A randomized clinical trial to evaluate the effects of rasagiline on depressive symptoms in non-demented Parkinson's disease patients.

BACKGROUND AND PURPOSE: Depressed mood is a common psychiatric problem associated with Parkinson's disease (PD), and studies have suggested a benefit of rasagiline treatment. METHODS: ACCORDO (see the ) was a 12-week, double-blind, placebo-controlled trial to evaluate the effects of rasagiline 1 mg/day on depressive symptoms and cognition in non-demented PD patients with depressive symptoms. The primary efficacy variable was the change from baseline to week 12 in depressive symptoms measured by the Beck Depression Inventory (BDI-IA) total score. Secondary outcomes included change from baseline to week 12 in cognitive function as assessed by a comprehensive neuropsychological battery; Parkinson's disease quality of life questionnaire (PDQ-39) scores; Apathy Scale scores; and Unified Parkinson's Disease Rating Scale (UPDRS) subscores. RESULTS: One hundred and twenty-three patients were randomized. At week 12 there was no significant difference between groups for the reduction in total BDI-IA score (primary efficacy variable). However, analysis at week 4 did show a significant difference in favour of rasagiline (marginal means difference ± SE: rasagiline -5.46 ± 0.73 vs. placebo -3.22 ± 0.67; P = 0.026). There were no significant differences between groups on any cognitive test. Rasagiline significantly improved UPDRS Parts I (P = 0.03) and II (P = 0.003) scores versus placebo at week 12. Post hoc analyses showed the statistical superiority of rasagiline versus placebo in the UPDRS Part I depression item (P = 0.04) and PDQ-39 mobility (P = 0.007) and cognition domains (P = 0.026). CONCLUSIONS: Treatment with rasagiline did not have significant effects versus placebo on depressive symptoms or cognition in PD patients with moderate depressive symptoms. Although limited by lack of correction for multiple comparisons, post hoc analyses signalled some improvement in patient-rated cognitive and depression outcomes.

Dynamic evaluation of spine kinematics in individuals with Parkinson's disease and freezing of gait.

BACKGROUND: Freezing of gait (FoG) is an episodic failure of gait exposing people with Parkinson's disease (PD) to a high risk of falling. Despite growing evidence of the interconnection between impaired trunk control and FoG, a detailed description of spinal kinematics during walking is still lacking in this population. RESEARCH QUESTION: Do spinal alterations impact gait performance in individuals with PD and FoG? METHODS: We analyzed kinematic data of 47 PD participants suffering (PD-FOG, N = 24) or not suffering from FoG (PD-NFOG, N = 23) and 15 healthy controls (HCO) during quiet standing and unperturbed walking. We estimated the main spinal variables (i.e., spinal length, lordosis and kyphosis angles, trunk inclination), the pelvis angles, and the shoulder-pelvis angles during gait and standing. We studied differences across conditions and groups and the relationships between postural and gait parameters using linear regression methods. RESULTS: During standing and walking, both PD groups showed increased trunk inclination and decreased lordosis angle with respect to HCO, as well as a decreased range in variation of kyphosis angle, pelvic obliquity, and shoulder-pelvis angles. Only PD-FOG participants showed reduced range of lordosis angle and spinal length compared to HCO. PD-FOG individuals were also not able to straighten their spine during walking compared to standing. Stride length and velocity were decreased in both patient groups compared to HCO, while swing duration was reduced only in the PD-FOG group. In individuals with FoG, trunk inclination and lordosis angle showed moderate but significant positive correlations with all gait alterations. SIGNIFICANCE: Spine alterations impacted gait performance in individuals with PD suffering from FoG. Excessive trunk inclination and poor mastering of the lordosis spinal region may create an unfavourable postural precondition for forward walking. Physical therapy should target combined spinal and stepping alterations in these individuals.

A cross-sectional multicenter study of cognitive and behavioural features in multiple system atrophy patients of the parkinsonian and cerebellar type.

Imaging and neuropathology studies have demonstrated significant abnormalities not only in subcortical, but also in cortical regions of patients with multiple system atrophy (MSA). This raises the possibility that cognitive dysfunction may contribute to the clinical spectrum of this disorder to a greater extent than it is currently not widely appreciated. In this cross-sectional multicenter study from the European multiple system atrophy study group ( http://www.emsa-sg.org ), we applied an extensive neuropsychological test battery in a series of 61 clinically diagnosed probable MSA patients. The results demonstrated that general cognitive decline as assessed by MMSE was uncommon (2 out of 61 patients <24). In contrast, frontal lobe-related functions (as measured by FAB) were impaired in 41 % of patients, with abstract reasoning and sustained attention less compromised. This pattern was similar to our control group of 20 patients with Parkinson's disease (matched for disease duration and age at onset). There was no difference in cognitive performance between MSA patients with the parkinsonian versus the cerebellar variant. Behaviourally, MSA patients had greater depression than PD and in the case of MSA of the cerebellar variant significantly lower anxiety. Our data show that cognitive abnormalities are relatively frequent in multiple system atrophy and this involves primarily frontal-executive functions. Their contribution to clinical disability and disease progression needs to be addressed in larger prospective studies.

Anthropometric indices of fat distribution and cardiometabolic risk in Parkinson's disease.

BACKGROUND & AIMS: To investigate the association between anthropometric indices of body fat distribution and cardiometabolic risk factors in a population of Parkinson's disease (PD) patients. METHODS & RESULTS: One hundred and fifty-seven PD patients (57.3% males) were studied measuring: waist circumference (WC), waist-hip ratio (WHR), waist-to-height ratio (WtHR), body fat percentage (BF%) by impedance, fasting glucose, serum lipids. Information was collected also on diabetes, hypertension and metabolic syndrome (MetS). Increased cardiometabolic risk was defined by ≥2 MetS component traits other than abdominal adiposity. In the whole population, prevalence of overweight and obesity were 35.0% and 19.2%, respectively. However, prevalence of MetS and elevated cardiometabolic risk were 14.6% and 18.5%, respectively. Prevalence was similar between genders, with one exception: adverse fat distribution according to WC and WHR was more common in females (P < 0.001). Using a multivariable model (adjustments: age, smoking status and disease duration), indices were highly correlated with BF% in both genders. WC and WtHR were associated with the number of MetS criteria and elevated risk. The only cardiometabolic parameters associated with anthropometric indices were HDL in men and triglycerides in women. After adjusting also for BMI all the associations found with anthropometric indices disappeared. CONCLUSIONS: Despite their correlation with BF%, anthropometric indices of body fat distribution appear to poorly account for the reduced cardiometabolic risk of the PD patient. This finding suggests a low metabolic activity within the adipose tissue. The implications of fat distribution on the cardiometabolic risk of PD patients clearly deserves further investigation.

Validity and metric of MiniMental Parkinson and MiniMental State Examination in Parkinson's disease.

The MiniMental Parkinson (MMP) has been derived from the MiniMental State Examination (MMSE) for the screening of cognitive impairment in Parkinson's disease by adding subtests that were focused on executive and visuo-spatial impairment more than on memory or language deficits. In this multicenter study, the psychometric and validity properties of the MMP have been evaluated in 69 cognitively intact and 52 cognitively impaired patients with Parkinson's disease, classified according to their performance at the Dementia Rating Scale. The MMP showed better metrics and convergent validity, and higher screening ability. However, its performance was not fully satisfying in terms of data distribution, coefficient of variation and specificity, and Receiver Operating Characteristic curves did not show clear cut superiority of either scale at their best sensitivity-specificity trade off. The MMP seems to be slightly preferable to the MMSE only at a cut off that favours sensitivity with respect to specificity, for screening purposes. The test is simple and quick, but has limitations in terms of validity.

Artistic productivity and creative thinking in Parkinson's disease.

BACKGROUND AND PURPOSE: Creative drive and enhanced artistic-like production may emerge in patients with Parkinson's disease (PD) during dopaminergic therapy. However, it has not been described to date whether this artistic-like production results from dopaminergic drugs triggering innate skills or it could be considered as a repeated behavior possibly associated with impulse control disorders (ICDs). METHODS: We investigated creative drive in a cohort of cognitively preserved patients with PD by means of the Torrance Test of Creative Thinking (TTCT). We also investigated a putative association between creative drive and ICDs in 36 PD patients with (PD-c) or without (PD-nc) increased artistic-like production and 36 healthy controls (HC). We considered artistic-like productivity to be enhanced if patients reported working on any form of art more than 2h per day after the introduction of dopaminergic treatment. The TTCT, the Barratt Impulsiveness Scale (BIS-11A), the Minnesota Impulsive Disorders Interview (MIDI), and the Punding Rating Scale were applied. RESULTS: Mean TTCT score of PD-c was found to be similar to HC (169.4±51.6 vs. 170.2±69.7, respectively), and both PD-c and HC had significantly higher TTCT scores than patients with PD-nc (125.4±46.1 P<0.05). TTCT did not correlate with any demographic or clinical data in both PD subgroups. No correlation was found between TTCT, BIS-11A, and MIDI. CONCLUSIONS: Our study suggests that newly acquired artistic-like production in patients with PD is not associated with impulsivity or ICDs. Artistic-like production might represent the emerging of innate skills in a subset of predisposed patients with PD on dopaminergic therapy.

Familial aggregation in Progressive Supranuclear Palsy and Corticobasal Syndrome.

BACKGROUND: Studies on familial aggregation might be of help to evaluate whether the genetic background has a key role in Progressive Supranuclar Palsy (PSP) and Corticobasal Syndrome (CBS). Only a few studies are available. OBJECTIVE: To evaluate the prevalence of positive family history (FH) in PSP and CBS in a large sample of patients. METHODS: Two hundred and thirty patients and 110 controls entered the study. Patients underwent an extensive clinical, neurological and neuropsychological assessment as well as a structural brain imaging study. A clinical follow-up further confirmed the diagnosis. Familial aggregation was carefully recorded by a standardised questionnaire. RESULTS: One hundred and twenty-nine PSP (age at onset = 66.6 +/- 7.3, female = 46.1%) and 101 CBS (age at onset = 62.8 +/- 8.9, female = 41.6%) were consecutively enrolled. Positive FH was found in 31.8% of PSP (n = 41) and in 31.7% of CBS (n = 32). Familial aggregation was lower in the age-matched control group compared to patient group (21.8%, P = 0.05). Patients with PSP had higher positive FH for Parkinsonism (63.4%) when compared to FH for dementia (36.6%). In CBS, FH was equally distributed between Parkinsonism (53.1%) and dementia (46.9%). In addition, FH was not associated with age at disease onset in PSP (FH+ versus FH-, 67.0 +/- 7.3 vs. 66.7 +/- 7.1, P = 0.788) and in CBS (62.6 +/- 7.9 vs. 62.9 +/- 9.5, P= 0.877). CONCLUSIONS: These results argue for familial aggregation in PSP and CBS, further underlying the importance of genetic background in these disorders. Further studies on possible genetic modulators or genetic epistasis contributing to PSP and CBS development are warranted.

Use of probiotics for the treatment of constipation in Parkinson's disease patients.

AIM: The aim of this paper was to assess the effects of milk fermented with the probiotic strain Lactobacillus casei Shirota on constipation in Parkinson's disease patients. Constipation is a common secondary symptom in patients suffering from Parkinson's Disease (PD), generally treated with dietary therapy, soluble fiber supplements and macrogol laxatives without sodium sulfate. There are no studies on the use of probiotics in the treatment of constipation in these patients. The effects of the administration of Lactobacillus casei Shirota on gastrointestinal symptoms have been assessed in two randomized controlled trials on patients suffering from chronic constipation. METHODS: Forty PD patients suffering from constipation according to Rome III criteria were recruited. We compared the characteristic of intestinal function during two periods with different treatments: in the first week the patients treated constipation only with dietetic therapy; in the following 5 weeks the patients treated constipation not only with dietetic therapy, but also taking a 65 mL fermented milk drink containing 6.5×109 CFU of Lactobacilus casei Shirota daily.They completed a daily diary for 6 weeks, recording details related to their intestinal function. RESULTS: After probiotic intake we observed a statistically significant increase in the number of days per week in which stools were of normal consistency (P<0.01) and significant reductions in the number of days per week in which patients felt bloated (P<0.01), experienced abdominal pain (P<0.01) and sensation of incomplete emptying (P<0.01). CONCLUSION: This pilot study showed that a regular intake of probiotics can significantly improve stool consistency and bowel habits in Parkinson's disease patients.

Cerebral activity modulation by extradural motor cortex stimulation in Parkinson's disease: a perfusion SPECT study.

Extradural motor cortex stimulation (EMCS) has been proposed as alternative to deep brain stimulation (DBS) in the treatment of Parkinson's disease (PD). Its mechanisms of action are still unclear. Neuroimaging evidenced motor cortical dysfunction in PD that can be reversed by therapy. We performed left hemisphere EMCS surgery in six advanced PD patients fulfilling CAPSIT criteria for DBS with the exception of age >70 years. After 6 months, we measured regional cerebral blood flow (rCBF) at rest with SPECT and Tc-99m cysteinate dimer bicisate off-medication with stimulator off and on. Clinical assessment included Unified Parkinson's Disease Rating Scale part II and III, Abnormal Involuntary Movement Scale and mean dopaminergic medication dosage. We used statistical parametric mapping for imaging data analysis. Clinically we observed no mean changes in motor scales, although blinded evaluation revealed some benefit in individual patients. We found significant rCBF decrements in the pre-central gyrus, pre-motor cortex and caudate nucleus bilaterally, left prefrontal areas and right thalamus. Perfusion increments were found in cerebellum bilaterally. EMCS determined significant modulation of neuronal activity within the cortico-basal ganglia-thalamo-cortical motor loop in our cohort of advanced PD patients. However, these effects were paralleled by mild and variable clinical efficacy.

Duodenal levodopa infusion improves quality of life in advanced Parkinson's disease.

BACKGROUND: A significant percentage of patients with Parkinson's disease (PD) continue to experience motor fluctuations and dyskinesias despite the association of dopamine agonists and levodopa with COMT or MAO-B inhibitors. The use of apomorphine infusion is limited by compliance while deep brain stimulation is feasible only for a small number of patients mostly because of age constraints. OBJECTIVE: To assess prospectively the effectiveness of duodenal levodopa infusion on quality of life as well as motor features in patients with advanced PD. In all but 1 case levodopa infusion was stopped at nighttime. METHODS: We report the outcome of 22 PD patients, followed for up to 2 years, who were on continuous duodenal levodopa/carbidopa infusion through percutaneous endoscopic gastrostomy. RESULTS: We found a significant reduction in 'off' period duration as well as dyskinesia severity (Unified Parkinson's Disease Rating Scale part IV, items 33 and 39). There was significant improvement in the 39-item Parkinson's Disease Quality of Life Questionnaire as well as in the Unified Parkinson's Disease Rating Scale part II up to the 2-year follow-up. Five patients withdrew: 2 for poor compliance and 3 for adverse events (1 was related to percutaneous endoscopic gastrostomy). CONCLUSIONS: These results demonstrate significant clinical improvements in quality of life and activities of daily living consistent with the occurrence of a satisfactory therapeutic response and a reduction in dyskinesia severity.

Multiparametric MR imaging of Parkinsonisms at 3 tesla: Its role in the differentiation of idiopathic Parkinson's disease versus atypical Parkinsonian disorders.

OBJECTIVES: The Nigrosome-1 and putaminal hypointensity depicted on susceptibility-weighted imaging (SWI), and midbrain atrophy assessed on T1-weighted are some of the most common radiological parameters to diagnose Parkinsonism at Magnetic Resonance (MR) imaging. Our aim is to assess the feasibility of these signs in the differentiation of Idiopathic Parkinson's disease (IPD) patients versus disease (DC) and healthy controls (HC) and in the assessment of the Atypical Progressive Parkinsonisms (APPs). METHODS: Presence or loss of the Nigrosome-1 was assessed retrospectively on multiple-echo SWI obtained on a 3 T scan by two neuroradiologists. Results were compared with the 123I-FP-CIT SPECT images. Morphologic diagnostic features suggestive of APPs such as midbrain atrophy and putaminal hypointensity were evaluated by qualitative scores. The midbrain and putaminal scores were summed (combined score) and then added to the Nigrosome-1 score (global score). RESULTS: The study included 126 patients with IPD (n = 56), APPs patients (n = 30; 18 PSP, 3 MSA-C, 9 MSA-P), 16 DC and 24 HC. Sensitivity and specificity of the Nigrosome-1 in discriminating IPD from controls were 96,43% and 85.00%, APPs from controls were 100% and 85%, IPD from APPs were 96,43% and 0% respectively. Combined score for midbrain atrophy and putaminal hypointensity resulted in the most accurate for distinguishing APPs from IPD with a value of ≥ 2 (AUC = 0.98). CONCLUSION: Nigrosome-1 is a valid tool to differentiate IPD-APPs from controls. The combined score of midbrain atrophy and putaminal hypointensity represents a valid diagnostic pointer in the differential diagnosis of APPs from IPD.

Clinical and imaging characterization of a patient with idiopathic progressive ataxia and palatal tremor.

We describe clinical and imaging features of a patient with sporadic progressive ataxia and palatal tremor (PAPT) of unknown etiology. There was hypertrophy of bilateral inferior olivary nuclei with hyperintense T2-weighted signal and mild cerebellar atrophy at brain magnetic resonance imaging. 18F-fluoro-2-desoxy-d-glucose positron emission tomography scanning (FDG-PET) showed hypometabolism in the red nucleus, external globus pallidus and precuneus while FP-CIT-SPECT imaging revealed mild and progressive loss of striatal dopaminergic terminals. Our findings suggest that in idiopathic PAPT involvement of the dentato-rubro-olivary pathway occurs along with some dopaminergic dysfunction.

Striatal dopamine transporter binding in patients with Parkinson's disease and severe occupational hydrocarbon exposure.

We used 123I-Ioflupane SPECT to study striatal dopamine transporter (DAT) binding in 36 Parkinson's disease (PD) patients with history of severe occupational exposure to hydrocarbons. Data were compared with 38 PD patients without exposure history as well as healthy controls. Both PD cohorts showed significant striatal uptake decrements compared with controls. We found significantly lower values in the whole striatum of exposed compared with non-exposed patients (0.83 +/- 0.25 vs. 1.05 +/- 0.39; P = 0.004), more pronounced in the putamen (0.61 +/- 0.24 vs. 0.85 +/- 0.42; P = 0.004). We conclude that severe occupational exposure to hydrocarbons may modify disease course and ultimately accelerate nigro-striatal denervation.

Parkinson's disease, chronic hydrocarbon exposure and striatal neuronal damage: a 1-H MRS study.

Several patients with Parkinson' s disease (PD) reveal an history of chronic exposure to hydrocarbon-solvents. Chronic exposure to hydrocarbon-solvents has been proposed as a risk factor for more severe forms of PD with earlier onset of symptoms and reduced response to dopaminergic therapy. A direct correlation between disease severity and exposure degree has been previously shown. Seven exposed PD patients (two with low degree exposure and five with high degree exposure), 10 unexposed PD patients matched for sex, age and Hoehn and Yahr scale (=3 in the "on" phase), and 10 unexposed PD patients matched for sex, age and l-dopa daily intake instead of disease severity (Hoehn and Yahr scale=3.5 in the "on" phase) were studied. Twenty normal subjects without previous exposure to hydrocarbon-solvents and matched for age and sex with HPD patients were studied for comparison. The purpose of the study was to assess neuronal degeneration in the striatum of exposed vs unexposed PD patients. The authors investigated whether neuronal damage/loss was detectable in the lentiform nucleus measuring N-acetylaspartate (NAA) levels by 1-H MRS. Multiple single voxel MRS water-suppressed spectra were obtained also from the white matter and the occipital lobe. NAA was normal in the lentiform nucleus of patients with low exposure as well as in patients with no exposure whereas it was decreased in PD patients with high degree exposure. White matter and occipital lobe NAA content was normal both in exposed and unexposed PD patients. Clinical expression is more severe in PD patients with previous high degree solvent exposure because of the associated post-synaptic damage of the nigro-striatal pathway.

Clinical correlates and cognitive underpinnings of verbal fluency impairment after chronic subthalamic stimulation in Parkinson's disease.

A decline in verbal fluency is the most consistent neuropsychological sequela of deep brain stimulation (DBS) for Parkinson's disease. We assessed clinical correlates and switching and clustering subcomponents in 26 parkinsonians undergoing subthalamic DBS. Post-surgical motor improvement was accompanied by worsening at both letter and category fluency tasks. Total number of words and switches decreased, while average cluster size was unchanged. Worsening tended to be prominent in patients with baseline poorer cognitive status and more depressed mood. Impairment of shifting suggests prefrontal dysfunction, possibly due to disruption of fronto-striatal circuits along the surgical trajectory and/or to high frequency stimulation itself.

The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson's disease and originates from a common ancestor.

BACKGROUND: Mutations in the gene Leucine-Rich Repeat Kinase 2 (LRRK2) were recently identified as the cause of PARK8 linked autosomal dominant Parkinson's disease. OBJECTIVE: To study recurrent LRRK2 mutations in a large sample of patients from Italy, including early (<50 years) and late onset familial and sporadic Parkinson's disease. RESULTS: Among 629 probands, 13 (2.1%) were heterozygous carriers of the G2019S mutation. The mutation frequency was higher among familial (5.1%, 9/177) than among sporadic probands (0.9%, 4/452) (p<0.002), and highest among probands with one affected parent (8.7%, 6/69) (p<0.001). There was no difference in the frequency of the G2019S mutation in probands with early v late onset disease. Among 600 probands, one heterozygous R1441C but no R1441G or Y1699C mutations were detected. None of the four mutations was found in Italian controls. Haplotype analysis in families from five countries suggested that the G2019S mutation originated from a single ancient founder. The G2019S mutation was associated with the classical Parkinson's disease phenotype and a broad range of onset age (34 to 73 years). CONCLUSIONS: G2019S is the most common genetic determinant of Parkinson's disease identified so far. It is especially frequent among cases with familial Parkinson's disease of both early and late onset, but less common among sporadic cases. These findings have important implications for diagnosis and genetic counselling in Parkinson's disease.

Stereotaxic implantation of autologous adrenal medulla into caudate nucleus in four patients with parkinsonism. One-year follow-up.

Four patients with levodopa-responsive parkinsonism (aged 26, 35, 45, and 49 years) received autologous adrenal medullary implants into or near the left caudate nucleus by stereotaxic implantation after flank adrenalectomy. All patients had an immediate response to implantation lasting several days, during which parkinsonian signs and symptoms decreased. This period was followed by a gradual reappearance of symptoms in all but one patient. This patient had had a dramatic increase in "on" time without dyskinesias and a decrease in the severity and duration of "off" time. He died of multifocal glioblastoma 1 year after transplantation. Autopsy revealed no surviving adrenal cells. In one case, the stereotaxic implantation missed the basal ganglia, resulting in the placement of the adrenal medullary tissue into the medial thalamus and near the third ventricle; the patient did not improve. In the other two cases, a modest but definite increase in "on" time without dyskinesia and a reduction in the severity and duration of "off" time has been observed. The role of autologous adrenal medullary transplantation in patients with parkinsonism remains to be determined. Patients with a family history of cerebral malignancy may be at increased risk for the development of transplant-induced malignancy.

Methionine-enkephalin, substance P, and homovanillic acid in the CSF of parkinsonian patients.

Methionine-enkephalin, substance P, and homovanillic acid concentrations were measured in the CSF of subjects not affected by neurologic disorders (group 1), and in parkinsonian patients who had a slight or moderate (group 2) or severe (group 3) disability. Homovanillic acid and substance P concentrations in the CSF of groups 2 and 3 were respectively lower and higher than in group 1. On the contrary, an increase in CSF methionine-enkephalin content was found only in group 2. Our results confirm in humans the close relation between the dopaminergic and peptidergic transmissions in the nigrostriatal system that has been observed in experimental animals.

A crossover, controlled study comparing pergolide with bromocriptine as an adjunct to levodopa for the treatment of Parkinson's disease.

A single-blind, crossover study was carried out to compare the efficacy and safety of pergolide against that of bromocriptine in 57 patients with Parkinson's disease who showed a declining response to levodopa therapy. Patients were randomly assigned to receive either bromocriptine followed by pergolide, or pergolide followed by bromocriptine. Both drugs were administered for 12 weeks. Patients were assessed by a clinician blinded to treatment assignment using the New York University Parkinson's Disease Scale. The average daily dose of pergolide was 2.3 +/- 0.8 mg and of bromocriptine 24.2 +/- 8.4 mg. Addition of pergolide or bromocriptine resulted in a significant improvement in total scores when compared with the previous treatment of levodopa alone (pergolide, p = 0.0001; bromocriptine, p = 0.0005). Pergolide was more effective than bromocriptine in daily living scores (p = 0.02) and motor scores (p = 0.038). No differences in the incidence of dyskinesias, dystonias, or psychosis were observed between groups. Fewer adverse events were recorded in the pergolide group, and most patients and physicians preferred pergolide to bromocriptine. Pergolide as adjunctive therapy to levodopa was more effective than bromocriptine in this short-term trial.