Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report describes a case of metrizamide encephalopathy with persistent disturbance of consciousness and extrapyramidal symptoms. These two conditions have rarely been reported among the various adverse effects of metrizamide. An 11-year-old girl had been in almost good health until she was ten years old, at which time she received a ventriculo-peritoneal shunt operation, suffering from hydrocephalus of unknown etiology. At the age of eleven, she was admitted to our hospital due to hydrocephalus recurrence. She was examined by metrizamide shunt-gram (1200 mg iodide/4 ml). On the next day, she became drowsy. The CT scan disclosed the periventricular penetration of metrizamide into the medial part of the thalamus and the caudate nucleus. Thirteen days later, disturbance of consciousness continued, and extrapyramidal symptoms, that is, rigo-spasticity and postural tremor, were observed. Oral administration of L-threo-DOPS, the direct precursor of noradrenaline, was effective against the persistent disturbance of consciousness and L-DOPA was effective against the extrapyramidal symptoms. She soon recovered almost to normal and no neurological deficit remained. We thus conclude that the CT scan findings and effects of L-threo-DOPS and L-DOPA suggest that metrizamide encephalopathy in this case were respectively due to its periventricular penetration into the medial part of the thalamus and the caudate nucleus, and the resultant deficiency of the ascending noradrenergic reticular activating system and the nigrostriatal dopaminergic system.
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PMID:[Metrizamide encephalopathy in a child with hydrocephalus--effects of L-threo-DOPS on persistent disturbance of consciousness and L-dopa on extrapyramidal symptoms]. 314 37

The adamantane derivative memantine (1-amino-3,5-dimethylaminoadamantane, D-145, Akatinol) is clinically used as well in the therapy of neurogenic motor diseases (e.g. spasticity) as in the treatment of cerebral disorders like coma, cerebrovascular and geronto-psychiatric disturbances. The aim of the paper is to summarize experimental evidences that may help to explain the clinical observations. Biochemical, pharmacological, and electrophysiological studies show that memantine interferes with the metabolism of the transmitters dopamine, noradrenaline (norepinephrine), and serotonin and modulates synaptic transMission. In order to explain the antispastic activity of memantine, a spinal action must be assumed in addition to the supraspinal effect on transmitter systems. Since memantine reduces the membrane resistance as well as the membrane conductance of sodium, potassium, and chloride ions, it is very likely that memantine Is directly involved in the generation of action potentials.
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PMID:[Pharmacodynamics and pharmacokinetics of memantine]. 635 2

The purpose of the present study was to investigate the potential impairment of normal motor function following chronic selective serotonin reuptake inhibitor treatment that may result from sensitisation of sigma receptors. Rats were chronically treated with either sertraline, citalopram, paroxetine or fluvoxamine and a selective sigma receptor ligand, di-o-tolylguanidine (DTG), for 28 days. All animals then received an acute intra-rubral injection of either DTG or saline. Following the direct injection of DTG into the red nucleus, rats chronically treated with DTG exhibit a maximal behavioural response characterised as a pronounced dystonia. Animals chronically treated with sertraline and citalopram elicited a response similar to that of control animals following the acute DTG challenge, whereas chronic treatment with paroxetine and fluvoxamine significantly decreased and increased the dystonic response, respectively. Facial spasticity and vacuous chewing movements were associated with, and reflected the extent of, the DTG-induced dystonia. Changes in regional biogenic amine concentrations were also determined. The concentrations of serotonin and noradrenaline were determined in the brain stem and cerebellum following the intra-rubral injection of either saline or DTG in animals that had been chronically treated with a selective serotonin reuptake inhibitor or DTG. There was a significant increase in serotonin concentration in the brain stem as a result of chronic DTG and fluvoxamine treatments. The increase in serotonin correlated with the reported potentiation of dystonia in animals that received 28 days treatment with these drugs. The potentiation of dystonia following chronic DTG and fluvoxamine treatments suggests that these drugs sensitise the sigma2 receptors, an effect that does not appear to be shared by citalopram, sertraline or paroxetine.
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PMID:The functional sensitisation of sigma receptors following chronic selective serotonin reuptake inhibitor treatment. 961 47

The Rett syndrome (RS) is a peculiar, sporadic, atrophic disorder, almost entirely confined to females. After the first six months of life there is developmental slowing with reduced communication and head growth for about one year. This is followed by a rapid destructive stage with severe dementia and loss of hand skills (with frequent hand wringing), apraxia and ataxia, autistic features and irregular breathing with hyperventilation. Seizures often supervene. Subsequently there is some stabilization in a pseudo-stationary stage during the preschool to school years, associated with more emotional contact but also abnormalities of the autonomic and skeletal systems. After the age of 15-20 years, a late motor deterioration occurs with dystonia and frequent spasticity but seizures become milder. RS has generally been considered an X-linked disorder in which affected females represent a new mutation, with male lethality. Linkage studies suggested a critical region at Xq28. In 1999, mutations in the gene MECP2 encoding X-linked methyl cytosine-binding protein 2 (MeCP2) were found in a proportion of Rett girls. This protein can bind methylated DNA. Analyses are leading to much further investigation of mutants and their effects on genes. Neuropathological and electrophysiological studies of RS are described. Description of neurometabolic factors includes reduced levels of dopamine, serotonin, noradrenaline and choline acetyltransferase (ChAT) in brain, also estimation of nerve growth factors, endorphin, substance P, glutamate and other amino acids and their receptor levels. The results of neuroimaging are surveyed, including volumetric magnetic resonance imaging (MRI) and positron emission tomography (PET).
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PMID:Rett syndrome: review of biological abnormalities. 1125 89

When spasticity produces a clinical disability by interfering with posture, motor capacity, nursing or daily living activities, medical treatment is recommended. It is mainly indicated when the muscle overactivity is diffusely distributed and should be implemented early, to prevent permanent musculoskeletal deformities or contractures. A pharmacological approach relies on the use of drugs which modulate neurotransmitters acting at the cortico-spinal level (GABA, glycine, glutamate, noradrenaline, serotonin). The aim of this treatment is to decrease spinal reflex excitability by reducing the release of excitatory neurotransmitters, or by potentiating the activity of inhibitory inputs. Evaluation of the efficacy of these drugs is determined by the therapeutic objectives which may be biomechanical, or functional. Diazepam increases presynaptic inhibition by stimulating GABA(A) receptors in the brainstem and spinal cord. In double-blind studies of patients with spinal cord lesions, antispastic efficacy has been shown, but side-effects are common. Baclofen stimulates GABA(B) receptors inducing a suppression of excitatory neurotransmitter release. Antispastic efficacy is sufficiently documented, but no definite effects on ambulation or activities of daily living have been proved. Tizanidine has an alpha2-agonist activity (at spinal and supraspinal level) and decreases the presynaptic activity of excitatory interneurones. The main clinical effects are a reduction in tonic stretch, polysynaptic reflexes, and co-contraction, with fewer side-effects but no definite functional change. The efficacy of several other antispastic drugs is documented in a few controlled studies, but the majority of information arises from open trials or anecdotal observations.
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PMID:The medical management of spasticity. 1191 47

The first part of this review deals with arguments that the essential properties and organization of spinal interneuronal systems in the cat and in man are similar. The second part is concerned with the possibility that some interneuronal systems may be responsible for motor disturbances caused by spinal cord injuries and that these interneurones may be defined. This possibility is discussed with respect to the hyperexcitability of alpha-motoneurones and the exaggeration of stretch reflexes in spastic patients. To this end, what is known about cat spinal interneurones and about the neuronal basis and pharmacological treatment of spasticity, is put together. Interneurones in di- and trisynaptic reflex pathways from group II muscle afferents are singled out, since they are depressed by the alpha(2) noradrenaline receptor agonists clonidine and tizanidine, which is a critical feature of interneurones expected to contribute to exaggerated stretch reflexes which are reduced by alpha(2) noradrenaline receptor agonists. Recent observations that reflex excitation of extensor motoneurones from group II afferents is enhanced in spastic patients and that the pathologically strong reflex actions of group II afferents are reduced by clonidine and tizanidine support this proposal. On the other hand, a lack of effect of clonidine and tizanidine upon other types of excitatory or inhibitory interneurones argues against any major contribution of such interneurones to the abnormally strong responses of alpha-motoneurones to muscle stretch.
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PMID:Spinal interneurones; how can studies in animals contribute to the understanding of spinal interneuronal systems in man? 1258 3

We review the evidence of botulinum toxins in the treatment of pain. Main indications of botulinum toxin treatment, dystonia and spasticity, involve pain. Increasing evidence suggests direct analgesic effects of botulinum. Botulinum inhibits release of pain mediators (substance P, CGRP, excitatory amino acids, ATP, noradrenaline). Clinical trials have consistently shown analgesic effect of botulinum toxin in post-stroke shoulder pain, bladder dysfunction, chronic migraine, neuropathic pain, bruxism and lateral epicondylitis. Other pain conditions have been studied with yet uncertain results. It seems that the number of patients who would benefit from botulinum toxin treatment will increase considerably in the future.
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PMID:[Botulinum toxins for pain]. 2223 20