To study the putative association of dopamine agonists with sleep attacks in patients with Parkinson's disease (PD) and their relation to daytime sleepiness, we performed a survey of 2,952 PD patients in two German counties. In 177 patients, sudden, unexpected, and irresistible sleep episodes while engaged in some activity were identified in a structured telephone interview. Ninety-one of these patients denied the occurrence of appropriate warning signs. A total of 133 patients (75%) had an Epworth Sleepiness Scale (ESS) score >10; 65 (37%) >15. Thirty-one patients (18%) had an ESS score < or =10 and yet experienced sleep attacks without warning signs. Thus, although a significant proportion of patients at risk for sleep attacks might be identified using the ESS, roughly 1% of the PD patient population seems to be at risk for sleep attacks without appropriate warning signs and without accompanying daytime sleepiness. Sleep attacks occurred with all dopamine agonists marketed in Germany (alpha-dihydroergocryptine, bromocriptine, cabergoline, lisuride, pergolide, pramipexole, ropinirole), and no significant difference between ergot and nonergot drugs was evident. Levodopa (L-dopa) monotherapy carried the lowest risk for sleep attacks (2.9%; 95% confidence interval [CI], 1.7-4.0%) followed by dopamine agonist monotherapy (5.3%; 95% CI, 1.5-9.2%) and combination of L-dopa and a dopamine agonist (7.3%; 95% CI, 6.1-8.5%). Neither selegeline nor amantadine or entacapone appeared to influence the occurrence of sleep attacks. A high ESS score, intake of dopamine agonists, and duration of PD were the main influencing factors for the occurrence of sleep attacks. The odds ratio for dopamine agonist therapy was 2.9 compared to 1.9 with L-dopa therapy and 1.05 for a 1-year-longer disease duration.
A renin-like enzyme is present in brain tissue and is independent of kidney and plasma renin. In the presence of homologous substrate it forms angiotensin. Administration of aldosterone significantly decreases this angiotensinforming enzyme activity, while administration of progesterone markedly enhances it.
Anhedonia, a core symptom of depression, correlates with motor alterations in major depressive disorder and has been assumed to be frequent in depressed patients with Parkinson's disease (PD). In the present study, the authors assessed for the first time frequency of anhedonia in patients with idiopathic Parkinson's disease (N = 657) and the relationship of anhedonia and parkinsonian motor deficits during treatment with pramipexole. Mild depression was present in 47% of the patients and moderate to severe depression in 22%. Anhedonic individuals included 45.7% of all patients and 79.7% of depressed Parkinson's disease patients. Anhedonic Parkinson's disease patients had greater motor deficits, restrictions in activities of daily living, and depression compared to nonanhedonic patients. Frequency of anhedonia and depression was significantly reduced during treatment with pramipexole. Future studies should further investigate antianhedonic efficacy of dopamine agonists including pramipexole in depressed patients with Parkinson's disease.
Sleep attacks are a common yet only recently recognized phenomenon in patients with Parkinson's disease (PD). Initially reported to occur only with particular dopamine agonists, sleep attacks have been observed with all dopaminergic drugs. [1][2][3] In the majority of affected patients, sleep attacks are a stable phenomenon and occur with and without excessive daytime sleepiness. 2 Presence or absence of warning signs preceding a sleep attack have received particular interest, as sleep attacks without warning signs might be especially dangerous.It is conceivable that intrinsic variations of the sleep regulating systems in interaction with dopaminergic drugs may provoke the occurrence of sleep attacks. To test if genetic variants of the different dopamine receptors or the serotonin transporter contribute to the etiology of sleep attacks, we examined four known polymorphisms of the genes for dopamine receptors 2, 3, and 4 (DRD2 141C del/ins; DRD2 TaqIA; DRD3 Ser9Gly; DRD4 48 base pair [bp] repeat), and the 5-HTTLPR polymorphism in the serotonin transporter gene (SERT) in a community based case control study. We found an association between sleep attacks without warning signs and the DRD4*2 (short) allele.
METHODSIn a survey of 2,952 German PD patients, we previously identified 177 patients with sleep attacks defined as "an event of falling asleep suddenly, unexpectedly, and irresistibly while engaged in some activity, e.g., during a meal, a telephone call, writing, or driving a car", using a self-rating scale and a structured telephone interview. Details of this study can be found in the June 2003 issue of Movement Disorders. 2 Special emphasis was placed on warning signs such as "yawning, closing of the eyelids, rapid decrease of mental alertness or acute onset of excessive tiredness immediately before falling asleep". 2 PD patients falling asleep while passive (e.g., watching TV or reading) were not considered for this association study. Information on intake of dopaminergic drugs at the time of sleep attacks was collected, and a control group of PD patients without sleep attacks was matched according to type of dopaminergic treatment (no dopa and no dopamine agonist; levodopa (L-dopa) only; dopamine agonist only; L-dopa plus dopamine agonist; L-dopa plus more than one dopamine agonist), disease duration, and age. Rank order for matching was type of treatment, followed by disease duration and age. All patients were of Caucasian ethnicity and gave written informed conDrs. Paus and Seeger contributed equally to this work.
1. Plasma noradrenaline was measured in 125 patients with stable essential hypertension (WHO 1-11) and in 107 normotensive control subjects lying and standing.2. In normotensive subjects and in patients with essential hypertension no sex-related differences of plasma noradrenaline were found between agematched groups.3. Plasma noradrenaline was not related to sodium balance indexed by urinary sodium/creatinine ratio.4. In patients with essential hypertension plasma noradrenaline increases with age.5. Mean plasma noradrenaline concentrations are significantly higher in patients with essential hypertension compared with age-matched normotensive subjects both lying and standing.6. In patients with essential hypertension diastolic blood pressure and heart rate correlated significantly with supine plasma noradrenaline concentrations.
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