Roy C. Martin

Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults

Objective: To study the acute and steady-state cognitive effects of three new antiepileptic drugs (AEDs): gabapentin, lamotrigine, and topiramate. Background: Several newer antiepileptic medications approved recently by the Food and Drug Administration are gaining attention as efficacious alternatives to established AEDs. Greater tolerability with fewer side effects are reported in some. However, the potential cognitive effects of these newer AEDs have received limited attention. Methods: Healthy young adults randomized to either of the three drugs were administered tests of attention, psychomotor speed, language, memory, and mood at baseline (predrug), acute single-dose period, and after 2 and 4 weeks on the drug. Results: Compared with baseline, the topiramate group had selective, statistically significant declines on measures of attention and word fluency at acute doses, whereas the other two AED groups had no performance changes. At the 2- and 4-week test periods, only the topiramate subjects continued to display neurocognitive effects from drug administration. Conclusions: Results demonstrate potential acute and steady-state adverse cognitive effects for topiramate, whereas minimal effects were displayed for either gabapentin or lamotrigine in young healthy adults.

Improved health care resource utilization following video-EEG-confirmed diagnosis of nonepileptic psychogenic seizures

The economic burden of epilepsy is well recognized. However, empirical investigation establishing costs associated with the diagnosis and treatment of non-epileptic psychogenic seizures (NEPS) is lacking. We studied 20 patients with video/EEG monitoring-confirmed NEPS to determine the effect of definitive diagnosis and treatment on medical costs and utilization. A medical resource utilization questionnaire and inpatient medical chart review were employed to calculate utilization information. Medication usage, outpatient visits, emergency room admissions, and diagnostic testing over a 6-month pre-diagnosis and a 6-month post-diagnosis period were compared. There was an 84% average reduction in total seizure-related medical charges in the 6 months following NEPS diagnosis. Average diagnostic testing charges declined 76%, average medication charges decreased 69%, outpatient clinic visits declined 80%, and emergency room visits reduced by 97%. A majority of patients obtaining a definitive inpatient video/EEG-seizure-monitoring-confirmed NEPS diagnosis experience substantial reductions in health care utilization and dollar costs.

Patient-oriented outcome assessment after temporal lobectomy for refractory epilepsy

Objective: To determine patient-oriented outcome after anterior temporal lobectomy (ATL) for refractory epilepsy. Background: Health-related quality of life (HRQOL) is an important component of the assessment of outcome from epilepsy surgery, but prior controlled studies of the effect of surgery on HRQOL are inconclusive. Direct assessment of the effect of surgery on patient concerns of living with epilepsy has not been reported. Methods: We used reliable and valid instruments to compare HRQOL and patient concerns of 125 patients who had received an ATL more than than one year previously to a clinically similar group of 71 patients who were awaiting ATL. All patients were selected for surgery based on similar criteria. We also used bivariate correlation analysis and multivariate regression modeling to determine the association of traditional outcome variables with HRQOL. Results: Patients who had undergone ATL reported significantly less concern of living with epilepsy in 16 of 20 items of the EFA Concerns Index and better HRQOL in 8 of 11 scales of the Epilepsy Surgery Inventory-55. Regression analysis in the postoperative group demonstrated that mood status, employment, driving, and antiepileptic drug (AED) cessation, but not seizure-free status or IQ, were associated with better HRQOL. Conclusions: Our findings support a positive affect of ATL on patient concerns and HRQOL in refractory temporal lobe epilepsy, although longitudinal studies are needed to corroborate these results. Mood, employment, driving ability, and AED use are important postoperative predictors of HRQOL.

Modulation of cerebral GABA by topiramate, lamotrigine, and gabapentin in healthy adults

BackgroundAnticonvulsant drugs have multiple mechanisms of action. Recent in vivo MRS studies suggest that cerebral &ggr;-aminobutyric acid (GABA) increases occur with the administration of certain anticonvulsants in humans. ObjectiveTo investigate the effect of topiramate, gabapentin, and lamotrigine on cerebral GABA concentrations in healthy volunteers and correlate the GABA concentrations with serum drug levels. MethodsSeventeen healthy adults were randomly assigned to receive topiramate, gabapentin, and lamotrigine and underwent GABA measurements using a 4.1-T magnet from a 13.5-mL volume over the occipital region. GABA concentrations and serum levels were measured at 3 and 6 hours following administration of an acute single dose of one of the drugs. Thereafter, drugs were titrated over 4 weeks to target doses, with GABA measurements performed at 2 and 4 weeks. ResultsCerebral GABA concentrations rose 70% in the acute phase compared with baseline for topiramate. GABA rose 48% at 6 hours with gabapentin but not with lamotrigine. With long-term dosing and once target doses were achieved at 4 weeks, significant elevations in GABA were observed compared with baseline for all three drugs (topiramate 46%, gabapentin 25%, lamotrigine 25%). ConclusionThis study demonstrates that single doses of topiramate and gabapentin increase cerebral GABA concentrations acutely (hours) in healthy individuals, but all drugs at clinically utilized doses increase cerebral GABA at 4 weeks. These results suggest that the mechanisms of action of anticonvulsant drugs are more complex and are likely to be multiple in nature.

Topiramate increases cerebral GABA in healthy humans

Topiramate (TOP) is a novel anticonvulsant drug with multiple mechanisms of action used in the treatment of epilepsy. Measurements of cerebral GABA were obtained in six controls using 1H MRS at baseline and at 3 and 6 hours following the administration of 3 mg/kg of TOP. Brain GABA concentrations rose by 72% at 3 hours and by 64% at 6 hours compared with baseline (p < 0.004). This study demonstrates that TOP significantly increases human cerebral GABA concentrations in healthy individuals.

The intracarotid amobarbital procedure as a predictor of memory failure following unilateral temporal lobectomy

We investigated the efficacy of the intracarotid amobarbital procedure to accurately predict post-temporal lobectomy anterograde amnesia. We presented items at 2 separate times during amobarbital assessment; both early and late item recall were decreased during the injection contralateral to seizure onset indicating sensitivity to bilateral temporal lobe dysfunction. Ten patients for whom follow-up neuropsychological assessment was available failed either the early or late item recognition portions of their amobarbital evaluation ipsilateral to seizure onset, but had hippocampus included in the temporal lobectomy by virtue of satisfactory performance on other tests of hippocampal function. None of these 10 patients displayed postoperative anterograde amnesia, although there was a reduction in material-specific memory in some patients. These results indicate that relying solely on amobarbital memory testing to assess the functional ability of the contralateral temporal lobe to sustain global memory prior to temporal lobectomy may needlessly exclude patients from a viable therapeutic option.

Declining financial capacity in mild cognitive impairment A 1-year longitudinal study

Objective: To investigate 1-year change in financial capacity in relation to conversion from amnestic mild cognitive impairment (MCI) to dementia. Methods: Seventy-six cognitively healthy older controls, 25 patients with amnestic MCI who converted to Alzheimer-type dementia during the study period (MCI converters), and 62 patients with MCI who did not convert to dementia (MCI nonconverters) were administered the Financial Capacity Instrument (FCI) at baseline and 1-year follow-up. Performance on the FCI domain and global scores was compared within and between groups using multivariate repeated-measures analyses. Results: At baseline, controls performed better than MCI converters and nonconverters on almost all FCI domains and on both FCI total scores. MCI converters performed below nonconverters on domains of financial concepts, cash transactions, bank statement management, and bill payment and on both FCI total scores. At 1-year follow-up, MCI converters showed significantly greater decline than controls and MCI nonconverters for the domain of checkbook management and for both FCI total scores. The domain of bank statement management showed a strong trend. For both the checkbook and bank statement domains, MCI converters showed declines in procedural skills, such as calculating the correct balance in a checkbook register, but not in conceptual understanding of a checkbook or a bank statement. Conclusions: Declining financial skills are detectable in patients with mild cognitive impairment (MCI) in the year before their conversion to Alzheimer disease. Clinicians should proactively monitor patients with MCI for declining financial skills and advise patients and families about appropriate interventions.

Frequency of epilepsy in patients with psychogenic seizures monitored by video-EEG

This study examined the frequency of epilepsy in a consecutive series of patients who received a definitive diagnosis of psychogenic nonepileptic seizures (PNES) after completing inpatient video-EEG (VEEG) monitoring. Of the 1,590 patients receiving definitive diagnosis, 514 (32.3%) were diagnosed with PNES. Twenty-nine (5.3%) of these patients were found to have both PNES and epilepsy. When strict diagnostic criteria are applied, there is little overlap between epileptic seizures and PNES among patients referred for VEEG monitoring.

Individual Memory Change After Anterior Temporal Lobectomy: A Base Rate Analysis Using Regression-Based Outcome Methodology

Summary: Purpose: To characterize patterns of base rate change on measures of verbal and visual memory after anterior temporal lobectomy (ATL) using a newly developed regression‐based outcome methodology that accounts for effects of practice and regression towards the mean, and to comment on the predictive utility of baseline memory measures on postoperative memory outcome.

Incidence and prevalence of epilepsy among older US Medicare beneficiaries

Objective: To determine the prevalence and incidence of epilepsy among US Medicare beneficiaries aged 65 years old and over, and to compare rates across demographic groups. Methods: We performed a retrospective analysis of Medicare administrative claims for 2001–2005, defining prevalent cases as persons with ≥1 claim with diagnosis code 345.xx (epilepsy) or 2 or more with diagnosis code 780.3x (convulsion) ≥1 month apart, and incident cases as prevalent cases with 2 years immediately before diagnosis without such claims. Prevalence and incidence rates were calculated for the years 2003–2005 using denominators estimated from a 5% random sample of Medicare beneficiaries. Results were correlated with gender, age, and race. Results: We identified 282,661 per year on average during 2001–2005 (a total of 704,243 unique cases overall), and 62,182 incident cases per year on average during 2003–2005. Average annual prevalence and incidence rates were 10.8/1,000 and 2.4/1,000. Overall, rates were higher for black beneficiaries (prevalence 18.7/1,000, incidence 4.1/1,000), and lower for Asians (5.5/1,000, 1.6/1,000) and Native Americans (7.7/1,000, 1.1/1,000) than for white beneficiaries (10.2/1,000, 2.3/1,000). Incidence rates were slightly higher for women than for men, and increased with age for all gender and race groups. Conclusions: Epilepsy is a significant public health problem among Medicare beneficiaries. Efforts are necessary to target groups at higher risk, such as minorities or the very old, and to provide the care necessary to reduce the negative effects of epilepsy on quality of life.