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)

The effect of chronic bilateral high-frequency stimulation of the subthalamic nucleus (STN) on levodopa-induced dyskinaesias was investigated in eight patients with fluctuating Parkinson's disease complicated by functionally disabling off-period dystonia. All of the patients also had severe diphasic and peak-dose chorea, so that it was possible to study the effect of high-frequency stimulation on the different types of levodopa-induced dyskinaesias. Off-period fixed dystonia was reduced by 90% and off-period pain by 66%. After acute levodopa challenge, high-frequency stimulation of the STN reduced diphasic mobile dystonia by 50% and peak-dose choreic dyskinaesias by 30%. The effect of bilateral high-frequency stimulation of the STN on the Unified Parkinson's Disease Rating Scale motor score had the same magnitude as the preoperative effect of levodopa. This allowed the levodopa dose to be reduced by 47%. The combination of reduced medication and continuous high-frequency stimulation of the STN reduced the duration of on-period diphasic and peak-dose dyskinaesias by 52% and the intensity by 68%. Acute high-frequency stimulation of the STN mimics an acute levodopa challenge, concerning both parkinsonism and dyskinaesias, and suppresses off-period dystonia. Increasing the voltage can induce repetitive dystonic dyskinaesias, mimicking diphasic levodopa-induced dyskinaesias. A further increase in voltage leads to a shift from a diphasic-pattern dystonia to a peak-dose pattern choreodystonia. Chronic high-frequency stimulation of the STN also mimics the benefit of levodopa on parkinsonism and improves all kinds of levodopa-induced dyskinaesias to varying degrees. Off-period dystonia, associated with neuronal hyperactivity in the STN is directly affected by stimulation and disappears immediately. The effect of chronic high-frequency stimulation of the STN on diphasic and peak-dose dyskinaesias is more complex and is related directly to the functional inhibition of the STN and indirectly to the replacement of the pulsatile dopaminergic stimulation by continuous functional inhibition of the STN. Chronic high-frequency stimulation of the STN allows a very gradual increase in stimulation parameters with increasing beneficial effect on parkinsonism while reducing the threshold for the elicitation of stimulation-induced dyskinaesias. In parallel with improvement of parkinsonism, the levodopa dose can be gradually decreased. As diphasic dystonic dyskinaesias are improved to a greater degree than peak-dose dyskinaesias, both direct and indirect mechanisms may be involved. Peak-dose choreatic dyskinaesias, associated with little evidence of parkinsonism and thus with low neuronal activity in the STN, are improved, mostly indirectly. Fixed off-period dystonia, mobile diphasic dystonia and peak-dose choreodystonia seem to represent a continuous clinical spectrum reflecting a continuous spectrum of underlying activity patterns of STN neurons.
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PMID:From off-period dystonia to peak-dose chorea. The clinical spectrum of varying subthalamic nucleus activity. 1035 65

Aside from physiological tremor, essential tremor (ET) is by far the most common cause of tremor in humans, affecting large numbers of individuals in every human population. The crude prevalence of ET has been conservatively estimated to be between 0.4% and 3.9%, although some estimates of the prevalence of ET among the elderly are higher than 20%. Essential tremor is the most prevalent adult-onset movement disorder, and is also regarded as one of the most common neurological disorders of adults, with a prevalence that is similar to or greater than that of stroke, Alzheimer disease, migraine headache, and lumbosacral pain syndromes. Essential tremor is as much as 20 times more prevalent than Parkinson disease.
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PMID:A new twist for stopping the shakes? Revisiting GABAergic therapy for essential tremor. 1040 81

High-frequency electrical stimulations of thalamic nuclei are currently used for the suppression of parkinsonian or essential tremor and for the relief of some types of intractable pain in man. However, the mechanisms by which such stimulations exert their therapeutic effects are essentially unknown. Attempts were made to provide some insight into these mechanisms by measuring the levels of the dopamine metabolites homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and met-enkephalin-like immunoreactivity in ventricular cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) or multiple sclerosis (MS) after a 30-minute therapeutic electrical stimulation of the ventralis intermedius nucleus of the thalamus. In nonstimulated control patients, the levels of these compounds did not significantly differ in two CSF samples taken 30 minutes apart. In stimulated patients, a decrease in dopamine metabolite levels associated with a relative increase in met-enkephalin-like immunoreactivity were observed in the CSF sample taken after the 30-minute stimulation as compared to the sample taken immediately before the stimulation. In contrast, the levels of 5-HIAA remained unaffected by the stimulation. These data confirmed the existence of negative interactions between dopaminergic and enkephalinergic systems in man similar to those previously demonstrated in rats. In addition, they suggest that alterations in dopaminergic or enkephalinergic neurotransmission might be involved in the therapeutic action of thalamic electrical stimulation in patients with parkinsonian symptoms and other patients.
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PMID:Opposite changes in dopamine metabolites and met-enkephalin levels in the ventricular CSF of patients subjected to thalamic electrical stimulation. 1044 54

Pallidotomy has been reported to improve parkinsonian symptoms, but its effects on levodopa-induced dyskinesia (LID) have not been thoroughly examined. We describe here the results of stereotactic, unilateral, posteroventral pallidotomy on LID in 42 patients (22 women), who were followed for up to 9 months. Their mean age was 60. 6+/-9.3 (range: 40-74), age at onset was 46.1+/-9.1 (range: 24-46), and duration of symptoms was 14.5+/-5.3 (range: 4-25) years. Three months following pallidotomy, the percent time with dyskinesia decreased from 37.0 to 17.3 (P<0.0001) and the percent time the patients were 'on' with dyskinesias decreased even more, from 71.0 to 22.9 (P<0.0001). Furthermore, the number of patients with troublesome (moderate to violent) dyskinesia had decreased from 36 (86%) prior to surgery to only 5 (12%) after surgery. The mean unified Parkinson disease rating scale (UPDRS) scores for LID-related disability and pain decreased from 1.95 to 0.74 (P<0. 0001) and from 1.02 to 0.17 (P<0.0001), respectively. Since the pre- and post-pallidotomy daily levodopa dosage remained essentially the same, the improvement in LID could not be attributed to a reduction in levodopa. Surgery-related complications occurred in eight (19%) patients, but none of them had persistent disability as a result of these complications. We conclude that pallidotomy is an effective and safe procedure in the treatment of medically intractable LID.
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PMID:Levodopa-induced dyskinesias treated by pallidotomy. 1050 Feb 64

Spontaneous magnetoencephalographic activity was recorded in awake, healthy human controls and in patients suffering from neurogenic pain, tinnitus, Parkinson's disease, or depression. Compared with controls, patients showed increased low-frequency theta rhythmicity, in conjunction with a widespread and marked increase of coherence among high- and low-frequency oscillations. These data indicate the presence of a thalamocortical dysrhythmia, which we propose is responsible for all the above mentioned conditions. This coherent theta activity, the result of a resonant interaction between thalamus and cortex, is due to the generation of low-threshold calcium spike bursts by thalamic cells. The presence of these bursts is directly related to thalamic cell hyperpolarization, brought about by either excess inhibition or disfacilitation. The emergence of positive clinical symptoms is viewed as resulting from ectopic gamma-band activation, which we refer to as the "edge effect." This effect is observable as increased coherence between low- and high-frequency oscillations, probably resulting from inhibitory asymmetry between high- and low-frequency thalamocortical modules at the cortical level.
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PMID:Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography. 1061 66

The purpose of this study was to analyze the effect of stereotactic neurophysiologically guided pallidotomy on health-related quality of life (QoL) of patients with Parkinson's disease (PD). Eleven patients with PD (seven men, four women; mean age, 57.2 years; mean duration of disease, 14 years) with motor complications refractory to medical therapy underwent unilateral pallidotomy. Clinical assessment was carried out a week before surgery and 4 months after the surgical procedure and was based on the Core Assessment Program for Intracerebral Transplantations protocol. QoL was measured by means of the PDQ-39. A set of rating scales (Hoehn & Yahr, Unified Parkinson's Disease Rating Scale, Schwab and England, Northwestern University Disability Scale of Walking, Abnormal Involuntary Movement Scale), timed tests, and self-evaluations of motor function and mood were applied. Improvement was found in dyskinesias (74%) and off-period disability (42%). Cardinal motor signs improved significantly (30%-59%). Four dimensions of the PDQ-39 (Mobility, ADL, Emotions, Bodily Pain) showed a significant improvement (p <0.01-0.001). The global effect on QoL, measured through the PDQ-39 Summary Index (35.3%; 95% confidence interval: 15.60-54.97), was also significant (p<0.01) but unrelated to major clinical changes. Pallidotomy significantly improves QoL in patients with advanced PD. QoL measurement provides relevant information that is probably not attainable by clinical assessment.
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PMID:Pallidotomy and quality of life in patients with Parkinson's disease: an early study. 1063 43

Parkinson's disease (PD) is a chronic progressive neurological disorder characterized by tremor, muscle rigidity, slowness of movement (bradykinesia), and gait instability. In early disease, PD is well managed in an office setting, however, as the disease progresses, a variety of syndromes may result in emergency department visits. The scenarios most likely to require an emergent evaluation are severe motor "off" periods with immobility, involuntary movements (dyskinesia), psychosis, acute confusion, panic disorder, and pain. Other less frequent presentations are also discussed. This article uses illustrative cases to provide a framework to discuss emergency department diagnosis and management issues in caring for these patients.
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PMID:Emergency department presentations of patients with Parkinson's disease. 1075 Sep 35

The achievements of Indian neurosurgeons in different fields of stereotactic surgery over the past decades have been discussed. This covers diverse areas like Parkinson's disease, abnormal movements, cerebral palsy, spasticity, pain relief, and sedative and functional neurosurgery. Recently, technological advances have made stereotactic surgery useful in many fields like deep biopsies, minimally invasive surgery and radiosurgery. Apart from these areas, there is still a big scope for revival of surgery on deep structures of the brain, as was practised earlier. This will lead to newer knowledge about brain function and also give relief to many patients. The future is bright, provided Indian neurosurgeons show a paradigm shift in their thinking and bring out new ideas. Interaction with other scientific disciplines is necessary in the future if new knowledge has to be added or new techniques have to be devised.
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PMID:Stereotactic surgery in India: the past, present and the future. 1075 7

Pain, defined as an unpleasant or distressing sensory experience, has been recognized as feature of Parkinson's disease (PD) since the first descriptions of the disorder. Pain is estimated to occur in approximately 40% of patients with PD, and in a minority of individuals becomes severe enough to overshadow the motor symptoms of the disorder. Recent studies based on patients' descriptions of pain have enabled a classification of painful sensations into 1 or more of 5 categories: musculoskeletal pain, neuritic or radicular pain, dystonia-associated pain, primary or central pain, and akathitic discomfort. The existence of a central pain syndrome, intrinsic to PD, finds support in a collection of case reports, but the precise mechanism is unknown, and a correlation with pathology has not been made. This review describes the clinical features of the pain syndromes in PD, and provides a framework for evaluating, classifying, and treating painful symptoms in PD.
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PMID:Pain in Parkinson's disease. 1078 30

Neuronal nicotinic acetylcholine receptors (nAChRs) are a class of ion channels with significant potential as molecular targets for the design of drugs to treat a variety of CNS disorders. The discovery that neuronal nAChRs are further subdivided into multiple subtypes suggests that drugs which act selectively at specific nAChR subtypes might effectively treat Parkinson's disease (PD), Alzheimer's disease (AD), schizophrenia, ADHD, depression, anxiety or pain without the accompanying adverse side effects associated with non-selective agents such as nicotine (1) and epibatidine. Altinicline (SIB-1508Y) is a novel, small molecule designed to selectively activate neuronal nAChRs and is undergoing clinical evaluation for the treatment of PD. It was selected from a series of compounds primarily on the basis of results from functional assays, including (a) measurement of Ca2+ flux in stable cell lines expressing specific recombinant human neuronal nAChR subtypes; (b) determination of in vitro and in vivo neurotransmitter release; (c) in vivo models of PD. Biological data on both altinicline and the series of compounds from which it was selected are reported.
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PMID:Recombinant human receptors and functional assays in the discovery of altinicline (SIB-1508Y), a novel acetylcholine-gated ion channel (nAChR) agonist. 1081 48


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