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)

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

Neuroprotective therapy is a pivotal aim in the treatment of the relentlessly progressive disorder Parkinson's disease. However, more than 60% of the dopaminergic neurons of the substantia nigra have already degenerated, when the diagnosis may be established. At this "advanced stage" neuroprotective strategies will - if at all - only have limited effect. It is, therefore, essential to establish markers to identify subjects at risk before motor manifestation. A number of such "premotor" signs have been discovered and investigated lately. Such signs include a genetic vulnerability and hyperechogenicity of the substantia nigra as well as premotor symptoms like olfactory and autonomic dysfunction, depression, REM sleep behaviour disorder, visual and neuropsychological impairment. Moreover, first signs of affection of the substantia nigra like PET and SPECT abnormalities and slight motor signs can be included, as they may be detected before a definite diagnosis can be made. Although most of these signs and symptoms are unspecific if singularly evaluated a combination of these features may indeed be valuable to detect a subgroup of the population at risk for PD. However, future studies are necessary to establish the predictive value of these "markers" singularly and in combination.
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PMID:Marker for a preclinical diagnosis of Parkinson's disease as a basis for neuroprotection. 1744 23

It has recently been reported that Parkinson's disease (PD) is preceded and accompanied by daytime sleep attacks, nocturnal insomnia, REM sleep behaviour disorder, hallucinations and depression, symptoms which are frequently as troublesome as the motor symptoms of PD. All these symptoms are present in narcolepsy, which is linked to a selective loss of hypocretin (Hcrt) neurons. In this study, the Hcrt system was examined to determine if Hcrt cells are damaged in PD. The hypothalamus of 11 PD (mean age 79 +/- 4) and 5 normal (mean age 77 +/- 3) brains was examined. Sections were immunostained for Hcrt-1, melanin concentrating hormone (MCH) and alpha synuclein and glial fibrillary acidic protein (GFAP). The substantia nigra of 10 PD brains and 7 normal brains were used for a study of neuromelanin pigmented cell loss. The severity of PD was assessed using the Hoehn and Yahr scale and the level of neuropathology was assessed using the Braak staging criteria. Cell number, distribution and size were determined with stereologic techniques on a one in eight series. We found an increasing loss of hypocretin cells with disease progression. Similarly, there was an increased loss of MCH cells with disease severity. Hcrt and MCH cells were lost throughout the anterior to posterior extent of their hypothalamic distributions. The percentage loss of Hcrt cells was minimal in stage I (23%) and was maximal in stage V (62%). Similarly, the percentage loss of MCH cells was lowest in stage I (12%) and was highest in stage V (74%). There was a significant increase (P = 0.0006, t = 4.25, df = 15) in the size of neuromelanin containing cells in PD patients, but no difference in the size of surviving Hcrt (P = 0.18, t = 1.39, df = 14) and MCH (P = 0.28, t = 1.39, df = 14) cells relative to controls. In summary, we found that PD is characterized by a massive loss of Hcrt neurons. Thus, the loss of Hcrt cells may be a cause of the narcolepsy-like symptoms of PD and may be ameliorated by treatments aimed at reversing the Hcrt deficit. We also saw a substantial loss of hypothalamic MCH neurons. The losses of Hcrt and MCH neurons are significantly correlated with the clinical stage of PD, not disease duration, whereas the loss of neuromelanin cells is significantly correlated only with disease duration. The significant correlations that we found between the loss of Hcrt and MCH neurons and the clinical stage of PD, in contrast to the lack of a relationship of similar strength between loss of neuromelanin containing cells and the clinical symptoms of PD, suggests a previously unappreciated relationship between hypothalamic dysfunction and the time course of the overall clinical picture of PD.
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PMID:Hypocretin (orexin) cell loss in Parkinson's disease. 1789 5

Rapid eye movement sleep behavior disorder (RBD) has rarely been associated with a psychiatric condition. We report a series of cases of RBD presenting as psychiatric disorders. These patients were assessed at a specialist sleep disorders center and investigated using polysomnography and, where appropriate, magnetic resonance imaging of the brain and neuropsychological tests. These cases of RBD highlight the varying presentations and causes of RBD that may involve psychiatrists, sleep specialists, and primary care physicians. These include idiopathic RBD presenting as depression, antidepressant-induced RBD, and a patient with undiagnosed Parkinson disease presenting with RBD. There is an increasing body of knowledge about RBD. At least 10% of patients with RBD are likely to present with psychiatric symptoms. It is essential that the condition is recognised and distinguished from other causes of sleep interruption. After recognizing the disorder, it is essential that the clinician undertake a thorough assessment, including a sleep history and formal investigation of sleep patterns at a specialized unit.
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PMID:REM sleep behavior disorder--psychiatric presentations: a case series from the United Kingdom. 1756 15

About 90% of neurodegenerative diseases with parkinsonism are associated with sleep disorders including daytime sleepiness, sleep-related breathing disorders and parasomnias. It is hard to define what ratio of insomnia and daytime hypersomnia is caused by the antiparkinsonian treatment, by the somatic and mental-emotional symptoms of the neurodegenerative disease and by the neurodegenerative brain process itself. Recent research suggests that the latter group is more important than expected. In Parkinson syndromes the structures included in sleep regulation--mainly within the brainstem--are also affected resulting in specific sleep disorders being the primary biological symptoms of these diseases. The recently described parasomnia--REM sleep behavior disorder--has a specific significance in this respect: it may prevent by several years a high ratio of the parkinsonian disorders--especially synucleinopathies--offering the possibility of prevention by identifying the affected individuals. There seems to exist a similar although less clarified association between daytime sleepiness and Parkinson disease. Analysing the behavior of the orexin system in neurodegenerative diseases may help to learn more about this, recently described neurohumoral system and may clear the association of narcolepsy with neurodegeneration. By understanding the associations of parkinsonian disorders and sleep disorders new therapeutical strategies may be invented and may offer new aspects to understand the mechanism of them.
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PMID:[Sleep disorders in Parkinson syndromes]. 1757 69

There is growing evidence that a variety of symptoms can precede the classical motor features of Parkinson's disease (PD). The period when these symptoms arise can be referred to as the premotor phase of the disease. Well-documented premotor symptoms in PD include constipation, loss of smell, sleep disturbances such as REM sleep behavior disorder (RBD), and mood disturbances like depression. Diagnostic and therapeutic implications linked to improved identification of these premotor features are discussed.
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PMID:The premotor phase of Parkinson's disease. 1768 39

Blink reflexes (BR) to electric stimuli of the supraorbital nerve were recorded in 26 patients with dementia with Lewy bodies (DLB), 26 patients with multiple system atrophy, 26 patients with Parkinson's disease, with or without REM sleep behaviour disorder (RBD), and in 20 patients with Alzheimer's disease and 20 with progressive supranuclear palsy without RBD, and compared with recordings in 30 healthy controls. BR were significantly delayed (p<0.001) only in DLB patients in comparison with controls and with the other groups of patients; 14 (53.8%) patients had BR latency above 2 SD of the control mean, ranging from 36.1 to 46.3 ms. BR latency was not related to the presence of RBD, while a Spearman correlation rho of 0.68 was found for scores assessing the presence of cognitive fluctuations. R2 delay was prominently (71.5%) bilateral.
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PMID:Delayed blink reflex in dementia with Lewy bodies. 1787 93

Many patients with assumed idiopathic REM sleep behavior disorder (RBD) may actually represent an early clinical manifestation of an evolving neurodegenerative disorder, such as the alpha-synucleinopathies, Parkinson's disease or multiple system atrophy. Early detection of these patients is clinically relevant for long-term prospective as well as future neuroprotective studies. For this purpose, we validated a 10-item patient self-rating questionnaire (maximum total score 13 points) covering the clinical features of RBD. The RBD screening questionnaire (RBDSQ) was applied to 54 patients with polysomnographically confirmed RBD (29 men; mean age 53.7 +/- 15.8 years), 160 control subjects (81 men; mean age 50.8 +/- 15.5 years) in whom RBD was excluded by history and polysomnography (PSG, control group 1) and 133 unselected healthy subjects (58 men; mean age 46.9 +/- 12.3 years; no PSG, control group 2). In most subjects (n = 153) of control group 1, other sleep-wake disturbances were present. The mean RBDSQ score in the RBD group was 9.5 +/- 2.8 points compared with 4.6 +/- 3.0 points in control group 1 (P < 0.0001). Considering an RBDSQ score of five points as a positive test result, we found a sensitivity of 0.96 and a specificity of 0.56. The RBDSQ poorly discriminated patients with the most challenging differential diagnoses such as sleepwalking or epilepsy. In control group 2, the mean RBDSQ score (2.02 +/- 1.78) was significantly lower than in the RBD group (P < 0.0005), revealing a specificity of 0.92. Due to its high sensitivity, the RBDSQ appears to be particularly useful as a screening tool.
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PMID:The REM sleep behavior disorder screening questionnaire--a new diagnostic instrument. 1789 37

Sleep disturbances are one of the most common of the nonmotor complications of Parkinson's disease (PD), and increase in frequency with advancing disease. The causes of sleep disturbance in PD are numerous, and many patients may have several factors that contribute. These disorders can be broadly categorized into those that involve nocturnal sleep and daytime manifestations such as excessive daytime sleepiness. Some sleep disorders, in particular REM sleep behavior disorder (RBD) and excessive daytime sleepiness (EDS) may arise as a primary manifestation of PD, reflecting the anatomic areas affected by the neurodegenerative process. Appropriate diagnosis of the sleep disturbance affecting a PD patient can lead to specific treatments that can consolidate nocturnal sleep and enhance daytime alertness.
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PMID:Sleep disorders in Parkinson's disease: an overview. 1817 98

EEG abnormalities have been reported for both dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Although it has been suggested that variations in mean EEG frequency are greater in the former, the existence of meaningful differences remains controversial. No evidence is as yet available for Parkinson's disease with dementia (PDD). The aim of this study was to evaluate whether EEG abnormalities can discriminate between DLB, AD and PDD in the earliest stages of dementia and to do this 50 DLB, 50 AD and 40 PDD patients with slight cognitive impairment at first visit (MMSE > or = 20) were studied. To improve clinical diagnostic accuracy, special emphasis was placed on identifying cognitive fluctuations and REM-sleep behaviour disorder. EEG variability was assessed by mean frequency analysis and compressed spectral arrays (CSA) in order to detect changes over time from different scalp derivations. Patients' initial diagnoses were revised at a 2-year follow-up visit with neuroimaging evaluation. Initial diagnoses were confirmed in 36 DLB, 40 AD and 35 PDD patients. The most relevant group differences were observed between the AD and DLB patients in EEGs from posterior derivations (P<0.001). Dominant frequencies were 8.3 +/- 0.6 Hz for the AD group and 7.4 +/- 1.6 Hz for the DLB group, in which most of the patients (88%) exhibited a frequency band of 5.6-7.9 Hz. Dominant frequency variability also differed between the AD (1.1 +/- 0.4 Hz) and DLB groups (1.8 +/- 1.2 Hz, P<0.001). Of note, less than a half (46%) of the patients with PDD exhibited the EEG abnormalities seen in those with DLB. Graded according to the presence of alpha activity, five different patterns were identified on EEG CSA from posterior derivations. A pattern with dominant alpha bands was observed in patients with AD alone while, in those with DLB and PDD, the degree to which residual alpha and 5.6-7.9 bands appeared was related to the presence and severity of cognitive fluctuations. At follow-up, EEG abnormalities from posterior leads were seen in all subjects with DLB and in three-quarters of those with PDD. Of interest, in four patients initially labelled as having AD, in whom the occurrence of fluctuations and/or REM-sleep behaviour disorder during the 2-year follow-up had made the diagnosis of AD questionable, the initial EEG was characterized by the features observed in the DLB group. If revised consensus criteria for DLB diagnosis are properly applied (i.e. emphasizing the diagnostic weight of fluctuations and REM sleep behaviour disorder), EEG recording may act to support discrimination between AD and DLB at the earliest stages of dementia, since characteristic abnormalities may even precede the appearance of distinctive clinical features.
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PMID:EEG comparisons in early Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease with dementia patients with a 2-year follow-up. 1820 5


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