Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We could quantify the tetrahydroisoquinoline derivative salsolinol in urine of patients with Parkinson's disease and normal control subjects by means of high performance liquid chromatography and electrochemical detection. Urine levels of salsolinol were positively related to the homovanillic acid/3-O-methyl-dopa ratio in the cerebrospinal fluid that reflects dopamine metabolism. In the patient group with visual hallucinations, mean salsolinol level was significantly increased to almost the 3-fold of those found in patients without hallucinations. Since the daily L-dopa doses of both patient groups were nearly identical this result is not due to different L-dopa medications. Additionally, either high values of the main serotonin metabolite, 5-hydroxyindole acetic acid (HIAA) or the L-dopa/3-O-methyl-dopa ratio were found in cerebrospinal fluid of patients with hallucinations. The enhanced salsolinol levels in patients with visual hallucinations seem to be due to an overloaded dopaminergic pathway with an imbalance between dopaminergic and serotonergic systems. Thus, salsolinol appears as a predictor for hallucinosis in Parkinson's disease.
 ...
PMID:Salsolinol, catecholamine metabolites, and visual hallucinations in L-dopa treated patients with Parkinson's disease. 961 86

Hallucinations, sensory perceptions without environmental stimuli, occur as simple experiences of auditory, gustatory, olfactory, tactile, or visual phenomena as well as mixed- or complex experiences of more than one simple phenomenon. The nature of the hallucination assists localization, differential diagnosis, and treatment planning. In particular, the presence of persistent visual hallucinations of persons with Parkinson's disease predicts dementia, rapid deterioration, permanent nursing home placement, and death. Hallucinations in persons with Alzheimer's disease are often associated with serious behavioral problems and predict a rapid cognitive decline. Theories of the etiology of hallucinations include (1) stimulation, e.g., neurochemical, electrical, seizure, and ephaptic, and (2) inhibition, e.g., destruction of normally inhibitory functions, resulting in disinhibition as in the Charles Bonnet and phantom limb syndromes. Functional neuroimaging procedures suggest anatomical associations for hallucinations. While hallucinations may be a symptom of medical, neurologic, and psychiatric disorders, they may also occur in a wide range of human experiences.
 ...
PMID:Hallucinations. 965 80

Selegiline (deprenyl), a selective, irreversible inhibitor of monoamine oxidase type B (MAO-B) is widely used in the treatment of Parkinson's disease. As the first MAO-B inhibitor approved for the treatment of Parkinson's disease, concerns were raised about the safety of the drug based on the adverse effect profiles of older, nonselective MAO inhibitors. Unlike the nonselective MAO inhibitors, selegiline does not significantly potentiate tyramine-induced hypertension (the 'cheese effect') at the dosages (5 to 10 mg daily) used for the treatment of Parkinson's disease. Selegiline has been well tolerated when given alone. The most frequent adverse events seen during monotherapy have been insomnia, nausea, benign cardiac arrhythmias, dizziness and headache. When combined with levodopa, selegiline can potentiate the typical adverse effects of levodopa, if the dose of levodopa is not reduced sufficiently. Thus, the most common adverse effects associated with this combination are nausea, dizziness, fatigue, constipation and insomnia. At the later stages of Parkinson's disease when fluctuations in disability occur, peak dose dyskinesias, psychiatric complications like hallucinations and insomnia, and orthostatic hypotension are further potentiated by selegiline. Mortality was recently reported to be increased when selegiline and levodopa were given together in comparison with treatment with levodopa alone, but a large meta-analysis of 5 long term studies and 4 separate studies did not support this conclusion. Selegiline seems to be generally well tolerated in combination with other drugs. However, when pethidine (meperidine) has been given to patients who are receiving selegiline therapy, severe adverse effects have been reported. Thus, the concomitant use of these drugs is not recommended. A low tyramine diet is recommended if selegiline is used together with nonselective MAO inhibitors or the selective, reversible MAO-A inhibitor, moclobemide. Several adverse effects have been reported when fluoxetine and selegiline have been used together. A recent survey revealed that the incidence of a true serotonin syndrome is, however, very low with this combination. Concomitant use of selegiline and other selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) like citalopram, which have generally less interactions than fluoxetine, seems to be well tolerated. Nevertheless, caution is advised when combining a SSRI or a tricyclic antidepressant and selegiline.
 ...
PMID:Safety of selegiline (deprenyl) in the treatment of Parkinson's disease. 967 55

We report a 74-year-old woman with parkinsonism and dementia, who died 4 years after the onset of the disease. She was well until 70 years of the age (1993) when she noted slowness in the movement in her left hand. She also developed gait disturbance and the similar symptoms spread to the right upper and lower extremities. Two years after the onset, she had difficulty in walk, and was admitted to our hospital on March 9, 1995. Her daughter had the onset of hand tremor at 50 years of the age and gait disturbance at 52. Her gait improved after levodopa treatment, but her MRI revealed a liner T2-high signal lesion along the outer surface of each putamen. On admission, the patient was alert but slighted demented. Higher cerebral functions were normal. She had a masked face and small voice. Her gait was of small step without arm swing. Retropulsion was present. Rigidity was noted in the neck but not in the limbs. She was bradykinetic but tremor was absent. She was treated with levodopa/carbidopa, dops, and bromocriptine with considerable improvement and was discharged on March 30, 1995. On January 19, 1996, she developed fever and hallucination; she became more akinetic and admitted again. She showed marked dementia and stage IV parkinsonism. She was treated by supportive measures with improvement in the general condition, but she was found to have a gastric cancer for which a subtotal gastrectomy was performed on March 11, 1996. Post-operative course was uneventful, but her parkinsonism progressed to stage V. She was transferred to another hospital on May 13, 1996. In July 21, 1996, she developed dyspnea and fever and was admitted to our hospital again. She was somnolent. Rigidity was moderate to marked and she was unable to stand or walk. By supportive cares, her general condition improved and was discharged to home on November 4, 1996. She developed fever on June 13, 1997 and admitted to our service again. Her BP was 150/90 mmHg. She was alert but markedly demented. Laboratory examination revealed increases in liver enzymes (GOT 75 IU/l, GPT 101 IU/l) and renal dysfunction (BUN 68 mg/dl, creatinine 3.27 mg/dl). Subsequent hospital course was complicated by renal failure and thrombocytopenia (33,000/ml). She expired on July 1, 1997. The patient was discussed in a neurologic CPC, and a chief discussant arrived at the conclusion that the patient had diffuse Lewy body disease and her daughter striatonigral degeneration. Some participants thought both the patient and her daughter had diffuse Lewy body disease. Post-mortem examination revealed marked degeneration of the substania nigra and the locus coeruleus. The medial part of the nigra also showed marked cell loss. Lewy bodies were found in the remaining nigral and coeruleus neurons. Cortical Lewy bodies were very few and the striatum was intact. Pathologic diagnosis was Parkinson's disease. Dementia was in part attributed to the marked degeneration of the medial part of the substantia nigra.
 ...
PMID:[A 74-year-old woman with parkinsonism and dementia who died four years after the onset]. 973 28

This study examined the relationship between deficits in color and contrast discrimination and visual hallucinations (VH) in patients with Parkinson's disease (PD) and normal visual acuity. Thirty-five nondemented and nonpsychotic PD patients with normal visual acuity and without major ophthalmologic disease were interviewed twice and divided into two groups: hallucinators (n = 14) and non-hallucinating controls (n = 21). The groups were compared for color vision (assessed by Lanthony D-15 [LD] and Farnsworth-Munsell 100 hue [FM] tests), and for contrast sensitivity (tested by Vis tech tables [VT] and monocular and binocular Pelli-Robson test [PR]). There was no difference in age, duration or stage of PD, or dosage or duration of levodopa therapy between the two groups. Parkinson's disease patients showed impairment on all visual tests, with the hallucinators performing worse than the controls on all tests. This difference was significant for the LD (p < 0.007), the VT at 1.5 and 3 cycles per degree (p < 0.037 and 0.043, respectively) and the monocular PR tests (p < 0.049). The results led the authors to conclude that in patients with normal visual acuity, those with VH show added visual deficits of color and contrast discrimination. These ophthalmopathies may therefore be facilitating factors for visual hallucinations in PD and justify more focused research on the pathophysiology of visual hallucinations in Parkinson's disease.
 ...
PMID:Poor visual discrimination and visual hallucinations in Parkinson's disease. 978 9

Complex visual hallucinations may affect some normal individuals on going to sleep and are also seen in pathological states, often in association with a sleep disturbance. The content of these hallucinations is striking and relatively stereotyped, often involving animals and human figures in bright colours and dramatic settings. Conditions causing these hallucinations include narcolepsy-cataplexy syndrome, peduncular hallucinosis, treated idiopathic Parkinson's disease, Lewy body dementia without treatment, migraine coma, Charles Bonnet syndrome (visual hallucinations of the blind), schizophrenia, hallucinogen-induced states and epilepsy. We describe cases of hallucinosis due to several of these causes and expand on previous hypotheses to suggest three mechanisms underlying complex visual hallucinations. (i) Epileptic hallucinations are probably due to a direct irritative process acting on cortical centres integrating complex visual information. (ii) Visual pathway lesions cause defective visual input and may result in hallucinations from defective visual processing or an abnormal cortical release phenomenon. (iii) Brainstem lesions appear to affect ascending cholinergic and serotonergic pathways, and may also be implicated in Parkinson's disease. These brainstem abnormalities are often associated with disturbances of sleep. We discuss how these lesions, outside the primary visual system, may cause defective modulation of thalamocortical relationships leading to a release phenomenon. We suggest that perturbation of a distributed matrix may explain the production of similar, complex mental phenomena by relatively blunt insults at disparate sites.
 ...
PMID:Complex visual hallucinations. Clinical and neurobiological insights. 979 40

In the last decade, a new degenerative dementia, probably the second most common after Alzheimer's disease (AD), has been increasingly recognized under the consensus name of dementia with Lewy bodies (DLB). This article reviews current clinical, genetic, and pathological DLB data and indicates directions for future research. DLB overlaps in clinical, pathological, and genetic features with AD and Parkinson's disease (PD). Clinically, it is characterized by progressive cognitive impairment with significant fluctuations in alertness, parkinsonism, and psychosis with recurrent hallucinations. The neuropathological hallmarks are the intracytoplasmic inclusions in substantia nigra typical of PD, known as Lewy bodies (LB) but distributed widely throughout paralimbic and neocortical regions. Most of the cases also coexist with a plaque predominant AD. It is probably the unique and differential distribution of the lesions throughout cortical and subcortical structures in each of these disorders that supports a specific clinical syndrome and may ultimately prove most useful in understanding their different etiologies. Several genes have recently been implicated in LB formation. Special interest arises from mutations in the alpha-synuclein gene, which appears to be responsible for autosomal dominant PD in several kindreds. This gene encodes a presynaptic protein, a fragment of which is present in AD plaques. Recent studies show intense and quite specific alpha-synuclein immunoreactivity in LB and related neurites, suggesting a potential role of this protein in the aggregation or precipitation of LB inclusions.
 ...
PMID:Dementia with Lewy bodies. 980 70

The majority of patients with Parkinson's disease develop psychiatric symptoms. 40% of the patients suffer from symptoms of depression, severely affecting daily functioning, motor symptoms, cognition, and quality of life for both the patients and their spouses. Antidepressants may alleviate the depressive symptoms, but treatment is complicated by complex pharmacodynamic interactions. Hallucinations, with or without delusions, occur in 15-20% of patients, and are usually caused by dopaminergic treatment. Patients suffering from dementia and depression are, however at particular risk of developing psychosis. Treatment consists of lowering the dose of dopaminergic agents, but many patients require symptomatic treatment with atypical antipsychotic drugs. Most Parkinsonian patients develop impairment of memory and executive functions, and more than 25% of patients develop dementia. Dementia increases with the age at onset and the duration of Parkinson's disease. Subcortical dementia is the most commonly observed syndrome, but symptoms of cortical dementia are also observed. No treatment is available, although cholinergic agents may prove useful.
 ...
PMID:[Emotional and cognitive disorders in Parkinson disease]. 983 Mar 42

Brain tissue obtained at autopsy continues to provide unique opportunities in current dementia research. Not only is tissue analysis still essential for diagnosis, but investigation of neurochemical pathology, at a level of resolution beyond current in vivo imaging, continues to provide new insights into the involvement of neurotransmitter signalling systems. These are relevant to therapy which, with respect to symptoms such as cognitive impairment, psychosis and depression, is currently targeted to specific transmitter (cholinergic, dopaminergic and serotonergic) systems. This paper focuses on dopaminergic, cholinergic and histaminergic parameters in Alzheimer's disease (AD), Dementia with Lewy bodies (DLB) and Parkinson's disease (PD). In the normal striatum the dopamine transporter and D2 receptor exhibit distinct rostral-caudal distributions and D2 binding is affected by genetic polymorphism at the Taq 1A locus. The transporter is reduced in both DLB and PD but not AD, correlating with severity of extrapyramidal dysfunction, and receptor abnormalities are apparent in DLB patients responding adversely to neuroleptics. Striatal nicotine receptors are lost in all 3 disorders, further reduced as a result of neuroleptic medication, and elevated as a result of tobacco use. In the thalamus there are selective reductions in presynaptic cholinergic activity in DLB in the reticular nucleus which relate to symptoms of hallucinations and fluctuating consciousness prevalent in this disorder. In the hippocampus coupling of muscarinic M1 receptors, relevant to response to cholinergic therapy, is impaired in areas most affected by beta-amyloid plaques and intact in less affected areas. Analysis of histamine H2 receptors indicates that, despite presynaptic histamine abnormalities in AD, receptor numbers are normal. Such clinically and therapeutically relevant observations on human brain neurochemistry provide a basis for improving therapeutic strategies and prospects of diagnostic in vivo chemical imaging.
 ...
PMID:Clinical neurochemistry: developments in dementia research based on brain bank material. 986 26

In a series of consecutively randomized outpatients who had Parkinson's disease (PD), we examined the association of three behaviors: sleep fragmentation, altered dream phenomena, and hallucinations/illusions. Using a log-linear model methodology, we tested the independence of each behavior. Sixty-two percent of the subjects had sleep fragmentation, 48% had altered dream phenomena, and 26% had hallucinations/illusions. Eighty-two percent of the patients with hallucinations/illusions experienced some form of sleep disorder. The three phenomena were not independent. The interaction between sleep fragmentation and altered dream phenomena was strongly statistically significant. Likewise, a significant interaction existed between altered dream phenomena and hallucinations/illusions. No interaction occurred between sleep fragmentation and hallucinations/illusions. Sleep fragmentation, altered dream phenomena, and hallucinations/illusions in PD should be considered distinct but often overlapping behaviors. The close association between altered dream phenomena and hallucinations suggests that therapeutic interventions aimed at diminishing dream-related activities may have a specific positive impact on hallucinatory behavior.
 ...
PMID:Hallucinations, sleep fragmentation, and altered dream phenomena in Parkinson's disease. 991 53


<< Previous 1 2 3 4 5 6 7 8 9 10