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Biomedical subjects

R Eugene Ramsay

Publications and source records attributed to R Eugene Ramsay.

7 recordsLinked to original sources

Vigabatrin.

Refractory epilepsies such as infantile spasms (IS) and complex partial seizures (CPS) can have a severe negative impact on the neurological integrity and quality of life of affected patients, in addition to drastically increasing their risk of premature mortality. Early identification of potentially effective pharmacotherapy agents is important. Vigabatrin has been shown to be a generally well tolerated and effective antiepileptic drug (AED) in a wide variety of seizure types affecting both children and adults, particularly those with IS and CPS. A bilateral, concentric constriction of the peripheral visual field characterizes the visual field defect (VFD) associated with vigabatrin, well characterized by numerous studies. This peripheral VFD presents in 30-50% of patients with exposure of several years; however, most of these patients are asymptomatic. In well-controlled studies, the earliest onset in patients with CPS is 11 months and at 5 months in infants, with average onsets being more than 5 years and 1 year, respectively. Patients with a peripheral VFD retain an average 65 degrees of lateral vision (normal, 90 degrees). The fact that many patients never develop the vigabatrin-related peripheral VFD, despite long-term exposure at high doses, may support the hypothesis that the injury is an idiosyncratic adverse drug reaction (as opposed to a strict dose- or duration-dependent toxicity). Effective testing methods are available to aid in the early detection and management of the peripheral VFD. This article discusses issues of importance to clinical decision-making in the use of vigabatrin to assist the physician and patient in assessing the benefits of vigabatrin therapy and understanding the potential risks of the VFD and uncontrolled seizures.

Animals↗

Outcomes research: clinical trials in the elderly.

Very few clinical trials have been done in the elderly. This report reviews results of two completed studies and describes one in progress. The largest published study was a United States Veterans Affairs Administration study in newly diagnosed patients with epilepsy. It compared carbamazepine to gabapentin and lamotrigine, and found that, although equivalent in efficacy, the newer antiepileptic drugs (AEDs) were better tolerated. This study also highlighted many of the difficulties in recruiting and retaining elderly patients in studies, the large number of comorbidities, and the problems of distinguishing seizures in the elderly from other symptoms. Another study of new-onset epilepsy suggested that a large percentage of elderly patients respond to initial AED therapy, but side effect profiles differ. More studies are needed to better define the risk/benefit relationships in elderly patients.

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Elders with epilepsy.

Why is it important to learn about epilepsy in the elderly? The answers are many. As this article has highlighted, compared with younger individuals epilepsy is more common and the causes are more structural and symptomatic than in younger patients (particularly stroke). The clinical presentation is different in the elderly. The diagnosis is more difficult and often delayed. The most common seizures are simple partial and complex partial seizures, which are more often extratemporal in location. Confusion and memory problems are common presenting symptoms and postictal deficits often are prolonged. The prognosis for epilepsy in the elderly generally is favorable for seizure control, but if untreated, depression and quality of life suffer and seizures frequently recur. Seizures respond well at lower serum concentrations of antiepileptic drugs but these patients are also more sensitive (less tolerant) to side effects at lower doses than younger adults.

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Special considerations in treating the elderly patient with epilepsy.

Epilepsy in elderly patients, compared with the younger adult population, differs in etiology, clinical presentation, and prognosis. Challenges in the pharmacologic treatment of epilepsy in the elderly include the following: the physiologic changes associated with aging; adverse events to which the elderly are especially vulnerable; the increased risk for these patients, who are often taking multiple medications; and toxicity from drug-drug interactions. This article presents data on efficacy and safety from clinical trials of newer antiepileptic drugs (AEDs) in elderly patients compared with older AEDs. We discuss the implications of the findings using newer-generation AEDs in the Veterans Affairs Cooperative Study (VACS) #428 in order to educate physicians involved in choosing appropriate AEDs for older patients. In the elderly patient population, an optimal treatment outcome of seizure control with minimal or no adverse events is dependent on the well-informed choice of an AED by a physician.

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Randomized, controlled clinical trial of zonisamide as adjunctive treatment for refractory partial seizures.

PURPOSE: This study was designed to evaluate efficacy and safety of zonisamide (ZNS) as adjunctive treatment for patients with refractory partial seizures. METHODS: This randomized, double-blind, placebo-controlled study was conducted at four epilepsy treatment centers. It included a baseline phase (8 to 12 weeks) and a double-blind treatment phase (12 weeks). Initially, patients randomized to ZNS treatment were given a 7-mg/kg/d dosage. When investigators found that adverse effects could be reduced by gradually introducing ZNS, patients were allowed to begin treatment at lower doses (100 mg or approximately 1.5 mg/kg/d) titrated over several weeks to a maximum of 400 to 600 mg/d. Primary and secondary efficacy measures were the median percentage reduction from baseline in seizure frequency and the proportion of patients achieving a > or =50% reduction from baseline (responder rate). Patient and physician global assessments also served as indicators of efficacy. Safety was assessed primarily by treatment-emergent adverse events. RESULTS: ZNS-treated patients had a 28.9% reduction in seizure frequency, which differed significantly from the 4.7% increase in placebo-treated patients. The responder rate for ZNS-treated patients was 26.9%, compared with 16.2% for placebo-treated patients. At study's end, 66.2% of ZNS-treated patients and 12.3% of placebo-treated patients considered their condition improved; similarly, physicians assessed 63.6% of ZNS-treated patients and 10.8% of placebo-treated patients as improved. The most frequently reported adverse events with ZNS treatment included somnolence, irritability, dizziness, nausea, and fatigue. CONCLUSIONS: As adjunctive treatment, ZNS was generally well tolerated and significantly improved seizure control among patients with refractory partial seizures.

Adolescent↗

Advances in antiepileptic drug treatments. A rational basis for selecting drugs for older patients with epilepsy.

Incidence of epilepsy increases rapidly after age 65; recent studies indicate that approximately 10% of nursing home residents are being treated with antiepileptic drugs (AEDs). Almost all are being treated with first generation AEDs. The average nursing home patient receives six medications, has age-related changes in protein binding, decreases in hepatic and renal clearance, and may have alterations in gastrointestinal absorption. AEDs that do not have drug-drug interactions, are not metabolized by the liver, and are readily absorbed may offer benefits in this population. New studies are demonstrating that the first generation AEDs have a number of shortcomings for treating older patients, whereas some of the newer AEDs may overcome these limitations. This paper reviews the present knowledge base and compares properties of the first generation AEDs with newer agents to develop a more rational approach for drug selection in older adults.

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