Antidepressants Trial in Parkinson's Disease (ADepT-PD): protocol for a randomised placebo-controlled trial on the effectiveness of escitalopram and nortriptyline on depressive symptoms in Parkinson's disease.

BACKGROUND: Depressive symptoms are common in patients with Parkinson's disease and depression is a significant predictor of functional impairment, reduced quality of life and general well-being in Parkinson's disease. Despite the high prevalence of depression, evidence on the effectiveness and tolerability of antidepressants in this population is limited. The primary aim of this trial is to establish the clinical and cost effectiveness of escitalopram and nortriptyline for the treatment of depression in Parkinson's disease. METHODS: This is a multi-centre, double-blind, randomised placebo-controlled trial in 408 people with Parkinson's disease with subsyndromal depression, major depressive disorder or persistent depressive disorder and a Beck Depression Inventory-II (BDI-II) score of 14 or above. Participants will be randomised into one of three groups, receiving either escitalopram, nortriptyline or placebo for 12 months. Trial participation is face-to-face, hybrid or remote. The primary outcome measure is the BDI-II score following 8 weeks of treatment. Secondary outcomes will be collected at baseline, 8, 26 and 52 weeks and following withdrawal, including severity of anxiety and depression scores as well as Parkinson's disease motor severity, and ratings of non-motor symptoms, cognitive function, health-related quality of life, levodopa-equivalence dose, changes in medication, overall clinical effectiveness, capability, health and social care resource use, carer health-related quality of life, adverse effects and number of dropouts. DISCUSSION: This trial aims to determine the effectiveness of escitalopram and nortriptyline for reducing depressive symptoms in Parkinson's disease over 8 weeks, to provide information on the effect of these medications on anxiety and other non-motor symptoms in PD and on impact on patients and caregivers, and to examine their effect on change in motor severity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03652870 Date of registration - 29th August 2018.

Experiences of advance care planning in Parkinson's disease and atypical parkinsonian disorders: a mixed methods systematic review.

BACKGROUND AND PURPOSE: Advance care planning allows people to plan for their future care needs and can include medical, psychological and social aspects. However, little is known on the use, experience of and attitudes towards advance care planning in patients with parkinsonian disorders, their family carers and healthcare professionals. METHODS: A systematic search of online databases was conducted in April 2019 using a narrative synthesis approach with thematic analysis and tabulation to synthesize the findings. RESULTS: In all, 507 articles were identified and 27 were included. There were five overarching themes: (i) what is involved in advance care planning discussions, (ii) when and how advance care planning discussions are initiated, (iii) barriers to advance care planning, (iv) the role of healthcare professionals and (v) the role of the family carer. This evidence was used to highlight eight effective components to support optimal advance care planning in parkinsonian disorders: advance care planning discussions should be individualized in content, timing and approach; patients should be invited to discuss advance care planning early and regularly; palliative care services should be introduced early; a skilled professional should deliver advance care planning; support to family carers should be offered in the advance care planning process; healthcare professionals should be educated on parkinsonian disorders and palliative care; advance care planning should be clearly documented and shared with relevant services; and healthcare professionals should be enabled to conduct effective advance care planning. CONCLUSIONS: These components can inform best practice in advance care planning in patients with parkinsonian disorders.

Impulse control and related behaviors in Parkinson's disease with dementia.

BACKGROUND AND PURPOSE: The objective was to determine the frequency, demographic and clinical correlates [such as age, sex, Parkinson's disease (PD) severity and dopaminergic treatment] of impulse control disorder (ICD) symptoms and related behaviors in patients with PD with (PD-D) and without (PD-ND) dementia. METHODS: We analyzed historical data from a national, multi-center, cross-sectional database and assessed ICDs and related behaviors with the Scale for Evaluation of Neuropsychiatric Disorders in Parkinson's Disease administered as a semi-structured interview to patients with PD-D (n = 85) and PD-ND (n = 444) and their informants. RESULTS: Dopamine agonist therapy use was common and similar in the two groups (78.8% in PD-D vs. 82.9% in PD-ND), but ICDs (23.5% vs. 13.3%, P = 0.02), hobbyism-punding (32.9% vs. 10.6%, P < 0.001) and dopaminergic medication abuse (8.2% vs. 3.2%, P = 0.03) were more common in the PD-D group. CONCLUSIONS: The finding that ICDs and related behaviors are more common in patients with PD frequently treated with dopamine agonists who also have comorbid dementia suggests that the neural substrates associated with PD dementia may also predispose to development of compulsive behaviors.

Experience of care for Parkinson's disease in European countries: a survey by the European Parkinson's Disease Association.

BACKGROUND: Few studies report on the experience of care for patients with Parkinson's disease (PD) from their own point of view. METHODS: An analysis was carried out of a survey in 11 European countries on self-reported access to services and satisfaction with different aspects of care. RESULTS: In all, 1775 people with PD (PwP) participated with disease duration ranging from <1 to 42 years. When referred to a specialist most were seen within 3 months but medication reviews occurred every 3 months in only 10%, every 6 months in 37%, once a year in 40% and every 2 years or less frequently in 13%. Waiting times to therapists were usually ≥4 months. Satisfaction with care was highest for involvement of PwP in decisions (63% of respondents satisfied) and involvement of family/carer (62%) followed by communication with PwP (57%), information received (54%), frequency of treatment reviews (52%) and suitability of treatment for the individual condition and circumstances (52%), but lowest for availability and accessibility of treatment when needed (48%) and collaborations between healthcare professionals in delivering care (41% satisfied). The main factors associated with overall satisfaction scores with care were the overall satisfaction with initial consultation (r = 0.26, P < 0.0001), the sensitivity with which the diagnosis was communicated, the quantity of information provided (both r = 0.24, P < 0.0001) and the frequency of medication review (r = 0.17, P < 0.0001). CONCLUSION: More coordinated and responsive care, tailored to the individual, with regular and timely medication reviews and information provision, is likely to improve satisfaction with care in current healthcare pathways.

EFNS/MDS-ES/ENS [corrected] recommendations for the diagnosis of Parkinson's disease.

BACKGROUND: A Task Force was convened by the EFNS/MDS-ES Scientist Panel on Parkinson's disease (PD) and other movement disorders to systemically review relevant publications on the diagnosis of PD. METHODS: Following the EFNS instruction for the preparation of neurological diagnostic guidelines, recommendation levels have been generated for diagnostic criteria and investigations. RESULTS: For the clinical diagnosis, we recommend the use of the Queen Square Brain Bank criteria (Level B). Genetic testing for specific mutations is recommended on an individual basis (Level B), taking into account specific features (i.e. family history and age of onset). We recommend olfactory testing to differentiate PD from other parkinsonian disorders including recessive forms (Level A). Screening for pre-motor PD with olfactory testing requires additional tests due to limited specificity. Drug challenge tests are not recommended for the diagnosis in de novo parkinsonian patients. There is an insufficient evidence to support their role in the differential diagnosis between PD and other parkinsonian syndromes. We recommend an assessment of cognition and a screening for REM sleep behaviour disorder, psychotic manifestations and severe depression in the initial evaluation of suspected PD cases (Level A). Transcranial sonography is recommended for the differentiation of PD from atypical and secondary parkinsonian disorders (Level A), for the early diagnosis of PD and in the detection of subjects at risk for PD (Level A), although the technique is so far not universally used and requires some expertise. Because specificity of TCS for the development of PD is limited, TCS should be used in conjunction with other screening tests. Conventional magnetic resonance imaging and diffusion-weighted imaging at 1.5 T are recommended as neuroimaging tools that can support a diagnosis of multiple system atrophy (MSA) or progressive supranuclear palsy versus PD on the basis of regional atrophy and signal change as well as diffusivity patterns (Level A). DaTscan SPECT is registered in Europe and the United States for the differential diagnosis between degenerative parkinsonisms and essential tremor (Level A). More specifically, DaTscan is indicated in the presence of significant diagnostic uncertainty such as parkinsonism associated with neuroleptic exposure and atypical tremor manifestations such as isolated unilateral postural tremor. Studies of [(123) I]MIBG/SPECT cardiac uptake may be used to identify patients with PD versus controls and MSA patients (Level A). All other SPECT imaging studies do not fulfil registration standards and cannot be recommended for routine clinical use. At the moment, no conclusion can be drawn as to diagnostic efficacy of autonomic function tests, neurophysiological tests and positron emission tomography imaging in PD. CONCLUSIONS: The diagnosis of PD is still largely based on the correct identification of its clinical features. Selected investigations (genetic, olfactory, and neuroimaging studies) have an ancillary role in confirming the diagnosis, and some of them could be possibly used in the near future to identify subjects in a pre-symptomatic phase of the disease.

Validation of the French version of the MSA health-related Quality of Life scale (MSA-QoL).

INTRODUCTION: Multiple system atrophy (MSA) has considerable impact on health-related quality of life. The MSA health-related Quality of Life scale (MSA-QoL) is a patient-reported questionnaire, which has been recently designed to evaluate the quality of life in MSA. The objective of the present study was to validate the French version of the MSA-QoL questionnaire. METHODS: One hundred and thirty-six consecutive MSA patients were included in the study. Four patients with more than 10% missing responses were excluded from the final analysis. Data quality, scaling assumptions, acceptability, reliability and validity were assessed similar to the original validation of the English version. RESULTS: Missing responses were low, item and subscale scores were evenly distributed and floor and ceiling effects were negligible. Item-total correlations were higher than the recommended greater than 0.30 and internal consistency was high for all subscales. Test-retest reliability was good for all subscales. Validity was supported by moderate interscale correlations between the subscales and the predicted correlations with other scales assessing motor disability, activities of daily living, quality of life and mood. DISCUSSION: The French version of the MSA-QoL displays robust psychometric properties similar to the English version. CONCLUSION: The French version of MSA-QoL seems suitable for assessing quality of life in French speaking MSA patients.

[MSA-QoL: disease-specific questionnaire to assess health-related quality of life in multiple system atrophy: validation of the German translation]. / MSA-QoL: spezifisches Bewertungsinstrument zur Erfassung der Lebensqualität bei Multisystematrophie : Validierung der deutschsprachigen Übersetzung.

BACKGROUND: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder which causes early sustained disability and quality of life impairment. Recently, a self-reported questionnaire focusing on MSA-specific symptoms (Multiple System Atrophy Quality of Life questionnaire, MSA-QoL) was developed in the English language. This article reports the validation of the German translation of the MSA-QoL. METHODS: Translation of the MSA-QoL was implemented in a 3-tiered approach including a forward translation, a back translation and an independent review. For the validation study 38 consecutive patients with MSA according to the consensus criteria were recruited by the participating centers in a German-Austrian cohort. Data were analyzed using standard psychometric procedures. RESULTS: As determined by the independent review, the German translation of the MSA-QoL was classified as fully equivalent to the English version. The validation study confirmed good psychometric properties of the rating scale. CONCLUSION: The German translation of the MSA-QoL was shown to be a reliable patient-reported rating scale to determine health-related quality of life in MSA patients.

Cognitive impairment in REM-sleep behaviour disorder and individuals at risk of Parkinson's disease.

BACKGROUND: Mild cognitive impairment (MCI) is commonly present at the time of Parkinson's Disease (PD) diagnosis, but its prevalence amongst individuals at increased risk of PD is unclear. METHODS: Cognition was assessed using the Montreal Cognitive Assessment (MoCA) in 208 participants in the PREDICT-PD study, and 25 participants with REM-sleep behaviour disorder (RBD). Prevalence of MCI level I was determined in all participants, and level II MCI in the RBD sub-group. RESULTS: Total MoCA scores were worse in the higher risk than the lower risk group defined as those below the 15th percentile of risk (p = 0.009), and in the RBD group compared to all healthy participants (p < 0.001). The prevalence of MCI level I was 12.8% in the lower-risk, 21.9% in the higher-risk (within the highest 15th percentile) and 64% in RBD participants; 66% of RBD participants had MCI level II with multi-domain MCI, but particularly attention and memory deficits. CONCLUSIONS: Cognitive impairment is increased in different groups at higher risk of PD, particularly in the subgroup formally diagnosed with RBD.

The motor prodromes of parkinson's disease: from bedside observation to large-scale application.

There is sufficient evidence that the pathological process that causes Parkinson's disease begins years before the clinical diagnosis is made. Over the last 15 years, there has been much interest in the existence of a prodrome in some patients, with a particular focus on non-motor symptoms such as reduced sense of smell, REM-sleep disorder, depression, and constipation. Given that the diagnostic criteria for Parkinson's disease depends on the presence of bradykinesia, it is somewhat surprising that there has been much less research into the possibility of subtle motor dysfunction as a pre-diagnostic pointer. This review will focus on early motor features and provide some advice on how to detect and measure them.

The late stage of Parkinson's -results of a large multinational study on motor and non-motor complications.

INTRODUCTION: There is little information on the late stages of parkinsonism. METHODS: We conducted a multicentre study in 692 patients with late stage parkinsonism in six European countries. Inclusion criteria were disease duration of ≥7 years and either Hoehn and Yahr stage ≥4 or Schwab and England score of 50 or less. RESULTS: Average disease duration was 15.4 (SD 7.7) years and mean total UPDRS score was 82.7 (SD 22.4). Dementia according to MDS-criteria was present in 37% of patients. Mean levodopa equivalence dose was 874.1 (SD 591.1) mg/d. Eighty two percent of patients reported falls, related to freezing (16%) or unrelated to freezing (21% of patients) or occurring both related and unrelated to freezing (45%), and were frequent in 26%. Moderate-severe difficulties were reported for turning in bed by 51%, speech by 43%, swallowing by 16% and tremor by 11%. Off-periods occurred in 68% and were present at least 50% of the day in 13%, with morning dystonia occurring in 35%. Dyskinesias were reported by 45% but were moderate or severe only in 7%. Moderate-severe fatigue, constipation, urinary symptoms and nocturia, concentration and memory problems were encountered by more than half of participants. Hallucinations (44%) or delusions (25%) were present in 63% and were moderate-severe in 15%. The association with overall disability was strongest for severity of falls/postural instability, bradykinesia, cognitive score and speech impairment. CONCLUSION: These data suggest that current treatment of late stage parkinsonism in the community remains insufficiently effective to alleviate disabling symptoms in many patients.

Heterogeneity in progression of prodromal features in Parkinson's disease.

BACKGROUND: In the pre-diagnostic phase of Parkinson's disease (PD), a range of motor and non-motor symptoms can occur. However, there is considerable variability in their onset and currently little information exists on the pattern of progression of clinical features before diagnosis. METHODS: We analysed data from a survey amongst patients with PD from 11 European countries by the European Parkinson's Disease Association. They completed questions on first occurrence of 21 pre-diagnostic features. A principal component analysis (PCA) with varimax rotation was performed to determine the co-occurrence of these features. FINDINGS: 1467 patients were included. Changes in movement were the most commonly reported features up to 4 years before diagnosis. However, at five or more years before diagnosis loss of sense of smell, sleep problems, fatigue and other non-motor features had been experienced most frequently. PCA of pre-diagnostic features' duration revealed three factors with eigenvalues over Kaiser's criterion of 1: a) a neuropsychiatric factor comprised of anxiety, depression, apathy, stress, and sleep problems; b) an axial factor defined by difficulty eating and/or swallowing problems, freezing, and falls/balance problems; and c) a motor factor with additional non-motor features. Bladder/bowel problems and tremor had low factor loadings on all components. However, in those with disease duration less than 5 years the autonomic features were associated with the axial factor and tremor loaded on both the motor and psychiatric symptom factors. INTERPRETATION: The identified symptom complexes in the pre-diagnostic stage of PD may be reflective of a shared pattern of pathological disease progression.

Are patients with somatization disorder highly suggestible?

OBJECTIVE: High suggestibility is widely regarded as an important feature of patients with medically unexplained symptoms (MUS), particularly those with multiple MUS [i.e. somatization disorder (SD)], although there are few empirical data attesting to this assumption. A study was therefore conducted to compare levels of non-hypnotic suggestibility in patients with SD and medical controls. METHOD: A modified version of the Barber Suggestibility Scale was administered to 19 patients with SD and 17 controls with an established organic dystonia. RESULTS: Patients with SD were no more suggestible than control patients. Dystonia controls were more likely to deliberately comply with suggestions than the SD patients. CONCLUSION: Contrary to popular belief, high suggestibility is not necessarily a feature of SD.

Patient experiences of receiving a diagnosis of Parkinson's disease.

OBJECTIVE: To report patients' own experiences of receiving a diagnosis of Parkinson's disease (PD) and to identify factors influencing this experience. METHODS: A survey by the European Parkinson's Disease Association in 11 European countries. RESULTS: 1775 patients with an average age of 69.7 years participated of whom 54% were male. Those living in rural areas reported having waited longer to seek medical help (p < 0.05). A possible diagnosis of PD was made at the first appointment in a third of respondents. When the diagnosis was made, only 50% reported that the diagnosis was communicated sensitively. 38% of patients reported having been given enough time to ask questions and discuss concerns, but 29% did not. 98% of participants reported having been given information about PD at the time of diagnosis but 36% did not find the information given helpful. Patient satisfaction with the diagnostic consultation was positively associated with more sensitive delivery of diagnosis, the helpfulness and quantity of the information provided and time to ask questions (all p < 0.001). Where diagnosis was given by a specialist, participants reported greater perceived satisfaction with the diagnostic consultation, greater sensitivity of communicating the diagnosis, time to ask questions, provision and helpfulness of information, and earlier medication prescription (all p < 0.0001). CONCLUSIONS: There is a need to improve how the diagnosis of PD is communicated to patients, the opportunity to ask questions soon after diagnosis, and the amount, timing and quality of life information provided, as this is associated with greater satisfaction with the diagnostic process.

Progression of dysautonomia in multiple system atrophy: a prospective study of self-perceived impairment.

To assess severity and progression of self-perceived dysautonomia and their impact on health-related quality of life (Hr-QoL) in multiple system atrophy (MSA), twenty-seven patients were recruited by the European MSA Study Group (EMSA-SG). At baseline, all patients completed the Composite Autonomic Symptom Scale (COMPASS) and the 36 item Short Form Health Survey (SF-36), and they were assessed using the 3-point global disease severity scale (SS-3) and the Unified MSA Rating Scale (UMSARS). After 6 months follow-up, the self completed COMPASS Change Scale (CCS), the SF-36, SS-3, and UMSARS were obtained. MSA patients showed marked self-perceived dysautonomia at baseline visit and pronounced worsening of dysautonomia severity on the CCS at follow-up. Severity and progression of dysautonomia did not correlate with age, disease duration, motor impairment and overall disease severity at baseline. There were no significant differences between genders and motor subtypes. Baseline COMPASS scores were, however, inversely correlated with SF-36 scores. Progression of self-perceived dysautonomia did not correlate with global disease progression. Hr-QoL scores were stable during follow-up. This is the first study to investigate self-perceived dysautonomia severity in MSA and its evolution over time. Our data suggest that dysautonomia should be recognized as a key target for therapeutic intervention in MSA.

Testing the validity of the PDQ-39 in patients with MSA.

We assessed the validity of the PDQ-39, a disease-specific health-related quality of life instrument for patients with Parkinson's disease, in patients with multiple system atrophy (MSA). Two hundred and seventy-nine patients completed the PDQ-39, the EQ-5D, the Hospital Anxiety and Depression Scale, and scales of life satisfaction and disease severity. Ceiling and floor effects were noted in some dimensions, and Mobility was skewed towards the severe end of the spectrum. Apart from the dimension of Social Support, all dimensions had high internal consistency. The factor structure of the PDQ-39 in MSA was stable, and convergent and divergent validity with other measures of quality of life and mental health were good. However, many of the specific features of MSA are not reflected in the PDQ-39. Higher order factor analysis did not support the use of a single summary index. We conclude that the PDQ-39 has only limited validity in patients with MSA.

Low-dose olanzapine for levodopa induced dyskinesias.

OBJECTIVE: To assess the usefulness of low-dose olanzapine (2.5 to 7. 5 mg/day) for Levodopa-induced-dyskinesias (LID) in patients with PD. METHODS: Ten patients with PD and LID took part in this randomized, placebo-controlled, double blind, crossover trial. Patients received a 2-week course of olanzapine or placebo in each treatment phase with 1-week washout in between. Dyskinesias were assessed at baseline and after each treatment period with an acute dopaminergic challenge and unified PD rating scale (UPDRS) questionnaires. Patients also kept on/off and dyskinesia diaries for the last 3 days prior to each assessment. RESULTS: There was a 41% difference in dyskinesia reduction on olanzapine compared to placebo, as measured by objective dyskinesia rating scales (mean percentage reduction abnormal involuntary movement score: 30% versus -11.2%, p < 0.02). Similar differences were demonstrated by patient diaries (mean reduction: 46% versus -2%, p < 0.02) and UPDRS items 32 and 33. Compared with placebo, treatment with olanzapine resulted in significant increases in 'off' time as measured by patient diaries (30% versus 2%) and reported adverse events (1.7 versus 0.1) including increased parkinsonism (1.1 versus 0.1) and a nonsignificant reported increase in drowsiness. CONCLUSIONS: Low-dose olanzapine is effective in reducing dyskinesias in PD, but even at very low doses can result in unacceptable increases in parkinsonism and 'off' time.

Novel three-stage ascertainment method: prevalence of PD and parkinsonism in South Tyrol, Italy.

BACKGROUND: A number of community-based studies on the prevalence of PD have been conducted worldwide, but they are often extremely costly and time consuming. OBJECTIVE: To assess the prevalence of PD and parkinsonism for the population aged between 60 and 85 years in South Tyrol, Northern Italy, using a novel population-based three-stage ascertainment method. METHODS: Seven hundred fifty persons aged 60 to 85 years from South Tyrol received a validated screening mail questionnaire for parkinsonism. In the second stage of the ascertainment method, trained primary care physicians (PCP) identified all persons with possible parkinsonism among those screened positive. In the third stage, movement disorders specialists excluded or confirmed the diagnosis in all identified people. RESULTS: The response rate was 87.6%. The prevalence rate per 100 population over 65 years of age was 1.5 (95% CI 0.6 to 2.3) for PD and 2.2 (95% CI 1.2 to 3.3) for parkinsonism after having been adjusted to the 1991 European standard population. Overall, 78% (95% CI 59 to 96%) of patients with parkinsonism were newly detected through the survey. CONCLUSIONS: The prevalence of PD and parkinsonism in people aged over 65 in South Tyrol was similar to that observed in door-to-door surveys in other European countries. The novel three-stage case ascertainment method employed proved a useful tool to substitute for expensive door-to-door surveys for prevalence studies of parkinsonism, detecting a high number of undiagnosed cases, particularly in geographically remote areas.

Differentiation of atypical parkinsonian syndromes with routine MRI.

OBJECTIVE: To evaluate the use of routine MRI in differentiating between patients with progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD) and control subjects. METHODS: Two neuroradiologists rated blindly and independently axial T2-weighted and proton density MR images of 54 patients with MSA, 35 patients with PSP, 5 patients with CBD, and 44 control subjects. RESULTS: More than 70% of patients with PSP and more than 80% of patients with cerebellar predominant MSA could be classified correctly with 0.5-T or 1.5-T scans, and no patient in these groups was misclassified. In the remaining patients an unequivocal differentiation could not be made. However, only approximately 50% of patients with parkinsonism-predominant MSA could be classified correctly, and 19% of them (all of whom had had 0.5-T scans) were misclassified. CONCLUSIONS: Characteristic findings on routine MRI, either 1.5 T or 0.5 T, can contribute to the identification of MSA and PSP. However, in a minority of patients no unequivocal diagnosis can be made using MRI findings alone.

Multiple system atrophy/progressive supranuclear palsy: alpha-Synuclein, synphilin, tau, and APOE.

Article abstract-Alpha synuclein, tau, synphilin, and APOE genotypes were analyzed in patients with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) and controls. The predisposing effect of the tau insertion polymorphism to the development of PSP is confirmed. However, no effect of alpha-synuclein, synphilin, or APOE variability on the development of PSP, or of tau, alpha-synuclein, APOE, or synphilin gene variability on the development of MSA, are demonstrated.

Iodine-123-iodo-lisuride SPECT in Parkinson's disease.

UNLABELLED: Recently, [123I]iodo-lisuride was synthesized for possible applications in SPECT studies. The purpose of this investigation was to compare the striatal binding and kinetics of this radioligand in patients with Parkinson's disease and normal controls. METHODS: Six patients with Parkinson's disease and three normal controls were examined. After intravenous injection of 111 MBq [123I]iodo-lisuride, sequential SPECT examinations at 20, 40, 80 and 120 min were performed. For each SPECT series the basal ganglia-to-cerebellum ratio of tracer accumulation was calculated. In one patient a repeat SPECT examination was undertaken under identical conditions to test the reproducibility of the procedure. In two other patients a second SPECT examination was performed after injection of cold lisuride as a receptor saturation study. In addition, the time course of the radioactivity was measured in the plasma and red blood cells in each individual. RESULTS: In both patients and controls, the highest tracer accumulation was found within the striatum. The basal ganglia-to-cerebellum ratio was 1.182 and 1.303 at 20 min, 1.353 and 1.450 at 40 min, 1.490 and 1.533 at 80 min, 1.550 and 1.583 at 120 min for patients and controls, respectively, which was not statistically different. In the saturation study, 50 micrograms and 100 micrograms cold lisuride led to a 28% and 33% reduction, respectively, of the basal ganglia-to-cerebellum ratio at 120 min. The ligand showed a rapid decline in plasma and red blood cells. The percent injected dose per liter was calculated to be 1.6 and 0.9, respectively, for plasma and red blood cells at 20 min. CONCLUSION: Iodine-123-iodo-lisuride SPECT seems useful for imaging intact striatal dopamine D2 receptors in patients with Parkinson's disease and may provide clinically relevant information for quantitative assessment of the availability and integrity of dopamine D2 receptors.