Features associated with the development of hallucinations in Parkinson's disease
ABSTRACT To identify features related to the development of hallucinations in Parkinson's disease (PD).
Seventy PD patients with hallucinations (group 1) and 60 PD patients without hallucinations (group 2) were evaluated for disease severity, presence of motor complications, rapid eye movement (REM) behavior disorder (RBD), and antiparkinsonian drug profile. The ages at the emergence of hallucinations and duration of disease in group 1 were matched with the ages at the last visit of those in group 2.
Disease severity and presence of motor complications were similar in both groups. RBD was more frequently encountered among hallucinators than among non-hallucinators (P = 0.007). The mean duration and daily doses of levodopa and other dopaminergic drugs did not differ in both groups; however, the usage of anticholinergics and amantadine were significantly more frequent in group 2, unexpectedly.
The presence of RBD was significantly more common in hallucinators; however, severity of PD, duration and daily doses of dopaminergic drugs were not associated with the emergence of hallucinations.
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ABSTRACT: 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.Brain 07/2007; 130(Pt 6):1577-85. DOI:10.1093/brain/awm090 · 9.20 Impact Factor
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ABSTRACT: 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.Brain 07/2007; 130(Pt 6):1586-95. DOI:10.1093/brain/awm097 · 9.20 Impact Factor
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ABSTRACT: In order to explore factors associated with the development of dementia in Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), we systematically investigated the clinical evaluation of PD and DLB patients hospitalized in the Department of Neurology at Tottori University Hospital, Japan. There were 208 patients diagnosed as having PD and 39 patients diagnosed with DLB in this study. Of the patients with PD, 67 (32%) developed dementia and only five PD+ patients were considered to have cognitive impairment attributable to Alzheimer's disease (AD) or vascular dementia (VaD). Fifty-four (81%) PDD patients had visual hallucinations (VH) with or without cognitive fluctuation. The onset age of parkinsonian motor symptoms of patients with PD dementia (PDD) did not differ from that of PD patients without dementia. There was a significant inverse correlation between the onset age of motor symptoms in PD and the onset of their dementia in PDD. Seventy-five (36%) patients with PD had experienced VH and most of the PDD patients had experienced VH within 1 year before or after diagnosis of PDD. These results indicate that aging and VH are important factors associated with dementia in PD.Acta Neurologica Scandinavica 10/2007; 116(3):190-5. DOI:10.1111/j.1600-0404.2007.00860.x · 2.40 Impact Factor