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

The primary dose-limiting adverse effects associated with foscarnet treatment of cytomegalovirus retinitis in patients with AIDS are renal impairment and ionized hypocalcemia. Dose-limiting renal impairment, consisting of significant alterations in serum creatinine levels or creatinine clearance or acute renal failure, has been observed in 10-20% of AIDS patients receiving foscarnet via intermittent i.v. infusion. Nephrotoxicity can be minimized by adjusting dosage according to creatinine clearance and by ensuring that adequate hydration is provided throughout foscarnet therapy. Transient decreases in serum or plasma ionized calcium levels appear to occur in all patients during foscarnet infusion, with these decreases being observed in the absence of changes in total calcium levels. Hypocalcemia produces mild symptoms in some patients and may play a role in unexplained cases of arrhythmia or seizure. Careful attention should be given to levels of total calcium and other minerals during foscarnet treatment, and the occurrence of symptomatic hypocalcemia should prompt evaluation of ionized calcium concentrations and foscarnet dose reduction. Another potentially treatment-limiting effect attributed to foscarnet is penile ulceration, which appears to result from exposure of the glans penis to unchanged foscarnet in the urine.
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PMID:Review of the toxicities of foscarnet. 153 39

In primary cultures of cerebellar granule cells, activation of the N-methyl-D-aspartate (NMDA) receptor leads to Ca2+ influx. Previous work showed that this response is selectively inhibited by acute exposure to low concentrations of ethanol. The present results demonstrate that the response to NMDA (measured as an increase in intracellular Ca2+ concentration, using fura-2 fluorescence) is significantly enhanced after chronic in vitro exposure of the cells to ethanol (100 mM for 2-4 days; 20 mM for 3 or more days). This enhancement is consistent with an increased number of NMDA receptors, with no change in receptor properties. Specifically, there was no change in the EC50 values for NMDA and glycine or in the magnitude of inhibition of the NMDA response by competitive or uncompetitive antagonists. There was also no change in the ability of acute ethanol to inhibit the NMDA response after chronic exposure of the cells to ethanol. Furthermore, chronic ethanol exposure did not alter depolarization-dependent increases in intracellular Ca2+ observed after exposure of the cells to 30 mM KCl. The data suggest that chronic ethanol exposure produces a selective up-regulation of NMDA receptor function. In the intact animal, such a change may be associated with particular symptoms of ethanol withdrawal, i.e., withdrawal seizures.
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PMID:Chronic exposure of cerebellar granule cells to ethanol results in increased N-methyl-D-aspartate receptor function. 153 16

This overview presents data showing that glucose use increases and that excitatory amino acids (i.e., glutamate, aspartate), taurine and ascorbate increase in the extracellular fluid during seizures. During the cellular hyperactive state taurine appears to serve as an osmoregulator and ascorbate may serve as either an antioxidant or as a pro-oxidant. Finally, a unifying hypothesis is given for seizure-induced brain damage. This unifying hypothesis states that during seizures there is a release of excitatory amino acids which act on glutamatergic receptors, increasing neuronal activity and thereby increasing glucose use. This hyperactivity of cells causes an influx of calcium (i.e., calcium stress) and water movements (i.e., osmotic stress) into the cells that culminate in brain damage mediated by reactive oxygen species.
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PMID:The osmotic/calcium stress theory of brain damage: are free radicals involved? 153 23

In several clinical situations, such as hyposmolar states and hypoxia-ischemia, reductions in the size of the extracellular space are associated with increased seizure susceptibility. Nonsynaptic interactions provide a likely means of mediating the effect of extracellular space on seizure susceptibility. Synchronous bursting of CA1 hippocampal neurons occurs via nonsynaptic mechanisms in solutions containing very low [Ca2+] and excitatory amino acid antagonists. We tested the hypothesis that lowering the osmolality of the extracellular medium could induce nonsynaptic bursting in the dentate gyrus, even though it is normally resistant to this treatment. Extracellular field potentials were recorded in the dentate gyrus and CA1 area of rat hippocampal slices. In the low-[Ca2+] solution with normal osmolality, bursts of population spikes were recorded from the dentate gyrus in only 7% of the slices, but solutions with decreased osmolality induced bursting in 63%. Corresponding values for the CA1 area were 60 and 73%, respectively. Mannitol, which reversed the hyposmolar state, abolished bursting in both regions. This study demonstrates that reducing the size of the extracellular space by lowering extracellular osmolality can transform a seizure-resistant area into one that exhibits robust epileptiform activity.
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PMID:Osmolality and nonsynaptic epileptiform bursts in rat CA1 and dentate gyrus. 154 52

The influx of Ca2+ into the neuron seems to play an important role in the genesis of epileptic seizures, and current research suggests that calcium entry blockers may have anticonvulsant activity. We used nimodipine, a calcium antagonist with high central nervous system affinity at a fixed dosage of 30 mg, t.i.d., in 21 patients with intractable epilepsy caused by organic brain lesions in addition to basal antiepileptic drug (AED) therapy. After a 12-week treatment period 14 patients (67%) showed a decrease in seizure frequency, four patients had no change, and three had an increase. In eight patients (38%) seizure frequency decreased by greater than 40%. The p value with one-tailed t-test was 0.0491. No significant modifications in AED or electrolyte serum levels were found. One patient had a lowering of blood pressure at this dosage.
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PMID:Calcium antagonist nimodipine in intractable epilepsy. 154 64

The movement of calcium into neurons may be the common denominator for the triggering and propagation of seizure activity. We report results of the first double-blind, placebo-controlled, crossover trial with the dihidropyridine calcium antagonist nifedipine (NFD) as adjuvant therapy in refractory epilepsy. Twenty-two students (12 male, 10 female, age 17-22 years) attending Lingfield Hospital School received NFD retard and matched placebo for 8 weeks in 2 doses (20 and 40 mg b.i.d. each for 4 weeks) with a washout period of 8 weeks between treatment phases. In the 20 students who completed the trial, fewer partial seizures (p less than 0.05) were documented during the first 2 weeks of NFD administration. Similarly, fewer seizure days (p less than 0.05) were reported in the first month of active treatment. This response was not sustained into the second month of the trial. Blind scoring of EEGs suggested a small improvement with NFD (p less than 0.05). More patients reported headache when receiving NFD (p less than 0.02) than placebo, but heart rate and erect and supine blood pressure remained unaffected. Mean maximum NFD concentrations were 13.1 +/- 10.4 ng/ml. A weak correlation was noted between total (p less than 0.05) and partial (p = 0.025) seizure numbers and NFD concentrations following 8 weeks of treatment. This study does not support important anticonvulsant efficacy for NFD as adjuvant therapy for refractory epilepsy at doses appropriate for the treatment of angina or hypertension. Further trials are recommended using higher doses of NFD in less severely affected patients.
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PMID:Nifedipine for epilepsy? A double-blind, placebo-controlled trial. 154 65

The K+ channel blocker 4-aminopyridine (4-AP) causes epileptiform activity in in vitro preparations and is a potent convulsant in animals and man. In mice, 4-AP produces behavioral activation, clonic limb movements and wild running, followed by tonic hindlimb extension and death (ED97, 13.3 mg/kg, s.c.). We evaluated the ability of a series of anticonvulsant drugs to protect against 4-AP-induced seizures using lethality as the endpoint. Drugs with a phenytoin-like profile of activity were protective with ED50 values (all in mg/kg, i.p.) of 34.4 for phenytoin, 18.6 for carbamazepine, 26.9 for felbamate, and 41.5 for zonisamide. Phenobarbital and valproate also protected against 4-AP-induced seizures and lethality (ED50s, 30.6 and 301, respectively). In contrast the NMDA antagonists (+/-)-CPP and (+)-MK-801 were inactive as were the GABA enhancers diazepam, vigabatrin and tiagabine; the antiabsence drug ethosuximide; and the L-type Ca2+ channel blocker nimodipine. We conclude that drugs like phenytoin which block seizure spread are effective antagonists of seizures induced by K+ channel blockade. Drugs with specific actions on other cellular targets may be weak or inactive, presumably because they are unable to attenuate the spread of intense (non-NMDA receptor mediated) excitation evoked by 4-AP.
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PMID:Effects of anticonvulsant drugs on 4-aminopyridine-induced seizures in mice. 156 41

Voltage-sensitive calcium (VSC) channels may contribute to epileptogenesis. A systematic examination of the anticonvulsant efficacy of different classes of VSC channel inhibitors, however, is lacking in chronic seizure models. The present study evaluated representatives from three different classes of VSC channel inhibitors for their protection against amygdala kindled seizures. Adult male rats (n = 12) were kindled to stage 5 seizures (GS), and a threshold intensity required to evoke a GS was determined. The Ca(++)-channel inhibitors (verapamil 0, 10, 20, 40 mg/kg; nimodipine 0, 5, 25, 50 mg/kg; nitrendipine 0, 25, 50, 100 mg/kg and flunarizine 0, 20, 40, 80 mg/kg) were administered 60-90 min prior to amygdala stimulation at the established threshold. None of the drugs altered threshold for inducing a seizure. Verapamil, a phenylalkylamine, and the dihydropyridines nimodipine and nitrendipine were without effect on kindled seizures. The diphenylalkylamine, flunarizine, was found to be the most efficacious, reducing AD duration and duration of clonic seizure activity by more than 60% in most animals. Flunarizine also decreased the severity of behavioral seizures, with 40% of the animals displaying Stage 1-2 seizures only. It is concluded that some VSC Ca(++)-channel inhibitors do possess anticonvulsant potential. Thus influx of extracellular calcium through VSC channels may contribute to the expression of kindled seizures.
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PMID:An examination of the anticonvulsant properties of voltage-sensitive calcium channel inhibitors in amygdala kindled seizures. 157 Mar 84

A case of alternating hemiplegia in a young girl is presented. The partial benefits of treatment with a calcium antagonist Flunarizine in this patient and in those reported in literature are reviewed. The onset of the disease in this girl was at three months of age with several episodes that were diagnosed as seizures; afterwards she presented, besides, repeated attacks of hemiplegia involving both sides of her body in an alternating way each time with daily frequency and hours of days of duration accompanied of bad mood and irritability as well as autonomic disturbances, oculomotor abnormalities, acquired mental retardation and residual focal neurological abnormalities. After one year of treatment with a calcium-entry blocker: Flunarizine, there was a 30% reduction in the attacks frequency as well as in its severity and stop of the progression of mental retardation. So we report the consequence of precocious diagnosis and treatment of this not well known entity whose clinical signs resemble paroxistic vascular anomalies in the brainstem territory.
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PMID:[Alternating hemiplegia. Partial effectiveness of treatment with flunarizine]. 157 Nov 84

Seizure is a common problem evaluated in pediatric emergency departments. Serum chemistry analysis is often performed as a routine part of the diagnostic evaluation of children who arrive in the ED with seizure. From this retrospective study, we sought to determine 1) how often serum electrolytes (Na, K, Cl, CO2), total calcium, magnesium, ammonia, and glucose chemistries were performed, 2) the frequency of abnormalities detected, and 3) whether abnormalities resulted in a change in patient care. Three hundred eight ED charts from 12 consecutive months were reviewed. Data collected included age, sex, ED diagnosis, medical history, and physical examination. Charts were also reviewed for diagnostic tests ordered and patient management. Children were classified as having febrile (FS) or nonfebrile seizures (NFS) to establish diagnostic evaluation practices for each group as well as to determine rates of laboratory abnormalities. Three hundred eight children were enrolled, 108 (35%) FS and 200 (65%) NFS. The mean ages of FS and NFS patients were 2.1 and 5.7 years, respectively (P less than 0.05, t-test). One hundred twenty-four of 308 (40%) children had at least one test performed; no abnormal test was thought to have caused seizure; none was treated. One hundred five of 308 (34%) were experiencing their first seizure. There was no difference in the likelihood of having a test ordered for children with a first seizure, regardless of seizure category. We concluded that 1) abnormal serum electrolytes, total calcium, magnesium, and glucose rarely cause seizure in children and 2) routine use of these tests in the ED is costly and does not contribute to seizure therapy.
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PMID:Emergency department laboratory evaluation of children with seizures: dogma or dilemma? 160 83


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