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Dopamine agonist medications with high affinity for the D3 dopamine receptor are commonly used to treat Parkinson's disease, and have been associated with pathological behaviors categorized under the umbrella of impulse control disorders (ICD). The aim of this study was to investigate whether ICD in Parkinson's patients are associated with greater D3 dopamine receptor availability. We used positron emission tomography (PET) radioligand imaging with the D3 dopamine receptor preferring agonist [¹¹C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO) in Parkinson's patients with (n = 11) and without (n = 21) ICD, and age-, sex-, and education-matched healthy control subjects (n = 18). Contrary to hypotheses, [¹¹C]-(+)-PHNO binding in D3 -rich brain areas was not elevated in Parkinson's patients with ICD compared with those without; instead, [¹¹C]-(+)-PHNO binding in ventral striatum was 20% lower (P = 0.011), correlating with two measures of ICD severity (r = -0.8 and -0.9), which may reflect higher dopamine tone in ventral striatum. In dorsal striatum, where [¹¹C]-(+)-PHNO binding is associated with D2 receptor levels, [¹¹C]-(+)-PHNO binding was elevated across patients compared with controls. We conclude that although D3 dopamine receptors have been linked to the occurrence of ICD in Parkinson's patients. Our findings do not support the hypothesis that D3 receptor levels are elevated in Parkinson's patients with ICD. We also did not find ICD-related abnormalities in D2 receptor levels. Our findings argue against the possibility that differences in D2/3 receptor levels can account for the development of ICD in PD; however, we cannot rule out that differences in dopamine levels (particularly in ventral striatum) may be involved.

Travel distance, growing disability, and uneven distribution of doctors limit access to care for most Parkinson's disease (PD) patients worldwide. Telemedicine, the use of telecommunications technology to deliver care at a distance, can help overcome these barriers. In this report, we describe the past, present, and likely future applications of telemedicine to PD. Historically, telemedicine has relied on expensive equipment to connect single patients to a specialist in pilot programs in wealthy nations. As the cost of video conferencing has plummeted, these efforts have expanded in scale and scope, now reaching larger parts of the world and extending the focus from care to training of remote providers. Policy, especially limited reimbursement, currently hinders the growth and adoption of these new care models. As these policies change and technology advances and spreads, the following will likely develop: integrated care networks that connect patients to a wide range of providers; education programs that support patients and health care providers; and new research applications that include remote monitoring and remote visits. Together, these developments will enable more individuals with PD to connect to care, increase access to expertise for patients and providers, and allow more-extensive, less-expensive participation in research.

Multidisciplinary care is considered an optimal model to manage Parkinson's disease (PD), but supporting evidence is limited. We performed a randomized, controlled trial (RCT) to establish whether a multidisciplinary/specialist team offers better outcomes, compared to stand-alone care from a general neurologist. Patients with PD were randomly allocated to an intervention group (care from a movement disorders specialist, PD nurses, and social worker) or a control group (care from general neurologists). Both interventions lasted 8 months. Clinicians and researchers were blinded for group allocation. The primary outcome was the change in quality of life (Parkinson's Disease Questionnaire; PDQ-39) from baseline to 8 months. Other outcomes were the UPDRS, depression (Montgomery-Asberg Depression Scale; MADRS), psychosocial functioning (Scales for Outcomes in Parkinson's disease-Psychosocial; SCOPA-PS), and caregiver strain (Caregiver Strain Index; CSI). Group differences were analyzed using analysis of covariance adjusted for baseline values and presence of response fluctuations. A total of 122 patients were randomized and 100 completed the study (intervention, n = 51; control, n = 49). Compared to controls, the intervention group improved significantly on PDQ-39 (difference, 3.4; 95% confidence interval [CI]: 0.5-6.2) and UPDRS motor scores (4.1; 95% CI: 0.8-7.3). UPDRS total score (5.6; 95% CI: 0.9-10.3), MADRS (3.7; 95% CI: 1.4-5.9), and SCOPA-PS (2.1; 95% CI: 0.5-3.7) also improved significantly. This RCT gives credence to a multidisciplinary/specialist team approach. We interpret these positive findings cautiously because of the limitations in study design. Further research is required to assess teams involving additional disciplines and to evaluate cost-effectiveness of integrated approaches. © 2012 Movement Disorder Society.

Although the Unified Huntington's Disease Rating Scale (UHDRS) is widely used in the assessment of Huntington disease (HD), the ability of individual items to discriminate individual differences in motor or behavioral manifestations has not been extensively studied in HD gene expansion carriers without a motor-defined clinical diagnosis (i.e., prodromal-HD or prHD). To elucidate the relationship between scores on individual motor and behavioral UHDRS items and total score for each subscale, a non-parametric item response analysis was performed on retrospective data from two multicentre, longitudinal studies. Motor and Behavioral assessments were supplied for 737 prHD individuals with data from 2114 visits (PREDICT-HD) and 686 HD individuals with data from 1482 visits (REGISTRY). Option characteristic curves were generated for UHDRS subscale items in relation to their subscale score. In prHD, overall severity of motor signs was low and participants had scores of 2 or above on very few items. In HD, motor items that assessed ocular pursuit, saccade initiation, finger tapping, tandem walking, and to a lesser extent saccade velocity, dysarthia, tongue protrusion, pronation/supination, Luria, bradykinesia, choreas, gait and balance on the retropulsion test were found to discriminate individual differences across a broad range of motor severity. In prHD, depressed mood, anxiety, and irritable behavior demonstrated good discriminative properties. In HD, depressed mood demonstrated a good relationship with the overall behavioral score. These data suggest that at least some UHDRS items appear to have utility across a broad range of severity, although many items demonstrate problematic features.

Udgivelsesdato: 2008-Aug-15 The ATP/ADP ratio reflects mitochondrial function and has been reported to be influenced by the size of the Huntington disease gene (HD) repeat. Impaired mitochondrial function has long been implicated in the pathogenesis of Parkinson's disease (PD), and therefore, we evaluated the relationship of the HD CAG repeat size to PD onset age in a large sample of familial PD cases. PD affected siblings (n = 495), with known onset ages from 248 families, were genotyped for the HD CAG repeat. Genotyping failed in 11 cases leaving 484 for analysis, including 35 LRRK2 carriers. All cases had HD CAG repeats (range, 15-34) below the clinical range for HD, although 5.2% of the sample (n = 25) had repeats in the intermediate range (the intermediate range lower limit = 27; upper limit = 35 repeats), suggesting that the prevalence of intermediate allele carriers in the general population is significant. No relation between the HD CAG repeat size and the age at onset for PD was found in this sample of familial PD.

This study investigated whether abnormalities in serotonin transporter binding occur in Parkinson's disease (PD) patients with concurrent depression. We estimated serotonin transporter levels in seven clinically depressed early-stage PD patients and in seven healthy matched-control subjects during a single positron emission tomography (PET) scan with the serotonin transporter radioligand, [11C]DASB. Depressed PD patients displayed a wide-spread increase (8–68%) in [11C]DASB specific binding outside of the striatum, which was significant in dorsolateral (37%) and prefrontal (68%) cortices. Elevated [11C]DASB binding was positively correlated with depressive symptoms but not with disease severity or duration. Compatible with recent PET/[11C]DASB findings in major depression, the present preliminary data suggest that increased [11C]DASB binding, possibly reflecting greater serotonin transporter density (up-regulation), might be a pathological feature of depression in Parkinson's disease—and possibly a characteristic of depressive illness in general. © 2008 Movement Disorder Society

With prospects improving for experimental therapeutics aimed at postponing the onset of illness in preclinical carriers of the Huntington's disease (HD) gene, we assessed agreement among experienced clinicians with respect to the motor manifestations of HD, a relevant outcome measure for preventive trials in this population. Seventy-five clinicians experienced in the evaluation of patients with early HD and six non-clinicians were shown a videotape compiled from the film archives of the United States–Venezuela Collaborative HD Research Project. Observers were asked to rate a 2–3-minute segment of the motor examination for each of 17 at-risk subjects. The rating scale ranged from 0 (normal) to 4 (unequivocal extrapyramidal movement disorder characteristic of HD). As measured by a weighted κ statistic, there was substantial agreement among the 75 clinicians in the judgment of unequivocal motor abnormalities comparing scale ratings of 4 with ratings that were not 4 (weighted κ = 0.67; standard error (SE) = 0.09). Agreement among the non-clinicians was only fair (weighted κ = 0.28; SE = 0.10). Even under the artificial conditions of a videotape study, experienced clinicians show substantial agreement about the signs that constitute the motor manifestations of illness in subjects at risk for HD. We expect these findings to translate to a similar level of interobserver agreement in the clinical trial setting involving experienced investigators examining live patients. © 2005 Movement Disorder Society

Levodopa is the most effective symptomatic agent in the treatment of Parkinson's disease (PD) and the "gold standard" against which new agents must be compared. However, there remain two areas of controversy: (1) whether levodopa is toxic, and (2) whether levodopa directly causes motor complications. Levodopa is toxic to cultured dopamine neurons, and this may be a problem in PD where there is evidence of oxidative stress in the nigra. However, there is little firm evidence to suggest that levodopa is toxic in vivo or in PD. Clinical trials have not clarified this situation. Levodopa is also associated with motor complications. Increasing evidence suggests that they are related, at least in part, to the short half-life of the drug (and its potential to induce pulsatile stimulation of dopamine receptors) rather than to specific properties of the molecule. Treatment strategies that provide more continuous stimulation of dopamine receptors provide reduced motor complications in MPTP monkeys and PD patients. These studies raise the possibility that more continuous and physiological delivery of levodopa might reduce the risk of motor complications. Clinical trials to test this hypothesis are underway. We review current evidence relating to these areas of controversy.

To study comorbidity in patients with Parkinsonism (PKM), relative hospitalization rates from 1994 to 1999 for 15,304 cases were compared with 30,608 controls. After correction for differential survival, the rates were higher for cases compared to controls for aspiration pneumonia (6.34; 95% confidence interval [CI], 5.23, 7.93), affective psychosis (2.71; 95% CI, 2.13, 3.32), hip fractures (2.56; 95% CI, 2.35, 2.76), other urinary tract disorders including infections (2.5; 95% CI, 2.17, 2.86), septicemia (2.39; 95% CI, 2.02, 2.85) and fluid and electrolyte disorders (2.27; 95% CI, 1.93,2.66). The rates for cardiac, cerebrovascular, and peripheral vascular disease were similar. Preventive measures and aggressive management of these conditions as outpatients may reduce the rates of hospitalization and improve the morbidity and mortality of PKM.

The consistent findings of decreased levels of the major antioxidant glutathione in substantia nigra of patients with idiopathic Parkinson's disease (PD) has provided most of the basis for the oxidative stress hypothesis of the etiology of PD. To establish whether a nigral glutathione deficiency is unique to PD, as is generally assumed, or is present in other Parkinsonian conditions associated with nigral damage, we compared levels of reduced glutathione (GSH) in postmortem brain of patients with PD to those with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). As compared with the controls, nigral GSH levels were decreased in the PD and PSP patient groups (P < 0.05 for PD [-30%], PSP [-21%]), whereas a similar decrease in the MSA patient group did not reach statistical significance (P = 0.078, MSA [-20%]). GSH levels were normal in all examined normal and degenerating extra-nigral brain areas in PSP and MSA. A trend for decreased levels of uric acid (antioxidant and product of purine catabolism) also was observed in nigra of all patient groups (-19 to -30%). These data suggest that glutathione depletion, possibly consequent to overutilisation in oxidative stress reactions, could play a causal role in nigral degeneration in all nigrostriatal dopamine deficiency disorders, and that antioxidant therapeutic approaches should not be restricted to PD.

The pathophysiology of chorea in systemic lupus erythematosus (SLE) is uncertain. Pathologic examination has not identified a specific location for the causative lesion(s) and immunologic mechanisms have been suggested in its etiology. In other choreic disorders, such as Huntington's disease and benign hereditary chorea, glucose hypometabolism in the striatum has been demonstrated by positron computed tomography (PCT) using [18F]deoxyglucose. With this technique we have studied four patients with chorea secondary to SLE. In these patients the regional distribution of cerebral glucose metabolism was normal. In particular, striatal glucose metabolism was within the normal range, even though the ratio of striatal to cortical glucose metabolism was increased. Our results show that striatal hypometabolism, as seen in other disorders manifesting chorea, is not the PCT correlate of the dyskinesia.