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 pathophysiology of sleep-related motor diseases and sleep dysfunction in movement disorders is widely unknown as yet. Functional brain imaging, in particular radioisotope and magnetic resonance techniques, are powerful tools to investigate possible pathomechanisms of combined sleep and motor dysregulation. In patients with Restless legs syndrome (RLS), only a subtle striatal dopamine deficit was found in PET and SPECT despite a good treatment effect of dopaminergic drugs. Functional MRI suggested a central generator of periodic limb movements during sleep (PLMs) in RLS. In contrast, a marked striatal dopamine depletion was demonstrated in patients with REM sleep behaviour disorder (RBD) as the base for the clinical and nosological overlap of RBD with parkinsonian disorders. PET and SPECT also suggested that sleep abnormalities in Parkinson's disease (PD), such as REM sleep diminution or increased PLMs, are indirect manifestations of the primary striatal dopamine deficiency.
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PMID:Functional brain imaging in combined motor and sleep disorders. 1675 81

In this study we have explored the nature and range of sleep dysfunction that occurs in untreated Parkinson's disease (PD) comparing data obtained from the use of the Parkinson's disease sleep scale (PDSS) in an untreated PD patient group compared to advanced PD and healthy controls. 25 untreated (drug-naive, DNPD) PD patients (mean age 66.9 years, range 53-80, 18 males) completed the validated Parkinson's disease sleep scale (PDSS), mean duration of PD was 2.1 years (1-10, up to 4 years in all except one patient with tremulous PD reporting tremor duration of 10 years) and mean Hoehn and Yahr score 1.9 (1-3). Data were compared to 34 advanced PD (mean age 70.2 years, range 51-88, 23 male), mean duration of PD 11 years (range 4-22), mean Hoehn and Yahr score 3.4 (3-5) and PDSS data obtained from 131 healthy controls (mean age 66.6 years, range 50-93, 56 males). Total PDSS scores and PDSS sub-items, except PDSS item 2, were highly significantly different (p<0.001) between DNPD, advanced PD and controls. Controls reported higher mean PDSS scores than both groups of patients, and advanced cases reported lower (mean+/-S.D.) PDSS scores (86.95+/-20.78) than drug-naive (105.72+/-21.5) (p<0.001). Logistic regression analysis showed that items PDSS8 (nocturia), PDSS11 (cramps), PDSS12 (dystonia), PDSS13 (tremor), and PDSS15 (daytime somnolence) were significantly impaired in DNPD compared to controls while PDSS7 (nighttime hallucinations) additionally separated advanced PD from DNPD. In a subgroup of 11 advanced PD cases (mean age 62 years, range=49-84 years, mean Hoehn and Yahr score 2.5, range=1-3) with high Epworth Sleepiness Scale (ESS) scores (mean 14.5), low item 15 PDSS score (mean 4.7) and complaints of severe daytime sleepiness, underwent detailed overnight polysomnography (PSG) studies, all showing abnormal sleep patterns. We conclude that nocturia, nighttime cramps, dystonia, tremor and daytime somnolence seem to be the important nocturnal disabilities in DNPD and some of these symptoms may be reminiscent of "off" period related symptoms even though patients are untreated. Furthermore, polysomnography in "sleepy" PD patients may help diagnose unrecognised conditions such as periodic limb movement of sleep (PLMS), obstructive sleep apnoea (OSA) and REM Sleep Behaviour Disorder.
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PMID:The range and nature of sleep dysfunction in untreated Parkinson's disease (PD). A comparative controlled clinical study using the Parkinson's disease sleep scale and selective polysomnography. 1678 Aug 88

Our paper discusses two experimental studies suggesting that Visual Hallucinations (VH) in Parkinson's Disease (PD) may have separate origins. The first is a prospective 8years study evaluating the appearance of VH, visual abnormalities assessed by Visual Evoked Potentials (VEPs) and REM sleep Behaviour Disorder (RBD), in 80 PD patients treated with l-Dopa and Dopaminoagonists (DA). In chronically treated, cognitively unimpaired, PD patients VH were statistically related (p=0.001) to RBD occurrence and high DA doses. Visual abnormalities were significantly reduced by l-Dopa or DA intake, and were statistically unrelated to VH. The second study involved PD patients placed in a Virtual Reality Environment, to decontextualize visual input. When motor symptoms worsened and VEP abnormalities developed patients consistently described hallucinatory dysperceptions of the virtual environment. The two studies therefore show that VH can occur in two seemingly distinct conditions, one is related to chronic treatment and to a sleep disorder frequently observed in PD, the other is probably related to a hypodopaminergic state. Our studies support a recently proposed integrative model of VH, and show that the neural circuits purported to explain VH must include the retinal dopaminergic system and the REM sleep regulatory system.
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PMID:Visual hallucinations in Parkinson's disease: clues to separate origins. 1680 69

Rapid eye movement sleep behavior disorder (RBD) occurs in approximately one third of patients with Parkinson's disease (PD) and is associated with a loss of muscle atonia during REM sleep and aggressive dream content. We examined the dream characteristics of PD patients to determine whether dream content differed between patients with RBD and without RBD, men and women with RBD, and men and women with PD. One hundred-twenty patients with a diagnosis of idiopathic PD were consecutively recruited from a movement disorders clinic and were assessed for RBD using clinical diagnostic criteria of the International Classification of Sleep Disorders Revised (2001). Verbatim dream content was obtained from each patient and categorized into dream themes that were coded into nominal categories. Fisher's exact tests determined whether particular dreams were correlated with RBD versus non-RBD, men and women with RBD, and men and women with PD. RBD patients had a higher percentage of violent dreams compared to non-RBD patients. There were no significant sex differences in the dream content of RBD patients. Men with PD had more aggressive dreams compared to females with PD. Aggressive dream content was characteristic of RBD patients and sex differences exist in the dream content of the PD population.
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PMID:Phenomenology of dreams in Parkinson's disease. 1713 61

The three different states of being (wakefulness, NREM and REM sleep) are associated with profound neurophysiological and neurochemical changes in the brain. These changes explain the existence of movement disorders appearing only or preferentially during sleep, and the effects of sleep on movement disorders. Sleep-related movement disorders are of clinical relevance for multiple reasons: 1) high frequency (e.g. restless legs syndrome (RLS)); 2) diagnostic relevance (e.g. REM sleep behavior disorder (RBD) as first manifestation of Parkinson disorder); 3) diagnostic uncertainty (e.g. parasomnias vs nocturnal epilepsy); 4) association with injuries (e.g. RBD, sleepwalking), sleep disruption/daytime sleepiness (e.g. RLS), and psycho-social burden (e.g. enuresis); 5) requirement of specific treatments (e.g. nocturnal epilepsy, stridor, RBD). This article gives an overview on clinical manifestations, pathophysiology, work-up and treatment of sleep-related movement disorders (e.g. RLS, bruxism), parasomnias (e.g. sleepwalking, RBD), sleep-related epilepsies, and on sleep-associated manifestations of movement disorders (e.g. Parkinson disease, multiple system atrophy).
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PMID:[Sleep and movement disorders]. 1722 27

Although normal subjects do not move during REM sleep, patients with Parkinson's disease may experience REM sleep behaviour disorder (RBD). The characteristics of the abnormal REM sleep movements in RBD have, however, not been studied. We interviewed one hundred consecutive non-demented patients with Parkinson's disease and their bed partners using a structured questionnaire assessing the presence of RBD. They rated the quality of movements, voice and facial expression during RBD as being better, equal or worse than in awake ON levodopa condition. Night-time sleep and movements were video-monitored during polysomnography in 51 patients to evaluate the presence of bradykinesia, tremor and hypophonia during REM sleep. Fifty-nine patients had clinical RBD with 53/59 bed partners able to evaluate them. All 53 (100%) reported an improvement of at least one component of motor control during RBD. By history, movements were improved in 87% patients (faster, 87%; stronger, 87%; smoother, 51%), speech was better in 77% patients (more intelligible, 77%; louder, 38%; better articulated, 57%) and facial expression was normalized in 47% patients. Thirty-eight per cent of bed partners reported that movements were 'much better', even in the most disabled patients. The video-monitored purposeful movements in REM sleep were also surprisingly fast, ample, coordinated and symmetrical, without obvious sign of parkinsonism. The movements were, however, jerky, violent and often repetitive. While all patients had asymmetrical parkinsonism when awake, most of the time they used the more disabled arm, hand and leg during the RBD (P = 0.04). Movements involved six times as often the upper limbs and the face as the lower limbs (OR: 5.9, P = 0.004). The percentage of time containing tremor EMG activity decreased with sleep stages from 34.9 +/- 15.5% during wakefulness, to 3.6 +/- 5.7% during non-REM sleep stages 1-2, 1.4 +/- 3.0% during non-REM sleep stages 3-4, and 0.06 +/- 0.2% during REM sleep (in this last case, it was subclinical tremor). The restored motor control during REM sleep suggests a transient 'levodopa-like' reestablishment of the basal ganglia loop. Alternatively, parkinsonism may disappear by REM sleep-related disjunction between pyramidal and extrapyramidal systems. We suggest the following model: the movements during the RBD would be generated by the motor cortex and would follow the pyramidal tract bypassing the extrapyramidal system. These movements would eventually be transmitted to lower motor neurons because of brainstem lesions interrupting the pontomedullary pathways which mediate the REM sleep atonia.
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PMID:Restoration of normal motor control in Parkinson's disease during REM sleep. 1723 26

Awareness of the clinical and pathophysiological importance of sleep disorders in Parkinson's disease (PD) has been growing in recent years. Sleep disorders are now regarded as important among non-motor symptoms in PD and as a significant variable of PD-related quality of life. Furthermore, some sleep disorders, namely REM behaviour disorder (RBD), has been hypothesised to herald PD by years. Subjective reports of disrupted nocturnal sleep and daytime sleepiness appear to be supported by descriptions of several sleep alterations at nocturnal polysomnographic investigation and Multiple Sleep Latency Test findings. Sleep alterations in PD are to be viewed from the multifactorial perspective of a framework of reciprocally interacting factors: pathophysiology of the disease itself, sleep-related motor symptoms, dopaminergic treatments, ageing, depression, restless legs, periodic limb movements (PMLs) and sleep-disordered breathing. Ad hoc questionnaires and scales such as the Parkinson's Disease Sleep Scale and the Short and Practical (SCOPA) Sleep Scale are now available for the evaluation of disordered sleep in PD patients and have been proved to be useful for preliminary screening of sleep disorders in PD. However in a few cases a video-polysomnography (V-PSG) is needed in order to confirm a diagnosis of sleep disorder in PD, particularly in diagnosing RBD. As for treatment of sleep disorders, combined pharmacological and non-pharmacological protocols appear to be particularly suitable in their treatment in PD.
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PMID:Sleep disorders in Parkinson's disease: facts and new perspectives. 1723 27

REM sleep behavior disorder (RBD) is a fascinating experiment in nature predicted by animal studies in 1964. A defining feature of REM sleep is active paralysis of all somatic musculature (sparing the diaphragm to permit respiration). RBD is characterized by the absence of REM atonia, permitting the appearance of dream-enacting behaviors. These oneiric behaviors may be violent or injurious. RBD typically affects men over the age of 50 years. Longitudinal follow-up has shown that the majority of individuals with RBD will eventually develop additional signs and symptoms of a number of neurodegenerative disorders, most notably one of the synucleinopathies (Parkinson's disease, dementia with Lewy body disease, multiple system atrophy, or pure autonomic failure), often after a prolonged interval lasting more than 10 years. RBD is also a common manifestation of narcolepsy. RBD may be induced by medications, especially the tricyclic antidepressants and serotonin-specific reuptake inhibitors. In most cases, clonazepam is a highly effective treatment.
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PMID:Pathophysiologic mechanisms in REM sleep behavior disorder. 1735 39

Insomnia, sleep fragmentation and excessive daytime sleepiness are common in Parkinson's disease (PD) and may contribute to the reduction of cognition and alertness in those patients. Melatonin has been shown to improve sleep in several conditions. In experimental models of PD, melatonin can ameliorate motor symptoms. To evaluate the effect of melatonin on sleep and motor dysfuntion in PD, we studied 18 patients (Hoehn & Yahr I to III) from a PD clinic. Prior to treatment, motor dysfunction was assessed by UPDRS II, III and IV. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence by the Epworth Sleepiness Scale (ESS). Full polysomnography (PSG) was performed in all subjects. Patients were then randomized to receive melatonin (3mg) or placebo one hour before bedtime for four weeks. All measures were repeated at the end of treatment. On initial assessment, 14 patients (70%) showed poor quality sleep (PSQI > 6) and eight (40%) excessive daytime sleepiness (ESS > 10). Increased sleep latency (50%), REM sleep without atonia (66%), and reduced sleep efficiency (72%) were found on PSG. Eight patients had an apnea/ hipopnea index greater than 15 but no severe oxygen desaturation was observed. Sleep fragmentation tended to be more severe in patients on lower doses of levodopa (p = 0.07). Although melatonin significantly improved subjective quality of sleep (p = 0.03) as evaluated by the PSQI index, PSG abnormalities were not changed. Motor dysfunction was not improved by the use of melatonin. Undetected differences in motor scores and PSG findings may have been due to a small sample size and a type II error.
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PMID:Effect of exogenous melatonin on sleep and motor dysfunction in Parkinson's disease. A randomized, double blind, placebo-controlled study. 1828 17

REM sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of normal skeletal muscle atonia during REM sleep with prominent motor activity accompanying dreaming. The terminology relating to RBD, and mechanisms underlying REM sleep without atonia and RBD based on data in cat and rat are presented. Neuroimaging data from the few published human cases with RBD associated with structural lesions in the brainstem are presented, in which the dorsal midbrain and pons are implicated. Pharmacological manipulations which alter RBD frequency and severity are reviewed, and the data from human neuropathological studies are presented. An anatomic framework and new schema for the pathophysiology of RBD are proposed based on recent data in rat regarding the putative flip-flop switch for REM sleep control. The structure in man analogous to the subcoeruleus region in cat and sublaterodorsal nucleus in rat is proposed as the nucleus (and its associated efferent and afferent pathways) crucial to RBD pathophysiology. The association of RBD with neurological disease ('secondary RBD') is presented, with emphasis on RBD associated with neurodegenerative disease, particularly the synucleinopathies. The hypothesized pathophysiology of RBD is presented in relation to the Braak staging system for Parkinson's disease, in which the topography and temporal sequence of synuclein pathology in the brain could explain the evolution of parkinsonism and/or dementia well after the onset of RBD. These data suggest that many patients with 'idiopathic' RBD are actually exhibiting an early clinical manifestation of an evolving neurodegenerative disorder. Such patients may be appropriate for future drug therapies that affect synuclein pathophysiology, in which the development of parkinsonism and/or dementia could be delayed or prevented. We suggest that additional clinicopathological studies be performed in patients with dementia or parkinsonism, with and without RBD, as well as in patients with idiopathic RBD, to further elucidate the pathophysiology and also characterize the clinical and pathophysiological relevance of RBD in neurodegenerative disease. Furthermore, longitudinal studies in patients with idiopathic RBD are warranted to characterize the natural history of such patients and prepare for future therapeutic trials.
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PMID:Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. 1741 31


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