Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The occurrence of irresistible sleep episodes ('sleep attacks') has been noted in patients with Parkinson's syndrome treated with dopa-agonists. This is the first report of 'sleep attacks' in a patient with restless legs syndrome in whom treatment with pergolide was reduced from 2 to less than 1 mg/day. 'Sleep attacks' were accompanied by a reduced mean sleep latency of 5 min and 20 s (without sleep onset REM periods) on a multiple sleep latency test. 'Sleep attacks' disappeared when pergolide was tapered off and substituted with pramipexol. The appearance of 'sleep attacks' as a 'withdrawal' effect of pergolide is consistent with a wakefulness-promoting action of postsynaptic dopaminergic receptors at higher doses of dopamine agonists.
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PMID:Pergolide-associated 'sleep attacks' in a patient with restless legs syndrome. 1459 19

Recent recognition of daytime sleepiness in Parkinson's disease (PD) has prompted a search for its causes. Sleepy patients may be more susceptible to sleep attacks after the use of dopamine agonists and the recognition of sleep disturbances in PD may influence important therapeutic decisions. To identify clinical factors influencing excessive daytime sleepiness (EDS) and sleep complaints in PD, we studied 86 consecutive patients with clinical diagnosis of PD using a sleep questionnaire, the Epworth Sleepiness Scale, the Unified Parkinson's Disease Rating Scale and the Montgomery and Asberg Depression Rating Scale. Patients with cognitive dysfunction were not included in the study. We found that 49 patients (53.3%) had insomnia, 45 (49.9%) restless legs syndrome (RLS), 51 (55.4%) vivid dreams, 61 (71.8%) snoring and 29 (31.5%) had EDS. RLS was more frequent in patients with longer duration of illness. Snoring was the most important risk factor associated with EDS (OR=3.64, 95% CI=1.11-11.9, P=0.03) and a marginal association between motor dysfunction and EDS was observed (OR=1.06, 95% CI=1.00-1.12, P=0.05).
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PMID:Snoring and excessive daytime sleepiness in Parkinson's disease. 1467 8

This review focuses on restless legs syndrome (RLS) and Parkinson's disease (PD). These conditions are frequently encountered in clinical sleep medicine and are among the most important of the "nonapnea" sleep disorders. RLS and PD share many features, including derangement of central dopaminergic systems as the putative cause, akathisia, and nocturnal motor fluctuations. In addition, both conditions increase in prevalence with aging, exhibit a beneficial response to dopaminergic therapy, and cause marked sleep disturbances. They frequently overlap, with about 20% of patients with PD having symptoms of RLS. Both conditions appear to have a genetic predisposition that is "turned on" by environmental factors. Adverse responses to levodopa occur in both RLS and PD, manifested as rebound and augmentation in RLS and as fluctuations in motor response and dyskinesias in PD. Newer dopaminergic agents are helpful in the management of both conditions.
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PMID:Movement disorders: a sleep specialist's perspective. 1500 59

Restless legs syndrome (RLS) is a sensory-motor disorder characterized by discomfort of and urge to move the legs, primarily during rest or inactivity, partial or total relief with movement, with presence or worsening exclusively in the evening. It is a relatively common but frequently unrecognized disorder, with a prevalence ranging from 2.5 to 15% of the general population, increasing with age and with a female preponderance. The diagnosis is clinical but polysomnography is useful to determine its profound impact on sleep (difficulties in sleep onset, maintaining sleep during the night, and sleep fragmentation) and for the evidence of periodic legs movements during sleep and wake. RLS is generally idiopathic, with familial association in 40-60% of the cases, but may also be symptomatic of such associated conditions (secondary forms) as peripheral neuropathies, uremia, iron deficiency (with or without anemia), diabetes, Parkinson's disease and pregnancy. Response to dopaminergic drugs indicates that dopamine receptors are implicated, and although much progress has been made in diagnosis and treatment in the last decade, more is needed for complete elucidation of the etiology and pathophysiology of RLS.
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PMID:Epidemiology and clinical findings of restless legs syndrome. 1516 38

Dopamine is a neurotransmitter that modulates diverse waking behaviors including movement, motivation, cognition, reward, and feeding. Interest in dopamine's additional contributions to normal and pathologic sleep-wake states has experienced a recent rebirth originating from two clinical disorders: Parkinson's disease and Restless Legs Syndrome. The former, the prototypical disorder of brain dopamine cell loss, is accompanied by marked sleep disruption and impairments in daytime alertness. The latter is exquisitively responsive to pharmacologic agents that act upon dopamine receptors. The potential neurobiological substrates underlying these observations are reviewed here. Converging lines of evidence suggest that mesocorticolimbic dopamine circuits are involved in promoting wakefulness, while a less studied diencephalospinal dopamine system might underly the sensorimotor dysfunction of Restless Legs Syndrome.
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PMID:Parkinson's disease and RLS: the dopaminergic bridge. 1516 42

We report on 4 new cases of valvular heart disease in Parkinson's disease patients treated with the ergot derivative dopamine agonists pergolide and cabergoline. Noninflammatory fibrotic degeneration of cardiac valves has been reported to occur in patients with carcinoid syndrome and to occasionally complicate therapies with the anti-migraine ergot alkaloid ergotamine and methysergide and with the appetite suppressants fenfluramine and dexfenfluramine. In these cases, the pathogenesis is suspected to involve serotonin-mediated abnormal fibrogenesis by means of the 5-HT2B receptors, which are expressed in the fibroblasts of heart valves. Based on strikingly similar echocardiographic and histopathological features, we strongly suspect that ergot-derived dopamine agonists may cause a valvular heart disease nearly identical to that seen in those conditions. These cases add to a rapidly growing and worrying list of similar published reports, suggesting that we may well be facing a novel, yet unrecognized, complication of this class of agents, which are widely used not only in Parkinson's disease but also in restless legs syndrome and various common endocrine dysfunctions. Therefore, until more is known about the true prevalence of this side effect, we propose that an assessment of cardiac function be performed before and in the course of a long-term therapy with ergot derivative dopamine agonists.
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PMID:Severe multivalvular heart disease: a new complication of the ergot derivative dopamine agonists. 1519 97

Orthostatic tremor (OT) is a rare condition characterized by unsteadiness when standing still that is relieved when sitting or walking and is thought to arise from a central generator in the cerebellum or brainstem. OT is considered to be a distinct, discrete condition, and little is known about its demographic characteristics, natural history, associated features, and treatment response. We have reviewed these aspects in 41 OT patients fulfilling current diagnostic criteria, seen at our institution between 1986 and 2001. We classified 31 (75%) as having idiopathic "primary OT" either with (n = 24) or without an associated postural arm tremor. We found that 10 of 41 (25%) cases had additional neurological features, and we defined this group as having "OT plus" syndrome. Of these 10, 6 had parkinsonism; 4 of these had typical Parkinson's disease (PD), 1 had vascular and 1 had drug-induced parkinsonism. Among the remaining 4 patients, 2 had restless legs syndrome (RLS), 1 had tardive dyskinesia, and 1 orofacial dyskinesias of uncertain etiology. One patient with PD and the patient with vascular parkinsonism also had RLS. Age at onset was significantly earlier in the "primary OT" (mean +/- SD, 50.4 +/- 15.1) than in the "OT plus" (61.8 +/- 6.4; z = 2.7; P =.006) group. In 7 of the 10 "OT plus" patients, OT leg symptoms preceded the onset of additional neurological features. OT appeared to be underdiagnosed, and on average, it took 5.7 years from the initial complaints until a diagnosis was made. In general, treatment response to a variety of drugs such as clonazepam, primidone, and levodopa was poor. In most cases, OT symptoms remain relatively unchanged over the years, but in 6 of 41 cases (15%), the condition gradually worsened over the years, and in some of these cases, symptoms spread proximally to involve the trunk and arms. OT may not be a discrete disorder as commonly believed and associated features like parkinsonism present in nearly 25% of cases. Dopaminergic dysfunction may have a role in the pathophysiology of this disorder.
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PMID:Natural history and syndromic associations of orthostatic tremor: a review of 41 patients. 1525 36

Depression, dementia, and physiologic changes contribute to the high prevalence of sleep disturbances in patients with Parkinson's disease (PD). Antiparkinsonian drugs also play a role in insomnia by increasing daytime sleepiness and affecting motor symptoms and depression. Common types of sleep disturbances in PD patients include nocturnal sleep disruption and excessive daytime sleepiness, restless legs syndrome, rapid eye movement sleep behavior disorder, sleep apnea, sleep walking and sleep talking, nightmares, sleep terrors, and panic attacks. A thorough assessment should include complete medical and psychiatric histories, sleep history, and a 1- to 2-week sleep diary or Epworth Sleepiness Scale evaluation. Polysomnography or actigraphy may also be indicated. Treatment should address underlying factors such as depression or anxiety. Hypnotic therapy for sleep disturbances in PD patients should be approached with care because of the risks of falling, agitation, drowsiness, and hypotension. Behavioral interventions may also be useful.
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PMID:Sleep disorders in Parkinson's disease. 1525 35

Iron is the most important element in the body, essential for almost all types of cells, including brain cells. The role of iron in the brain has been known for years. Iron deficiency and iron excess have been associated with pathophysiology of different brain disorders. Iron deficiency has been reported to have a role in brain development and the pathophysiology of restless legs syndrome. Iron accumulation has been related to some neurologic disorders such as Alzheimer disease, Parkinson disease, type I neurodegeneration with brain iron accumulation, and other disorders. Despite years of investigation, the reason for iron imbalance in the brain is not known. It also is not known whether the accumulation of iron in the brain is primary or secondary to development of neurodegenerative disorders. This review summarizes the present knowledge on the role of iron in human brain disorders.
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PMID:Iron and brain disorders. 1529 51

Abnormal motor behaviors during sleep can be classified into four categories, ranging from myoclonic jerks to complex and integrated motor behaviors There have been recent developments in several of these conditions, in particular restless legs syndrome (RLS) and rapid-eye-movement sleep behavior disorder (RBD). RLS is one of the major causes of insomnia. Familial aggregation of RLS has been demonstrated by several groups, and molecular genetics studies have suggested the presence of susceptibility genes on chromosomes 12q and 14q. Pharmacologic and brain imaging studies suggest the involvement of dopaminergic mechanisms in RLS, but recent work has focused on brain iron metabolism. Studies indicate that RBD patients may eventually develop Parkinson's disease (PD). Conversely, RBD has been found in patients already diagnosed with PD. Single-photon emission computed tomography and positron emission tomography studies have shown a decrease in binding to presynaptic dopamine transporter in both idiopathic RBD and PD. Patients with RBD (associated or unassociated with PD) also have neuropsychological deficits. RBD may therefore represent the prodrome of a neurodegenerative disease leading to multiple system atrophy and Lewy body dementia. Understanding the underlying pathophysiology of abnormal sleep motor behaviors may prove useful in the management of insomnia.
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PMID:Abnormal motor behavior during sleep. 1530 95


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