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The interaction between primidone and phenytoin was studied in an epileptic patient treated with primidone only and primidone plus phenytoin for 3 months. Plasma and urine levels of drugs and metabolites were monitored daily by GC and GC-MS. The addition of phenytoin to the regimen increased steady-state plasma levels of phenobarbitone and phenylethylmalonamide (PEMA), metabolites of primidone, and decreased levels of primidone and unconjugated p- hydroxyphenobarbitone (p-OHPB), a metabolite of phenobarbitone. After withdrawal of phenytoin, plasma phenobarbitone and primidone levels slowly returned to previous steady-state levels, PEMA rapidly decreased to lower levels than before, and p-OHPB levels rose rapidly. Urinary excretion of primidone and its metabolites paralleled the changes in their plasma levels after the addition of phenytoin but the percentage of unconjugated p-OHPB in urine was unchanged during the course of the study. In conclusion phenytoin initially induces the conversion of primidone to PEMA and phenobarbitone, although each to a different extent, but it appears to inhibit the hydroxylation of phenobarbitone. Thus, two apparently contradictory phenomena seem to be involved in the primidone-phenytoin interaction. The net effect is an enhanced increase in plasma phenobarbitone levels. [ABSTRACT FROM AUTHOR]

Background: Adult moyamoya disease is rare in the United States, and patients mostly present with cerebral ischemia. However, clinical and neurodiagnostic correlates of ischemia are not well known in this population. We sought to characterize the clinical and radiographic features of moyamoya disease in a large urban center in the United States, with a focus on angiographic and neuroimaging patterns of ischemia., Methods and Results: We retrospectively reviewed charts of consecutive adult moyamoya disease patients evaluated at 2 centers in Houston, Texas from January 2002 to December 2011. We reviewed all available cerebral angiograms and neuroimaging studies to evaluate the Suzuki grades, presence of intracranial hemorrhage or ischemia, infarct patterns, and vascular territory distribution. Our analysis was mainly descriptive. We identified 31 adults with moyamoya disease who met our inclusion criteria. The female-to-male ratio was 2.4:1. The majority of patients were white, followed by Hispanic, black, and Asian. Most presented with ischemia (61%), followed by headaches, and intracranial hemorrhage. Of the 22 patients with available neuroimaging, 72.7% had ischemic findings, with the vast majority having a watershed pattern (81.3%)., Conclusions: We observed a high burden of ischemia, mostly watershed pattern on neuroimaging in our adult moyamoya disease patients. Long-term monitoring of adult moyamoya disease patients in the United States would be useful to better understand the natural history of this condition., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Eating-induced seizures are an uncommon presentation of reflex epilepsy, a condition characterized by seizures provoked by specific stimuli. Most reports have identified aetiology associated with malformations of cortical developmental, hypoxic brain injury, previous meningoencephalitis or static encephalopathy. We present a patient with eating-induced reflex seizures, which began several years after treatment for an opercular primitive neuroectodermal tumour (PNET), and who subsequently underwent in-depth clinical and video-EEG analysis for her seizures. This patient noted rapid improvement with decreased frequency of seizure activity after treatment with valproic acid. We discuss the aetiology of reflex epilepsy, the anatomical basis of eating-induced epilepsy, and review the current literature.

Objective: Reports on zonisamide monotherapy are limited despite favourable preliminary data, and typically restricted to tertiary referral centres. The goal of this study is to report clinical experience with zonisamide monotherapy in a large, multi-group clinic setting., Methods: We reviewed the charts of patients treated with zonisamide monotherapy in the Neurology Department of the Kelsey-Seybold Clinic (Houston, Texas) during an 18-month period. We analysed subgroups of patients who were naive to antiepileptic drug (AED) therapy (Group 1) and those who had previous exposure to AEDs (Group 2)., Results: The study included 54 paediatric and adult patients with a variety of seizure types: 15 patients in Group 1 and 39 patients in Group 2. Mean maintenance zonisamide dosages in the two groups were similar (193 mg/day in Group 1 vs. 218 mg/day in Group 2). Thirty-eight patients (70.4%) continued zonisamide monotherapy, with 7 patients (13.0%) adding a second AED and 9 patients (16.7%) switching to a different drug. Of the 24 patients who became seizure free on zonisamide monotherapy, 11 were on the 100-mg initial dosage. Zonisamide monotherapy was well tolerated., Conclusions: Zonisamide monotherapy is safe and effective for a variety of seizure types and may be appropriate as first-line therapy in some cases.

Purpose: To provide 1995 estimates of the lifetime and annual cost of epilepsy in the United States using data from patients with epilepsy, and adjusting for the effects of comorbidities and socioeconomic conditions., Methods: Direct treatment-related costs of epilepsy from onset through 6 years were derived from billing and medical chart data for 608 population-based incident cases at two sites in different regions of the country. Indirect productivity-related costs were derived from a survey of 1,168 adult patients visiting regional treatment centers. Direct costs separate the effects of epilepsy and comorbidity conditions. Indirect costs account for the effects of other disabilities and socioeconomic conditions on foregone earnings and household activity. The estimates were applied to 1995 population figures to derive national projections of the lifetime and annual costs of the disorder., Results: The lifetime cost of epilepsy for an estimated 181,000 people with onset in 1995 is projected at $11.1 billion, and the annual cost for the estimated 2.3 million prevalent cases is estimated at $12.5 billion. Indirect costs account for 85% of the total and, with direct costs, are concentrated in people with intractable epilepsy., Conclusions: Direct costs attributable to epilepsy are below previous estimates. Indirect costs adjusted for the socioeconomic conditions of patients are above previous estimates. Findings indicate that epilepsy is unique in the large proportion of costs that are productivity-related, justifying further investment in the development of effective interventions.

Purpose: Studies of the incidence of epilepsy are limited to a few populations in which new cases can be ascertained. Health maintenance organization (HmO) populations were studied to determine the incidence in a multiethnic, urban United States population., Methods: Cases of initial unprovoked seizure disorder or epilepsy while enrolled in an HMO between 1988 and 1994 were ascertained. Ethnicity was obtained from the medical records and was part of a nested case-control study., Results: There were 197 incidence cases of epilepsy and 275 of initial unprovoked seizure diagnosis. The incidence rate in the age range 0-64 years was 35.5 per 100,000 for epilepsy and 50.9 for initial unprovoked seizure. When compared with population-based studies, rates were slightly higher in children younger than 15, similar for the 15- to 24-year age group, but lower for ages 25-64 years. The ethnicity-specific odds ratios for initial unprovoked seizure, by using non-Hispanic white as the referent, were 1.04 (0.73-1.49) for African-American, 0.97 (0.64-1.48) for Hispanic, and 0.25 (0.08-0.84) for Asian-American., Conclusions: The lower rate in the HMO population is presumably due to a healthy-worker effect. The ethnicity-specific incidence rates do not differ in this population.

This review of 126 reports on catamenial epilepsy describes seizure exacerbations associated with the menses. The importance of hormonal measurements, the influence of antiepileptic drugs and oral contraceptives, and the significance of hormonal changes on epilepsy are evaluated. The EEG changes during menses are discussed. Explanations for conflicting data are offered, and potential future investigations on catamenial epilepsy are suggested.

We evaluated the relationship between findings from EEG, transmission computed tomography (CT), and positron emission tomography in 23 adults with gliomas. The cortical metabolic rate was suppressed in patients with and without focal slowing. Focal delta activity was not related to involvement of gray or white matter. Rhythmic delta activity and focal attenuation of background amplitude on EEG, however, were correlated with involvement of the thalamus.

We used serial positron emission tomography scans with [18F]2-deoxyglucose to study the effect of phenytoin on human cerebral glucose metabolism in 10 patients with seizure disorders. Local CMRglu for each patient was measured in 10 regions of interest. EEGs were performed during each procedure to match scans for state of consciousness and exclude data from scans with ictal activity. Serial scans without a drug change were performed in six control patients. Metabolic rates were significantly lower in two cortical regions while patients were taking phenytoin. No significant changes on repeat scan were seen in the control population. Measured across all regions of interest, metabolic rates were 13% higher when patients were off phenytoin (p less than 0.02).

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.

Positron emission tomography with simultaneous electroencephalographic monitoring was performed with [18F]fluorodeoxyglucose in 20 patients with complex partial seizures who had normal computed tomographic scans. Seven patients had only unilateral epileptiform discharges on the electroencephalogram, 3 had predominantly unilateral discharges, and 10 had nonlocalized epileptiform abnormalities. Positron emission tomography showed a hypometabolic lesion in 16 of the 20 patients. Pathological changes in the hypometabolic region were found in postoperative specimens in 4 of 5 patients studied. Positron emission tomography was unaffected by the seizure frequency, state of alertness, or number of spike discharges during the scan. There was a tendency for patients to have higher overall metabolic rates when taking less medication. Seizures occurring during [18F]fluorodeoxyglucose uptake in 3 patients produced a hypermetabolic area at the interictal hypometabolic focus. Positron emission tomography sometimes showed more widespread hypometabolism than suspected on the basis of the scalp-recorded electroencephalogram. The frontal lobe showed a greater degree of hypometabolism than the temporal lobe in 3 patients. Focal lesions may be identified by positron emission tomography even if the electroencephalographic abnormality is not well localized.

The clinical efficacy of phensuximide and methsuximide was studied in relation to plasma concentrations of these compounds and their desmethyl metabolites. Single- and chronic-dose studies of each drug were carried out in five patients with intractable seizures. Patients were evaluated before and during treatment by 6-hour simultaneous video and telemetered electroencephalographic recordings to characterize the seizure type and by daily determinations of plasma antiepileptic drug concentrations. Phensuximide had a mean half-life of 7.8 hours and accumulated to an average fasting level of only 5.7 micrograms per milliliter. Desmethylphensuximide averaged only 1.7 micrograms per milliliter with a similar half-life. Methsuximide had an even shorter half-life, averaging 1.4 hours, but its desmethyl metabolite had a mean half-life of 38 hours and therefore accumulated to levels in excess of 40 micrograms per milliliter. The addition of phensuximide to their regimens benefited none of the patients, but two had an excellent response to methsuximide. The failure of phensuximide and its desmethyl metabolite to accumulate to reasonable levels is the likely explanation for the relatively weak antiepileptic effect of phensuximide as compared with methsuximide.

The use of antiepileptic drugs has become increasingly effective through several factors: new techniques that allow better diagnosis of the seizure disorder and its underlying cause; the development of new medications and increased knowledge of old ones; and the widespread use of antiepileptic drug-level determinations. The choice of a drug depends heavily on an accurate diagnosis of seizure type, which may determine the response to the medication. Because of better diagnostic criteria and intensive monitoring procedures, the correct seizure disorder can be more easily diagnosed and, therefore, the proper medication selected. Minimal efficacious and toxic blood concentrations have now been identified for most antiepileptic drugs. Several, including primidone, carbamazepine, methsuximide, and mephenytoin, have pharmacologically active metabolites that affect both the toxicity and efficacy of the prescribed drug and can now be measured in the plasma. The most effective use of the antiepileptic drugs depends on a combination of reliable blood level measurements, clinical observation, and knowledge of their pharmacokinetics and biotransformation.