Interictal epileptiform discharge effects on neuropsychological assessment and epilepsy surgical planning.

Both animal research and human research suggest that interictal epileptiform discharges (IEDs) may affect cognition, although the significance of such findings remains controversial. We review a wide range of literature with bearing on this topic and present relevant epilepsy surgery cases, which suggest that the effects of IEDs may be substantial and informative for surgical planning. In the first case, we present a patient with epilepsy with left anterior temporal lobe (TL) seizure onset who experienced frequent IEDs during preoperative neuropsychological assessment. Cognitive results strongly lateralized to the left TL. Because the patient failed performance validity tests and appeared amnestic for verbal materials inconsistent with his work history, selected neuropsychological tests were repeated 6 weeks later. Scores improved one to two standard deviations over the initial evaluation and because of this improvement, were only mildly suggestive of left TL impairment. The second case involves another patient with documented left TL epilepsy who experienced epileptiform activity while undergoing neurocognitive testing and simultaneous ambulatory EEG recording. This patient's verbal memory performance was impaired during the period that IEDs were present but near normal when such activity was absent. Overall, although the presence of IEDs may be helpful in confirming laterality of seizure onset, frequent IEDs might disrupt focal cognitive functions and distort accurate measurement of neuropsychological ability, interfering with accurate characterization of surgical risks and benefits. Such transient effects on daily performance may also contribute to significant functional compromise. We include a discussion of the manner in which IED effects during presurgical assessment can hinder individual patient presurgical planning as well as distort outcome research (e.g., IEDs occurring during presurgical assessment may lead to an underestimation of postoperative neuropsychological decline).

Impact of nonadherence to antiepileptic drugs on health care utilization and costs: findings from the RANSOM study.

PURPOSE: To study the impact of nonadherence to antiepileptic drugs (AEDs) on health care utilization and direct medical costs in a Medicaid population. METHODS: A retrospective cohort design was employed using state Medicaid claims data from Florida, Iowa, and New Jersey during the period from January 1997 to June 2006. Patients aged >or=18 years with one or more neurologist visit with an epilepsy diagnosis and two or more pharmacy claims for AEDs were included. Medication possession ratio (MPR) was used to evaluate AED adherence with MPR >or= 0.80 considered adherent and <0.80 considered nonadherent. The association of nonadherence with utilization outcomes [hospitalizations, inpatient days, emergency department (ED), and outpatient visits] was assessed with univariate and multivariate Poisson regressions. Quarterly per-patient inpatient, outpatient, ED, and pharmacy costs were calculated across nonadherent and adherent quarters for the younger than 65 population (under-65) and cost differences were computed. Adjusted incremental costs of nonadherence were estimated with multivariate Tobit regression models. RESULTS: A total of 33,658 patients were included (28,470 under-65), together contributing 388,564 treated quarters (26% nonadherent). In multivariate analyses, AED nonadherence was associated with significantly higher incidence of hospitalizations [incident rate ratio (IRR) = 1.39, 95% confidence interval (CI) = 1.37-1.41], inpatient days (IRR = 1.76, 95% CI = 1.75-1.78), and ED visits (IRR = 1.19, 95% CI = 1.18-1.21). Nonadherence was associated with cost increases related to serious outcomes, including inpatient ($4,320 additional cost per quarter, 95% CI = $4,077-$4,564) and ED services ($303 additional cost per quarter, 95% CI = $273-$334), but lower costs for outpatient and pharmacy services, likely because of nonadherent behavior. DISCUSSION: Nonadherence to AEDs appears to be associated with serious outcomes, as evidenced by increased utilization and costs of inpatient and ED services.

Kaplan-Meier analysis on seizure outcome after epilepsy surgery: do gender and race influence it?

OBJECTIVE: To evaluate seizure outcome following epilepsy surgery for patients with temporal lobe epilepsy and evaluate is gender and race/ethnicity influence it. METHODS: Data were obtained from the discharge database of the University of Alabama at Birmingham, Epilepsy Center, between 1985 and 2001. The sample consisted of all patients with a primary diagnosis of medically intractable temporal lobe epilepsy (TLE) who underwent anterior temporal lobectomy. Seizure recurrence was tabulated at 7 days, 2 months, 6 months, 1, 2, 3, 4, 5, and 6 years following surgery. Logistic regression analysis was used to model the presence of seizure recurrence after anterior temporal lobectomy for all patients. Kaplan-Meier analysis was done to obtain estimates and 95% CIs of seizure freedom from baseline. Baseline variables--age at surgery, age at seizure onset, sex, side of resection, immediate postoperative seizures, and pathology results--were assessed as potential predictors of each outcome by comparing the survival curves within each variable with a log rank test. RESULTS: Three hundred sixty-eight patients underwent surgical treatment for TLE, mean age of 30.2 years. Thirty-five patients were African American, 43% were men. Immediate postoperative seizures were seen in 23 patients, while seizure recurrence occurred in 27.3% patients within a year after surgery, and in 33.6% within 6 years. Logistic regression results showed no differences between African Americans and whites, between males and females. The occurrence of immediate postoperative seizures was a strong predictor of late seizure recurrence only at 1 year after surgery. CONCLUSIONS: The occurrence of seizures in the immediate postoperative period is a strong predictor of later seizure recurrence. Sex and race/ethnicity do not appear to be predictors of long-term outcome following surgery for temporal lobe epilepsy.

In vivo hippocampal metabolic dysfunction in human temporal lobe epilepsy.

BACKGROUND: The nature of functional metabolic disturbances in mesial temporal lobe epilepsy remains unclear. OBJECTIVES: To compare in vivo measures of hippocampal metabolic abnormalities in mesial temporal lobe epilepsy, as acquired with fludeoxyglucose F 18 positron emission tomography and proton magnetic resonance spectroscopic imaging, and to determine the relationship between N-acetylaspartate (NAA) disturbances and well-established derangements of glucose metabolism. DESIGN: Measures of hippocampal glucose metabolism from fludeoxyglucose F 18 positron emission tomography were normalized to whole brain counts to provide a glucose uptake metabolic index. Proton magnetic resonance spectroscopic imaging was performed at 4.1 T, and measures of creatinine/NAA ratio were made from mostly hippocampal-only voxels. Direct comparisons and correlation analysis of measures were performed. SETTING: Presurgical evaluations for treatment of intractable epilepsy. PATIENTS: Twenty-nine patients between July 1994 and June 1996 who were candidates for anterior-medial temporal lobectomy at the epilepsy centers of the University of Alabama at Birmingham and Vanderbilt University schools of medicine were studied. RESULTS: The mean ipsilateral hippocampal glucose metabolic index (0.85) was normal, while the contralateral metabolic index (0.95) was nearly significant for an abnormally elevated measure. The mean ipsilateral hippocampal creatinine/NAA (1.26) was abnormally elevated; the mean contralateral creatinine/NAA (0.88) was normal. Hippocampal glucose and creatinine/NAA measures did not correlate; asymmetry measures also did not correlate. CONCLUSIONS: Hippocampal metabolic disturbances in mesial temporal lobe epilepsy as measured by fludeoxyglucose F 18 positron emission tomography vs proton magnetic resonance spectroscopic imaging reflect different mechanisms of biochemical dysfunction. This lack of correlation is hypothesized to reflect a differential effect of varying degrees of disturbed cellular energy metabolism on mechanisms of glucose use and biosynthesis of NAA.

Nonlinear Trends in Hippocampal Metabolic Function and Verbal Memory: Evidence of Cognitive Reserve in Temporal Lobe Epilepsy?

The present study explored the possibility of nonlinear trends in the relationship between verbal memory and hippocampal function in a series of 33 patients with temporal lobe epilepsy (TLE). Right and left hippocampal metabolic function was quantified using levels of hippocampal creatine to N-acetylaspartate (Cr/NAA) derived from (1)H magnetic resonance spectroscopic imaging. An exploratory neural network analysis (multi-layer perceptron) suggested the possibility of either a quadratic or cubic trend in the relationship between left hippocampal Cr/NAA and verbal retention. Using regression-based curve estimation, the cubic function was found to optimally fit the data, explaining 41% of the variance in the relationship between verbal memory and hippocampal metabolic function. This was contrasted to the 28% variance explained by simple linear regression. These findings suggest that (1) the relationship between verbal retention and hippocampal function in patients with TLE is nonlinear, and (2) this could be explained in terms of a possible "cognitive reserve." Clinical implications are discussed.

Race/ethnicity: a predictor of temporal lobe epilepsy surgery outcome?

PURPOSE: The success of epilepsy surgery in temporal lobe epilepsy reaches a 64% rate of seizure freedom, based on a randomized control trial. Observational studies from epilepsy centers worldwide indicate seizure freedom rates up to 93% when the etiology is unilateral hippocampal sclerosis. Several risk factors are attributed to the recurrence of seizures following the surgical procedure. Nonetheless, whether race influences the outcome of temporal lobe surgery is unknown. The purpose of this study was to evaluate if race plays a role in outcome following surgery. METHODS: Data were obtained from the discharge database of the University of Alabama at Birmingham video/EEG monitoring unit, between 1998 and 2003, as well as the clinical charts. Seizure recurrence was evaluated 1 year following surgery. The sample consisted of all patients with a primary diagnosis of mesial temporal sclerosis (MTS) who underwent anterior temporal lobectomy. Multiple logistic regression analysis was used to model the presence of seizure recurrence after anterior temporal lobectomy for MTS. Two sets of logistic regression models were estimated to generate odds ratios (ORs) for seizure recurrence after an anterior temporal lobectomy for African-Americans or other possible ethnic/racial group present relative to non-Hispanic Caucasians. The first model incorporated only ethnicity as the independent variable and generated unadjusted ORs for seizure recurrence following the surgical procedure. The second set included the independent variables: duration of epilepsy, history of febrile seizures, lateralization of epileptogenic focus, handedness, and age. RESULTS: Seventy patients underwent surgical treatment and all of them had pathologic confirmation of MTS. Follow-up information for six was not available. Analysis of the remaining 64 patients revealed that African-Americans were more likely than non-Hispanic Caucasians to have seizure recurrence after surgery (OR=2.1, 95% CI=0.6-8.0). After potential confounders (duration of epilepsy, history of febrile seizures, lateralization of epileptogenic focus, handedness, and age) were controlled, this finding did not change (OR=1.7, 95% CI=0.3-10.7). CONCLUSION: Our data suggest that race may be an important factor related to seizure outcome following temporal lobectomy.

Efficacy and tolerability of the new antiepileptic drugs, I: Treatment of new-onset epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society.

PURPOSE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 until September 2002, with selected manual searches up to 2003. RESULTS: Evidence exists, either from comparative or dose-controlled trials, that GBP, LTG, TPM, and OXC have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. Evidence also shows that LTG is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. CONCLUSIONS: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Efficacy and tolerability of the new antiepileptic drugs, II: Treatment of refractory epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society.

PURPOSE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) [gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS)] in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 to March 2003. RESULTS: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. GBP can be effective for the treatment of mixed seizure disorders, and GBP, LTG, OXC, and TPM for the treatment of refractory partial seizures in children. Limited evidence suggests that LTG and TPM also are effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox-Gastaut syndrome. CONCLUSIONS: The choice of AED depends on seizure and/or syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes for which more evidence is necessary.