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)

A prospective study is reported of antiepileptic drug withdrawal in 62 neurologically intact adult patients who had become seizure-free at least 3 years previously. No single clinical or laboratory finding was reliably predictive of outcome and in particular the presence of epileptiform EEG activity prior to AED withdrawal or appearance of such activity during withdrawal was not associated with relapse. A multivariate model was however developed which suggested that patients capable of remaining seizure-free without medication could be reliably identified at a much reduced cost of relapses in the remainder.
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PMID:Clinical and EEG prediction of seizure recurrence following antiepileptic drug withdrawal. 350 3

Groups of rats drank either a solution of the ultrashort-acting benzodiazepine midazolam or water under schedule-induced polydipsia conditions in chronic, daily, 3-hr sessions. In Experiment 1, the physical dependence status of animals was tested after 9 months by the precipitated withdrawal method using the benzodiazepine-blocking agent Ro 15-1788 and by exposure to a brief audio stimulus at 1.5, 12 and 24 hr following drug withdrawal. Ro 15-1788 failed to produce withdrawal signs, while the audio stimulus plus withdrawal did. In Experiment 2, similar groups were periodically tested for susceptibility to audiogenically-induced seizures at 3, 6, 12, 15, 18, 21, 24 and 26 weeks 90 minutes after their drug or vehicle intake sessions. In the midazolam-drinking group, physical dependence developed at about 12 weeks and increased in severity over the course of the study. Serum measures confirmed that continuous elevation of drug and active metabolite levels are not necessary for the development of physical dependence. A chronic, daily, single elevation of a few hr was sufficient.
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PMID:Development of physical dependence on midazolam by oral self-administration. 360 36

The effects of suloctidil (MY103) on the central (CNS) and peripheral nervous systems were investigated with single and consecutive administration. The general behavior in mice, awareness and motor activity were slightly depressed with the dose above 300 mg/kg, p.o. of MY 103. Soft stool was also marked in the dose above 100 mg/kg, p.o. in beagles and 1000 mg/kg, p.o. in mice. In beagles, vomiting was another syndrome with 100 and 300 mg/kg, p.o. of MY 103. Spontaneous motor activity was significantly decreased after MY 103 by p.o. administration in the dose above 100 mg/kg in mice and 300 mg/kg in rats. In sleep anesthesia studies, MY 103 and iproniazid did not potentiate the effect of a subthreshold dose of barbital, but those two drugs significantly prolonged the sleeping time of pentobarbital as chlorpromazine did. No anticonvulsive effect was observed with MY 103 in chemo- and electroshock seizure tests. My 103 of 300 mg/kg, p.o. significantly decreased the acetic acid induced writhing number, but no analgesic activity was found in the Haffner's method in mice. In the rotarod test, MY 103 of 30-300 mg/kg, p.o. inhibited the motor coordination dose-dependently. MY 103 antagonized the m-amphetamine group toxicity. A cataleptogenic effect was observed following the relatively high dose of MY 103 by an i.p. route. This effect was antagonized by atropine. The spinal reflexes in the immobilized cat, and spontaneous rabbit EEG were not affected by MY 103. The conditioned avoidance response (CAR) was also not changed with MY 103 in rats. In the isolated phrenic-nerve diaphragm preparation, 10(-4)M MY 103 irreversively inhibited the muscle twitches elicited by nerve and muscle stimulation, but suloctidil at 300 micrograms/kg, i.v., did not suppress the tibialis muscle twitches in vivo. In the consecutive administration study, MY 103 suppressed the CAR in rats and prolonged the thiopental-sleeping time in an administration period-related manner. These changes disappeared rapidly after drug withdrawal. Taking these evidences together, it can be concluded that MY 103 has little effect on the CNS with single administration, but the tendency to depress the CNS was observed after the repeated administration of MY 103.
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PMID:[Effects of suloctidil on the central and peripheral nervous systems]. 631 48

Monotherapy with the experimental antiepileptic drug cinromide was evaluated in 11 adult outpatients with uncontrolled partial epilepsy. They were treated with phenytoin for 2 months, cinromide for 4 months, and carbamazepine for 4 months. Four patients withdrew from the study during or shortly after crossover to cinromide due to increased seizure frequency or severity. Of the remainder, three preferred carbamazepine, two cinromide, and two phenytoin, based on both seizure control and degree of toxicity. Overall seizure control was not significantly different with any of the three agents, but during cinromide administration secondarily generalized seizure control was uniformly worst and there was also a tendency toward decreased performance on neuropsychological tests. CNS toxicity and gastrointestinal toxicity were prominent during the first month of cinromide treatment, but subsided with time or dose reduction. No abnormalities requiring drug withdrawal were found with laboratory testing. The results suggested, at best, a very limited clinical usefulness for cinromide, and it has been withdrawn from testing by its manufacturer.
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PMID:Cinromide in epilepsy: a pilot study. 640 98

This paper presents a series of 20 epileptic patients operated on at our Institute, with a clinical, EEG and drug plasma level follow-up, for periods from 48 to 60 months. Following surgery a group of 12 patients were seizure-free in a 3 year period of follow-up, and anticonvulsant medication was gradually withdrawn. While in 8 of these patients drug interruption uneventful, in 4 cases drug withdrawal caused the seizure to reappear. These 4 patients became seizure-free again, following a reintroduction of pharmacological therapy, which appeared to be effective also at low doses. Another group of 8 patients continued to have seizure also after surgery. Following quantitative and qualitative adjustments of their anticonvulsant medication, 5 patients became again seizure-free, while 3 continued to have seizures. Our experience suggests that in patients in whom the epileptogenic lesions have been surgically removed, anticonvulsant therapy can be safely withdrawn and removed after a seizure-free period of 3 years. Reappearance of seizures after drug withdrawal has a good prognosis, since a simple readjustment of medical therapy is usually effective in preventing further seizures to occur.
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PMID:[Interruption of antiepileptic therapy in seizure-free patients following surgery to remove the epileptogenic lesion]. 641 3

We investigated the conversion of mephenytoin to nirvanol in five patients with uncontrolled complex partial seizures. After a 50-mg single oral dose, mean peak mephenytoin level was 0.48 microgram/ml and nirvanol 0.37 microgram/ml. After 400 mg, peak mephenytoin level was 3.9 micrograms/ml and nirvanol 2.5 micrograms/ml. On 400 mg daily, mephenytoin reached a mean steady-state level of 1.5 micrograms/ml. Nirvanol mean steady-state level was 18 micrograms/ml. Mean plasma half-life was 17 hours for mephenytoin and 114 hours for nirvanol. Two patients had reduced seizures during mephenytoin therapy and one a transient increase during drug withdrawal. No toxicity was seen, but mephenytoin was not more effective than phenytoin.
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PMID:Disposition of mephenytoin and its metabolite, nirvanol, in epileptic patients. 643 15

Of over 40 known epileptogenic mechanisms, some 10 vary from hour to hour, depending upon habit factors and the daily activities of the patients. Tension states, alterations of level of consciousness, sleep deprivation, disturbances of water and acid-base balances, sensory and drug stimulation, and drug withdrawal are the principal factors involved. Their importance varies widely in patients, as well as with time. This fact and the concentration of physicians upon drug therapy have served to deemphasize this aspect of antiepileptic therapy. This point was clearly verified by reviews of the literature. In a prospective study of 500 drug-resistant patients, such seizure-inducing mechanisms were studied. Methods of identification, evaluation, and regulation were developed. The results indicate that in selected patients the regulation of such factors may play a significant role in the stabilization and improvement of the underlying epileptic condition. In 17% of a refractory group, such factors were found to be of crucial importance. In spite of intensive efforts with drug therapy over the past 4 decades, the incidence of drug-resistant cases remains high. The more comprehensive approach suggested offers an attractive, partial solution to this difficult problem.
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PMID:The importance of seizure-inducing factors in the control of refractory forms of epilepsy. 661 87

After reaching an apparent steady state, plasma phenytoin (PHT) levels may then undergo inexplicable changes, a phenomenon called " pseudosteady state". We evaluated 13 pseudosteady -state periods in 10 inpatients with complex partial seizures. Eleven of the periods occurred after a change in PHT dosage and two after drug withdrawal. The pseudosteady -state period began 2 to 12 days (means = 5.7 days) after dosage change and lasted 5 to 10 days (means = 6.3 days), during which plasma PHT levels were stable (+/- 5%). Plasma PHT levels thereafter fluctuated spontaneously by greater than 25% for 5 to 22 days (means = 10.8 days). A final steady-state level was reached 13 to 31 days (means = 21.4 days) after the first dosage change. Falling plasma PHT levels increased seizure frequency in two patients, and a level of 52 micrograms/ml led to medication toxicity in another.
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PMID:Phenytoin: the pseudosteady-state phenomenon. 673 35

To evaluate the risk of relapse in children with epilepsy whose anticonvulsant therapy has been withdrawn after prolonged control, we studied 148 such children for 15 to 23 years or until relapse. Forty-one of the 148 patients (28 per cent) had recurrence of seizures; of these, 35 (85 per cent) had relapses within five years of drug withdrawal. Factors associated with an increased risk of relapse were a long duration of epilepsy before control, neurologic dysfunction, and jacksonian seizures or combinations of seizure types. We found no association between risk of recurrence and age at onset of epilepsy, total number of seizures before control, age at discontinuation of therapy, electroencephalographic abnormalities, or family history of epilepsy. We conclude that children who do not have the additional risk factors noted above have an excellent chance of remaining seizure free after the withdrawal of anticonvulsant drugs.
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PMID:Prognosis in childhood epilepsy: additional follow-up of 148 children 15 to 23 years after withdrawal of anticonvulsant therapy. 680 11

The effectiveness of valproic acid (V.P.A.) in the symptomatic treatment of child's seizures is well established. Its lack of side-effects detrimental to the child's development and, on the contrary, its often positive action on awareness and attention should lead to choose V.P.A. as the first and main therapy. All night sleep recordings have been largely used to study the consequences of drug intake and drug withdrawal. It seemed interesting a) to control the effects of V.P.A. on sleep parameters when it was given as first treatment and b) to compare its effects to those of barbiturates when it was given in substitution. The study of sleep parameters seems to evidence that the often obtained clinical efficiency of V.P.A. parallels the restoration of a physiological functioning of the central nervous system normal or closer to normal.
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PMID:[Readjustment of anticonvulsive therapy in children. Monitoring of the effects of sodium valproate after barbiturate withdrawal by electrophysiologic sleep studies]. 682 Jun 43


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