Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0426980 (motor symptom)
 471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A matter of debate is the impact of levodopa (LD) application in patients with Parkinson disease (PD) on altered force development and coordination, which are also influenced by the strength of muscles used. The objectives were to compare the motor response, the development of grip strength, and the pharmacokinetic behavior of LD and its main peripheral metabolite 3-O-methyldopa (3-OMD) after intake of 200-mg retarded-release levodopa/carbidopa (LD/CD) and of 150-mg LD/CD/entacapone (LD/CD/EN). Twelve patients with PD received both LD formulations within a standardized setting under double-blind conditions with a crossover design 1 day after the other. Motor symptoms significantly improved, LD plasma concentrations went up, and grip strength increased after both LD/CD and LD/CD/EN administration. There were no significant differences between both conditions with regard to motor response and LD pharmacokinetics. The 3-OMD levels were significantly lower during catechol-O-methyltransferase (COMT) inhibition with entacapone. The LD/CD/EN compound was superior over the retarded-release LD formulation, indicating the impact of LD on grip force. This may be caused by the interference of 3-OMD with the blood-brain barrier transport of LD; therefore, LD delivery is greater during the LD/CD/EN condition. Because the rating scale used does not consider the grip strength, this effect of better blood barrier transport of LD was not reflected. Another hypothesis may be that more acidic metabolites appear during peripheral LD metabolism by means of COMT, whereas COMT inhibition is accompanied by more basic LD metabolites (ie, the tyrosine aminotransferase-dependent substrates dihydroxyphenylpyruvate acetate and trihydroxyphenylacetate). This antiacid scenario may support a better muscle function with a positive impact on muscle excitability and contractibility.
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PMID:Catechol-O-methyltransferase inhibition improves levodopa-associated strength increase in patients with Parkinson disease. 1852 Sep 80

Our objective was to understand the impact of motor and nonmotor symptoms of patients with early and middle stage Parkinson's disease (PD) on their spouses' caregiver strain and depression. A sample of 219 spouse caregivers of PD patients participating in a clinical trial was evaluated for six dimensions of caregiver strain and depression using the Family Care Inventory. Motor and nonmotor (i.e., psychological) clinical symptoms collected from PD patients as part of the clinical trial protocol were used as predictors. Seven hierarchical regression analyses were used to determine the contribution of the motor and nonmotor clinical symptoms in explaining variation in each of the seven caregiver-dependent variables. Clinical symptoms explained 9-16% of the variance in caregiver strain and 10% of depression. Motor symptoms explained 0-6% of the variance and nonmotor psychological symptoms explained 7-13% of the variance in caregiver strain. Comparing our findings with literature that is deemed clinically relevant for patient symptoms that predict caregiver strain, we concluded that PD patient symptoms are important predictors of caregiver strain and depression. Patient nonmotor psychological symptoms have a much greater impact on caregiver strain and depression than patient motor symptoms.
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PMID:Do motor and nonmotor symptoms in PD patients predict caregiver strain and depression? 1852 98

A potent 5-hydroxytryptamine (5-HT)2A receptor inverse agonist and antagonist, ACP-103 [N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1, active:salt)], was evaluated for its ability to reduce the primary motor symptom of tremor using tacrine-induced tremulous jaw movements in rats, which is an animal model of parkinsonian tremor. Furthermore, ACP-103 was evaluated for its ability to reduce levodopa-induced dyskinesias in monkeys rendered parkinsonian with MPTP [1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine]. ACP-103 reduced tacrine-induced tremulous jaw movements in rats. In addition, ACP-103 administered in combination with levodopa caused a dose-related reduction in dyskinesias in monkeys. These data suggest that ACP-103 may have the potential to reduce tremor and levodopa-induced dyskinesias in Parkinson's disease.
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PMID:A 5-HT2A receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model. 1853 70

Head and eye turning is frequently observed during seizures. Versions with tonic and/or clonic symptoms can be differentiated from smooth head deviations. Head turning as a prominent symptom of status epilepticus has not previously been reported. We present eight case reports, (7 women/1 man, mean age 41 years, median 41.5, range 10 to 74), of status epilepticus (SE), with head turning as a prominent motor symptom. Six were accompanied by continuous frontal, occipital and temporal ictal epileptiform discharges. Furthermore, two patients had absence status with rhythmic and clonic head versions. While the localizing significance of head turnings in SE is low, in our cases, the direction was away from the discharging hemisphere in all cases of focal SE regardless of whether the turning was classified as version (three cases) or deviation (three cases). In this small series of SE, the classical observation of a patient looking away from the discharging hemisphere is still valid.
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PMID:Head turning as a prominent motor symptom in status epilepticus. 1853 62

Genital dysfunction and testosterone deficiency occur frequently in Parkinson's disease and represent a typical non-motor symptom of the disorder. Despite that, to our knowledge no study investigated whether at experimental level this can be reproduced with classic Parkinsonism-inducing neurotoxins. In this study we evaluated the effects produced in the testis following administration of the Parkinsonism-inducing neurotoxin 1-methyl, 4-phenyl, 1,2,3,6-tetrahydropyridine in mice. At 7 days following treatment, in the presence of a severe nigrostriatal dopamine depletion, we found a marked decrease in testosterone plasma levels in 1-methyl, 4-phenyl, 1,2,3,6-tetrahydropyridine-treated mice. Such testosterone loss occurred concomitantly with loss of Leydig cells and the presence of altered morphology in the interstitium with severe mitochondrial degeneration in spared Leydig cells. The loss of Leydig cells was accompanied by a marked decrease in TH immunohistochemistry and TH protein in the interstitium. This was accompanied by a significant decrease in norepinephrine levels in the testis. These effects shed novel light to understand genital dysfunction and testosterone deficiency in Parkinsonism, while offering a new experimental model to reproduce genital dysfunction in Parkinson's disease.
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PMID:MPTP-induced Parkinsonism is associated with damage to Leydig cells and testosterone loss. 1864 55

This review describes symptoms and pathophysiology of Parkinson's diseases (PD) and restless legs syndrome (RLS), and discusses the relationship between clinical outcome of DA agonists and their receptor-binding and pharmacokinetics. Oral DA agonists are divided into 2 classes; the ergots and the non-ergots. Both classes are in general equally effective against PD motor symptoms. Ergots (apart from bromocriptine) stimulate the DA D(1) subreceptor and increase dyskinesia. Furthermore, valvular heart disease (VHD) and pulmonary and retroperitoneal fibrosis appear to represent a class effect of 8beta-aminoergolines as cabergoline and pergolide The side effects profile therefore seems more beneficial for non-ergots than ergots. The main improvement of motor functions by DA agonists is related to D(2) agonism. However, in monotheraphy, the selective D(2)-receptor DA agonist sumanirole seemed less effective than ropinirole which is selective for D(2)-like DA-receptors (D(2), D(3) and D(4)). Given as adjunctive to L-dopa both drugs had equal efficacy on motor-symptoms, indicating that D(2)-receptor activity must be accompanied with stimulation of other DA receptors for optimizing the efficacy on motor symptoms. Striatal D(3) receptor loss may be more important than D(2) receptor loss for reduced response to dopaminergic treatment. D(3) stimulation may also be beneficial for the non-motor symptom depression/mood in PD and for neuron-protection. This makes D(3)-receptors a potential therapeutic target in PD. 5-HT(1A)-receptor agonism and alpha(2) adrenergic antagonism may contribute to prevention of dyskinesia. However, 5-HT-receptor activity is also associated with side effects. 5-HT(2B) agonism (and possibly 5-HT(1B) agonism) is associated with fibrotic reactions, and valvular heart disease (VHD). By interfering with the CYP450 system DA agonists may contribute to drug-drug interactions. Lack of CYP2D6 activity is also suggested as important for etiology and CNS-symptoms of PD. Based on current knowledge D2-like receptor activities (preferences for the D(3) receptor) seem most beneficial. 5-HT(1A)-receptor agonism (prevention of dyskinesia), 5-HT(2B) antagonism or no 5-HT(2B)-receptor activity also seems beneficial. Development of DA agonists containing these properties, without interfering with CYP2D6 may be beneficial.
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PMID:Receptor-binding and pharmacokinetic properties of dopaminergic agonists. 1869 Nov 32

Levodopa has been the mainstay of symptomatic therapy for Parkinson Disease (PD) for 40 years providing benefit to virtually all patients. Levodopa therapy results in improved activities of daily living, enhanced quality of life, and improved mortality. However, the long-term use of levodopa is associated with the development of motor fluctuations and dyskinesia. In addition, levodopa therapy has further limitations. It has little or no effect on certain motor features (e.g. gait and balance dysfunction) and a non-motor symptom complex (autonomic dysfunction, pain syndromes, sleep disorders, mood disturbances, dementia). Further, multiple case reports illustrate the potential of levodopa and other dopaminergic agents to cause or reveal a series of impulse control disorders. This review highlights the levodopa unresponsive symptoms in PD.
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PMID:Levodopa unresponsive symptoms in Parkinson disease. 1878 79

Spatial navigation is a complex process requiring integration of visuoperceptual information. The present study examined how visuospatial function relates to navigational veering in Parkinson's disease, a movement disorder in which visuospatial cognition is affected by the degeneration of the basal ganglia and resulting dysfunction of the parietal lobes. We hypothesized that patients whose initial motor symptoms start on the left versus right side of the body (LPD, predominant right-hemisphere dysfunction; RPD, predominant left-hemisphere dysfunction) would display distinct patterns of navigational veering associated with the groups' dissimilar visuospatial profiles. Of particular interest was to examine the association of navigational veering (lateral deviation along the medio-lateral axis) with perception of egocentric coordinates and of radial optic flow patterns, both of which are mediated by the parietal lobes. Thirty-one non-demented Parkinson's disease patients (16 LPD, 15 RPD) and 18 healthy control (HC) adults received visuospatial tests, of whom 23 Parkinson's disease patients and 17 HC also underwent veering assessment. The participants were examined on three visual-feedback navigation conditions: none (eyes closed), natural, and optic flow supplied by a virtual-reality headset. All groups veered to the left when walking with eyes closed, women with Parkinson's disease more so than the other participants. On the navigation assessments with visual feedback, only LPD patients deviated right of centre. On tests of visuospatial function, the perceived midline was shifted rightward in LPD (men and women), increasingly so with the addition of visual input. In contrast, men with RPD showed leftward deviation. RPD patients and HC perceived optic flow in the left hemifield as faster than in the right hemifield, with a trend for the opposite pattern for LPD. Navigational veering in LPD was associated with deviation of the perceived egocentric midline and not with perception of optic flow speed asymmetries, and in RPD it was also associated with visual dependence, though in fact LPD subjects were more visually dependent than those with RPD. Our results indicate that (i) parietal-mediated perception of visual space is affected in Parkinson's disease, with both side of motor symptom onset and gender affecting spatial performance, and (ii) visual input affects veering.
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PMID:Impact of optic flow perception and egocentric coordinates on veering in Parkinson's disease. 1895 54

Non-motor symptoms, such as psychiatric symptoms and autonomic dysfunction, are common co-morbid conditions in Parkinson's disease (PD) and major contributors to poor quality of life and disability. Within the group of neuropsychiatric conditions, depressive symptoms are the most common condition. Despite their frequency and importance, depressive symptoms can be difficult to assess and diagnose and thus depression in PD is frequently unrealized. Diagnostic challenges include the overlap of depressive symptoms with motor and non-motor symptoms of PD, such as dementia and apathy. Furthermore, there are no definite standards to assess and diagnose depression in PD leading also to the lack of exact data on the epidemiology of this non-motor symptom in PD. Depending on the diagnostic test and the study design the prevalence of depression in PD is reported between 7 and 72% of PD patients with approximately 40% in most cross-sectional studies. In contrast, the pathogenesis and long-term course of depression in PD remain elusive. Current hypothesis, however, includes that depressive symptoms are part of the core condition of PD when regarded as an entity. The present review summarizes the current knowledge on epidemiology, pathogenesis and diagnosis of depression in PD and proposes on this data base a standard procedure for screening and diagnosis of depressive symptoms in PD.
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PMID:[Depression in Parkinson's disease. Part 1: epidemiology, signs and symptoms, pathophysiology and diagnosis]. 1901 23

The aim of this article was to determine which aspects of Huntington's disease (HD) are most important with regard to the health-related quality of life (HrQOL) of patients with this neurodegenerative disease. Seventy patients with HD participated in the study. Assessment comprised the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive and functional capacity sections, and the Beck Depression inventory. Mental and physical HrQOL were assessed using summary scores of the SF-36. Multiple regression analyses showed that functional capacity and depressive mood were significantly associated with HrQOL, in that greater impairments in HrQOL were associated with higher levels of depressive mood and lower functional capacity. Motor symptoms and cognitive function were not found to be as closely linked with HrQOL. Therefore, it can be concluded that, depressive mood and greater functional incapacity are key factors in HrQOL for people with HD, and further longitudinal investigation will be useful to determine their utility as specific targets in intervention studies aimed at improving patient HrQOL, or whether other mediating variables. As these two factors had a similar association with the mental and physical summary scores of the SF-36, this generic HrQOL measure did not adequately capture and distinguish the true mental and physical health-related HrQOL in HD.
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PMID:Health-related quality of life in Huntington's disease: Which factors matter most? 1909 81


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