Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rett syndrome (RS) is one of the most frequent causes of mental retardation in females. As there are no known biochemical, genetic, or morphological markers, diagnosis is based on clinical phenotype including severe dementia, autism, truncal ataxia/apraxia, loss of purposeful hand movements, breathing abnormalities, stereotypies, seizures, and extrapyramidal signs. Myoclonus, although reported in some series, has never been characterized. We studied 10 RS patients, age 3 to 20 years, and observed myoclonus in 9. Severity of myoclonus did not correlate with that of the other symptoms or with age. Multifocal, arrhythmic, and asynchronous jerks mainly involved distal limbs. Electromyographic bursts lasted 48 +/- 12 msec. Burst-locked electroencephalographic averaging generated a contralateral centroparietal premyoclonus transient preceding the burst by 34 +/- 7.2 msec. Motor evoked potentials showed normal latencies, indicating integrity of the corticospinal pathway. Somatosensory evoked potentials were enlarged. The C-reflex was hyperexcitable and markedly prolonged (62 +/- 4.3 msec), mainly due to increase in cortical relay time (28.4 +/- 4.5 msec). We conclude that RS patients show a distinctive pattern of cortical reflex myoclonus with prolonged intracortical delay of the long-loop reflex.
 ...
PMID:Cortical reflex myoclonus in Rett syndrome. 954 28

Formerly thought to be a neurodegenerative disease, Rett syndrome (RS) is a neurodevelopmental arrest of the brain that almost exclusively affects females and occurs in a variety of racial and ethnic groups worldwide. RS begins in late infancy and is characterized by autistic and dementia-like behavior, ataxia, and purposeless hand movements. Its cause and mode of transmission are unknown in over 90% of cases; however, there is strong and convincing evidence that genetic factors play a major role. The reported incidence varies, but in the US, as many as one quarter to one third of female children in mental wards/institutions may be affected. RS has been mistaken for numerous other conditions, including autism, cerebral palsy, and mental retardation, but the clinical picture is unique: No other condition has a period of rapid deterioration followed by apparent stabilization or even improvement in autistic features, eye contact, seizure activity, and hand stereotypies. The diagnosis is supported by deceleration of head growth, evidence of neurologic regression with associated neurologic signs, and purposeless hand stereotypies, with a clinical history of developmental regression. The differential diagnosis often involves ruling out syndromes with similar signs of neurodevelopmental arrest--for example, meningitis or encephalitis; chromosomal disorders such as Angelman's syndrome and Prader-Willi syndrome; metabolic disorders such as ornithine carbamoyltransferase deficiency; disorders of organic acids and amino acids; neurovisceral storage diseases; mitochondrial cytopathy; and Batten disease, or infantile neuronal ceroid lipofuscinosis. Management encompasses a comprehensive medical, therapeutic, educational, and psychosocial approach, best provided through a team in collaboration with the community agencies that serve families and children with special needs.
 ...
PMID:Understanding, Recognizing, and Treating Rett Syndrome. 974 85

Dextromethorphan (DM), a widely used and well-tolerated centrally acting antitussive, has been tested in several clinical trials for its antiepileptic and neuroprotective properties. However, the use of DM in these new clinical indications requires higher doses than antitussive doses, which may therefore induce phencyclidine (PCP)-like side-effects (memory and psychotomimetic disturbances) through its metabolic conversion to the active metabolite dextrorphan (DX), a more potent PCP-like non-competitive antagonist at the N-methyl-D-aspartate (NMDA) receptor than DM. Thus, we compared the behavioural effects in rats of intraperitoneal administration of DM and DX on motor activity in an open field and on learning and memory in the Morris water maze. DM (20, 30, 40 mg/kg) produced a dose-dependent decrease in both locomotion and stereotyped behaviour with a slight ataxia for the highest dose. DX (20, 30, 40 mg/kg) induced a dose-dependent increase in locomotion and stereotypies (swaying, turning) with moderate ataxia. Assessments of learning and memory were performed with lower doses of DM (10, 20, 30 mg/kg) and DX (5, 10, 15 mg/kg) because of motivational deficits (40 mg/kg of DM, 20-40 mg/kg of DX) and motor disorders (30, 40 mg/kg of DX) in the cue learning procedure. DX (10, 15 mg/kg) impaired spatial learning with a long-lasting effect for the highest dose whereas 5 mg/kg of DX and DM (10-30 mg/kg) did not. Only 15 mg/kg of DX appeared to slightly impair working memory. DM (10-30 mg/kg) and DX (5-15 mg/kg) did not impair reference memory. Thus, the two antitussives DM and DX induced different behavioural effects suggesting sedative effects for DM and PCP-like effects for DX. However, PCP-like side-effects with DM remain possible through its metabolic conversion to DX, with very high doses and/or in extensive metabolizers and/or in aged subjects prone to cognitive dysfunction. Therefore, the identification of DM metabolism phenotype, an adapted prescription and a pharmacological modulation of the DM metabolism may avoid adverse effects.
 ...
PMID:Dextromethorphan and dextrorphan in rats: common antitussives--different behavioural profiles. 979 51

Lippia multiflora (L.m.) is a verbenacea used in Congo as conventional tea decoction. No traditional indication is known in this country. Nevertheless, in Ghana the plant is used for the treatment of arterial hypertension. The aim of this study is to investigate the psychotropic activity of the aqueous extract of L.m. using the classical tests of experimental psychopharmacology. The extract of L.m. is constituted by lyophilisated powder obtained from an infusion of dried leaves. Different doses are prepared: 200, 400, 600, 800, 1,000 and 1,200 mg/kg dissolved in 1 ml of NaCl 0.9%. L.m. is administered by intraperitoneal or oral route. The wistar rats of both sexes, weighing between 150-200 g, are used. Animal's behaviour is observed macroscopically. The spontaneous motor activity is appreciated by using the number of squares crossed by animal with the four paws in ten minutes (Martin and al. method slightly modified). The rectal temperature is measured. The effect of L.m. on stereotypies induced by apomorphin and anesthesia induced by phenobarbital are studied. The traction test is used to investigate the muscle relaxant effect of L.m. and analgesic activity is evaluated by using acetic acid and hot plate methods by comparison with diazepam 2 and 4 mg/kg. Fischer-t test is used for the statistical analysis of results. L.m. is well tolerated by rats. No mortality is observed with the doses used. So the doses of 200, 400 and 600 mg/kg were selected for experiments. At theses doses L.m. caused: a precocious ataxia, a sedation, a ptosis and a yellow coloration of urines, these effects are dose dependent; a significant reduction of spontaneous motor activity: control 61.60 +/- 6.48, L.m. 200: 16.40 +/- 5.68 (P < 0.01), L.m. 400: 12.20 +/- 2.01 and L.m. 600: 9.60 +/- 1.90 (P < 0.01); no modification of rectal temperature and apomorphin stereotypies; a reduction of sleep latence: control 22.40 +/- 1.89 min, L.m. 200: 17.20 +/- 2.74 min (P < 0.01), L.m. 400: 13.80 +/- 1.81 min (P < 0.01) and L.m. 600: 13.40 +/- 2.16 min (P < 0.01); a potentiation of phenobarbital anesthesia: L.m. 200: 209.80 +/- 29.58 min (N.S.), L.m. 400: 336.40 +/- 22.23 min (P < 0.01), L.m. 600: 342.20 +/- 16.28 min (P < 0.01) and control: 199.40 +/- 2.90 min; an increase at the dose of 400 mg/kg of the time necessary for the restoration of the paws to the metallic bar in the traction test: control; 0.8 +/- 0.1 s, L.m. 400: 7.04 +/- 2.29 s (P < 0.05); a reduction of abdominal cramps induced by acetic acid. This number is respectively 18.40 +/- 4.49 (P < 0.05); 15.00 +/- 2.90 (P < 0.01), 14.20 +/- 3.89 (P < 0.01), 11.60 +/- 4.75 (P < 0.01), 13.00 +/- 2.00 (P < 0.01) and 33.80 +/- 5.04 for L.m. 200 mg/kg, L.m. 400 mg/kg, L.m. 600 mg/kg, Diazepam 2 and 4 mg/kg and control; an increase of reaction time on the hot plate: L.m. 200: 3.26 +/- 0.46 s (N.S.), L.m. 400: 4.50 +/- 0.80 s (P < 0.01), L.m. 600: 10.50 +/- 1.56 s (P < 0.001), diazepam 2 mg/kg: 2.90 +/- 0.51 s (N.S.), diazepam 4 mg/kg: 5.90 +/- 1.09 s (P < 0.01) and control 2.10 +/- 0.26 s. Those results demonstrated that L.m. possess a tranquilizer and analgesic activities as Diazepam. But, anticonvulsant and anxiolytic tests are necessary to confirm the psychopharmacological profile of this medicinal plant.
 ...
PMID:[Psychopharmacologic properties of Lippia multiflora]. 985 Aug 19

The authors report eight children, who presented in the first year of life with isolated head stereotypies, that corresponded neither to the usual normal 'rhythmic habit patterns of infancy', nor to various types of abnormal repetitive head movements described in young children. Their head stereotypies closely resembled those described in bobble-head doll syndrome. The neurological status evidenced axial hypotonia, ataxia, oculomotor abnormalities, motor and language delay. The patients were followed for several years clinically and with video recordings. No single aetiology was found. Computed tomography (CT) or magnetic resonance imaging (MRI) show a congenital cerebellar abnormality in two children but no hydrocephalus. The outcome of these children showed in all but one patient a normal cognitive and psychosocial development, even though the head stereotypies are still present in six of eight patients and all remain significantly clumsy. The association of head stereotypies and motor delay should prompt a search for cerebellar congenital malformation. The outcome of those patients was much better than originally anticipated and these head stereotypies are not related either to mental retardation, or to psychopathology. The possible mechanisms involved are also discussed.
 ...
PMID:A special type of head stereotypies in children with developmental (?cerebellar) disorder: description of 8 cases and literature review. 1236 1

Two brothers presented in their mid-forties with movement disorders including atypical parkinsonism, choreiform movements, stereotypies, ataxia and dysarthria. Both brothers showed putaminal lucencies on imaging and, in the proband, a deficiency of the pyruvate dehydrogenase complex (PDHC) was found on skin fibroblast assay.
 ...
PMID:Late-onset presentation of pyruvate dehydrogenase deficiency. 1519 21

Noncompetitive N-methyl-D-aspartate (NMDA) antagonists such as ketamine represent useful pharmacological tools to model, in both healthy humans and rodents, behavioral and cerebral abnormalities of schizophrenia. These compounds are thought to exert some of their disruptive effects by impairing glutamatergic transmission in corticolimbic circuits including the nucleus accumbens (NAc). In this study, we investigated in freely moving rats behavioral changes as well as electrophysiological and neurochemical alterations in the NAc following acute systemic injection of a subanesthetic dose (25 mg/kg) of ketamine. We found that ketamine induced an immediate behavioral activation, characterized by hyperlocomotion, stereotypies and ataxia, and abolished latent inhibition in a conditioned-fear paradigm when injected at the pre-exposure stage. We also observed that during expression of motor effects which are thought to be related to the positive symptoms of schizophrenia, ketamine potentiated synaptic efficacy in the prefrontal-accumbens pathway and increased the extracellular levels of glutamate in the NAc. These results, taken together with previous findings, suggest that the psychotic-like effects of noncompetitive NMDA antagonists may be, in part, mediated by an increase in glutamate release in the NAc associated with synaptic changes in accumbens glutamatergic inputs including enhancement of synaptic efficacy in the prefrontal input.
 ...
PMID:Ketamine, at a dose that disrupts motor behavior and latent inhibition, enhances prefrontal cortex synaptic efficacy and glutamate release in the nucleus accumbens. 1652 15

There is experimental evidence indicating that the non-competitive NMDA receptor antagonist MK-801 impairs cognition and produces a series of schizophrenia-like symptoms in rodents (hypermotility, stereotypies, and ataxia). The present study was designed to investigate the efficacy of the nitric oxide (NO) donor molsidomine in counteracting these MK-801-induced behavioral effects in the rat. In a first study, post-training administration of molsidomine (at 4 but not 2 mg/kg) successfully antagonized MK-801-induced performance deficits in a recognition memory test. In a subsequent study, molsidomine (2 and 4 mg/kg) was shown to be unable to reverse MK-801-induced hypermotility but attenuated stereotypies (continuous movement whole cage, body sway, and head weaving) produced by MK-801. Moreover, at 4 mg/kg this NO donor counteracted MK-801-induced ataxia. Our findings indicate that molsidomine attenuates behavioral effects related to the hypofunction of the NMDA receptor suggesting that NO might be involved in the psychotomimetic effects of non-competitive NMDA receptor antagonists.
 ...
PMID:Nitric oxide donor molsidomine attenuates psychotomimetic effects of the NMDA receptor antagonist MK-801. 1671 Aug 46

Rett syndrome (RTT) is a neurodevelopmental disorder characterized by cognitive regression, loss of purposeful hand movements and speech, stereotypies, ataxia, seizures, mental retardation and acquired microcephaly. Mutations in MECP2, encoding methyl-CpG-binding protein 2, are responsible for approximately 90% of classic RTT cases. RTT displays phenotypic overlap with Angelman syndrome, a disorder caused by loss of expression of the imprinted gene UBE3A. MeCP2 binds to methylated DNA and may alter the expression of imprinted genes, thereby suggesting a mechanistic link between the two disorders. Here, we tested the hypothesis that MeCP2 deficiency affects expression of Ube3a in mouse models of RTT. As Ube3a is only imprinted in brain, we evaluated Ube3a expression in brains of 15 different litters of neonatal or 8-week-old male Mecp2 mutant mice by real-time quantitative RT-PCR and western blot analysis. We found no significant differences between Mecp2(tm1.1Bird/Y) or Mecp2(tm1.1Jae/Y) mutants and their wild-type male siblings that served as negative controls. In positive control mice carrying a maternally inherited Ube3a deletion, Ube3a sense transcript and protein levels were drastically reduced. Our data contrast with two recent reports of substantially decreased Ube3a expression in brain tissues of MeCP2-deficient mice. We, therefore, challenge the conclusion that decreased UBE3A/Ube3a expression contributes to the pathophysiology of RTT.
 ...
PMID:Ube3a expression is not altered in Mecp2 mutant mice. 1675 45

There are experimental evidences indicating that the non-competitive NMDA receptor antagonist MK-801 impairs cognition and produces a series of schizophrenia-like symptoms in rodents (hypermotility, stereotypies and ataxia). The present study was designed to investigate the efficacy of the selective 5-HT(6) receptor antagonist Ro 04-6790 in counteracting these MK-801-induced behavioural effects in the rat. The effects of Ro 04-6790 in antagonizing MK-801-induced memory deficits were assessed using the object recognition task. The ability of this 5-HT(6) receptor antagonist in counteracting hypermotility, stereotypies and ataxia produced by MK-801 were evaluated in a motor activity cage. Post-training administration of Ro 04-6790 (10 and to some extent also 3mg/kg) antagonized MK-801-induced performance deficits in a recognition memory test. In a subsequent study, Ro 04-6790 (3 and 10 mg/kg) reversed hypermotility and ataxia produced by MK-801. This 5-HT(6) receptor antagonist also alleviated MK-801-induced certain stereotypies. Our findings indicate that Ro 04-6790 attenuates behavioural effects related to the hypofunction of the NMDA receptor suggesting that this compound might be involved in the psychotomimetic effects of non-competitive NMDA receptor antagonists.
 ...
PMID:The selective 5-HT(6) receptor antagonist Ro 04-6790 attenuates psychotomimetic effects of the NMDA receptor antagonist MK-801. 1816 78


<< Previous 1 2 3 4 Next >>