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)

Intrathecal baclofen (ITB) therapy is widely used in the management of spastic hypertonia and dystonia resulting from a multitude of conditions that present with upper motor neuron syndrome signs, such as cerebral palsy, stroke, brain and spinal injuries, and multiple sclerosis. We report successful management of posttraumatic hemiballismus and dystonia with ITB in a 43-yr-old man who sustained a traumatic brain injury secondary to an assault in 1978. He subsequently developed hemiballismus in the right lower limb and dystonia of the distal right upper limb spreading proximally to involve the shoulder. The ballistic movement of the lower limb was severe enough to cause the patient to fall out of his chair and limit his ability to perform activities of daily living safely. He had been on various oral medications and received botulinum toxin and phenol injections, but none alleviated the symptoms. The patient elected to receive the ITB pump. Before ITB, he had an average of 10-12 ballism episodes of the right lower limb per hour. During observed episodes, the right hip would flex up to about 90 degrees, with a fully extended knee. After ITB pump implantation and upward dose titration, the frequency of ballistic right leg movements decreased to about three per day, and the right hip flexed to only 30 degrees. In addition, there was increased ability to isolate individual distal joint movements in the right lower limb. The patient currently receives 202.4 microg/day ITB and continues to benefit almost 6 yrs after ITB pump implantation. This report highlights the emerging role of ITB in managing movement disorders other than dystonia spastic hypertonia and dystonia.
 ...
PMID:Successful treatment of posttraumatic hemiballismus with intrathecal baclofen therapy. 1692 90

We introduced an intramuscular injection of botulinum toxin type A (hereafter, BTX-A) in 5 cases of cervical dystonia (CD) with generalized muscular hypertonia (GMH). The patients all had severe motor and intellectual disabilities (SMID). The initial injections (first and second) of BTX-A exerted a focal muscular relaxant effect in all 5 cases. It is interesting that they decreased hypertonia in the lower extremities, which resulted in an improved activity of daily living (ADL) in 4 cases (80%). This fact reveals the involvement of many muscles in regard to CD and GMH, especially in patients with severe cerebral palsy. As for adverse effects, a mild increase of saliva and cough indicated transient misswallowing in 2 cases (40%) and changes in the pattern of head movement and posture in 2 cases (40%). These effects were all mild and did not disturb ADL in any patient. BTX-A is considered to be safer and worthier of trying to decrease complaints related to CD and GMH than we expected. Furthermore, a modified Tsui's score cannot explain the many benefits from BTX-A in the treatment of SMID. For a reliable assessment of BTX-A therapy used to treat CD and GMH, especially in persons with SMID, more expressible and specific assessment methods will need to be established.
 ...
PMID:[Initial efficacy of intramuscular injection of botulinum toxin type A against cervical dystonia and general muscular hypertonia in persons with severe motor and intellectual disabilities]. 1709 61

The most hazardous manganese exposures occur in mining and smelting of ore. Recently, the poisoning has been frequently reported to be associated with welding. In occupational exposure, manganese is absorbed mainly by inhalation. Manganese preferentially accumulates in tissues rich in mitochondria. It also penetrates the blood brain barrior and accumulate in the basal ganglia, especially the globus pallidus, but also the striatum. Manganese poisoning is clinically characterized by the central nervous system involvement including psychiatric symptomes, extrapyramidal signs, and less frequently other neurological manifestations, Psychiatric symptomes are well described in the manganese miners and incrude sleep disturbance, disorientation, emotional lability, compulsive acts, hallucinations, illusions, and delusions. The main characteristic manifestations usually begin shortly after the appearance of these psychiatric symptomes. The latter neurological signs are progressive bradykinesia, dystonia, and disturbance of gait. Bradykinesia is one of the most important findings. There is a remarkable slowing of both active and passive movements of the extremities. Micrographia is frequently observed and a characteristic finding. The patients may show some symmetrical tremor, which usually not so marked. The dystonic posture of the limbs is often accompanied by painfull cramps. This attitudal hypertonia has a tenndency to decrease or disappear in the supine position and to increase in orthostation. Cog-wheel rigidity is also elisited on the passive movement of all extremities. Gait disturbance is also characteristic in this poisoning. In the severe cases, cook gait has been reported. The patient uses small steps, but has a tendency to elevate the heels and to rotate them outward. He progress without pressing on the flat of his feet, but only upon the metatarsophalangeal articulations, mainly of the fourth and fifth toes. Increased signal in T1-weighted image in the basal ganglia has been reported in patients with the poisoning. Thus, increasd signal intensities as a target site dose can be a more useful biomakers of the manganese than other biological indicies such as ambient manganese concentration or blood manganese concentration on individual basis. Manganese poisoning ultimately becomes chronic. However, if the disease is diagnosed while still at the early stages and the patient is removed from exposure, the course may be reversed. Once well established, it becomes progressive and irreversible, even when exposure is terminated. Levodopa therapy is not effective for the management of manganese poisoning. Levodopa unresponsiveness may be usefull to distinguish manganese-induced parkinsonism from Parkinson disease.
 ...
PMID:[Occupational neurotoxicology due to heavy metals-especially manganese poisoning]. 1758 89

Intrathecal baclofen (ITB) has evolved into a standard treatment for severe spasticity of both spinal and cerebral origin. The accumulated promising data from reported series of patients receiving ITB therapy together with the fact that spastic hypertonia commonly coexists with other neurological disorders have constituted a solid basis for offering this kind of treatment to patients suffering from other movement disorders. These include motor disorders such as dystonia, amyotrophic lateral sclerosis, status dystonicus, Hallervorden-Spatz disease, Freidreich's ataxia, "stiff-man" syndrome, but also vegetative states after revere brain trauma, anoxic encephalopathy or other pathology and more recently, various chronic pain syndromes. In this article, on the basis of the established applications of ITB therapy, we review the important emerging indications of this rewarding neuromodulation method and attempt to identify its future potential beneficial role in other chronic and otherwise refractory neurological disorders.
 ...
PMID:Intrathecal baclofen in current neuromodulatory practice: established indications and emerging applications. 1769 70

In children, increased tone in a joint can be caused by spasticity, dystonia, rigidity, or mechanical limitations such as contracture. Determination of the cause of hypertonia is important for selection of appropriate therapy, but distinction between the types of hypertonia is difficult in a clinical setting. We present results of a pilot test of the use of a portable surface electromyography (EMG) device for the evaluation of hypertonia. Seven children 5-17 years of age with hypertonia due to cerebral palsy were each examined by 6 clinicians, both with and without the use of surface EMG. The use of surface EMG resulted in an increase in interrater agreement as well as an increase in the self-reported confidence of the clinicians in their assessment. These results support the importance of further testing of surface EMG as an adjunct to the clinical examination of childhood hypertonia.
 ...
PMID:Use of surface electromyography (EMG) in the diagnosis of childhood hypertonia: a pilot study. 1834 54

Hypertonia, which is characterized by stiff gait, abnormal posture, jerky movements, and tremor, is associated with a number of neurological disorders, including cerebral palsy, dystonia, Parkinson's disease, stroke, and spinal cord injury. Recently, a spontaneous mutation in the gene encoding trafficking protein, kinesin-binding 1 (Trak1), was identified as the genetic defect that causes hypertonia in mice. The subcellular localization and biological function of Trak1 remain unclear. Here we report that Trak1 interacts with hepatocyte-growth-factor-regulated tyrosine kinase substrate (Hrs), an essential component of the endosomal sorting and trafficking machinery. Double-label immunofluorescence confocal studies show that the endogenous Trak1 protein partially colocalizes with Hrs on early endosomes. Like Hrs, both overexpression and small-interfering-RNA-mediated knockdown of Trak1 inhibit degradation of internalized epidermal growth factor receptors through a block in endosome-to-lysosome trafficking. Our findings support a role for Trak1 in the regulation of Hrs-mediated endosomal sorting and have important implications for understanding hypertonia associated with neurological disorders.
 ...
PMID:Hypertonia-associated protein Trak1 is a novel regulator of endosome-to-lysosome trafficking. 1867 23

A 32 years female presented with gradually progressive dysarthria, dysphagia, oromandibular dystonia and mild generalized weakness. She had several episodes of acute psychotic behavior. She had abnormal saccadic eye movements, generalized hypertonia and exaggerated jerks in upper limbs. She was previously treated in a peripheral hospital for severe vomiting and diarrhea. MRI of brain revealed symmetrical T-2 weighted hyperintensities in bilateral putaminal and caudate region along with pons and midbrain suggesting demyelination due to a metabolic insult. Her power improved gradually over days and the dysarthria, dysphagia and oromandibular dystonia improved gradually over several weeks with supportive measures but the psychiatric manifestations are still persisting.
 ...
PMID:Oromandibular dystonia and persistent psychiatric symptoms in extra-pontine myelinolysis. 1870 90

Hyperekplexia is characterised by neonatal hypertonia and an exaggerated startle reflex in response to acoustic or tactile stimuli. Genetic analysis of this disorder has revealed mutations in genes for several postsynaptic proteins involved in glycinergic neurotransmission, including the glycine receptor (GlyR) alpha1 and beta subunits, gephyrin and collybistin. However, new research suggests that mutations in the gene encoding the presynaptic glycine transporter GlyT2 are a second major cause of human hyperekplexia, as well as congenital muscular dystonia type 2 (CMD2) in cattle. These findings raise the intriguing possibility that both presynaptic and postsynaptic causes of disease might also exist in related disorders, such as idiopathic generalised epilepsies, where mutations in inhibitory GABA(A) receptor subunit genes have already been identified.
 ...
PMID:The genetics of hyperekplexia: more than startle! 1870 91

Spasticity is usually observed along with paralysis, hyperreflexia, Babinski sign and abnormal associated movements associated with dysfunction of central motor tracts. In spasticity, exaggeration of the stretch reflex results in increased resistance during passive movements. Therefore, spasticity is pathophysiologically described as increased muscle tone whose pathognomonic sign is decreased passivity. Resistance is more strongly felt during rapid passive movements than during slow movements. The resistance felt at the beginning of the passive movement abruptly diminishes, which is well known as the clasp-knife phenomenon. Another character of spasticity is the distribution of the increment in the muscle tone. Not only rigidity, dystonia, and muscle stiffness demonstrating increased muscle tone, but also Gegenhalten and contracture of joint with normal muscle tone should be differentiated. No neurophysiological parameters reflect the degree of spasticity in a strictly parallel fashion. However, neurophysiological examinations provide some supportive objective data. Surface electromyography is useful to distinguish spasticity from rigidity and other conditions with increase muscle tone. The increased amplitude ratio and the decreased threshold ratio of the H-wave to the M-wave, and increased amplitude and persistence of the F-wave are observed the patients with spasticity. Magnetic stimulation is a useful tool to detect corticospinal tract lesions that induce leading to spasticity. Transcranial magnetic stimulation, magnetic brainstem stimulation, and magnetic spinal motor root stimulation are used to examine the entire motor pathway. Since positive correlation between spasticity and shortening of the silent period is reported, many investigations including paired-pulse magnetic stimulation will be necessary for understanding pathophysiology of spasticity. Patients with mild and reversible spasticity are usually treated with medications. Significant variations exist in the use of these therapies, because the treatments often depend on the clinicians' experience. It will be necessary to clarify the action mechanism of drugs, to develop new effective drugs, and to perform randomized controlled trails so that clinicians can select the optimal medication based on evidence.
 ...
PMID:[Clinical signs, neurophysiological evaluation, and medication of spasticity--review]. 1911 Jul 51

It is often assumed that co-contraction of antagonist muscles is responsible for increased resistance to passive movement in hypertonic dystonia. Although co-contraction may certainly contribute to hypertonia in some patients, the role of reflex activation has never been investigated. We measured joint torque and surface electromyographic activity during passive flexion and extension movements of the elbow in 8 children with hypertonic arm dystonia due to dyskinetic cerebral palsy. In all cases, we found significant phasic electromyographic activity in the lengthening muscle, consistent with reflex activity. By correlating activation with position or velocity of the limb, we determined that some children exhibit position-dependent activation, some exhibit velocity-dependent activation, and some exhibit a mixed pattern of activation. We conclude that involuntary or reflex muscle activation in response to stretch may be a significant contributor to increased tone in hypertonic dystonia, and we conjecture that this activation may be more important than co-contraction for determining the resistance to passive movement.
 ...
PMID:Hypertonia in childhood secondary dystonia due to cerebral palsy is associated with reflex muscle activation. 1935 33


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