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

Brain imaging experiments identify plausible circuits involved in the genesis of the cardinal symptoms of Parkinson's disease. Akinesia is linked to hypoactivation of the supplementary motor area secondary to insufficient thalamocortical facilitation. Overactivation in other areas such as the lateral premotor and parietal cortex probably represents a compensatory mechanism. Bradykinesia is associated with abnormal functioning within intrinsic basal ganglia circuitry for scaling movements to appropriate magnitude. Parkinson's disease tremor is localized to pontine- and mesencephalic-cerebellar-thalamic circuits, with abnormalities of both dopamine and serotonin neurotransmission. There is a need to understand the anatomic intersections where information is shared across these circuits.
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PMID:Contributions of functional imaging to understanding parkinsonian symptoms. 1558 73

We report a 75-year-old Japanese woman with probable dementia with Lewy bodies (DLB). At the age of 64, she showed left hand resting tremor, and gradually developed bradykinesia, and rigidity. She was diagnosed as having parkinsonism and took medication. At the age of 70, she showed hallucination and dementia. As she had developing cognitive dysfunction and hallucination and parkinsonism, she was diagnosed to have probable DLB. At the age of 75, after administration of donepezil, she showed severe psychosis and worsened parkinsonism, and was admitted to hospital. On neurological examination, she showed severe rigidity and akinesia, and behavioral immobility like "waxy flexibility" or motiveless resistance to maintenance of rigid posture against attempts to be moved. The phenomena, she presented as motor abnormalities, were thought to be catatonia. In consideration of clinical course, her catatonia and worsened parkinsonism was thought to be induced by donepezil and she was stopped the administration of donepezil. After treatment with trihexiphenizil, she had improvement of motor abnormalities and worsened parkinsonism. It is important to recognize that donepezil may induce catatonia on the patients of parkinsonism with severe dementia.
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PMID:[A patient with probable dementia with Lewy bodies, who showed catatonia induced by donepezil: a case report]. 1560 76

Current neurosurgical strategies target overactive brain regions including the subthalamic nucleus, globus pallidus and thalamus to control various symptoms of Parkinson's disease. Subthalamotomy improves akinesia and can induce postural deficits in both parkinsonian humans and animals, pallidotomy improves limb dyskinesia and more variably, distal bradykinesia whilst thalamotomy improves tremor. Because the SNr also becomes overactive in PD and there are few surgical studies in parkinsonian primates, we therefore evaluated the effects of lesioning the SNr in hemiparkinsonian marmosets to establish the effects on symptomatology. Nine monkeys received unilateral 6-hydroxydopamine (6-OHDA) lesions. Seven weeks later, four received kainic acid lesions of the SNr. Behavioural tests were performed prior to 6-OHDA surgery and then fortnightly for 14 weeks. Unilateral 6-OHDA lesions induced ipsilateral postural bias, ipsilateral rotation after amphetamine injection and bradykinesia. Whilst, SNr lesions significantly altered the direction of head position and amphetamine-induced rotation relative to 6-OHDA lesions, there was no improvement in 6-OHDA-induced reaching deficits or sensorimotor neglect. Unbiased quantitation of the nigral lesions showed on average 88% loss of dopaminergic neurons after 6-OHDA lesions and 77% loss of non-dopaminergic neurons after SNr lesions. Our results demonstrate that the SNr is important in body orientation changes in parkinsonism.
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PMID:Postural changes after lesions of the substantia nigra pars reticulata in hemiparkinsonian monkeys. 1586 23

To further define the role of the external segment of the globus pallidus (GPe) in the development of parkinsonian motor signs, two rhesus monkeys were made parkinsonian with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Behavioral assessments of bradykinesia and akinesia as well as single neuron recordings in the internal segment of the globus pallidus (GPi) were performed in both monkeys before and after ablating the sensorimotor portion of GPe. The effects of apomorphine on behavior and neuronal activity were also assessed in the parkinsonian monkeys before and after GPe ablation. We found that lesions in GPe exacerbated parkinsonian symptoms, altered neuronal activity in GPi, and reduced the therapeutic effects of apomorphine. These results support the hypothesis that GPe can influence GPi neuronal activity and is directly involved in parkinsonism. In addition, these data suggest that the inclusion of GPe in pallidotomy lesions for the treatment of Parkinson's disease can block the beneficial effects of antiparkinsonian medications and should be avoided.
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PMID:Lesions in monkey globus pallidus externus exacerbate parkinsonian symptoms. 1692 Jan 2

Strong synchronization of neuronal activity occurs in the 8-35 Hz band in the subthalamic nucleus (STN) of patients with Parkinson's disease (PD) and is evident as oscillatory local field potential (LFP) activity. To test whether such synchronization may contribute to bradykinesia and rigidity, we sought correlations between the suppression of synchronization at 8-35 Hz in STN and the reduction in Parkinsonism with levodopa. LFPs were recorded on and off medication from STN deep-brain stimulation electrodes in nine PD patients. LFP power was calculated over the frequencies of the most prominent spectral peak within the 8-35 Hz frequency band on each of 17 sides (off medication), and over the frequencies of any peak in the 60-90 Hz band, if present (seven sides, on medication). Levodopa-induced reduction of LFP power over these two frequency ranges was then correlated with improvement in motor impairment as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). The reduction in peak activity in the 8-35 Hz band with levodopa positively correlated with the improvement in the contralateral hemibody motor UPDRS score with levodopa (r = 0.811, P < 0.001) as well as with hemibody subscores of akinesia-rigidity (r = 0.835, P < 0.001), but not tremor. A trend for negative correlations was found between peak 60-90 Hz LFP power and UPDRS hemibody score, suggesting that positive correlations were relatively frequency-specific. Our results support a link between levodopa-induced improvements in bradykinesia and rigidity and reductions in population synchrony at frequencies < 35 Hz in the region of the STN in patients with PD.
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PMID:Reduction in subthalamic 8-35 Hz oscillatory activity correlates with clinical improvement in Parkinson's disease. 1662 53

The homeobox transcription factors Engrailed-1 and Engrailed-2 are required for the survival of mesencephalic dopaminergic neurons in a cell-autonomous and gene-dose-dependent manner. Because of this requirement, the cells die by apoptosis when all four alleles of the Engrailed genes are genetically ablated (En1-/-;En2-/-). In the present study, we show that viable and fertile mice, heterozygous null for Engrailed-1 and homozygous null for Engrailed-2 (En1+/-;En2-/-), have an adult phenotype that resembles key pathological features of Parkinson's disease. Specifically, postnatal mutant mice exhibit a progressive degeneration of dopaminergic neurons in the substantia nigra during the first 3 mo of their lives, leading to diminished storage and release of dopamine in the caudate putamen, motor deficits similar to akinesia and bradykinesia, and a lower body weight. This genetic model may provide access to the molecular etiology for Parkinson's disease and could assist in the development of novel treatments for this neurodegenerative disorder.
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PMID:Slow progressive degeneration of nigral dopaminergic neurons in postnatal Engrailed mutant mice. 1701 29

Parkinsonism is a clinical syndrome characterized by bradykinesia, hypo-/ akinesia, muscular rigidity, and resting tremor, mainly caused by Parkinson's disease (PD). Progressive loss of nigral neurons with Lewy bodies is considered an essential neuropathological feature. Recent studies, however, indicate that nigral degeneration is only a part of this synucleinopathy, and clinical symptoms go far beyond motor parkinsonism. Olfactory disturbances, autonomic dysfunction, pain, sleep fragmentation, depression, and dementia with or without psychosis are frequently seen. The variability in the expression of these signs and symptoms suggests multiple causes and/or pathogeneses within the present diagnostic disease entity. In this article, a recently proposed staging of PD-related brain pathology will be correlated with the various clinical expressions. It will be argued that the specific topographical sequence of the pathology, depending on the extent and progression of the degenerative process at defined sites, may explain the individually variable expression of this disease.
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PMID:Parkinson's disease: premotor clinico-pathological correlations. 1701 46

Parkinson's disease is the second most common neurodegenerative disease. It is charaterized by a progressive loss of dopamine (DA) producing neurons in the midbrain, which result in a decline of DA innervations present in the forebrain, in particular, the striatum. The disease leads to appearance of motor symptoms involving akinesia/bradykinesia, gait disturbances, postural imbalance and tremor. Oral administration of L-3,4-dihydroxyphenylalanine (L-DOPA), the precursor of DA, provides very good symptomatic relief, but this intermittent and pharmacological treatment is compromised by severe side effects, such as the appearance of abnormal involuntary movements. Viral vector-mediated direct gene transfer techniques are currently being explored in order to provide continuous and stable synthesis of DA in the brain. This review focuses on the basic idea of DA replacement, first describing the enzymatic machinery important for DA synthesis and secondly the various alternative strategies pursued in several laboratories. The DOPA delivery strategy, based on the co-transduction of tyrosine hydroxylase (TH), and GTP cyclohydrolase 1 (GCH1) genes, has been shown to be a powerful approach providing a robust behavioral recovery and reversal of side effects of the pulsatile administration of L-DOPA medication. The DA delivery strategy, on the other hand, aims at triple transduction of the TH, GCH1 and aromatic amino-acid decarboxylase (AADC) enzymes, and thereby provide a higher rate of conversion of DOPA to DA. Finally, transduction of AADC alone has been proposed as a means to improve the conversion of peripherally administered L-DOPA. As the basic scientific rationale behind these strategies are well understood and the results of the animal experiments are very encouraging, we are now entering into an exciting phase with increasing momentum toward the first clinical applications using this experimental therapy in patients suffering from PD.
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PMID:Restoration of the striatal dopamine synthesis for Parkinson's disease: viral vector-mediated enzyme replacement strategy. 1743 Jan 30

Parkinsonism is a clinical syndrome characterized by bradykinesia, hypo-/akinesia, muscular rigidity, and resting tremor, mainly caused by Parkinson's disease (PD). Symptoms of PD are due to a progressive loss of nigral neurons causing striatal dopaminergic denervation. However, nigral degeneration is only a part of the underlying synucleinopathy, and clinical symptoms go far beyond motor parkinsonism. Olfactory disturbances, fatigue, pain, autonomic dysfunction, sleep fragmentation, depression, and dementia with or without psychosis are frequently seen. The variability in the expression of these signs and symptoms, as discussed in this paper, might be explained by the specific topographical sequence of the pathology, depending on the extent and progression of the degenerative process at defined sites. Better insight in the clinicopathological correlations of this disease may help to further develop early diagnosis and adequate therapeutic strategies.
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PMID:Variability in the clinical expression of Parkinson's disease. 1785 36

Parkinson's disease is known to result from basal ganglia dysfunction. Electrophysiological recordings in parkinsonian patients and animals have shown the emergence of abnormal synchronous oscillatory activity in the cortico-basal ganglia network in the pathological condition. In addition, previous studies pointed out an altered response pattern during movement execution in the pallidum of parkinsonian animals. To investigate the dynamics of these changes during disease progression and to relate them to the onset of the motor symptoms, we recorded spontaneous and movement-related neuronal activity in the internal pallidum of nonhuman primates during a progressive dopamine depletion process. Parkinsonian motor symptoms appeared progressively during the intoxication protocol, at the end of which both animals displayed severe akinesia, rigidity and postural abnormalities. Spontaneous firing rates did not vary significantly after intoxication. During the early phase of the protocol, voluntary movements were significantly slowed down and delayed. At the same time, the neuronal response to movement execution was modified and inhibitory responses disappeared. In contrast, the unitary and collective dynamic properties of spontaneous neuronal activity, as revealed by spectral and correlation analysis, remained unchanged during this period. Spontaneous correlated activity increased later, after animals became severely bradykinetic, whereas synchronous oscillatory activity appeared only after major motor symptoms developed. Thus, a causality between the emergence of synchronous oscillations in the pallidum and main parkinsonian motor symptoms seems unlikely. The pathological disruption of movement-related activity in the basal ganglia appears to be a better correlate at least to bradykinesia and stands as the best candidate to account for this motor symptom.
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PMID:Late emergence of synchronized oscillatory activity in the pallidum during progressive Parkinsonism. 1788 Apr 1


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