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)

We have established that the frequency of LRRK2 mutations in a series of 118 cases of familial Parkinson's disease is 5.1%. In the largest family with autosomal dominant, late-onset Parkinson's disease where affected subjects share a Y1699C missense mutation we provide a detailed clinical, pathological and imaging report. The phenotype in this large British kindred included asymmetrical, levodopa-responsive parkinsonism where unilateral leg tremor at onset and foot dystonia were prominent features. There was no significant abnormality of cognition but there was prominent behavioural disorder. We observed a lower age of onset in successive generations. Histopathology in one patient showed substantia nigra cell loss and Lewy body formation, with small numbers of cortical Lewy bodies. 18F-dopa positron emission tomography (PET) in another patient showed a pattern of nigrostriatal dysfunction typical of idiopathic Parkinson's disease. 18F-dopa-PET scans in unaffected family members prior to identifying the disease locus did not detect subclinical nigrostriatal dysfunction. Olfaction was assessed in affected subjects and Lewy bodies were identified in the olfactory bulb as well as cortex and brainstem of one deceased patient. In order to assess the role of mutations in this gene in other familial cases we undertook a mutation screen of all 51 exons of LRRK2 in 117 other smaller British kindreds with familial Parkinson's disease. The commonest mutation was G2019S and we also identified two novel mutations, R1941H and T2356I, in the coding sequence. These data suggest that parkinsonism caused by mutations in LRRK2 is likely to represent the commonest locus for autosomal dominant Parkinson's disease with a phenotype, pathology and in vivo imaging similar to idiopathic, late-onset Parkinson's disease.
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PMID:Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data. 1631 Dec 69

The North American Multiple System Atrophy Study Group involves investigators in 12 US medical centers funded by a grant from the National Institutes of Health. The objectives are to examine the environmental and genetic risk factors for MSA; elucidate pathogenic mechanisms underlying the disorder; and refine evaluations used for assessment. During its first year, the group enrolled 87 patients, implemented four cores, and initiated four scientific projects. Most patients among the 87 had parkinsonian features, which frequently began asymmetrically and remained asymmetrical; one-third responded to levodopa and many developed levodopa complications; almost two-thirds of the patients had cerebellar dysfunction, of these 90% had ataxia; urinary incontinence occurred commonly, and sleep disorders affected most. The investigators studied the effects of oxidative and nitrative stress upon the formation of alpha-synuclein inclusions; generated transgenic models of alpha-synuclein accumulation that recapitulate several behavioral and neuropathological features of MSA; and compared the severity of the autonomic features of MSA, Parkinson's disease and dementia with Lewy bodies.
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PMID:The North American Multiple System Atrophy Study Group. 1628 10

Early in Parkinson's disease (PD) physical activity becomes difficult resulting in a more sedentary lifestyle. Clinical and experimental studies have found that increased activity following striatal dopamine loss leads to increased motor function. Decreased physical activity early in PD along with findings that increased physical activity results in functional improvement suggested to us that decreased physical activity during the period of nigrostriatal degeneration may not only be a symptom of the injury, but may also act to potentiate the degeneration. Using the bilateral MPTP mouse model of PD, we restricted use of one forelimb for the first 7 days post-injection. This transient behavioral manipulation during the period of dopamine degeneration resulted in a long-lasting deficit of the restricted forelimb. This was manifested as sustained asymmetrical use of the forelimbs during wall exploration, as well as a neurochemical imbalance between striatal hemispheres measured by immunoreactivity of the dopamine terminal markers, DAT, VMAT2 and TH. These results show a significant interaction between behavior and neurochemistry and suggest that a reduction in activity level may further exacerbate degeneration.
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PMID:Use-dependent behavioral and neurochemical asymmetry in MPTP mice. 1746 55

Bimanual coordination involves the simultaneous performance of either symmetrical (in-phase) or asymmetrical (anti-phase) movements with both hands and is known to be impaired in Parkinson's disease (PD). At present, it is unclear whether this aspect of motor function is already impaired in early stage, untreated PD patients. Therefore, we investigated the accuracy of bimanual coordination in 13 early stage, untreated PD patients and 13 age- and sex-matched healthy controls. Each subject performed bimanual coordination tasks at two different movement frequencies (1 and 1.75 Hz) and with two different phase relationships (in-phase and anti-phase). The percentage of unsuccessful trials (as a measure of overall task performance) in PD patients was significantly higher than in healthy subjects. PD patients performed high frequency in-phase and anti-phase bimanual coordination tasks less accurately with their non-dominant hand than healthy subjects. Furthermore, PD patients had more difficulty than healthy subjects in maintaining a constant phase relationship between the hands in the anti-phase condition at low movement frequency. This study demonstrates that bimanual coordination dysfunction is a very early sign of PD. Bimanual coordination tasks, in particular those involving high frequency anti-phase movements, might prove useful in the early diagnosis of PD.
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PMID:Bimanual coordination dysfunction in early, untreated Parkinson's disease. 1662 59

Excitotoxicity has been suggested to play a pivotal role in the pathogenesis of Parkinson disease (PD). As subthalamic nucleus (STN) neurons express glutamate and are overactivated in parkinsonism, it seems that in PD dopaminergic (DA) neurons are under the influence of abnormally high levels of glutamate and consequently might be more vulnerable to neurodegeneration. To determine the contribution of the overactivated STN-SN pathway to the progression of PD, we studied the effect of prior unilateral STN lesion on the toxicity induced by subsequent administration of 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine (MPTP) to non-human primates. In animals from group 1, kainic-induced lesion of the STN was performed prior to the administration of MPTP whereas in animals from group 2, STN lesion was caused after animals had been chronically treated with MPTP. The lesion of the STN elicited a contralateral hemiballism in animals from group 1, and they developed an asymmetrical parkinsonism after being exposed to MPTP. The STN lesion produced an improvement in the contralateral parkinsonism and mild choreic movements in animals from group 2. Cell counting of tyrosine hydroxylase immunoreactive (TH-ir) cells was performed by stereology and showed a similar loss of TH-ir cells (approximately 85%) in the ipsilateral and contralateral SN to the lesioned STN. These data indicate that the surgical removal of the excitatory drive from the STN to SN neurons does not protect dopaminergic neurons against a chronic and extended toxic effect of MPTP and do not support the assumption that STN blockade might delay the progression of PD.
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PMID:Does increased excitatory drive from the subthalamic nucleus contribute to dopaminergic neuronal death in Parkinson's disease? 1680 73

The relation of body side of motor symptom onset in Parkinson's disease (PD) to memory measures associated with hemispheric dominance was examined. Fourteen patients with right body side motor symptom onset (RPD, inferred left hemisphere dysfunction) and 16 patients with left side onset (LPD, right hemisphere dysfunction) were administered measures of verbal (Hopkins Verbal Learning Test-Revised) and visual memory (Brief Visual Memory Test-Revised), that require similar task demands and are associated with left or right hemisphere dominance, respectively. The LPD group demonstrated poorer visual than verbal memory, both within group and in comparison to the RPD group. By contrast, the RPD group showed poorer verbal than visual memory within group. These findings suggest that side of motor symptom onset is associated with asymmetrical memory dysfunction.
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PMID:Body side of motor symptom onset in Parkinson's disease is associated with memory performance. 1696 53

The clinical criteria of Parkinson's disease are akinesia in combination with at least one of the following three symptoms: tremor (asymmetrical resting tremor), rigidity, impairment of posture, gait and balance. Symptomatic and atypical parkinsonian syndromes are ruled out by history, clinical examination, cranial CT, MRI, SPECT or PET. Patients with Parkinson's disease respond to levodopa or dopaminagonists throughout the course of the disease. Parkinson's disease is also characterised by various vegetative symptoms, impairment of olfaction, anxiety, depression, and with increasing age also by cognitive deficits and dementia.
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PMID:[Clinical criteria of Parkinson's disease]. 1722 18

Although normal subjects do not move during REM sleep, patients with Parkinson's disease may experience REM sleep behaviour disorder (RBD). The characteristics of the abnormal REM sleep movements in RBD have, however, not been studied. We interviewed one hundred consecutive non-demented patients with Parkinson's disease and their bed partners using a structured questionnaire assessing the presence of RBD. They rated the quality of movements, voice and facial expression during RBD as being better, equal or worse than in awake ON levodopa condition. Night-time sleep and movements were video-monitored during polysomnography in 51 patients to evaluate the presence of bradykinesia, tremor and hypophonia during REM sleep. Fifty-nine patients had clinical RBD with 53/59 bed partners able to evaluate them. All 53 (100%) reported an improvement of at least one component of motor control during RBD. By history, movements were improved in 87% patients (faster, 87%; stronger, 87%; smoother, 51%), speech was better in 77% patients (more intelligible, 77%; louder, 38%; better articulated, 57%) and facial expression was normalized in 47% patients. Thirty-eight per cent of bed partners reported that movements were 'much better', even in the most disabled patients. The video-monitored purposeful movements in REM sleep were also surprisingly fast, ample, coordinated and symmetrical, without obvious sign of parkinsonism. The movements were, however, jerky, violent and often repetitive. While all patients had asymmetrical parkinsonism when awake, most of the time they used the more disabled arm, hand and leg during the RBD (P = 0.04). Movements involved six times as often the upper limbs and the face as the lower limbs (OR: 5.9, P = 0.004). The percentage of time containing tremor EMG activity decreased with sleep stages from 34.9 +/- 15.5% during wakefulness, to 3.6 +/- 5.7% during non-REM sleep stages 1-2, 1.4 +/- 3.0% during non-REM sleep stages 3-4, and 0.06 +/- 0.2% during REM sleep (in this last case, it was subclinical tremor). The restored motor control during REM sleep suggests a transient 'levodopa-like' reestablishment of the basal ganglia loop. Alternatively, parkinsonism may disappear by REM sleep-related disjunction between pyramidal and extrapyramidal systems. We suggest the following model: the movements during the RBD would be generated by the motor cortex and would follow the pyramidal tract bypassing the extrapyramidal system. These movements would eventually be transmitted to lower motor neurons because of brainstem lesions interrupting the pontomedullary pathways which mediate the REM sleep atonia.
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PMID:Restoration of normal motor control in Parkinson's disease during REM sleep. 1723 26

Parkinson's disease (PD) typically manifests with asymmetric motor symptom onset. Ventricular enlargement, a nonspecific measure of brain atrophy, has been associated with cognitive decline in PD, but not with motor symptom asymmetry. Asymmetrical ventricular enlargement on magnetic resonance images was explored in a monozygotic twin pair discordant for PD and in nine healthy monozygotic twin pairs. The left-right lateral ventricular volumetric difference of the PD-twin was greater than that of his twin and all other healthy twins, with the larger ventricle observed contralateral to the more symptomatic side. Moreover, the lateral ventricle asymmetry difference between twin pairs was significantly higher for the discordant PD-twin pair than for the healthy twin pairs. This is the first report to suggest the presence of asymmetrical ventricular enlargement in PD, findings that may be worthy of further study.
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PMID:Asymmetrical ventricular enlargement in Parkinson's disease. 1758 38

A cardinal feature of Parkinson's disease (PD) is muscle hypertonicity, i.e. rigidity. Little is known about the axial tone in PD or the relation of hypertonia to functional impairment. We quantified axial rigidity to assess its relation to motor symptoms as measured by UPDRS and determine whether rigidity is affected by levodopa treatment. Axial rigidity was measured in 12 PD and 14 age-matched controls by directly measuring torsional resistance of the longitudinal axis to twisting (+/-10 degrees ). Feet were rotated relative to fixed hips (Hip Tone) or feet and hips were rotated relative to fixed shoulders (Trunk Tone). To assess tonic activity only, low constant velocity rotation (1 degrees /s) and low acceleration (<12 degrees /s(2)) were used to avoid eliciting phasic sensorimotor responses. Subjects stood during testing without changing body orientation relative to gravity. Body parts fixed against rotation could translate laterally within the boundaries of normal postural sway, but could not rotate. PD OFF-medication had higher axial rigidity (p<0.05) in hips (5.07 N m) and trunk (5.30 N m) than controls (3.51 N m and 4.46 N m, respectively), which did not change with levodopa (p>0.10). Hip-to-trunk torque ratio was greater in PD than controls (p<0.05) and unchanged by levodopa (p=0.28). UPDRS scores were significantly correlated with hip rigidity for PD OFF-medication (r values=0.73, p<0.05). Torsional resistance to clockwise versus counter-clockwise axial rotation was more asymmetrical in PD than controls (p<0.05), however, there was no correspondence between direction of axial asymmetry and side of disease onset. In conclusion, these findings concerning hypertonicity may underlie functional impairments of posture and locomotion in PD. The absence of a levodopa effect on axial tone suggests that axial and appendicular tones are controlled by separate neural circuits.
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PMID:Axial hypertonicity in Parkinson's disease: direct measurements of trunk and hip torque. 1769 15


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