Structural and functional alterations of the heart in Parkinson’s disease

Parkinson’s disease (PD) patients have most frequently heart failure. The cause of this increased prevalence is not known. We designed a study to assess the cardiac function and cardiac structure in patients with PD compared to a control group.

Methods: Cross-sectional study with 50 PD patients and 50 healthy matched controls. We performed electro and echocardiograms to all patients and controls. The measurements were blind. In addition, we performed a neurological assessment.

Results: PD patients had higher left ventricular mass index (114.2 ± 38.4 vs. 94.1 ± 26.4 g/m²; P = 0.003) and higher left atrial volume (30.1 ± 7.9 vs. 26.7 ± 6.2 ml/m²; P = 0.01). PD was an independent risk factor for elevated left ventricular filling pressures (OR = 2.7, CI 95% 2.2–6.3; P = 0.004). Concentric remodeling and left ventricular hypertrophy were associated with more advanced Hoehn and Yahr stages. Moreover, patients with more dysautonomia symptoms showed more left ventricular hypertrophy. Finally, PD group had longer QT interval than control group regardless of the drugs.

Conclusions: PD is significantly associated with increased concentric left ventricular hypertrophy and diastolic dysfunction. Advanced stages of PD are associated with a more severe cardiac affection. These findings can explain the increase of heart failure in PD patients. Cardiomyopathy could be a non-motor parkinsonian symptom.     

Anhedonia in Japanese patients with Parkinson's disease

Aim: Anhedonia has been proposed as a specific mood disorder related to the dopaminergic nerve dysfunction seen in Parkinson's disease (PD). This study examined hedonic tone in patients with PD using the Snaith–Hamilton Pleasure Scale (SHAPS) and investigated the associations with depressive mood by the Self‐Rating Questionnaire for Depression (SRQ‐D). Methods: This study examined 100 patients with PD and 111 age‐matched controls (C2) recruited from 300 healthy subjects (C1) to compare the frequency of anhedonia and to clarify whether anhedonia in PD is associated with depression and anti‐Parkinson medication. Results: Forty‐six percent of PD patients revealed possible/probable depression and 10 patients (10%) with PD showed anhedonia as compared to 3.3% in C1 and 2.7% in C2. The reduction in hedonic tone was related to depression in PD. Among 10 PD patients with anhedonia, seven were in anhedonia with depression and three were in anhedonia without depression. There was no sex difference in anhedonia and depression. No patients treated with pramipexole showed anhedonia but also the highest proportion of normal hedonic tone was found in patients treated with pramipexole among PD patients. In analysis of each SHAPS item, no significant difference was seen on social interaction scores in contrast to the significant reduction of interest/pastimes and sensory experience and food/drink scores between PD patients and C1/C2. Conclusion: Anhedonia may overlap depressive syndrome but some PD patients without depression presented anhedonia. Pramipexole could maintain hedonic tone. The PD patients could enjoy attracting attention and wish to do things helpful for others. Geriatr Gerontol Int 2011; 11: 275–281.     

A randomly assigned double-blind cross-over study examining the relative anti-parkinsonian tremor effects of pramipexole and pergolide

This study examined the relative anti-Parkinson's disease (PD) tremor potencies of pergolide and pramipexole in people with PD, using a 3-month double-blind cross-over design. Patients were randomly assigned to receive either pergolide and then pramipexole (n=9) or vice versa (n=8). The dose of the respective dopamine agonist was increased according to a titration schedule up to a maximum 1.5 mg t.d.s., with cross-over at 10 weeks. Assessments were performed at baseline, 4, 8 and 12 weeks. The primary outcome measures were the differences in the clinical (rest and postural) tremor scores on pergolide versus pramipexole. Seventeen PD patients (11 females and six males) with a mean age 68.4 years (range: 55-84 years) and a mean disease duration of 3.9 years (range: 2 months to 13 years) participated in the study. Twelve of the patients were taking other anti-parkinsonian medications. Two patients dropped out of the study whilst on pergolide. Fifteen of 16 patients were able to cross-over from one dopamine agonist to the other, without major retitration. There were no significant differences between the effects of the two drugs on the primary outcome measures, suggesting that the anti-PD tremor efficacies of dopaminergic medications are not dependent on differential affinities for dopamine receptor types.     

Beneficial effect of pramipexole for motor function and depression in Parkinson’s disease

We examined whether pramipexole (PPX) can influence depressive scale in normal and mild depressive parkinsonian patients. In an open study of PPX as an add-on to L-dopa therapy or single administration, 36 nondemented outpatients with Parkinson’s disease (PD) were entered first. All were in the stage II or III of Hoehn and Yahr scale (H&Y). PPX were started at 0.125 mg/day and daily doses were increased to 1.5 mg/day. At 3 months after PPX treatment, patients were re-evaluated. Hamilton Depression Rating Scale (HAM-D), Unified Parkinson’s Disease Rating Scale III, H&Y stage, and freezing of gait questionnaire were compared in patients before and after PPX treatment. These scores were significantly improved after PPX administration. There were no correlations between HAM-D and those motor functions. We suggest that PPX treatment has antidepressant effects in depressive PD patients and also ameliorates HAM-D score in nondepressive PD patients in addition to motor function.     

Abnormal behaviours during pramipexole treatment for Cotard's syndrome: a case report

Cotard's syndrome is a relatively rare condition that involves a delusion of negation in which an individual believes he or she has lost his or her soul, is dead, or is without functional body systems. This syndrome is observed in various neuropsychiatric disorders but most commonly in mood disorders. Pramipexole has often been used in the adjunctive treatment of both bipolar and unipolar depression, and it is known to cause rare but serious adverse effects such as compulsive behaviours in the treatment of Parkinson's disease. Here we report a case of Cotard's syndrome in treatment‐resistant major depression associated with abnormal behaviours that might be caused by pramipexole. In the present case, the patient's abnormal behaviours gradually disappeared about 2 months after the discontinuation of pramipexole. The hypoperfusion in the bilateral parieto‐occipital lobe found on single‐photon emission computed tomography suggests the presence of Lewy body disease pathology. Nonetheless, the patient's abnormal behaviours disappeared after the discontinuation of pramipexole, indicating that they are mainly attributable to pramipexole treatment. However, the possible existence of Lewy body pathology could facilitate the emergence of abnormal behaviours after treatment with pramipexole. The patient's abnormal behaviours, such as eating other patients' food and taking her medicine before the scheduled time, might differ from typical compulsive behaviours induced by pramipexole (such as pathological gambling and hypersexuality), but they could be regarded as disinhibition. Therefore, we should follow up on the clinical course of this case carefully through neuroimaging investigation and neurocognitive assessment.     

Toxicity assessment of pramipexole in juvenile rhesus monkeys

Pramipexole (PPX) is a dopamine agonist approved for the treatment of the signs and symptoms of idiopathic Parkinson's disease as well as restless leg syndrome. The objective of this study was to investigate the toxicity of PPX when administered orally to juvenile rhesus monkeys once daily for 30 weeks, and to assess the reversibility of toxicity during a 12-week recovery. Rhesus monkeys (N = 4 males and 4 females/group; 22–24 months of age) were orally treated daily for 30 weeks with 0.0, 0.1, 0.5 or 2.0 mg/kg PPX, and subjects were assessed daily using the NCTR Operant Test Battery (OTB). Clinical chemistry, hematology, ophthalmology and other standard postmortem toxicological evaluations, including histopathology and neuropathology as well as toxicokinetics were performed. The systemic exposure to PPX was higher than that at therapeutic doses in man and AUC(0–24 h)-data increased proportionally to dose. Blood pressure significantly decreased over time in all groups including control. Near the end of treatment, there were statistically significant decreases in heart rate for the 0.5 and 2.0 mg/kg/day groups compared to control. After 4 weeks of dosing, serum prolactin was significantly decreased in all treatment groups compared to control. This decrease remained at the end of treatment in the 0.5 and 2.0 mg/kg/day groups. In summary, administration of PPX at doses of up to 2.0 mg/kg/day for 30 weeks to juvenile rhesus monkeys produced adverse findings which were attributable to its pharmacological properties, including hypoprolactinemia.     

Efficacy of pramipexole in restless legs syndrome: a six-week, multicenter, randomized, double-blind study (effect-RLS study).

We evaluated the efficacy of pramipexole versus placebo in restless legs syndrome (RLS) for 6 weeks. Overall, 345 patients were randomly assigned in a 1:2 ratio to receive either placebo (n = 115) or pramipexole (n = 230) with a starting dose of 0.125 mg/day. The dose was individually optimized according to the Patient Global Impression (PGI) assessment, up to a maximum of 0.75 mg/day. The primary endpoint consisted of two assessments: the change from baseline in the International RLS Study Group Rating Scale (IRLS) and the proportion of patients with Clinical Global Impressions-Improvement (CGI-I) assessments of "much/very much improved" (CGI-I responders) at week 6. Secondary endpoints included PGI and IRLS responder rates. Patient demographics and baseline characteristics were comparable between treatment groups. At baseline, mean IRLS scores were 24.9 (placebo) and 24.7 (pramipexole), representing severely affected patients. After 6 weeks, adjusted mean reductions (+/-SE) in IRLS score were 5.7 (+/-0.9) for placebo (median dose 0.47 mg/day) and 12.3 (+/-0.6) for pramipexole (median dose 0.35 mg/day; P < 0.0001). CGI-I responder rates were 32.5% (placebo) and 62.9% (pramipexole) (P < 0.0001). For all secondary endpoints, pramipexole showed superior results. Pramipexole was well tolerated throughout the study.