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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between the susceptibility to convulsions, the content of pyridoxal 5'-phosphate and the activity of pyridoxal kinase (EC 2.7.1.35) and glutamate decarboxylase (EC 4.1.1.15) in brain, was studied in the developing mouse. Seizures were induced by pyridoxal phosphate-gamma-glutamyl hydrazone (PLPGH), a drug previously reported to reduce the levels of pyridoxal 5'-phosphate and as a consequence to inhibit the activity of glutamate decarboxylase in brain of adult mice. It was found that the seizure pattern, as well as the time of appearance of convulsions, differed between 2- and 5-day old mice and 10-day old or older mice, indicating a progressive increase in seizure susceptibility during development. In brain, pyridoxal kinase activity and pyridoxal 5'-phosphate levels were decreased by the administration of PLPGH at all ages studied, whereas glutamate decarboxylase activity was inhibited less than 25% in 2- and 5-day old mice, and about 50% thereafter. Parallelly, the activation of glutamate decarboxylase by pyridoxal 5'-phosphate added in vitro to control homogenates was less in 2- and 5-day old mice than in older animals. It is concluded that the increase in the susceptibility to seizures induced by PLPGH during development is probably related to the increase observed in the sensitivity of glutamate decarboxylase in vivo to a decrease of pyridoxal 5'-phosphate levels. The correlation between pyridoxal 5'-phosphate, glutamate decarboxylase, and seizure susceptibility seems to be established at about 10 days of age.
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PMID:Seizure susceptibility in the developing mouse and its relationship to glutamate decarboxylase and pyridoxal phosphate in brain. 17 40

Experimental procedures are described which are believed to yield results that reflect, within certain limits, the in vivo changes of the size of the GABA pool in nerve endings in comparison with those of all other GABA pools. Two irreversible GABA-T inhibitors, vinyl GABA and acetylenic GABA, two GAD inhibitors, 3-mercaptopropionic acid and pyridoxal phosphate glutamyl-gamma-hydrazone, and di-n propylacetate, a clinically useful anticonvulsant, have been studied to determine their effects on GABA compartmentalization in mouse brain cortex. The changes elicited by these drugs in subcellular fractions of brain cortex homogenates support the notion that measurement of amino acid concentrations in crude synaptosomal fractions and in supernatant fractions under controlled conditions allow one to draw conclusions about relative changes of pool sizes in vivo. In particular this work showed that a specific increase in the concentration of GABA within the nerve endings is more important than a large increase of total brain GABA as a means of decreasing susceptibility to a variety of chemically or physically induced seizures.
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PMID:Metabolic inhibitors and subcellular distribution of GABA. 39 22

This paper reports the effect of acupuncturing "Renzhong" (GV26) and "Chengjiang" (GV24) points on OHP*-induced convulsion in mice. The results are as follows: 1. Convulsion induced by 6 ATA OHP were accompanied with a decrease in the brain GABA concentration. 2. When electro-acupuncture was applied for 15 minutes prior to exposure to hyperoxic chamber, the latency of convulsions was lengthened and the symptoms of seizures were alleviated. Besides, the brain GABA concentration was also elevated remarkably. 3. Administration of vitamin B6 enhanced the effect of acupuncture on convulsions and increased brain GABA concentration. 4. The latency of convulsions was well correlated with the GABA concentration of the brain (r = 0.9867). The above results indicate that acupuncture may elevate endogenous GABA levels in the brain and prevent the hyperbaric-oxygen-induced the decrease in the brain GABA content. Therefore. It is of protective effect against oxygen convulsions. Vitamin B6 may facilitate the effect of acupuncture by improving the GABA metabolism in the brain. In short, the effect of acupuncture against oxygen convulsions may be closely related to the increase in the brain GABA levels.
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PMID:[The effect of acupuncture on high oxygen pressure-induced convulsion and its relationship to the brain GABA concentration in mice]. 128 20

We recently reported that the mammalian brain has two forms of the GABA synthetic enzyme glutamate decarboxylase (GAD, E.C. 4.1.1.15), which are the products of two genes. The two forms, which we call GAD65 and GAD67, differ from each other in sequence, molecular size, subcellular distribution, and interactions with the cofactor pyridoxal phosphate (PLP), with GAD65 activity more dependent than that of GAD67 on the continued presence of exogenous PLP. The existence of two GAD genes suggests that individual GABA neurons may be subject to differential regulation of GABA production. We have examined the expression of these two forms of GAD during postnatal development of the rat striatum to determine whether different classes of GABA neurons selectively express different amounts of the two GAD mRNAs. Here we present evidence for a dramatic developmental difference in the expression of the two mRNAs during postnatal development of the rat striatum. Using in situ hybridization to the two GAD mRNAs, we observed a selective increase in GAD65 mRNA during the second postnatal week, at the time when striatal matrix neurons innervate the substantia nigra (SN). PLP-dependent enzyme activity in the midbrain increases in parallel with increased expression of GAD65 mRNA in the striatum. We hypothesize that the innervation of the SN by striatal neurons triggers an increase in GAD65. The changing ratios of GAD65 and GAD67 in the striatum may contribute to the well-documented changes in seizure susceptibility that occur in early life.
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PMID:Transient increase in expression of a glutamate decarboxylase (GAD) mRNA during the postnatal development of the rat striatum. 151 45

A randomized prospective trial has shown that folic acid started before conception and continued for the first trimester reduces the risk of recurrence of neural tube defects by 72% in women with a previously affected child. Carbamazepine exposure in utero is associated with a 1% risk of spina bifida. Long-term follow-up of antenatal exposure to phenobarbital and carbamazepine in two groups of infants shows no neurologic differences between the two groups. Magnesium sulfate is more effective in prevention of recurrent eclamptic seizures than phenytoin. During pregnancy, the need for thyroxine increases in many women. Vitamin B6 and ginger are both effective for nausea and vomiting in early pregnancy. Low-dose aspirin does not change the course of preeclampsia when it is started after the diagnosis is made. Angiotensin-converting enzyme inhibitors cause significant disturbances of fetal and neonatal renal function. Prophylactic beta-adrenergic agents fail to prevent prematurity in twins. Oral tocolysis with magnesium chloride or ritodrine is no more effective than observation alone. The risk of primary pulmonary hypertension in the newborn after indomethacin tocolysis is increased with prolonged therapy. Lithium causes polyhydramnios from fetal diabetes insipidus in utero. Treatment of Ureaplasma urealyticum infection with erythromycin during pregnancy does not eliminate the organism from the lower genital tract and does not improve perinatal outcome.
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PMID:Drug therapy during pregnancy. 154 29

Twenty patients with infantile spasms were treated with high doses of vitamin b6, valproic acid, or both. Three of 13 patients (23%) treated initially with high doses of vitamin B6 demonstrated a definite reduction in seizures; 2 patients had no improvement on electroencephalography. Vitamin B6 therapy alone was continued in a single patient (8%) who remained seizure-free during the 15-month follow-up period. Initial treatment with vitamin B6 and valproic acid improved the electroencephalogram significantly more (P less than 0.05) than initial vitamin B6 treatment alone. The group which had valproic acid added to vitamin B6 therapy had significantly fewer seizures (P less than 0.05) and better electroencephalograms (P less than 0.01) than did the group treated initially with vitamin B6 alone. There were no significant differences among the group treated initially with vitamin B6, the group treated initially with valproic acid, and the group in which valproic acid was substituted for vitamin B6. ACTH was more effective in abolishing seizures than was valproic acid or vitamin B6 and valproic acid. ACTH had an excellent effect on seizures in 86% of patients who did not respond well to vitamin B6, valproic acid, or both; however, many of these patients had later recurrence of infantile spasms. The combination of vitamin B6 and valproic acid is effective and safe in the treatment of infantile spasms.
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PMID:Vitamin B6 and valproic acid in treatment of infantile spasms. 164 74

We reported a female infant with early myoclonic encephalopathy (EME). She was diagnosed on the basis of clinical and laboratory features including electroencephalographic and magnetic resonance image (MRI) findings. Frequent erratic myoclonic seizures appeared since 28 days after birth and EEG showed a typical suppression-burst pattern. We administered a high-dose pyridoxal phosphate, thyrotropin-releasing hormone analogue (TRH), and then ACTH, but could not control the seizures at all. With seizure types, we observed the change from erratic myoclonus to tonic spasms in series, with concomitant EEG change to hypsarhythmia at the age of 6 months. Cranial MRI revealed delayed myelination in the white matter but no brain malformation. We administered ACTH to her again and succeeded partially in the decrease of the seizure frequency, and significantly in the improvement of EEG findings. It is supposed that the responsiveness to ACTH treatment changed with age as the seizure patterns developed from erratic myoclonus to tonic spasm.
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PMID:[A longitudinal study of clinical and electroencephalographic findings in a female infant with early myoclonic encephalopathy]. 165 45

Combination therapy of high-dose pyridoxal phosphate (PAL-P, 40-50 mg/kg/day) and low-dose ACTH beta 1-24-Z (tetracosactide acetate-Zn, Cortrosyn Z, 0.01 mg/kg/day) was instituted in 26 children suffering from West syndrome and related disorders--pretreated without success with high-dose PAL-P alone; 18 with West syndrome (14 with symptomatic and 4 with cryptogenic types), 2 with symptomatic Lennox-Gastaut syndrome, 5 with cerebral palsy with hypsarhythmia or diffuse slow spike-waves and one with myoclonic seizures (secondary generalized epilepsy). Clinical, electroencephalographic and neurochemical investigations were carried out. The results were summarized as follows. 1) Only one of 27 children with West syndrome and related disorders pretreated using high-dose PAL-P alone before ACTH showed a clinically excellent response. 2) Clinical seizures were completely suppressed in 19 of 21 children who initially had seizures (90%) after this combination therapy. 3) Twenty-one of the total 26 children (80%) had disappearance of hypsarhythmia or diffuse slow spike-waves in EEG after this therapy. 4) During PAL-P treatment alone transient increases in liver enzymes occurred in 37 percent. The brain shrinkage of CT and the significant rise in CSF NSE were seen in 95% and 78% after ACTH, respectively. 5) Twenty-three children have been followed for one to 29 months after tapering off of ACTH. No relapses were experienced in 11 of 18 who initially had seizures (61%) and 13 of 23 with hypsarhythmia or diffuse slow spike-waves (57%). 6) Postictal PRL elevations were suppressed during high-dose PAL-P. 7) No significant changes in the CSF levels of HVA and 5-HIAA were seen during this combination therapy. The CSF levels of HVA were significantly lower than the controls. 8) Daily ACTH therapy transiently suppressed the secretion of anterior pituitary hormones (GH, TSH, PRL, LH and FSH) and thyroid hormones (T3 free T3, T4 and free T4). It is recommended that the combination therapy of high-dose PAL-P and low-dose ACTH is a promising new method and should be tried in children with West syndrome and related disorders. The mechanism of action of this combination therapy remains obscure although some information has been obtained from our investigations.
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PMID:Combination treatment of high-dose pyridoxal phosphate and low-dose ACTH in children with West syndrome and related disorders. 170 36

The hippocampus, a component of the limbic system, is a prominent subcortical structure, which not only contains high concentrations of zinc, but also exhibits regional variations in this essential element, with concentrations being highest in the hilar region and lowest in the fimbria. For example, the concentration of zinc in the mossy fiber axons has been estimated to approach 300-350 microM. Both zinc and pyridoxal phosphate (PLP) deficiency and excess have been reported to produce epileptiform seizures, which are blocked by gamma-aminobutyric acid (GABA). The proposed mechanism is that at physiological concentrations zinc stimulates the activity of the hippocampal pyridoxal kinase (50% stimulation at 1.7 x 10(-7) M), enhancing the formation of PLP, whereas in pharmacological doses zinc inhibits the activity of glutamate decarboxylase (GAD) directly (50% inhibition at 6.5 X 10(-4) M) by preventing the binding of PLP to HoloGAD. Furthermore, recent studies have shown that two forms of GAD are found in the rat brain. One form (GAD A) does not require PLP for maximal activity, while another form (GAD B) does. Furthermore, the ratio between GAD A and GAD B is nonuniform throughout brain areas, and the hippocampus contains twice as much GAD B (the PLP-requiring GAD) as GAD A. Although the hippocampus is a common target of exogenous neurotoxic agents, "free" zinc in greater than physiological concentrations should be considered an endogenous central neurotoxin. For example, iontophoretically applied zinc in the frontoparietal cortex enhances and prolongs the firing rate of neurons in urethane-anesthetized rat. In addition, zinc (50-500 microM) significantly depresses the paired-pulse potentation in the hippocampal CA3 subfield. Moreover, zinc selectively blocks the action of N-methyl-D-aspartate on cortical neurons and enhances the quisqualate receptor-mediated injury. Finally zinc competitively inhibits the calcium-dependent release of transmitter by inhibiting the entry of Ca2+ into the nerve terminals. Since zinc in a concentration of 300-350 microM could not possibly remain "unbound" in the hippocampus, we searched for and identified a metallothionein-like protein (MT) in the bovine hippocampus, which produces two isoforms on reverse-phase HPLC and lacks aromatic amino acids, but possesses metallomercaptide bonds. We believe that the hippocampal metallothionein, by donating zinc to an extensive number of zinc-activated, PLP-mediated biochemical reactions, modulates synaptic functions. Furthermore, by virtue of its inducibility, metallothionein binds additional amounts of zinc, maintains its steady-state concentration, prevents inhibition of an extensive number of sulfhydryl-containing enzymes and receptor sites, and hence averts metal-related neurotoxicity.
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PMID:Hippocampal zinc thionein and pyridoxal phosphate modulate synaptic functions. 219 11

A patient of pyridoxine dependent seizures was reported. He was born at 34 weeks' gestation and weighted 2,760 g. Apgar scores were 6 and 9 at 1 and 5 minutes, respectively. He showed the first seizure 2 hours after his birth. Phenobarbital, phenytoin, sodium valproate, diazepam and clonazepam were not effective. Pyridoxal phosphate (50 mg) was given intravenously, resulting in suppression of convulsions. However, muscle tonus was severely depressed. In EEG, a discontinuous pattern was found in quiet and indeterminate sleep on the 2nd day of life. At 5th week multifocal spikes were found, and the discontinuous pattern persisted. Ictal discharges at 13th week showed generalized, continuous, irregular and high voltage slow waves with multifocal spikes. At 27th week of life, high voltage slow waves disappeared and multifocal spike discharges decreased. At 2 years and 10 months of age, the patient was suffering from athetotic cerebral palsy and severe mental retardation. Pyridoxal phosphate at the doses of 35-40 mg/kg/day had been administered. Irritability sometimes occurred and additional 50 mg of pyridoxal phosphate controlled this irritability effectively.
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PMID:[Chronological change of EEG findings in a case of pyridoxine dependency seizures]. 222 90


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