Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy.

PURPOSE: We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy. METHODS: Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation. RESULTS: One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and "most severe" seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events. DISCUSSION: Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.

Report of the American Epilepsy Society and the Epilepsy Foundation joint task force on sudden unexplained death in epilepsy.

The American Epilepsy Society and the Epilepsy Foundation jointly convened a task force to assess the state of knowledge about sudden unexplained death in epilepsy (SUDEP). The task force had five charges: (1) develop a position statement describing if, when, what, and how SUDEP should be discussed with patients and their families and caregivers; (2) design methods by which the medical and lay communities become aware of the risk of SUDEP; (3) recommend research directions in SUDEP; (4) explore steps that organizations can take to perform large-scale, prospective studies of SUDEP to identify risk factors; and (5) identify possible preventive strategies for SUDEP. Some of the major task force recommendations include convening a multidisciplinary workshop to refine current lines of investigation and to identify additional areas of research for mechanisms underlying SUDEP; performing a survey of patients and their families and caregivers to identify effective means of education that will enhance participation in SUDEP research; conducting a campaign aimed at patients, families, caregivers, coroners, and medical examiners that emphasizes the need for complete autopsy examinations for patients with suspected SUDEP; and securing infrastructure grants to fund a consortium of centers that will conduct prospective clinical and basic research studies to identify preventable risk factors and mechanisms underlying SUDEP. For now, the principal effort in preventing SUDEP should be prompt and optimal control of seizures, especially generalized convulsive seizures.

Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy.

OBJECTIVE: To report long-term efficacy and safety results of the SANTE trial investigating deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy. METHODS: This long-term follow-up is a continuation of a previously reported trial of 5- vs 0-V ANT stimulation. Long-term follow-up began 13 months after device implantation with stimulation parameters adjusted at the investigators' discretion. Seizure frequency was determined using daily seizure diaries. RESULTS: The median percent seizure reduction from baseline at 1 year was 41%, and 69% at 5 years. The responder rate (≥50% reduction in seizure frequency) at 1 year was 43%, and 68% at 5 years. In the 5 years of follow-up, 16% of subjects were seizure-free for at least 6 months. There were no reported unanticipated adverse device effects or symptomatic intracranial hemorrhages. The Liverpool Seizure Severity Scale and 31-item Quality of Life in Epilepsy measure showed statistically significant improvement over baseline by 1 year and at 5 years (p < 0.001). CONCLUSION: Long-term follow-up of ANT deep brain stimulation showed sustained efficacy and safety in a treatment-resistant population. CLASSIFICATION OF EVIDENCE: This long-term follow-up provides Class IV evidence that for patients with drug-resistant partial epilepsy, anterior thalamic stimulation is associated with a 69% reduction in seizure frequency and a 34% serious device-related adverse event rate at 5 years.

Valproic acid doses, concentrations, and clearances in elderly nursing home residents.

VPA daily dose and total VPA concentrations for 146 elderly (> or =65 years) nursing home residents collected from June 1998 to December 2000 in homes located throughout the United States are presented. Average age was 78.5+/-8.0 years old. The mean VPA daily dose was 16.2+/-11.2mg/kg and mean total VPA concentration was 48.5+/-24.8 mg/L. The majority (56.2%) of the VPA residents are being maintained at total VPA levels <50mg/L. Mean daily dose (19.4+/-11.4, 16.3+/-12.1, and 11.3+/-7.6 mg/kg/day; p=0.003) and total VPA concentration (56.4+/-25.8, 47.7+/-22.6, and 38.7+/-23.1mg/kg/day; p=0.003) decreased by age groups (65-74, 75-84, and > or =85 years). Daily dose and total VPA concentration were not different in residents receiving inhibitory or inducing co-medications, between men and women, or by albumin level. Total VPA clearance was similar between men and women, among age groups, or according to inducing or inhibiting co-medications.

Phenytoin use in elderly nursing home residents.

BACKGROUND: Phenytoin (PHT) dosing regimens are often determined based on experience in those aged <65 years rather than in those aged >or=65 years. OBJECTIVE: The goal of this study was to determine the impact of sex, age, receipt of concomitant inhibitors or inducers of PHT metabolism, and albumin levels on doses and total serum concentrations of PHT in elderly nursing home residents. METHODS: Consulting pharmacists to nursing homes located throughout the United States collected data from June 1998 to December 2000. The mean daily dose per person and mean total serum PHT concentration were tested for statistical differences by sex, age group (6-74, 75-84, and >or=85 years), coadministration of PHT inhibitors or inducers, and albumin levels. RESULTS: Data were collected from 387 residents (259 women, 128 men) of 112 nursing homes in 19 states who received PHT and for whom PHT concentrations were available. The mean (SD) age of the study population was 79.4 (7.8) years; women constituted 67.0% of the study population. The mean (SD) total daily dose and total PHT concentration were 4.9 (1.8) mg/kg and 11.7 (6.4) mg/L, respectively. In general, women received higher mean (SD) daily doses of PHT compared with men (5.1 [1.8] vs 4.6 [1.6] mg/kg, respectively; P=0.017) to achieve similar total serum concentrations (11.6 [6.4] and 12.0 [6.6] mg/L). PHT doses and serum concentrations were similar between age groups. There were no differences in daily doses (mg/kg or mg/d) or total serum concentrations of PHT based on concomitant use of inhibitors or inducers of PHT metabolism or on albumin levels, CONCLUSIONS: In this study in elderly nursing home residents, women received higher doses of PHT than men to achieve similar total serum PHT concentrations. There were no differences in doses or total serum PHT concentrations by age group, use of concomitant inducers or inhibitors of PHT metabolism, or albumin levels.

Electrical stimulation of the anterior nucleus of the thalamus for the treatment of intractable epilepsy.

PURPOSE: Animal studies and sporadic case reports in human subjects have suggested that intermittent electrical stimulation of the anterior nucleus of the thalamus reduces seizure activity. We embarked on an open-label pilot study to determine initial safety and tolerability of bilateral stimulation of the anterior nucleus of the thalamus (ANT), to determine a range of appropriate stimulation parameters, and to begin to gather pilot efficacy data. METHODS: We report an open-label pilot study of intermittent electrical stimulation of the anterior nucleus of the thalamus in five patients (three men, two women; age range, 24-47 years), with follow-up between 6 and 36 months. All patients had intractable partial epilepsy. Four of the five patients also had secondarily generalized seizures. Stimulation was delivered by bilateral implantable, programmable devices by using an intermittent, relatively high-frequency protocol. Stimulation parameters were 100 cycles per second with charge-balanced alternating current; pulse width, 90 ms; and voltages ranging between 1.0 and 10.0 V. Seizure counts were monitored and compared with preimplantation baseline. RESULTS: Four of the five patients showed clinically and statistically significant improvement with respect to the severity of their seizures, specifically with respect to the frequency of secondarily generalized tonic-clonic seizures and complex partial seizures associated with falls. One patient showed a statistically significant reduction in total seizure frequency. No adverse events could clearly be attributed to stimulation. None of the patients could determine whether the stimulator was on or off at these parameters. CONCLUSIONS: Electrical stimulation of the ANT appears to be well tolerated. Preliminary evidence suggests clinical improvement in seizure control in this small group of intractable patients. Further controlled study of deep brain stimulation of the anterior nucleus is warranted.