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

The effects of excessive doses of phenylalanine on seizure susceptibility were examined in animal models in the past, primarily because of their relevance to phenylketonuria. It was thought that such effects might involve brain monoaminergic mechanisms. Recently, this issue has been pursued with a renewed interest but for a different reason. The dipeptide sweetener, aspartame, contains a phenylalanine residue. In the last three years, a number of studies involving as many as nine animal models of seizures have reexamined the effects of phenylalanine (and aspartame) on seizure thresholds. Data from these studies are in general agreement that aspartame at dosage levels below 1,000 mg/kg, or phenylalanine at equimolar doses, is without an effect on seizure susceptibility in animals. When the dosage level of aspartame reaches 1,000 mg/kg, the findings between various laboratories and from different animal models of seizures are inconsistent, showing either no effect or a proconvulsant effect. The Acceptable Daily Intake of aspartame in humans set by the Food and Drug Administration is 50 mg/kg/day. Thus, the data from the excessive bolus doses in rodents do not appear to be relevant to human use. This article provides a detailed review of the data from both early and recent studies and points out the methodological problems apparent at such high doses.
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PMID:Pharmacological effects of phenylalanine on seizure susceptibility: an overview. 265 69

Phenylketonuria (PKU) is a congenital defect involving failure to metabolize phenylalanine to tyrosine because of the absence of phenylalanine hydroxylase. Untreated PKU causes severe mental retardation, musty odor, hyperactivity, seizures, eczema and hypopigmentation. Without therapy, the child may develop with an IQ of less than 20. Restricting dietary phenylalanine before the onset of brain damage is necessary, to maintain the phenylalanine concentration at 3-8 mg/dl. Thirteen thousand three hundred and ninety-seven mentally retarded outpatients, aged 4 months to 24 years, from the year 1963 to 1987 were studied for PKU. Seven patients had positive PKU test by ferric chloride test and Phenistix, six PKU confirmed by paper chromatography. Two PKU by fluorometry and one PKU by amino acid analyzer. The incidence is 1:1,900 mentally retarded patients or 1:1,200,000 population. So, the incidence seems to be lower than in other countries which have neonatal screening for PKU. Because early diagnosis is essential in order to avoid the severe effects of PKU, neonatal screening has become widespread in the U.S., Australia, Great Britain, and other European Countries. The incidence of 1 PKU out of 1:1,200,000 Thai population seems to be not important enough for initiation of a PKU screening program in Thai newborns.
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PMID:The incidence of phenylketonuria in Thailand. 280 57

We measured local cerebral glucose utilization in 19 patients with Lennox-Gastaut syndrome (LG), partial seizures (PS), atypical and classical phenylketonuria (PKU), Leigh disease, and subacute sclerosing panencephalitis (SSPE), using positron emission tomography (PET). The mean values of regional glucose utilization in interictal scans of LG were significantly reduced in all brain regions when compared with that of PS (P less than 0.005). PET studies of glucose utilization in LG revealed more widespread hypometabolism than in PS. Two siblings with dihydropteridine reductase deficiency, a patient with classical PKU, and a boy with cytochrome c oxidase deficiency showed reduced glucose utilization in the caudate and putamen. A marked decrease in glucose utilization was found in the cortical gray matter of a patient with rapidly progressive SSPE, despite relatively preserved utilization in the caudate and putamen. The PET study of a patient with slowly progressive SSPE revealed patterns and values of glucose utilization similar to those of the control. Thus, PET provided a useful clue toward understanding brain dysfunction in LG, PS, PKU, Leigh disease, and SSPE.
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PMID:Cerebral glucose utilization in pediatric neurological disorders determined by positron emission tomography. 349 26

Ethical and legal traditions recognize prenatal duties to avoid harm to offspring. However, applying the harm principle to pregnancy requires a careful balancing of a baby's welfare with a pregnant woman's interest in liberty and bodily integrity. In the case of maternal PKU the mother can prevent harm to her baby by returning to the admittedly unpleasant diet that prevented her from being retarded. Informing, counseling, and access to medical care should be the primary policy. Seizures and forced treatment cannot be justified in this case, and only rarely in other situations.
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PMID:Pregnancy and prenatal harm to offspring: the case of mothers with PKU. 366 47

Pregnant rats injected with phenylacetate produced pups who had structurally abnormal cortical pyramidal cell dendrites. Neurons whose perikarya were in layer 5 had apical dendritic arbors with reduced numbers of dendritic spines which were longer and thinner than controls. Pyramidal cells of other cortical layers, as well as hippocampal pyramidal cells, were qualitatively and quantitatively normal. These results may be pertinent to children born to mothers with hyperphenylalaninemia (untreated PKU), many of whom have microcephaly, seizures and mental retardation. Application of findings in this rat model of maternal PKU to affected human children is uncertain until human histologic data become available.
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PMID:Cortical dendritic spine loss in rat pups whose mothers were prenatally injected with phenylacetate ('maternal PKU' model). 370 82

Biotinidase deficiency is the primary defect in most individuals with late-onset multiple carboxylase deficiency. We have reviewed the presenting clinical features of 31 children with the disorder. Seizures, either alone or with other neurological or cutaneous findings, are the most frequent initial symptom observed. Other neurological symptoms, such as hypotonia, ataxia, hearing loss, optic atrophy, and developmental delay, are seen, in addition to skin rash and alopecia. The disorder is also characterized by ketolactic acidosis and organic aciduria. Biotinidase activity may be diagnosed using a simple, rapid, semiquantitative colorimetric procedure. Samples of whole blood spotted on the same filter paper used by most states to screen for phenylketonuria and other inborn errors of metabolism may be sent to an appropriate reference laboratory. None of the common anticonvulsants or sedatives used to treat newborns and children interfere with the test. Because biotinidase deficiency can be treated readily with biotin, this disorder should be considered in children with infantile seizures, especially in the presence of other characteristic neurological or cutaneous features.
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PMID:Biotinidase deficiency: initial clinical features and rapid diagnosis. 407 53

The frequency of the various degrees of the intellectual defect and convulsive syndrome was studied in 473 patients with phenylketonuria divided into four groups as regards the phenylalanine blood level, that was 150 to 199 mg/l in group I, 200 to 299 mg/l in group II, 300 to 399 mg/l in group III, and 400 mg/l and higher in group IV. A substantial increase of the number of patients with grave mental derangement and epileptic seizures was noted in groups II and IV: this shows that the risk of the grave mental affection is the greater the higher the phenylalanine serum level. An increased number of patients with a slight intellectual derangement in group I (43.2%) was noted, while in all other groups, the frequency of the mild course of the disease remained stable (about 7.5%). Possibility of existence of several pathogenic thresholds of hyperphenylalaninemia, as well as possible mechanisms of brain protection are discussed.
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PMID:[Relationship between the severity of brain damage in phenylketonuria and the degree of hyperphenylalaninemia]. 722 98

To determine the importance of an abnormal EEG in phenylketonuria (PKU), we reviewed 137 EEGs from 48 patients with PKU. Patients were divided into three groups: group 1 (n = 14) had only normal EEGs, group 2 (n = 20) had only abnormal EEGs, and group 3 (n = 14) initially had normal EEGs that later became abnormal. The most common EEG abnormality was focal paroxysmal discharge. Patients in group 2 started treatment at a later age an had a greater frequency of seizures and mental retardation. Phenylalanine levels greater than 20 mg/dL were more often associated with abnormal EEGs. Older patients were more likely to have abnormal EEGs; 78% of the 41 patients who had EEGs at age 6 or older had abnormal records, whereas only 15% of the 26 patients who had EEGs before the age of 6 had abnormal records. Conventionally treated patients with classic PKU and normal EEGs in infancy may have abnormal EEGs when retested later even though they remain on a restricted diet. Although not usually associated with clinical deterioration, abnormal EEGs may unveil the presence of CNS dysfunction even when a child is in satisfactory clinical condition.
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PMID:EEG in phenylketonuria. Attempt to establish clinical importance of EEG changes. 746 35

We report our experience with the deficiency of 6-pyruvoyltetrahydropterin synthase, the most common form of tetrahydrobiopterin deficiency. We investigated 5200 patients suspected of having some inborn error of metabolism in a 10-year period, and detected 30 cases (from 28 sibships) of hyperphenylalaninaemias, HPA. From these, 4 sibships (5 patients) were affected by deficiency of 6-pyruvoyltetrahydropterin synthase. All of them were ethnically mixed, with some European ancestry detected in all. The age of diagnosis ranged from 2 to 9 years, and all were initially referred for investigation by having mental retardation and seizures. All of them showed low urinary biopterin levels and a marked elevation of neopterin. Although we detected only a few cases of HPA (30), 5 cases of 6-pyruvoyltetrahydropterin account for almost 20% of this total. The literature, however, reports a proportion of around 0.5%. As the frequency of classical phenylketonuria in our region is similar to that found in Caucasians (1/12,500), we believe that the frequency of this disease in South Brazil may be higher than expected (of the order of 1/400,000). We speculate that this finding could be related to a genetic drift (or founder effect).
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PMID:Possible high frequency of tetrahydrobiopterin deficiency in south Brazil. 796 77

The near-microscopic resolution of the mouse brain, by magnetic resonance imaging (MRI) at 9.4 T, permits in situ examination of the entire brain and longitudinal studies of neural development. MRI can be utilized to reveal brain structure at a resolution of 100 microns in the X, Y, and Z planes of brain, to differentiate the gray from white (myelin-rich) matter, and to reveal the ventricular compartments. The present report describes the structure of normal BALB/c mouse brain as revealed by imaging at 9.4 T and by histological stains; the structure of normal brain is compared with that from a phenylalanine hydroxylase-deficient mouse mutant line (Pah(enu2)) and those from normal littermates. The brains of patients with phenylketonuria (PKU) were reported to have demyelination and other structural abnormalities revealed by magnetic resonance imaging (MRI). Therefore, high-resolution MRI was used to examine the brain of this mutant, an animal model for the study of human phenylketonuria. Our study revealed no evidence of demyelination or other abnormalities in the brains of Pah(enu2) mice. Histologically, the mutant and normal mouse brains appear similar. This is consistent with a recent study from our laboratory which demonstrated that the histology of the brain of an untreated male patient, who died with PKU at the age of 29, was similar to control brain with the exception of changes directly related to visual blindness and seizures experienced by the patient.
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PMID:Near-microscopic magnetic resonance imaging of the brains of phenylalanine hydroxylase-deficient mice, normal littermates, and of normal BALB/c mice at 9.4 Tesla. 934 73


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