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

Lipoxygenase pathway products of arachidonic acid (AA) metabolism (known as leukotrienes, LTs) are produced in the brain during pathologic conditions such as ischemia, hemorrhage, trauma, and seizure in which the release of AA is sustained by the activation of local phospholipases. The most common type of LT in the central nervous system is an LTC4 which is a highly potent vasoconstrictor leading to increase in vascular permeability. In this study, we compared the serum (S) and cerebrospinal fluid (CSF) prostaglandin E2 (PGE2) and LTC4 levels in 13 consecutively admitted patients with acute cerebral ischemia aged 55-80 years with 10 age-matched controls. Patients with previous glucocorticosteroid and antiinflammatory drug usage were not included in the study. S and CSF samples were drawn during the first 72 h of the attack, and samples were evaluated by bioassay. There was no significant difference in S PGE2 and LTC4 values, whereas a significant difference was observed between CSF PGE2 and LTC4 values as compared with the control group. The high levels of CSF PGE2 and LTC4-like activity in acute cerebral ischemia may indicate that these mediators have a role to play in cerebral edema. The CSF PGE2/LTC4 ratio was also found to be reduced in the ischemic group implying higher LTC4 synthesis than PGE2 synthesis. In the light of these findings, we suggest that use of a selective antagonist of LTs may be helpful in reducing the ischemic penumbra during acute cerebral ischemia by controlling the vasogenic edema.
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PMID:Leukotriene C4 and prostaglandin E2 activities in the serum and cerebrospinal fluid during acute cerebral ischemia. 194 52

Leukotrienes and prostaglandins are formed from arachidonic acid by activation of local phospholipases in pathological conditions such as cerebral ischemia, subarachnoid hemorrhage, cerebral tumors and seizures. These mediators, especially leukotrienes have a very potent vasoconstrictor effect on cerebral arteries. Experimental studies have shown that this effect, by increasing vascular permeability causes vasogenic edema that contributes to the ischemic penumbra. In this study, after developing an experimental animal model simulating the concept of ischemic penumbra in the rat, the levels of leukotriene C and prostaglandin E2 produced in the forebrain were measured and the effects of these mediators in prolonged ischemia were investigated. The results, in the first 4 min of ischemia, showed that the arachidonic acid metabolites, particularly, leukotriene C4, reached a peak in the ischemic cerebral tissue in association with leukocyte accumulation. Later in the 15th min, significant decreases in leukotriene C4 and prostaglandin E2 levels were seen. In the 1st and 4th h, probably due to the stimulation of the relevant enzymes by free oxygen radicals in the ischemic tissue; the levels increase again, returning to control values by the 12th h. It is concluded that the use of lipoxygenase inhibitors and free radical scavengers may be helpful to limit the infarct area in the first 4 h of ischemia.
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PMID:The alterations of leukotriene C4 and prostaglandin E2 levels following different ischemic periods in rat brain tissue. 201 13

In a series of 102 patients with angiographically proven cerebral sinus venous thrombosis (SVT) significant differences with arterial cerebrovascular disease were noted with respect to disease onset, reversibility of symptoms, occurrence of epileptic seizures and headache, cerebral blood flow under resting and stimulated conditions, occurrence of intracranial bleedings, and response to heparin therapy. From these findings pathophysiological differences are hypothesized: Whereas arterial cerebral ischemia usually is a monophasic abrupt thrombotic process and there is only a small penumbra, SVT is a continuing process of disequilibrium between prothrombotic and thrombolytic mechanisms; large areas of the brain are only functionally or metabolically disturbed but not irreversibly damaged. Intracranial bleeding in SVT is a consequence of increased venous and capillary pressure and thus occurs more frequently than in arterial thrombotic disease in which capillary pressure is reduced by the thrombosis and bleeding occurs during reperfusion of tissue damaged by ischemia. Heparin treatment in SVT is effective since it shifts the equilibrium away from the prothrombotic side and is able to save large areas of brain tissue that are only reversibly damaged. It improves venous outflow and thus decreases the risk of intracranial hemorrhage, in contrast with the arterial thrombotic disease where heparin increases the risk or at least the severity of intracranial bleedings.
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PMID:Pathophysiological aspects of cerebral sinus venous thrombosis (SVT). 801 60

It is the purpose of this review to critically consider and organize the literature dealing with the ephemeral electroencephalographic (EEG) pattern periodic lateralized epileptiform discharges (PLEDs). Although the retrospective nature of these studies limits their ability to discuss accurately the clinical and pathophysiological aspects of this EEG entity, the available data strongly emphasize stroke as the dominant etiology and its high association with seizures. Recent evidence, particularly from functional neuroimaging studies, strongly suggests that PLEDs might reflect a key pattern for focal hyperexcitability in the penumbra zone of ischemic stroke. The authors prefer to consider PLEDs as an EEG signature of a dynamic pathophysiological state in which unstable neurobiological processes create an ictal-interictal continuum, with the nature of the underlying neuronal injury, the patient's preexisting propensity to have seizures, and the co-existence of any acute metabolic derangements all contributing to whether seizures occur or not. This review underlines the need for further sophisticated prospective controlled studies implementing early continuous EEG monitoring in order to contribute to an understanding of the incidence, dynamics, and relevance of this pattern.
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PMID:Periodic lateralized epileptiform discharges--a critical review. 897 24

In vivo intracellular recording from cat thalamus and cortex was performed during spontaneous spike-wave seizures characterized by synchronously firing cortical neurons correlated with the electroencephalogram. During these seizures, thalamic reticular (RE) neurons discharged with long spike bursts riding on a depolarization, whereas thalamocortical (TC) neurons were either entrained into the seizures (40%) or were quiescent (60%). During quiescence, TC neurons showed phasic inhibitory postsynaptic potentials (IPSPs) that coincided with paroxysmal depolarizing shifts in the simultaneously recorded cortical neuron. Computer simulations of a reciprocally connected TC-RE pair showed two major modes of TC-RE interaction. In one mode, a mutual oscillation involved direct TC neuron excitation of the RE neuron leading to a burst that fed back an IPSP into the TC neuron, producing a low-threshold spike. In the other, quiescent mode, the TC neuron was subject to stronger coalescing IPSPs. Simulated cortical stimulation could trigger a transition between the two modes. This transition could go in either direction and was dependent on the precise timing of the input. The transition did not always follow the stimulation immediately. A larger, multicolumnar simulation was set up to assess the role of the TC-RE pair in the context of extensive divergence and convergence. The amount of TC neuron spiking generally correlated with the strength of total inhibitory input, but large variations in the amount of spiking could be seen. Evidence for mutual oscillation could be demonstrated by comparing TC neuron firing with that in reciprocally connected RE neurons. An additional mechanism for TC neuron quiescence was assessed with the use of a cooperative model of gamma-aminobutyric acid-B (GABA(B))-mediated responses. With this model, RE neurons receiving repeated strong excitatory input produced TC neuron quiescence due to burst-duration-associated augmentation of GABA(B) current. We predict the existence of spatial inhomogeneity in apparently generalized spike-wave seizures, involving a center-surround pattern. In the center, intense cortical and RE neuron activity would be associated with TC neuron quiescence. In the surround, less intense hyperpolarization of TC neurons would allow low-threshold spikes to occur. This surround, an "epileptic penumbra," would be the forefront of the expanding epileptic wave during the process of initial seizure generalization. Therapeutically, we would then predict that agents that reduce TC neuron activity would have a greater effect on seizure onset than on ongoing spike-wave seizures or other thalamic oscillations.
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PMID:Dynamic interactions determine partial thalamic quiescence in a computer network model of spike-and-wave seizures. 911 29

Positron emission tomography (PET) has been widely used in the study of stroke and related cerebrovascular diseases. It has shown the various stages leading to cerebral infarction and defined the significance of the ischaemic penumbra. PET scan can predict the clinical outcome of patients with acute ischaemic stroke. Several types of diaschisis can also be demonstrated by PET. They reflect different pathophysiological changes in supratentorial infarcts. Post-apoplectic seizures are shown to increase the ischaemic damage in the affected cerebral hemisphere. PET has contributed also to the concept of multi-infarct dementia, although the significance of chronic ischaemia in the pathogenesis of vascular dementia has not been fully investigated.
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PMID:Is positron emission tomography useful in stroke? 934 87

The aim of the study was to determine the relationships between seizures during the early phase of stroke (early seizures, ES) and stroke outcome, and to identify predictors of ES. The study was prospective, consecutive and community-based, and included 1197 patients with acute stroke. We determined the number and type of seizures, initial stroke severity, infarct size, mortality, and outcome in survivors. Stroke severity was measured on admission, weekly, and at discharge using the Scandinavian Stroke Scale (SSS). Multiple logistic and linear regression outcome analyses included relevant confounders and potential predictors. Fifty patients (4.2%) had seizures within 14 days of the stroke. In the multivariate analyses, only initial stroke severity was related to ES. For each 10-point increase in stroke severity (SSS score), the relative risk of ES increased by a factor of 1.65 (95% confidence interval, 1.4 to 1.9) (p < 0.0001). ES did not influence the risk of death during hospital stay (p = 0.56). In survivors, ES was related to a better outcome, equivalent to an improvement in SSS score of 5.7 points (SE [b] = 1.8; p = 0.002). The decisive factor of ES was initial stroke severity. ES per se was not related to mortality. Surprisingly, in survivors, ES predicted a better outcome. We explain this finding by a relatively larger ischaemic penumbra in patients who have ES after a stroke.
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PMID:[Seizures in acute apoplexy. Predisposing factors and significance for prognosis]. 985 27

Since the nineteenth century, various abnormalities of cortical development resulting from migration defect, disorders of maturation, and disorders of cortical organization were described in brains at autopsy. Cortical dysplasia then was recognized in tissue resected during surgical treatment of patients with intractable epilepsy, but this finding remained largely unappreciated until the development of modern imaging. CT allowed glimpses of the more obvious malformations, but it was the advent of MRI that enabled the recognition and classification of the different types of lesions. In the Taylor type of cortical dysplasia, it became clear that there was a wide range in the severity and, above all, in the extent of the abnormality. The lesions range from small areas, often difficult to identify, to extensive lesions surrounded by a halo or penumbra of presumably less severe, but still clinically significant, structural abnormality. Functional imaging (SPECT, PET, and MRS) have provided additional insights and led to strategies for surgical treatment. Even lesions involving the central strip may at times be successfully resected, but in such patients much depends on the preoperative neurologic status. Recognition of the fact that dysplastic lesions are in themselves epileptogenic has been another milestone in our understanding of these abnormalities. Subcortical heterotopias, in particular periventricular nodular heterotopias, have been recognized as causing intractable epilepsy in some but not in all patients. Surgical approaches to these lesions are now being planned. The hereditary nature of the lesions in some patients has explained the familial occurrence of epilepsy in a number of instances. Generalized epileptic abnormalities and generalized disorders of migration and maturation have been described as band heterotopia or the double-cortex syndrome. Here, too, sex-linked dominant inheritance may occur, and progress has been made in our understanding of the mechanisms of these genetically determined lesions. Focal resection in patients with band heterotopia, however, has been of little value in the small number of patients in whom it has been carried out. Cortical malformations due to disorganization, occurring later in intrauterine life, are represented by micropolygyria. These lesions are often bilateral and perisylvian, but at times they are unilateral and in some patients may be occipital or frontal. Several syndromes have emerged, the most common being the one characterized by severe pseudobulbar palsy and mild pyramidal deficit (31). In some patients with such cortical abnormalities, particularly those with micropolygyria, the epilepsy may not be intractable, and full control may be obtained by medical treatment (32). Interesting and important clinical features of patients with bilateral perisylvian polymicrogyria were described by Guerrini et al. (33) and Caraballo et al. (34). In some patients who develop a secondary generalized electrographic abnormality and drop attacks early in the first decade, there is eventual improvement and cessation of the epileptic abnormality toward the end of the first decade or somewhat later. These investigators stressed that callosotomy should be considered with caution in patients with micropolygyria and this electroclinical pattern. Hypothalamic hamartomata and the associated epileptic syndrome have been better understood in recent years. Despite the risks of surgery, resection of the lesion offers hope of improvement in seizure control and of the often extremely severe behavioral abnormalities. On the other hand, patients with small lesions leading only to a "need to laugh" without more overt epileptic or behavioral manifestations are now being recognized. Finally, initial investigations have begun to uncover the transmitter abnormalities in patients with cortical dysplasia. (ABSTRACT TRUNCATED)
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PMID:Cortical dysplasias and epilepsy: a review of the architectonic, clinical, and seizure patterns. 1109 90

It is well known that diabetes aggravates brain damage in experimental and clinical stroke subjects. Diabetes accelerates maturation of neuronal damage, increases infarct volume, and induces postischemic seizures. The mechanism by which diabetes increases ischemic brain damage is still elusive. Our previous experiments indicate that mitochondria dysfunction may play a role in neuronal death. The objective of this study is to determine whether streptozotocin-induced diabetes activates cell death pathway after a brief period of focal cerebral ischemia. Both diabetic and nondiabetic rats were subjected to 30 min of transient middle cerebral artery occlusion, followed by 0, 0.5, 3, and 6 h of reperfusion. We first determined the pathological outcomes after 7 days of recovery by histopathology, and then detected key components of programmed cell death pathway using immunocytochemistry coupled with confocal laser-scanning microscopy and Western blot analysis. The results show that the cytosolic cytochrome c increased mildly after reperfusion in nondiabetic samples. This increase was markedly enhanced in diabetic rats in both ischemic focus and penumbra. Subsequently, caspase-3 was activated and poly-ADP ribose polymerase (PARP) was cleaved. Our results suggest that activation of apoptotic cell death pathway may play a pivotal role in exaggerating brain damage in diabetic subjects.
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PMID:Diabetes activates cell death pathway after transient focal cerebral ischemia. 1254 Jun 24

Neuroserpin is a member of the serine proteinase inhibitor (serpin) gene family that reacts preferentially with tissue-type plasminogen activator (tPA) and is primarily localized to neurons in regions of the brain where tPA is also found. Outside of the central nervous system (CNS) tPA is predominantly found in the blood where its primary function is as a thrombolytic enzyme. However, tPA is also expressed within the CNS where it has a very different function, promoting events associated not only with synaptic plasticity but also with cell death in a number of settings, such as cerebral ischemia and seizures. Neuroserpin is released from neurons in response to neuronal depolarization and plays an important role in the development of synaptic plasticity. Following the onset of cerebral ischemia there is an increase in both tPA activity and neuroserpin expression in the area surrounding the necrotic core (ischemic penumbra), and treatment with neuroserpin following ischemic stroke or overexpression of the neuroserpin gene results in a significant decrease in the volume of the ischemic area as well as in the number of apoptotic cells. TPA activity and neuroserpin expression are also increased in specific areas of the brain by seizures, and treatment with neuroserpin slows the progression of seizure activity throughout the CNS and results in significant neuronal survival in the hippocampus. Mutations in human neuroserpin result in a form of autosomal dominant inherited dementia which is characterized by the presence of intraneuronal inclusion bodies and is known as Familial Encephalopathy with Neuroserpin Inclusion Bodies.
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PMID:Neuroserpin: a selective inhibitor of tissue-type plasminogen activator in the central nervous system. 1498 20


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