Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One in every 250 newborns is exposed to antiepileptic drugs (AEDs) in utero. Various studies have attributed a teratogenic effect to these AEDs, mainly consisting of major malformations, minor anomalies, intrauterine or postnatal growth failure, and psychomotor retardation. Prospective studies confirm the increased risk of major malformations. The absolute risk of 7-10% is about 3-5% higher than that in the general population. Barbiturates and phenytoin (PHT) are particularly associated with congenital heart malformations, facial clefts, and some other malformations. Valproate (VPA) and carbamazepine (CBZ) are associated predominantly with spina bifida aperta (1-2 and 0.5-1.0% risk, respectively) and hypospadias. Bilateral radial aplasia is a rare but specific effect of VPA. Several studies identified additional risk factors, i.e., high daily AED dosage, high maternal serum AED concentrations, low folate levels, or polytherapy [phenobarbital (PB) plus primidone (PRM) plus PHT or CBZ plus VPA plus PB with or without PHT]. The few prospective studies controlled for socioeconomic factors or that considered parental findings indicate that risk of specific cognitive defects rather than risk of overall mental retardation may be increased, that early growth retardation is followed by a catch-up growth to normal, and that ocular hypertelorism and nail hypoplasia are the only minor anomalies causally related to PHT exposure. However, no final conclusions can be made. Genetic predisposition to the teratogenic side effects of AEDs plays a role, codetermining the recurrence risk if the woman has previously given birth to a child with a major malformation. The molecular genetic basis of this predisposition is unclear.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pregnancy and the risk of teratogenicity. 142 93

The authors report the results obtained in 42 patients affected by infantile spasms syndrome during treatment with Sodium Dipropylacetic acid. The subjects were divided into two groups according to the aetiology: idiopathic and secondary. In the first group the use of DPK as determined the disappearance of the seizures in 6 cases (40%), reduction of the crises beyond 50% in 7 cases (46.6%), while in 2 subjects (13.3%) the crises persisted. In the secondary group the crises ceased in 3 cases (11.1%), in 17 (62.9%) there were a reduction of the crises beyond 50%, no response to the drug was observed in 7 subjects (25.9%). In 10 patients the anticonvulsant treatment was progressively diminished and was substituted with hormonal treatment. The long term follow up (1-6 years) gives the following results: the seizures persisted in 2 cases (18.18%) among the idiopathic form and in 6 cases (28.57%) among the secondary group. Mental retardation was found in 4 subjects (36.36%) among the idiopathic group and in 12 patients (57.14%) among the secondary group. The authors shortly report the side effect of the hormonal treatment: they prefer the initiation of treatment of I.S. with anticonvulsant drug and suggest to resort to the ACTH when the initial treatment is unsuccessful.
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PMID:[Therapy of infantile spasms (West syndrome) with sodium dipropylacetate]. 301 74

Oral administration of antiepileptic drugs can temporarily be impossible under certain conditions, such as altered states of consciousness, spike-wave stupour, gastro-intestinal disturbances with nausea and vomiting, prior to or during surgery or certain diagnostic procedures, and because of drug refusal in patients with mental retardation or psychiatric problems. Although rectal administration of sodium valproate (NaVPA) has been shown to be a possible alternative route, little is known about the bioavailability and local effects during repeated administration of NaVPA suppositories. These aspects were investigated in 13 epileptic children and adolescents on chronic NaVPA therapy. Eight patients were treated with the oral solution (Group A; mean age 10.6 years) and five patients with enteric coated tablets (Group B, mean age 16.4 years). In every patient five serum levels of VPA over a 24 h period were measured under steady-state conditions. Thereafter, suppositories were administered for 2-7 days and serum levels were again determined (identical dosing and sampling times). Bioavailability of NaVPA was calculated on the basis of the area under the concentration vs. time curve over 24 h. The average bioavailability for suppositories compared with the oral form was 112.4% in Group A and 99.5% in Group B. Fluctuations of serum VPA levels were very similar with suppositories and oral solution, and more pronounced than with the enteric coated tablets. Stool frequency was not increased by repeated administration of suppositories, except for a three-fold increase in one patient. There was no objective or subjective evidence of local irritation from the suppositories. In conclusion, NaVPA suppositories have the same bioavailability under steady-state conditions as oral preparations and they are well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bioavailability of sodium valproate suppositories during repeated administration at steady state in epileptic children. 311 82

The literature on the correlation of epilepsy and psychosis is reviewed briefly. The terms "forced normalization" and "alternative psychosis" and further the risk factors in the genesis of psychosis in epilepsy are underlined with special emphasis on childhood and adolescence. Furthermore the case of a girl aged 16.7 years is reported. This girl developed blinking fits at the age of 7 years and in 1978 at the age of 16 paranoid-hallucinatory symptoms with temporarily increasing paroxysmal potentials in the EEG following an initial depressive phase. Phenytoin and Valproate was administered. The psychotic and epileptic symptoms diminished with simultaneous amelioration of the EEG. After discharge a neuroleptic medication was added temporarily due to slight exacerbation of the psychotic symptoms. Finally risk factors of psychosis in epilepsy are considered with special respect of mental retardation and age of the patient.
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PMID:[Coincidence of epilepsy and psychosis in a 16-year old female patient (author's transl)]. 677 84

A 32-year-old man with mental retardation and uncontrolled complex partial epilepsy receiving carbamazepine (CBZ) and divalproex sodium (VPA), developed frequent episodes of forced upward gaze after increase in the daily VPA dosage. CBZ dosage was decreased, with prompt resolution of symptoms. The upward gaze problem recurred several months later. CBZ dosage was decreased further with subsequent resolution of symptoms. Therefore, the oculogyric crisis (OGC) appeared to be induced by CBZ.
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PMID:Oculogyric crisis induced by carbamazepine. 758 63

A 14-year-old boy with mental retardation presented with severe thrombocytopenia, macrocytic anaemia and allergic dermatitis. He had been treated with valproate for seizures since the age of 2 years. Clinical examination showed severe purpura, mucous bleeding and extensive dermatitis. Tests to detect serum direct antiplatelet antibodies were positive and bone marrow examination revealed myelodysplastic abnormalities. Valproate was discontinued and both dermatitis and general condition of the child improved with normalization of the full blood count. This report suggests that valproate may produce both peripheral immune thrombocytopenia and severe bone marrow depression several years after the initiation of the therapy.
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PMID:Haematological disturbances during long-term valproate therapy. 803 31

Valproic acid is a useful antiepileptic drug, with occasional gastrointestinal side effects. Hepatotoxicity is the most serious adverse reaction and, although rare, it can be fatal. Risk factors for hepatotoxicity are an age of less than two years, polytherapy and mental retardation; it has been rarely reported in adults. We report three mentally retarded adult patients receiving polytherapy, who developed valproic acid induced hepatotoxicity. Two patients had a symptomatic hepatitis with a concomitant paradoxical increase in seizure frequency and one an asymptomatic alteration of hepatic function tests. After discontinuing the drug, the hepatitis subsided. We conclude that hepatotoxicity must be considered as a possible side effect of valproic acid and we suggest some recommendations for its early detection.
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PMID:[Hepatotoxicity induced by valproic acid in adults. Report of 3 cases]. 808 69

Exposure to antiepileptic drug (AED) treatment in utero occurs in 1 of every 250 newborns. The absolute risk of major malformations in these infants is about 7-10%, approximately 3-5% higher than in the general population. Specific risk factors include high maternal daily dosage or serum concentrations of AED, low folate levels, polytherapy, and generalized seizures during pregnancy. Adverse pregnancy outcomes, including congenital heart malformations, facial clefts, spina bifida aperta, hypospadias, growth retardation, and psychomotor and mental retardation, are associated with, although not necessarily caused by, AED exposure. Specific cognitive defects, hypertelorism, and nail hypoplasia can be causally related to specific AED exposures. To prevent teratogenic side effects, the prospective mother should be treated with AEDs only when absolutely necessary. Monotherapy with the AED that is most effective in the lowest possible daily dose (divided into at least two or three administrations) should be prescribed. High-dose folate supplementation (4-5 mg/day) reduces the risk of a neural tube defect in a child whose sibling had such a defect, but its impact on the specific teratogenic risks of AEDs is unknown. A substantial proportion of fetal malformations may be secondarily prevented by prenatal diagnosis, consisting of a fetal structural ultrasound examination at weeks 18 and 20 of gestation and, with VPA or CBZ administration, an alpha 1-fetoprotein analysis of amniotic fluid at week 16. Determination of a specific defect prevention strategy depends largely on parental attitudes toward prenatal diagnosis and termination of pregnancy, which should be discussed before conception.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Teratogenic effects of antiepileptic drugs: implications for the management of epilepsy in women of childbearing age. 817 16

Congenital bilateral perisylvian syndrome (CBPS) is a recently described, neuronal migration disorder, characterized by pseudobulbar palsy, epilepsy and mental retardation and bilateral perisylvian dysplasia. A 15-year-old boy was diagnosed with CBPS according to the typical clinical, and magnetic resonance imaging (MRI) features. The patient was suffering from atypical absence seizures, repeating daily in spite of antiepileptic drug therapy, since age 7 years. He had also experienced rare generalized tonic-clonic seizures and complex partial seizures. Neurological examination showed severe restriction of tongue movements, severe dysarthria, dysphagia, facial diplegia, mild pyramidal signs and moderate mental retardation. A computed tomographic (CT) scan demonstrated bilateral perisylvian enlargement. The diagnosis was corrected with MRI after six years. Frequent irregular generalized spike and wave abnormalities and focal sharp and slow waves over the posterior regions of both hemispheres were shown by electroencephalograms (EEG). The patient was treated with Na-Valproate, carbamazepine and lamotrigine but did now show any significant change in seizure frequency in the eight-year follow-up period. Intractable seizures, mental retardation and particularly congenital pseudobulbar palsy suggest this congenital entity. Those patients who exhibit these typically clinical features, must have MRI.
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PMID:A clinically recognizable neuronal migration disorder: congenital bilateral perisylvian syndrome. Case report with long-term clinical and EEG follow-up. 953 Sep 47

Ornithine transcarbamylase deficiency is an X linked disorder and the most common inherited cause of hyperammonaemia. Fluctuating concentrations of ammonia, glutamine, and other excitotoxic amino acids result in a chronic or episodically recurring encephalopathy. A heterozygous female patient first presented with protein intolerance, attacks of vomiting, and signs of mental retardation in early childhood. At the age of 16 complex partial seizures occurred which were treated with sodium valproate. Seven days after initiation of valproate therapy, she developed severe hyperammonaemic encephalopathy with deep somnolence. The maximum concentration of ammonia was 480 micromol/l. After withdrawal of valproate, three cycles of plasma dialysis, and initiation of a specific therapy for the inborn metabolic disease, ammonia concentrations fell to normal values. The patient remitted, returning to her premorbid state. Valproate can cause high concentrations of ammonia in serum in patients with normal urea cycle enzymes and may worsen a pre-existing hyperammonaemia caused by an enzymatic defect of the urea cycle. Sufficient diagnostic tests for the detection of metabolic disorders must be performed before prescribing valproate for patients with a history of encephalopathy.
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PMID:Hyperammonaemic encephalopathy after initiation of valproate therapy in unrecognised ornithine transcarbamylase deficiency. 959 92


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