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

The anticonvulsant potency and neurological toxicity of two new catalytic inhibitors of GABA-transaminase have been assessed in acute experiments in baboons with a natural syndrome of photic epilepsy. gamma-Acetylenic GABA, 160--200 mg/kg, or gamma-vinyl GABA, 450--950 mg/kg, intravenously, gave complete protection against generalised myoclonus or seizure responses induced by photic stimulation (in baboons without or with priming with subconvulsant doses of allylglycine). The protection became maximal 1--3 h after injection, and continued for 7--24 h. Signs characteristic of the acute toxicity of anticonvulsant drugs (nystagmus and ataxia) were not seen. The potential use of these compounds in human epilepsy deserves investigation.
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PMID:Blockade of epileptic responses in the photosensitive baboon, Papio papio, by two irreversible inhibitors of GABA-transaminase, gamma-acetylenic GABA (4-amino-hex-5-ynoic acid) and gamma-vinyl GABA (4-amino-hex-5-enoic acid). 10 Aug 12

Acrylamide, widely employed as a vinyl monomer in the polymer industry, is a potent neurotoxin to man and to animals. The cumulative effect of prolonged, low-level exposure to acrylamide monomer is the insidious development of a progressive peripheral neuropathy. Sensory symptoms begin in the hands and feet (numbness, pins and needles), certain reflexes are lost and, with severe exposure, muscle weakness and atrophy occur in the extremities. The peripheral neuropathy may be supplemented by symptoms indicative of central nervous system damage (ataxia, tremor, somnolence and mental changes). The neuropathologic basis for this clinical picture has been determined in cats. Here, chronic acrylamide intoxication produces selective peripheral and central nerve fiber degeneration. Degeneration first occurs in the extremities of long and large nerve fibers which later undergo a progressive, seriate proximal axonal degeneration known as dying-back. Especially vulnerable are sensory axons supplying Pacinian corpuscles and muscle spindles in the hindfoot toepads, while adjacent motor nerve axons die back later. Distal central nerve fiber degeneration is seen in the medulla and the cerebellum. The neurotoxic property of acrylamide is of practical concern in two areas. One major problem is the protection of factory workers engaged in the manufacture of acrylamide. A sensitive test of neurologic function in these individuals, i.e., touch sensation, based on the experimental observation of the exquisite vulnerability of Pacinian corpuscles in acrylamide intoxicated cats, is presently under consideration. The second area for concern is the exposure of the populace to minute amounts of neurotoxic acrylamide monomer which contaminate acrylamide polymers currently deployed in the environment. Federal restrictions on the maximum permitted exposure to acrylamide, based on a largely clinical study of acrylamide neurotoxicity conducted ten years ago, may require a re-evaluation in the light of recent advances which have pinpointed the initial sites of nerve fiber degeneration.
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PMID:Nervous system degeneration produced by acrylamide monomer. 17 76

1. The anticonvulsant potency of vigabatrin (gamma-vinyl GABA, GVG) was studied in an open trial in a group of 21 mentally handicapped patients with drug-resistant epilepsy. 2. With this treatment one third of these patients had more than 50% reduction in seizure frequency. The anticonvulsant effect appeared during the first month of therapy and was maintained during a 7-month study. The side effects were mild: mainly tiredness, aggressiveness, and ataxia. Other anticonvulsant drugs remained at baseline levels during GVG therapy. GVG was not found to modulate EEG recordings. 3. According to our results, GVG is effective for treating intractable epilepsy in mentally handicapped patients.
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PMID:Vigabatrin in epilepsy in mentally retarded patients. 275 2

Tetrahydroisoxazolopyridinol (THIP), a GABA receptor agonist, gamma-acetylenic-GABA(GAG) and gamma-vinyl-GABA(GVG), two GABA transaminase inhibitors were given in single parenteral doses to three Cebus apella monkeys with persistent dyskinetic movements induced by earlier long-term administration of haloperidol. High doses of THIP temporarily abolished dyskinesias but also caused bradykinesia, ataxia, dystonia and myoclonic jerks. GAG and GVG reduced dyskinesias to a lesser extent and with fewer side effects. Whether the observed antidyskinetic effect is secondary to the concomitant general toxic effects or if these drugs have a specific antidyskinetic action remains an open question.
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PMID:GABA agonists in cebus monkeys with neuroleptic-induced persistent dyskinesias. 289 37

We studied the antiepileptic potency of vigabatrin (gamma-vinyl GABA, GVG) as an open trial in a group of 36 mentally handicapped patients with drug-resistant epilepsy (30 had seizures of partial onset and 6 had primary generalized [PG] tonic-clonic convulsions). With this treatment, 13 (43%) of the patients with seizures of partial onset and 2 (33%) with PG had more than 50% reduction in seizure frequency. The antiepileptic effect appeared during the first month of therapy and continued throughout the 7-month study. The side effects were mild: tiredness, aggressiveness, and ataxia. Other antiepileptic drugs remained at baseline levels during GVG therapy. GVG did not alter EEG recordings. Our results suggest that GVG is effective for treatment of intractable epilepsy, especially the partial type, in mentally retarded patients. Longer follow-up is needed, however, to determine that the clinical effect is maintained and that no severe side effects appear.
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PMID:Effect of vigabatrin on epilepsy in mentally retarded patients: a 7-month follow-up study. 336 72

The efficacy and tolerability of vigabatrin (gamma-vinyl GABA, GVG), given as add-on therapy to 23 adult outpatients with severe drug-resistant epilepsy (17 with partial seizures), were studied using a double-blind, placebo-controlled, crossover design. The study consisted of two 7-week periods during which vigabatrin and placebo were administered in random sequence. Dosage was 1.0 g twice daily for patients weighing less than or equal to 65 kg and 1.5 g twice daily for patients weighing greater than 65 kg. Three patients were dropped from the study, two for reasons unrelated to treatment and one because of the appearance of vertigo, headache, dysarthria, and ataxia, which subsided rapidly when vigabatrin was stopped (3 g daily). Sixteen of the 20 patients available for analysis showed a decrease in the total number of seizures as compared with the placebo period. Of these, 12 showed a greater than 50% reduction in seizure frequency and 4 of the 12 showed a greater than 75% reduction. Both the total number of seizures and the number of partial seizures were significantly reduced by vigabatrin (p less than 0.01). Only in the patient who dropped out were severe adverse effects seen. The most frequently reported unwanted effect was mild drowsiness, which developed in seven patients on vigabatrin and in one on placebo. Positive effects, however, were also seen with six patients who reported an improved sense of well-being while receiving vigabatrin as compared with only 1 during the placebo period. No consistent changes in electrocardiogram (ECG), electroencephalogram (EEG), and visual-, auditory-, and somatosensory-evoked potentials were seen during the study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vigabatrin in the treatment of epilepsy: a double-blind, placebo-controlled study. 353 69

The antiepileptic effect of vigabatrin (gamma-vinyl GABA, VGB) in children has been demonstrated in controlled and open studies. According to the literature, results were good to excellent in partial seizures (with and without becoming secondarily generalized) and promising in infantile spasms (IS). In patients with myoclonic epilepsies of early childhood and especially those with Lennox-Gastaut syndrome (LGS), the effect of VGB has been investigated only to a limited extent and the pattern of response was variable. The present open, add-on, dose-ranging study was initiated to assess the long-term effect and safety of VGB in a cohort of 20 children with LGS who were not responding sufficiently to first-line drug monotherapy with valproate (VPA) instead of adding classical second-line antiepileptic drugs [AEDs: benzodiazepines (BZD), phenobarbital (PB), primidone (PRM)], which usually are associated with rapid diminution of their antiepileptic properties and a high frequency of side effects. Eighty-five percent of children experienced a 50-100% reduction in seizure frequency, even after dose reduction of VPA. No serious side effects occurred except in 1 patient who experienced dyskinesia. Mood changes, sedation, ataxia, and hypersalivation, well-known complications of other AEDs, were not observed.
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PMID:Gamma-vinyl-GABA (vigabatrin) in the therapy of Lennox-Gastaut syndrome: an open study. 792 71

The acute toxicity and primary irritancy of the industrial chemicals 5-ethylidene-2-norbornene (ENB) and 5-vinyl-2-norbornene (VNB) were studied. They are of moderate acute peroral toxicity in the rat, with LD50 values for ENB of 2.54 (male) and 5.66 (female) ml kg(-1), and for VNB of 5.90 (male) and 11.9 (female) ml kg(-1). Percutaneous toxicity is slight in the rabbit by 24-h occluded contact, with no mortalities for ENB up to 8.0 ml kg(-1) and only one mortality (male) at 16.0 ml kg(-1) VNB. Dynamically generated saturated vapor atmosphere LT50 values for ENB in the rat were 75 (male) and 125 (female) min, and for VNB they were 28 (male) and 37 (female) min. The 4-h LC50 values for ENB were 2717 (male) and 3015 (female) ppm, and for VNB they were 2231 (male) and 2518 (female) ppm. Intravenously, the ENB LD50 ranged from 0.09 (male rabbit) to 0.11 ml kg(-1) (female); corresponding LD50 values for VNB were 0.10-0.05 mg kg(-1). Acute neurotoxic signs were seen by the intravenous and inhalation routes of exposure, including tremors, ataxia and convulsions; the latter were sufficient to cause vertebral column luxation or fracture, producing spinal cord compression and resultant hindlimb paralysis. Both ENB and VNB are moderately irritating to the skin (rabbit), causing erythema and edema, but not necrosis. Both materials cause slight conjunctival hyperemia and chemosis in rabbits, but not corneal injury.
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PMID:Comparative acute toxicity and primary irritancy of the ethylidene and vinyl isomers of norbornene. 928 33

The authors describe the case of a 3-year-old boy with a giant congenital vertex hemangioma who underwent presurgical embolization with Onyx (ethylene-vinyl alcohol copolymer dissolved in dimethyl sulfoxide) and Glubran ( N-butyl-2-cyanoacrylate). This vascular tumor had no intracranial vascular communication as assessed by pre-embolization MRI and catheter angiography. All embolizations were performed by direct percutaneous injection. One week following the last embolization procedure the child presented with a 24-hour history of ataxia and extrapyramidal tremor. He was diagnosed with a possible immune-mediated reaction to Onyx or Glubran, which was treated with an urgent surgical excision of the hemangioma followed by intravenous administration of immunoglobulin and steroids. To the authors' knowledge, this is the first case of possible immune-mediated toxicity secondary to either Onyx or Glubran administration. This case highlights the need for awareness of potential toxic reactions to these embolic agents in the treatment of hemangiomas in the pediatric patient.
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PMID:Possible toxicity following embolization of congenital giant vertex hemangioma: case report. 2793 67