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)

Hypocretin (orexin) cerebrospinal fluid (CSF) levels have been previously found normal or decreased in Dementia with Lewy bodies and Parkinson disease, two synucleinopathies commonly associated with excessive daytime sleepiness (EDS). We evaluated CSF hypocretin-1 levels in 15 patients with moderately severe multiple system atrophy (MSA), another synucleinopathy where sleep disorders occur frequently and EDS has been reported, performing additional electrophysiological studies in 5 of them to assess the presence of EDS and sleep onset REM (SOREM) periods. Despite relatively low sleep efficiencies in nocturnal sleep, mean sleep latencies in the Multiple Sleep Latency Test were normal with no SOREM periods. All patients had CSF hypocretin-1 levels in the normal range (>200 pg/mL) suggesting that the hypocretin system is not altered in MSA, at least in patients with a moderately severe disease.
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PMID:Cerebrospinal fluid hypocretin-1 levels in multiple system atrophy. 1765 46

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

In Parkinson's disease (PD) the presence of REM parasonnias as REM Behaviour Disorder (RBD) or vivid dreams/nightmares, is recognized as largely associated with hallucinations, even if the risk of the development of hallucinations seem not to depend on how long the REM parasomnias had been occurring. The aim of this study was to establish if RBDs occurring earlier than hallucinations in PD are predictive of cognitive impairment development. Three groups of PD patients: i) group 1, without RBD and without hallucinations; ii) group 2, with RBD but without hallucinations; iii) group 3, with RBD and hallucinations have been prospectively investigated at baseline and after two years throughout a clinical and neuropsychological evaluation. After two years, the group 1 continued to present normal neuropsychological tests and did not present either RBDs or hallucinations. In the group 2, the frontal impairment evidenced at baseline was confirmed; the onset of newly hallucinations was reported in a subgroup of 12 patients, who proved to be older, with a more severe executive impairment at baseline and with a more severe motor symptoms progression than those RBD patients who had not manifested hallucinations. The group 3, characterized at baseline by a more severe cognitive impairment presented, after two years, a cognitive worsening and a higher mortality rate. The longitudinal but at preliminary step investigation identified a PD subgroup of patients, in whom a common background disease profile, including the presence of RBD, could represent a "red flag" in developing further cognitive impairment.
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PMID:REM behavior disorder, hallucinations and cognitive impairment in Parkinson's disease: a two-year follow up. 1851 49

The pathogenesis of sleep attacks in Parkinson's disease (PD) is still unresolved. We investigated seven matched pairs of PD patients with and without a history of sleep attacks using continuous sleep EEG recording. According to the event marker altogether 12 sleep attacks were identified in three patients with a history of sleep attacks. All sleep attacks were characterized by NREM stage 1 and 2 sleep, whereas no sleep onset REM episodes were recorded. Five sleep attacks fulfilled our criteria for microsleep episodes lasting less than 120 s. The cumulative duration of microsleep episodes during the day was 27.7+/-20 min in patients with a history of sleep attacks vs. 6.4+/-4.1 min in patients without a history of sleep attacks (p=0.03), i.e., the majority of microsleep episodes were not perceived by the patients. In summary, our study suggests that sleep attacks are intrusions of NREM stage 1 and 2 sleep into wakefulness and can be identical to microsleep episodes. Future studies should systematically address the awareness of short sleep episodes in patients with PD and other disorders with increased daytime sleepiness.
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PMID:Continuous sleep EEG monitoring in PD patients with and without sleep attacks. 1861 93

The neuropathology of human sleep remains an ill-defined issue. The data concerning the main structures of human brain areas involved, or supposed to be implicated, in sleep organisation are reviewed. Five levels of organisation can be schematically recognized: (i) the ascending arousal system, (ii) the non REM and REM systems (iii) regulated by hypothalamic areas, (iv) and the biological clock, (v) modulated by a number of "allostatic" influences. These are briefly described, with emphasis on the location of structures involved in humans, and on the recently revised concepts. Current knowledge on the topography of lesions associated with the main sleep disorders in degenerative diseases is recalled, including REM sleep behavior disorders, restless legs syndrome and periodic leg movements, sleep apneas, insomnia, excessive daily sleepiness, secondary narcolepsy and disturbed sleep-wake rhythms. The lesions of sleep related structures observed in early and late stages of four degenerative diseases are then reviewed. Two synucleinopathies (Lewy lesions associated disorders, including Parkinson's disease and Dementia with Lewy bodies, and Multiple System Atrophy) and two tauopathies (Progressive Supranuclear Palsy and Alzheimer's disease) are dealt with. The distribution of lesions usually found in affected patients fit with that expected from the prevalence of different sleep disorders in these diseases. This confirms the current opinion that these disorders depend on the distribution of lesions rather than on their biochemical nature. Further studies might throw insight on the mechanism of normal and pathological sleep in humans, counterpart of the increasing knowledge provided by animal models. Specially designed prospective clinicopathological studies including peculiar attention to sleep are urgently needed.
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PMID:[The neuropathology of sleep in human neurodegenerative diseases]. 1876 Apr 29

REM sleep behavior disorders (RBD) are vigorous, complex movements corresponding to enacted dreams. They may disturb sleep, and injure the patients or their bed partner. RBD are frequently associated with neurodegenerative diseases, especially synucleopathies. They can precede parkinsonism or dementia by five to 10 years. These presymptomatic RBDs are frequently associated with EEG slowing, reduced olfaction, mild visuospatial cognitive impairment, and decreased dopamine transport in functional brain imaging. In Parkinson's disease, 15 to 60% patients speak, laugh, shout, kick, punch or fight invisible enemies during REM sleep. In contrast to sleepwalkers, patients with RBD rarely stand up or walk, but can fall out of bed. Sleep monitoring indicates an imperfect abolition of muscle tone during REM sleep in these patients. RBD are probably caused by nondopaminergic pontine lesions in the REM sleep atonia system. This condition may also expose patients with Parkinson's disease to a higher risk of daytime and nighttime hallucinations, and to more frequent cognitive impairment. Interestingly, several spouses reported that they observed a sharp contrast between the slow, limited movements, and poorly intelligible, low voice of their affected spouse when awake, and the fast, vigorous movements with loud voice that the very same patient exhibited during enacted dreams. We recently demonstrated that parkinsonism indeed disappears during RBD, in a large study combining the interview of 100 couples and the sleep and video monitoring of 50 patients. The mechanism of this improvement is now being explored.
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PMID:[REM sleep behavior disorders and their characteristics in Parkinson's disease]. 1880 2

Pathology and imaging studies have shown that patients with Parkinson disease (PD) have a prolonged period of uncertain duration when vulnerable neuronal populations are degenerating, but typical motor symptoms have not yet developed. This provides both an opportunity-it may be best to test new medications and, ultimately, treat PD patients during this early phase of disease--and a challenge--how to find these premotor PD subjects? Imaging biomarkers targeting the premotor period are critical to elucidate both the onset and progression of premotor PD. Widespread data have demonstrated that dopaminergic imaging can detect PD subjects at the motor symptom threshold. Novel strategies combining dopaminergic imaging with known genetic mutations for PD or early clinical signs and PD-associated symptoms, such as olfactory loss and sleep disturbances like REM behavior disorder, have begun to be used to identify individuals at risk for PD before motor symptoms become manifest. Early studies also have used imaging targeting norepinephrine, serotonin, cholinergic, or other neuronal systems to focus on early cardiac, cognitive, and behavioral symptoms. Imaging of nondopaminergic targets such as inflammation or alpha-synuclein deposition may provide further insight into the etiology of PD. Given the multiple genetic etiologies for PD already identified, the marked variability in the loss of dopaminergic markers measured by imaging at motor symptom onset, and the clear heterogeneity of clinical symptoms at PD onset, it is certain that many imaging biomarkers with a focus ranging from clinical symptoms to PD pathobiology to molecular genetic mechanisms, will be necessary to fully map PD risk.
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PMID:Can we image premotor Parkinson disease? 1922 10

The motor symptoms of Parkinson's disease (PD), bradykinesia, muscular rigidity, and tremor depend upon degeneration of the dopaminergic neurons in the substantia nigra pars compacta. Recent neuropathological studies show that the Lewy bodies, the intraneuronal landmark of PD, accumulate in several neuronal cell types in the brain. An ascending gradient of pathological involvement, from the medulla oblongata to neocortical areas has been reported. Thus the original view of PD as a disease characterized by selective damage of the dopaminergic neurons in the mesencephalon should be updated into the concept of a severe multisystemic neurodegenerative disorder. Additionally, the neuropathological alterations outside the substantia nigra are soundly correlated with the non-motor symptoms of PD. As a result of these findings, interest is growing in the identification of prodromal non-motor symptoms of PD. Indeed, data from the literature suggest that autonomic disturbances, olfactory dysfunctions, depression and sleep disorders (in particular REM-sleep behavior disorder) may represent prodromal non-motor symptoms of PD. Several tests are available to detect most of these symptoms. Thus, the identification of prodromal non-motor symptoms may contribute to the precocious diagnosis of PD, and might be useful in the future to test the efficacy of neuroprotective agents.
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PMID:Prodromal non-motor symptoms of Parkinson's disease. 1930 May 44

REM sleep behavior disorder (RBD) is characterized by vigorous movements associated with unpleasant dreams and increased electromyographic activity during REM sleep. Polysomnography with audiovisual recording is needed to confirm the diagnosis of RBD and to exclude other sleep disorders that can mimic its symptoms including obstructive sleep apnea, nocturnal hallucinations and confusional awakenings. RBD may be idiopathic or related to neurodegenerative diseases, particularly multiple system atrophy, Parkinson's disease and dementia with Lewy bodies. RBD may be the first manifestation of these disorders, antedating the onset of parkinsonism, cerebellar syndrome, dysautonomia, and dementia by several years. RBD should thus be considered an integral part of the disease process. When effective, neuroprotective strategies should be considered in subjects with idiopathic RBD. Patients with other neurodegenerative diseases, though, such as spinocerebellar ataxias, may also present with RBD. When clinically required, clonazepam at bedtime is effective in decreasing the intensity of dream-enacting behaviors and unpleasant dreams in both the idiopathic and secondary forms. When part of a neurodegenerative disorder the development of RBD is thought to reflect the location and extent of the underlying lesions involving the REM sleep centers of the brain (e.g., locus subceruleus, amygdala, etc.), leading to a complex multiple neurotransmitter dysfunction that involves GABAergic, glutamatergic and monoaminergic systems. RBD is mediated neither by direct abnormal alpha-synuclein inclusions nor by striatonigral dopaminergic deficiency alone.
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PMID:The clinical and pathophysiological relevance of REM sleep behavior disorder in neurodegenerative diseases. 1939 52

To replicate the sleep-wake disorders of Parkinson's disease (PD) and to understand the temporal relationship between these sleep disturbances and the occurrence of parkinsonism, we performed long-term continuous electroencephalographic monitoring of vigilance states in unrestrained rhesus monkeys using an implanted miniaturized telemetry device and tested the effect of MPTP intoxication on their sleep-wake organization. MPTP injection yielded a dramatic disruption of sleep-wake architecture with reduced sleep efficacy that persisted years after MPTP administration. Primary deregulation of REM sleep and increased daytime sleepiness occurring before the emergence of motor symptoms were a striking feature of the MPTP effect. This was concomitant with a breakdown of dopaminergic homeostasis, as evidenced by decreased dopamine turnover measured after a single MPTP injection. In the long term, partial re-emergence of REM sleep paralleled the partial adaptation to parkinsonism, the latter being known to result from compensatory mechanisms within the dopaminergic system. Altogether, these findings highlight the suitability of the MPTP model of PD as a tool to model the sleep/wake disturbances of the human disease. Ultimately, this may help in deciphering the specific role of dopamine depletion in the occurrence of these disorders.
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PMID:Sleep disorders in Parkinson's disease: the contribution of the MPTP non-human primate model. 2006 10


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