Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this chapter, the pathophysiology and neurochemical pathology of epileptic brain damage is discussed on the basis of an integrative approach in which a comparison is made to cell necrosis resulting from ischemia and hypoglycemia. Two main questions are asked. First, is the brain damage resulting from these three disorders of cerebral energy metabolism similar in distribution and structural characteristics, as previously proposed? Second, is it possible to identify one or several neurochemical events, at the cellular and subcellular level, that qualify as the final common pathways leading to neuronal necrosis? A related question is, will seizures cause structural damage even if they do not critically curtail cellular oxygen supply? A review of the literature and of recent results obtained in animals with long-term recovery following status epilepticus of known duration suggests that although brain damage caused by epilepsy shows some similarities to that incurred due to ischemic and hypoglycemic insults, it is far from identical. In well oxygenated animals with an adequate cardiovascular function, 2 hr of status epilepticus causes moderate neuronal necrosis in the cerebral cortex (layers 3-4), the hippocampus (CA4 and CA1 pyramidal cells), and the thalamus (ventromedial nuclei). In rats, status epilepticus of 30 min duration or longer invariably causes infarction of the substantia nigra (pars reticularis), with some affectation of globus pallidus as well. Notably, CA3 pyramids and dentate neurons are spared, as is the pars compacta of the substantia nigra. Neurochemical events in ischemia, hypoglycemia, and status epilepticus show some striking dissimilarities, yet all three conditions lead to neuronal necrosis. In complete or near-complete ischemia, in which metabolic rate virtually ceases; deterioration of tissue energy state is rapid and extensive, with dramatic loss of ion homeostasis; cellular redox systems are reduced; and acidosis is marked to excessive. In hypoglycemic coma, oxygen consumption continues, albeit at a reduced rate; loss of high energy phosphates is extensive but less than complete, as is loss of ion homeostasis; cellular redox system become oxidized; and acidosis is absent. In epileptic seizures, finally, metabolic rate is markedly enhanced; perturbation of tissue energy state and of ion homeostasis is minimal to small; and acidosis is moderate. Results obtained in experimental animals suggest that neuronal necrosis, when incurred, is unrelated to energy failure and occurs in spite of adequate cellular oxygenation. Four neurochemical events are common to all three conditions discussed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Epileptic brain damage: pathophysiology and neurochemical pathology. 287 25

Hyperinsulinemia, a common cause of persistent hypoglycemia in infants and children, can result in permanent damage to the central nervous system. Thus, early diagnosis and treatment are important. The typical clinical manifestation of hyperinsulinemic hypoglycemia is symptomatic hypoglycemia that responds poorly to medical therapy. Affected infants may have tremors, jitteriness, apnea, cyanosis, or seizures. If initial medical therapy (frequent feedings, large amounts of intravenously administered glucose, diazoxide, and glucocorticoids) fails to stabilize plasma glucose levels, subtotal pancreatectomy is indicated. This surgical intervention does not completely correct the hypoglycemia in all patients, but it effectively reduces the severity of the condition. Surgical treatment of pediatric patients with Cushing's syndrome or aldosteronoma has also been effective. In our experience, survival of patients with adrenocortical adenomas has been 100%, whereas only five of nine children with adrenocortical carcinomas survived, and four of the five were younger than 10 years of age.
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PMID:Endocrine disorders of the pancreas and adrenal cortex in pediatric patients. 287 83

Kainic acid administration induces status epilepticus seizures in the rat which damage CA1 and CA3 hippocampal neurons. Rats made hypoglycemic prior to seizure had enhanced volumes of damage, when compared to normo- or hyperglycemic rats. The mild hypoglycemia was not in the range which, itself, typically produces hippocampal damage. This suggests that limited energy availability compromised the ability of neurons to survive seizures. Our data also suggest that the CA1 damage seen after status epilepticus is not hypoxic-ischemic in origin, since elevating pre-seizure glucose concentrations to a range which typically exacerbates hypoxic-ischemic CA1 damage did not augment status-epilepticus CA1 damage.
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PMID:Status epilepticus-induced hippocampal damage is modulated by glucose availability. 291

An 8-year-old boy with insulin-dependent diabetes mellitus and a seizure disorder demonstrated transient visual loss after severe seizure activity. The role of hypoglycemia in relation to his transient cortical blindness remains indeterminate. The nature of the cortical involvement, the rate of visual recovery, and prior reports of postictal phenomena emphasize the relatively benign nature of this condition in children.
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PMID:Transient postictal cortical blindness. 295 7

The mean age of the 13 patients studied (9 women, 7 men) was 50.5 +/- 15.7 years. The disease was discovered on account of malaise (3 cases), behavioural disorders (4 cases), coma (3 cases), syncope (1 case) or right hemiparesis (1 case) or in the course of systematic examination (1 case). Eleven patients consulted for evaluation of hypoglycaemia and 2 for behavioural disorders. The history was characteristic, with malaise, loss of consciousness, severe neurological disorders (seizures, hemiparesis, hemiplegia or coma) and psychiatric disorders. These symptoms typically occurred in the morning before breakfast or between meals in 9 patients, and atypically at any point of time or after meals in 4 patients. Their hypoglycaemic nature was demonstrated by blood glucose determination in 11/13 cases and by response to ingestion of sugar in 12/13 cases. The mean period elapsed between the initial symptoms and the final diagnosis was 20.3 +/- 17.3 months. Inappropriate insulin secretion was elicited a.m. before breakfast, during Conn's diet or fasting test, or by calculating the blood insulin/glucose ratio or Turner's coefficient. Prior to surgery, the insulinoma was located by ultrasonography in 3/8 cases, by computerized tomography in 2/6 cases, by selective arteriography in 6/11 cases, and by phlebography with spleno-portal catheterization and staged sampling for insulin and C-peptide assays in 8/9 cases. Histological examination after surgery (11 cases) or necropsy (1 case) showed an adenoma without evidence of malignancy.
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PMID:[Insulinoma: diagnostic elements. 13 cases]. 299 55

Suppression of an adrenocorticotropic hormone (ACTH) response to insulin hypoglycemia has been reported in ACTH-treated adults. There are no guidelines for withdrawal of ACTH treatment in children. After observing suppressed morning cortisol in several children, insulin tolerance tests were performed in five children within 48 hours after tapered withdrawal of ACTH treatment for myoclonic seizures. ACTH response, as determined by cortisol and beta-endorphin radioimmunoassay, was adequate in four of the children. One child showed low basal levels and minimal elevation during hypoglycemia for both beta-endorphin (0 to 3 pg/ml) and cortisol (3.6 to 4.4 micrograms/dL) on initial testing, but normal responses six weeks later. Measurement of beta-endorphin response supported a central basis for suppression in the child, who had had an adrenal hemorrhage during gram-negative sepsis while on ACTH. ACTH release is transiently suppressed in some children after exogenous ACTH treatment. Tapered withdrawal and stress coverage is recommended.
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PMID:Suppressed pituitary ACTH response after ACTH treatment of infantile spasms. 303 33

Symptomatic hypoglycemia developed 5 to 45 months after transplantation in nine children who had renal transplants before 6 years of age. During hypoglycemia, serum glucose levels ranged from 14 to 39 mg/dl (0.8 to 2.1 mmol/L). Hypoglycemic episodes occurred between 1.7 and 7.5 years of age. Six patients had generalized seizures; the remaining three had diaphoresis with stupor or lethargy. None of the children had serious infections, diabetes, congenital defects of glucose metabolism, or a history of treatment with insulin or oral hypoglycemic agents. Six patients had hypoglycemic symptoms after a prolonged fast, and at least four had ketosis. Eight of the nine patients were receiving propranolol when hypoglycemia occurred. No differences in the daily prednisone dose, the number of transplant rejection episodes, or the frequency of treatment with medications other than propranolol were noted between hypoglycemic patients and 56 normoglycemic age-matched renal transplant recipients. All hypoglycemic patients were subsequently treated with frequent feedings and discontinuation of propranolol. No further hypoglycemic episodes have occurred in eight of nine patients. Symptomatic hypoglycemia should be recognized as a potentially devastating complication of pediatric renal transplantation.
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PMID:Hypoglycemia in pediatric renal allograft recipients. 305 55

The effect of insulin-induced hypoglycemia following 10.5 minutes of forebrain ischemia was studied in the rat. All groups received preischemic glucose loading (2 gm/kg) to promote brain infarction. Following completion of ischemia, rats received either 2 to 3 IU/kg (low-dose group) or 8 to 20 IU/kg (high-dose group) insulin. During the survival period, blood glucose concentrations were maintained in the ranges of 1.2 to 2.9 mM and 2.9 to 4.9 mM, respectively, for the low-dose and high-dose insulin groups. Control rats were given 2 gm/kg glucose immediately following ischemia. During the recovery period, until perfusion at 7 days, they were given glucose, 2 gm/kg, twice daily by intraperitoneal injection, and their drinking water was supplemented with 25% glucose. Mortality (p less than 0.05) and postischemic seizure incidence (p less than 0.01) were significantly reduced in the low-dose insulin group compared to the control group. Mortality was increased in the high-dose insulin group compared to the control group and was associated with an increased incidence of postischemic seizures. Neuropathological examination revealed no cortical infarction in the low-dose or high-dose insulin-treated rats compared to a 60% incidence of cortical infarction in the control group. In addition, the high-dose insulin-treated group showed a significant reduction in striatal and hippocampal CA1 selective neuronal necrosis compared to control rats with comparable survivals (p less than 0.05). The findings suggest that postischemic blood glucose concentrations play an important role in modulating both ischemic infarction and selective neuronal necrosis.
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PMID:The effect of postischemic blood glucose levels on ischemic brain damage in the rat. 305 89

Mechanisms for sudden unexpected infant deaths remain unproven but the possibilities include cardiac arrhythmias, hypoglycaemia, prolonged apnoea from central respiratory control failure, seizure-induced apnoea, prolonged airway obstruction and alveolar atelectasis. Many of these mechanisms could be treated if the infant at risk could be identified. To date, identification programmes have not been sufficiently sensitive or specific. All the evidence presently available suggests that clinical and socioeconomic factors alone will not be sufficient and that as yet unidentified physiological or biochemical measurements must be included in a scoring system if such an approach is to be effective. Epidemiological studies have shown that a suboptimal intrauterine environment and respiratory tract infections during early infancy are present to excess in future victims. Improvements in antenatal and postnatal care, particularly to mothers from areas of socioeconomic deprivation, will almost certainly reduce the incidence of sudden infant deaths. Certain respiratory tract infections may induce episodes of severe hypoxaemia due to abnormal apnoea and therefore it is not only essential that the infection risk in young infants from pertussis is minimized by immunization of the childhood population but also that methods of preventing other infections, such as respiratory syncytial virus, are developed and applied as soon as possible. Re-organization of mother and baby clinics and mother and baby social groups in order to minimize contact between young infants and pre-school children may reduce cross-infection by respiratory tract pathogens.
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PMID:Can we predict or prevent sudden unexpected deaths during infancy? 306 58

A concern for the possible role of the blood-brain barrier (BBB) in the epilepsies was based on ultrastructural studies that demonstrated increased micropinocytosis in cerebral capillaries during seizures. Continued interest in the structure of the BBB has led to the demonstration that, in human psychomotor epilepsy, there is a thickening of the capillary basement membrane. These studies also suggest that an increase in capillary mitochondria and interendothelial tight junctions may characterize seizure-traumatized brain regions. These studies forecast an increased interest and understanding of the ultrastructural events associated with capillaries in seizure states. Additional focus on the BBB comes from the clinical use of anticonvulsant drug levels in the control and treatment of seizures. Debate as to whether free drug levels are appropriate continues. The brain capillary is the interface between blood-borne drug and the target site, and thus an increased understanding of the events associated with brain-plasma exchange has been sought. The concept that only that fraction of drug that is freely dialyzable is available for equilibration across the BBB is not supported by recent studies, which demonstrate that protein-bound ligands are able to dissociate and gain access to the brain in the course of a single capillary transit. It has been established that albumin-bound fatty acids, steroids, and anticonvulsant drugs more readily distribute into tissues than previously believed. Thus, traditional free drug hypotheses need to be expanded to account for the fact that dissociation constants measured in vitro are not the same as those measured in vivo. The BBB also regulates nutrient availability to the brain, and under normal conditions excess substrate is made available to the brain for metabolism. Indirect evidence is available to suggest that during seizures, BBB transport may indeed be the rate-limiting step. Specifically, glucose availability to the seizing brain may be restricted to such a degree that brain glucose utilization rates are no longer independent of plasma glucose levels. If it can be proven that BBB transport is the rate-limiting step during seizures, then it would be possible to augment brain glucose utilization rates by increasing plasma glucose levels. In addition, a depression of brain glucose utilization could be achieved by inducing hypoglycemia. It is not fully understood whether BBB rate limitation would persist postically, nor is it known whether BBB alterations may be global or restricted to the seizure focus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Epilepsy and the blood-brain barrier. 308 37


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