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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While optimal treatment strategies are widely established for daytime treatment of Parkinson's disease (PD), nighttime problems of PD are often not adequately addressed in clinical practice. Nocturnal/sleep disturbance is common in PD and occurs due to a combination of the disease process and effect of dopaminergic and other treatments. The role of dopamine and other neuropeptides such as hypocretin is being investigated in the causation of sleep problems in PD. The impact of sleep dysfunction in PD on daytime fatigue and sleepiness is also being explored as such issues have important implications. The recently described Parkinson's disease sleep scale aims to measure the causes of sleep dysfunction in PD in a semi-quantitative manner and using this scale we have shown that sustained dopaminergic stimulation initiated at bedtime may help with improving motor symptoms at night and secondarily improve sleep and daytime functioning in PD.
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PMID:The basis for day and night-time control of symptoms of Parkinson's disease. 1246 20

The origins of excessive daytime sleepiness in Parkinson disease (PD) are unclear. The authors hypothesize that orexin neurons, a recently identified wake promoting system, could contribute to its pathophysiology. They measured orexin-A/hypocretin-1 concentration in ventricular CSF in 19 parkinsonian patients and compared it with neurologic controls. Orexin levels were lower in patients and decreased with the severity of the disease. The authors suggest that orexin neurons contribute to daytime sleepiness in late stage PD.
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PMID:Low levels of ventricular CSF orexin/hypocretin in advanced PD. 1472 34

Narcolepsy is a chronic neurologic disease characterized by excessive daytime sleepiness and one or more of three additional symptoms (cataplexy, or sudden loss of muscle tone; vivid hallucinations; and brief periods of total paralysis) related to the occurrence of rapid eye movement (REM) sleep at inappropriate times. The daytime sleepiness typically presents as a sudden overwhelming urge to sleep, followed by periods of sleep that last for seconds or minutes, or even longer. During daytime sleep episodes, patients may exhibit "automatic behavior," performing conventionalized functions (eg, taking notes), but not remembering having done so once they are awake. About 10% of narcoleptics are members of familial clusters; however, genetic factors alone are apparently insufficient to cause the disease, inasmuch as the most common genetic disorder, a mutation in chromosome 6 controlling the HLA antigen immune complex, although seen in 90% to 100% of patients, also occurs in as many as 50% of people without narcolepsy. A dog model of narcolepsy exhibits a mutation on chromosome 12 that disrupts the processing of the peptide neurotransmitter hypocretin. No such mutation characterizes human narcolepsy; however, cerebrospinal fluid (CSF) hypocretin levels are profoundly depressed in narcoleptic patients, and a specific reduction in hypocretin-containing neurons has been described. One hypothesis concerning the pathophysiology of narcolepsy proposes that the HLA subtype resulting from the mutation on chromosome 6 increases the susceptibility of hypocretin-containing brain neurons to immune attack. Because hypocretin may normally participate in the maintenance of wakefulness, the loss of neurons that release this peptide might allow REM sleep to occur at inappropriate times, ie, while the patient is awake, in contrast to its normal cyclic appearance after a period of slow-wave sleep. The cataplexy, hallucinations, and/or paralysis associated with REM episodes normally are unnoticed-or, at least, not remembered-when the transition to REM follows slow wave sleep, as is normally the case; however, they are remembered when, in people with narcolepsy, the REM episode starts during a period of wakefulness. The association of narcolepsy with a deficiency in a specific neurotransmitter, in this case, hypocretin, is reminiscent of the associations between Parkinson disease and dopamine, or early Alzheimer disease and acetylcholine.
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PMID:Narcolepsy and the hypocretins. 1697 25

Excessive daytime sleepiness has been widely accepted as a common problem not only in Parkinson's disease (PD) but also in other related disorders. Lowered excretion of orexin A (hypocretin 1) into the cerebrospinal fluid (CSF) is known to play a pathological role in narcolepsy and secondary hypersomnia due to hypothalamic dysfunction. Although the levels of CSF orexin in PD have been previously examined, the results have been controversial, and no systematic investigation of CSF orexin excretion has been conducted on PD related disorders. In this study, orexin was measured in CSF collected by lumbar puncture in 62 patients with PD, 13 patients with dementia with Lewy bodies (DLB), 16 patients with progressive supranuclear palsy (PSP), and 7 patients with corticobasal degeneration (CBD). Levels of CSF orexin (mean+/-SD pg/ml) were 302+/-38 in PD, 297+/-48 in DLB, 258+/-37 in PSP, 246+/-90 in CBD. The occurrence of low orexin levels (<or=110pg/ml) was rare in both PD and DLB, and orexin levels were significantly lower in the PSP and CBD groups compared to PD (PSP: p<0.001, CBD: p<0.05). Orexin levels were inversely correlated with duration of morbidity in PSP but not in the other conditions studied. These findings suggest that loss of orexin neurons or impaired orexin neurotransmission might exist as a part of the neurodegeneration associated with advanced PSP with long duration of morbidity.
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PMID:CSF orexin levels of Parkinson's disease, dementia with Lewy bodies, progressive supranuclear palsy and corticobasal degeneration. 1700 2

Much has been learned about the pathophysiology of narcolepsy over the last several decades. It is likely that hypocretin-producing cells in the lateral hypothalamus are selectively destroyed in genetically susceptible individuals carrying 1 or more alleles of HLA DQB1*0602. Despite advances, the causes of narcolepsy and how to prevent it remain elusive. Classic epidemiology aims not only to enumerate occurrence of disease in populations, but also to identify etiologic risk factors. This review details what the application of classic epidemiology has taught us so far about narcolepsy and suggests directions for future studies to clarify its etiology. The prevalence of narcolepsy with cataplexy has been examined in many studies and falls between 25 and 50 per 100,000 people. Information on incidence is limited, with 1 study finding the incidence of narcolepsy with cataplexy to be 0.74 per 100,000 person-years. The search for etiologic risk factors has yet to yield important associations. Factors most thoroughly examined include body mass index, immune responses, and stressful life events. Such associations may reflect a consequence rather than a cause of disease. As with other diseases characterized by selective cell loss, such as Parkinson disease or type 1 diabetes mellitus, narcolepsy is likely caused by environmental exposures before the age of onset in genetically susceptible individuals. Matching efforts in these other diseases and using large well-designed epidemiologic studies of narcolepsy, investigators must intensify the search for these exposures, focusing on the first 2 decades of life. Identification of modifiable risk factors will help to prevent this disease.
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PMID:The epidemiology of narcolepsy. 1731 Aug 60

The hypothalamic hypocretin (orexin) system plays a central role in the regulation of various functions, including sleep/wake regulation and metabolism. There is a growing interest in hypocretin function in Parkinson's disease (PD), given the high prevalence of non-motor symptoms such as sleep disturbances in this disorder. However, studies measuring CSF hypocretin levels have yielded contradictory results. In PD patients and matched controls, we (i) estimated the number of hypocretin neurons in post-mortem hypothalami using immunocytochemistry and an image analysis system (ii) quantified hypocretin levels in post-mortem ventricular CSF and (iii) prefrontal cortex using a radioimmunoassay. Furthermore, presence of Lewy bodies was verified in the hypothalamic hypocretin cell area. Data are presented as median (25th-75th percentile). We showed a significant decrease between PD patients and controls in (i) the number of hypocretin neurons (PD: 20 276 (13 821-31 229); controls: 36 842 (32 546-50 938); P = 0.016); (ii) the hypocretin-1 concentration in post-mortem ventricular CSF (PD: 365.5 pg/ml (328.0-448.3); controls: 483.5 (433.5-512.3); P = 0.012) and (iii) the hypocretin-1 concentrations in prefrontal cortex (PD: 389.6 pg/g (249.2-652.2); controls: 676.6 (467.5-883.9); P = 0.043). Hypocretin neurotransmission is affected in PD. The hypocretin-1 concentration in the prefrontal cortex was almost 40% lower in PD patients, while ventricular CSF levels were almost 25% reduced. The total number of hypocretin neurons was almost half compared to controls.
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PMID:Hypocretin (orexin) loss in Parkinson's disease. 1789 5

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

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

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

The symptoms of restless legs syndrome (RLS) have a circadian pattern and central nervous system dopamine has been implicated in the pathogenesis of the condition. We sought to characterize circadian variation in dopamine and related compounds in human cerebro-spinal fluid (CSF). CSF was continuously withdrawn for 22 h from an implanted lumbar intradural catheter and sampled from three patients with RLS, three patients with Parkinson's disease (PD) and three healthy volunteers. Patients had moderate disease severity and took no medications. We assayed CSF dopamine (DA), homovanillic acid (HVA), dihydroxy-phenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5-HIAA) from samples every 30 min by reversed-phase HPLC coupled with electrochemical detection. We also measured CSF levels of hypocretin-1 every hour by RIA. The procedure was well-tolerated. One patient ended the study early due to lumbar radicular pain and was not included in the analysis. There were no changes in CSF cell counts or protein levels from the first to the last samples. There was no difference in any of the compounds between groups, so we fit 24-h cosines to examine if the entire group had significant phase consistency. There was a peak for dopamine at 10 a.m. (p<0.025) and for HVA at 2 p.m. (p<0.01), but no evidence of a significant 24-h rhythm for DOPAC, 5-HIAA, the HVA/5-HIAA ratio, or hypocretin-1. These results demonstrate a circadian rhythm for CSF dopamine and HVA concentrations in humans, with higher levels in the daytime than at nighttime. This circadian variation could underlie the symptoms of RLS and sleep-related variation in motor function in PD.
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PMID:Circadian rhythm of CSF monoamines and hypocretin-1 in restless legs syndrome and Parkinson's disease. 1901 1


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