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 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

In the aging population of many countries in the world, neurodegenerative diseases like Parkinson's disease (PD) are becoming an increasing burden. Therefore, early therapy and ultimately disease prevention is essential, which is only possible with an early diagnosis. Besides a genetic predisposition, a number of biomarkers are being discussed to indicate vulnerability to PD, some of them many years before disease manifestation. These include hyperechogenicity of the substantia nigra as well as premotor symptoms like olfactory and autonomic dysfunction, depression, REM sleep behavior disorder, 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 according to motor symptoms can be made. Interestingly, other frequent neurodegenerative disorders like Alzheimer's disease (AD) are also characterized by a long preclinical period, with several biomarkers discussed as indicative for disease vulnerability including cerebrospinal fluid, serum, and neuroimaging biomarkers, olfactory dysfunction as well as subtle neuropsychological deficits. However, future studies are necessary, which establish the predictive value of these markers singularly and in combination to detect a subgroup of the population at risk for PD and AD not only to accelerate research on etiology and pathophysiology but also to promote testing for neuroprotective strategies.
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PMID:Biomarkers for the early detection of Parkinson's and Alzheimer's disease. 1832 70

REM sleep behavior disorder (RBD) is commonly associated with Parkinson disease (PD), but it is unclear whether this association has implications for disease manifestations. We evaluated 36 PD patients for the presence of RBD by polysomnography. Patients underwent an extensive evaluation by a movement disorders specialist blinded to polysomnography results. Severity of motor manifestations, autonomic, visual, psychiatric, and olfactory dysfunctions and quality of life (QOL) were assessed, and compared using regression analysis that adjusted for disease duration, age and sex. Severity of motor manifestations did not differ between groups. However, the presence of RBD in PD was strongly associated with symptoms and signs of orthostatic hypotension (systolic blood pressure lying to standing = -25.7 +/- 13.0 mmHg vs. -4.9 +/-14.1, P < 0.001); and orthostatic symptom prevalence = 71% vs. 27%, P = 0.0076). There was no association between RBD and other autonomic symptoms. Color vision was worse in patients with RBD, but olfactory dysfunction did not differ between groups. The prevalence of depression, hallucinations, paranoia, and impulse disorders did not differ between groups. Emotional functioning and general health QOL measures were lower in those with RBD, but there were no differences between groups on disease-specific indices or on measures of overall physical QOL. These findings suggest that the pathophysiology of RBD and nonmotor manifestations of PD, particularly autonomic dysfunction, are linked.
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PMID:Manifestations of Parkinson disease differ in association with REM sleep behavior disorder. 1870 86

Idiopathic REM sleep behavior disorder (RBD) predicts Parkinson's disease (PD) and dementia. However, the nature of the disease that emerges from RBD has not been fully characterized. Since 2004, we have been conducting a prospective study of idiopathic RBD patients, providing an opportunity to directly observe patients as they transitioned to a defined neurodegenerative syndrome. Patients with idiopathic RBD underwent an extensive annual evaluation of motor function, olfaction, color vision, autonomic function, cognition and psychiatric symptoms. Neurodegenerative disease was defined according to standard criteria. We compared these measures in patients who had developed PD to those with dementia, all within the first year of developing disease. Of 67 patients, 6 developed PD and eleven developed dementia. Except for cognitive functioning, all tests of olfaction, color vision, autonomic function, depression, and quantitative measures of motor speed were similar in patients with PD and dementia. Of dementia patients, seven met criteria for probable Lewy body dementia (LBD) and four for Alzheimer's disease (or, possible LBD). In all probable LBD cases, the diagnosis was made because of parkinsonism, with no patient experiencing hallucinations or fluctuations. Patients with "Alzheimer's disease" seemed to have LBD, as they demonstrated typical LBD cognitive profiles on neuropsychological testing and were indistinguishable from LBD patients in ancillary measures. Therefore, among RBD patients with new-onset LBD, hallucinations or fluctuations are absent, suggesting that RBD is a reliable early sign of LBD. The indistinguishability of dementia and PD in all ancillary measures suggests a single unitary "RBD-then-neurodegeneration" process, the clinical presentation of which depends upon selective neuronal vulnerability.
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PMID:Idiopathic REM sleep behavior disorder in the transition to degenerative disease. 1976 14

Parkinson's disease is the second most common neurodegenerative disorder, after Alzheimer's disease. It predominantly affects the elderly. Age is the most clearly established risk factor and there is a male:female ratio of 1.5:1. Current incidence in the general population is 8.4-19 per 100,000 population per year with an approximate prevalence of 120 per 100,000 population. NICE recommends that patients with suspected Parkinson's disease should be referred untreated to a specialist with expertise in parkinsonian disorders. The diagnosis is primarily clinical. Parkinson's disease should be suspected in all patients presenting with bradykinesia (which is essential for the diagnosis of any form of parkinsonism, including Parkinson's disease), muscular rigidity, resting tremor (4-6 Hz) and postural instability not caused by a primary visual, vestibular, cerebellar, or proprioceptive dysfunction. At present, there are no specific biochemical, imaging or genetic tests to assist in the diagnosis of Parkinson's disease. Structural brain imaging (MRI or CT) has no role in the diagnosis of Parkinson's disease but may be useful to exclude cerebrovascular disease, hydrocephalus and Wilson's disease in selected cases. Parkinson's disease is a condition that results in both motor and non-motor symptoms. Morbidity associated with non-motor symptoms in Parkinson's disease is becoming increasingly recognised and some non-motor symptoms such as hyposmia, apathy, depression and REM sleep behaviour disorder may precede the onset of motor symptoms.
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PMID:Non-motor symptoms may herald Parkinson's disease. 1987 55

Parkinson's disease (PD) is the second most common neurodegenerative disease and primarily considered as a movement disorder defined by the presence of motor symptoms, such as bradykinesia, tremor and rigidity. However, it is nowadays widely recognized that in addition there is impairment of cognitive function, mood and the autonomic nervous system in a high percentage of PD patients, which is sometimes even more harming quality of life. These symptoms not only occur during the course of the disease but may even precede the onset of motor symptoms. Typical examples of non-motor features of PD are depression, constipation, REM sleep behaviour disorder, and hyposmia.
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PMID:Non-motor features of Parkinson's disease: depression and dementia. 2008 17

So far, the diagnosis of an idiopathic Parkinson-syndrome was based on the British Brain Bank Criteria, that is the occurrence of bradykinesia together with at least one more of the cardinal symptoms, i. e. resting tremor, rigidity or postural instability. The latter symptom is not useful, since it occurs only in the Hoehn and Yahr stage III which is seen in advanced PD patients. Thus, this symptom is certainly not useful for EARLY diagnosis. Early signs for PD are hyposmia, constipation, REM sleep behaviour disorder and depression. Early diagnosis is still a clinical one, which can be supported by a levodopa test. It can be expected that in the near future gene chips will be available for patients with a positive family history for PD or with an early onset. As long as a blood test for PD is not available, methods such as SPECT and PET are extremely useful in patients with an unclear clinical symptomatology. In my own view, each PD patient should receive once in his career a cranial CT or MRI.
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PMID:[Future standards in diagnosing Parkinson syndrome]. 2019 42


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