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Biomedical subjects

R H Mattson

Publications and source records attributed to R H Mattson.

At least 19 recordsLinked to original sources
PubMed1992

A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group.

BACKGROUND: Valproate is approved for use primarily in patients with absence seizures, but the drug has a broad spectrum of activity against seizures of all types. Partial or secondarily generalized tonic-clonic seizures are often difficult to control adequately with standard treatment, usually carbamazepine or phenytoin. METHODS: We conducted a multicenter, double-blind trial that compared valproate with carbamazepine in the treatment of 480 adults with complex partial seizures (206 patients) or secondarily generalized tonic-clonic seizures (274 patients). The patients were randomly assigned to treatment with carbamazepine or divalproex sodium (valproate) at doses adjusted to achieve blood levels in the middle of the therapeutic range. Patients were followed for one to five years or until seizures became uncontrollable, treatment had unacceptable adverse effects, or both these events occurred. RESULTS: For the control of secondarily generalized tonic-clonic seizures, carbamazepine and valproate were comparably effective (in 136 patients and 138 patients, respectively). For complex partial seizures, four of five outcome measures favored carbamazepine (100 patients) over valproate (106 patients): the total number of seizures (2.7 vs. 7.6, P = 0.05), the number of seizures per month (0.9 vs. 2.2, P = 0.01), the time to the first seizure (P less than 0.02), and the seizure-rating score (P = 0.04). Carbamazepine was also superior according to a composite score that combined scores for the control of seizures and for adverse effects (P less than 0.001). Valproate was associated more frequently than carbamazepine with a weight gain of more than 5.5 kg (12 lb) (20 percent vs. 8 percent, P less than 0.001), with hair loss or change in texture (12 percent vs. 6 percent, P = 0.02), and with tremor (45 percent vs. 22 percent, P less than 0.001). Rash was more often associated with carbamazepine (11 percent vs. 1 percent, P less than 0.001). CONCLUSIONS: Valproate is as effective as carbamazepine for the treatment of generalized tonic-clonic seizures, but carbamazepine provides better control of complex partial seizures and has fewer long-term adverse effects.

Adolescent↗
PubMed1992

Occipital lobe epilepsy: clinical characteristics, seizure spread patterns, and results of surgery.

Twenty-five patients with occipital lobe seizure origin were retrospectively evaluated to determine clinical seizure characteristics and electroencephalographic manifestations. Certain symptoms and signs served to identify occipital lobe origin in 22 (88%). These included elementary visual hallucinations, ictal amaurosis, eye movement sensations, early forced blinking or eyelid flutter, and visual field deficits. Eye or head deviation, or both, was observed frequently and was contralateral to the side of seizure origin in 13, but 3 patients exhibited ipsilateral deviation in some or all their seizures. After the initial signs and symptoms, clinical seizure characteristics resembled those of seizures originating elsewhere. Seizures typical of temporal lobe origin with loss of contact and various types of automatic, semipurposeful activity occurred in 11 patients. Seizures in 3 patients exhibited asymmetrical tonic or focal clonic motor patterns characteristic of frontal lobe seizures. Eleven of the 25 patients had, on two occasions, two or more distinctly different seizure types. Scalp electroencephalographic findings were seldom helpful for occipital lobe localization and were frequently misleading. Intracranial electroencephalographic recording correctly identified occipital lobe seizure origin in most, but not all, patients who had such studies. Intracranial electroencephalic recording also proved the variability in clinical seizure characteristics was related to different seizure spread patterns, medially or laterally above and below the sylvian fissure, both ipsilateral and contralateral to the occipital lobe of seizure origin. Eighteen patients had occipital lobe lesions detected with computed tomographic or magnetic resonance imaging scans or both. Resection of the lesions in 16 patients produced excellent results in 14 (88%). Five patients had temporal lobectomies, with good results in 3, but poor results in 2. Two patients with unlocalized seizures had complete section of the corpus callosum, 1 with a good result and the other with a poor result.

Adolescent↗
PubMed1992

Parietal lobe epilepsy: diagnostic considerations and results of surgery.

Eleven patients, evaluated between 1983 and 1988, with parietal lobe seizure origin as determined by circumscribed lesion detection in all and successful surgery in 10, were retrospectively evaluated in terms of clinical seizure characteristics and electroencephalographic (EEG) findings. Seven of 11 patients reported auras prior to seizures. In 4 patients, auras were lateralized somatosensory sensations, but in 1 they were ipsilateral to the side of seizure origin, and in 2 they had only occurred many years previously when seizures began. Other auras were either nonspecific or suggested seizure origin outside of the parietal lobe. Observed seizures were of two types: asymmetrical tonic seizures with or without clonic activity and complex partial seizures with loss of contact and automatisms. Four patients had only the first type of seizure and an equal number had only the second type. Three patients had both types of seizures during different episodes. Scalp EEGs correctly localized the side and region of seizure onset in only 1 patient. Three additional patients with congruent parietal localization on scalp EEG had additional misleading EEG findings. All patients had lesions detected with neuroimaging, but in 5 this detection occurred after they had been initially evaluated. These 5 patients had intracranial EEG studies designed to localize the region of seizure origin, and correct seizure onset localization was achieved in 2. Of the other 3 patients, false localization occurred in 1, and 2 could not be localized. Four patients with known lesions and 2 of the patients in whom lesions were detected after initial intracranial evaluations were studied with subdural grid electrodes placed over the lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

"Central" and "peripheral" benzodiazepine receptors: opposite changes in human epileptogenic tissue.

We measured the density of two benzodiazepine (BZ) receptor subtypes in neurosurgically obtained hippocampal tissue from the seizure focus of patients with temporal lobe epilepsy (TLE) showing mesial temporal sclerosis, the most common pathologic finding in TLE. We performed quantitative in vitro receptor autoradiography with [125I]Ro 16-0154, a probe for the central-type BZ receptor and with [3H]PK 11195, a probe for the peripheral-type BZ receptor. In comparison with autopsy and neurosurgical control groups, patients with mesial temporal sclerosis had regionally selective decreased central-type and increased peripheral-type BZ receptors. These changes paralleled regional losses of neurons and proliferation of glia. Decreases of the inhibitory central-type BZ receptor may be a component of the enhanced excitability of the seizure focus and also may allow localization of the focus by in vivo neuroreceptor imaging. Single photon emission computed tomography (SPECT) imaging of two TLE patients with [123I]Ro 16-0154 suggests that this technique may provide a more sensitive means of localizing the seizure focus than current imaging methods relying on changes in blood flow or glucose metabolism.

Adult↗
PubMed1992

Drug treatment of uncontrolled seizures.

The success of AED therapy for epileptic seizures varies according to epilepsy and seizure type. The outcome is excellent in the idiopathic generalized epilepsies, poor in the secondary generalized epilepsies and intermediate for the partial epilepsies. For this latter group, a table of outcome is described in Table I. Overall, approximately 70% of patients can be reasonably managed using one AED, although several may need to be tried before considering monotherapy to be a failure. Of the 30% unsatisfactorily managed by monotherapy, approximately another one-third can be adequately managed given a combination of two drugs. Combinations of more than two drugs provide little if any additional benefit. Evidence that such combinations have efficacy is inferred from the observation of seizure exacerbation when one drug is removed purposely to elicit seizures during evaluation for possible epilepsy surgery. The remaining patients are often considered for trial of an investigational drug although prospects for important improvement are very small even with use of agents shown to be effective and introduced for treatment of epilepsy. Thus, 15% of patients may conservatively be considered for surgical therapy. This would not suggest that all such patients are appropriate candidates from other aspects, but at least they can be considered to have failed all reasonable drug therapy.

Anticonvulsants↗
PubMed1991

Comparison of bitemporal and unitemporal epilepsy defined by depth electroencephalography.

Of 166 consecutive patients studied with depth electroencephalography (EEG), 87 had seizures arising from one temporal lobe and 23 had seizures arising independently from each temporal lobe. We retrospectively reviewed and compared those patients with unitemporal and those with bitemporal seizures. There was no statistically significant differences between the two groups in terms of age at onset of seizures, duration of epilepsy, localization of scalp EEG abnormalities, surgical results, or pathological findings. The bitemporal group, however, had significantly fewer patients with a history of febrile seizures (p less than 0.025). Two patients with bitemporal seizures were later found to have extratemporal lesions, and one an extrahippocampal temporal lesion, on magnetic resonance scans; one patient's extratemporal lesion was resected and all habitual seizures stopped. These findings suggest that a single pathophysiological process accounts for unitemporal and some bitemporal epilepsy, but that independent onset of seizures from each temporal lobe detected by depth EEG may also indicate extratemporal foci.

Adolescent↗
PubMed1991

Temporal lobectomy in patients with bitemporal epilepsy defined by depth electroencephalography.

Patient selection for temporal lobectomy was reviewed for 23 patients with seizures that arose independently from each temporal lobe as detected by depth electroencephalography (EEG). Although neuropsychological testing, interictal EEG findings, imaging studies, and subclinical seizures were also considered, all patients offered temporal lobectomy had (1) at least 50% of the clinical seizures originating from the lobe to be resected, (2) adequate contralateral memory on testing with amobarbital, and (3) no clear evidence of an extratemporal focus. Eleven patients underwent temporal lobectomy. Pathological findings were considered positive in all nine specimens reviewed. Nine patients had no seizures, one had greater than 75% reduction in seizure frequency, and 1 had 50 to 75% reduction. Pathological features and clinical outcome were similar in the 6 patients with fewer than 80% and the 5 patients with at least 80% of seizures originating from the resected lobe. Thus, having fewer than 80% of seizures originate from one temporal lobe should not be an absolute contraindication for temporal lobectomy.

Adolescent↗
PubMed1991

A method for prediction of phenytoin levels in the acute clinical setting.

Phenytoin (PHT) administration is complicated by saturation kinetics within the therapeutic range, causing marked changes in drug concentration with small changes in dose. The "half-life" increases with concentration, varying from 8-24 hr up to weeks, making it difficult to obtain the steady state levels needed by most prediction algorithms and nomograms. A Bayesian prediction program (Epidose) is presented which explicitly models PHT absorption and elimination kinetics in the non-steady state. The algorithm accounts for the interdependency of closely spaced sequential samples. Estimates of future PHT concentration were made on 20 hospital inpatients, most of whom were acutely ill and received other medications. Future (mean = 4 day) PHT concentrations were predicted over a range from 4 to 22 micrograms/ml (mean 13.9 micrograms/ml) with a median absolute error of 1.0 microgram/ml. These data demonstrate that the program can be used for accurate PHT concentration predictions in sick patients.

Adult↗
PubMed1991

Feeling-of-knowing in temporal lobe epilepsy: monitoring knowledge inaccessible to conscious recall.

Feeling-of-Knowing was compared in left temporal, right temporal, and control subjects. Seizure patients, like controls, demonstrate knowledge of information that is not accessible to conscious recall, but they are less accurate in FOK judgements. Furthermore, there are significant differences between seizure patients and controls in the relationship between Feeling-of-Knowing and object level memory scores: (1) Controls spend more time searching memory for inaccessible information that is correctly identified on a later recognition test than they do for information that is incorrectly recognized. (2) Latency of correct recognition decreases as strength of FOK increases among controls, suggesting that controls correctly anticipate the outcome of memory search. These patterns of performance, which are consistent with an efficient memory search termination device, were not observed among seizure patients. The findings suggest that inaccurate Feeling-of-Knowing may play a role in inefficient memory search mechanisms in temporal lobe epilepsy.

Adult↗
PubMed1991

Multicenter long-term safety and efficacy study of vigabatrin for refractory complex partial seizures: an update.

We followed 66 patients with refractory complex partial seizures and a favorable initial response to vigabatrin for 5 to 72 (median, 43) months. Thirty-seven patients discontinued vigabatrin for the following reasons: benefit-to-risk evaluation, 8; seizure breakthrough, 6; adverse events, 6; seizure breakthrough and adverse events, 5; moved or lost, 4; no longer eligible for study, 2; non-drug-related death, 2; narcotic abuse, 1; and patient request, three. There were no clinically significant abnormalities in laboratory studies including SMA 12, complete blood count, ECG, EEG, and visual evoked response testing, and no toxicity other than reversible, dose-dependent side effects. Based on this and other long-term data, clinical trials of vigabatrin have resumed in the United States and Canada.

Aminocaproates↗
PubMed1991

A method of assessing the efficacy of memory rehabilitation techniques using a "real-world" memory task: learning a computer language.

A software program developed to assess the effectiveness of memory rehabilitation techniques is described. This project addresses current weaknesses in the research literature on memory rehabilitation: 1) remediation strategies are evaluated in terms of performance on a practical, real-world memory task, rather than a laboratory learning task; 2) the program allows maximum flexibility in assessing a wide variety of remediation strategies and training schedules; and, 3) the software, which provides sensitive outcome measures and detailed feedback about performance, is adaptable to the needs of patients with widely varying degrees of memory impairment. The results of a demonstration project are included to illustrate the use of this technology in determining the usefulness of different mnemonic strategies for patients with specific patterns of memory deficit. The importance of assessing maintenance of rehabilitation training over time is stressed.

Computer Graphics↗
PubMed1991

Emotional effects on seizure occurrence.

Emotional factors can alter the likelihood of seizure occurrence, and they usually increase the frequency of attacks. Our case studies showed that such activation is brought about through missed medication, sleep deprivation, and hyperventilation. Less well documented is the possibility that increased excitability and seizures may be due to direct neuronal activation of limbic circuits, although such a mechanism would be quite plausible.

Adult↗
PubMed1990

Selection of drugs for the treatment of epilepsy.

Antiepileptic drug selection is based on efficacy for specific seizure types and epileptic syndromes. For idiopathic generalized epilepsies with absence, tonic-clonic, and myoclonic seizures, the drug of choice is valproate. Secondary generalized epilepsies with tonic, atonic, and other seizure types are difficult to treat with any single drug or combination of drugs. The drugs of choice for absence seizures are ethosuximide and valproate. For control of tonic-clonic seizures, any of the other major antiepileptic drugs can be effective. If valproate cannot be used, carbamazepine, phenobarbital, phenytoin, or primidone is effective, but ethosuximide or a benzodiazepine needs to be added to control associated absence or myoclonic seizures. The drugs of first choice for partial epilepsies with partial and secondarily tonic-clonic seizures are carbamazepine and phenytoin. Increasing evidence suggests that valproate may be a third alternative. Phenobarbital and primidone are second choice selections because of side effects. A combination of two of these five major antiepileptic drugs may be necessary for inadequately controlled patients. Other epilepsy syndromes such as neonatal and infantile epilepsies, febrile epilepsy, and alcoholic epilepsy require specific drug treatment. For all these seizure types and epilepsy syndromes, treatment ultimately must be selected to provide maximal efficacy and minimal adverse effect for each individual patient.

Anticonvulsants↗
PubMed1990

In vivo determination of valproate binding constants during sole and multi-drug therapy.

Valproate (VPA) is present in humans and is largely bound to protein. Only free drug is metabolized, and antiepileptic and toxic effects are probably related to free concentrations. By measuring serial free and total serum VPA levels after routine oral doses, we have determined individual in vivo protein binding parameters for 37 patients after a total of 49 separate drug administrations. Binding site concentrations and dissociation constants were fitted using a nonlinear algorithm. On sole VPA (n = 28) the mean dissociation constant was 91 mumol/L, and the mean concentration of binding sites was 1,176 mumol/L. Evidence suggests a second, nonsaturable binding site. Fraction of unbound VPA ranged from 5.4% at low levels up to 38.7%, rising with increasing total concentration. Concurrent therapy with phenytoin (n = 7) or carbamazepine (n = 8) did not cause displacement of VPA. Changes in free fraction were consistently observed during the interdose interval. The data demonstrate that the binding changes are not a factor in decreased VPA levels during coadministration of other antiepileptic drugs.

Binding, Competitive↗
PubMed1990

Compliance declines between clinic visits.

Adherence to prescribed drug dosing regimens declined substantially during the interval between clinic visits and drug level tests. Using microelectronic monitors to observe pill-taking habits, 20 patients averaged 88% compliance before and 86% compliance after the visit, but this dropped to 67% compliance a month later. These data indicate that spot drug levels do not represent long-term "steady-state" drug serum concentrations.

Anticonvulsants↗
PubMed1989

How often is medication taken as prescribed? A novel assessment technique.

The evaluation of the efficacy of medication is confounded when patients do not adhere to prescribed regimens. Overdosing, underdosing, and erratic dosing intervals can diminish drug action or cause adverse effects. Using a new method with epilepsy as a model, we assessed compliance with long-term medications among newly treated and long-term patients. Medication Event Monitor Systems (Aprex Corporation, Fremont, Calif) are standard pill bottles with micro-processors in the cap to record every bottle opening as a presumptive dose. Compliance rates averaged 76% during 3428 days observed: 87% of the once daily, 81% of the twice daily, 77% of the three times a day, and 39% of the four times a day dosages were taken as prescribed. Coefficients of variation of drug serum concentrations had no significant relationship to compliance rates. Pill counts overestimated compliance increasingly as compliance with the prescribed regimen declined. Neither drug serum concentrations nor pill counts would have identified the frequency of missed doses that were revealed with continuous dose observations.

Adult↗