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

The mechanism of epileptic seizures so far remains unclear. Immunological disturbances may be one of the possible mechanisms. The assumption that primary epilepsy is an autoimmune disease lacks an experimental basis. In order to search any relationship between generalized epileptic seizures and autoimmune we examined and measured the serum anti-acetylcholine receptor antibody (A AchR Ab) and anti-synaptic premembrane antibody (A PrM Ab) in 12 patients with typical absences, 20 patients with generalized tonic-clonic seizures (GTC) and 6 patients with Lennox-Gastaut Syndrome. 2 (16.7%) out of 12 patients with absences showed positive both A AchR Ab and A PrM Ab, positive A AchR Ab in 1 patient. Among 20 patients with GTC both A AchR Ab and A PrM Ab were positive in 7 patients (35%), A PrM Ab was positive in 1 patient. Totally in 8 patients A PrM Ab was positive. However, the difference between the two Antibodies was not significant (1.1:1). The two kinds of antibody were positive in 5 (83%) out of 6 patients and A PrM Ab was positive, but A AchR Ab was doubtful in another one patient with Lennox-Gastaut syndrome. Therefore, all the patients with Lennox-Gastaut syndrome showed positive antibody. Our data suggested that different types of generalized epileptic-seizures showed different severity of autoimmune dysfunction. The meaning of this kind of immune dysfunction needs further investigation.
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PMID:[Auto-cholinergic synapse dysfunction in patients with generalized epileptic seizures. A preliminary report]. 188 27

Lesions of the nucleus basalis magnocellularis and the medial septal area have been shown to produce both deficits in memory and decreases in choline acetyltransferase levels. In order to determine whether functional changes in acetylcholine receptor sensitivity also occur, the present experiment examined the ability of acetylcholine, 40 micrograms intraventricularly, to induce motor seizures in nucleus basalis magnocellularis-medial septal area lesioned versus control rats. While choline acetyltransferase activity was only modestly reduced in lesioned rats vs control rats (30%), the seizure scores were considerably higher in lesioned vs. control rats (270%). These results suggest that there is an increased functional response to acetylcholine following bilateral nucleus basalis magnocellularis-medial septal area lesions.
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PMID:Behavioral evidence for increased acetylcholine receptor sensitivity after nucleus basalis magnocellularis lesions in the rat. 318 Dec 90

Rats treated intravenously with an organophosphorus anticholinesterase compound, paraoxon or soman, were sacrificed 2 to 131 min later, using 0.7 sec of focused microwave irradiation (25 kW at 915 MHz). Brain regional rates of glucose utilization during 3-min intervals were determined with labeled glucose and fluorodeoxyglucose as tracers. Levels of glucose, lactate, ATP, and creatine phosphate were assayed in the same samples. The two compounds differed markedly in their effects on brain metabolism. Paraoxon (0.8 LD50) depressed rates of glucose use in all brain regions, without causing consistent changes in brain metabolite levels. This depressant effect was most pronounced during the first 30 min after toxin exposure and had largely disappeared by 2 hr. Soman (0.8-0.95 LD50) was variable in its effects. Animals that showed seizure-like behavior had marked increases in glucose use in diencephalon and cerebrum but no changes in cerebellum or brain stem. Rapid rates of glucose use were associated with high levels of lactic acid and lower levels of creatine phosphate. In cerebrum, but not diencephalon, levels of ATP fell by as much as 50% in strongly affected animals by 30-130 min after soman. All of these effects were reversible with atropine. Soman-treated animals that did not have seizure-like activity did not exhibit these brain metabolic changes. These results and those of others show that cholinergic compounds vary greatly in their effects on brain glucose and energy metabolism. Although noncholinergic mechanisms are a possibility, the most parsimonious explanation for these findings is that cholinesterase inhibitors vary in their affinity for different central nervous system (CNS) acetylcholine receptor populations.
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PMID:Cerebral metabolic effects of organophosphorus anticholinesterase compounds. 350 39

The present study was designed to determine the types of acetylcholine receptors involved in the initiation of epileptic seizures from the zona incerta and surrounding structures by cholinergic stimulation in rats. Unilateral intracerebral microinjection of the mixed muscarinic and nicotinic agonist carbachol (3 micrograms) produced generalized seizures in 12 of 20 rats studied. Local pretreatment with equimolar doses of acetylcholine receptor antagonists was used as a method of determining the receptor type involved in the initiation of cholinergically induced seizures in the rat diencephalon. Pretreatment with the M1 muscarinic receptor antagonist, pirenzepine (7 micrograms), abolished carbachol-induced seizures in 91% of the animals tested. The M2 muscarinic receptor antagonist, methoctramine (12 micrograms) and the nicotinic receptor antagonist, mecamylamine (3 micrograms), were relatively ineffective in antagonizing seizures in 9% and 27%, respectively. The results suggest that M1 muscarinic receptors are preferentially involved in the initiation of generalized epileptic seizures in the basal diencephalon of the rat.
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PMID:Involvement of M1 muscarinic receptors in the initiation of cholinergically induced epileptic seizures in the rat brain. 803 10

We described a 12-year-old girl with systemic lupus erythematosus (SLE) associated with myasthenia gravis (MG). She had absence seizures from 6 years old. She admitted to our hospital at 12 years of age because of absence seizures and dyspnea. The diagnosis of SLE was made on the basis of convulsion, arthritis, pleurisy, and positive antinuclear factor and was started therapy with prednisolone. The clinical course was complicated by the appearance of dysphagia and hoarseness. On the basis of positive Tensilon test and a high level of serum anti-acetylcholine receptor antibody, we made a diagnosis of the systemic type of MG. Her condition was improved by methylprednisolone pulse therapy and gamma-globulin therapy after plasmapheresis. The association of early-onset SLE with MG is rare.
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PMID:[A childhood case of systemic lupus erythematosus associated with myasthenia gravis]. 929 15

We describe a Norwegian family with clusters of brief nocturnal motor seizures with hyperkinetic or tonic manifestations. Seizures started in childhood. Neurological examination and neuroimaging were normal. Interictal EEG registrations were mostly normal, ictal EEG registrations disclosed left frontal epileptiform discharges in two of three patients examined and just shallow arousal preceding the attack in one of the three patients. Segregation analysis indicated an autosomal dominant inheritance pattern, and the patients were subsequently diagnosed as having autosomal dominant nocturnal frontal lobe epilepsy, a disorder first described in 1995. A missense mutation in the gene for the alpha-4 subunit of the neuronal nicotinergic acetylcholine receptor was recently described in an Australian family with this disorder. Our Norwegian family proved to have a novel insertion mutation (776ins3) in the same gene. This mutation affects the second transmembrane domain (M2) which forms the critical section of the ion channel. This is the first case of idiopathic partial epilepsy where the underlying molecular defect has been found. The fact that a dysfunction of the nicotinergic acetylcholine receptor may give rise to frontal epileptic seizures was surprising and may shed new light on the basic mechanisms of epileptogenesis. Manipulations of the cholinergic system may open up a new therapeutic approach.
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PMID:[Autosomal dominant nocturnal frontal lobe epilepsy. An electroclinical and genetic description of a Norwegian family with ten affected members]. 952 68

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an uncommon, idiopathic partial epilepsy characterized by clusters of motor seizures occurring in sleep. We describe a mutation of the beta2 subunit of the nicotinic acetylcholine receptor, effecting a V287M substitution within the M2 domain. The mutation, in an evolutionary conserved region of CHRNB2, is associated with ADNFLE in a Scottish family. Functional receptors with the V287M mutation are highly expressed in Xenopus oocytes and characterized by an approximately 10-fold increase in acetylcholine sensitivity. CHRNB2 is a new gene for idiopathic epilepsy, the second acetylcholine receptor subunit implicated in ADNFLE.
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PMID:CHRNB2 is the second acetylcholine receptor subunit associated with autosomal dominant nocturnal frontal lobe epilepsy. 1110 62

A 55-year-old man presented with fever, malaise, dysarthria, and intermittent twitching of his right hand. He progressed rapidly to aphasia, intractable myoclonic seizures, and unresponsiveness. Magnetic resonance imaging (MRI) of the head demonstrated multiple nonenhancing areas of signal abnormality involving the cortex of both cerebral hemispheres. Extensive evaluation revealed no infectious cause for his symptoms. Muscle acetylcholine receptor binding and modulating antibodies, striational antibodies, and a neuronal autoantibody specific for collapsin response-mediator protein were detected. An invasive thymoma was discovered and resected. Brain biopsy revealed microglial activation, gliosis, and scant perivascular lymphocytic inflammation. His condition worsened despite treatment with anticonvulsants, intravenous corticosteroids, and antimicrobials. Plasma exchange was performed. The myoclonus stopped; he regained consciousness and gradually improved to the point that he could talk and ambulate with assistance. An MRI revealed regression of the lesions with residual cortical atrophy. This case demonstrates that paraneoplastic encephalitis may occur with thymoma and may extend to cortical regions outside the limbic system.
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PMID:Fulminant autoimmune cortical encephalitis associated with thymoma treated with plasma exchange. 1112 43

Genetic defects have been recently identified in certain inherited epilepsy syndromes in which the phenotypes are similar to common idiopathic epilepsies. Mutations in the neuronal nicotinic acetylcholine receptor 4 and 2 subunit genes have been detected in families with autosomal dominant nocturnal frontal lobe epilepsy. Both receptors are components of neuronal acetylcholine receptor, a ligand-gated ion channel in the brain. Furthermore, mutations of two K+-channel genes were also identified as the underlying genetic abnormalities of benign familial neonatal convulsions. Mutations in the voltage-gated Na+-channel 1, 2 and 1 and the gamma aminobutyric acid (GABAA) receptor 2 subunit genes were found as a cause of generalized epilepsy with febrile seizures plus, a clinical subset of febrile convulsions. Na+-channels, GABAA receptor and their auxiliaries may be involved in the pathogenesis of this subtype and even in simple febrile convulsions. Mutation of a voltage-gated K+-channel gene can cause partial seizures associated with periodic ataxia type 1 and some forms of juvenile myoclonic epilepsy and idiopathic generalized epilepsy can result from mutations of a Ca2+-channel. This line of evidence suggests the involvement of channels expressed in the brain in the pathogenesis of certain types of epilepsy. Our working hypothesis is to view certain idiopathic epilepsies as disorders of ion channels, i.e. 'channelopathies'. Such hypothesis should provide a new insight to our understanding of the genetic background of epilepsy.
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PMID:Genetic abnormalities underlying familial epilepsy syndromes. 1201 63

Genetic defects have been recently identified in certain inherited epilepsy syndromes in which the phenotypes are similar to those of common idiopathic epilepsies. Mutations in the neuronal nicotinic acetylcholine receptor alpha4 and beta2 subunit genes have been detected in families with autosomal dominant nocturnal frontal lobe epilepsy. Both receptors are components of neuronal acetylcholine receptor, a ligand-gated ion channel in the brain. Furthermore, mutations of two K+ channel genes also were identified as the underlying genetic abnormalities of benign familial neonatal convulsions. Mutations in the voltage-gated Na+-channel alpha1 and beta1 subunit genes were found as the cause of generalized epilepsy with febrile seizures plus, a clinical subset of febrile convulsions. Mutation of a voltage-gated K+-channel gene can cause partial seizures associated with periodic ataxia type 1 and some forms of juvenile myoclonic epilepsy can result from mutations of a Ca2+ channel. This line of evidence suggests the involvement of channels expressed in the brain in the pathogenesis of certain types of epilepsy. Our working hypothesis is to view certain idiopathic epilepsies as disorders of ion channels (i.e., "channelopathies"). Such a hypothesis should provide a new insight into our understanding of the genetic background of epilepsy.
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PMID:Molecular genetics of human familial epilepsy syndromes. 1238 75


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