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Biomedical subjects

R H Mattson

Publications and source records attributed to R H Mattson.

At least 127 records · Page 7Linked to original sources
PubMed1982

The localizing value of depth electroencephalography in 32 patients with refractory epilepsy.

Clinical seizure manifestations, physical examination, radiological studies, neuropsychological tests, and scalp and depth electroencephalographic (EEG) studies were done to localize seizure foci in 32 patients, 23 of whom have undergone surgery with more than one year of follow-up. Of 16 patients with unlocalized scalp EEGs, depth EEG detected a consistent focal seizure onset in 3. Of 15 patients with localized scalp EEGS, depth EEG revealed multiple foci in 3 and inaccurate localization of the focus by scalp EEG in 4. Therefore, localization by scalp EEG was inaccurate in 10 of 31 patients. When depth EEG revealed a consistent focal seizure onset and this localization was used to determine to surgical resection site, good to excellent results were obtained in 12 of 13 patients. When depth EEG revealed additional foci of seizure origin, surgical results were fair or poor in all patients. No other localizing criteria predicted depth EEG results or surgical success with such accuracy. Furthermore, some criteria, including neuropsychological tests and radiological abnormalities, were falsely localizing at times. Therefore, of the presently available localizing criteria, depth EEG appears to be the most accurate.

Adolescent↗
PubMed1982

Interaction between valproic acid and carbamazepine: an in vitro study of protein binding.

Valproic acid (VPA) is highly bound to plasma protein (92-96%) and is likely to compete with carbamazepine (CBZ), another drug that is bound extensively (75%). CBZ protein binding was evaluated in vitro by ultrafiltration at concentrations within the therapeutic range (6, 8, and 12 micrograms/ml), while also varying VPA concentrations (0, 50, and 100 micrograms/ml). Using ultrafiltration, we found a significant elevation (p less than 0.01) in free and percent-free CBZ for every CBZ concentration tested as the total VPA concentration increased. Maximal effect was evident at 12 micrograms/ml CBZ. The free fraction increased from 23.5% free CBZ controls (2.85% micrograms/ml free) to 29.5% free CBZ (3.56% micrograms/ml free), with 100 micrograms/ml VPA a 25% increase in free CBZ. This in vitro study demonstrates that VPA competes with CBZ for plasma protein binding sites, resulting in a significant increase in free CBZ that may be clinically important.

Blood Proteins↗
PubMed1981

Ictal effects of anticonvulsant medication withdrawal in epileptic patients.

Medication withdrawal is used in selected instances to precipitate seizures during evaluation of epileptic patients. Whether such medication manipulation can alter electrical seizure onset or clinical seizure type is not known. Information regarding the effects of anticonvulsant withdrawal on depth EEG onset and clinical manifestations of seizures was reviewed in 25 patients with partial complex seizures in whom intracranial electrodes were implanted. For the purposes of this study, the withdrawal period was defined as the time after abrupt cessation of medication between one and five half-lives of the drug and the base-line state as all other times. Ten patients were withdrawn from carbamazepine, 6 from phenobarbital, 2 from phenytoin, and 3 from primidone. Overall effects of anticonvulsant withdrawal in 18 patients and 21 instances of withdrawal with a total of 89 withdrawal and 71 base-line seizures were notable. Focal electrical onset and typical clinical seizure type during withdrawal were entirely consistent with electrical and/or clinical characteristics of seizures occurring during the base-line state in 13 instances. "New" clinical and/or electrical seizure types occurred during withdrawal only in a number of patients in whom bilateral or multifocal seizure onset was confirmed electrographically outside of the withdrawal period. In only 1 patient did withdrawal produce atypical clinical and electrical seizures when the base-line state showed a clinically typical seizure of clear-cut localized onset. After surgery this patient was shown to have unequivocal multifocal seizure onset. Thus, for purposes of localizing single epileptic foci, information obtained during the anticonvulsant withdrawal period provided no misleading information in this group of patients, while condensing the time needed for evaluation.

Adolescent↗
PubMed1980

Valproic acid and ethosuximide interaction.

The addition of valproic acid to ethosuximide in treatment to prevent seizures caused increased serum concentration of ethosuximide in four of five patients observed. Ethosuximide levels increased from 73 to 112 microgram/ml (53% higher), with concomitant toxicity. Both were reversed by reduction of the ethosuximide dose from 27.4 to 20.4 mg/kg. Serum concentrations of these two drugs should be monitored closely when they are given together.

Adolescent↗
PubMed1980

Memory function in focal epilepsy: a comparison of non-surgical, unilateral temporal lobe and frontal lobe samples.

Three well-matched groups of non-surgical, pharmacologically controlled epileptic patients with unilateral seizure foci in either the left temporal lobe, the right temporal lobe or a frontal lobe, and a normal control group were compared on several verbal and non-verbal memory tasks. Results revealed significant impairment of verbal memory in left temporal epileptic subjects, and significant impairment of non-verbal, visual memory in right temporal epileptic subjects. Seizure patients with unilateral frontal lobe foci did not differ from the control sample on any measure. Results support previous research which emphasizes the importance of temporal lobe systems in memory function. The findings are discussed with regard to the nature and specificity of the observed deficits.

Adolescent↗
PubMed1979

Isoprinosine in subacute sclerosing panencephalitis.

An open therapeutic trial of isoprinosine was conducted in 15 patients with subacute sclerosing panencephalitis (SSPE). Long-term remissions occurred in 5 (33 percent), with documented improvement sustained for 2 or more years. Another patient was in remission 9 months after starting treatment, and three patients had transient remissions or stabilization. The disease was unaltered in five patients who had rapidly progressive SSPE when treatment started. These results compare with an average remission rate of about 5 percent in several series of untreated cases of SSPE or in cases treated with other antiviral agents. Patients in remission continued to have elevated cerebrospinal fluid (CSF) IgG and measles antibody titers, with one exception. Isoprinosine was tolerated for several years without side effects, except for mild hyperuricemia.

Adolescent↗
PubMed1979

Valproic acid: in vitro plasma protein binding and interaction with phenytoin.

Because valproic acid (VPA) is highly bound to plasma protein, several variables affecting binding will significantly alter the quantity of free drug which is pharmacologically active. Therefore, total VPA plasma concentrations do not reflect the therapeutic strength of the drug in tissue. We have performed equilibrium dialysis and ultrafiltration studies of VPA binding to plasma protein. The converging data in these in vitro studies indicate a clinically significant alteration in the percent of free VPA when total drug concentration exceeds 80 micrograms/ml. Saturation of drug binding sites probably occurs in this range. At 20--60 micrograms/ml VPA there is 5% free drug, with a significant increase to 8% free at 80 micrograms/ml; free drug increases to over 20% at 145 micrograms/ml total VPA. Human plasma, which is low in albumin, has twice the quantity of free VPA as normal plasma (10 versus 5% free). The clinical evidence of interaction between VPA and phenytoin is confirmed in vitro by the increase in the free fraction of both drugs. VPA binding decreases by 3--6%, while phenytoin binding decreases 5--6% as both drugs reach high plasma concentrations. When appropriate, laboratory reports should be available defining concentration of free drug in plasma for optimal interpretation of drug concetrations relative to clinical effects.

Blood Proteins↗
PubMed1978

Valproic acid in epilepsy: clinical and pharmacological effects.

The antiepileptic drug valproic acid was studied in an open clinical trial as adjunct medication for 23 patients with uncontrolled seizures of a generalized or partial type. Two-thirds of the patients experienced reduction in seizure frequency ranging from 25 to 100%. Extensive testing revealed no evidence of serious systemic toxicity due to the drug. Minor side effects (e.g., nausea, vomiting, or sedation) were usually transient. Sodium valproate syrup and valproic acid in capsules gave equivalent mean low (23.3 microgram/ml) and maximum (42.5 microgram/ml) serum concentrations. The drug had a relatively short half-life of 8.7 hours, necessitating administration in divided daily doses. During initiation of valproate therapy there was evidence of a decline in total serum phenytoin concentration (16.5 to 10.2 microgram/ml; p less than 0.001) while the percentage of free phenytoin increased (10.9 to 20%). The quantity of unbound phenytoin was relatively stable throughout. This observation was interpreted as a drug interaction: valproic acid competed with phenytoin for access to plasma protein binding sites.

Adult↗
PubMed1976

Eterobarb therapy in epilepsy.

A group of 27 patients with various types of epilepsy were selected for a 6-month double-blind crossover study to compare the anticonvulsant effect and toxicity of eterobarb and phenobarbital. No statistically significant differences in seizure frequency were found among the 21 patients who completed the 6-month trial, but three others, in whom status epilepticus developed during the crossover from eterobarb to phenobarbital, had to be removed from the trial. The study provided some indication that when eterobarb and phenobarbital were used in high dosage with corresponding high serum barbiturate levels (over 30 mug per milliliter), eterobarb had a superior therapeutic effect. Side effects from both drugs included tiredness, sleepiness, nystagmus, and infrequently ataxia, but serious systemic toxicity did not occur. This study showed that eterobarb is a safe and potent anticonvulsant comparable in efficacy to phenobarbital, and the superior results obtained in some patients with eterobarb therapy indicate that it is an effective alternative anticonvulsant.

Adolescent↗