aim of this study is to determine the diagnostic value of nonmotor symptoms in patients presenting with Parkinsonism and tremor. Methods. All new patients seen between January 2007 and May 2013 in the Movement Disorders Specialist Clinics of the Royal Melbourne Hospital (RMH), who were referred with a possible neurodegenerative syndrome or concerns of Parkinsonism and/or tremor, were included. Patients underwent routine evaluation with the four-minute “Sniffin Sticks” test, RBD, depression, and constipation. Results. 291 patients were included in the analysis. Conclusion. We found that lower olfaction scores based on “Sniffin Sticks” testing combined with reports of depression and constipation are independent predictors for the diagnosis of the spectrum of Lewy body Parkinsonian disorders (LBPD). Parkinson’s disease (PD) cannot be reliably clinically differentiated from other causes of Parkinsonism that share symptomatology and structural abnormalities. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

A 56-year-old man presented with gait disturbance, personality change, and behavioral disturbances. He subsequently developed falls, postural instability, and axial rigidity. The cognitive problems progressed and he developed aphasia and later eye movement abnormalities. He died after 9 years of disease. Experts discuss the syndromal diagnosis and predict the underlying pathology. The pathological diagnosis is given and clinical learning points are considered. © 2011 Movement Disorder Society [ABSTRACT FROM AUTHOR]

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 11C-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 11C-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 11C-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. [ABSTRACT FROM AUTHOR]

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. © 2010 Movement Disorder Society [ABSTRACT FROM AUTHOR]

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. © 2010 Movement Disorder Society [ABSTRACT FROM AUTHOR]

There is growing awareness of impulsive-compulsive spectrum behaviors (ICBs) in patients with Parkinson's disease (PD) treated with dopamine replacement therapy (DRT). These include pathological gambling, hypersexuality, compulsive shopping, binge eating, punding and compulsive use of DRT, or dopamine dysregulation syndrome. In PD, difficulties exist in separating the effects of DRT from the underlying disease process and aberrant dopaminergic systems in determining the aetiology of ICBs. Recent reports of ICBs associated with dopamine agonist use for conditions other than PD may suggest a significant etiological role for these medications, but currently published cases thus far lack pathological confirmation of diagnoses. We present three cases of pathologically confirmed progressive supranuclear palsy who developed ICBs in association with dopamine agonist use. Pathological comparisons between these three cases and other case series of progressive supranuclear palsy are made. © 2010 Movement Disorder Society [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Plastic changes within the striatum resulting from pulsatile dopaminergic stimulation are thought to lead to dyskinesia in patients with Parkinson's disease (PD). The basal ganglia play a role in processing pain. We hypothesized that the plastic changes that lead to dyskinesia may also mediate pain responses. Our objective was to compare the change in pain sensitivity after levodopa administration between stable responders, fluctuators without dyskinesia, and dyskinetic patients, and to compare pain sensitivity between PD and healthy subjects. Fifty patients with PD were assessed with cold water immersion after overnight withdrawal of dopaminergic medications and again after a standard levodopa challenge, and carefully classified into stable responder (n = 12), fluctuator (n = 15), and dyskinetic (n = 23) groups. Twenty age-matched controls were also tested. PD patients 'off'-medication had a lower threshold ( P = 0.016) and tolerance ( P < 0.0001) to cold pain compared to controls. After levodopa administration, dyskinetic patients experienced a large increase in cold pain threshold (48%) and tolerance (66%) that was absent in stable responders ( P = 0.038 and P = 0.015); there was no significant difference in pain sensitivity change scores between the fluctuator and either the stable responder or dyskinetic groups. Our results suggest that dyskinesia and pain may share common pathophysiological mechanisms in PD. © 2008 Movement Disorder Society [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The presence of punding in Parkinson's disease (PD) has been associated with inappropriate excessive use of dopaminergic medication but its relation to the severity of dyskinesias is not known. Through the use of clinical examination and medical chart review, the presence of punding and the severity of interdose dyskinesias were evaluated by two different observers. Punding was associated with more frequent interventions to reduce dyskinesias and with greater dyskinesia severity. We suggest the neural systems mediating the expression of dyskinesias and punding might overlap and that punding should be looked for systematically in PD patients presenting with disabling severe dyskinesias. © 2006 Movement Disorder Society [ABSTRACT FROM AUTHOR]

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 123I-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. © 2004 Movement Disorder Society [ABSTRACT FROM AUTHOR]

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. © 2004 Movement Disorder Society [ABSTRACT FROM AUTHOR]

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. © 2010 Movement Disorder Society [ABSTRACT FROM AUTHOR]

The article presents the case of a 42-year-old man with Parkinson's disease that demonstrates the phenomenon of punding, which is characterized by pointless repetitive behaviors that are performed for long periods of time. He developed a tendency of spending up to 10 hours doing housework. This tendency disrupted his sleep pattern.