Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A prospective long-term semiquantitative evaluation of the results of ventral intermediate-posterior ventral oral nucleus thalamotomy on the different aspects of dystonia was made in 29 patients with secondary disease, 12 with nonfamilial, eight with (non-Jewish) familial, and seven with atypical DMD. The effect of disease progression, even in secondary patients, on surgical outcome was reviewed. Thalamotomy resulted in a long-term improvement in limb function of more than 25% to 50% in 23% of the patients, over 50% in 34% of patients, but midline features responded poorly. Manual dexterity was little changed in secondary cases because of underlying paralysis but improved 38% in cases of DMD. Involvement of neck and trunk, of three to four limbs, and progressive disease prognosticated for a poorer result, but phasic and tonic, familial, and nonfamilial dystonia respond equally well and age at surgery made no difference. Significant complications in 29 secondary cases included one death 31 days postoperative, one case of worsened hemiparesis, two cases of worsened dysarthria, two cases of worsened locomotion, one case of hydrocephalus requiring shunting, and one case of need for permanent tracheotomy. In 27 cases of typical and atypical DMD, there were two instances of hemiparesis, two of significant speech deterioration, three of hand ataxia, one of postoperative seizures, and one of hydrocephalus requiring shunting for an overall significant morbidity rate of 21%. The limiting factor in treating secondary dystonia is the underlying spastic paralysis but that in DMD is the relentless postoperative progression. The overall results of this study are remarkably similar to those of other published series: a quarter of the patients improved by 25% to 50%, a quarter to a third by more than 50%. The analysis of effect on specific features of the disease may be useful in the future for predicting outcome in a particular patient.
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PMID:Thalamotomy in generalized dystonia. 340 May 14

A survey was made of the clinical characteristics of wheelchair-users at the Children's Rehabilitation Centre in Saskatoon, Saskatchewan. 261 patients were studied, of whom 214 had cerebral palsy, 34 had myelomeningocele and 13 had Duchenne muscular dystrophy. Among the patients with cerebral palsy it was found that the attributes likely to define a wheelchair-user were spastic quadriplegia, functional level III and IV, seizures and severe sensory handicap; among patients with myelomeningocele, wheelchair use ws related to level of lesion; and in the muscular dystrophy group it ws related to age. These results have been of help to rehabilitation centres and related service agencies in formulating long-term plans to meet the needs of wheelchair-users.
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PMID:Wheelchair users at a children's rehabilitation center: attributes and management. 710 4

Linkage analysis was performed in three generations of a French family segregating a syndromal form of X-linked mental retardation. All affected males had neonatal hypotonia, seizures, muscular hypodevelopment, and severe mental deficiency. A peak lod score of 2.90 at a recombination fraction of theta = 0 was detected for DXS 1052 and DXS 451 (Xp22.13). Recombination between the disease locus and the polymorphic markers in DXS7163 and DXS1238 suggested a gene mapping to the Xp22.13-Xp21.2 region. Three candidate genes in this region were investigated: the cDNA for kinase Rsk-2 involved in Coffin-Lowry syndrome, the brain-specific exon of a transcript in the DMD locus (DP140 isoform of dystrophin), and exon 18 of the glycerol kinase gene, which is specific to fetal brain transcripts. All three sequences were normal.
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PMID:Evidence for a new X-linked mental retardation gene in Xp21-Xp22: clinical and molecular data in one family. 1049

Utrophin, the autosomal homologue of dystrophin, the Duchenne muscular dystrophy gene product, is a cytoskeletal protein found in many tissues. In muscle fibers, the level and localization of utrophin depend on their state of differentiation and innervation. Transgenic overexpression of utrophin prevents degeneration of dystrophin-deficient muscle fibers. In brain, in addition to its enrichment in blood vessels, utrophin is associated primarily with the plasma membrane of large sensory and motor brainstem neurons, suggesting a contribution to their structural stability. Here, we examined the role of utrophin for long-term survival of dentate granule cells, which become markedly hypertrophic in a mouse model of temporal lobe epilepsy. This morphogenetic change is induced several weeks after a unilateral intrahippocampal injection of kainic acid (KA), while mice experience chronic focal seizures. Using in situ hybridization and immunohistochemistry, we show that dispersion and hypertrophy of granule cells in KA-treated wildtype mice are accompanied by a strong and long-lasting expression of utrophin in somata and proximal dendrites. Utrophin knockout mice had a normal hippocampal cytoarchitecture but were more sensitive to KA-induced excitotoxicity, as shown by increased mortality and faster progression of the lesion. At 6 weeks post-KA, the numerical density of granule cells and thickness of the granule cell layer were significantly reduced ipsilaterally in mutant mice, indicating a profound reduction in total cell number in the absence of utrophin. These findings suggest that utrophin contributes to protect CNS neurons against pathological insults, in particular, stimuli leading to massive neuronal hypertrophy.
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PMID:Increased vulnerability to kainate-induced seizures in utrophin-knockout mice. 1202 57

Duchenne muscular dystrophy is characterized by a defect in dystrophin, which often causes mental retardation in addition to progressive muscular weakness. As dystrophin is localized in synaptic regions of the CNS, cognitive abnormalities associated with Duchenne muscular dystrophy are attributable to synaptic dysfunction. We report that dystrophin-deficient mdx mice were more resistant to kainic acid-induced seizures but not to GABA antagonist-induced seizures compared with the control mice. The kainic-acid receptor density in the brain was significantly lower in the mdx than in the control, although the density of muscarinic cholinergic receptors, another important neurotransmitter receptor for cognitive function, was normal. Moreover, mdx had significantly lower Timm staining intensity in the mossy fibers, which originate from the dentate granule cells and terminate on the pyramidal cells in the CA3 of the hippocampus. These results suggest that an instability of neurotransmitter receptors, such as kainate-type glutamate receptors, on synaptic membranes due to the disruption of dystrophin complex induces inefficient neurotransmission in Duchenne muscular dystrophy patients.
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PMID:Abnormal kainic acid receptor density and reduced seizure susceptibility in dystrophin-deficient mdx mice. 1261 79

In the present study, the susceptibility of the mdx mouse, a dystrophin-deficient genetic model of Duchenne muscular dystrophy (DMD), to various convulsant stimuli has been evaluated and compared to three related mice strains (C57BL/6J, C57BL/10 and DBA/2 mice). Animals were treated with chemical convulsants impairing gamma-aminobutyric acid (GABA) neurotransmission [pentylenetetrazole, picrotoxin, bicuculline, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), methyl-beta-carboline-3-carboxylate (beta-CCM)], enhancing glutamatergic neurotransmission [N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainic acid (KA)] or a K(+) channel blocker (4-aminopyridine). Occurrence of clonic and/or tonic seizures was evaluated to observe possible differences in seizure susceptibility. In addition, all strains of mice were repeatedly treated with a subconvulsant dose of pentylenetetrazole (PTZ) for possible differences in kindling development. The mdx mice exhibited no difference in seizure susceptibility for all convulsant drugs with the exception of a significantly lower sensitivity to AMPA and KA than the other mice strains. This study demonstrates that mdx mice possess a decreased susceptibility to some convulsant stimuli. However, mdx mice showed an enhanced seizure severity and a shorter latency in the development of chemical kindling produced by administration of PTZ. The present data suggests that the dystrophin deficiency in mdx mice affects the pathophysiology and pharmacology of acute and chronic epileptic seizures in an opposite manner.
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PMID:Seizure susceptibility to various convulsant stimuli in dystrophin-deficient mdx mice. 1528 97

We describe a patient with Duchenne muscular dystrophy (DMD) who additionally suffered from intractable seizures, severe mental retardation, and a marked macroglossia. He also had endocrinologic abnormalities consisting of growth hormone deficiency, delayed puberty, and adrenal hypoplasia. We detected a duplication of DMD exon 18 and flanking introns that caused a frame-shift and was not removed by corrective splicing. A coincident mutation in the FKRP gene was excluded by direct sequencing. Complex DNA rearrangements, deletions, and duplications >100 kb were excluded through microarray-comparative genomic hybridization (CGH), although we were not able to exclude a second coincident mutation with certainty. In conclusion, we present a case of DMD that conflicts with current understanding of genotype-phenotype relations and discuss putative pathogenetic mechanisms for this uncommon phenotype.
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PMID:Tandem duplication of DMD exon 18 associated with epilepsy, macroglossia, and endocrinologic abnormalities. 1714 88

Macroglossia is rare in patients of Duchenne muscular dystrophy (DMD), and its occurrence without any endocrinologic abnormality, seizures or an abnormal karyotype is even rarer. We describe a patient of DMD with isolated macroglossia with 271 bp deletion in exon 50 of the dystrophin gene and speculate a relationship in this regard.
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PMID:Macroglossia associated with 271 bp deletion in exon 50 of dystrophin gene. 2165 6

Cognitive and behavioral difficulties occur in approximately a third of patients with Duchenne muscular dystrophy. The aim of our study was to assess the prevalence of epilepsy in a cohort of 222 DMD patients. Epileptic seizures were found in 14 of the 222 DMD patients (6.3%). The age of onset ranged from 3 months to 16 years (mean 7.8). Seizures were more often focal epilepsy (n=6), generalized tonic-clonic seizures (n=4) or absences (n=4). They were present in 12 of the 149 boys with normal IQ (8.1%) and in two of the 73 with mental retardation (2.7%). In two cases the parents did not report any past or present history of seizures but only 'staring episodes' interpreted as a sign of 'poor attention'. In both patients EEG showed the typical pattern observed in childhood absence epilepsy. Our results suggest that the prevalence of epilepsy in our study (6.3%) is higher than in the general pediatric population (0.5-1%). The risk of epilepsy does not appear to increase in patients with mental retardation.
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PMID:Duchenne muscular dystrophy and epilepsy. 2346 56

The TRPC1 ion channel was the first mammalian TRP channel to be cloned. In humans, it is encoded by the TRPC1 gene located in chromosome 3. The protein is predicted to consist of six transmembrane segments with the N- and C-termini located in the cytoplasm. The extracellular loop connecting transmembrane segments 5 and 6 participates in the formation of the ionic pore region. Inside the cell, TRPC1 is present in the endoplasmic reticulum, plasma membrane, intracellular vesicles, and primary cilium, an antenna-like sensory organelle functioning as a signaling platform. In human and rodent tissues, it shows an almost ubiquitous expression. TRPC1 interacts with a diverse group of proteins including ion channel subunits, receptors, and cytosolic proteins to mediate its effect on Ca(2+) signaling. It primarily functions as a cation nonselective channel within pathways controlling Ca(2+) entry in response to cell surface receptor activation. Through these pathways, it affects basic cell functions, such as proliferation and survival, differentiation, secretion, and cell migration, as well as cell type-specific functions such as chemotropic turning of neuronal growth cones and myoblast fusion. The biological role of TRPC1 has been studied in genetically engineered mice where the Trpc1 gene has been experimentally ablated. Although these mice live to adulthood, they show defects in several organs and tissues, such as the cardiovascular, central nervous, skeletal and muscular, and immune systems. Genetic and functional studies have implicated TRPC1 in diabetic nephropathy, Parkinson's disease, Huntington's disease, Duchenne muscular dystrophy, cancer, seizures, and Darier-White skin disease.
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PMID:TRPC1. 2475 1


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