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)

The recent cloning of two GABA(B) receptor subunits, GABA(B1) and GABA(B2), has raised the possibility that differences in GABA(B) receptor subunit composition may give rise to pharmacologically or functionally distinct receptors. If present, such molecular diversity could permit the selective targeting of GABA(B) receptor subtypes specifically involved in pathologies such as drug addiction, spasticity, pain, and epilepsy. To address these issues we have developed a GABA(B1) subunit knockout mouse using gene targeting techniques. In the brains of GABA(B1) null mice, all pre- and postsynaptic GABA(B) receptor function was absent demonstrating that the GABA(B1) subunit is essential for all GABA(B) receptor-mediated mechanisms. Despite this, GABA(B1) null mice appeared normal at birth, although by postnatal week four their growth was retarded and they developed a generalized epilepsy that resulted in premature death. In addition, GABA(B1) heterozygote animals showed enhanced prepulse inhibition responses compared to littermate controls, suggesting that GABA(B1) deficient mice exhibit increased sensorimotor gating mechanisms. These data suggest that GABA(B) receptor antagonists may be of benefit in the treatment of psychiatric and neurological disorders in which attentional processing is impaired.
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PMID:Epileptogenesis and enhanced prepulse inhibition in GABA(B1)-deficient mice. 1141 94

Glutamate is the major excitatory neurotransmitter of the central nervous system. Besides its importance in many physiological processes, increased glutamate release and subsequent excessive stimulation of the various glutamate receptors are thought to play critical roles in the pathophysiological mechanisms underlying many neurologic diseases. Experimental data suggest that blockade of glutamate receptors or inhibition of glutamate release has positive effects in many disease models. Glutamate antagonists are already in clinical use for the treatment of Parkinson's disease, epilepsy, spasticity, and neuropathic pain. Overall, glutamate antagonists have not been found clinically effective for neuroprotective treatment of cerebral ischemia or chronic neurodegenerative diseases, with one exception. Side effects of glutamate antagonists can be mainly attributed to central mechanisms and include psychosis, agitation, and disorientation. It is to be hoped that further development of new glutamate antagonists that block disease-relevant subtypes of glutamate receptors will lead to more effective drugs with fewer side effects.
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PMID:[Glutamate antagonists in neurology]. 1143 98

Hereditary spastic paraparesis (HSP) is a clinically and genetically heterogeneous neurodegenerative disorder characterised by progressive lower limb spasticity and weakness. Some forms have been associated with white matter lesions and complex phenotypes. This study was prompted by the diagnosis of multiple sclerosis (MS) in two sisters from a large pedigree with hereditary spastic paraparesis. Twelve affected members of the extended family were examined (MRI and EEG were carried out and evoked potentials measured in five), and historical information was obtained from six affected deceased persons. The inherited disease phenotype was confirmed as autosomal dominant hereditary spastic paraparesis associated with epilepsy in four affected persons. None of the extended family had evidence of MS. Genetic analysis of the family has shown linkage to chromosome 2p and sequencing of the spastin gene has identified a 1406delT frameshift mutation in exon 10. This kindred demonstrates the clinical heterogeneity of HSP associated with spastin mutations. The possible relevance of the concurrence of HSP and MS in the sib pair is discussed.
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PMID:A large family with hereditary spastic paraparesis due to a frame shift mutation of the spastin (SPG4) gene: association with multiple sclerosis in two affected siblings and epilepsy in other affected family members. 1172 4

Though the AMPA receptor has been implicated in several neurodegenerative processes (epilepsy, ischemia, spasticity), its role in cognition is yet to be clarified. The aim of this study was to assess in the rat the effects of the AMPA receptor antagonist NBQX (3.5, 7, 10, 20 and 30 mgkg(-1), i.p.) on learning and memory. For this purpose, the object recognition task was chosen. NBQX, at the higher doses used (20 and 30 mgkg(-1)) caused respectively, depression of motility and ataxia, while given at lower doses (3.5, 7 and 10 mgkg(-1)) it did not influence animals performance in the object recognition paradigm. All rats acquired similarly well the task. In conclusion, these results would support and broaden previous observations on the lack of major involvement of AMPA receptors in the rat working memory mechanisms.
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PMID:The non-NMDA receptor antagonist NBQX does not affect rats performance in the object recognition task. 1182 Aug 60

BEST REMEMBERED FOR his description of the dermatomes in man, Otfrid Foerster was also an adept neurosurgeon and an innovative experimental neurophysiologist. As a neurologist, his contributions included conceptualizing rhizotomy as a cure for spasticity, anterolateral cordotomy for pain, the hyperventilation test in epilepsy, Foerster's syndrome, and the first electrocorticogram of a brain tumor. As a neurosurgeon, Foerster was able to excise intraventricular, hypophyseal, and quadrigeminal lesions and to perform epilepsy surgery under primitive conditions without clips, diathermy, or suction. The results were good and reflected his consummate knowledge of neuroanatomy and neurophysiology. As an investigator, Foerster emphasized clinically orientated neurophysiology and was able to forge a link between his observations and proposed methods of treatment. A prolific writer, he published more than 300 scientific monographs encompassing every aspect of the nervous system, including tabes, movement disorders, spasticity, extrapyramidal diseases, dermatomes, epilepsy, cortical localization, brain tumors, peripheral nerve injuries, and pain. Foerster's superb command of languages led to his popularity as a speaker in Europe and North America. Students who flocked to learn from his encyclopedic knowledge and skill were privy to Foerster's legendary hospitality and charm. A man of delicate constitution, he was single-minded in his quest to unravel the mysteries of the nervous system. The inscription "Patriae scientiae inserviendo" or "In the service of science and Fatherland" was chosen by Foerster for his Institute of Neurology and is a fitting memorial to this neurosurgical giant.
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PMID:The contributions of Otfrid Foerster (1873-1941) to neurology and neurosurgery. 1205 Nov 94

We present two siblings with pontocerebellar hypoplasia who have progressive microcephaly, mental and motor retardation, truncal ataxia, strabismus, and progressive spasticity and hyperreflexia of the lower limbs. Extrapyramidal dyskinesia and epilepsy, other main clinical features of pontocerebellar hypoplasia, are absent. The older sibling also has a high arched palate, triangular-shaped face, thoracolumbar scoliosis, pectus carinatum, kyphosis, cubitus valgus, arachnodactyly, long extremities, and a tall stature, which were not previously reported in association with pontocerebellar hypoplasia. The clinical phenotype should be expanded, especially within type II, with the reports of additional cases.
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PMID:Pontocerebellar hypoplasia in two siblings with dysmorphic features. 1191 77

To assess the clinical impact of microcephaly among children with developmental disabilities, we reviewed the charts of 1393 consecutive patients from birth to 5 years of age referred to our child development center. Comparisons were made between normal and low IQ microcephalic patients and between children with cerebral palsy with and without small head circumference. Microcephaly was detected in 15.4% of patients. Although mental retardation was more common among microcephalic children (P < .001), almost half had normal intelligence. Prematurity (P < .001), perinatal asphyxia (P < .001), small for gestational age (P < .001), respiratory distress syndrome (P < .001), and brain hemorrhage (P < .001) were associated with microcephaly. Hypotonia (P < .001) and spasticity (P < .001) were the most common neurologic findings. Cerebral palsy (P < .001), growth retardation (P < .001), epilepsy (P < .001), and strabismus (P < .001) were the main associated diagnoses found. Mental retardation was significantly more common among microcephalic patients with cerebral palsy than among normocephalic ones (P < .0004). Microcephaly is common among children evaluated for developmental disabilities. Many of these patients have normal or borderline IQ. Of several perinatal conditions associated with later microcephaly, respiratory distress syndrome and intraventricular hemorrhage show the strongest correlation. Mental retardation is not a risk factor for other neurologic complications in microcephalic children. However, in children with cerebral palsy, microcephaly is a risk factor for mental retardation.
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PMID:Significance of microcephaly among children with developmental disabilities. 1195 71

Serial neuroimaging studies in Alexander's disease were obtained on an African-American girl who died at 4z\x years of age. She presented with macrocephaly, psychomotor retardation, spasticity, a seizure disorder, and hydrocephalus. A thorough metabolic evaluation of defined leukodystrophies, including Krabbe's disease, adrenoleukodystrophy, metachromatic leukodystrophy, Canavan's disease, and Leigh disease, was negative. A diagnosis of Alexander's disease was made based on the clinical features and ruling out all other possible causes. It was confirmed by pathologic findings of numerous subpial, subependymal, and perivascular Rosenthal fibers throughout the entire cerebrum. Interestingly, autopsy also identified the stenotic sylvian aqueduct owing to Rosenthal fiber accumulation, explaining the origin of hydrocephalus. The evolution of magnetic resonance imaging findings appears to be unique in this disease.
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PMID:Infantile Alexander's disease: serial neuroradiologic findings. 1217 72

X-linked hereditary spastic paraplegias (HSPs) present with two distinct phenotypes: pure and complicated. The pure form is characterized by slowly progressive weakness and spasticity of the lower limbs, whereas the complicated forms have additional features (optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, epilepsy, ataxia, ichthyosis, mental retardation, and deafness). Three X-linked loci have been identified for the complicated HSP, while mutations in the proteolipid gene (PLP) (locus SPG2) were implicated in both pure and complicated forms. The absence of identified mutations in the PLP gene in families with both complicated and pure HSP, linked to the SPG2 locus, suggests the existence of another gene in close proximity. We had previously reported a large pedigree with an X-linked form of pure HSP affecting 24 males [Zatz et al., 1976: J Med Genet 13:217-222]. Here, we present the results of linkage analysis in 19 members of this Brazilian family with markers in or near the PLP locus. Positive LOD scores were obtained with markers at the PLP locus (Zmax = 2.41 at Theta = 0); however, no mutation was found in the coding region of PLP, the intron-exon boundaries, or part of the promoter region. The possibility of a duplication of the PLP gene was also excluded. These results suggest either that there is another X-linked gene in close proximity to the PLP gene or that a novel mutation in the noncoding regions of the PLP gene may cause the disease in this family.
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PMID:Further evidence for a fourth gene causing X-linked pure spastic paraplegia. 1221 Mar 42

The arguments over the nomenclature of the syndrome are reviewed. Ethical considerations favour replacing the present eponyms with the title of panthothenate kinase-associated neurodegeneration (PKAN), now that more is known about the cause of the condition. The symptoms and signs of the syndrome are described, and these can present from infancy to adult life. Dystonia, involuntary movements and spasticity are prominent causes of disability. If the onset is delayed the presentation can be unusual. Tests that can help in diagnosis are reviewed, especially the "eye of the tiger" revealed by magnetic resonance imaging scanning. Death usually occurs about 10 years after the onset, but the course may be more prolonged. The findings on autopsy are also considered, with the typical findings of iron pigment deposits and axonal spheroids. Then the causes are discussed. Once the responsible gene PANK2 had been discovered on chromosome 20 it was found that this encoded for pantothenate kinase which is essential for the synthesis of coenzyme A from pantothenate; and this is integral to fatty acid synthesis and energy metabolism. Also this can lead to a concentration of cysteine in the basal ganglia, and then to an accumulation of iron in these areas. The cysteine-iron complex will result in tissue damage by promoting oxidative stress, as in some other neurodegenerative diseases. The syndrome of PKAN can therefore be identified as a disorder of pantothanate, vitamin B5, metabolism. Infantile neuroaxonal dystrophy is briefly described as there have been suggestions that it is a variety of PKAN, but the evidence is in favour of the two diseases being separate entities. There may as yet be no specific treatment for this syndrome, but much can be done to help these children. Drugs may be needed to control epilepsy, and when dystonia is severe it may be possible to alleviate this by medical or surgical means. Also there will be other problems needing expert management, such as the provision of alternative means of communication if dysarthria is marked. The hope for the future is that now the cause has been found it will be possible to use methods such as antioxidative therapy and gene induction procedures.
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PMID:Pantothenate kinase-associated neurodegeneration (Hallervorden-Spatz syndrome). 1237 76


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