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Summary: Objective: Hippocampal dentation (HD) is a "toothlike" morphological feature observed on the inferior aspect of the human hippocampus. It has been found that HD varies dramatically in healthy adults and is positively associated with verbal and visual memory. In this work, we evaluate the loss of HD and its association with memory dysfunction in patients with temporal lobe epilepsy (TLE) who have hippocampal sclerosis (HS). Methods: Fifty‐eight unilateral HS patients with neuropsychological data were identified from a retrospective database. T1‐weighted magnetization‐prepared rapid acquisition gradient echo images (~1 mm resolution) were upsampled to.25 mm and were processed using ASHS software to obtain ultra‐high‐resolution segmentations and three‐dimensional renderings. Dentes were counted on the epileptic and contralateral sides, and associations were tested between dentation on the epileptic versus contralateral sides and measures of verbal and visuospatial memory with respect to the dominant versus nondominant hemisphere. Results: The median number of dentes in epileptic hippocampi was significantly lower than in contralateral hippocampi (p <.0001). Among cases with HS in the dominant hemisphere, verbal memory was significantly correlated with contralateral nondominant hemisphere dentation (r =.43, p =.04). Similarly, among cases of HS in the nondominant hemisphere, visual memory was significantly correlated with contralateral dominant hemisphere dentation (r =.48, p =.04). All other analyses were not significant. Significance: This is the first study characterizing dentation in TLE patients with HS and its memory correlates. There is marked loss of dentation in sclerotic hippocampi compared to the unaffected contralateral hippocampi. Material‐specific measures of memory performance are paradoxically correlated with dentation contralateral to the side with HS, suggesting that contralateral functional capacity explains some of the variation in memory across TLE patients. HD is an important variable to consider in understanding memory loss in TLE. [ABSTRACT FROM AUTHOR]

Objective: To examine health care costs in diverse older Medicare beneficiaries with epilepsy. Methods: Using 2008‐2010 claims data, we conducted a longitudinal cohort study of a random sample of Medicare beneficiaries augmented for minority representation. Epilepsy cases (n = 36 912) had ≥1 International Classification of Diseases, Ninth Edition (ICD‐9) 345.x or ≥2 ICD‐9 780.3x claims, and ≥1 antiepileptic drug (AED) in 2009; new cases (n = 3706) had no seizure/epilepsy claims nor AEDs in the previous 365 days. Costs were measured by reimbursements for all care received. High cost was defined as follow‐up 1‐year cost ≥ 75th percentile. Logistic regressions examined association of high cost with race/ethnicity, adjusting for demographic, clinical, economic, and treatment quality factors. In cases with continuous 2‐year data, we obtained costs in two 6‐month periods before and two after the index event. Results: Cohort was ~62% African Americans (AAs), 11% Hispanics, 5% Asians, and 2% American Indian/Alaska Natives. Mean costs in the follow‐up were ~$30 000 (median = $11 547; new cases, mean = $44 642; median = $25 008). About 19% white compared to 27% AA cases had high cost. AA had higher odds of high cost in adjusted analyses (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.11‐1.29), although this was only marginally significant when adjusting for AED adherence (OR = 1.09, 95% CI = 1.01‐1.18, P = 0.03). Factors associated with high cost included ≥1 comorbidity, neurological care, and low AED adherence. Costs were highest at ~$17 000 in the 6 months immediately before and after the index event (>$29 000 for new cases). Significance: The financial sequelae of epilepsy among older Americans disproportionally affect minorities. Studies should examine contributors to high costs. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of older Americans with epilepsy receiving concomitant prescriptions for antiepileptic drugs (AEDs) and non-epilepsy drugs (NEDs) which could result in significant pharmacokinetic (PK) interaction, and to assess the contributions of racial/ethnic, socioeconomic, and demographic factors. Methods: Retrospective analyses of 2008-2010 Medicare claims for a 5% random sample of beneficiaries ≥67 years old in 2009 augmented for minority representation. Prevalent cases had ≥1 ICD-9 345.x or ≥2 ICD-9 780.3x, and ≥1 AED. Among them, incident cases had no seizure/epilepsy claim codes nor AEDs in preceding 365 days. Drug claims for AEDs, and for the 50 most common NEDs within ± 60 days of the index epilepsy date were tabulated. Interacting pairs of AEDs/NEDs were identified by literature review. Logistic regression models were used to examine factors affecting the likelihood of interaction risk. Results: Interacting drug pairs affecting NED efficacy were found in 24.5% of incident, 39% of prevalent cases. Combinations affecting AED efficacy were found in 20.4% of incident, 29.3% of prevalent cases. Factors predicting higher interaction risk included having ≥ 1 comorbidity, being eligible for Part D low Income Subsidy, and not living in the northeastern US. Protective factors were Asian race/ethnicity, and treatment by a neurologist. Significance: A substantial portion of older epilepsy patients received NED-AED combinations that could cause important PK interactions. The lower frequency among incident vs. prevalent cases may reflect changes in prescribing practices. Avoidance of interacting AEDs is feasible for most persons because of the avail- ability of newer drugs. [ABSTRACT FROM AUTHOR]

Objective Disparities in epilepsy treatment are not uncommon; therefore, we examined population-based estimates of initial antiepileptic drugs ( AEDs) in new-onset epilepsy among racial/ethnic minority groups of older US Medicare beneficiaries. Methods We conducted retrospective analyses of 2008-2010 Medicare administrative claims for a 5% random sample of beneficiaries augmented for minority representation. New-onset epilepsy cases in 2009 had ≥1 International Classification of Diseases, Ninth Revision ( ICD-9) 345.x or ≥2 ICD-9 780.3x, and ≥1 AED, AND no seizure/epilepsy claim codes or AEDs in preceding 365 days. We examined AED use and concordance with Quality Indicators of Epilepsy Treatment ( QUIET) 6 (monotherapy as initial treatment = ≥30 day first prescription with no other concomitant AEDs), and prompt AED treatment (first AED within 30 days of diagnosis). Logistic regression examined likelihood of prompt treatment by demographic (race/ethnicity, gender, age), clinical (number of comorbid conditions, neurology care, index event occurring in the emergency room (ER)), and economic (Part D coverage phase, eligibility for Part D Low Income Subsidy [ LIS], and ZIP code level poverty) factors. Results Over 1 year of follow-up, 79.6% of 3,706 new epilepsy cases had one AED only (77.89% of whites vs. 89% of American Indian/Alaska Native [ AI/ AN]). Levetiracetam was the most commonly prescribed AED (45.5%: from 24.6% AI/ AN to 55.0% whites). The second most common was phenytoin (30.6%: from 18.8% Asians to 43.1% AI/ AN). QUIET 6 concordance was 94.7% (93.9% for whites to 97.3% of AI/ AN). Only 50% received prompt AED therapy (49.6% whites to 53.9% AI/ AN). Race/ethnicity was not significantly associated with AED patterns, monotherapy use, or prompt treatment. Significance Monotherapy is common across all racial/ethnic groups of older adults with new-onset epilepsy, older AEDs are commonly prescribed, and treatment is frequently delayed. Further studies on reasons for treatment delays are warranted. Interventions should be developed and tested to develop paradigms that lead to better care. [ABSTRACT FROM AUTHOR]

Objective Neurologic diseases such as stroke are risk factors for new-onset epilepsy in older adults. Recent evidence suggests that psychiatric disorders independently predict epilepsy in older male veterans. Our aim was to examine the relationship between these disorders in a population-based study of older adults that also included women and minorities. Methods We used a national 5% random sample of 2005 Medicare beneficiaries including all 50 US states and Washington, DC. Beneficiaries were 65 years of age or older, with continuous Medicare Part A and Part B coverage and not in managed care plans. Epilepsy cases were identified from claims for physician visits, hospitalizations, and outpatient procedures. We used logistic regressions for the overall sample and stratified by gender to determine whether risk of new-onset epilepsy was associated with prior history of psychiatric (i.e., depression, psychosis, bipolar disorder, schizophrenia, posttraumatic stress disorder ( PTSD), adjustment disorder, and substance abuse/dependence) and neurologic conditions (i.e., cerebrovascular disease, dementia, traumatic brain injury, brain tumor, metastatic cancer). Results Preexisting psychiatric disorders were significantly associated with new-onset epilepsy in the study population as were the neurologic conditions evaluated. Five of the seven psychiatric disorders examined were independently associated with new-onset epilepsy; substance abuse, psychosis, bipolar disorder, schizophrenia, and depression. Gender interaction effects were found for substance abuse/dependence and brain tumors. Significance Both neurologic and psychiatric factors significantly predicted new-onset epilepsy in a population-based sample of male and female older adults. These results support earlier findings and extend the understanding of risk models for new-onset epilepsy in broader older adult populations. A PowerPoint slide summarizing this article is available for download in the Supporting Information section . [ABSTRACT FROM AUTHOR]

Purpose: Given the strong association of stroke and epilepsy in older persons, and the existence of a Stroke Belt in the United States, we hypothesized that geographic variation in epilepsy prevalence would follow geographic patterns similar to stroke. Methods: We used a 2005 5% random sample of Medicare beneficiaries 65 and older in 48 U.S. contiguous states. Epilepsy was identified from claims for physician visits, hospitalizations, and outpatient procedures. Prevalence was obtained by state and county. Logistic regressions determined the independent association of the likelihood of epilepsy (prevalent or new case) and residence in Stroke Belt states, controlling for residence in highest epilepsy prevalence states, demographics (race, age, gender), comorbid conditions, cerebrovascular disease, dementia, and county characteristics. Key Findings: Of 1,212,015 beneficiaries, 11.9 per 1,000 had prevalent and 2.9 new cases of epilepsy. Nine of 11 Stroke Belt states were among the 20 states with the highest epilepsy prevalence. Counties in the 10 highest epilepsy prevalence states were more likely to be large urban counties with a higher number of neurologists or neurosurgeons per capita. The higher likelihood of prevalent epilepsy cases associated with Stroke Belt residence was explained by beneficiaries' race; that associated with residence in high epilepsy prevalence states was not. The likelihood of new epilepsy cases was negatively associated with Stroke Belt residence when controlling for covariates. Significance: The geographic variation in epilepsy prevalence is not explained by variations in known risk factors. Further research should investigate why eastern U.S. states have higher frequency of epilepsy. [ABSTRACT FROM AUTHOR]

Purpose:To examine cognitive functioning in community-dwelling older adults with chronic partial epilepsy and demographically matched healthy older adults.Methods:Standardized measures of neurocognitive function were collected as part of an ongoing study investigating health-related quality-of-life issues in older adults with epilepsy. Cognitive tests consisted of the Mattis Dementia Rating Scale (subscales include attention, initiation/perseveration, construction, conceptualization, memory), Logical Memory subtest from the WMS-III (immediate and delayed recall scores), and word fluency. Mood was measured with the Geriatric Depression Scale. Older adults with epilepsy (n= 25) and healthy older adults (n= 27) completed testing. All participants were at least 60 years old, living independently in the community, and had no history of drug/alcohol abuse or life-threatening medical conditions. All older adults with epilepsy had been diagnosed as having medically intractable partial complex seizures, including those with histories of secondary generalization.Results:Older adults with epilepsy demonstrated impairments across all cognitive measures compared with the healthy controls. Seizure onset (age) and seizure duration (years) were not statistically associated with neurocognitive function or self-reported mood. Older adults with epilepsy who were receiving antiepileptic drug (AED) polytherapy (n= 11) displayed worse performance on the attention, initiation/perseveration, and memory subscales of the DRS and Logical Memory delayed recall score compared with those older adults with epilepsy receiving monotherapy (n= 14). The number of AEDs taken was not associated with seizure frequency.Conclusions:Negative effects on cognitive function are experienced by older adults with chronic partial epilepsy. AED polytherapy may increase the risk for negative cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Summary: Is it a seizure? This question can be difficult for a clinician to answer, and it may be more critical if the possible seizure lasts >30 min. Long-duration questionable seizure activity changes the question to, “Is it status epilepticus?” Status epilepticus (SE) can be divided into convulsive and nonconvulsive types. Convulsive SE is the most easily recognized, whereas nonconvulsive SE is more clinically variable and controversial. The term nonconvulsive SE is more often applied to patients who are severely obtunded or comatose with minimal or no motor movements, or in a stupor of altered consciousness reflecting generalized ictal activity. Nonconvulsive SE also can be caused by focal seizure activity, sometimes restricted to deep small volumes of brain in which scalp EEG may not be diagnostic. We present the case of a patient who had dominant limbic hippocampal SE, but in whom the diagnosis could not be confirmed until a modified novel use of the sodium amytal test was performed. [ABSTRACT FROM AUTHOR]

Summary: Purpose: Reliable change indices (RCIs) and standardized regression-based (SRB) change scores norms were established for the recently revised Wechsler Adult Intelligence Scale–III (WAIS-III) and Wechsler Memory Scale–III (WMS-III) in patients with complex partial seizures. Establishment of such standardized change scores can be useful in determining the effects of epilepsy surgery on cognitive functioning independent of test–retest artifacts including practice effects. Methods: Forty-two nonoperated-on adult patients with complex partial seizures (primarily of temporal lobe onset) were administered the WMS-III and WAIS-III on two occasions (mean 7-month interval). All patients were receiving stable antiepileptic drug (AED) treatment at both testings. RCI and SRB change scores were calculated. Confidence interval cutoff scores (90% and 80%) and standardized regression equations were calculated for each of the WAIS-III and WMS-III Primary Indices and individual subtests. Age, gender, education, test–retest interval, preoperative test performance, seizure onset, and seizure duration were predictor variables for the SRB equations. Results: Test–retest reliabilities for the WAIS-III and WMS-III Primary Indices were within acceptable ranges, although considerable individual subtest variability was found. Preoperative performance was the single largest contributor to each of the predictive regression equations. Age, gender, education, seizure onset, and seizure duration contributed modest variance to several of the regression equations. Conclusions: We calculated both RCI and SRB change score indices for the recently revised Wechsler instruments. These formulas help control for test–retest methodologic artifacts and provide a standardized method with which to examine both individual and group level cognitive change after epilepsy surgery. [ABSTRACT FROM AUTHOR]

Purpose: To examine the relationship between hippocampal volumes, H magnetic resonance spectroscopy (MRS)-identified hippocampal metabolic function, and verbal memory in patients with unilateral mesial temporal lobe epilepsy (MTLE). Methods: Hippocampal volumes, H MRS-derived hippocampal creatine to N-acetylaspartate (Cr/NAA), and verbal memory assessment were obtained preoperatively in 22 patients (six right, 16 left) with EEG-defined unilateral MTLE. Results: Left hippocampal volume correlated significantly with left hippocampal Cr/NAA (r = -0.549, p < 0.01), whereas right volume correlated significantly with right Cr/NAA (r = -0.478, p < 0.05). Verbal memory correlated significantly with left hippocampal Cr/NAA (r = -0.594, p < 0.01), but not with left hippocampal volume or right hippocampal measures. Conclusions: Hippocampal volumes and H MRS-derived metabolite ratios are statistically related, but share only a small percentage of variance, suggesting separate but related pathophysiologic processes. Left hippocampal Cr/NAA appears to be more sensitive to verbal memory function than volumes. [ABSTRACT FROM AUTHOR]

Summary: Purpose: This study compared the cognitive effects of carbamazepine (CBZ) and gabapentin (GBP) in healthy senior adults by using a randomized, double-blind crossover design. Methods: Thirty-four senior adults were randomized to receive one of the two drugs followed by a 5-week treatment period. A 4-week washout phase preceded initiation of the second drug. Antiepileptic drugs (AEDs) were titrated to target doses of either CBZ (800 mg/day) or GBP (2,400 mg/day). Primary outcome measures were standardized neuropsychological tests of attention/vigilance, psychomotor speed, motor speed, verbal and visual memory, and the Profile of Mood State (POMS), yielding a total of 17 variables. Each subject received cognitive testing at predrug baseline, end of first drug phase, end of second drug phase, and 4 weeks after completion of the second drug phase. Results: Fifteen senior adults (mean age, 66.5 years; range, 59–76 years) completed the study. Seniors completing the study did not differ significantly from noncompleting seniors in terms of demographic features or baseline cognitive performances. Fifteen of the 19 seniors not completing the study dropped out while receiving CBZ. Adverse events were frequently reported for both AEDs, although they were more common for CBZ. Mean serum levels for the completers were within midrange clinical doses (CBZ, 6.8 μg/ml; GBP, 7.1 μg/ml). Significant differences between CBZ and GBP were found for only one of 11 cognitive variables, with better attention/vigilance for GBP, although the effect was modest. Performances on the nondrug average were significantly better on 45% of cognitive variables compared with CBZ and 36% compared with GBP. The overall pattern of means favored GBP over CBZ on 15 of 17 (p < 0.001), nondrug over CBZ on 17 of 17 (p < 0.0000), and nondrug over GBP on eight of 17 (NS). Conclusions: Mild cognitive effects were found for both AEDs compared with the nondrug average condition. The... [ABSTRACT FROM AUTHOR]

Summary: Purpose: To examine the lateralization utility of preoperative verbal retention in patients with and without bilateral hippocampal atrophy. Methods: The sample consisted of 74 patients with EEG-defined unilateral temporal lobe epilepsy (TLE) who had also undergone volumetric magnetic resonance imaging (MRI). Verbal retention was operationalized by the Logical Memory percentage retention subtest (LM%) of the Wechsler Memory Scale. Patients were divided into groups with (a) bilaterally normal hippocampal volumes, (b) unilateral atrophy, or (c) bilateral atrophy. Two different thresholds (empirically derived vs. normative) were used to lateralize on the basis of LM%. LM% lateralization was then examined by group using χ2, sensitivity, positive predictive values, and odds ratios. Analyses were also conducted separately in the subset of patients who were seizure free after surgery. Results: Mean LM% performance was significantly lower in patients with left versus right TLE in the subset with bilateral hippocampal atrophy (p = 0.018), but not in patients with a normal MRI (p = 0.918) or unilateral atrophy (p = 0.087). The odds of a correct lateralization by LM% increased from 1.67 in patients with normal MRI to 36.11 in patients with bilateral hippocampal atrophy. The power of a right and left lateralization prediction by LM% was 100% and 75%, respectively, in patients with bilateral hippocampal atrophy. Similar results were obtained when analysis was restricted to patients who were seizure free after surgery. Conclusions: Preoperative verbal retention as measured by LM% may provide meaningful lateralization information in patients who are difficult to lateralize via MRI. [ABSTRACT FROM AUTHOR]

A correction to the article "Determining Reliable Cognitive Change Following Epilepsy Surgery: Development of Reliable Change Indices and Standardized Regression-Based Change Norms for the WMS-3 and WAIS-3" that was published in the January 2006 issue is presented.