RESUMO
Epilepsy is a dominant trait in EL mice, a model for human complex partial seizures. We recently mapped the major gene, El-1, to chromosome 9 near the predicted location for the ceruloplasmin (Cp) gene. We now present evidence for a partial duplication in the Cp gene in EL mice. This Cp duplication is coinherited with seizures in backcross generations and is associated with enhanced expression of Cp mRNA and increased Cp oxidase activity. Moreover, the duplication is associated with an enhanced frequency of double recombinants, simulating negative interference. The findings are relevant to the basic mechanisms of epilepsy and to theories of genetic recombination and gene mapping.
Assuntos
Ceruloplasmina/genética , Modelos Animais de Doenças , Epilepsia Parcial Complexa/genética , Camundongos Endogâmicos/genética , Camundongos Mutantes Neurológicos/genética , Família Multigênica , Animais , Ceruloplasmina/biossíntese , Mapeamento Cromossômico , Cobre/fisiologia , Cruzamentos Genéticos , Troca Genética , Epilepsia Parcial Complexa/enzimologia , Regulação Enzimológica da Expressão Gênica , Humanos , Fígado/enzimologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Recombinação GenéticaRESUMO
Sprouting of mossy fibers in the hippocampus of rats that underwent limbic epileptogenesis by amygdala kindling or kainate injection was studied at the light microscopic and ultrastructural levels by cytochemical demonstration of the enzyme 5'-nucleotidase. This adenosine-producing ectoenzyme has previously been shown to characterize malleable terminals during brain development and lesion-induced synaptogenesis, but to be otherwise associated with glial membranes. At the light microscopic level, kainate-treated but not control or kindled rats showed 5'-nucleotidase activity in the CA3 region and in the inner molecular layer of the dentate gyrus. At the ultrastructural level, in control animals, the synapses of the molecular and granular layers were enzyme negative. Only some mossy fiber boutons of the dentate hilus exhibited 5'-nucleotidase activity. In epileptic rats, synaptic labeling within the hilus appeared more intense. Moreover, 5'-nucleotidase-containing terminals within the inner molecular layer, presumably ectopic mossy fiber boutons, were found in both kindled and kainate-treated rats. It is concluded that, in both the normal and epileptic hippocampus, 5'-nucleotidase is associated with axons capable of a plastic sprouting response. The synaptic enzyme may attenuate the glutamatergic transmission of mossy fibers, in particular of the aberrant mossy fibers in epileptic rats, by producing the inhibitory neuromodulator adenosine. Alternatively, 5'-nucleotidase may influence synapse formation by its putative non-enzymatic, adhesive functions.
Assuntos
5'-Nucleotidase/metabolismo , Giro Denteado/citologia , Giro Denteado/enzimologia , Epilepsia Parcial Complexa/enzimologia , Fibras Musgosas Hipocampais/enzimologia , Tonsila do Cerebelo/fisiologia , Animais , Giro Denteado/patologia , Estimulação Elétrica , Epilepsia Parcial Complexa/induzido quimicamente , Epilepsia Parcial Complexa/patologia , Agonistas de Aminoácidos Excitatórios , Feminino , Histocitoquímica , Ácido Caínico , Microscopia Eletrônica , Fibras Musgosas Hipocampais/patologia , Fibras Musgosas Hipocampais/ultraestrutura , Ratos , Ratos WistarRESUMO
UNLABELLED: The activities of gamma-aminobutyrate aminotransferase (GABA-T) and monoamine oxidase (MAO-A and -B) were measured in blood platelets from 27 patients and hippocampal tissues from eight (GABA-T) and ten (MAO) patients with complex partial seizures. The activity of platelet GABA-T was found to be higher in the epileptic patients (43.37 +/- 13.53 pmol/min/mg protein, P < 0.005) in comparison with that found in 14 healthy volunteer subjects (29.59 +/- 13.14 pmol/min/mg protein). This difference was most pronounced in patients treated with carbamazepine (CBZ) (P < 0.01) and phenytoin (PHT) (P < 0.01). Contrary to the platelets, the activity of GABA-T in the hippocampi from the epileptic patients (6.937 +/- 2.204 nmol/min/mg protein) did not differ significantly from that found in seven non-epileptic control cases (7.158 +/- 0.951 nmol/min/mg protein). The increase in GABA-T activity in the blood platelets from the epileptic patients could not be explained by a direct effect of the antiepileptic compounds, since there were no changes in the activities on exposure to PHT, CBZ or VPA in vitro, either of blood platelets or of brain tissue. With regard to platelet MAO, no difference in the activity was found between the two groups, whereas the MAO-B activity in the hippocampi was significantly higher in the epileptic patients (3.51 +/- 1.32 nmol/mg/mg protein) than in the control cases (1.21 +/- 0.73 nmol/mg/mg protein) (P < 0.0004). There was no difference in MAO-A activity in the hippocampi between epileptic patients and controls. CONCLUSION: In the hippocampi from patients with complex partial seizures the activities of the mitochondrial enzymes GABA-T and MAO-A were similar to those found in control subjects. The activity of MAO-B, however, was significantly higher indicating that there is an increased proportion of reactive astrocytes in epileptic hippocampus.
Assuntos
4-Aminobutirato Transaminase/metabolismo , Plaquetas/enzimologia , Encéfalo/enzimologia , Epilepsia Parcial Complexa/enzimologia , Monoaminoxidase/metabolismo , 4-Aminobutirato Transaminase/sangue , Adulto , Epilepsia Parcial Complexa/sangue , Feminino , Hipocampo/enzimologia , Humanos , Masculino , Pessoa de Meia-Idade , Monoaminoxidase/sangueAssuntos
Proteínas do Tecido Nervoso/sangue , Fosfopiruvato Hidratase/sangue , Estado Epiléptico/enzimologia , Adolescente , Adulto , Idoso , Biomarcadores , Dano Encefálico Crônico/sangue , Dano Encefálico Crônico/etiologia , Epilepsia Parcial Complexa/complicações , Epilepsia Parcial Complexa/enzimologia , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estado Epiléptico/complicações , Estado Epiléptico/terapia , Resultado do TratamentoRESUMO
We report the presence of serum autoantibodies directed against glutamic acid decarboxylase in a patient with epilepsy and palatal myoclonus not associated with brain lesions. Glutamic acid decarboxylase antibody reactivity was dependent on the presence of carboxy-terminal amino acids, similar to that reported in patients with stiff-man syndrome. Marked reduction in the frequency of epileptic attacks and improvement in palatal myoclonus occurred when benzodiazepine was administered and phenytoin was gradually tapered. Testing for anti-glutamic acid decarboxylase antibodies may be indicated in patients with palatal myoclonus and with convulsive disorders refractory to therapy.
Assuntos
Anticorpos/análise , Epilepsia Parcial Complexa/enzimologia , Epilepsia Parcial Complexa/imunologia , Glutamato Descarboxilase/imunologia , Mioclonia/enzimologia , Mioclonia/imunologia , Palato Mole , Adulto , Feminino , HumanosRESUMO
The hypofrontality theory of the pathogenesis of schizophrenia predicts that cortical lesions cause psychosis. During a search for abnormalities of catecholaminergic neurotransmission in patients with complex partial seizures of the mesial temporal lobe, we discovered an increase of the rate of metabolism of an exogenous dopa tracer (6-[18F]fluoro-L-dopa) in the neostriatum of a subgroup of patients with a history of psychosis. When specifically assayed for this abnormality, patients with schizophrenia revealed the same significant increase of the rate of metabolism in the striatum. The finding is consistent with the theory that a state of psychosis arises when episodic dopamine excess is superimposed on a trait of basic dopamine deficiency in the striatum. The finding is explained by the hypothesis that cortical insufficiency, a proposed pathogenetic mechanism of both disorders, causes an up-regulation of the enzymes responsible for dopa turnover in the neostriatum as well as the receptors mediating dopaminergic neurotransmission.
Assuntos
Encéfalo/enzimologia , Dopa Descarboxilase/metabolismo , Transtornos Psicóticos/enzimologia , Adulto , Animais , Di-Hidroxifenilalanina/metabolismo , Epilepsia Parcial Complexa/enzimologia , Feminino , Humanos , Masculino , Neostriado/enzimologia , Esquizofrenia/enzimologia , Tomografia Computadorizada de EmissãoRESUMO
PURPOSE: To determine whether complex partial status epilepticus (CPSE) causes brain injury in humans. Serum neuron-specific enolase (s-NSE) is an accepted marker of acute brain injury, and increases in s-NSE have been correlated with the duration and outcome of generalized convulsive status epilepticus. s-NSE levels in CPSE are unknown. Increase in s-NSE in CPSE would provide new information about the degree of brain injury in CPSE and would help confirm that CPSE is a medical emergency. METHODS: This was a pilot prospective study of serial levels of s-NSE and outcome in CPSE. Eight patients with confirmed CPSE and no acute neurologic deficit were identified prospectively. Results were compared with those of normal and epileptic control groups, and outcome was assessed at hospital discharge or at 7 days with the Glasgow Oucome Scale (GOS). RESULTS: The mean peak s-NSE was 21.81 ng/ml, which for the 8 patients with CPSE was four times higher than that of normal controls (mean s-NSE = 5.36 SD = 1.66, p = 0.0003) and epileptic controls (mean s-NSE = 4.61 SD = 1.74, p. = 0.001). CONCLUSION: The increase in s-NSE provides new evidence that CPSE causes brain injury in humans.
Assuntos
Encéfalo/fisiopatologia , Epilepsia Parcial Complexa/enzimologia , Fosfopiruvato Hidratase/sangue , Estado Epiléptico/enzimologia , Biomarcadores , Encéfalo/enzimologia , Eletroencefalografia , Epilepsia Parcial Complexa/sangue , Epilepsia Parcial Complexa/fisiopatologia , Escala de Coma de Glasgow , Humanos , Avaliação de Resultados em Cuidados de Saúde , Fosfopiruvato Hidratase/metabolismo , Projetos Piloto , Estudos Prospectivos , Radioimunoensaio , Estado Epiléptico/sangue , Estado Epiléptico/fisiopatologiaRESUMO
A 29 year old woman is described with severe hyperemesis gravidarum, atypical migraine, numerous admissions to hospital for psychiatric illness, non-epileptic seizures, and valproate-induced coma. Metabolic studies and measurement of [9,10(n)-3H]palmitate oxidation by cultured fibroblasts suggested a multiple acyl-CoA dehydrogenation disorder. Treatment with riboflavin abolished headaches and abnormal behaviour and normalised the plasma free carnitine level. Subtle defects in mitochondrial beta oxidation may be a treatable cause of disordered behaviour in adults.
Assuntos
Coma/induzido quimicamente , Epilepsia Parcial Complexa/tratamento farmacológico , Ácidos Graxos Dessaturases/deficiência , Flavoproteínas/fisiologia , Proteínas Ferro-Enxofre , Mitocôndrias/enzimologia , Complexos Multienzimáticos/deficiência , Testes Neuropsicológicos , Oxirredutases atuantes sobre Doadores de Grupo CH-NH , Riboflavina/administração & dosagem , Ácido Valproico/efeitos adversos , Ácidos/urina , Adulto , Coma/enzimologia , Flavoproteínas Transferidoras de Elétrons , Epilepsia Parcial Complexa/enzimologia , Ácidos Graxos Dessaturases/fisiologia , Feminino , Humanos , Mitocôndrias/efeitos dos fármacos , Complexos Multienzimáticos/fisiologia , Exame Neurológico , Ácido Valproico/administração & dosagemRESUMO
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.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/complicações , Amônia/sangue , Anticonvulsivantes/efeitos adversos , Encefalopatias Metabólicas/induzido quimicamente , Doença da Deficiência de Ornitina Carbomoiltransferase , Ácido Valproico/efeitos adversos , Adolescente , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/enzimologia , Erros Inatos do Metabolismo dos Aminoácidos/genética , Anticonvulsivantes/uso terapêutico , Encefalopatias Metabólicas/diagnóstico , Encefalopatias Metabólicas/enzimologia , Diagnóstico Diferencial , Quimioterapia Combinada , Epilepsia Parcial Complexa/tratamento farmacológico , Epilepsia Parcial Complexa/enzimologia , Epilepsia Parcial Complexa/genética , Feminino , Triagem de Portadores Genéticos , Humanos , Ácido Valproico/uso terapêuticoRESUMO
Neuron-specific enolase (NSE) is a marker of brain injury after acute neurologic insults. We report changes in serum NSE (s-NSE) in 25 patients (15 with epilepsy and 10 patients with nonepileptic events) during continuous inpatient video/EEG monitoring. s-NSE was significantly increased as compared with baseline and normal controls after the first ictal event in the epileptic group, especially in patients with secondarily generalized tonic-clonic seizures (p = 0.01), but s-NSE was not increased in patients with nonepileptic events. These preliminary data indicate that s-NSE may be increased after complex partial seizures--and generalized tonic-clonic seizures (GTCS).
Assuntos
Encéfalo/fisiopatologia , Eletroencefalografia , Epilepsia/enzimologia , Hospitalização , Fosfopiruvato Hidratase/sangue , Adulto , Barreira Hematoencefálica/fisiologia , Eletroencefalografia/métodos , Epilepsia/diagnóstico , Epilepsia Parcial Complexa/diagnóstico , Epilepsia Parcial Complexa/enzimologia , Epilepsia Tônico-Clônica/diagnóstico , Epilepsia Tônico-Clônica/enzimologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Transtornos Psicofisiológicos/diagnóstico , Transtornos Psicofisiológicos/enzimologia , Gravação de VideoteipeRESUMO
PURPOSE: To evaluate the discriminative power of serial, simultaneous determinations of serum neuron-specific enolase (NSE), prolactin (PRL) and creatine kinase (CK) in differentiating psychogenic non-epileptic seizures (PNES) from epileptic seizures (ES). METHODS: Prospective measurement of the three markers after 44 single seizures (32 ES and 12 PNES) during continuous video-EEG monitoring at seven different sampling points. RESULTS: Patients with ES had a significantly greater increase in PRL at 10, 20, 30 min, 1 and 6 h. The sensitivity for elevated NSE and CK was low. PRL showed a higher sensitivity. However, the corresponding positive predictive value was lower than in CK and NSE. Additionally, PRL had the lowest specificity of all parameters. CONCLUSIONS: The limited discriminative power of PRL, CK, and NSE calls into question if these markers are helpful in differentiating PNES and ES.