Acute and chronic antiepileptic drug effect on the T complex interhemispheric latency difference.
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Adolescent↗
Biomedical subjects
J K Penry
Publications and source records attributed to J K Penry.
Active noncompliance as a cause of uncontrolled seizures.
A 26-year-old woman with intractable seizures and fluctuating plasma phenytoin concentrations is described. Noncompliance with prescribed drug regimens was suspected. Phenytoin was first given as a capsule and then as an elixir. Ingestion of the capsule was monitored, and active non-compliance was proved and admitted by the patient. The causes of inadequate plasma phenytoin concentrations are few and can be determined either by specific laboratory methods or by changing the form of the drug.
Adult↗
Changes in brain metabolites induced by convulsants or electroshock: effects of anticonvulsant agents.
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Animals↗
[Development of tolerance of phenobarbital after administration over several days (author's transl)].
In mice daily testing by maximal electroshock (MES) and pentylenetetrazole infusion (PTZ) 2 h after an i.p. injection of 25 mg/kg penobarbital (PB) was performed on days 1, 2, 4 through 8. The first twitch was delayed as compared to NaCl controls (50.4 +/- 4.8 s; 36.6 +/- 3.6 s; n = 53) on day 2, 4, 6 through 8. There was no tolerance of the PTZ induced tonic extension with Pb-treatment. In contrast, MES-tested mice developed tolerance, at day 5 the number of protected animals fell to about 50%. In view of the constant phenobarbital levels in plasma, a functional tolerance was assumed. The development of tolerance seemed to be connected with the spread of the discharge but not with discharge of the neurones themselves since it was observed only with MES but not wih PTZ-testing.
Animals↗
Hemispheric differences in the auditory evoked response.
The separation of the 80-250 msec portion of the AER to click stimulation into N1P2, produced by large areas of cortex, and the T complex, probably produced by secondary auditory cortex, was recently described (Wolpaw and Penry 1975). The present study investigated the ipsilateral vs. contralateral and right vs. left hemispheric differences in N1P2 and T complex latencies and amplitudes. One msec clicks at 60 dB above threshold were presented at 4.7 sec intervals monaurally to 32 normal adults and binaurally to 13 of the 32. AERs were recorded from vertex and temporal referred to a balanced non-cephalic reference electrode. For monaural stimulation, N1P2 and T complex amplitudes were significantly greater and T complex latency was significantly less over the contralateral and right hemispheres. The ipsilateral vs. contralateral and right vs. left hemispheric amplitude differences were significanlty greater for the T complex than for N1P2. Binaural results, which provided in additional measure of right vs. left hemispheric differences, were in agreement with the monaural findings. The results are consistent with neurophysiologic and behavioral findings in regard to ipsilateral vs. contralateral and right vs. left hemispheric differences and support the hypothesis that the T complex is produced by secondary auditory cortex.
Adult↗
Diagnostic and therapeutic reevaluation of patients with intractable epilepsy.
Intensive monitoring techniques were used to improve seizure diagnosis and control in 23 patients with intractable epilepsy: (1) Video recording of clinical seizures and the ictal EEG, (2) long-term telemetered EEG recordings, and (3) frequent determination of plasma antiepileptic drug concentrations. Patients were monitored in the hospital for an average of 8 weeks and after discharge were followed for an average of 8 months. At follow-up, 70 percent of the patients continued to have improved seizure control as compared with baseline studies, 83 percent had decreased toxicity, and about half had made gains in social adjustment. Use of the techniques described can make a significant contribution to patients previously considered intractable to therapy.
Adolescent↗
Interlaboratory variability in determination of plasma antiepileptic drug concentrations.
The usefulness of plasma antiepileptic drug concentrations in treatment of epilepsy has been established, and many laboratories provide this service. A "blind" survey utilizing pooled patient plasma samples was conducted among 197 laboratories in the United States and Canada to establish the interlaboratory reproducibility. Three "patient specimens" containing different amounts of phenobarbital, phenytoin (diphenylhydantoin), primidone, and ethosuximide were employed; 112 laboratories reported results within five weeks. The average cost for analyzing four drugs in a single sample was $43.27. Half of the laboratories reported results outside +/- 1 standard deviation of the mean of five reference laboratories. Wide interlaboratory variability must be considered by the practicing physician. Until certified antiepileptic drug standards in a biologic matrix are available from the National Bureau of Standards, a volunteer quality control program among laboratories is needed.
Anticonvulsants↗
Computer recognition of generalized spike-wave discharges.
Twelve 12h daytime telemetered EEGs were read for generalized spike-wave (S-W) bursts by a computer and independently by three experienced electroencephalographers. The computer system was a hybrid of analog devices (tape-recorder, voltage summator, and high-pass filters) and a multipurpose laboratory digital device (PDP-12). The computer was programmed to identify only the location on the record and the duration of the generalized S-W paroxysms. From 1,462 discharges identified by both the readers and the computer, a consensus list of 609 was derived by selecting only those bursts identified by all three readers. The computer recognized 516 (85%) of those bursts on the consensus list; the computer's accuracy, as compared with the consensus, rose to 92% when portions of the EEG containing sleep were discounted. The computer also recognized as generalized S-W paroxysms 15 high-voltage transients, which none of the three readers selected. Ten of these, however, occurred during sleep. When the computer results were added to those of the three readers to permit a four-way inter-reader comparison, the computer was found to have had about as many isolated decisions as any of the three readers. In the number of bursts recognized, the computer tended to be about as conservative as the reader under whose guidance it was originally programmed. The computer's accuracy in measuring burst duration was not evaluated statistically.
Computers, Hybrid↗
Prognostic factors in absence seizures.
A prospective follow-up study was conducted on 48 epileptic patients (22 males and 26 females) who had participated in a collaborative study of absence seizures about 7 years earlier. Multivariate analysis showed that the significant prognostic factors for absence seizures were normal or above normal intelligence and normal electroencephalographic background activity. For any seizure type, significant prognostic factors were a negative history of generalized tonic-clonic seizures, normal or above normal intelligence, and a negative family history of seizure disorders. Nearly 90 percent of the patients with all significant prognostic factors for both absence seizures and seizures of all types ceased having seizures.
Adolescent↗
The efficacy of carbamazepine combinations in epilepsy.
The efficacy and bioavailability, and tolerance to carbamazepinee when administered with phenobarbital or phenytoin or with both drugs were evaluated in a prospective, double-blind study of patients whose seizures were not completely controlled by currently available antiepileptic drugs in usually therapeutic dosages as determined by serum levels. During each of four 21-day treatment periods, one fourth of the patients received daily doses of: (1) carbamazepine (1,200 mg) and phenytoin (300 mg); (2) carbamazepine (1,200 mg) and phenobarbital (300 mg); (3) phenytoin (300 mg) and phenobarbital (300 mg); or (4) carbamazepine (1,200 mg), with phenytoin (300 mg) and phenobarbital (300 mg). The treatment periods were separated by 2 wk of each patient's usual prestudy medication. Treatment with all three drugs was the most efficacious for seizure control. Serum carbamazepine concentration was significantly decreased when the drug was administered with either phenytoin or phenobarbital or both.
Adult↗
Photic sensitivity of children with absence seizures in slow wave sleep.
Consequent upon previous studies on the effect of sleep on spike-wave discharges in absence seizures, photically sensitive spike-wave paroxysms were studied in 4 children with absence seizures, including identical twins, during various sleep stages. Sensitivity to stimuli at all frequencies and intensities was minimal during slow-wave sleep (stages 3 and 4), although photic driving could still be discerned. Trains of paired stimuli were effective in triggering polyspike responses during slow-wave sleep at frequencies of 6-8 c/sec and at flash intervals of 50 msec. The morphology of the discharges was similar to that seen in spontaneous discharges in deep sleep. The discharges, however, were stimulus-bound and there were no poststimulation spike-wave afterdischarges, which characterized wakefulness and REM sleep. The findings imply that, in deep sleep, while the cortical response to photic stimulation via the specific pathway system remains intact, the cortex appears to be functionally disconnected from those subcortical mechanisms essential for afterdischarge perpetuation.
Adolescent↗
A temporal component of the auditory evoked response.
We studied the 75-225 msec portion of the auditory evoked response (AER) in 32 normal adults at vertex (Cz) and temporal (T3 and T4) placements referred to a balanced, noncephalic reference electrode using a monaural 1 msec click stimulus delivered every 4.7 sec at 60 dB above threshold. The tape-recorded EEG was filtered at 1-25 c/sec, and 128 individual responses were summed, sampling every 0.5 msec for 250 msec post-stimulation. The Cz AERs showed the classic vertex response, a negative peak, N1, at 100 msec, followed by a positive peak, P2, at 160-200 msec. The T3 and T4 AERs were similar to the Cz AERs from 0 to 80 msec and from 200 to 250 msec. They differed significantly from the Cz AERs from 80 to 200 msec. The difference is best explained by the hypothesis that the Cz AERs consisted of N1P2, while the T3 and T4 AERs consisted of N1P2 plus an additional superimposed component, which we called the T complex, comprising a positive peak, Ta, at 105-110 msec, and a negative peak, Tb, at 150-160 msec. By computer, the corresponding Cz and T3 or T4 AERs were normalized to equalize their amplitudes, and the former was subtracted from the latter, thus isolating the T complex. The Ta peak was found to occur 1.5 +/- 1.6 msec earlier at the electrode contralateral to stimulation, and 2.2 +/- 4.0 msec earlier at the T4 (right) electrode. Both differences were statistically significant. The T complex amplitude was greater at the electrode contralateral to stimulation and at the T4 electrode. These findings appear to resolve current controversies concerning the form of the temporal AER. While N1P2 is apparently a product of widespread areas of cortex, we conclude that the T complex is probably a product of secondary auditory cortex.
Acoustic Stimulation↗
Simultaneous recording of absence seizures with video tape and electroencephalography. A study of 374 seizures in 48 patients.
Forty-eight patients, 4 to 24 years of age, with recurring absence seizures were studied prospectively for twenty-seven months. Each patient and his EEG were recorded simultaneously by a multicamera videotape technique and each recording was repeatedly viewed and described in writing by two observers who subsequently resolved any differences by joint viewing. From the 48 patients, 374 clinical absence seizures were recorded and classified according to the International Classification of Epileptic Seizures. Automatisms accompanied at least one attack in 88 per cent of the patients. Mild clonic components occurred in 71 per cent, and decreased postural tone in 41 per cent. Only one patient experienced an attack comprising only "blank staring" accompanied by unawareness and amnesia, but 40 per cent of patients exhibited this type of attack in addition to more complex absence attacks. Seizures of ten seconds or less in duration occurred among 85 per cent of patients. Each of the 374 seizures were readily classified according to the International Classification, but simple absence constituted only 9-4 per cent of the seizures. The others most often contained, in order of prevalence, either automatisms, mild clonic components, or decreased postural tone, or a combination of two or more of these features. The relationship between increased duration of the seizures and the occurrence of automatisms was significant. The findings are discussed in relation to differential diagnosis and mechanisms of automatisms. Absence seizures differ from complex partial (temporal lobe, psychomotor) seizures because an aura does not precede the abruptly beginning absence attack, the seizure usually lasts less than ten seconds, and mental clarity returns instantly at the end of the seizure.
Adolescent↗
Sodium di-N-propylacetate (DPA) in the treatment of epilepsy. A review.
The literature on clinical and experimental studies of sodium dipropylacetate (DPA), a branched chain carboxylic acid with a unique antiepileptic structure, is critically reviewed. The clinical antiepileptic properties are evaluated by seizure type. DPA appears to be most efficacious in the treatment of absence seizures. The literature also provides evidence for efficacy in the treatment of generalized tonic-clonic seizures and partial seizures with elementary symptomatology. The clinical pharmacology of DPA has not been thoroughly investigated. Simple, accurate, and reproducible gas-liquid chromatographic methods are available for determining the concentration of DPA in body tissues and fluids. The plasma half-life in humans is 8 to 15 hr. The most frequently observed adverse effects are gastrointestinal disturbances. In patients receiving additional antiepileptic drugs, potentially serious sedative effects have also been noted, which may be due to an interaction between DPA and concurrently administered medications.
Adolescent↗
A single-dose study of mexiletine (Kö 1173).
Serum concentrations of mexiletine after a single dose were determined in 8 adult Caucasian males with complex partial seizures who were continuing to receive other antiepileptic drugs. Two patients each received a single dose of either 100, 200, 300, or 400 mg mexiletine. Serum concentrations were determined by two gas chromatographic methods. Serum concentrations ranged up to 795 ng/ml. Peak concentrations occurred 1 to 3 hr after administration of the drug and were significantly different between the 100- and 300-mg, 100- and 400-mg, 200- and 300-mg, and 200- and 400-mg doses. Differences between the other doses were not significant. Serum concentrations declined monoexponentially. Half-life ranged from 2.7 to 7.2 hr. Numerous papers have appeared in the European literature on the use of mexiletine to treat cardiac arrhythmias. Preliminary studies in the United States suggest the use of mexiletine as an adjunct for therapy of epilepsy.
Adult↗
A multiple-dose study of mexiletine (Kö 1173).
In preparation for a prospective controlled study of mexiletine in the treatment of epilepsy, a preliminary study of serum concentrations after multiple doses was performed with 8 institutionalized Caucasian adult males with uncontrolled seizures and similar weight, medical regimen, and seizure classification. Two patients each received daily dosages of 200, 400, 600 or 800 mg mexiletine administered in capsules four times a day for 7 days, in addition to their usual medication. Serum concentrations of mexiletine were determined by the Kupferberg-Yonekawa method. After the first day, serum concentrations of mexiletine were significantly higher for the 600 and 800-mg dosages than for the 200- and 400-mg dosages. The differences in serum concentration between the 200- and 400-mg dosages and between the 600- and 800-mg dosages were not significant. Serum concentrations for the 200-mg and 400-mg dosages were generally below 400 ng/ml, whereas at dosages of 600- and 800-mg, serum concentrations ranged from 400 to over 1,100 ng/ml, after the first day. Optimal dosage for this population appeared to be at least 800 mg/day. Half-life ranged from 3.5 to 7.8 hr.
Adult↗
Serum clonazepam concentrations in children with absence seizures.
Clonazepam, a chlorinated derivative of nitrazepam, was administered to 10 children with absence seizures. Serum concentrations were measured after 8 weeks of treatment, at steady state. Seizure frequency reports and the 12-hour telemetered electroencephalogram were studied before and after 8 weeks of treatment to determine the frequency and duration of generalized spike-wave paroxysms. The clonazepam dosage ranged from 0.028 to 0.111 mg per kilogram and was reflected in serum levels ranging from 13 to 72 ng per milliliter, with an excellent correlation between dose and serum level. Eight of the 10 patients showed a significant decrease in seizure frequency, with three experiencing no seizures at all. Six patients had side effects, predominantly drowsiness and ataxia. This preliminary study shows clonazepam to be useful in the treatment of absence seizures in children and to merit further study.
Adolescent↗
Ethosuximide in the treatment of absence (peptit mal) seizures.
Thirty-seven patients with previously untreated absence seizures were treated with ethosuximide. Seizures were completely controlled in 7 patients (19 percent); 90 to 100 percent control was achieved in 18 patients (49 percent) and 50 to 100 percent control in 35 (95 percent). Plasma ethosuximide concentration increased with dose, but variability in the plasma concentration produced by a given ethosuximide dose made it impossible to predict a patient's plasma concentration from the dose. The therapeutic range of plasma ethosuximide concentration was 40 to 100 mug per milliliter. Patients with evidence of structural central nervous system abnormalities responded as well or better to the drug as patients without such evidence. Ethosuximide did not impair psychometric performance, but rather resulted in improved performance in 17 cases. The side effects of ethosuximide were minor, and rarely required withdrawal of the drug.
Adolescent↗