Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nature of sleep is one of the major sources of dissatisfaction with the quality of life among patients with Parkinson's disease (PD). Difficult sleep maintenance (light and fragmented sleep) and difficulties with sleep initiation are the earliest and most frequent sleep disorders observed in these patients. Sleep disorders are also common in the normal elderly population, suggesting that normal aging may play a role in the etiology of sleep disorders in PD. Factor et al. examined the frequency of various sleep disorders in PD and compared them to those of normal elderly subjects. Sleep fragmentation and spontaneous daytime dozing occurred much more frequently in PD patients than in controls. Sleep fragmentation in PD may be due to an increased skeletal muscle activity, disturbed breathing and REM/non-REM variations of the dopaminergic receptor sensitivity. In parkinsonian patients who developed motor fluctuations (on-off phenomenon, wearing-off) during the day, other common sleep-related motor complaints including nocturnal akinesia, dystonia and painful cramps are observed. In a double-blind cross-over study, we compared the efficacy of a single dose of a chronic release formulation of levodopa/carbidopa (Sinemet CR) with that of a placebo in improving sleep-related motor disturbances in a group of 40 fluctuating PD patients. Sinemet CR significantly improved nocturnal akinesia and increased the hours of sleep in this group of patients. Initiation and maintenance of sleep are problems that may not be solved with antiparkinsonian treatment.
 ...
PMID:Sleep disorders in Parkinson's disease. 961 17

Forty-six patients who had 50 stereotactic procedures (36 pallidotomies and 14 thalamotomies) were assessed clinically with regard to akinesia, tremor, dyskinesias and dystonias, and underwent a stereotactic imaging study 6 months after surgery. The surgical results were rated as excellent, good/fair or no change, respectively, for each symptom, and were correlated to the volume and location of the stereotactic lesion. The effect of pallidotomy on akinesia was moderate and correlated with a larger lesion volume. The positive effect of pallidotomy on dyskinesias, dystonia and tremor was more pronounced and unrelated to the size of the lesion. The effect of thalamotomy on tremor was also unrelated to the lesion volume. The location of the pallidal lesions correlated only with the effect on akinesia: the more posterior the lesion in the pallidum, the better the effect on this symptom. For thalamotomy, there was no relationship between lesion location and effect on tremor. It is concluded that improvement in akinesia following pallidotomy is more difficult to obtain than improvement of the other parkinsonian symptoms, and this improvement requires a larger lesion which is located very posterior in the ventral pallidum.
 ...
PMID:Is there a relationship between size and site of the stereotactic lesion and symptomatic results of pallidotomy and thalamotomy? 971 32

We prospectively studied motor symptoms in 32 patients with CT- or MRI-proven acute pure parietal stroke. A transient, mild, 'pseudoparesis' of the hand (90%), was noted, improved by visual attention and prompting, associated with non-awareness of muscle power (53%), transient soft pyramidal signs (50%), unilateral akinesia (100%) and motor hemineglect (37%) in non-dominant lesions. Lower motoneurone-type atrophy was not observed in this acute phase. We called 'poikilotonia' the striking unpredictable variations in muscle tone, ranging from extreme hypertonia to hypotonia, found in all patients. When maintaining postures, patients showed large oscillations (100%), laterodeviation or levitation of the arm (60%), especially in the case of large or posterior lesions, or, occasionally (3%), motor persistence or even hemicatalepsy (3%). Limb kinetic and manipulatory apraxia, with inadequate organization and anticipation of motor sequences and synergies, motor arrests, perplexity, unrecognizable gestures and loss of bimanual coordination, was a constant finding (100%). Other apraxias (62%) and difficulty in copying intransitive gestures of the hand (84%) were associated with posterior lesions involving the supramarginal gyrus. When reaching towards objects, all patients showed abnormal anticipatory hand shaping, but visuomotor ataxia (3%) was only seen with bilateral posterior stroke. Sensory (70%) or pseudocerebellar (4%) ataxia, was seen in both anterior and posterior lesions. Avoidance behaviors (34%) were not uncommon, but had no localizing value. Of the dyskinesias, hand dystonia (84%) was frequent, but athetosis (16%), asterixis (15%), postural tremor (15%), myoclonus (9%) and stereotypia (9%), were uncommon. The abnormal eye movements were unilateral hypo-akinesia of exploratory saccades (43%), abnormal ipsilateral pursuit and contralateral optokinetic nystagmus in the case of posterior lesions, and oculomotor apraxia with bilateral posterior lesions. In conclusion, parietal motor syndrome can be recognized during bedside examination, and probably reflects the loss of multiple sensory feedback to motor programs, especially those directed to the extrapersonal space.
 ...
PMID:Parietal motor syndrome: a clinical description in 32 patients in the acute phase of pure parietal strokes studied prospectively. 987 53

Common marmosets show parkinsonian motor deficits following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration and develop dyskinesias during chronic L-dopa exposure. The D1 agonists A-77636 [(1R, 3S) 3-(1'-adamantyl)-1-aminomethyl-3, 4-dihydro-5, 6-dihydroxy-1H-2-benzopyran HCl] and A-86929 [(-)-trans 9, 10-hydroxy-2-propyl-4, 5, 5a, 6, 7, 11b-hexahydro-3-thia-5-azacyclopent-1-ena[c]phenanthrene hydrochloride] possess potent antiparkinsonian activity in the MPTP-treated marmoset and we now assess their influence on L-dopa-induced dyskinesias. MPTP-treated marmosets with stable motor deficits were treated with L-dopa plus carbidopa for 28 days to induce dyskinesias. Subsequently, they received A-86929 for 10 days, initially at 0.5 micromol/kg and then at 1.0 micromol/kg for a further 5 days. Several months later, L-dopa 12.5 mg/kg plus carbidopa 12.5 mg/kg was given orally twice daily for 7 days, followed by A-77636 1 micromol/kg for 10 days, and then both A-77636 and L-dopa plus carbidopa were given concurrently for 3 further days. In these L-dopa-primed animals, A-86929 effectively reversed akinesia and produced dose-dependent dyskinesias which were significantly less intense than those produced by L-dopa administration. A degree of behavioral tolerance was encountered, but antiparkinsonian activity was preserved and elicited behaviour was free of hyperkinesis and stereotypy and more naturalistic than that seen with L-dopa. After a week of twice-daily L-dopa dosing, administration of the long-acting D1 agonist A-77636 initially dramatically enhanced locomotion and reproduced dyskinesia with prominent dystonia, but after repeated administration of A-77636, dyskinesia and in particular chorea, gradually disappeared. Tolerance to locomotor stimulation greater than with A-86929 occurred, although activity remained significantly above baseline levels. There was a marked reduction in L-dopa-induced climbing, stereotypy and hyperkinesis and behaviour more closely resembled that of normal unlesioned marmosets. Upon reintroduction of L-dopa concurrently with continued A-77636 administration, dystonic, but virtually no choreic dyskinesias appeared and behaviour was once again free of stereotypy and hyperkinesis, contrasting dramatically with the presence of these behaviours along with abundant chorea when L-dopa is given alone. These results show a lesser liability of A-86929 and A-77636 to reproduce dyskinesia in L-dopa-primed MPTP-lesioned subjects while maintaining effective antiparkinsonian activity and producing a more naturalistic motor response. The differential effects of A-77636 on chorea and dystonia, with suppression of chorea and stereotypy on co-administration with L-dopa, may reflect an altered balance of activity in the direct and indirect striatofugal pathways. These results suggest a possible role for D1 agonists in the treatment of Parkinson's disease.
 ...
PMID:Actions of the D1 agonists A-77636 and A-86929 on locomotion and dyskinesia in MPTP-treated L-dopa-primed common marmosets. 1010 82

Pramipexole (SND 919), a potent non-ergot dopamine agonist, or placebo, was administered to 69 patients with advanced Parkinson's disease (33 received placebo, 36 received pramipexole) in a double-blind, randomized, multi-center study in which individually optimized doses of L-dopa plus a dopa decarboxylase inhibitor were associated with dyskinesia, "on-off" fluctuation, dystonia, akinesia, or end-of-dose deterioration. Study medication was titrated over 7 weeks to the maximal tolerated dose or to the maximal dose allowed by the study (5 mg/day in four divided doses). Dosing was maintained for 4 weeks and then tapered during the final week. Total score on the Unified Parkinson's Disease Rating Scale (UPDRS) for the intent-to-treat population was significantly improved in the pramipexole-treated group compared with the placebo-treated group (16.9 +/- 14.9 vs 9.0 +/- 16.1; p = 0.0184). By the end of maintenance, the mean reduction in L-dopa requirement was -150.7 mg for pramipexole-treated patients compared to -10.6 for placebo-treated patients. The most common adverse events (< 10%) were dizziness, insomnia, nausea, and postural hypotension. Aggravated parkinsonism occurred only after withdrawal of the study medication. Treatment with pramipexole in doses up to 5 mg/day was safe and well tolerated by patients with advanced Parkinson's disease.Copyright Lippincott-Raven Publishers
 ...
PMID:A double-blind, placebo-controlled, randomized, multi-center study of pramipexole in advanced Parkinson's disease. 1021 Aug 37

After 10 years of clinical practice (1987-1997), chronic thalamic deep brain stimulation (DBS) is considered to be effective in the treatment of drug-resistant parkinsonian tremor. DBS has produced few side-effects, which are usually reversible. More recently, DBS has been applied to other movement disorders (akinesia and rigidity, dyskinesias, dystonia), using new targets: internal pallidum, subthalamic nucleus. These targets have been selected on the basis of neurophysiological or anatomo-clinical data suggesting they could be effective. Control of L-Dopa peak-dose dyskinesias by thalamic ventralis intermedius nucleus (V.im.) stimulation has been reported by the Lille team, but not by the Grenoble team. We therefore re-examined all teleradioanatomical data of both teams, and compared them with the therapeutic effects. Location of 99 monopolar electrodes of thalamic stimulation, applied to treat parkinsonian tremor, has been retrospectively measured. The Lille team included 21 patients (22 electrodes); the Grenoble team included 52 patients (74 electrodes). L-Dopa dyskinesias were suppressed in all 9 patients in Lille, and improved clearly in only 8 out of 32 patients in Grenoble. The mean center of electrodes was significantly different between both teams, being deeper, more posterior and medial in Lille. This did not correspond to the coordinates of the V.im., but seems to be closer to those of the centromedian and parafascicular complex (CM-Pf), according to stereotactic atlases. Considering only the dyskinetic patients, the therapeutic effects on L-Dopa dyskinesias were related to the differences observed in the electrode position, but not to the team membership. Improvement of L-Dopa dyskinesias was significantly associated with deeper and more medial placement of electrodes. Retrospective analysis of ventriculographic data confirmed that the electrode position and therapeutic effects of DBS are strongly related. Our study suggested that CM-Pf stimulation could control both tremor and L-Dopa dyskinesias. This hypothesis is consistent with neuro-anatomical data showing that CM-Pf is connected to internal pallidum, the stimulation of which controls specifically L-Dopa dyskinesias.
 ...
PMID:[The effect of thalamic stimulation on levodopa induced dyskinesias--evaluation of a new target: the center parafascicular median]. 1048 44

The effects of the novel compound, (-)-OSU6162 ((S)-(-)-3-methylsulfonylphenyl-1-propylpiperidine), on rotational behavior induced by dopamine receptor agonists was investigated in common marmosets (Callithrix jacchus) with unilateral 6-hydroxydopamine lesions. (-)-OSU6162 per se displayed no effect on the animals' behavior. On the other hand, pretreatment with (-)-OSU6162 attenuated rotational behavior induced by apomorphine (apomorphini hydrochloridum), L-DOPA (3,4-dihydroxyphenylalanine), and the dopamine D2 receptor agonist, quinpirole (trans-(-)-4aR-4,4a, 5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolol[3,4-g]quinoline hydrochloride), without inducing motor impairment such as akinesia or dystonia. In addition, treatment with (-)-OSU6162 for 5 consecutive days almost completely abolished the rotational behavior provoked by apomorphine and produced a transient subsensitization of such apomorphine-induced effects after it was discontinued. Moreover, pretreatment with (-)-OSU6162 in two monkeys augmented the rotational behavior elicited by the dopamine D1 receptor agonists, SKF-81297 (R(+)-6-chloro-7,8,dihydroxy-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine hydrobromide) and A-77636 ((-)-(1R, 3S)-3-adamantyl-1-(aminomethyl)-3,4-dihydro-5, 6-dihydroxy-1H-2-benzopyran hydrochloride). The findings indicate that (-)-OSU6162 can exert indirect state-dependent effects that differentially affect dopamine D1 and dopamine D2 receptor agonist-induced behavior.
 ...
PMID:Motor effects of (-)-OSU6162 in primates with unilateral 6-hydroxydopamine lesions. 1068 84

Microelectrode-guided stereotactic operations performed in 29 parkinsonian patients allowed the recording of 86 cells located in the globus pallidus and 563 in thalamic nuclei. In the globus pallidus, the average firing rate was significantly higher in the internal (91+/-52 Hz) than in the external (60+/-21 Hz) subdivision. This difference was further accentuated when the average firing rate in the external subdivision was compared with that of the internal part of the internal subdivision (114+/-30 Hz). A rhythmic modulation in globus pallidus activities was observed in 19.7% of the cells, and this only during rest tremor episodes. In these cases, modulation frequency of unit activities was not statistically different from the rest tremor frequency (average: 4.6+/-0.5 vs 4. 4+/-0.4 Hz, respectively). In the medial thalamus, four types of unit activities could be defined. A sporadic type was mainly found in the parvocellular division of the mediodorsal nucleus (96.8% of the cells recorded) and in the centre median-parafascicular complex (74.2%). Two other types of activities characterized by random or rhythmic bursts fulfilling the extracellular criteria of low-threshold calcium spike bursts were concentrated in the central lateral nucleus (62.3%) and the paralamellar division of the mediodorsal nucleus (34.1%). These activities could be recorded independently of the presence of a rest tremor. When a tremor episode occurred, the rhythmic low-threshold calcium spike bursts had an interburst frequency similar to rest tremor frequency, although they were not synchronized with it. The fourth type, the so-called tremor locked, was also characterized by rhythmic bursts which, however, did not display low-threshold calcium spike burst properties. These bursts occurred only when a rest tremor was present and was in-phase with the electromyographic bursts. All tremor-locked cells were located in the centre median-parafascicular complex. In the lateral thalamus, cells exhibiting random or rhythmic low-threshold calcium spike bursts were found preponderantly in the ventral anterior nucleus (53.4%) and in the ventral lateral anterior nucleus (52.7%). Tremor-locked units were confined to the ventral division of the ventral lateral posterior nucleus (35.4%). None of the random or rhythmic low-threshold calcium spike bursting units responded to somatosensory stimuli or voluntary movements, either in the medial or in the lateral thalamus. The presence of low-threshold calcium spike bursts at the thalamic level, together with the paucity (8%) of responses to voluntary movements compared to what is found in normal non-human primates, demonstrate a pathological state of inhibition due to the overactivity of the internal subdivision of the globus pallidus units. Activities of the thalamic cells producing low-threshold calcium spike bursts are not synchronized with each other or with the tremor. However, this does not exclude a causal role of these activities in the generation of tremor. Indeed, it has been demonstrated that even random electrical stimulations of the rolandic cortex in parkinsonian patients induce tremor episodes, probably due to the triggering of rhythmic, low-threshold calcium spike-dependent, thalamocortical activities. Similarly, low-threshold calcium spike bursts could be at the origin of rigidity and dystonia through an activation of the supplementary motor area and of akinesia when reaching the pre-supplementary motor area. We conclude that the intrinsic oscillatory properties of individual neurons, combined with the dynamic properties of the thalamocortical circuitry, are responsible for the three cardinal parkinsonian symptoms.
 ...
PMID:Single-unit analysis of the pallidum, thalamus and subthalamic nucleus in parkinsonian patients. 1071 35

Chronic high frequency (130 Hz) stimulation (HFS) of the thalamic target Vim has replaced thalamotomy as a treatment of tremor of various origins and was extended to two other targets (Subthalamic nucleus (STN) and the medial pallidus (GPi)), since 1993 based on recent experimental data in rats and monkeys. STN appears to be a target of major interest, able to control the three cardinal symptoms and to allow the decrease or suppression of levodopa treatment, which then suppresses also levodopa induced dyskinesias. The mechanisms of action of HFS are not fully understood, but are definitely related to high frequency and are probably different depending on the target. Inhibition of cellular activity or of network functions could be induced, by jamming of a retroactive loop for tremor, or by shutdown of neurotransmitter release in STN. All cardinal symptoms are alleviated from tremor to akinesia and rigidity. The effects remain stable over more than five years chronic HFS of STN, as the method of choice when a surgical procedure is indicated for the treatment of Parkinson's disease and even more when a bilateral procedure is necessary. Recent data show that STN stimulation could be useful in the treatment of dystonia as well as some forms of epilepsies. It is therefore possible that DAS in STN as well as in other targets could become a potent therapeutic tool in the future for neurological disorders. The future of brain stimulation will depend on new technologies (new circuits, electrodes, web based programmers), waveforms (alternatives to square waves, random distribution), targets (hypothalamic nuclei, locus coeruleus) and indications (dystonia, epilepsy, eating disorders.
 ...
PMID:Future prospects of brain stimulation. 1076 16

Many patients who receive antipsychotic medications experience dystonia, akinesia, dyskinesia, and akathisia, collectively called Extrapyramidal Symptom Side Effects (EPS). The purpose of this study was to establish interrater reliability for a Nursing EPS Assessment Scale developed to focus on all four symptom areas. Twenty RNs and 12 patients participated in the instrument development studies. After several revisions, interrater reliability significance was demonstrated at the 0.01 level. It was concluded that the Nursing EPS Assessment Scale possessed good interrater reliability for nursing assessment of EPS.
 ...
PMID:Establishment of interrater reliability for a nursing Extrapyramidal Side Effects (EPS) Assessment Scale. 1082 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>