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)

Electrophysiology of BZR ligands has been reviewed from different points of view. A great effort was made to critically discuss the arguments for and against the temporarily leading hypothesis of the mechanism of action of BZR ligands, the GABA hypothesis. As has been discussed at length in the present article, an impressive body of electrophysiological and biochemical evidence suggests an enhancement of GABAergic inhibition in CNS as a mechanism of action of BZR agonists. Biochemical data even indicate a physical coupling between GABA recognition sites and BZR which, together with the effector site build-up by Cl- channels, form a supramolecular GABAA/BZR complex. By binding to a specific site on this complex, BZR agonists allosterically increase and BZR inverse agonists decrease the gating of GABA-linked Cl- channels, whereas BZR antagonists bind to the same site without an appreciable intrinsic activity and block the binding and action of both agonists as well as inverse agonists. While this model is supported by many electrophysiological experiments performed with BZR ligands in higher nanomolar and lower micromolar concentrations, it does not explain much controversial data from animal behavior and, more importantly, is not in line with electrophysiological effects obtained with low nanomolar BZ concentrations. The latter actions of BZR ligands in brain slices occur within a concentration range compatible with concentrations of BZ observed in CSF fluid, which would be expected to be found in the biophase (receptor level) during anxiolytic therapy in man. Enhanced K+ conductance seems to be a suitable candidate for this effect of BZR ligands. This direct action on neuronal membrane properties may underlie the many electrophysiological observations with extremely low systemic doses of BZR ligands in vivo which demonstrated a depressant effect on spontaneous neuronal firing in various CNS regions. Skeletomuscular spasticity and epilepsy are two neurological disorders, where both the enhanced GABAergic inhibition and increased K+ conductance may contribute to the therapeutic effect of BZR agonists, since electrophysiological and behavioral studies strongly support GABA-dependent as well as GABA-independent action of BZR ligands elicited by low to intermediate doses of BZ necessary to evoke anticonvulsant and muscle relaxant effects. Somewhat higher doses of BZR ligands, inducing sedation and sleep, lead perhaps to the only pharmacologically relevant CNS concentrations (ca. 1 microM) which might be due entirely to increased GABAergic inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Electrophysiology of benzodiazepine receptor ligands: multiple mechanisms and sites of action. 285 56

Recent pharmacological investigations have support the hypothesis that spinal modulation of nociception as well as motor coordination is related to the activity of spinal interneurons and that certain spinal transmitters are involved in the control of both regulatory systems. Opioids and benzodiazepines, i.e. endorphin- or GABA-induced mechanisms, may be of importance for spinal treatment of spasticity in the near future. In order to clinically evaluate the interactions of these spinal processes we performed in vitro-experiments, animal studies and clinical investigations on the compatibility and antispastic efficacy of spinally administered opiates and benzodiazepines. Preclinical studies on tissue- and CSF-tolerance of different benzodiazepines (pH, tonometry, turbidimetry, histological findings in animals) are in favour of midazolam, a water-soluble compound, which is active against pharmacologically induced spasms in animals (strychnine application in cats with chronical catheterization of the subarachnoid space) after lumbar intrathecal injection. Using an appropriate dosage of intrathecal midazolam selective blockade of spasticity of the hind legs may be demonstrated with integrated EMG. Clinical investigations (neurological assessment using rating scores for spasticity) in 16 patients, including a double-blind comparison of epidural morphine or midazolam, indicate that both drugs are effective against spinal spasticity of different origin. Efficacy of spinally applied agents depends on the severity of spasms and on the duration and extent of systemic pretreatment.
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PMID:[Spasticity treatment with spinal morphine or midazolam. In vitro experiments, animal studies and clinical studies on compatibility and effectiveness]. 294 90

Epileptiform activity was induced in area CA3 of hippocampal slices by superfusion of medium containing 50 microM bicuculline and 3.5 mM K, 50 microM bicuculline and 5 mM K, 50 nM kainic acid and 3.5 mM K, or 7 mM K. Burst potentials were recorded at rates between 5 and 44/min, depending on the convulsant treatment. Baclofen reduced the frequency of burst firing in all slices tested in a dose-dependent manner, with little change in the morphology of individual bursts. Thus baclofen primarily affected the initiation of epileptiform discharges. IC50 values varied between 27 and 500 nM and were positively correlated with the rate of bursting. These experiments indicate that baclofen, at concentrations present in the CSF of patients treated for spasticity, has an anticonvulsant-like effect in the hippocampal formation and suggest that its mode of action is to reduce the excitability of pyramidal cells.
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PMID:Baclofen suppresses bursting activity induced in hippocampal slices by differing convulsant treatments. 301 16

Tropical spastic paraparesis (TSP) is a common myeloneuropathy with primary and predominant involvement of the pyramidal tract and minimal sensory loss. The epidemic form of TSP is related to toxic nutritional factors, but the endemic form occurs in clusters in tropical areas, especially in India, Africa, the Seychelles, Colombia, and areas of the Caribbean. We describe the clinical and epidemiological features of 25 TSP patients from Martinique (French West Indies) with serum antibodies to human T-lymphotropic virus type I (HTLV-I). Furthermore, all 11 patients who were seropositive for HTLV-I had specific HTLV-I antibodies in their CSF. All were women. The age of onset varied from 25 to 60 years (mean, 45 years). The main clinical features are spastic paraparesis or paraplegia with spasticity of the upper limbs, minimal sensory loss, and bladder dysfunction. Minimal estimated incidence and prevalence are 1 per 100,000 inhabitants per year and 8 per 100,000, respectively. Seventeen percent of the relatives of patients with HTLV-I-associated TSP have HTLV-I antibodies (1 husband and 7 children). In Martinique, the prevalence of HTLV-I antibodies in the general population is about 2% and reaches 10% for neurological disorders other than TSP. Since our initial report, the association between spastic paraparesis and HTLV-I has been confirmed in Jamaica, Colombia, and Japan, suggesting the neurotropism of this lymphotropic human retrovirus.
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PMID:Endemic tropical spastic paraparesis associated with human T-lymphotropic virus type I: a clinical and seroepidemiological study of 25 cases. 303 Jan 90

We have studied the clinical presentation and course of a chronic inflammatory disease occurring in childhood and observed in 30 patients. The first symptoms were generally present at birth, except in a few patients where they were first noticed in early infancy. All the patients had the association of three main symptoms: neurological, cutaneous and articular. The skin rash was the first symptom observed in all the patients and looked like a chronic non pruritic urticaria varying during the day. The articular manifestations involved knees, ankles and feet, elbows, wrists and hands unaffecting the other joints. They could be mild giving arthritis during flare-ups or severe with major radiological modifications affecting the epiphysis, metaphysis and growth cartilage. The neurological manifestations were characterized by a chronic meningitis and symptoms indicating meningeal irritation: headaches, seizures, spasticity of legs. Most patients had a cerebral atrophy and a low IQ. Sensory organ involvement occurred progressively during the follow-up: ocular inflammation with optic atrophy, deafness and hoarseness. Common morphological features characterized these patients with short stature, head enlargement, saddle back nose and short and thick extremities with clubbing of fingers. The course was that of a chronic inflammatory disease with numerous flare-ups associating fever, splenomegaly and adenomegaly. Except for a high level of eosinophils in blood, CSF and tissues, the biology was non specific and only exhibited features of inflammation. Except for two families, the disease was sporadic. A high frequency of prematurity with features resembling a foetal infection was observed but no proof of a possible causal virus has so far been found so that etiology remains unknown.
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PMID:A chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome. A specific entity analysed in 30 patients. 348 35

Using a specific radioimmunoassay we have measured somatostatin-like immunoreactivity (SLIR) of CSF in patients with brain atrophy, spinal spasticity, seizures, brain tumors and inflammatory disorders. Patients with marked brain atrophy had significantly decreased somatostatin levels in CSF. In patients with spinal spasticity significantly higher levels were observed. Seizure patients had reduced levels but the difference was not significant. In patients with inflammatory disorders and malignant brain tumors SLIR levels were significantly elevated but not in patients with benign brain tumors. A possible pathophysiologic meaning of SLIR in spasticity and seizures is discussed. The altered levels in brain atrophy, tumors and inflammatory disorders are probably indirect signs of altered somatostatin turnover or increased somatostatin leakage from damaged CNS.
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PMID:Somatostatin-like immunoreactivity in the cerebrospinal fluid of neurological patients. 612 89

This report is on six cases of a chronic relentlessly progressive encephalitis occurring in boys with congenital hypogammaglobulinemia presumably of the x-linked type, which are thought to represent a separate neurological entity. Intellectual deterioration, dysarthria, spasticity, ataxia, optic atrophy and an increase of lymphocytes in the cerebrospinal fluid, were the main clinical signs. The pathological picture was that of a viral encephalitis, but all virological investigations on brain biopsies and CSF were negative. The significance of intra-cisternal tubuloreticular inclusions in brain endothelial cells, similarities with chronic rubella encephalitis, and the role of the immunological deficiency are discussed. Sofar, the cause of this new type of encephalitis remains obscure.
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PMID:Chronic progressive encephalitis in children with x-linked hypogammaglobulinemia. 625 8

In a patient with hyperargininemia, oral administration of sodium benzoate or phenylacetic acid together with an essential amino acid mixture was used to prevent hyperammonemia and to decrease plasma and CSF concentrations of arginine. Sodium benzoate reduced the plasma ammonia levels, which was confirmed by the increase of urinary excretion of hippuric acid. Phenylacetic acid also controlled hyperammonemia, and EEG findings also improved. By these treatments, plasma and CSF concentrations of arginine showed a slight decrease, but were far above the normal range. There was no clinical improvement, and spasticity of the lower and upper extremities was progressive with mental deterioration.
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PMID:Hyperargininemia: clinical course and treatment with sodium benzoate and phenylacetic acid. 667 Jul 11

Nine children treated for acute leukemia or lymphosarcoma developed subacute encephalopathy starting with listlessness, depression and impairment of speech. Walking difficulties, ataxia, spasticity and sphincter disorders developed later. Transient intracranial hypertension and abnormal movements respectively developed in two patients. EEG frontal slow waves, raised CSF protein, abnormal white matter radioisotope uptake and CT scan hypodensity with patchy contrast enhancement were evident at the onset. Later, dilated ventricles and calcification appeared in the younger patients. Post-mortem neuropathological studies of three patients disclosed predominantly perivascular myelin loss in areas of white matter necrosis, abnormalities of small vessels and numerous axonal swellings. The spinal cord showed secondary degeneration of the corticospinal tracts. Analysis of the aetiological factors in this series points to the prevailing danger of cranial radiotherapy, probably increased by the young age of patients and by associated drug administration.
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PMID:Necrotising leukoencephalopathy complicating treatment of childhood leukaemia. 669 15

There is a growing body of evidence that the central nervous system (CNS), even in the adult animal, is capable of adaptation and reorganization not only as a result of partial damage to the CNS but also in response to stimulation. Environmental stimulation produces changes including expansion of visual cortex, increases in dendritic branching, glia and cholinesterase. Environmental stimulation also produces behavioural changes. Experimental electrical stimulation produces changes in synapse size, synaptic vesicle change, dendritic branching and changes in synaptic transmission. In man, repetitive electrical stimulation via epidural electrodes increases plasma levels of norepinephrine, epinephrine, and dopamine, and CSF levels of norepinephrine. Repetitive electrical stimulation in man dates back to 1967 and has been used for the control of pain, to improve spasticity, bladder control, motor deficit and the autonomic hyperreflexia of spinal cord injury. In addition, improvement has been reported in epilepsy, cerebral palsy, torticollis and peripheral vascular diseases. The best controlled studies are in multiple sclerosis and peripheral vascular disease, and these results will be presented in more detail.
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PMID:Rehabilitation following brain damage: some neurophysiological mechanisms. The effects of repetitive stimulation in recovery from damage to the central nervous system. 718 88


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