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)

Selected examples from three series of isomeric (alkylthio)-1,2,4-triazoles were prepared and examined for anticonvulsant activity versus strychnine-, maximal-electroshock-, pentylenetetrazole-, and 3-mercaptopropionic-acid-induced seizures in mice. A number of 5-aryl-3-(alkylthio)-4H-1,2,4-triazoles were selective antagonists of strychnine-induced convulsions. The isomeric 3-aryl-5-(alkylthio)- and 5-aryl-3-(alkylthio)-1H-1,2,4-triazoles were essentially inactive as anticonvulsants. The most potent antagonist of strychnine-induced convulsions was 5-(2-fluorophenyl)-4-methyl-3-(methylthio)-4H-1,2,4-triazole (3s), while the most selective antagonist was 5-(3-fluorophenyl)-4-methyl-3-(methylsulfonyl)-4H-1,2,4-triazole (3aa). The anticonvulsant profiles of these 4H-1,2,4-triazoles suggested that they were acting functionally like glycine receptor agonists. Since it has recently been postulated that compounds possessing glycine-agonist-like properties might be useful in the treatment of spasticity, we examined 5-phenyl-4-methyl-3-(methylsulfonyl)-4H-1,2,4-triazole (3c) in an in vivo model of spasticity. In this regard, 3c reduced the occurrence of hyperreflexia in rats that had received spinal transections 5-10 weeks previously. While triazole 3c appeared to possess glycine-agonist-like properties in vivo, it did not displace [3H]strychnine binding from rat brain stem/spinal cord membranes in vitro. On the other hand, 3c enhanced muscimol-stimulated 36Cl influx in a rat cerebellar membrane preparation, indicating a possible interaction of these triazoles with the GABAA receptor.
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PMID:5-Aryl-3-(alkylthio)-4H-1,2,4-triazoles as selective antagonists of strychnine-induced convulsions and potential antispastic agents. 828 85

We report the clinical and EEG findings in three patients presenting with seizures associated with intrathecal baclofen application for treatment of spasticity. All patients had a history of traumatic brain injury, while one patient also suffered a spinal cord injury. Two patients experienced their first seizure following intrathecal baclofen test bolus injection. Another patient had convulsions on two occasions: following postoperative baclofen dose adjustment, and after sleep deprivation. Structural brain disease seems prerequisite for baclofen to exert epileptogenic activity, since seizures have not occurred in patients receiving intrathecal baclofen for spasticity of solely spinal origin. Antiepileptic medication permitted the continuation of intrathecal baclofen treatment in the three patients.
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PMID:Epileptic seizures associated with intrathecal baclofen application. 829 85

Three children with pronounced livedo reticularis present since birth (cutis marmorata-telangiectasia congenita) have been followed to the ages of eight, 17 and 21 years. During childhood they developed frequent recurrent transient stroke-like hemipareses, affecting either side of the body, associated with ipsilateral pain, headache, visual symptoms, dysphasia, fits and confusion. Intellectual failure and, in one, progressive spasticity have followed. Attacks were more frequent in winter. Other problems have included abnormal peripheral vascular responses to temperature change, gastro-intestinal bleeding, glaucoma, local tissue hypertrophy and, in the two older patients, renal involvement with hypertension. Their condition represents a form of congenital vasculopathy. Anticonvulsants, anti-migraine agents, anti-platelet drugs and flunarizine have been ineffective. Nifedipine prevented further attacks in one patient and reduced attacks in another, but has not helped the third child. Adequate clothing and warmth may also be important.
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PMID:Congenital livedo reticularis and recurrent stroke-like episodes. 840 21

Two sisters were presented, 16 years old and 12 years old, who showed similar clinical courses. They had had mental retardation since early childhood, and then ataxia began. They suffered from astatic and tonic seizures from early school age, which gradually evolved to intractable epilepsies. Spasticity progressed, and they deteriorated both physically and mentally. They revealed photo-sensitivity; convulsions were induced by the flickering of light. They were attacked by myoclonic seizures as well as choreoathetosis, and became bedridden by the latter part of the elementary school age. There were no fruitful results of any kind from the laboratory examinations for metabolic disorders. EEG showed that the epileptic seizure discharges were induced by photic stimulation; there were frequent 3-4 Hz diffuse spike-and-wave short bursts during waking and sleep periods. MRI findings of the elder sister at the age of 16 revealed remarkable diffuse brain atrophy. Gene analysis showed abnormally enlarged DNA fragments localized on the short arm of chromosome 12. This meant expanded CAG trinucleotide repeats. The younger sister died at the age of 12 years. Autopsy findings revealed degeneration of both dentatorubral and pallidoluysian pathways. There were especially remarkable gliosis and neuronal cell loss in the outer segment of globus pallidus, and moderate neuronal cell loss and typical grumose degeneration in the dentate nucleus. The diagnosis of juvenile-type hereditary dentatorubral-pallidoluysian atrophy was compatible with the pathologic findings. This diagnosis will be made possible before death through the understanding of the clinical symptoms and molecular genetics.
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PMID:[Sisters with early onset hereditary dentatorubral-pallidoluysian atrophy of childhood--DNA analysis and clinicopathological findings]. 853 13

We present the two siblings with X-linked hydrocephalus (XLH) and discuss the clinical features and genetical analysis of them. Case 1. The proband, a male, was delivered by the emergency cesarean section because of enlarged head circumference (44cm). His head circumference at 24 years old was 92cm. Neurological examination revealed adducted thumbs, horizontal nystagmus, hyperreflexia and spasticity of legs. He had tonic convulsions. MRI revealed a very thin layer of cerebral cortex. Molecular analysis revealed a deletion of 5 bases in exon 8 of the cell adhesion molecule L1 (L1CAM) gene located at chromosome Xq28. Case 2. The younger maternal half brother of case 1 was also born by the cesarean section, with 48cm in head circumference. A ventriculoatrial shunt was placed at the first month old. Epileptic seizures were seen. At the age of 21 years he had a head circumference of 59cm. A physical examination showed bilateral adducted thumbs, upward deviation of eyes, hyperreflexia and spasticity of legs. CT showed marked generalized ventricular enlargement including the fourth ventricle. Molecular analysis confirmed the same mutations as that of case 1. A maternal uncle had a previous diagnosis of hydrocephalus, and a sister is identified as a heterozygous carrier from molecular genetical analysis. Our results indicate that HLX is caused by the mutations in the gene for neural L1CAM in our family.
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PMID:[A family with X-linked hydrocephalus resulting from mutations in the neural cell adhesion molecule L1]. 874 50

The combination of X-linked mental retardation (XLMR) and neurological disorders occurs in a number of syndromes. Differential diagnosis mostly depends on clinical data and mapping of responsible genes by linkage analysis. We present a Belgian family with severe XLMR and a progressive neurological disorder with ataxia, spasticity and convulsions. Biochemical investigations, neuroimaging and neuropathology were normal. Linkage analysis pointed to region Xq27-28 as the probable locus for the genetic defect. The sequence of the L1CAM cDNA, a possible candidate gene, proved to be normal in the patients. This suggests the presence of a genetic factor on Xq27-28, different from L1CAM, which can lead to severe XLMR and a progressive neurological disorder.
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PMID:X-linked severe mental retardation and a progressive neurological disorder in a Belgian family: clinical and genetic studies. 937 4

Feeding difficulty and malnutrition are common in disabled children. Intake may be reduced because of anorexia, chewing and swallowing difficulties, or vomiting. Feeding is often time consuming, unpleasant, and may result in aspiration. Malnutrition may result in impaired growth and neurodevelopment, and impaired cardiorespiratory, gastrointestinal, and immune functions. Multidisciplinary assessment is recommended and should include a feeding history, oral-motor examination, and nutritional assessment. The energy requirements of most disabled children are less than those for a normal child of the same age but may be increased by spasticity, athetosis, convulsions, and recurrent infections. Micronutrient deficiencies may occur even in children receiving nutritionally complete feeds if the volume is reduced because of low energy requirements. Oral intake may be improved by a change of posture, special seating, feeding equipment, oral desensitization, mashing or pureeing of lumpy food, thickening of liquids, use of calorie supplements, and treatment of reflux/esophagitis. Non-oral feeding should be considered when oral feeding is unsafe, not enjoyable, inadequate, or very time consuming. Long-term support requires a gastrostomy. This is less obtrusive than a nasogastric tube, less likely to become displaced, less traumatic, and is associated with improved quality of life, but is also associated with significant morbidity. If there is symptomatic reflux a fundoplication may be required, but this is associated with significant mortality and substantial morbidity.
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PMID:Feeding the disabled child. 978 66

We report on a family with an X linked neurodegenerative disorder consisting of mental retardation, blindness, convulsions, spasticity, and early death. Neuropathological examination showed mild hypomyelination. By linkage analysis, the underlying genetic defect could be assigned to the pericentromeric region of the X chromosome with a maximum lod score of 3.30 at theta=0.0 for the DXS1204 locus with DXS337 and PGK1P1 as flanking markers.
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PMID:A new X linked neurodegenerative syndrome with mental retardation, blindness, convulsions, spasticity, mild hypomyelination, and early death maps to the pericentromeric region. 1005 Oct 14

Pelizaeus-Merzbacher disease (PMD) is a hereditary disorder with myelin dysplasia in the central nervous system. The connatal type is a more severe form compared to the classical type and shows developmental arrest or deterioration, nystagmus, spasticity, and/or convulsions in the neonatal period. A 1 1/4-year-old Japanese boy diagnosed as connatal type PMD is reported here. Soon after his birth, he demonstrated horizontal and rotatory nystagmus and opisthotonic posture. At the age of 10 months, he had difficulty in feeding. At the age of 1 year, he presented more severe opisthotonic posture and frequent vomiting. He showed deterioration in gross motor development. His chromosome analysis showed a normal male karyotype. Electroencephalogram did not show a sleep spindle. Auditory evoked brainstem responses (ABR) showed only wave I on both sides. Visual evoked potentials (VEP) showed prolongation of latencies. These results were compatible with PMD. Nuclear magnetic resonance imaging (MRI) demonstrated in the white matter of cerebrum and brainstem no high intensities on T1-weighted images and diffuse high intensities on T2-weighted images. Such absence of myelination including the brainstem was characteristic to the connatal type PMD. The diffuse disturbance of myelination appeared to correlate with the severity of clinical symptoms.
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PMID:[Connatal type of Pelizaeus-Merzbacher disease: a case report]. 1019 41

Paroxysmal dyskinesias are genetically and clinically heterogeneous. Paroxysmal kinesigenic choreoathetosis is frequently familial, with autosomal-dominant transmission. Benign infantile convulsions can be observed in these families and both diseases as linked to the pericentromeric region of chromosome 16. Two different forms of paroxysmal dystonic choreoathetosis are distinguished on clinical grounds, by the presence or absence of spasticity, and genetically, as they are linked with loci on different chromosomes. Among the paroxysmal disorders, these diseases may belong to the group of channelopathies.
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PMID:Paroxysmal dyskinesias as a paradigm of paroxysmal movement disorders. 1097 65


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