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

A 10-year-old girl presented with progressive dystonia with diurnal fluctuation. Response to low dose L-Dopa was dramatic and sustained with no complications. Recurrence of symptoms was observed on attempted withdrawal. Because of the dramatic response to therapy, dopa-responsive dystonia must be considered in the differential diagnosis of disorders presenting as gait disorders in childhood.
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PMID:Dopa responsive dystonia with diurnal fluctuation (Segawa's syndrome). 809 Jan

A group of four monkeys was rendered parkinsonian with the toxin MPTP. They were then treated chronically with L-DOPA/benserazide 50/12.5 mg/kg given orally daily for 2 months. This dose produced a striking antiparkinsonian effect, but all animals manifested dyskinesia. A series of agents acting primarily on neurotransmitters other than dopamine were then tested in combination with L-DOPA to see if the dyskinetic movements would be modified. Several drugs, including clonidine, physostigmine, methysergide, 5-MDOT, propranolol, and MK-801, markedly reduced the dyskinetic movements but at the cost of a return of parkinsonian symptomatology. However, yohimbine and meperidine reduced predominantly the dyskinetic movements. Baclofen was also useful in one monkey against a more dystonic form of dyskinesia. Atropine converted the dystonic movements into chorea.
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PMID:Effect of nondopaminergic drugs on L-dopa-induced dyskinesias in MPTP-treated monkeys. 810 50

Forty-one patients with Parkinson's disease and severe dyskinesias were analyzed retrospectively to determine if some general principles would emerge to aid physicians handling this complication of treatment. Dyskinesia type (high dopa chorea [HDC], low dopa chorea [LDC], high dopa dystonia [HDD], and low dopa dystonia [LDD]) predicted response to treatment and whether or not levodopa dose reduction would benefit dyskinesias without producing unacceptable "offs." High dopa chorea improved best but at the expense of increased "off" time, followed by LDD, HDD, and LDC. Levodopa reduction was an acceptable strategy in ameliorating HDC and LDD only. Adjunctive therapy benefited all dyskinesia types, although the majority of patients (12/17) helped by selegiline had LDD or LDC. Generally, low doses of dopamine agonists were helpful (bromocriptine < 20 mg/day; pergolide < 2 mg/day). When adding adjunctive therapy (except for selegiline or controlled-release carbidopa/levodopa), concomitant reduction in daily dose of levodopa was not an effective strategy to decrease dyskinesias. Serial trials of multiple drug regimens are useful in these patients.
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PMID:An analysis of treatment options and outcome in patients with Parkinson's disease and severe dyskinesias. 814 65

The pathophysiology of the movement disorders arising from basal ganglia disorders has been uncertain, in part because of a lack of a good theory of how the basal ganglia contribute to normal voluntary movement. An hypothesis for basal ganglia function is proposed here based on recent advances in anatomy and physiology. Briefly, the model proposes that the purpose of the basal ganglia circuits is to select and inhibit specific motor synergies to carry out a desired action. The direct pathway is to select and the indirect pathway is to inhibit these synergies. The clinical and physiological features of Parkinson's disease, L-DOPA dyskinesias. Huntington's disease, dystonia and tic are reviewed. An explanation of these features is put forward based upon the model.
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PMID:Physiology of basal ganglia disorders: an overview. 822 80

We report a case of a 67-year-old woman who had dopa-responsive dystonia of late onset with diurnal fluctuations. She was well until the age of 65 years, when she noted the insidious onset of involuntary movements mainly involving the neck and trunk. She had no family history of movement disorders and had never received neuroleptics. Two years after her symptoms began, she visited our clinic. Neurological examination revealed slow repetitive extension and flexion movements of the neck and trunk, and irregular slow movements involving the mouth, tongue and limbs. The cranial nerves, cerebellar function, muscle strength, deep reflexes and sensory function were intact. Clinically and electromyographically, dystonia was characteristic of her involuntary movements. No parkinsonian features were present. The involuntary movements showed diurnal fluctuations that improved after sleep and the administration of L-DOPA and trihexyphenidyl. Dopamine receptor blocking agents aggravated her condition. Routine blood chemistry including copper metabolism, cerebrospinal fluid findings, and brain CT scan were all normal. Dopa-responsive dystonia is characterized by onset in childhood or adolescence and is frequently associated with parkinsonian features. Our patient had non-hereditary neck and trunk dystonia of late onset that responded to L-DOPA. Her disorder may constitute a specific form of dopa-responsive dystonia.
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PMID:[A form of dopa-responsive dystonia of late onset with diurnal fluctuations]. 833

A study of parkinsonian signs was conducted in 29 patients fulfilling Lees' criteria for progressive supranuclear palsy, or Steele-Richardson-Olszewski syndrome, and 2 patients with incomplete ophthalmoplegia but 4 other cardinal features. The patients comprised 17 men and 14 women and their ages at onset ranged from 52 to 77 yrs (mean, 65.1). Parkinsonian features: akinesia, rigidity or resting tremor were present in 29 cases and appeared a mean 0.5 yrs (range 0-3) after onset. In 9 cases (29 p. 100), the parkinsonian features were similar to those of Parkinson's disease, including a resting tremor in 6 cases. The parkinsonian syndrome was initially the sole manifestation in 7 patients, who were diagnosed as having Parkinson's disease. Levodopa was effective in 6 cases, for more than a year in 3. In the other 20 cases (64 p. 100) parkinsonian signs were atypical, usually with a predominantly axial distribution. Levodopa or dopamine agonists showed transient efficacy in 6 cases. In most patients, the treatment with levodopa (n = 27) or bromocriptine (n = 15) was well tolerated. Only two disclosed akinetic fluctuations. The other main clinical features included postural instability with falls (n = 30; mean time after onset 1.8 yrs, range 0-7 yrs); characteristic ophthalmoplegia (n = 29; mean interval 4.4., range 0-18 yrs); intellectual decline and/or frontal signs (n = 22; mean interval 2.4, range 0-8 yrs); axial rigidity (n = 18; mean interval 4.2, range 1-11 yrs); pseudo-bulbar palsy (n = 18; mean interval 3, range 0-8 yrs). An upper limb dystonia was present in an autopsy-proven case.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Parkinsonian features of Steele-Richardson-Olszewski syndrome]. 833 59

Parkinsonism without dystonia has been reported in several older members of families with DRD. This raises the question whether such patients represent a variant in the clinical picture of DRD, or a separate disease, IP. We employed 6-FD PET to study the nigrostriatal dopaminergic function in a woman with typical DRD and two of her relatives with late-onset parkinsonism. These two had an excellent and prolonged therapeutic response to small doses of L-DOPA, without complications. We found that the dystonic patient and the women with "benign" parkinsonism had normal striatal 6-FD uptake. In conjunction with other clinical evidence, our PET study indicates that the biochemical lesion in these members may be "proximal" to dopa decarboxylase, as is suggested in DRD patients. We conclude that the adult-onset parkinsonism in DRD families is due to the same pathophysiological mechanism as the childhood-onset dystonia in the disease. DRD may display substantial clinical heterogeneity depending on the age of onset.
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PMID:Clinical heterogeneity of dopa-responsive dystonia: PET observations. 842 Jan 95

Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-DOPA), the rate-limiting step in the biosynthesis of dopamine. Recently, we described a point mutation in hTH (Q381K) in a family of two siblings suffering from progressive L-DOPA-responsive dystonia (DRD), representing the first reported mutation in this gene. We here describe the cloning, expression and steady-state kinetic properties of the recombinant mutant enzyme. When expressed by a coupled in vitro transcription-translation system and in E. coli, the mutant enzyme represents a kinetic variant form, with a reduced affinity for L-tyrosine. The 'residual activity' of about 15% of the corresponding wild-type hTH (isoform hTH1), at substrate concentrations prevailing in vivo, is compatible with the clinical phenotype of the two Q381K homozygote patients carrying this recessively inherited mutation.
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PMID:Recessively inherited L-DOPA-responsive dystonia caused by a point mutation (Q381K) in the tyrosine hydroxylase gene. 852 10

Four patients with neurological Wilson's disease were investigated using magnetic resonance imaging (MRI) and positron emission tomography (PET). All patients had dystonia as their major clinical manifestation but also had dysarthria and at the presentation of the disease had choreoathetoid movements in at least one limb. A multitracer approach with PET was used to visualize various aspects of dopaminergic function; [11C]-(+)-nomifensine (NMF), [11C]raclopride (RAC) and [11C]-L-DOPA (one patient). Correlation analysis of RAC and NMF binding as well as putamen/caudate uptake ratios showed corresponding reductions. The patient investigated with [11C]-L-DOPA had a normal striatal uptake. Generally, structural changes as shown by MRI corresponded to reductions both in NMF and RAC binding. There was no evident correspondence between PET findings and the severity of clinical symptoms seen in the individual patient. In two patients with discrete neurological impairment at the time of investigation, PET showed serious presynaptic dopaminergic lesions in the putamen. Our data suggest that the striatal degeneration seen in Wilson's disease comprises a complex pathology involving both afferent and efferent projections. The discrete neurological impairment seen in some patients with gross striatal pathology might be due to concomitant lesions in functionally counteracting basal ganglia circuits.
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PMID:Neurological Wilson's disease studied with magnetic resonance imaging and with positron emission tomography using dopaminergic markers. 855 11

Chronic electrical subthalamic nucleus (STN) stimulation is under investigation for alleviating parkinsonian symptoms. STN alterations may carry the risk of provoking abnormal involuntary movements (AIMs). We took advantage of the reversibility of the stimulation technique to assess the possibility of inducing AIMs, using different electrical variables with or without concomitant levodopa intake. Above a given threshold voltage, stimulation could induce contralateral distal mobile AIMs or hemiballism in the off-drug condition in two patients. AIMs occurred after a latency that varied from a few minutes up to several hours after switching on the stimulator. Hemiballism immediately disappeared upon switching off the stimulator. In these patients, levodopa had never provoked that type of AIMs before surgery. Levodopa-induced AIMs were not modified by electrical stimulation, but off-phase dystonia disappeared in one patient. Stimulation of the STN induced AIMs that resembled both those observed following spontaneous lesions of the STN and levodopa-induced diphasic AIMs in parkinsonian patients. As electrical stimulation provoked AIMs and antiparkinsonian benefit occurred with different electrical variables and different timing, the mechanisms responsible for these two effects could be distinct.
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PMID:Abnormal involuntary movements induced by subthalamic nucleus stimulation in parkinsonian patients. 872 37


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