Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0233565 (bradykinesia)
 2,352 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tremor is commonly the first neurologic sign of Parkinson's disease (PD) that leads patients to see a physician. Knowing how to differentiate the resting tremor of PD from essential tremor is an important diagnostic skill. Unlike patients with essential tremor, those with PD have other neurologic findings. A diagnosis of PD is likely if the patient has two of three major clinical features: resting tremor, bradykinesia, and rigidity. Minor signs may also be seen, including cognitive slowing, speech abnormalities, depression, dysautonomia, and sleep disturbances. The history and physical exam can determine if the patient has parkinsonism and whether the cause is Parkinson's disease.
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PMID:Tremor: how to determine if the patient has Parkinson's disease. 959 78

We sought to estimate the frequency and nature of sleep disturbances in Indian Parkinson's disease (PD) patients. One hundred forty nine consecutive PD patients attending the Movement Disorders Clinic of the All India Institute of Medical Sciences, New Delhi, India and 115 age-matched healthy controls participated. After clinical evaluation, sleep assessment was done using a 23-question, validated sleep questionnaire. Mean age of PD patients and the duration of illness were 58.37 (S.D. 10.45) years and 5.7 (S.D. 3.85) years, respectively. The mean age of the controls was 56.50 (S.D. 11.45) years (P > 0.05). Sleep problems were seen in 63 (42%) PD patients compared to 12% of controls. These were: insomnia in 32%, nightmares in 32%, and excessive day time sleepiness in 15% of PD patients as compared with 5%, 5% and 6%, respectively, in controls (P < 0.025). Presence of nightmares was significantly associated with higher Hoehn and Yahr score (P < 0.002), high unified Parkinson's disease rating scale (UPDRS) Part I score (P < 0.000) and levodopa dose (P < 0.025). Excessive daytime sleepiness correlated with higher Hoehn and Yahr stage (P < 0.004), and levodopa dose (P < 0.040). The sleep latency was longer in PD patients as compared to controls (P < 0.000). Multiple logistic regression analysis showed association of sleep disturbances with UPDRS Part III, Schwab and England score, levodopa dose, rigidity score, and bradykinesia score. Sleep problems are much more common in PD patients compared to controls (P < 0.001), and correlate with increased severity of disease.
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PMID:Sleep disorders in Parkinson's disease. 1221 Aug 75

Parkinson's disease is a progressive disorder of the central nervous system. Degeneration of the dopaminergic neurons is the main cause of the disease. The basic symptoms of Parkinson's disease are bradykinesia, rigidity and resting tremor. Disturbances of the autonomous nervous system, depression, dementia and sleep disorders are common, too. People with Parkinson's disease suffer from insomnia, excessive daytime sleepiness, "sleep attacks", nightmares, REM sleep behaviour disorder, periodic limb movement in sleep, restless legs syndrome and sleep apnea syndrome. The main cause of sleep disorders in Parkinson's disease are age-connected changes in sleep architecture, disturbances of neurotransmission, movement disturbances in sleep, medications and concomitant diseases. The authors present the current state of knowledge on sleep disorders in Parkinson's disease, especially, the role of dopaminergic therapy, methods of diagnostics and treatment as well as the influence of sleep disturbances on patient's quality of life.
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PMID:[Sleep disturbances in Parkinson's disease]. 1627 62

Viable dopamine neurons in Parkinson's disease express the dopamine transporter (DAT) and release dopamine (DA). We postulated that potent DAT inhibitors, with low affinity for the serotonin transporter (SERT), may elevate endogenously released extracellular dopamine levels to provide therapeutic benefit. The therapeutic potential of eight DAT inhibitors was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated cynomolgus monkeys (Macaca fascicularis), with efficacy correlated with DAT occupancy as determined by positron emission tomography imaging in striatum. Four potent DAT inhibitors, with relatively high norepinephrine transporter, but low SERT affinities, that occupied the DAT improved activity in parkinsonian monkeys, whereas three high-affinity DAT inhibitors with low DAT occupancy did not. 2beta-Carbomethoxy-3alpha-(3,4-dichlorophenyl)-7beta-hydroxy-8-methyl-8-azabicyclo[3.2.1.]octane (O-1163) occupied the DAT but had short-lived pharmacological effects. The benztropine analog difluoropine increased general activity, improved posture, reduced body freeze, and produced sleep disturbances at high doses. (1R)-2beta-(1-Propanoyl)-3alpha-(4-fluorophenyl)tropane (O-1369) alleviated parkinsonian signs in advanced parkinsonian monkeys, by increasing general activity, improving posture, reducing body freeze, and sedation, but not significantly reducing bradykinesia or increasing locomotor activity. In comparison with the D(2)-D(3) DA receptor agonist quinelorane, O-1369 elicited oral/facial dyskinesias, whereas quinelorane did not improve posture or reduce balance and promoted stereotypy. In conclusion, DAT inhibitors with therapeutic potential combine high DAT affinity in vitro and high DAT occupancy of brain striatum in vivo with enduring day-time effects that do not extend into the nighttime. Advanced parkinsonian monkeys (80% DAT loss) respond more effectively to DAT inhibitors than mild parkinsonian monkeys (46% DAT loss). The therapeutic potential of dopamine transport inhibitors for Parkinson's disease warrants preclinical investigation.
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PMID:Dopamine transporter (DAT) inhibitors alleviate specific parkinsonian deficits in monkeys: association with DAT occupancy in vivo. 1688 33

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

The paraneoplastic syndrome caused by Ma2/Ta antibodies alone (not in conjunction with Ma1 or Ma3 antibodies) varies in presentation from classic limbic encephalitis. The Ma2 syndrome may present with symptoms referable to the brainstem, diencephalon, and limbic system. These clinical symptoms are accompanied by MRI changes and abnormal electroencephalographic findings. It is important to recognize when the encephalitic syndrome is secondary to Ma2 paraneoplastic antibodies, as the patients improve or stabilize most often when the underlying carcinoma is treated. Treatment of the paraneoplastic syndrome begins with recognition of the symptoms, such as memory impairment, seizures, sleep disturbances, bradykinesia or hypokinesia, and eye movement abnormalities. If a primary tumor is discovered during the workup, it should be removed and treated with the most up-to-date oncologic treatment available. In addition to oncologic treatment, the syndrome may be treated with an immunosuppressant regimen to optimize the neurologic outcome. Leaving the patient untreated will result in decline and eventual death from the cancer itself or from complications of the paraneoplastic syndrome.
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PMID:Treatment of anti-Ma2/Ta paraneoplastic syndrome. 1909 36

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by the loss of dopamine neurons in the substantia nigra pars compacta, culminating in severe motor symptoms, including resting tremor, rigidity, bradykinesia, and postural instability. In addition to motor deficits, there are a variety of nonmotor symptoms associated with PD. These symptoms generally precede the onset of motor symptoms, sometimes by years, and include anosmia, problems with gastrointestinal motility, sleep disturbances, sympathetic denervation, anxiety, and depression. Previously, we have shown that mice with a 95% genetic reduction in vesicular monoamine transporter expression (VMAT2-deficient, VMAT2 LO) display progressive loss of striatal dopamine, L-DOPA-responsive motor deficits, alpha-synuclein accumulation, and nigral dopaminergic cell loss. We hypothesized that since these animals exhibit deficits in other monoamine systems (norepinephrine and serotonin), which are known to regulate some of these behaviors, the VMAT2-deficient mice may display some of the nonmotor symptoms associated with PD. Here we report that the VMAT2-deficient mice demonstrate progressive deficits in olfactory discrimination, delayed gastric emptying, altered sleep latency, anxiety-like behavior, and age-dependent depressive behavior. These results suggest that the VMAT2-deficient mice may be a useful model of the nonmotor symptoms of PD. Furthermore, monoamine dysfunction may contribute to many of the nonmotor symptoms of PD, and interventions aimed at restoring monoamine function may be beneficial in treating the disease.
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PMID:Nonmotor symptoms of Parkinson's disease revealed in an animal model with reduced monoamine storage capacity. 1982 98

The cardinal characteristics of Parkinson disease (PD) include resting tremor, rigidity, and bradykinesia. Patients may also develop autonomic dysfunction, cognitive changes, psychiatric symptoms, sensory complaints, and sleep disturbances. The treatment of motor and non-motor symptoms of Parkinson disease is addressed in this article.
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PMID:Medical treatment of Parkinson disease. 1955 24

Parkinson's disease (PD) is an age-related, progressive, multisystem neurodegenerative disorder resulting in significant morbidity and mortality, as well as a growing social and financial burden in an aging population. The hallmark of PD is loss of dopaminergic neurons of the substantia nigra pars compacta, leading to bradykinesia, rigidity and tremor. Current pharmacological treatment is therefore centred upon dopamine replacement to alleviate symptoms. However, two major problems complicate this approach: (i) motor symptoms continue to progress, requiring increasing doses of medication, which result in both short-term adverse effects and intermediate- to long-term motor complications; (ii) dopamine replacement does little to treat non-dopaminergic motor and non-motor symptoms, which are an important source of morbidity, including dementia, sleep disturbances, depression, orthostatic hypotension, and postural instability leading to falls. It is critical, therefore, to develop a broader and more fundamental therapeutic approach to PD, and major research efforts have focused upon developing neuroprotective interventions. Despite many encouraging preclinical data suggesting the possibility of addressing the underlying pathophysiology by slowing cell loss, efforts to translate this into the clinical realm have largely proved disappointing in the past. Barriers to finding neuroprotective or disease-modifying drugs in PD include a lack of validated biomarkers of progression, which hampers clinical trial design and interpretation; difficulties separating symptomatic and neuroprotective effects of candidate neuroprotective therapies; and possibly fundamental flaws in some of the basic preclinical models and testing. However, three recent clinical trials have used a novel delayed-start design in an attempt to overcome some of these roadblocks. While not examining markers of cell loss and function, which would determine neuroprotective effects, this trial design pragmatically tests whether earlier versus later intervention is beneficial. If positive (i.e. if an earlier intervention proves more effective), this demonstrates disease modification, which could result from neuroprotection or from other mechanisms. This strategy therefore provides a first step towards supporting neuroprotection in PD. Of the three delayed-start design clinical trials, two have investigated early versus later start of rasagiline, a specific irreversible monoamine oxidase B inhibitor. Each trial has supported, although not proven, disease-modifying effects. A third delayed-start-design clinical trial examining potential disease-modifying effects of pramipexole has unfortunately reportedly been negative according to preliminary presentations. The suggestion that rasagiline is disease modifying is made all the more compelling by in vitro and PD animal-model studies in which rasagiline was shown to have neuroprotective effects. In this review, we examine efforts to demonstrate neuroprotection in PD to date, describe ongoing neuroprotection trials, and critically discuss the results of the most recent delayed-start clinical trials that test possible disease-modifying activities of rasagiline and pramipexole in PD.
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PMID:Disease modification in Parkinson's disease. 2181 97

Parkinson's disease (PD) is a common neurodegenerative disorder diagnosed by the presence of bradykinesia and at least 1 of the symptoms of rigidity, resting tremor, or postural instability. It is increasingly recognized that nonmotor symptoms are common and can adversely affect quality of life, yet they often are not diagnosed and consequently are often untreated. Nonmotor symptoms include neuropsychiatric issues such as anxiety, depression, hallucinations, impulse control disorders, and cognitive impairment, as well as autonomic dysfunction, which may present as gastrointestinal, urinary, and sexual disturbances. Nonmotor symptoms also include excessive sweating, orthostatic hypotension, and sleep disturbances. Management of PD requires recognition of both motor and nonmotor symptoms as well as an understanding of the relationship between these symptoms and how they can be affected by treatments for PD. Therapy should be individualized for each patient, as treatments for the motor symptoms of PD can improve some nonmotor symptoms while they can worsen others. In many cases, symptom-specific treatments are necessary to control nonmotor symptoms of PD.
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PMID:The impact and management of nonmotor symptoms of Parkinson's disease. 2208 51


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