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

We investigated two unrelated children with an isolated defect of mitochondrial complex III activity. The clinical picture was characterized by a progressive encephalopathy featuring early-onset developmental delay, spasticity, seizures, lactic acidosis, brain atrophy and MRI signal changes in the basal ganglia. Both children were compound heterozygotes for novel mutations in the human bc1 synthesis like (BCS1L) gene, which encodes an AAA mitochondrial protein putatively involved in both iron homeostasis and complex III assembly. The pathogenic role of the mutations was confirmed by complementation assays, using a DeltaBcs1 strain of Saccharomyces cerevisiae. By investigating complex III assembly and the structural features of the BCS1L gene product in skeletal muscle, cultured fibroblasts and lymphoblastoid cell lines from our patients, we have demonstrated, for the first time in a mammalian system, that a major function of BCS1L is to promote the maturation of complex III and, more specifically, the incorporation of the Rieske iron-sulfur protein into the nascent complex. Defective BCS1L leads to the formation of a catalytically inactive, structurally unstable complex III. We have also shown that BCS1L is contained within a high-molecular-weight supramolecular complex which is clearly distinct from complex III intermediates.
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PMID:Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy. 1740 14

Epilepsy is the more frequent clinical manifestation of hemispheric cavernomas in 50 to 75% of symptomatic cases; the annual risk of a first seizure is evaluated from 1.5 to 2.5%. As for all epileptogenic lesions, many questions arise: Is the pathologic tissue or the perilesional cortex responsible for the epileptic symptoms? Is the risk related with the topography of the lesion? Is the prognosis of the epilepsy related with the number of seizures? Can the epilepsy become drug-resistant? Can surgical treatment cure the epilepsy? When surgery is indicated, should lesionectomy alone or lesionectomy plus perilesional tissue resection be performed? The iron and the hemosiderin deposits induce metabolic perturbations and tissue reorganization (gliosis and sclerosis) around the cavernoma. These cortical modifications seem to be responsible for the epileptic discharges but this is difficult to demonstrate. Epileptic discharges have been recorded in the perilesional tissue in only one study of the literature. Drug therapy can usually control the seizures, but it appears that surgery is more effective when the epilepsy is recent and the seizures are not too frequent. For these reasons it would appear licit to propose the resection of the lesion when the surgical risk is not too great. In case of drug-resistant epilepsy, the same function-targeted surgical strategy may be used as for the management of any severe epilepsy.
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PMID:[Epileptogenicity and evaluation of epileptic risk]. 1750 46

The iron-induced model of post-traumatic chronic focal epilepsy in rats was studied by depth-electrode mapping to investigate the spread of epileptiform activity into subcortical brain structures after its onset in the cortical epileptic focus. Electrical seizure activity was recorded in the hippocampal CA1 and CA3 areas, amygdala and caudate-putamen, in rats with iron-induced chronic cortical focal epilepsy. These experiments showed that the epileptiform activity with its onset in the cortical focus synchronously propagated into the studied subcortical brain areas. Seizure behaviours seemed to increase in correspondence with the spread of the epileptic electrographic activity in subcortical areas. Comparison of the cortical focus electroencephalographic and associated multiple-unit action potential recordings with those from the subcortical structures showed that the occurrence and evolution of the epileptiform activity in the subcortical structures were in parallel with that in the cortical focus. The intracerebral anatomic progression and delineation of seizure spread (mapped by field potential (EEG) and multiple-unit action potentials (MUA) recordings) indicated participation of these regions in the generalization of seizure activity in this model of epilepsy. The seizure-induced activation of the hippocampus appeared to evolve into an epileptic focus independent of the cortical focus. The present study demonstrates the propagation of epileptic activity from the cortical focus into the limbic and basal ganglia regions. Treatment of iron-induced epileptic rats with ethosuximide, an anti-absence drug, resulted in suppression of the epileptiform activity in the cortical focus as well as in the subcortical brain areas.
Seizure 2007 Dec
PMID:Iron-induced experimental cortical seizures: electroencephalographic mapping of seizure spread in the subcortical brain areas. 1762 12

Women with epilepsy (WWE) face particular challenges during their pregnancy. Among the several obstetric issues for which there is some concern and the need for further investigation are: the effects of seizures, epilepsy, and antiepileptic drugs on pregnancy outcome and, conversely, the effects of pregnancy and hormonal neurotransmitters on seizure control and antiepileptic drug metabolism. Obstetric concerns include preclampsia/eclampsia, preterm delivery, placental abruption, spontaneous abortion, stillbirth, and small-for-date babies in WWE whether or not they are taking antiepileptic drugs. The role of nutritional health elements, including body mass index, caloric and protein intake, vitamins and iron, and phytoestrogens, warrants further study. During the course of obstetric management, there is a need for a fuller understanding by neurologists of the risk-benefit calculations for various types and frequencies of fetal imaging, including CT, MRI, and ultrasound, as well as for the screening standards of care. As part of the Health Outcomes in Pregnancy and Epilepsy (HOPE) project, this expert panel provides a brief overview of these concerns, offers some approaches to management, and outlines potential areas for further investigation. More detailed information and guidelines are available elsewhere.
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PMID:Obstetric risks for women with epilepsy during pregnancy. 1799 36

Hypocalcemia due to hypoparathyroidism (HPT) is a late complication of iron-overloaded patients with b-thalassaemia major (TM). The majority of patients have mild disease with parasthesias, while in the more severe form tetany, seizures or cardiac failure may occur. In the last 20 years we observed heart failure in 2 out of 38 (5.2%) TM patients (aged 18 and 22 years) with hypocalcemia secondary to HPT associated to iron overload. Calcium supplementation and vitamin D induced correction of hypocalcemia and resulted in an improvement of cardiac function. Calcium plays a key role in the maintenance and regulation of normal cardiac function. Extra-cellular calcium is indispensable for the contractile process since the sarcoplasmatic reticulum is unable to maintain a sufficient amount of calcium to trigger myocardial contraction. In conclusion, our observations stress the importance of a regular iron chelation therapy, adherence to treatment of endocrine complication and regular follow-up of TM patients with hypocalcemia.
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PMID:A rare cause of heart failure in iron-overload thalassaemic patients-primary hypoparathyroidism. 1840 23

A model is a simplified preparation that reproduces only the most critical features of a disease. To be considered as a validated animal model, such an experimental preparation must fulfill three criteria: isomorphism or similarities of the symptoms; predictivity or identical pharmacological reactivity; homology or etiological similarity. In epilepsy, the use of animal models helps our understanding of physiological and pathological networks involved in the genesis, maintenance, and propagation of seizures. The animal models of epilepsy are also useful in designing and testing new surgical therapeutical strategies, in particular using deconnection or neuromodulation in drug-resistant focal epilepsies. Here we describe three animal models of focal epilepsy, adapted to addressing experimental surgery issues. Kindling consists in the regular liminar stimulation of a given brain structure in the rodent to develop a focal discharge that is secondarily generalized. The local application of epileptogenic agents such as cobalt, iron, or penicillin leads to focal discharges that do not generalize in the rodent or the primate. It is a model of focal neocortical epilepsy without secondary generalization. The focal application of kainate, an excitotoxic glutamate agonist, in the dorsal hippocampus of the adult mouse results, after a latent period, in spontaneous and recurrent focal discharges, behavioral interictal troubles, drug resistance, and histological anomalies reminiscent of hippocampal sclerosis. This constitutes a model of mesial-temporal epilepsy. Better knowledge, in these models, of the neural networks generating, propagating, and/or controlling the seizures should make it possible to design innovative surgical approaches for the treatment of drug-resistant epilepsies.
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PMID:[Animal models to develop surgery of focal epilepsies?]. 1841 67

Polymorphisms of the haptoglobin (HP) gene and deletions in alpha-globin gene (alpha-thalassaemia) are common in malaria-endemic Africa. The same region also has high incidence rates for childhood acute seizures. The haptoglobin HP2-2 genotype has been associated with idiopathic generalized epilepsies and altered iron metabolism in children with alpha-thalassaemia can potentially interfere with neurotransmission and increase the risk of seizures. We investigated the hypothesis that the HP2-2 genotype and the common African alpha-globin gene deletions are associated with the increased risk of seizures. 288 children aged 3-156 months admitted with acute seizures to Kilifi District Hospital (Kenya), were matched for ethnicity to an equal number of community controls. The proportion of cases (72/288 [25.0%]) and controls (80/288 [27.8%]) with HP2-2 genotype was similar, p=0.499. The allele frequency of HP2 gene in cases (49.3%) and controls (48.6%) was also similar, p=0.814. Similarly, we found no significant difference between the proportion of cases (177/267 [66.3%]) and controls (186/267 [69.7%]) with deletions in alpha-globin gene (p=0.403). Among cases, HP2-2 polymorphism and deletions in alpha-globin gene were neither associated with changes in the type, number or duration of seizures nor did they affect outcome. We conclude that the HP2-2 polymorphism and deletions in alpha-globin gene are not risk factors for acute seizures in children. Future studies should examine other susceptibility genes.
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PMID:Haptoglobin HP2-2 genotype, alpha-thalassaemia and acute seizures in children living in a malaria-endemic area. 1855 71

Traumatic brain injury causes development of posttraumatic epilepsy. Bleeding within neuropil is followed by hemolysis and deposition of hemoglobin in neocortex. Iron from hemoglobin and transferring is deposited in brains of patients with posttraumatic epilepsy. Iron compounds form reactive free radical oxidants. Microinjection of ferric ions into rodent brain results in chronic recurrent seizures and liberation of glutamate into the neuropil, as is observed in humans with epilepsy. Termination of synaptic effects of glutamate is by removal via transporter proteins. EAAC-1 is within neurons while GLT-1 and GLAST are confined to glia. Persistent down regulation of GLAST production is present in hippocampal regions in chronic seizure models. Down regulation of GLAST may be fundamental to a sequence of free radical reactions initiated by brain injury with hemorrhage. Administration of antioxidants to animals causes interruption of the sequence of brain injury responses induced by hemorrhage, suggesting that such a strategy needs to be evaluated in patients with traumatic brain injury.
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PMID:Posttraumatic epilepsy: hemorrhage, free radicals and the molecular regulation of glutamate. 1878 8

A 55-year-old man presented with generalized seizures and postictal left hemiparesis. Computed tomography scanning of his head showed a low density area in the right frontal lobe. Cerebral angiography demonstrated a partial defect in the superior sagittal sinus and cortical veins, indicating the presence of cerebral venous thrombosis. He had bleeding from a peptic ulcer and the laboratory data revealed iron deficiency anemia concomitant with an elevation of D-dimer and thrombin-antithrombin III complex (TAT). After the anemia resolved with the treatment of the peptic ulcer and iron supplementation, the TAT and D-dimer levels were normalized, and the occluded veins were recanalized. In a cerebral venous thrombosis associated with iron deficiency anemia, treatment for the anemia may improve hypercoagulable state without antithrombotic therapy, although the long-term monitoring of TAT and D-dimer levels is required.
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PMID:Cerebral venous thrombosis associated with iron deficiency anemia. 1898 40

The purpose of the study was to investigate whether dietary intake of curcumin can inhibit the onset and progression of seizures and their associated pathophysiology in experimental FeCl(3)-induced epileptogenesis. Curcumin was considered for this study because it can cross the blood-brain barrier and bind redox-active metal ions. It is also well known for its antioxidative, anticancer, and anti-inflammatory properties. In the present study, seizures were induced by intracortical injection of FeCl(3) into young rats. Synchronized video/EEG recordings were obtained to diagnose the progression of seizures. Short-term treatment with a curcumin-supplemented diet (1500 pp mw/w) significantly inhibited the onset of grade III and IV seizures in rats with iron-induced epilepsy. The lower dose of curcumin (500 ppm) was not effective in inhibiting grade III seizures, but retarded the onset and progression of generalized seizures. The seizure-suppressing potential of curcumin is explained by the observed biochemical, behavioral, and ultrastructural results. Our results indicate that curcumin significantly prevents generalization of electroclinical seizure activity as well as the pathogenesis associated with iron-induced epileptogenesis.
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PMID:Curcumin protects against electrobehavioral progression of seizures in the iron-induced experimental model of epileptogenesis. 2012 35


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