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)

Parkinson's disease is associated with classical Parkinsonian features that respond to dopaminergic therapy. Neuropsychiatric sequelae include dementia, major depression, dysthymia, anxiety disorders, sleep disorders, and sexual disorders. Panic attacks are particularly common. With treatment, visual hallucinations, paranoid delusions, mania, or delirium may evolve. Psychosis is a key factor in nursing home placement, and depression is the most significant predictor of quality of life. Clozapine may be the safest treatment for psychotic features, but more research is needed to establish the efficacy of antidepressant treatments. Dementia with Lewy bodies, the second most common dementia in the elderly, may present in association with systematized delusions, depression, or RBD. Early evidence suggests the utility of rivastigmine, donepezil, low-dose olanzapine, and quetiapine in treating DLB. Parkinson-plus syndromes generally lack a good response to dopaminergic treatment and evidence additional features, including dysautonomia, cerebellar and pontine features, eye signs, and other movement disorders. MSA is associated with dysautonomia and RBD. SND (MSA-P) is associated with frontal cognitive impairments, but dementia, psychosis, and mood disorders have not been strikingly apparent unless additional pathological findings are present. In SDS (MSA-A), impotence is almost ubiquitous; urinary incontinence is frequent; depression is occasional, and sleep apnea should be treated to avoid sudden death during sleep. OPCA neuropsychiatric correlates await further definition. Progressive supranuclear palsy neuropsychiatric features include apathy, subcortical dementia, pathological emotionality, mild depression and anxiety, and lack of appreciable response to donepezil. CBD usually is recognized by early frontal dementia with ideomotor apraxia, often in the right upper extremity, attended later by poorly responsive unilateral Parkinsonism, with additional signs including cortical reflex myoclonus, limb dystonia, alien limb, oculomotor apraxia when asked to look horizontally, depression, personality changes, and, occasionally, Kluver-Bucy syndrome. The neuropsychiatry of FTDP-17 involves apraxia, executive impairment, personality changes, hyperorality, and occasional psychosis. Future research in these Parkinsonian disorders should target the characterization of neuropsychiatric sequelae and their treatment.
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PMID:The neuropsychiatry of Parkinson's disease and related disorders. 1555 Feb 93

Parkinson's disease (PD) is a chronic disease associated with motor impairments (bradykinesia, rigidity, tremor and postural disorders), cognitive disorders and dysautonomia. Most symptoms are greatly improved by dopatherapy during the first stages, then signs of treatment ineffectiveness or intolerance occur that signal the beginning of motor and cognitive decline. This evolution signified the need to develop an effective tool to measure the effectiveness of drugs or surgery in PD and has had the Movement Disorder Society to propose 20 years ago a tool to assess such patients: the Unified Parkinson's Disease Rating Scale (UPDRS). This scale has a good internal consistency and a good interrater reliability. Yet, some impairments, especially of cognitive origin, are evaluated too succinctly and need complementary scales. As well, other disorders such as bladder disorders are not included, nor is quality of life studied despite the impact of PD on daily life. Specific scales have been proposed. UPDRS may be well-adapted to PD follow-up in the physical medicine and rehabilitation context by measuring treatment effectiveness, detecting Dopa ineffectiveness or complications and assessing patients' handicap in daily activities. The evolution of UPDRS will improve the qualities of the scale and contribute to better determining the various stages of the disease.
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PMID:[Assessment of idiopathic Parkinson's disease in physical medicine and rehabilitation]. 1593 79

Despite the current efficacious symptomatic approaches, the search is on for new therapies for Parkinson's disease that can control the cardinal symptoms of the disease (tremor, rigidity and bradykinesia), control/prevent motor complications induced by long-term levodopa, act on non-motor disease symptoms (dementia, dysautonomia, pain, insomnia, falls) and halt disease progression. Rasagiline is a monoamine oxidase-B inhibitor that has demonstrated efficacy against the cardinal symptoms of Parkinson's disease when used as monotherapy in early Parkinson's disease, and as an adjunct to levodopa in advanced disease stages. It reduces the duration and severity of poor symptom response episodes in fluctuating patients. Preliminary results allow discussion of putative effects of rasagiline on some non-motor signs and disease progression. This article outlines the evidence surrounding the efficacy and safety of rasagiline, and discusses its potential to address some of the currently unmet needs of Parkinson's disease therapy.
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PMID:Rasagiline in the pharmacotherapy of Parkinson's disease--a review. 1619 59

Parkinson's disease (PD) patients have a ninefold increased risk of recurring falls compared to healthy controls. The risk of falling due to cardiovascular dysautonomia (CVD) is not quantifiable. But, CVD is an integral part of the disease and at least 20% of PD patients suffer from orthostatic hypotension, an expression of CVD. One way to reduce falls due to CVD in PD patients could be to give adequate information on the relationship between falling risks and cardiovascular dysautonomia to patients and their caregivers. Moreover, drugs given for PD might contribute to OH and we propose that education and non-pharmacological strategies for its treatment might be preferable, especially because of the low efficacy of drugs available for the treatment of OH and the frailty of elderly PD patients.
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PMID:Cardiovascular dysautonomia as a cause of falls in Parkinson's disease. 1662 60

In cholinergic neurons, the presynaptic choline transporter (CHT) mediates high-affinity choline uptake (HACU) as the rate-limiting step in acetylcholine (ACh) synthesis. It has previously been shown that HACU is increased by behaviorally and pharmacologically-induced activity of cholinergic neurons in vivo, but the molecular mechanisms of this change in CHT function and regulation have only recently begun to be elucidated. The recent cloning of CHT has led to the generation of new valuable tools, including specific anti-CHT antibodies and a CHT knockout mouse. These new reagents have allowed researchers to investigate the possibility of a presynaptic, CHT-mediated, molecular plasticity mechanism, regulated by and necessary for sustained in vivo cholinergic activity. Studies in various mouse models of cholinergic dysfunction, including acetylcholinesterase (AChE) transgenic and knockout mice, choline acetyltransferase (ChAT) heterozygote mice, muscarinic (mAChR) and nicotinic (mAChR) receptor knockout mice, as well as CHT knockout and heterozygote mice, have revealed new information about the role of CHT expression and regulation in response to long-term alterations in cholinergic neurotransmission. These mouse models highlight the capacity of CHT to provide for functional compensation in states of cholinergic dysfunction. A better understanding of modes of CHT regulation should allow for experimental manipulation of cholinergic signaling in vivo with potential utility in human disorders of known cholinergic dysfunction such as Alzheimer's disease, Parkinson's disease, schizophrenia, Huntington's disease, and dysautonomia.
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PMID:The high-affinity choline transporter: a critical protein for sustaining cholinergic signaling as revealed in studies of genetically altered mice. 1672 48

Parkinson's disease is a progressive neurological disorder characterized by tremor, bradykinesia, rigidity, gait and postural instability and a variety of nonmotor symptoms. While these and other motor signs typically improve with levodopa, the so-called axial signs, such as dysarthria, dysphagia, postural instability and freezing, and most nonmotor signs, such as depression, cognitive decline and dysautonomia, usually do not respond satisfactorily to levodopa. Furthermore, the use of levodopa may be limited by the development of motor fluctuations, dyskinesias and other adverse effects. This manuscript reviews the medical management of advanced Parkinson's disease, focusing on the treatment of motor fluctuations and dyskinesias and of nonmotor and nonlevodopa responsive symptoms.
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PMID:Treatment of advanced Parkinson's disease. 1689 46

In Guadeloupe, there is an abnormally high frequency of atypical parkinsonism. Only one-third of the patients that develop parkinsonian symptoms were reported to present the classical features of idiopathic Parkinson disease and one-third a syndrome resembling progressive supranuclear palsy (PSP). The others were unclassifiable, according to established criteria. We carried out a cross-sectional study of 160 parkinsonian patients to: (i) define more precisely the clinical phenotypes of the PSP-like syndrome and the parkinsonism that was considered unclassifiable in comparison with previously known disorders; (ii) define the neuropsychological and brain imaging features of these patients; (iii) evaluate to what extent a candidate aetiological factor, the mitochondrial complex I inhibitor annonacin contained in the fruit and leaves of the tropical plant Annona muricata (soursop) plays a role in the neurological syndrome. Neuropsychological tests and MRI were used to classify the patients into those with Parkinson's disease (31%), Guadeloupean PSP-like syndrome (32%), Guadeloupean parkinsonism-dementia complex (PDC, 31%) and other parkinsonism-related disorders (6%). Patients with a PSP-like syndrome developed levodopa-resistant parkinsonism, associated with early postural instability and supranuclear oculomotor dysfunction. They differed, however, from classical PSP patients by the frequency of tremor (>50%), dysautonomia (50%) and the occurrence of hallucinations (59%). PDC patients had levodopa-resistant parkinsonism associated with frontosubcortical dementia, 52% of these patients had hallucinations, but, importantly, none had oculomotor dysfunction. The pattern of neuropsychological deficits was similar in both subgroups. Cerebral atrophy was seen in the majority of the PSP-like and PDC patients, with enlargement of the third ventricle and marked T2-hypointensity in the basal ganglia, particularly the substantia nigra. Consumption of soursop was significantly greater in both PSP-like and PDC patients than in controls and Parkinson's disease patients. In conclusion, atypical Guadeloupean parkinsonism comprises two forms of parkinsonism and dementia that differ clinically by the presence of oculomotor signs, but have similar cognitive profiles and neuroimaging features, suggesting that they may constitute a single disease entity, and both were similarly exposed to annonaceous neurotoxins, notably annonacin.
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PMID:Atypical parkinsonism in Guadeloupe: a common risk factor for two closely related phenotypes? 1730 92

In the field of neurology, Parkinson's disease (PD) is commonly perceived to be a disorder affecting only the (extrapyramidal) motor system, characteristically manifesting as bradykinesia, rigidity, tremor and postural instability. Although non-motor symptoms such as behavioural abnormalities, dysautonomia, sleep disturbances and sensory dysfunctions are also common and quite disabling manifestations of the disease, they are often not formally assessed and thus are frequently misdiagnosed and/or under diagnosed. For this reason, in this review we have concentrated on the pathophysiological and clinical basis of non-motor involvement such as olfactory dysfunction, depression, dementia, dysautonomia and sleep disorders in PD. The early recognition of these symptoms may well perhaps lead to an earlier diagnosis of PD, but in any case should lead to more prompt and effective treatment of the relatively unrecognized non-motor problems associated with PD.
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PMID:Non-motor dysfunction in Parkinson's disease. 1734 13

Our collective thinking about Parkinson disease (PD) has been heavily influenced by the dramatic response to dopamine replacement therapy. For progress to continue, however, we need to take a broad view of this disorder, which includes recognition of the following. First, substantial evidence now indicates that dopamine oxidation is unlikely to substantially contribute to the pathogenesis of PD. Second, levodopa therapy is not associated with neurotoxicity. Third, the first neurons affected in PD are nondopaminergic; the substantia nigra and other dopaminergic nuclei are affected only later in the course. Thus, PD is much more than degeneration of the dopaminergic nigrostriatal system. Fourth, in the current era, most of the disability of advancing PD is from involvement of nondopaminergic systems, including levodopa-refractory motor symptoms, dementia, and dysautonomia. Motor complications associated with levodopa therapy can be problematic, but they can be controlled in most, using available medications and deep brain stimulation surgery. We have reached the point of diminishing therapeutic returns with drugs acting on dopamine systems; more dopaminergic medications will provide only modest incremental benefit over current therapies. Finally, the benefits from transplantation surgeries aimed at restoring dopaminergic neurotransmission will be limited because later-stage PD disability comes from nondopaminergic substrates. Scale.
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PMID:Beating a dead horse: dopamine and Parkinson disease. 1900 Dec 60

Nonmotor symptoms have recently become a focus of renewed clinical interest and research in Parkinson's disease (PD). Autonomic and cognitive dysfunction are among the most prevalent of these nonmotor aspects of the disease. Although exact clinico-pathological correlations have not been established, alpha-synuclein pathology with Lewy body formation in the central and peripheral autonomic nervous system as well as in neocortical areas are generally believed to be driving factors for autonomic failure and cognitive decline in PD. Recent pathological and clinical studies have suggested greater prevalence of clinical dysautonomia and cardiac sympathetic denervation in PD dementia and dementia with Lewy bodies as compared with PD without dementia. This raises the possibility that spread of synuclein pathology to involve neocortical areas producing cognitive decline could be somehow linked to involvement of the autonomic nervous system in PD.
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PMID:Dysautonomia and cognitive dysfunction in Parkinson's disease. 1817 99


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