David M Labiner

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Scholarly Contributions

Chapters

• Sim, Y., & Labiner, D. M. (2019). System-Based Issues in Epilepsy. In see cv. Cambridge University Press. doi:10.1017/9781108754200.027
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  Individuals with epilepsy, and their family and friends, are impacted by system-based barriers arising from public policies, affecting their quality of lives. Policies on driving, education, employment, ethics, and research are widespread, and often lead to unwarranted complications.
• Gumnit, R. J., Labiner, D. M., Fountain, N. B., & Herman, S. T. (2012). Data on Specialized Epilepsy Centers: Report to the Institute of Medicine's Committee on the Public Health Dimensions of the Epilepsies. In see cv. National Academies Press (US).
• Foltz, E., & Labiner, D. (2008). The Psychotropic Effects of Vagus Nerve Stimulation in Epilepsy. In see cv. Elsevier Inc. doi:10.1016/B978-0-12-374006-9.00019-9
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  There is a better understanding of comorbid conditions associated with epilepsy, particularly psychiatric disorders that have led to new treatment strategies. Based on similar sites and mechanisms of action, as well as effects on mood noted in the treatment of epilepsy, several antiepileptic medications have subsequently been studied for use in the treatment of psychiatric conditions. Carbamazapine, valproic acid, and lamotrigine, among others, have been used in the treatment of bipolar disorder. These agents have also been used as adjunctive treatment for depression. Vagus nerve has been briefly explained; it contains approximately 80% afferent fibers and 20% efferent fibers. Sensory information from the head, neck, thorax, and abdomen is carried to the nucleus of the solitary tract (NTS). From the NTS, there are bilateral projections to several areas in the brain, including the cerebellum, the periaqueductal gray, the raphe nucleus, the locus coeruleus, the limbic system, and the cerebral cortex. Thus, the Vagus nerve has a potential role in regulating seizure activity, emotion, mood, and pain. © 2008 Elsevier Inc. All rights reserved.
• Labiner, D. (2008). Status Epilepticus After a Long Day of White-Water Rafting in the Grand Canyon. In see cv. Elsevier Inc. doi:10.1016/B978-0-12-374005-2.00020-X
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  This chapter explores the case of a woman who developed her first ever seizure, after a long day of white-water rafting on the Colorado River in the Grand Canyon. She was diagnosed with status epilepticus associated with aminolevulinic acid dehydratase deficiency porphyria. The patient was intubated and on a ventilator. Extensive evaluation of serum, spinal fluid, and urine were initially unrevealing. After approximately 90 days, a diagnosis of aminolevulinic acid dehydratase deficiency porphyria was made by red blood cell enzyme analysis. The patient had no further convulsive activity once gabapentin was initiated. Her dose was further increased in increments of no greater than 300 mg twice a week. Seizure control was significantly improved at 1800 mg/day with no significant side effects. At higher doses, the patient had significant side effects, particularly somnolence and confusion. This case represented an unusual case of partial epilepsy caused by a metabolic disorder. Seizures are not a major manifestation of the porphyrias, and the diagnosis was not made for 3 months despite appropriate screening 2 weeks after the onset of her symptoms. Gabapentin was not yet available in the USA nor was it known to be safe in treating seizures related to porphyria. Because of the desperate situation of this patient, the doctors sought and obtained compassionate use of this drug based on what was known at the time about its lack of hepatic metabolism. © 2008 Elsevier Inc. All rights reserved.

Journals/Publications

• Connor, G. S., Labiner, D. M., Schabert, V. F., Weingarten, M., Wade, C. T., Stern, S., & Becker, D. A. (2024). Greater need for treatment optimization in patients with epilepsy initiating adjunctive therapy: Results of a retrospective claims analysis of antiseizure medication drug load in the United States. Epilepsy & behavior : E&B, 152, 109649.
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  This retrospective, observational study used US claims data to assess changes in antiseizure medication (ASM) drug load for a cohort of patients with epilepsy.
• Labiner, D. M., Harris, R. B., Chong, J. W., Malone, D. C., & Ip, Q. (2018). Economic impact of epilepsy and the cost of nonadherence to antiepileptic drugs in older Medicare beneficiaries. Epilepsy & Behavior.
• Sepulveda, R., Chong, J., Shegog, R., Martin, K., Begley, C., Addy, R., Rosales, O., Soto, S., Rosales, C., Labiner, D., & Nuño, T. (2024). Experiences of using the MINDSET Self-Management mobile health app among Hispanic Patients:Results of a qualitative study. Epilepsy and Behavior, 153(Issue). doi:10.1016/j.yebeh.2024.109702
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  Background: Interventions focusing on epilepsy self-management (ESM) are vital for promoting the health of people living with epilepsy. E-technology and mobile health (mHealth) tools are becoming increasingly integrated into practice to promote self-management strategies for chronic diseases, enhance care delivery, and reduce health disparities. Management Information and Decision Support Epilepsy Tool (MINDSET), a bilingual decision support tool (available in English and Spanish), was found to be both feasible and effective in facilitating goal-based ESM in the clinic. Purpose: To assess the experience of using MINDSET as an ESM intervention among Hispanic patients with epilepsy to inform future interventional studies. Methods: This study used a Qualitative Descriptive (QD) framework to provide a rich and straightforward description of patients’ subjective experiences using MINDSET. Participants were enrolled in the intervention group of a larger parent study (RCT) to assess the efficacy of MINDSET among Hispanic People with Epilepsy (PWE). The purposive, convenient, criterion-based sample for this qualitative analysis comprised of 42 patients who agreed to participate in a semi-structured interview at the end of the larger RCT. This RCT was conducted between August 2017 and January 2019. Spanish and English-speaking Hispanic adult patients (n = 94) with epilepsy in Arizona (n = 53) and Texas (n = 41) were randomly assigned within 6 neurology clinics to treatment (MINDSET plus Usual Care, hereafter referred to as MINDSET; n = 46) and comparison (Usual Care Only; n = 48) conditions. Results: Patient demographics, epilepsy conditions, and ESM behavioral characteristics were representative of the intervention group. Study participants were Hispanic, mainly of Mexican descent (94 %), with a mean age of 39 years, mostly female (53 %), and most of the participants reported having had one or more seizures per month (54 %). The MINDSET intervention revealed five ESM themes: (1) Awareness and Realization of Epilepsy Self-Management, (2) Communication and Partnership with Health Care Providers HCP, (3) Epilepsy Self-Management and Quality of Life, (4) Seizure Control, and (5) Optimism and Agency. Conclusion: The participants who used MINDSET as a self-management intervention reported an overall positive experience. Qualitative data in this study show that MINDSET is a valuable ESM tool for Hispanic patients with epilepsy. Findings from this qualitative study were consistent with results from a larger parent study that recognized MINDSET as an effective platform for improving epilepsy self-management adherence.
• Sprissler, R., Hammer, M., Labiner, D., Joshi, N., Alan, A., & Weinand, M. (2024). Leukocyte differential gene expression prognostic value for high versus low seizure frequency in temporal lobe epilepsy. BMC Neurology, 24(1). doi:10.1186/s12883-023-03459-1
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  Background: This study was performed to test the hypothesis that systemic leukocyte gene expression has prognostic value differentiating low from high seizure frequency refractory temporal lobe epilepsy (TLE). Methods: A consecutive series of patients with refractory temporal lobe epilepsy was studied. Based on a median baseline seizure frequency of 2.0 seizures per month, low versus high seizure frequency was defined as ≤ 2 seizures/month and > 2 seizures/month, respectively. Systemic leukocyte gene expression was analyzed for prognostic value for TLE seizure frequency. All differentially expressed genes were analyzed, with Ingenuity® Pathway Analysis (IPA®) and Reactome, to identify leukocyte gene expression and biological pathways with prognostic value for seizure frequency. Results: There were ten males and six females with a mean age of 39.4 years (range: 16 to 62 years, standard error of mean: 3.6 years). There were five patients in the high and eleven patients in the low seizure frequency cohorts, respectively. Based on a threshold of twofold change (p < 0.001, FC > 2.0, FDR < 0.05) and expression within at least two pathways from both Reactome and Ingenuity® Pathway Analysis (IPA®), 13 differentially expressed leukocyte genes were identified which were all over-expressed in the low when compared to the high seizure frequency groups, including NCF2, HMOX1, RHOB, FCGR2A, PRKCD, RAC2, TLR1, CHP1, TNFRSF1A, IFNGR1, LYN, MYD88, and CASP1. Similar analysis identified four differentially expressed genes which were all over-expressed in the high when compared to the low seizure frequency groups, including AK1, F2R, GNB5, and TYMS. Conclusions: Low and high seizure frequency TLE are predicted by the respective upregulation and downregulation of specific leukocyte genes involved in canonical pathways of neuroinflammation, oxidative stress and lipid peroxidation, GABA (γ-aminobutyric acid) inhibition, and AMPA and NMDA receptor signaling. Furthermore, high seizure frequency-TLE is distinguished prognostically from low seizure frequency-TLE by differentially increased specific leukocyte gene expression involved in GABA inhibition and NMDA receptor signaling. High and low seizure frequency patients appear to represent two mechanistically different forms of temporal lobe epilepsy based on leukocyte gene expression.
• Weinand, M. E., Weinand, M. E., Weinand, M. E., Hammer, M., Hammer, M., Hammer, M., Lau, B., Lau, B., Lau, B., Labiner, D. M., Labiner, D. M., Labiner, D. M., Walter, C. M., Walter, C. M., Walter, C. M., Bernas, M. J., Bernas, M. J., Bernas, M. J., Witte, M. H., , Witte, M. H., et al. (2018). Leukocyte expression profiles reveal gene sets with prognostic value for seizure-free outcome following stereotactic laser amygdalohippocampotomy. Nature Scientific Reports.
• Hammer, M., Joshi, N., Labiner, D., Sprissler, R., & Weinand, M. (2023). Leukocyte gene expression predicts human temporal lobe epilepsy seizure frequency. see CV. doi:10.21203/rs.3.rs-2070618/v1
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  Abstract Introduction : This study was performed to test the hypothesis that systemic leukocyte gene expression has prognostic value differentiating low from high seizure frequency refractory temporal lobe epilepsy (TLE). Methods : A consecutive series of sixteen patients with refractory temporal lobe epilepsy was studied. Based on a median baseline seizure frequency of 2.0 seizures per month, low versus high seizure frequency was defined as < 2 seizures/month and > 2 seizures/month, respectively. Systemic leukocyte gene expression was analyzed for prognostic value for TLE seizure frequency. All differentially expressed genes were analyzed, with Ingenuity® Pathway Analysis (IPA®) and Reactome, to identify leukocyte gene expression and biological pathways with prognostic value for seizure frequency. Results : There were ten males and six females with a mean age of 39.4 years (range: 16 to 62 years, standard error of mean: 3.6 years). There were five patients in the high and eleven patients in the low seizure frequency cohorts, respectively. Based on a threshold of 2-fold change (p < 0.001, FC > 2.0, FDR < 0.05) and expression within at least two pathways from both Reactome and Ingenuity® Pathway Analysis (IPA®), 13 differentially expressed leukocyte genes were identified which were all over-expressed in the low when compared to the high seizure frequency groups, including NCF2, HMOX1, RHOB, FCGR2A, PRKCD, RAC2, TLR1, CHP1, TNFRSF1A, IFNGR1, LYN, MYD88, and CASP1. Similar analysis identified four differentially expressed genes which were all over-expressed in the high when compared to the low seizure frequency groups, including AK1, F2R, GNB5, and TYMS. Conclusions : Low and high seizure frequency TLE are predicted by the respective upregulation and downregulation of specific leukocyte genes involved in canonical pathways of neuroinflammation, oxidative stress and lipid peroxidation, GABA (γ-aminobutyric acid) inhibition, and AMPA and NMDA receptor signaling. Furthermore, high seizure frequency-TLE is distinguished prognostically from low seizure frequency-TLE by differentially increased specific leukocyte gene expression involved in GABA inhibition and NMDA receptor signaling. High and low seizure frequency patients appear to represent two mechanistically different forms of temporal lobe epilepsy based on leukocyte gene expression.
• Abraham, A., Beghi, E., Begley, C., Kwon, C., Labiner, D., Newton, C., Wagner, R. G., & Winkler, A. S. (2022). The global cost of epilepsy: A systematic review and extrapolation. Epilepsia, 63(4), 892-903. doi:10.1111/epi.17165
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  Global action for epilepsy requires information on the cost of epilepsy, which is currently unknown for most countries and regions of the world. To address this knowledge gap, the International League Against Epilepsy Commission on Epidemiology formed the Global Cost of Epilepsy Task Force.We completed a systematic search of the epilepsy cost-of-illness literature and identified studies that provided a comprehensive set of direct health care and/or indirect costs, followed standard methods of case identification and cost estimation, and used data on a representative population or subpopulation of people with epilepsy. Country-specific costs per person with epilepsy were extracted and adjusted to generate an average cost per person in 2019 US dollars. For countries with no cost data, estimates were imputed based on average costs per person of similar income countries with data. Per person costs for each country were then applied to data on the prevalence of epilepsy from the Global Burden of Disease collaboration adjusted for the treatment gap.One hundred one cost-of-illness studies were included in the direct health care cost database, 74 from North America or Western Europe. Thirteen studies were used in the indirect cost database, eight from North America or Western Europe. The average annual cost per person with epilepsy in 2019 ranged from $204 in low-income countries to $11 432 in high-income countries based on this highly skewed database. The total cost of epilepsy, applying per person costs to the estimated 52.51 million people in the world with epilepsy and adjusting for the treatment gap, was $119.27 billion.Based on a summary and extrapolations of this limited database, the global cost of epilepsy is substantial and highly concentrated in countries with well-developed health care systems, higher wages and income, limited treatment gaps, and a relatively small percentage of the epilepsy population.
• Labiner, D. M., & Labiner, D. M. (2021). Accreditation of Epilepsy Centers.. Epilepsy currents, 21(2), 132-133. doi:10.1177/1535759721991568
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  In 2012, the Institute of Medicine recommended that a formal process be developed for the accreditation of epilepsy centers in the United States. This article provides some of the background and processes that led to the criteria by which epilepsy centers are now accredited.
• Van Marter, L. J., Pennell, P. B., Brown, C., Hartman, A. L., May, R. C., McElrath, T., Ippolito, D., Meador, K. J., Bagic, A., Barkley, G., Cavitt, J., DeWolfe, J., French, J., Gedzelman, E., Gerard, E., Hwang, S., Kalayjian, L., Krauss, G., Labiner, D., , McCabe, P., et al. (2021). Neonatal Outcomes in the MONEAD Study of Pregnant Women with Epilepsy. Journal of Pediatrics: X, 7(Issue). doi:10.1016/j.ympdx.2021.100073
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  Objective: To determine whether growth measures at birth differ between offspring of pregnant women with epilepsy and healthy pregnant women. Study design: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a National Institutes of Health–funded, prospective, observational, multicenter investigation of pregnancy outcomes for mothers and their infants. Between 2012 and 2016, pregnant women with epilepsy and healthy pregnant women were enrolled at 20 US epilepsy centers. Pregnant women with epilepsy were exposed to various antiepileptic drugs. The main outcome measure was small for gestational age at birth. Principal univariate and multivariate analyses compared outcomes between pregnant women with epilepsy and healthy pregnant women. Secondary analyses focused on outcomes among mothers receiving different antiepileptic drug therapies. Results: In total, 345 infants were born to 331 pregnant women with epilepsy and 106 infants were born to 102 healthy pregnant women. No differences were seen between infants born to pregnant women with epilepsy vs healthy pregnant women in preterm births, major congenital malformations, 5-minute Apgar
• Addy, R. C., Begley, C. E., Chong, J., Halavacs, N., Labiner, D. M., Martin, K., Rosales, O., Sepulveda, R., & Shegog, R. (2020). MINDSET: Clinic-based decision support demonstrates longitudinal efficacy for increased epilepsy self-management adherence among Spanish speaking patients.. Epilepsy & behavior : E&B, 113(Issue), 107552. doi:10.1016/j.yebeh.2020.107552
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  MINDSET, a bilingual (Eng./Span.) decision support tool was found feasible for facilitating goal-based epilepsy self-management (ESM) in the clinic..To evaluate the efficacy of MINDSET to increase ESM adherence among Hispanic patients..A RCT was conducted from August 2017 through January 2019. Spanish and English speaking Hispanic adult patients (n=94) with epilepsy in Arizona (n=53) and Texas (n=41) were randomly assigned within 6 neurology clinics to treatment (MINDSET plus Usual Care, hereafter referred to as MINDSET; n=46) and comparison (Usual Care Only; n=48) conditions. Self-reported self-management behavior (assessed through the Epilepsy Self-management scale) were categorized as adherent if performed 'usually' or 'always.' The proportion of adherence was compared between study conditions for 36 individual ESM behaviors and 5 ESM domains using Fischer's exact test..The average time between visit 1 through 3 was 350+/-79 days with retention at 96.8%. Participants in the treatment condition had more college education and less unemployment. Self-management adherence improved across visits for all self-management behaviors irrespective of study condition. Compared to usual care MINDSET use led to greater ESM adherence for 86.1% behaviors (5 with statistical significance; p
• Fishman, J., Martin, M., Labiner, D. M., Lew, C. R., & Johnson, B. H. (2019). Healthcare resource utilization and costs before and after lacosamide initiation as adjunctive therapy among patients with epilepsy in the United States. Epilepsy & behavior : E&B, 99, 106331.
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  The objective of this study was to evaluate all-cause and epilepsy-specific healthcare resource utilization and costs following lacosamide (LCM) initiation as adjunctive therapy for the treatment of epilepsy.
• Hammer, M. F., Sprissler, R., Bina, R. W., Lau, B., Johnstone, L., Walter, C. M., Labiner, D. M., & Weinand, M. E. (2019). Altered expression of signaling pathways regulating neuronal excitability in hippocampal tissue of temporal lobe epilepsy patients with low and high seizure frequency. Epilepsy research, 155, 106145.
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  Despite recent advances in our understanding of synaptic transmission associated with epileptogenesis, the molecular mechanisms that control seizure frequency in patients with temporal lobe epilepsy (TLE) remain obscure. RNA-Seq was performed on hippocampal tissue resected from 12 medically intractable TLE patients with pre-surgery seizure frequencies ranging from 0.33 to 120 seizures per month. Differential expression (DE) analysis of individuals with low (LSF, mean = 4 seizure/month) versus high (HSF, mean = 60 seizures/month) seizure frequency identified 979 genes with ≥2-fold change in transcript abundance (FDR-adjusted p-value ö0.05). Comparisons with post-mortem controls revealed a large number of downregulated genes in the HSF (1676) versus LSF (399) groups. More than 50 signaling pathways were inferred to be deactivated or activated, with Signal Transduction as the central hub in the pathway network. While neuroinflammation pathways were activated in both groups, key neuronal system pathways were systematically deactivated in the HSF group, including calcium, CREB and Opioid signaling. We also infer that enhanced expression of a signaling cascade promoting synaptic downscaling may have played a key role in maintaining a higher seizure threshold in the LSF cohort. These results suggest that therapeutic approaches targeting synaptic scaling pathways may aid in the treatment of seizures in TLE.
• Sprissler, R., Bina, R., Kasoff, W., Witte, M. H., Bernas, M., Walter, C., Labiner, D. M., Lau, B., Hammer, M. F., & Weinand, M. E. (2019). Leukocyte expression profiles reveal gene sets with prognostic value for seizure-free outcome following stereotactic laser amygdalohippocampotomy. Scientific reports, 9(1), 1086.
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  Among patients with intractable epilepsy, the most commonly performed surgical procedure is craniotomy for amygdalohippocampectomy (AH). Stereotactic laser amygdalohippocampotomy (SLAH) has also been recently employed as a minimally invasive treatment for intractable temporal lobe epilepsy (TLE). Among patients treated with AH and SLAH approximately 65% and 54% of patients become seizure-free, respectively. Therefore, selection criteria for surgical candidates with improved prognostic value for post-operative seizure-free outcome are greatly needed. In this study, we perform RNA sequencing (RNA-Seq) on whole blood leukocyte samples taken from 16 patients with intractable TLE prior to SLAH to test the hypothesis that pre-operative leukocyte RNA expression profiles are prognostic for post-operative seizure outcome. Multidimensional scaling analysis of the RNA expression data indicated separate clustering of patients with seizure free (SF) and non-seizure-free (NSF) outcomes. Differential expression (DE) analysis performed on SF versus NSF groups revealed 24 significantly differentially expressed genes (≥2.0-fold change, p-value 
• Weinand, M. E., Hammer, M., Lau, B., Labiner, D. M., Walter, C. M., Bernas, M. J., Witte, M. H., Kasoff, W., Bina, R., & Sprissler, R. (2019). Leukocyte expression profiles reveal gene sets with prognostic value for seizure-free outcome following stereotactic laser amygdalohippocampotomy. Nature Scientific Reports.
• Chong, J., Sepulveda, R., Addy, R. C., Begley, C. E., Halavacs, N., Labiner, D. M., Martin, K., & Shegog, R. (2018). MINDSET: Clinical feasibility of utilizing the revised epilepsy self-management tool for Spanish speaking patients.. Epilepsy & behavior : E&B, 88, 218-226. doi:10.1016/j.yebeh.2018.09.021
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  This paper describes the expanded English/Spanish version of the Management Information and Decision Support Epilepsy Tool (MINDSET) as well as the methods and findings from a feasibility study conducted from July 2016 through February 2017 with 43 Spanish and English-speaking Hispanic people living with epilepsy (PWE) in Arizona (n = 23) and Texas (n = 20) over two consecutive regular clinic visits. The expansion of MINDSET added goal setting and strategy selection to improve self-management (S-M) in PWE. The previous study tested the feasibility of English MINDSET, which was designed to facilitate the identification and discussion of S-M issues between the patient and healthcare provider (HCP) during a regular clinic visit. Results indicate MINDSET feasibility for use in the following: 1) identifying S-M issues across several domains; 2) selecting and assessing confidence in tailored S-M goals/strategies for improvement; 3) discussing S-M issues/goals/strategies/confidence with a HCP; and 4) creating an action plan (AP) and tracking achievement during regular clinic visits. Across two visits, 80-90% of patients agreed that the revised version of MINDSET was helpful, understandable, trustworthy, promoted careful thinking about management, was of appropriate duration, and would be helpful in future management and communication with HCP. Participating HCPs agreed that MINDSET improved the ease, thoroughness, and accuracy in identifying patient S-M issues and establishing a plan for improvement.
• Ip, Q., Malone, D. C., Chong, J. W., Harris, R. B., & Labiner, D. M. (2018). An update on the prevalence and incidence of epilepsy among older adults. Epilepsy Research, 139, 107-112.
• Ip, Q., Malone, D. C., Chong, J., Harris, R. B., & Labiner, D. M. (2018). An update on the prevalence and incidence of epilepsy among older adults. Epilepsy research, 139, 107-112.
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  To estimate the prevalence and incidence of epilepsy among beneficiaries of Arizona Medicare aged 65 and over.
• Ip, Q., Malone, D. C., Chong, J., Harris, R. B., & Labiner, D. M. (2018). Economic impact of epilepsy and the cost of nonadherence to antiepileptic drugs in older Medicare beneficiaries. Epilepsy & behavior : E&B, 80, 208-214.
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  Epilepsy is most prevalent among older individuals, and its economic impact is substantial. The development of economic burden estimates that account for known confounders, and using percent incremental costs may provide meaningful comparison across time and different health systems. The first objective of the current study was to estimate the percent incremental healthcare costs and the odds ratio (OR) for inpatient utilization for older Medicare beneficiaries with epilepsy and without epilepsy. The second objective was to estimate the percent incremental healthcare costs and the OR for inpatient utilization associated with antiepileptic drug (AED) nonadherence among Medicare beneficiaries with epilepsy. The OR of inpatient utilization for cases compared with controls (i.e., non-cases) were 2.4 (95% CI 2.3 to 2.6, p-value
• Joyce, N. R., Fishman, J., Green, S., Labiner, D. M., Wild, I., & Grabowski, D. C. (2018). Cost sharing for antiepileptic drugs: medication utilization and health plan costs. The American journal of managed care, 24(6), e183-e189.
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  To examine the association between health plan out-of-pocket (OOP) costs for antiepileptic drugs and healthcare utilization (HCU) and overall plan spending among US-based commercial health plan beneficiaries with epilepsy.
• Labiner, D. M., Leppik, I. E., & Riker, E. (2018). Robert J. Gumnit, MD (1931–2017). Neurology, 90(18), 825-826. doi:10.1212/wnl.0000000000005460
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  When he first proposed to colleagues to use the phrase “Our Goal: No Seizures, No Side Effects,” the initial response was reluctance. Now the phrase is accepted orthodoxy in the epilepsy community and lives on despite the passing of its author, Robert J. Gumnit, who died on October 15, 2017, at age 86. When we consider the great names in epilepsy care in the United States, we think of Lennox, Merritt, Putnam, Penry, and Dreifuss. Although he did not seek recognition and was humble about his accomplishments, Bob Gumnit has earned a place on this list.
• Shih, J. J., Fountain, N. B., Herman, S. T., Bagic, A., Lado, F., Arnold, S., Zupanc, M. L., Riker, E., & Labiner, D. M. (2018). Indications and methodology for video-electroencephalographic studies in the epilepsy monitoring unit. Epilepsia, 59(1), 27-36.
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  Although the epilepsy and neurology communities have position papers on a number of topics pertaining to epilepsy diagnosis and management, no current paper exists for the rationale and appropriate indications for epilepsy monitoring unit (EMU) evaluation. General neurologists, hospital administrators, and insurers also have yet to fully understand the role this type of testing has in the diagnosis and management of individuals with paroxysmal neurologic symptoms. This review outlines the indications for long-term video-electroencephalography (VEEG) for typical elective admissions to a specialized inpatient setting. The common techniques used in EMUs to obtain diagnostic information are reviewed. The added benefit of safety measures and clinical testing above that available for routine or long-term ambulatory electroencephalography is also discussed. The indications for admission to the EMU include differential diagnosis of paroxysmal spells, characterization of seizure types, presurgical epilepsy evaluations, seizure quantification, monitoring medication adjustment in a safe setting, and differentiation between seizures and side effects. We conclude that the appropriate use of this specialized testing can lead to an early and correct diagnosis in a variety of clinical circumstances. The EMU evaluation is considered the gold standard test for the definitive diagnosis of epilepsy and seizure-like spells.
• Weinand, M. E., Weinand, M. E., Hammer, M., Hammer, M., Labiner, D. M., Labiner, D. M., Walter, C. M., Walter, C. M., Bernas, M. J., Bernas, M. J., Witte, M. H., Witte, M. H., Sprissler, R. S., Sprissler, R. S., Kasoff, W., Kasoff, W., Bina, R. W., & Bina, R. W. (2018). Leukocyte RNA expression: Prognostic value for seizure-free outcome following stereotactic laser amygdalohippocampotomy. Neurosurgery, 65(1), 94.
• Arnold, S., Bagic, A., Fountain, N. B., Herman, S. T., Labiner, D. M., Lado, F., Riker, E., Shih, J. J., & Zupanc, M. L. (2017). Indications and methodology for video‐electroencephalographic studies in the epilepsy monitoring unit. Epilepsia, 59(1), 27-36. doi:10.1111/epi.13938
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  Summary Although the epilepsy and neurology communities have position papers on a number of topics pertaining to epilepsy diagnosis and management, no current paper exists for the rationale and appropriate indications for epilepsy monitoring unit (EMU) evaluation. General neurologists, hospital administrators, and insurers also have yet to fully understand the role this type of testing has in the diagnosis and management of individuals with paroxysmal neurologic symptoms. This review outlines the indications for long‐term video‐electroencephalography (VEEG) for typical elective admissions to a specialized inpatient setting. The common techniques used in EMUs to obtain diagnostic information are reviewed. The added benefit of safety measures and clinical testing above that available for routine or long‐term ambulatory electroencephalography is also discussed. The indications for admission to the EMU include differential diagnosis of paroxysmal spells, characterization of seizure types, presurgical epilepsy evaluations, seizure quantification, monitoring medication adjustment in a safe setting, and differentiation between seizures and side effects. We conclude that the appropriate use of this specialized testing can lead to an early and correct diagnosis in a variety of clinical circumstances. The EMU evaluation is considered the gold standard test for the definitive diagnosis of epilepsy and seizure‐like spells.
• Escoffery, C., Escoffery, C., Thompson, N. J., Thompson, N. J., Begley, C. E., Begley, C. E., Devinsky, O., Devinsky, O., Fraser, R. T., Fraser, R. T., Helmers, S. L., Helmers, S. L., Horvath, K. J., Horvath, K. J., Jobst, B. C., Jobst, B. C., Johnson, E. K., Johnson, E. K., Kobau, R., , Kobau, R., et al. (2017). Self-management in epilepsy: Why and how you should incorporate self-management in your practice.. Epilepsy & behavior : E&B, 68(Issue), 220-224. doi:10.1016/j.yebeh.2016.11.015
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  Epilepsy presents many challenges for those affected by the disease as well as for family members and providers [ 1 Institute of Medicine Epilepsy across the spectrum: promoting health and understanding. National Academies Press, Washington, DC2012 Google Scholar , 2 McAuley J.W. Elliot J.O. Patankar S. Hart S. Long L. Moore J.L. et al. Comparing patients’ and practitioners’ views on epilepsy concerns: a call to address memory concerns. Epilepsy Behav. 2010; 19: 580-583 Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar ]. Epilepsy providers routinely educate and counsel patients on their epilepsy and related health issues. Yet, people with epilepsy spend almost all of their time outside of their doctor's office. Providers cannot support and monitor treatment adherence, mood, or enhance their patients' healthful behaviors, coping skills, and quality of life on a daily basis. Providers may also fail to recognize or treat common comorbidities such as depression, anxiety, cognitive impairment, and sleep disorders that can adversely affect seizure control and quality of life [ 3 Osman A. Seri S. Cavanna A.E. Clinical characteristics of patients with epilepsy in a specialist neuropsychiatry service. Epilepsy Behav. 2016 May; 58: 44-47https://doi.org/10.1016/j.yebeh.2016.02.033 Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar , 4 Tao K. Wang X. The comorbidity of epilepsy and depression: diagnosis and treatment. Expert Rev Neurother. 2016; 16: 1321-1333 Crossref PubMed Scopus (16) Google Scholar ]. Often lacking a multidisciplinary team, or having insufficient time in clinical encounters, providers cannot fully address these and related psychosocial needs of their patients with epilepsy [ [5] Clark N.M. Stoll S. Sweetman M. Youatt E.J. Derry R. Gorelick A. Fostering epilepsy self-management: the perspectives of professionals. Epilepsy Behav. 2010; 19: 255-263 Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar ]. Introducing and encouraging access to patients self-management support can address these gaps in care, ultimately transferring “ownership” of care from provider to patient [ 6 Brady T.J. Anderson L.A. Kobau R. Chronic disease self-management support: public health perspectives. Front Public Health. 2015; 2: 1-5 Google Scholar , 7 Institute of Medicine (IOM) Crossing the quality chasm: A new health system for the 21st century. National Academy Press, Washington, D.C2001 Google Scholar ]. At the individual level, self-management aims to increase patients' skills and confidence in monitoring symptoms, problem-solving, decision-making, goal-setting, communicating, and adopting healthful behaviors to improve health and quality of life [ 8 Chassin M.R. Loeb J.M. The ongoing quality improvement journey: next stop, high reliability. Heatlh Aff (Millwod). 2011; 30: 559-568 Crossref PubMed Scopus (205) Google Scholar , 9 Institute of Medicine Living well with chronic illness: A call for public health action. The National Academy Press, Washington, DC2012 Google Scholar , 10 Escoffery C. Bamps Y.A. LaFrance Jr., W.C. Stoll S. Shegog R. Buelow J. et al. Factor analyses of an Adult Epilepsy Self-Management Measurement Instrument (AESMMI). Epilepsy Behav. 2015; 50: 184-189 Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar , 11 Buelow J.M. Johnson J. Self-management of epilepsy. Dis Manag Health Out. 2000; 8: 327-336 Crossref Scopus (38) Google Scholar ]. Self-management is a partnership between the patient and provider, incorporating patients' preferences and goals—making it patient-centered. Self-management also facilitates positive health—inclusive of physical, mental, and social resources that actively promote well-being [ [12] Huber M. Knottnerus J.A. Green L. van der Horst H. Jadad A.R. Kromhout D. et al. How should we define health?. BMJ. 2011; 343: d4163https://doi.org/10.1136/bmj.d4163 Crossref PubMed Scopus (1263) Google Scholar ]. Epilepsy self-management domains (e.g., treatment adherence, tracking seizures and medication side effects, stress reduction, sleep, safety, communication) have been extensively reviewed [ 10 Escoffery C. Bamps Y.A. LaFrance Jr., W.C. Stoll S. Shegog R. Buelow J. et al. Factor analyses of an Adult Epilepsy Self-Management Measurement Instrument (AESMMI). Epilepsy Behav. 2015; 50: 184-189 Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar , 11 Buelow J.M. Johnson J. Self-management of epilepsy. Dis Manag Health Out. 2000; 8: 327-336 Crossref Scopus (38) Google Scholar , 13 Smith G. Wagner J.L. Commentary on “Care delivery and self-management strategies for children with epilepsy.” Evidence-Based Child Health. Cochrane Rev J. 2012; 7: 241-243https://doi.org/10.1002/ebch.1818 Crossref Scopus (6) Google Scholar ].
• Gallek, M. J., Skoch, J., Ansay, T., Behbahani, M., Mount, D., Manziello, A., Witte, M., Bernas, M., Labiner, D. M., & Weinand, M. E. (2016). Cortical gene expression: prognostic value for seizure outcome following temporal lobectomy and amygdalohippocampectomy. Neurogenetics, 17(4), 211-218.
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  Whole genome analyses were performed to test the hypothesis that temporal cortical gene expression differs between epilepsy patients rendered seizure-free versus non-seizure-free following anterior temporal lobectomy with amygdalohippocampectomy (ATL/AH). Twenty four patients underwent ATL/AH to treat medically intractable seizures of temporal lobe origin (mean age 35.5 years, mean follow-up 42.2 months); they were then dichotomized into seizure-free and non-seizure-free groups. Tissue RNA was isolated from the lateral temporal cortex and gene expression analysis was performed. Whole genome data were analyzed for prognostic value for seizure-free outcome following ATL/AH by logistic regression. Genes that could distinguish seizure outcome groups were identified based on providing an accuracy of >0.90 judging by area under the receiver operating characteristic curve, AUC, with a P value of the slope coefficient of
• Gallek, M. J., Skoch, J., Ansay, T., Behbahani, M., Mount, D., Manziello, A., Witte, M., Bernas, M., Labiner, D. M., & Weinand, M. E. (2016). Cortical gene expression: prognostic value for seizure outcome following temporal lobectomy and amygdalohippocampectomy. Neurogenetics, 17(Issue 4). doi:10.1007/s10048-016-0484-2
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  Whole genome analyses were performed to test the hypothesis that temporal cortical gene expression differs between epilepsy patients rendered seizure-free versus non-seizure-free following anterior temporal lobectomy with amygdalohippocampectomy (ATL/AH). Twenty four patients underwent ATL/AH to treat medically intractable seizures of temporal lobe origin (mean age 35.5 years, mean follow-up 42.2 months); they were then dichotomized into seizure-free and non-seizure-free groups. Tissue RNA was isolated from the lateral temporal cortex and gene expression analysis was performed. Whole genome data were analyzed for prognostic value for seizure-free outcome following ATL/AH by logistic regression. Genes that could distinguish seizure outcome groups were identified based on providing an accuracy of >0.90 judging by area under the receiver operating characteristic curve, AUC, with a P value of the slope coefficient of
• Manacheril, R., Faheem, U., Labiner, D. M., Drake, K. W., Chong, J. W., Manacheril, R., Faheem, U., Labiner, D. M., Drake, K. W., & Chong, J. W. (2016). Psychosocial Impact of Epilepsy in Older Adults. Healthcare.
• McCallum, A. P., Gallek, M. J., Ramey, W., Manziello, A., Witte, M. H., Bernas, M. J., Labiner, D. M., & Weinand, M. E. (2016). Cortical gene expression correlates of temporal lobe epileptogenicity. Pathophysiology : the official journal of the International Society for Pathophysiology, 23(3), 181-90.
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  Despite being one of the most common neurological diseases, it is unknown whether there may be a genetic basis to temporal lobe epilepsy (TLE). Whole genome analyses were performed to test the hypothesis that temporal cortical gene expression differs between TLE patients with high vs. low baseline seizure frequency.
• Sleeth, C., Drake, K., Labiner, D. M., & Chong, J. (2016). Felt and enacted stigma in elderly persons with epilepsy: A qualitative approach. Epilepsy & behavior : E&B, 55, 108-112.
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  Stigma is a common psychological consequence of chronic diseases, including epilepsy; however, little research has been done to determine the effect of stigma on persons with epilepsy, especially the elderly. We interviewed 57 older adults with epilepsy to discover the extent and consequences of, and reasons for, epilepsy-related stigma in their lives. Felt stigma was more frequently reported than enacted stigma, with over 70% having experienced this form of stigma. Participants described ignorance and fear of the disease as the foundation of epilepsy-related stigma. The most common response to stigmatizing events was a decrease in epilepsy disclosure to family or friends. Results from this study could inform interventions designed for elderly persons with epilepsy and their support networks, as well as educational campaigns for the general public.
• Sleeth, C., Drake, K., Labiner, D. M., & Chong, J. (2016). Felt and enacted stigma in elderly persons with epilepsy: A qualitative approach. Epilepsy and Behavior, 55. doi:10.1016/j.yebeh.2015.12.026
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  Stigma is a common psychological consequence of chronic diseases, including epilepsy; however, little research has been done to determine the effect of stigma on persons with epilepsy, especially the elderly. We interviewed 57 older adults with epilepsy to discover the extent and consequences of, and reasons for, epilepsy-related stigma in their lives. Felt stigma was more frequently reported than enacted stigma, with over 70% having experienced this form of stigma. Participants described ignorance and fear of the disease as the foundation of epilepsy-related stigma. The most common response to stigmatizing events was a decrease in epilepsy disclosure to family or friends. Results from this study could inform interventions designed for elderly persons with epilepsy and their support networks, as well as educational campaigns for the general public.
• Kaiboriboon, K., Malkhachroum, A. M., Zrik, A., Daif, A., Schiltz, N. M., Labiner, D. M., & Lhatoo, S. D. (2015). Epilepsy surgery in the United States: Analysis of data from the National Association of Epilepsy Centers. Epilepsy research, 116, 105-9.
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  To examine trends in epilepsy-related surgical procedures performed at major epilepsy centers in the US between 2003 and 2012, and in the service provision infrastructure of epilepsy centers over the same time period.
• Labiner, D. M. (2015). William A. Sibley, MD (1925–2015). Neurology, 85(12), 1016.
• Labiner, D. M., Chong, J. W., Tang, D. H., Malone, D. C., Warholak, T. L., Armstrong, E. P., Slack, M. K., & Hsu, C. H. (2015). Healthcare Resource Burden of Newly Diagnosed Epilepsy in the US Low-Income Elderly Population. European Geriatric Medicine, 6, 251-256.
• Lhatoo, S. D., Kaiboriboon, K., & Labiner, D. (2015). Response to "The persistent under-utilization of epilepsy surgery". Epilepsy research, 118, 70-1.
• Manacheril, R., Faheem, U., Labiner, D. M., Drake, K. W., & Chong, J. W. (2015). Psychosocial Impact of Epilepsy in Older Adults.. Healthcare.
• Nicole, A., Boatman, L., Cox, E. R., Grudzinski, A. N., Hakim, Z., & Labiner, D. M. (2015). Economic Assessment of the Relationship between Disease Exacerbations and the Cost of Multiple Sclerosis. Journal of Managed Care Pharmacy, 6(1), 19-24. doi:10.18553/jmcp.2000.6.1.19
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  OBJECTIVE: The primary purpose of this study was to define the cost of multiple sclerosis (MS) from the perspective of a managed care organization (MCO). This study also estimated the cost of a disease exacerbation to predict the cost that may be offset by the use of disease-modifying pharmaceutical agents. DESIGN: Retrospective (1995-96) claims of a managed care medical and pharmacy database were used as data sources. Multiple linear regression was used to identify the determinants of cost and to estimate the cost of treating an MS disease exacerbation.
• Nokes, B., Sim, Y., Gibson, B., Byreddy, S., Labiner, D. M., Coull, B., & Chong, J. (2015). Assessment of stroke risk in southern Arizona, the pairing of acculturation and stroke risk factor development. Journal of immigrant and minority health / Center for Minority Public Health, 17(2), 513-8.
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  Stroke is a leading cause of mortality in the United States. Hispanics have the same incidence of stroke, but are more likely to have subsequent strokes than non-Hispanic whites. This difference in outcome may be attributable to differences in stroke risk factor awareness. Patients at a community health center in Tucson, AZ completed an anonymous survey regarding existing and perceived health issues. Patient responses were compared in terms of ethnicity and acculturation, as indicated by language preference. Patient responses (n = 301, Spanish: 150, English: 151) indicated that proportionately fewer non-acculturated Hispanics than acculturated Hispanic and non-Hispanic patients indicated that they were at risk for stroke. Acculturated Hispanics and non-Hispanics displayed similar morbidity trends, including increased obesity, hypertension, diabetes, heart problems, depression, and previous stroke. These findings suggest that Hispanics become less healthy and more at risk for stroke and stroke risk factors as they become acculturated.
• Tang, D. H., Malone, D. C., Warholak, T. L., Chong, J. W., Armstrong, E. P., Slack, M. K., Hsu, C. H., Labiner, D. M., Tang, D. H., Malone, D. C., Warholak, T. L., Chong, J. W., Armstrong, E. P., Slack, M. K., Hsu, C. H., & Labiner, D. M. (2015). Healthcare Resource Burden of Newly Diagnosed Epilepsy in the US Low-Income Elderly Population. European Geriatric Medicine.
• Tang, D. H., Malone, D. C., Warholak, T. L., Chong, J., Armstrong, E. P., Slack, M. K., Hsu, C. H., & Labiner, D. M. (2015). Prevalence and Incidence of Epilepsy in an Elderly and Low-Income Population in the United States. Journal of clinical neurology (Seoul, Korea), 11(3), 252-61.
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  The purpose of this study was to estimate the incidence and prevalence of epilepsy among an elderly and poor population in the United States.
• Weinand, M. E., Hammer, M., Lau, B., Labiner, D. M., Walter, C. M., Bernas, M. J., Witte, M. H., Kasoff, W., Bina, R., & Sprissler, R. (2018). Leukocyte expression profiles reveal gene sets with prognostic value for seizure-free outcome following stereotactic laser amygdalohippocampotomy. Scientific Reports, 9(1), 1086. doi:10.1038/s41598-018-37763-5
• Denski, K. M., & Labiner, D. M. (2014). Should I offer vagus nerve stimulation as part of my neurology practice?. Neurology. Clinical practice, 4(4), 313-318.
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  Vagus nerve stimulation (VNS) is a safe and effective adjunctive therapy approved for patients with partial-onset seizures. A pulse generator, which is implanted in the chest wall, delivers programmed electrical pulses through an electrode that is attached to the left vagus nerve. VNS plays an important role in the treatment of patients with drug-resistant epilepsy. It is currently offered in academic as well as private practice settings. After a comprehensive workup is performed, VNS should be offered to patients with drug-resistant epilepsy who are not candidates for surgery.
• Gross, R. E., Willie, J. T., Cascino, G. D., Couture, D. E., Curry, D. J., Labiner, D. M., Laxton, A. W., Marsh, W. R., Popli, G., Sharan, A. D., Shih, J. J., Sperling, M. R., Tatum, W. O., Weinand, M. E., Wharen, R. E., Wilfong, A. A., & Worrell, G. A. (2014). 103 Stereotactic Laser Amygdalohippocampotomy for Mesial Temporal Lobe Epilepsy: Collective Experience From 7 Single-Center, Prospective, Investigator-Initiated Studies. Neurosurgery, 61(Supplement 1), 192. doi:10.1227/01.neu.0000452377.10458.80
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  INTRODUCTION: Stereotactic laser amygdalohippocampotomy (SLAH) is a minimally-invasive potential alternative to open resection for mesial temporal lobe epilepsy (MTLE), but outcome data are limited (Willie et al, 2014). Here we present data on effectiveness, safety, and related findings collected from investigator-initiated, prospective, observational studies at 7 centers. METHODS: Fifty-one subjects who met entry criteria for surgical treatment of MTLE were enrolled in IRB-approved prospective data collection and underwent SLAH. Screening and follow-up visits were arranged per protocol at a given center, typically at 1, 3, 6, and/or 12-months, with some variation by center. Data captured via case report forms included medical/surgical history, number of anti-epileptic drugs (AEDs) tried, duration from epilepsy diagnosis to screening for this study, seizure count since last visit, concomitant medications, adverse events, radiographic findings, neuropsychological tests, and healthcare utilization variables including length-of-stay and level-of-care during hospitalization. RESULTS: Median age was 40 years (5-70 years). AEDs were kept constant throughout the 1-year course by most centers. At 6-month follow-up of all available consecutive subjects (ie, since 10/20/10) for whom data was available, 52% (20/39) at 6-months and 48% (14/29) at 12-months follow-up were seizure-free. However, for procedures performed after 7/1/12, at 6-month follow-up 63% (15/24), and at 12-months 69% (9/13) were seizure-free, suggesting improved outcome with experience. Similarly, 64% (9/14) for procedures performed after 1/1/13 were seizure-free at 6-months. Procedure-related adverse events recorded in all patients included headache (N = 10), visual field disturbance (N = 3), psychiatric disturbance (N = 3), hemorrhage (N = 2), and cellulitis (N = 1). Median length-of-stay was 1 day. Four patients underwent anterior temporal lobectomy for persistent seizures. CONCLUSION: SLAH appears to be a safe procedure and achieves seizure-freedom for a substantial proportion of patients with MTLE. Data support a procedural “learning curve,” plateauing at ∼65% seizure-free. Further prospective study, with greater numbers of subjects, could help elucidate and/or strengthen these findings.
• Sim, Y., Nokes, B., Byreddy, S., Chong, J., Coull, B. M., & Labiner, D. M. (2014). Healthcare utilization of patients with epilepsy in Yuma County, Arizona: do disparities exist?. Epilepsy & behavior : E&B, 31, 307-11.
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  The aim of this study was to describe the disparities in healthcare utilization and costs between Hispanic and non-Hispanic patients with seizures or epilepsy. We reviewed the insurance status and healthcare resource utilization data from 2005 to 2008 for all patients with seizures and epilepsy seen at the Yuma Regional Medical Center (YRMC). Charges for medical services provided to Hispanic patients with epilepsy between the ages of 18 and 49 were significantly less than those for non-Hispanic patients with epilepsy (Hispanic: $3167.63 versus non-Hispanic: $5154.36, P
• Arumaithurai, K., Drake, K., Labiner, D. M., Putta, S., & Shah, A. (2013). Significance of Newer Generation Anti Epileptic Drug Levels during Pregnancy: An Observational Study (P01.043). Neurology, 80(7_supplement). doi:10.1212/wnl.80.7_supplement.p01.043
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  OBJECTIVE: Significance of fluctuating levels of newer antiepileptic drugs (AEDs) during pregnancy is poorly understood. We propose that clinical circumstances should guide dose titrations for newer AEDs, not medication levels. BACKGROUND: Pregnancy causes pharmacokinetic changes in AEDs. This results in increased seizures during pregnancy in one third of patients, while 65% have no change or decreased seizure frequency. Newer AEDs with lower protein binding properties still have level changes during pregnancy. DESIGN/METHODS: We performed a retrospective analysis of 37 women (age 30 years± 6 years) with epilepsy (23 partial and 14 generalized) during the course of their pregnancies. Their AED levels, dose changes and seizures were monitored. Relevance of frequent monitoring of levetiracetam and zonisamide levels was also assessed. RESULTS: We observed 39 successful pregnancies and 2 miscarriages. Pre- pregnancy, patients were taking levetiracetam(19%), lamotrigine(16%), topiramate(13.5%), zonisamide(13.5%), oxcarbazepine(13.5%), phenytoin(11%), carbamazepine(8%) and the remainder(8%) were on valproic acid, ethosuximide, or felbamate (4 on multiple AEDs). 27 pregnancies with prior monotherapy continued the same medication. 5 patients had their AEDs changed, while 2 patients had additional medication added. Fifteen patients had breakthrough seizures during pregnancy. Among all patients, 42 dose adjustments were noted. Half of these were due to seizures, the remainder for declining AED levels. Dose titration for levetiracetam(n=3) during pregnancy was secondary to seizures that occurred despite therapeutic drug levels. Declining drug levels led to dose titration for zonisamide(n=3) even in absence of seizures. Four of the seven patients, who had lamotrigine dose titration during pregnancy, had seizures associated with decline in medication levels. CONCLUSIONS: During pregnancy, medications were adjusted for sub-therapeutic levels or breakthrough seizures. Low lamotrigine levels correlated with increased seizure incidence. Our study shows dose titration based on serum levels of zonisamide or levetiracetam do not correlate with changes in seizures frequency. Disclosure: Dr. Putta has nothing to disclose. Dr. Shah has nothing to disclose. Dr. Arumaithurai has nothing to disclose. Dr. Drake has nothing to disclose. Dr. Labiner has received research grants from, is a consultant for, or is on the speakers bureau of the following companies: Cyberonics, Eisai, GlaxoSmithKline, UCB Pharm. Dr. Labiner has received research grants from Eisai, UCB Pharm, Sunovian.
• Arumaithurai, K., Shah, A., Drake, K., & Labiner, D. (2013). Observational Analysis of EEG in Patients with Intractable Seizures before and after Lobectomies (P06.167). Neurology, 80(7_supplement). doi:10.1212/wnl.80.7_supplement.p06.167
• Chong, J., Byreddy, S., Coull, B. M., Drake, K., Labiner, D. M., Nokes, B., & Sim, Y. (2013). Assessment of Stroke Risk Factors in Southern Arizona (P02.054). Neurology, 80(7_supplement). doi:10.1212/wnl.80.7_supplement.p02.054
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  OBJECTIVE: To determine differences in concerns about stroke and stroke risk factors among Hispanic and non-Hispanic community health center patients and their preferred sources for medical information and health promotion programs. BACKGROUND: Hispanics have a higher incidence of strokes and poorer prognosis than non-Hispanic whites. To determine the pertinent factors that should be considered for a stroke prevention program, attitudes toward stroke risk factors and preferences for obtaining health related information was collected. DESIGN/METHODS: We collected 272 surveys (141 Hispanic, 131 non-Hispanic) in June 2012 containing quantitative and qualitative questions regarding chronic diseases, preferred sources of care, barriers to care, as well as the types of prevention programs potentially of interest to the patient population. All statistical analyses were performed using IBM SPSS. RESULTS: Proportionately fewer Hispanic (7.7%) than non-Hispanic (16.9%) patients indicated that stroke was among the most important diseases affecting their community. Hispanics were less likely to consider stroke-associated risk factors such as cholesterol and hypertension to be problematic. However, Hispanics endorsed obesity, diabetes and heart disease as important health concerns. Hispanics were more likely to consult their provider for medical advice (p CONCLUSIONS: Despite a higher incidence of stroke, Hispanic concern regarding stroke risk factors is much lower than non-Hispanics. This suggests that knowledge linking risk factors for stroke and incident stroke may be lacking in Hispanic communities. Lessened concern regarding stroke risk factors may contribute to an increase incidence in stroke and to a worse outcome in this population. Hispanics increased interest in health promotion programs may afford one approach to addressing this problem. This data suggest that despite historically worse stroke outcomes, preventative efforts may be beneficial in raising stroke risk factor awareness and improving outcomes in Hispanic patients. Disclosure: Dr. Nokes has nothing to disclose. Dr. Sim has nothing to disclose. Dr. Byreddy has nothing to disclose. Dr. Chong has nothing to disclose. Dr. Drake has nothing to disclose. Dr. Labiner has received research grants from, is a consultant for, or is on the speakers bureau of the following companies: Cyberonics, Eisai, GlaxoSmithKline, UCB Pharm. Dr. Labiner has received research grants from Eisai, UCB Pharm, Sunovian. Dr. Coull has nothing to disclose.
• Chong, J., Hesdorffer, D. C., Thurman, D. J., Lopez, D., Harris, R. B., Hauser, W. A., Labiner, E. T., Velarde, A., & Labiner, D. M. (2013). The prevalence of epilepsy along the Arizona-Mexico border. Epilepsy research, 105(1-2), 206-15.
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  This study describes the epidemiology of epilepsy on the Arizona-Mexico border.
• Kapoor, A., Korya, D., & Labiner, D. M. (2013). Ischemic Stroke in a 28-Year-Old Woman after Smoking Synthetic THC (P06.250). Neurology, 80(7_supplement). doi:10.1212/wnl.80.7_supplement.p06.250
• Labiner, D. M., & Drake, K. W. (2013). Formularies, costs, and quality of care: Formulary restrictions are not the answer, especially for epilepsy. Neurology. Clinical practice, 3(1), 71-74.
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  The goal of treating an individual with epilepsy is to have no seizures and no side effects. Limiting availability of medications appears to be a simple way of controlling costs of patient care. This approach potentially jeopardizes both efficacy and safety. We argue, in this edition of Current Controversies, that limiting costs by restricting formularies is detrimental to the patients from an efficacy, safety, and cost perspective.
• Bateman, L. M., Begley, C. E., Ben-Menachem, E., Berg, A. T., Berkovic, S. F., Cascino, G. D., Drazkowski, J., Edwards, J. C., Engel, J., French, J. A., Gilliam, F. D., Hoerth, M. T., Jehi, L. E., Kanner, A. M., Krauss, G. L., Labiner, D. M., Loddenkemper, T., Luders, H. O., McKhann, G. M., , McLachlan, R., et al. (2012). Overcoming barriers to successful epilepsy management. Epilepsy currents / American Epilepsy Society, 12(4), 158-60.
• Chong, J., Drake, K., Atkinson, P. B., Ouellette, E., & Labiner, D. M. (2012). Social and family characteristics of Hispanics with epilepsy. Seizure, 21(1), 12-6.
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  The purpose of this study is to determine how acculturation, social support, family emotional involvement, perceived family criticism and stigma are associated with epilepsy self-efficacy and depression. A principal components analysis (PCA) was used to describe the salience of these characteristics within a sample of Hispanics with epilepsy. A total of 50 Hispanic adults of Mexican descent identified in our Epilepsy Clinic participated in this study. The PCA identified four distinct types, two were relatively culture-free, and two were distinctly culturally oriented. The first non-culture affiliated type described a well-adjusted group of individuals that tended to be males with moderate self-efficacy, who received social support, and who were unlikely to have depression or feel stigmatized. The second non-culture affiliated type described a dimension in which family emotional involvement tended to co-occur with perceived criticism. The Anglo-oriented group had a family environment that did not appear to criticize the individual with epilepsy and had good self-efficacy. The Mexican-oriented group had high self-efficacy and was unlikely to have depression. Results suggest that acculturation variables must be taken into consideration among ethnic groups because social, psychological and acculturation variables interact in complex ways. Additionally, it is clear that a diagnosis of epilepsy does not automatically lead to poor quality of life, stigma, or depression.
• Helmers, S. L., Begnaud, J., Cowley, A., Corwin, H. M., Edwards, J. C., Holder, D. L., Kostov, H., Larsson, P. G., Levisohn, P. M., De Menezes, M. S., Stefan, H., & Labiner, D. M. (2012). Application of a computational model of vagus nerve stimulation. Acta neurologica Scandinavica, 126(5), 336-43.
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  The most widely used and studied neurostimulation procedure for medically refractory epilepsy is vagus nerve stimulation (VNS) Therapy. The goal of this study was to develop a computational model for improved understanding of the anatomy and neurophysiology of the vagus nerve as it pertains to the principles of electrical stimulation, aiming to provide clinicians with a systematic and rational understanding of VNS Therapy.
• Kleinman, N. L., Sadosky, A., Seid, J., Martin, R. C., & Labiner, D. M. (2012). Costs, work absence, and adherence in patients with partial onset seizures prescribed gabapentin or pregabalin. Epilepsy research, 102(1-2), 13-22.
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  Few studies have examined cost of illness of epileptic partial onset seizures (POS) from the employer perspective or compared users of gabapentin and pregabalin in treatment of POS. This study compares pharmacotherapy, direct/indirect costs, and work absences of patients with POS newly started on gabapentin or pregabalin.
• Labiner, D. M., & Cascino, G. D. (2012). Are neurologists really data driven in selecting epilepsy treatment?. Neurology, 78(16), 1194-5.
• Pennell, P., Klein, A., Browning, N., Baker, G., Clayton-Smith, J., Kalayjian, L., Liporace, J., Privitera, M., Crawford, T., Loring, D., Meador, K., Labiner, D., Moon, J., Sherman, S., Cantrell, D., Silver, C., Goyal, M., Schoenberg, M., Pack, A., , Palmese, C., et al. (2012). Differential effects of antiepileptic drugs on neonatal outcomes. Epilepsy and Behavior, 24(4). doi:10.1016/j.yebeh.2012.05.010
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  Offspring of women with epilepsy (WWE) on AEDs are at increased risks for major congenital malformations and reduced cognition. They may be at risk for other adverse neonatal outcomes. Women with epilepsy on carbamazepine (CBZ), lamotrigine (LTG), phenytoin (PHT), or valproate (VPA) monotherapy were enrolled in a prospective, observational, multicenter study of the neurodevelopmental effects of AEDs. The odds ratio for small for gestational age (SGA) was higher for VPA vs. PHT, VPA vs. LTG, and CBZ vs. PHT. Microcephaly rates were elevated to 12% for all newborns and at 12. months old, but normalized by age 24. months. Reduced Apgar scores occurred more frequently in the VPA and PHT groups at 1. min, but scores were near normal in all groups at 5. min. This study demonstrates increased risks for being born SGA in the VPA and CBZ groups, and transiently reduced Apgar scores in the VPA and PHT groups. Differential risks among the AEDs can help inform decisions about AED selection for women during childbearing years. © 2012 Elsevier Inc..
• Labiner, D., & Helmers, S. (2011). Reply from the authors. Neurology, 76(6). doi:10.1212/WNL.0b013e3181fe719e
• Ouellette, E., Chong, J., Drake, K., & Labiner, D. M. (2011). Emergency department care of seizure patients: demographic trends in southern Arizona. Epilepsy & behavior : E&B, 21(4), 382-6.
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  The aim of this study was to describe the epidemiology of epilepsy and characteristics of patients with seizures who presented at the Yuma Regional Medical Center Emergency Department (YRMC ED) from 2005 to 2008. A seizure diagnosis was present in 2.7% of the patients, and accounted for 1.7% of all ED visits. Visits by patients identified as having epilepsy accounted for 0.3% of all ED visits. Patients with seizures were 2.8 times more likely to have used the ED for 2 or more years of the study period compared with control patients. Patients with at least one ED visit because of seizures were more likely to have multiyear visits, 43.6% visiting the ED within 2 or more years. Patients with epilepsy and seizures were significantly younger than the no-seizure control group. Patients who had ever been admitted to the ED for seizures or epilepsy had higher ED utilization even if the subsequent admissions were not seizure related.
• Stern, J. M., Labiner, D. M., Gilliam, F. G., Penovich, P. E., Onofrey, M., Eagan, C. A., & Holmes, G. L. (2011). More effective assessment of adverse effects and comorbidities in epilepsy: results of a Phase II communication study. Epilepsy & behavior : E&B, 22(3), 552-6.
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  Research was conducted to evaluate conversations about epilepsy between community-based neurologists and patients. Adverse effects of antiepileptic drugs and mood/behavioral issues were infrequently discussed, and neurologists and patients disagreed about these issues postvisit. Follow-up research was conducted to assess the impact of a previsit assessment tool on discussions of epilepsy. Twenty neurologists reviewed a tool incorporating questions from validated instruments (Adverse Events Profile [AEP] and Neurological Disorders Depression Inventory for Epilepsy [NDDI-E]). Naturally occurring interactions between neurologists and 60 patients were recorded. Neurologists and patients were interviewed separately. All components were transcribed and analyzed using sociolinguistics. Using the previsit assessment tool increased the number of discussions about adverse effects and mood/behavioral issues and increased neurologist-patient agreement about issues postvisit. Visit length did not increase significantly when the tool was used. Ten months after follow-up research, 50% of neurologists reported continuing to use the tool in everyday practice with patients with epilepsy.
• Thurman, D. J., Beghi, E., Begley, C. E., Berg, A. T., Buchhalter, J. R., Ding, D., Hesdorffer, D. C., Hauser, W. A., Kazis, L., Kobau, R., Kroner, B., Labiner, D., Liow, K., Logroscino, G., Medina, M. T., Newton, C. R., Parko, K., Paschal, A., Preux, P., , Sander, J. W., et al. (2011). Standards for epidemiologic studies and surveillance of epilepsy. Epilepsia, 52 Suppl 7, 2-26.
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  Worldwide, about 65 million people are estimated to have epilepsy. Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy. However, different definitions and epidemiologic methods complicate the tasks of these studies and their interpretations and comparisons. The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population-based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health. We discuss: (1) conceptual and operational definitions of epilepsy, (2) data resources and recommended data elements, and (3) methods and analyses appropriate for epidemiologic studies or the surveillance of epilepsy. Variations in these are considered, taking into account differing resource availability and needs among countries and differing purposes among studies.
• Chong, J., Kudrimoti, H. S., Lopez, D. C., & Labiner, D. M. (2010). Behavioral risk factors among Arizonans with epilepsy: Behavioral Risk Factor Surveillance System 2005/2006. Epilepsy & behavior : E&B, 17(4), 511-9.
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  Modifiable risk factors to help improve health outcomes for people with epilepsy in Arizona were identified using the 2005-2006 Arizona Behavioral Risk Factor Surveillance System (BRFSS). Of 9524 adults who participated in this survey, 125 reported ever being diagnosed with epilepsy (lifetime prevalence=1.3%, 95% CI=1.1-1.6%). Individuals with active epilepsy (those who had seizures in the prior 3 months and/or were taking anticonvulsants) had an overall lower quality of life. This likely resulted from a large number of medical comorbidities and poor mental and physical health days. Regression models suggested that for individuals with active epilepsy, physical activity was associated with fewer activity-limited days, whereas for individuals with inactive epilepsy, medical comorbidity was positively associated with activity-limited days. Further research is needed to increase the reliability of the findings.
• Cramer, J. A., Eagan, C. A., Gilliam, F., Holmes, G. L., Labiner, D. M., Mathis, E., Onofrey, M., Penovich, P. E., & Stern, J. M. (2010). Corrigendum to ‘‘Conversations between community-based neurologists and patients with epilepsy: Results of an observational linguistic study” [Epilepsy & Behavior 16, Issue 2 (2009) 315–320]. Epilepsy & Behavior, 17(2), 305. doi:10.1016/j.yebeh.2009.11.004
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  On page 1, the first line of the first paragraph in the right column should read ‘‘Prior to study initiation, a working group consisting of epilepsy experts (F.G., P.P., J.S., G.H., D.L., and J.C.) and linguistic specialists (C.E., M.O. and E.M.) convened to discuss study objectives, methodology, and analyses, with the goal of studying communication surrounding epilepsy in real-world office visits,” instead of ‘‘Prior to study initiation, a working group consisting of epilepsy experts (F.G., P.P., D.L., G.H., and J.C.) and linguistic specialists (C.E., M.O., and E.M.) convened to discuss study objectives, methodology, and analyses, with the goal of studying communication surrounding epilepsy in real-world office visits.”
• Drake, K., & Labiner, D. M. (2010). Lamotrigine: Once Daily Add-on Therapy for Epilepsy in Adults Experiencing Partial Onset Seizures. Clinical Medicine Reviews in Therapeutics, 2010(2), 21-30. doi:10.4137/cmrt.s1645
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  Lamotrigine (LTG) is a newer antiepileptic medication that has multiple indications for epilepsy including add-on therapy for partial onset epilepsy in adults. The primary antiseizure mechanism of action is blockage of voltage-sensitive sodium channels which stabilizes neuronal membranes and inhibits excitatory presynaptic neurotransmitter release. It has linear pharmacokinetics with rapid absorption with a tmax < 3 hours and no first pass metabolism. Bioavailability is nearly 100% with approximately 55% protein binding. Glucuronidation is the mechanism of elimination with a half life of approximately 24 hours. Co administration with an enzyme inducer shortens the half life to approximately 15 hours while enzyme inhibitors such as valproic acid lengthen the half life to over 60 hours. Immediate release preparations can be given once a day alone or with enzyme inhibitors and the recently available extended release preparation can be given once a day even with enzyme inducers. Pregnancy and oral contraceptive pills significantly alter the metabolism of LTG. Efficacy has been demonstrated in multiple clinical trials with a satisfactory safety profile. The most commonly reported CNS related adverse events include dizziness, diplopia, ataxia, headache and somnolence. The most commonly reported non-CNS related adverse event is rash, which is typically benign and self limited with only rare occurrence of Stevens-Johnson syndrome. LTG is a particularly good choice of antiepileptic medication in persons with comorbid mood disorders as it also has an indication for treatment of bipolar disorder and in the elderly population due to its tolerability, lack of interaction with anticoagulants and antiplatelet agents and linear pharmacokinetics.
• Drake, K., & Labiner, D. M. (2010). Severe constipation associated with the use of rufinamide (Banzel) in an adolescent. Epilepsy & behavior : E&B, 18(1-2), 132.
• Helmers, S. L., Paradis, P. E., Manjunath, R., Duh, M. S., Lafeuille, M., Latrémouille-Viau, D., Lefebvre, P., & Labiner, D. M. (2010). Economic burden associated with the use of generic antiepileptic drugs in the United States. Epilepsy & behavior : E&B, 18(4), 437-44.
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  This study quantifies the economic burden associated with generic-versus-branded use of antiepileptic drugs (AEDs) in the United States. Adult patients with epilepsy receiving carbamazepine, gabapentin, phenytoin, primidone, or zonisamide were selected from the PharMetrics database. By use of an open-cohort design, patients were classified into mutually exclusive periods of generic-versus-branded AED use. Annualized cost differences (CDs) between periods were estimated using multivariate regressions. Results were stratified into stable versus unstable epilepsy and newer-generation versus older-generation AEDs. A total of 33,625 patients (52% male, mean age=51 years) were observed. Periods of generic AED treatment were associated with higher medical service costs (adjusted CD [95% CI]=$3186 [$2359; $4012]), stable pharmacy costs ($69 [$-34; $171]), and greater total costs ($3254 [$2403; $4105]) versus brand use. Epilepsy-related costs represented 30% of incremental costs. Similar findings were observed for patients with stable and unstable epilepsy and users of newer-generation and older-generation AEDs. Significantly higher health care costs were observed during generic AED use across seizure control and AED subgroups.
• Labiner, D. M., Bagic, A. I., Herman, S. T., Fountain, N. B., Walczak, T. S., Gumnit, R. J., & , N. A. (2010). Essential services, personnel, and facilities in specialized epilepsy centers--revised 2010 guidelines. Epilepsia, 51(11), 2322-33.
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  This document was developed by the members of the Committee to Revise the Guidelines for Services, Personnel, and Facilities at Specialized Epilepsy Centers. After discussions with the general membership they were adopted by the Board of the National Association of Epilepsy Centers. The Guidelines will be reviewed and updated when considered necessary by the Board.
• Labiner, D. M., Paradis, P. E., Manjunath, R., Duh, M. S., Lafeuille, M., Latrémouille-Viau, D., Lefebvre, P., & Helmers, S. L. (2010). Generic antiepileptic drugs and associated medical resource utilization in the United States. Neurology, 74(20), 1566-74.
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  To evaluate whether generic substitution was associated with any difference in medical resource utilization for 5 widely used antiepileptic drugs (AEDs) in the United States.
• Gilliam, F., Penovich, P. E., Eagan, C. A., Stern, J. M., Labiner, D. M., Onofrey, M., Holmes, G. L., Mathis, E., & Cramer, J. (2009). Conversations between community-based neurologists and patients with epilepsy: results of an observational linguistic study. Epilepsy & behavior : E&B, 16(2), 315-20.
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  An in-office linguistic study was conducted to assess neurologist-patient discussions of epilepsy. Naturally occurring interactions among 20 neurologists and 60 of their patients with epilepsy were recorded. Participants were interviewed separately postvisit. Transcripts were analyzed using sociolinguistic techniques. Of 59 patients taking antiepileptic drugs previsit, 44 (75%) discussed side effects with their neurologist. Side effect discussions were most often neurologist initiated. Postvisit, patients and neurologists often disagreed about which side effects were experienced. The presence of a caregiver (e.g., spouse) usually resulted in lengthier, more detailed discussions of side effects, without drastically increasing overall visit length. Discussions of mood- and behavior-related comorbidities occurred infrequently (14 of 60 visits); postvisit, neurologists stated that they felt that management of these conditions was outside their area of expertise. Communication gaps observed in discussions of epilepsy and its treatment warrant further exploration. Additional research is currently underway to assess the efficacy of a previsit assessment tool.
• Labiner, D. M., Ettinger, A. B., Fakhoury, T. A., Chung, S. S., Shneker, B., Tatum Iv, W. O., Mitchell Miller, J., Vuong, A., Hammer, A. E., & Messenheimer, J. A. (2009). Effects of lamotrigine compared with levetiracetam on anger, hostility, and total mood in patients with partial epilepsy. Epilepsia, 50(3), 434-42.
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  To assess anger/hostility during treatment with lamotrigine adjunctive therapy versus levetiracetam adjunctive therapy in patients with partial seizures.
• Thayer, J. F., Sollers, J. J., Labiner, D. M., Weinand, M., Herring, A. M., Lane, R. D., & Ahern, G. L. (2009). Age-related differences in prefrontal control of heart rate in humans: a pharmacological blockade study. International journal of psychophysiology : official journal of the International Organization of Psychophysiology, 72(1), 81-8.
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  The Neurovisceral Integration Model is based on the premise of significant central nervous system-peripheral nervous system interactions. In support of this model we have previously shown that the prefrontal cortex tonically inhibits cardioacceleratory circuits as evidenced by increased heart rate (HR) when the prefrontal cortex is inactivated by injections of sodium amobarbitol (ISA) into the internal carotid artery. In this report we re-examine these data to investigate possible age-related differences in the prefrontal control of HR in humans. Seventy-three patients were divided into three groups based on a tertile split with mean ages of 20, 34, and 47, respectively. There were significant age-related differences in cortical control of HR as evidenced by a significant three way interaction of age (young, middle, old) by side (left versus right) by time (baseline and epochs 1-10 of inactivation) [Roy's Root (10,59)=0.378, p=0.028]. Results showed significant HR increases that did not differ between hemispheres in the youngest age group, significant increases in the middle age group that were larger in the right hemisphere than in the left, and significant HR increases in the oldest group in the right hemisphere only. The findings suggest important age-related differences in cortical inhibitory control of HR that appear less lateralized in the youngest group and significantly attenuated in the oldest age group. These results have important implications for the understanding of age-related differences in cognitive, affective, behavioral, and physiological functioning. In addition they support the importance of investigating central nervous system-peripheral nervous system relationships.
• Weinand, M., Serxner, B., Labiner, D., & Ahern, G. (2009). Interhemispheric propagation time and temporal lobe epileptogenicity. Pathophysiology : the official journal of the International Society for Pathophysiology / ISP, 16(1), 39-42.
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  Long-term subdural electroencephalographic (EEG) recording was performed in a series of patients with medically intractable complex partial seizures to test the hypothesis that ictal interhemispheric propagation time (IHPT) is correlated with temporal lobe epileptogenicity. In 41 patients, the duration from initial subdural EEG seizure onset to the first appearance of subdural EEG epileptic activity in the contralateral hemisphere (IHPT) was measured in seconds and analyzed for a quantitative relationship to temporal lobe seizure interval (frequency⁻¹), in hours. A statistically significant, nonlinear correlation between IHPT and seizure interval was found (Arctan y=-0.009x²+0.598x+75.187, y=IHPT, in seconds, x=seizure interval, in hours, r=0.326, d.f.=39, t=2.15, p
• Antonucci, S. M., Beeson, P. M., Labiner, D. M., & Rapcsak, S. Z. (2008). Lexical retrieval and semantic knowledge in patients with left inferior temporal lobe lesions. Aphasiology, 22(3), 281-304.
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  BACKGROUND: It has been proposed that anomia following left inferior temporal lobe lesions may have two different underlying mechanisms with distinct neural substrates. Specifically, naming impairment following damage to more posterior regions (BA 37) has been considered to result from a disconnection between preserved semantic knowledge and phonological word forms (pure anomia), whereas anomia following damage to anterior temporal regions (BAs 38, 20/21) has been attributed to the degradation of semantic representations (semantic anomia). However, the integrity of semantic knowledge in patients with pure anomia has not been demonstrated convincingly, nor were lesions in these cases necessarily confined to BA 37. Furthermore, evidence of semantic anomia often comes from individuals with bilateral temporal lobe damage, so it is unclear whether unilateral temporal lobe lesions are sufficient to produce significant semantic impairment. AIMS: The main goals of this study were to determine whether anomia following unilateral left inferior temporal lobe damage reflected a loss of semantic knowledge or a post-semantic deficit in lexical retrieval and to identify the neuroanatomical correlates of the naming impairment. METHODS #ENTITYSTARTX00026; PROCEDURES: Eight individuals who underwent left anterior temporal lobectomy (L ATL) and eight individuals who sustained left posterior cerebral artery strokes (L PCA) completed a battery of language measures that assessed lexical retrieval and semantic processing, and 16 age- and education-matched controls also completed this battery. High-resolution structural brain scans were collected to conduct lesion analyses. OUTCOMES #ENTITYSTARTX00026; RESULTS: Performance of L ATL and L PCA patients was strikingly similar, with both groups demonstrating naming performance ranging from moderately impaired to unimpaired. Anomia in both groups occurred in the context of mild deficits to semantic knowledge, which manifested primarily as greater difficulty in naming living things than nonliving things and greater difficulty in processing visual/perceptual as opposed to functional/associative semantic attributes. Lesion analyses indicated that both patient groups sustained damage to anterior inferior temporal lobe regions implicated in semantic processing. CONCLUSIONS: These results contribute to a better understanding of the cognitive mechanism of naming impairment in patients with temporal lobe damage and support the notion that pure anomia and semantic anomia represent two endpoints along a continuum of semantic impairment. Unilateral left temporal lobe lesions in our patients resulted in relatively mild semantic deficits that were apparent primarily in lexical production tasks, whereas severe semantic impairment likely requires bilateral temporal lobe damage.
• Sankar, R., Bainbridge, J. L., Bebin, M., Benbadis, S. R., Cantrell, D. T., Faught, R. E., Glauser, T. A., Gruenthal, M., Hershkowitz, L. L., Holmes, G. L., Husain, A. M., Labiner, D. M., Montouris, G., Naritoku, D. K., Olson, B. J., Pellock, J. M., Penovich, P., Privitera, M., Ramsay, R. E., , Rho, J. M., et al. (2008). Core elements of epilepsy diagnosis and management: expert consensus from the Leadership in Epilepsy, Advocacy, and Development (LEAD) faculty.. Current medical research and opinion, 24(12), 3463-77. doi:10.1185/03007990802561148
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  Although epilepsy is relatively common, only a limited number of specialized epilepsy centers exist in the United States. Therefore, epilepsy diagnosis and management frequently occur in the community setting. This can complicate patient management and suboptimal care is a potential concern. Delayed recognition and inadequate treatment increase the risk of subsequent seizures, brain damage, disability, and death from seizure-related injuries. To identify core elements of epilepsy management that should be offered to all patients, the Leadership in Epilepsy, Advocacy, and Development (LEAD) faculty assessed current practical issues and identified practices to improve patient care and outcomes..This paper presents a consensus opinion formed from a survey of 26 current LEAD faculty members, who answered 105 questions about epilepsy diagnosis and patient evaluation, treatment decisions, lifelong monitoring, and the management of special patient subgroups. Consensus agreement was concluded when >or=50% of the faculty provided the same answer. The results were compiled and areas of consensus are included in this report. The recommendations provided in this commentary are limited by the scope of the survey..Consensus was reached on several minimum standard patient management practices. Primary among these minimum standards of care is the need for diagnosis including a detailed medical history, neurological examination, discussions with caregivers, and diagnostic tests including electroencephalograms and magnetic resonance imaging. As the overall goals of therapy include seizure freedom, minimizing side effects, and improving quality of life and long-term safety, therapy decisions should consider parameters that affect these goals, including potential adverse effects of therapy. Antiepileptic drug selection should consider coexisting conditions for possible exacerbation of disease and potential drug-drug interactions..The core elements of epilepsy management identified here suggest minimum standards that can be used across all settings to improve consistency and quality of epilepsy diagnosis and care.
• Ahern, G. L., & Labiner, D. M. (2007). Vagus nerve stimulation therapy in depression and epilepsy: therapeutic parameter settings.. Acta neurologica Scandinavica, 115(1), 23-33. doi:10.1111/j.1600-0404.2006.00732.x
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  Vagus nerve stimulation (VNS) therapy is an effective adjunctive treatment for chronic or recurrent treatment-resistant depression in adults, and for pharmacoresistant epilepsy in adults and adolescents. VNS therapy is administered through an implanted pulse generator that delivers programmed electrical pulses through an implanted lead to the left vagus nerve. Programmable pulse parameters include output current, frequency, pulse width, and ON/OFF times. Within a range of typical values, individual patients respond best to different combinations of parameter settings. The physician must identify the optimum settings for each patient while balancing the goals of maximizing efficacy, minimizing side effects, and preserving battery life. Output current is gradually increased from 0.25 mA to the maximum tolerable level (maximum, 3.5 mA); typical therapeutic settings range from 1.0 to 1.5 mA. Greater output current is associated with increased side effects, including voice alteration, cough, a feeling of throat tightening, and dyspnea. Frequency is typically programmed at 20 Hz in depression and 30 Hz in epilepsy. Pulse width is typically 250 or 500 micros. The recommended initial ON time is 30 s, followed by 5 min OFF; OFF time > ON time is recommended. As with pharmacotherapy, VNS therapy must be adjusted in a gradual, systematic fashion to individualize therapy for each patient.
• Ahern, G. L., Farley, C., Hussain, N. S., Labiner, D. M., & Weinand, M. E. (2007). Time from ictal subdural EEG seizure onset to clinical seizure onset: an electrocorticographic time factor associated with temporal lobe epileptogenicity.. Neurological research, 29(8), 862-70. doi:10.1179/016164107x223548
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  Long-term subdural video/electroencephalographic (EEG) monitoring was performed in a series of patients with medically intractable complex partial seizures, in a study of diagnostic accuracy, to test the hypothesis that the time from ictal subdural EEG seizure onset to clinical seizure onset (ECOT) is correlated with temporal lobe epileptogenicity and confirm measures of validity of ECOT for predicting seizure-free outcome following anterior temporal lobectomy and amygdalohippocampectomy (ATL/AH). In 34 patients with refractory temporal lobe epilepsy, subdural EEG monitoring localized the ictal epileptogenic focus to a single temporal lobe. In each patient, ECOT was analysed for correlation with temporal lobe epileptogenicity as measured by seizure interval in hours. Patients in whom ECOT was equal to or less than the mean (i.e. subdural EEG seizure onset preceding clinical seizure onset by at least 11.7 seconds) had a significantly greater likelihood of becoming seizure-free following ATL/AH compared to patients in whom ECOT was greater than the mean (i.e. subdural EEG seizure onset preceding clinical seizure onset by less than 11.7 seconds) (x(2) = 5.78, p
• Atkinson, P. B., & Labiner, D. M. (2007). Shocking the Wandering Nerve Vagus Nerve Stimulation After a Decade of Widespread Use. European neurological review, 14. doi:10.17925/enr.2007.00.01.14
• Drazkowski, J. F., Hinni, M. L., Hoerth, M. T., Labiner, D. M., Sirven, J. I., & Smith, B. E. (2007). Vocal cord paralysis after vagus nerve stimulator battery replacement successfully treated with medialization thyroplasty.. Clinical neurology and neurosurgery, 109(9), 788-90. doi:10.1016/j.clineuro.2007.06.004
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  The vagus nerve stimulator (VNS) has been used effectively for partial seizure disorders, however many patients suffer from side effects of alterations in voice. This case describes a new remediable adverse effect of the VNS. A patient with medically intractable epilepsy had improvement of his seizure control with VNS therapy after titrating him to a high output and rapid cycling paradigm with essentially no side effects. After a battery replacement, he was restarted on his previous settings and subsequently developed a hoarse voice. He was found to have complete left vocal cord paralysis, an adverse effect attributed to a rapid titration to his previous high output and rapid cycling paradigm. This side effect has not been previously described in the literature. The patient subsequently had a medialization thyroplasty with resolution of his hoarse voice.
• Hayes, S. M., Melin, J. D., Dupuis, M., Murray, S., & Labiner, D. M. (2007). Assessing the true learning needs of health care professionals in epilepsy care. Epilepsy & behavior : E&B, 11(3), 434-41.
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  This needs assessment, initiated by the American Epilepsy Society (AES) in cooperation with AXDEV Group Inc. (AXDEV), used a mixed-method approach to explore the educational and clinical practice needs of health care professionals in epilepsy care and to identify significant barriers to caring for people with epilepsy. The multiphase assessment began with key informant interviews with AES educational leaders. In Phase II, 26 stakeholders, including epileptologists, neurologists, professionals in epilepsy care, and people with epilepsy, shared their experiences in epilepsy care during four focus groups at the AES annual meeting. In Phase III, a quantitative online survey based on Phase II results was distributed to 228 respondents, including epileptologists (n=84), neurologists (n=55), professionals in epilepsy care (n=69), and others (n=20). Results of the comprehensive analysis of Phase III quantitative data are presented here. They reveal the unmet needs of health care professionals in this therapeutic domain and are discussed in terms of their implications for epilepsy care.
• Weinand, M., Farley, C., Hussain, N., Labiner, D., & Ahern, G. (2007). Time from ictal subdural EEG seizure onset to clinical seizure onset: An electrocorticographic time factor associated with temporal lobe epileptogenicity. Neurological Research, 29(8). doi:10.1179/016164107X223548
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  Long-term subdural video/electroencephalographic (EEC) monitoring was performed in a series of patients with medically intractable complex partial seizures, in a study of diagnostic accuracy, to test the hypothesis that the time from ictal subdural EEG seizure onset to clinical seizure onset (ECOT) is correlated with temporal lobe epileptogenicity and confirm measures of validity of ECOT for predicting seizure-free outcome following anterior temporal lobectomy and amygdalohippocampectomy (ATL/AH). In 34 patients with refractory temporal lobe epilepsy, subdural EEG monitoring localized the ictal epileptogenic focus to a single temporal lobe. In each patient, ECOT was analysed for correlation with temporal lobe epileptogenicity as measured by seizure interval in hours. Patients in whom ECOT was equal to or less than the mean (i.e. subdural EEG seizure onset preceding clinical seizure onset by at least 11.7 seconds) had a significantly greater likelihood of becoming seizure-free following ATL/AH compared to patients in whom ECOT was greater than the mean (i.e. subdural EEG seizure onset preceding clinical seizure onset by less than 11.7 seconds) (x2=5.78, p
• Ahern, G. L., Hussain, N. S., Labiner, D. M., & Weinand, M. E. (2006). Correlation of electrocorticographic to clinical seizure onset and interhemispheric propagation times in temporal lobe epilepsy.. Pathophysiology : the official journal of the International Society for Pathophysiology, 13(4), 233-6. doi:10.1016/j.pathophys.2006.08.002
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  This study was performed to test the hypothesis that, in human temporal lobe epilepsy, electrocorticographic time factors involved in the ictal EEG to clinical ictal transition (electrocorticographic to clinical seizure onset time, ECOT) and the interhemispheric propagation of epileptic activity (interhemispheric propagation time, IHPT), which are independently correlated with temporal lobe epileptogenicity and predictive of seizure-free outcome following temporal lobectomy, are correlated with one another in a quantitative fashion. A series of 37 patients with medically intractable temporal lobe seizures was studied with long-term subdural videoelectroencephalographic monitoring. Temporal lobe seizure interhemispheric propagation time (IHPT) was found to be a negative, exponential function of electrocorticographic to clinical seizure onset time (ECOT) (f(x)=8.201x10(-0.016x), r=0.347, d.f.=35, t=2.19, p
• Ahern, G. L., Labiner, D. M., & Torres, M. R. (2005). Seizures and Epilepsy: An Approach to Diagnosis and Management. Journal of Clinical Outcomes Management, 12(2), 103-113.
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  Epilepsy is a chronic brain disorder characterized by recurrent seizures. A seizure is an abnormal discharge of cortical neurons that can result in a variety of clinical manifestations. Epilepsy affects more than 2.5 million individuals in the United States, or approximately 1% of the population. It has been estimated that nearly 10% of the population will have a seizure at some point in their lifetime [1]. The economic impact of epilepsy is considerable, reaching $12.5 billion in direct and indirect costs [2]. Many patients with a single seizure or with recurrent seizures (epilepsy) can be safely and appropriately managed in the primary care setting. In this article, we present a case that illustrates key diagnostic and therapeutic considerations in the management of an individual with seizures.
• Ahern, G. L., Gonzalez-portillo, G., Labiner, D. M., Rivero, S., & Weinand, M. E. (2004). Normalization of periictal bihemispheric cerebral perfusion in temporal lobe epilepsy.. Pathophysiology : the official journal of the International Society for Pathophysiology, 11(1), 31-34. doi:10.1016/j.pathophys.2003.12.001
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  Under normal circumstances, cerebral blood flow (CBF), between the two hemispheres is coupled in a direct (i.e. positive slope), linear fashion. However, in temporal lobe epilepsy, the relationship between the two temporal cortices, during the interictal and postictal periods, is the inverse of normal (i.e. correlation is with negative slope and linear). Long-term combined temporal lobe thermal diffusion flowmetry (TDF) subdural regional cerebral blood flow and electroencephalographic (EEG) recording was performed to test the hypothesis that, during the 10min periictal period (i.e. 5min before and 5min following clinical seizure onset), the cerebral perfusion relationship between epileptic and nonepileptic cortex returns to normal (i.e. becomes direct, with positive slope, and linear). A consecutive series of 13 patients with complex partial epilepsy was studied. During continuous monitoring of clinical phenomenology in time sequence with subdural CBF/EEG, the 10min periictal period was characterized by a direct, linear correlation between epileptic and nonepileptic temporal cortical blood flow ( [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] ). The fact that this pertubation in the CBF relationship between the bilateral temporal cortices begins prior to and continues for 5min following clinical and subdural EEG seizure onset raises the interesting possibility that normalization of periictal bilateral cerebral perfusion may be associated with temporal lobe epileptogenesis.
• Carpenter, L. L., Moreno, F. A., Kling, M. A., Anderson, G. M., Regenold, W. T., Labiner, D. M., & Price, L. H. (2004). Effect of vagus nerve stimulation on cerebrospinal fluid monoamine metabolites, norepinephrine, and gamma-aminobutyric acid concentrations in depressed patients. Biological Psychiatry, 56(Issue 6). doi:10.1016/j.biopsych.2004.06.025
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  Vagus nerve stimulation (VNS) has shown promising antidepressant effects in treatment-resistant depression, but the mechanisms of action are not known. Cerebrospinal fluid (CSF) studies in epilepsy patients show that VNS alters concentrations of monamines and γ-aminobutyric acid (GABA), neurotransmitter systems possibly involved in the pathogenesis of depression. Twenty-one adults with treatment-resistant, recurrent, or chronic major depression underwent standardized lumbar puncture for collection of 12 mL CSF on three separate but identical procedure days during participation in the VNS D-02 clinical trial. All subjects remained on stable regimens of mood medications. Collections were made at baseline (2 weeks after surgical implantation but before device activation), week 12 (end of the acute-phase study), and week 24. Cerebrospinal fluid concentrations of norepinephrine (NE), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were determined with high-performance liquid chromatography. Concentrations of GABA were assayed with mass spectrometry. Comparison of sham versus active VNS revealed a significant (mean 21%) VNS-associated increase in CSF HVA. Mean CSF concentrations of NE, 5-HIAA, MHPG, and GABA did not change significantly. Higher baseline HVA/5-HIAA ratio predicted worse clinical outcome. Although several of the CSF neurochemical effects we observed in this VNS study were similar to those described in the literature for antidepressants and electroconvulsive therapy, the results do not suggest a putative antidepressant mechanism of action for VNS.
• Reminger, S. L., Kaszniak, A. W., Labiner, D. M., Littrell, L. D., David, B. T., Ryan, L., Herring, A. M., & Kaemingk, K. L. (2004). Bilateral hippocampal volume predicts verbal memory function in temporal lobe epilepsy. Epilepsy and Behavior, 5(Issue 5). doi:10.1016/j.yebeh.2004.06.006
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  The present study used quantitative volume estimates of the hippocampus based on structural magnetic resonance imaging (MRI) to predict memory performance of individuals with epilepsy of temporal lobe origin (TLE). Twenty individuals with TLE completed standardized neuropsychological tests and a quality of life inventory, and participated in a brain MRI protocol designed to obtain high-resolution images of the hippocampus. The combined volume of the left and right hippocampi was found to be the best predictor of objective verbal memory performance. This finding is consistent with the functional adequacy model of hippocampal function. In contrast, the asymmetry between right and left hippocampal volume was the best predictor of subjective ratings of cognitive functioning, which is consistent with the functional reserve model. The collective and complementary functions of the left and right hippocampi merit further exploration in prospective studies of memory function and TLE. © 2004 Elsevier Inc. All rights reserved.
• Drazkowski, J. F., Fisher, R. S., Sirven, J. I., Demaerschalk, B. M., Uber-Zak, L., Hentz, J. G., & Labiner, D. (2003). Seizure-related motor vehicle crashes in Arizona before and after reducing the driving restriction from 12 to 3 months. Mayo Clinic Proceedings, 78(Issue 7). doi:10.4065/78.7.819
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  Objective: To evaluate whether changing the seizurefree interval in Arizona from 12 months to 3 months affected the number of seizure-related motor vehicle crashes. Methods: We performed a time trend study with analysis of motor vehicle crash reports in the state of Arizona 3 years before (1991-1993) and 3 years after (1994-1996) the seizure-free interval was decreased from 12 to 3 months. The number of motor vehicle crashes related to seizures, other medical conditions, and other nonmedical crashes was compared before and after the law changed. Other population trends, including population growth, registered vehicles, and registered drivers, are also reported. Results: Seizure-related crashes increased from 125 to 136 for the 3 years before and 3 years after the law changed, respectively. The total rate of seizure-related crashes did not increase on the basis of an incidence rate difference of -0.03/109 miles (95% confidence interval [CI], -0.30 to 0.24) and a relative risk of 0.98 (95% CI, 0.77 to 1.24). Over the same time interval, crashes related to other medical conditions increased from 288 to 310, respectively, for an incidence rate difference of -0.09/109 miles (95% CI, -0.51 to 0.33) and a relative risk of 0.97 (95% CI, 0.82 to 1.13). Fatalities due to seizure-related crashes decreased during the same period, whereas the number of multiple vehicle crashes increased. Conclusion: The rate of seizure-related crashes did not significantly increase in the state of Arizona after the seizure-free interval was reduced from 12 to 3 months.
• Labiner, D. (2002). Lamotrigine and rash: Scratching beneath the surface. Journal of Clinical Psychiatry, 63(11). doi:10.4088/JCP.v63n1109
• Labiner, D. M. (2002). Herbal Medicines and Epilepsy. To the Editor.. Epilepsy & behavior : E&B, 3(2), 200-201. doi:10.1006/ebeh.2002.0326
• Labiner, D. M., Weinandt, M. E., Brainerd, C. J., Ahern, G. L., Herring, A. M., & Melgar, M. A. (2002). Prognostic value of concordant seizure focus localizing data in the selection of temporal lobectomy candidates. Neurological Research, 24(Issue 8). doi:10.1179/016164102101200843
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  This study was performed to test the hypotheses that (a) resection of the temporal lobe epileptic focus, amenable to noninvasive as opposed to invasive localization, is associated with superior seizure outcome and (b) that quadruple (versus lesser degrees of) concordance of seizure focus localizing data predicts superior seizure-free outcome. Eighty-three patients underwent invasive (subdural-EEG) and/or noninvasive (video/scalp-EEG, SPECT, PET, MRI, neuropsychological testing) evaluation. All patients underwent anterior temporal lobectomy and amygdalohippocampectomy (A TL/AH) and seizure outcome was assessed at minimum one-year follow-up. At 34.8±2.5 months following ATL/AH, outcome was superior for patients in whom the seizure focus was amenable to noninvasive compared to invasive localization (80% versus 40% seizure-free, X2= 14.03, p < 0.05). Seizure outcome was superior for patients with quadruple, compared to all lesser degrees of, concordance of seizure focus localizing data (85% versus 51% seizure-free, X2 = 7.34, p < 0.05). Post-A TL/AH, seizure outcome is superior in patients (1) harboring an epileptic focus amenable to noninvasive localization and (2) with quadruple concordance of seizure focus localizing data. These findings support the development of temporal lobectomy selection criteria including up to four invasive and/or noninvasive concordant seizure focus localizing techniques.
• McAuley, J., Moore, J., Labiner, D., & Spinella, M. (2002). Herbal medicine and epilepsy (multiple letters) [3]. Epilepsy and Behavior, 3(2). doi:10.1006/ebeh.2002.0325
• Ahern, G. L., Labiner, D. M., & Weinand, M. E. (2001). Integration of Perceptual and Mnemonic Dysfunction: Sensory Auras Are Associated with Left Hemispheric Memory Impairment.. Epilepsy & behavior : E&B, 2(5), 423-432. doi:10.1006/ebeh.2001.0236
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  Memory function during the intracarotid amobarbital test was studied to test the hypothesis that left hemisphere memory impairment is associated with sensory auras. In a series of 37 patients undergoing preoperative evaluation for epilepsy surgery, the quantitative memory scores during amobarbital inactivation of right and left hemisphere were analyzed for correlation with habitual epileptic auras classified as either (a) experiential, forced emotion, or whole-body dysphoria or (b) sensory hallucinations and/or illusions or localized dysesthesias. The left hemispheric memory score impairment was significantly worse in association with auras classified as sensory hallucinations and/or illusions or localized dysesthesias compared with auras classified as experiential, forced emotion, or whole-body dysphoria (P < 0.05). This finding may assist in predicting left-sided hemispheric memory dysfunction in patients with seizures beginning as auras involving sensory material. The results suggest an integration of perceptual and mnemonic dysfunction in which sensory auras are associated with left hemispheric memory impairment.
• Ahern, G. L., Sollers, J. J., Lane, R. D., Labiner, D. M., Herring, A. M., Weinand, M. E., Hutzler, R., & Thayer, J. F. (2001). Heart rate and heart rate variability changes in the intracarotid sodium amobarbital test. Epilepsia, 42(Issue 7). doi:10.1046/j.1528-1157.2001.042007912.x
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  Purpose: Changes in heart rate and heart rate variability have been found in prior studies performed during the intracarotid sodium amobarbital (ISA) test. However, these results are not entirely consistent with current models of differential cerebral involvement in the modulation of the heart. This study was designed to re-investigate this topic with a larger N than has heretofore been used. Methods: The electrocardiogram was recorded during left and right ISAs in 73 subjects. Raw heart rate and heart rate variability were calculated. Results: Raw heart rate increased during inactivation of either hemisphere, but more so for the right hemisphere. Heart rate variability changes consistent with decreasing parasympathetic tone also were found to occur during either ISA, but to a significant degree, only during right ISA. Conclusions: The right hemisphere appears to have a greater role in cerebral regulation of cardiac function, perhaps by virtue of the modification of parasympathetic effects.
• Skaff, P., & Labiner, D. (2001). Status epilepticus due to human parvovirus B19 encephalitis in an immunocompetent adult. Neurology, 57(7). doi:10.1212/WNL.57.7.1336
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  Human parvovirus (HPV) B19 is a rare cause of encephalitis in children and immunocompromised adults. The authors describe a case of an otherwise healthy woman who developed encephalitis complicated by prolonged status epilepticus. Human parvovirus B19 infection was suggested by a prodromal, malar rash and established by the presence of specific IgM and IgG antibodies in the patient's serum. This is the first reported case of HPV B19 encephalitis in an immunocompetent adult.
• Weinand, M. E., Kester, M. M., Labiner, D. M., & Ahern, G. L. (2001). Time from ictal subdural EEG seizure onset to clinical seizure onset: Prognostic value for selecting temporal lobectomy candidates. Neurological Research, 23(Issue 6). doi:10.1179/016164101101199072
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  Long-term subdural EEG recording was performed to test the hypothesis that the duration from ictal subdural EEG seizure onset (ECOT) is prognostic for seizure-free outcome following temporal lobectomy. In 48 patients with complex partial seizures, temporal lobectomy was based on invasive localization of the ictal seizure focus. Subdural EEG data were analyzed for association with seizure-free outcome (seizure-free: yes or no) at a minimum of one year following temporal lobectomy. As the duration from ictal subdural EEG seizure onset to clinical seizure onset increased, the odds of being seizure-free post-operatively increased. The best fitting statistical model for predicting seizure-free outcome included seizure onset (unilateral vs. bilateral) and duration from ictal subdural EEG seizure onset to clinical seizure onset. While selection of temporal lobectomy candidates has increasingly emphasized noninvasive recording, some scalp-EEG monitored patients cannot be offered surgery for various reasons, one of which may include ictal EEG seizure onset following clinical seizure onset. When subdural EEG monitoring is performed for selection of temporal lobectomy candidates, analysis of the duration from subdural EEG seizure onset to clinical seizure onset should improve the prognostic value of the subdural EEG data for seizure-free outcome following temporal lobectomy.
• Weinand, M., Labiner, D., & Ahern, G. (2001). Temporal lobe seizure interhemispheric propagation time depends on nonepileptic cortical cerebral blood flow. Epilepsy Research, 44(1). doi:10.1016/S0920-1211(00)00205-9
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  In some patients with epilepsy, activation of eloquent cortex using various forms of environmental stimulation and mental activity may induce seizures. The increased neuronal activity resulting from cortical stimulation may be associated with increased regional cerebral blood flow. The vascular steal theory of temporal lobe epilepsy suggests that as nonepileptogenic cortical cerebral blood flow (CBFn) increases, temporal lobe epileptogenicity increases as a result, in part, of decreasing interhemispheric propagation time (IHPT). Recently, IHPT has been shown to be a quantitative electrocorticographic measure of temporal lobe epileptogenicity. In the current study, long-term combined subdural-EEG and surface cortical cerebral blood flow (CBF) monitoring was performed to test the hypothesis that IHPT depends upon CBFn. The results show that IHPT is a nonlinear (negative exponential) function of nonepileptic cortical CBF (r = 0.507, df = 32, t = -2.204, P < 0.05). In temporal lobe epilepsy, nonepileptic cortical hypoperfusion may represent a protective mechanism for delaying interhemispheric seizure propagation. The fact that IHPT decreases exponentially with increasing CBFn suggests that small increases in CBFn should substantially decrease IHPT and increase epileptogenicity. This study confirms that inter-hemispheric propagation time depends upon perfusion of nonepileptogenic cortex. © 2001 Elsevier Science B.V.
• Ahern, G. L., Deogaonkar, M., Kester, M., Labiner, D. M., & Weinand, M. E. (2000). Electrocorticographic factors associated with temporal lobe epileptogenicity.. Pathophysiology : the official journal of the International Society for Pathophysiology, 7(1), 33-39. doi:10.1016/s0928-4680(99)00035-8
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  Continuous subdural electrocorticographic (ECoG) monitoring was performed to test the hypothesis that human temporal lobe epileptogenicity, during long-term monitoring following antiepileptic drug (AED) withdrawal, regardless of the specific AED regimen, is dependent upon ECoG ictal onset and interhemispheric spread of epileptic activity. In 121 patients, ECoG parameters were analyzed for association with seizure frequency, a clinical measure of epileptogenicity. Significantly associated with increased seizure frequency were: ictal medial temporal lobe onset, absence of ictal frontal lobe desynchronization and short interhemispheric propagation time (IHPT). Seizure frequency during long-term ECoG monitoring was not predictive of post-operative seizure outcome. It is concluded that, following AED withdrawal, regardless of the specific AED regimen, increased seizure frequency is associated with medial temporal lobe ictal onset, short IHPT and absence of frontal lobe desynchronization. The results confirm the hypothesis that human temporal lobe epileptogenicity, after withdrawal, is dependent upon ECoG ictal onset and interhemispheric spread of epileptic activity. Future development of procedures which promote ECoG factors associated with increased seizure frequency following AED withdrawal might decrease duration of invasive long-term monitoring and improve efficiency for the pre-surgical selection of temporal lobectomy candidates. Intervention producing ictal frontal lobe desynchronization and increased IHPT might inhibit temporal lobe epileptogenicity and should be evaluated for therapeutic efficacy outside of the long-term monitoring context.
• Ahern, G. L., Herring, A. M., Hutzler, R., Labiner, D. M., & Weinand, M. E. (2000). Affective self-report during the intracarotid sodium amobarbital test: group differences.. Journal of the International Neuropsychological Society : JINS, 6(6), 659-67. doi:10.1017/s1355617700666031
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  Emotional reactions are sometimes observed during the intracarotid sodium amobarbital test. For instance, euphoric/indifference reactions can be seen during right hemisphere inactivation and catastrophic reactions may accompany left hemisphere inactivation. Less dramatic changes can also be detected in affective self-report during left and right hemisphere amobarbital tests, with more negative affect reported during left hemisphere inactivation and either neutral or mildly positive affective states reported during right hemisphere inactivation. The current study not only replicated this effect, but in addition, found significant group differences. The first group (right way) showed a pattern of affective self-report during left and right amobarbital tests entirely consistent with prior findings, while a second group (wrong way) showed results that behaved in a diametrically opposite fashion. A third group (no change) showed little, if any, difference in affective self-report during left and right amobarbital tests. The major factor distinguishing the wrong way group from the other two appeared to be an asymmetrical distribution of left and right temporal lobe lesions in the former group. In contrast, the factor differentiating the right way group from the no change group appeared to be the relative degree of left hemisphere inactivation during the left hemisphere amobarbital test. The results are discussed not only in terms of their impact on theories of cerebral lateralization for emotion, but also in terms of methodological issues in this field.
• Ahern, G., Herring, A., Labiner, D., Weinand, M., & Hutzler, R. (2000). Affective self-report during the intracarotid sodium amobarbital test: Group differences. Journal of the International Neuropsychological Society, 6(6). doi:10.1017/S1355617700666031
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  Emotional reactions are sometimes observed during the intracarotid sodium amobarbital test. For instance, euphoric/indifference reactions can be seen during right hemisphere inactivation and catastrophic reactions may accompany left hemisphere inactivation. Less dramatic changes can also be detected in affective self-report during left and right hemisphere amobarbital tests, with more negative affect reported during left hemisphere inactivation and either neutral or mildly positive affective states reported during right hemisphere inactivation. The current study not only replicated this effect, but in addition, found significant group differences. The first group (right way) showed a pattern of affective self-report during left and right amobarbital tests entirely consistent with prior findings, while a second group (wrong way) showed results that behaved in a diametrically opposite fashion. A third group (no change) showed little, if any, difference in affective self-report during left and right amobarbital tests. The major factor distinguishing the wrong way group from the other two appeared to be an asymmetrical distribution of left and right temporal lobe lesions in the former group. In contrast, the factor differentiating the right way group from the no change group appeared to be the relative degree of left hemisphere inactivation during the left hemisphere amobarbital test. The results are discussed not only in terms of their impact on theories of cerebral lateralization for emotion, but also in terms of methodological issues in this field.
• Bergen, D., Cibula, J. E., Dasheiff, R., Harvey, J., Holmes, M. D., Labar, D., Labiner, D. M., Morris, G. L., Nadkarni, M., Naritoku, D. K., O'donovan, C. A., Ojemann, L. M., Richards, B., Ristanovic, R., Sanchez, J. D., Scales, D., Schachter, S. C., Sirven, J. I., Sperling, M. R., & Wilensky, A. J. (2000). Vagus nerve stimulation therapy for epilepsy in older adults.. Neurology, 54(5), 1179-82. doi:10.1212/wnl.54.5.1179
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  The authors assessed the efficacy, safety, and tolerability of vagus nerve stimulation (VNS) for refractory epilepsy in 45 adults 50 years of age and older. They determined seizure frequency, adverse effects, and quality of life. At 3 months, 12 patients had a >50% decrease in seizure frequency; at 1 year, 21 of 31 studied individuals had a >50% seizure decrease. Side effects were mild and transient. Quality of life scores improved significantly with time.
• DeGiorgio, C. M., Schachter, S. C., Handforth, A., Salinsky, M., Thompson, J., Uthman, B., Reed, R., Collin, S., Tecoma, E., Morris, G. L., Vaughn, B., Naritoku, D. K., Henry, T., Labar, D., Gilmartin, R., Labiner, D., Osorio, I., Ristanovic, R., Jones, J., , Murphy, J., et al. (2000). Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures. Epilepsia, 41(Issue 9). doi:10.1111/j.1528-1157.2000.tb00325.x
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  Purpose: To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date. Methods: Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal EO5 study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute E05 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study. Results: The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures. Conclusions: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures.
• Rapcsak, S. Z., Cohen, R. A., Comer, J. F., Galper, S. R., Kaszniak, A. W., Labiner, D. M., Laguna, J. F., Nielsen, L., Reminger, S. L., & Verfaellie, M. (2000). Fear recognition deficits after focal brain damage: a cautionary note.. Neurology, 54(3), 575-81. doi:10.1212/wnl.54.3.575
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  To test the hypothesis that fear recognition deficits in neurologic patients reflect damage to an emotion-specific neural network..Previous studies have suggested that the perception of fear in facial expressions is mediated by a specialized neural system that includes the amygdala and certain posterior right-hemisphere cortical regions. However, the neuropsychological findings in patients with amygdala damage are inconclusive, and the contribution of distinct cortical regions to fear perception has only been examined in one study..We studied the recognition of six basic facial expressions by asking subjects to match these emotions with the appropriate verbal labels..Both normal control subjects (n = 80) and patients with focal brain damage (n = 63) performed significantly worse in recognizing fear than in recognizing any other facial emotion, with errors consisting primarily of mistaking fear for surprise. Although patients were impaired relative to control subjects in recognizing fear, we could not obtain convincing evidence that left, right, or bilateral lesions were associated with disproportionate impairments of fear perception once we adjusted for differences in overall recognition performance for the other five facial emotion categories. The proposed special role of the amygdala and posterior right-hemisphere cortical regions in fear perception was also not supported..Fear recognition deficits in neurologic patients may be attributable to task difficulty factors rather than damage to putative neural systems dedicated to fear perception.
• Sirven, J., Sperling, M., Naritoku, D., Schachter, S., Labar, D., Holmes, M., Wilensky, A., Cibula, J., Labiner, D., Bergen, D., Ristanovic, R., Harvey, J., Dasheiff, R., Morris, G., O'Donovan, C., Ojemann, L., Scales, D., Nadkarni, M., Richards, B., & Sanchez, J. (2000). Vagus nerve stimulation therapy for epilepsy in older adults. Neurology, 54(5). doi:10.1212/WNL.54.5.1179
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  The authors assessed the efficacy, safety, and tolerability of vagus nerve stimulation (VNS) for refractory epilepsy in 45 adults 50 years of age and older. They determined seizure frequency, adverse effects, and quality of life. At 3 months, 12 patients had a >50% decrease in seizure frequency; at 1 year, 21 of 31 studied individuals had a >50% seizure decrease. Side effects were mild and transient. Quality of life scores improved significantly with time.
• Weinand, M., Deogaonkar, M., Kester, M., Ahern, G., & Labiner, D. (2000). Electrocorticographic factors associated with temporal lobe epileptogenicity. Pathophysiology, 7(1). doi:10.1016/S0928-4680(99)00035-8
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  Continuous subdural electrocorticographic (ECoG) monitoring was performed to test the hypothesis that human temporal lobe epileptogenicity, during long-term monitoring following antiepileptic drug (AED) withdrawal, regardless of the specific AED regimen, is dependent upon ECoG ictal onset and interhemispheric spread of epileptic activity. In 121 patients, ECoG parameters were analyzed for association with seizure frequency, a clinical measure of epileptogenicity. Significantly associated with increased seizure frequency were: ictal medial temporal lobe onset, absence of ictal frontal lobe desynchronization and short interhemispheric propagation time (IHPT). Seizure frequency during long-term ECoG monitoring was not predictive of post-operative seizure outcome. It is concluded that, following AED withdrawal, regardless of the specific AED regimen, increased seizure frequency is associated with medial temporal lobe ictal onset, short IHPT and absence of frontal lobe desynchronization. The results confirm the hypothesis that human temporal lobe epileptogenicity, after withdrawal, is dependent upon ECoG ictal onset and interhemispheric spread of epileptic activity. Future development of procedures which promote ECoG factors associated with increased seizure frequency following AED withdrawal might decrease duration of invasive long-term monitoring and improve efficiency for the pre-surgical selection of temporal lobectomy candidates. Intervention producing ictal frontal lobe desynchronization and increased IHPT might inhibit temporal lobe epileptogenicity and should be evaluated for therapeutic efficacy outside of the long-term monitoring context. Copyright (C) 2000 Elsevier Science Ireland Ltd.
• D, C. S., Galus, M. A., Labiner, D. M., Liporace, J., Morrell, M. J., Yerby, M. S., & Zahn, C. (1999). Management issues for women with epilepsy [1] (multiple letters). Neurology, 53(3), 656-657. doi:10.1212/wnl.53.3.656
• Deogaonkar, M., Labiner, D. M., & Weinand, M. E. (1999). Role of Invasive Monitoring in Surgical Decision Making in Epilepsy Surgery. Neurosurgery, 45(3), 699-699. doi:10.1097/00006123-199909000-00080
• Griffiths, R. I., Labiner, D. M., Morris, G. L., Schrammel, P. N., Strauss, M. J., & Wills, S. H. (1999). Payer costs of patients diagnosed with epilepsy.. Epilepsia, 40(3), 351-8. doi:10.1111/j.1528-1157.1999.tb00717.x
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  To identify the annual cost to a third-party payer of inpatient and outpatient services and prescription drugs for patients diagnosed with epilepsy or convulsions..Retrospective study using administrative and claims data from a private insurer in the Northeast United States with >1.8 million covered lives. Health plan members were included if they had a claim for epilepsy or convulsions and a claim for an antiepileptic drug (AED) between January 1992 and December 1996. Annual costs and frequencies of all medical services, and of services related to epilepsy, were compared among five groups of patients defined by the most intensive procedure they received: invasive therapeutic procedure (group 1); invasive diagnostic procedure without an invasive therapeutic procedure (group 2); noninvasive diagnostic procedure without an invasive procedure (group 3); neurologist or neurosurgeon visit without an invasive procedure or noninvasive diagnostic procedure (group 4); or none of the preceding services (group 5)..In the cohort of 9,090 patients meeting the inclusion criteria, mean age was 38 years, 53% were female, 30% had malignant disease, and 25% had cardiac disease. The mean annual cost of all medical services was $9,617. Mean annual costs of all services were $43,333, $29,847, $11,300, $4,362, and $5,855, and annual costs of inpatient and outpatient encounters coded as epilepsy plus AEDs were $24,369, $10,330, $3,127, $1,079, and $1,086, in groups 1-5, respectively. Services used to stratify patients into the groups accounted for 37% of the total costs..The annual costs of medical services for patients with epilepsy are high and vary considerably because of treatment of epilepsy and management of comorbidities.
• Huxtable, R. J., Labiner, D. M., Weinand, M. E., & Yan, C. C. (1999). Disturbances of amino acids from temporal lobe synaptosomes in human complex partial epilepsy.. Neurochemical research, 24(11), 1379-83. doi:10.1023/a:1022528522373
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  We have studied the levels of neuroactive amino acids in synaptosomes (P2 fraction) isolated from brain tissue of ten patients with medically intractable epilepsy who were undergoing temporal lobectomy. First, lateral temporal tissue (nonfocal) was removed followed by medial temporal tissue (focal). A synaptosomal fraction (P2) was immediately prepared from each tissue and analyzed for free amino acid concentrations. Statistically significant reductions were seen in glutamine and GABA concentrations in focal tissue compared to nonfocal tissue. The ratio of excitatory amino acids (aspartate and glutamate) to inhibitory amino acids (taurine and GABA) was significantly higher in focal tissue compared to nonfocal. The glutamine/glutamate ratio was significantly reduced. These data support the hypothesis that alterations in the balance between excitatory and inhibitory amino acids may be involved in the expression of epilepsy.
• Labiner, D. M. (1999). Data vs opinion, phenytoin vs fosphenytoin: The saga continues. Archives of Internal Medicine, 159(Issue 22). doi:10.1001/archinte.159.22.2631
• Labiner, D., Yan, C., Weinand, M., & Huxtable, R. (1999). Disturbances of amino acids from temporal lobe synaptosomes in human complex partial epilepsy. Neurochemical Research, 24(11). doi:10.1023/A:1022528522373
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  We have studied the levels of neuroactive amino acids in synaptosomes (P2 fraction) isolated from brain tissue of ten patients with medically intractable epilepsy who were undergoing temporal lobectomy. First, lateral temporal tissue (nonfocal) was removed followed by medial temporal tissue (focal). A synaptosomal fraction (P2) was immediately prepared from each tissue and analyzed for free amino acid concentrations. Statistically significant reductions were seen in glutamine and GABA concentrations in focal tissue compared to nonfocal tissue. The ratio of excitatory amino acids (aspartate and glutamate) to inhibitory amino acids (taurine and GABA) was significantly higher in focal tissue compared to nonfocal. The glutamine/glutamate ratio was significantly reduced. These data support the hypothesis that alterations in the balance between excitatory and inhibitory amino acids may be involved in the expression of epilepsy.
• Takacs, I., Ahern, G. L., Labiner, D. M., Takacs, I., & Weinand, M. E. (1999). Nonepileptic cortical cerebral blood flow and temporal lobe epileptogenicity. Pathophysiology, 6(2), 135-141. doi:10.1016/s0928-4680(99)00014-0
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  Abstract Long-term combined electrocorticographic (ECoG) and surface cerebral blood flow (CBF) monitoring was performed to test the hypothesis that human temporal lobe epileptogenicity (i.e. seizure frequency) depends on perfusion of nonepileptic cortex. ECoG and CBF data were continuously recorded from homotopic regions of nonepileptic and epileptic temporal lobes. During the 2-h peri-ictal and 5-min pre- and post-ictal periods, seizure frequency was a positive linear function of non epileptic CBF ( r =0.599, df=48, P r =0.794, df=130, P r =0.610, df=1040, P
• Weinand, M., Takacs, I., Labiner, D., & Ahern, G. (1999). Nonepileptic cortical cerebral blood flow and temporal lobe epileptogenicity. Pathophysiology, 6(2). doi:10.1016/S0928-4680(99)00014-0
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  Long-term combined electrocorticographic (ECoG) and surface cerebral blood flow (CBF) monitoring was performed to test the hypothesis that human temporal lobe epileptogenicity (i.e. seizure frequency) depends on perfusion of nonepileptic cortex. ECoG and CBF data were continuously recorded from homotopic regions of nonepileptic and epileptic temporal lobes. During the 2-h peri-ictal and 5-min pre- and post-ictal periods, seizure frequency was a positive linear function of nonepileptic CBF (r=0.599, df=48, P
• Ahern, G. L., Herring, A. M., Labiner, D. M., Weinand, M. E., & Weinand, A. M. (1998). Quantitative analysis of hemispatial neglect in the intracarotid sodium amobarbital (ISA) test.. Journal of the International Neuropsychological Society : JINS, 4(2), 99-105. doi:10.1017/s135561779800099x
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  There are dramatic changes in the electroencephalogram of the inactivated hemisphere in the intracarotid sodium amobarbital test. One of the more profound behavioral changes during this procedure is left hemispatial neglect accompanying right hemisphere inactivation. The present study was designed to ascertain whether there was a clear relationship between the degree of hemispheric inactivation (as measured by the electroencephalogram) and the degree of left hemispatial neglect during this procedure. Sixty-nine participants undergoing right hemisphere intracarotid sodium amobarbital testing were presented with a random letter cancellation test at various points during the procedure. Neglect was quantified as significant, moderate, minimal, or none, based on how many target letters the patients missed. The simultaneous electroencephalogram from each of these testing points was spectrally analyzed and topographic maps were generated. The degree of neglect was then compared with the comparable topographic map. It was found that as the amobarbital-induced right hemispheric dysfunction regressed, the degree of neglect lessened in a systematic fashion, as did the profound electroencephalographic changes induced by the drug. Thus, there is a clear relation between the degree of hemispheric inactivation induced by the amobarbital and the degree of left hemispatial neglect. This relationship held regardless of side of hemispheric language dominance or epileptic focus. These results replicate previous findings that right hemisphere inactivation during the intracarotid sodium amobarbital test results in left hemispatial neglect. They extend these findings by clearly showing that neglect changes in a quantitative fashion (rather than being an all-or-none phenomenon) and further, show that there is a clear relationship between the severity of neglect and the degree of hemispheric dysfunction.
• Ahern, G., Herring, A., Labiner, D., & Weinand, M. (1998). Quantitative analysis of hemispatial neglect in the intracarotid sodium amobarbital (ISA) test. Journal of the International Neuropsychological Society, 4(2). doi:10.1017/S135561779800099X
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  There are dramatic changes in the electroencephalogram of the inactivated hemisphere in the intracarotid sodium amobarbital test. One of the more profound behavioral changes during this procedure is left hemispatial neglect accompanying right hemisphere inactivation. The present study was designed to ascertain whether there was a clear relationship between the degree of hemispheric inactivation (as measured by the electroencephalogram) and the degree of left hemispatial neglect during this procedure. Sixty-nine participants undergoing right hemisphere intracarotid sodium amobarbital testing were presented with a random letter cancellation test at various points during the procedure. Neglect was quantified as significant, moderate, minimal, or none, based on how many target letters the patients missed. The simultaneous electroencephalogram from each of these testing points was spectrally analyzed and topographic maps were generated. The degree of neglect was then compared with the comparable topographic map. It was found that as the amobarbital-induced right hemispheric dysfunction regressed, the degree of neglect lessened in a systematic fashion, as did the profound electroencephalographic changes induced by the drug. Thus, there is a clear relation between the degree of hemispheric inactivation induced by the amobarbital and the degree of left hemispatial neglect. This relationship held regardless of side of hemispheric language dominance or epileptic focus. These results replicate previous findings that right hemisphere inactivation during the intracarotid sodium amobarbital test results in left hemispatial neglect. They extend these findings by clearly showing that neglect changes in a quantitative fashion (rather than being an all-or-none phenomenon) and further, show that there is a clear relationship between the severity of neglect and the degree of hemispheric dysfunction.
• Collins, S. D., D, C. S., Labiner, D. M., Morrell, M. J., Yerby, M. S., & Zahn, C. A. (1998). Management issues for women with epilepsy: a review of the literature.. Neurology, 51(4), 949-56. doi:10.1212/wnl.51.4.949
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  A review of literature referable to management issues for women with epilepsy (WWE) was undertaken for the development of a practice parameter..Epilepsy is a common neurologic condition with gender-related management implications. Although reviews of this topic often focus on pregnancy-related issues for WWE, specific health concerns for WWE are present throughout all phases of reproductive life..An OVID MEDLINE literature search was conducted for 1965 to 1997 using the following key words/phrases and cross referencing: epilepsy/ seizures and pregnancy, anticonvulsants, antiepileptic drugs (AEDs), teratogenesis, oral contraceptives, birth defects, folate/folic acid, vitamin K, metabolic bone disease, and breast-feeding..Pregnancy outcome literature for WWE spans several decades. Methodology varies and interpretation is complicated by modern management strategies. Contributions of socioeconomic factors, AEDs, maternal epilepsy, and seizures during pregnancy to adverse pregnancy outcomes have not been clearly delineated. There is a biologic basis for recommendations concerning contraception, folate supplementation, vitamin K use in pregnancy, breast-feeding, metabolic bone disease, catamenial epilepsy, and reproductive endocrine disorders, but no outcome studies afford a strong evidence base for practice recommendation..WWE face health issues for which there is no available outcome literature to guide decision making. The urgent need for studies in many of these areas is highlighted by expanded treatment options with new AEDs and epilepsy surgery.
• Coons, S. J., Grudzinski, A. N., Hakim, Z., & Labiner, D. M. (1998). Use of the QOLIE-31 in Routine Clinical Practice. Journal of Epilepsy, 11(1), 34-47. doi:10.1016/s0896-6974(97)00110-2
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  Abstract The most important outcome of medical care may be the patient's perception of his or her functioning and well-being, or quality of life. However, patient-reported quality of life is not often routinely and/or adequately assessed. This study examined the usefulness of health-related quality of life (HRQoL) information in predicting patient-reported health status when compared with information routinely obtained in a physician–patient interaction. A survey instrument was administered to 40 patients immediately prior to a scheduled epilepsy clinic visit. The instrument included the 31-item Quality of Life in Epilepsy Inventory (QOLIE-31) and 21 additional items that assessed, among other things, information routinely obtained in a physician–patient interaction regarding adverse drug effects and seizure frequency. Regression analysis revealed that information regarding seizure frequency and adverse drug effects provided little insight into patients' self-perceived health status. Only 11.25% of the variance in patients' self-reported health status was explained by variations in these traditional measures. The addition of QOLIE-derived data to traditional information significantly improved the ability to predict patients' self-reported health status. The results of this study indicate that the administration of an HRQoL instrument in routine clinical practice offers additional insight into patients' self-perceived health status. Furthermore, the study indicated that this additional information can be collected in a reasonable amount of time.
• Degiorgio, C. M., Wheless, J. W., Collins, S. D., D, C. S., Gilmartin, R. C., Handforth, A., Henry, T. R., Jones, J. C., Labar, D. R., Labiner, D. M., Morris, G. L., Murphy, J. V., Naritoku, D. K., Ney, G. C., Osorio, I., Ristanovic, R. K., Salinsky, M. C., Schachter, S. C., Tecoma, E. S., , Uthman, B. M., et al. (1998). Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial.. Neurology, 51(1), 48-55. doi:10.1212/wnl.51.1.48
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  The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation..Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures..Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline..Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred..Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.
• Grudzinski, A., Hakim, Z., Coons, S., & Labiner, D. (1998). Use of the QOLIE-31 in routine clinical practice. Journal of Epilepsy, 11(1). doi:10.1016/S0896-6974(97)00110-2
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  The most important outcome of medical care may be the patient's perception of his or her functioning and well-being, or quality of life. However, patient-reported quality of life is not often routinely and/or adequately assessed. This study examined the usefulness of health-related quality of life (HRQoL) information in predicting patient-reported health status when compared with information routinely obtained in a physician- patient interaction. A survey instrument was administered to 40 patients immediately prior to a scheduled epilepsy clinic visit. The instrument included the 31-item Quality of Life in Epilepsy inventory (QOLIE-31) and 21 additional items that assessed, among other things, information routinely obtained in a physician-patient interaction regarding adverse drug effects and seizure frequency. Regression analysis revealed that information regarding seizure frequency and adverse drug effects provided little insight into patients' self-perceived health status. Only 11.25% of the variance in patients' self-reported health status was explained by variations in these traditional measures. The addition of QOLIE-derived data to traditional information significantly improved the ability to predict patients' self- reported health status. The results of this study indicate that the administration of an HRQoL instrument in routine clinical practice offers additional insight into patients' serf-perceived health status. Furthermore, the study indicated that this additional information can be collected in a reasonable amount of time.
• Handforth, A., DeGiorgio, C., Schachter, S., Uthman, B., Naritoku, D., Tecoma, E., Henry, T., Collins, S., Vaughn, B., Gilmartin, R., Labar, D., Morris, G., Salinsky, M., Osorio, I., Ristanovic, R., Labiner, D., Jones, J., Murphy, J., Ney, G., & Wheless, J. (1998). Vagus nerve stimulation therapy for partial-onset seizures: A randomized active-control trial. Neurology, 51(1). doi:10.1212/WNL.51.1.48
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  Objective: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. Background: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. Methods: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. Results: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. Conclusions: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.
• Wheless, J. W., D, C. S., Degiorgio, C. M., Gilmartin, R. C., Handforth, A., Henry, T. R., Jones, J. C., Labar, D., Labiner, D. M., Morris, G. L., Murphy, J. V., Naritoku, D. K., Ney, G. C., Osorio, I., Ristanovic, R., Salinsky, M. C., Schachter, S. C., Tecoma, E. S., Uthman, B. M., , Vaughn, B. V., et al. (1998). Vagus nerve stimulation therapy for partial-onset seizures. Neurology, 51(1).
• Carter, L. P., El-saadany, W. F., Labiner, D. M., Oommen, K. J., Sioutos, P. J., & Weinand, M. E. (1997). Cerebral blood flow and temporal lobe epileptogenicity.. Journal of neurosurgery, 86(2), 226-32. doi:10.3171/jns.1997.86.2.0226
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  Long-term surface cerebral blood flow (CBF) monitoring was performed to test the hypothesis that temporal lobe epileptogenicity is a function of epileptic cortical perfusion. Forty-three bitemporal 2-hour periictal CBF studies were performed in 13 patients. Homotopic regions of temporal cortex maintained interictal epileptic cortical hypoperfusion and nonepileptic normal cortical CBF. At 10 minutes preictus, a statistically significant, sustained increase in CBF was detected on the epileptic temporal lobe. Two minutes preictus, there was approximation of CBF in the epileptic and nonepileptic temporal lobes. Thereafter, electrocorticographic (ECoG) and clinical seizure onset occurred. The linear relationship between CBF in the two hemispheres (epileptic and nonepileptic) was the inverse of normal (y = -0.347x + 62.767, r = 0.470, df = 95, p < 0.05). The data indicated a direct linear correlation between epileptic cortical CBF and seizure interval (frequency-1), a clinical measure of epileptogenicity (r = 0.610, df = 49, p < 0.05). Epileptogenicity was also found to be a logarithmic function of the difference between nonepileptic and epileptic cortical perfusion (r = 0.564, df = 58, t = 5.20, p < 0.05). The results showed that progressive hypoperfusion of the epileptic focus correlated with a decreased seizure interval (increased epileptogenicity). Increased perfusion of the epileptic focus correlated with an increased seizure interval (decreased epileptogenicity). The fact that CBF alterations precede ECoG seizure activity suggests that vasomotor changes may produce electrical and clinical seizure onset.
• Ahern, G. L., Carter, L. P., El-saadany, W. F., Labiner, D. M., Oommen, K. J., Talwar, D., & Weinand, M. E. (1996). Abnormal vasomotor response of human epileptogenic cortex to reversal of hyperventilation A long-term surface cerebral blood flow monitoring study. Pathophysiology, 3(1), 41-45. doi:10.1016/0928-4680(95)00050-x
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  Abstract Human epileptogenic and nonepileptogenic surface cerebral blood flow (CBF) was studied during hyperventilation (HV) recovery. Bilateral subdural temporal lobe CBF probes were placed for long-term monitoring. Epileptic cortex became ischemic as an inverse linear function of HV duration ( r = 0.923, df=9, P P r = 0.890, df=9, P r = 0.784, df=5, P r = 0.782, df=9, P
• Carter, L. P., El-saadany, W. F., Labiner, D. M., Oommen, K. J., Sioutos, P. J., & Weinand, M. E. (1996). Cerebral blood flow and temporal lobe epileptogenicity. Neurosurgical Focus, 1(5), E5. doi:10.3171/foc.1996.1.5.6
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  Long-term surface cerebral blood flow (CBF) monitoring was performed to test the hypothesis that temporal lobe epileptogenicity is a function of epileptic cortical perfusion. Forty-three bitemporal 2-hour periictal CBF studies were performed in 13 patients. Homotopic regions of temporal cortex maintained interictal epileptic cortical hypoperfusion and nonepileptic normal cortical CBF. At 10 minutes preictus, a statistically significant, sustained increase in CBF was detected on the epileptic temporal lobe. Two minutes preictus, there was approximation of CBF in the epileptic and nonepileptic temporal lobes. Thereafter, electrocorticographic (ECoG) and clinical seizure onset occurred. The linear relationship between CBF in the two hemispheres (epileptic and nonepileptic) was the inverse of normal (y = -0.347x + 62.767, r = 0.470, df = 95, p < 0.05). The data indicated a direct linear correlation between epileptic cortical CBF and seizure interval (frequency-1), a clinical measure of epileptogenicity (r = 0.610, df = 49, p < 0.05). Epileptogenicity was also found to be a logarithmic function of the difference between nonepileptic and epileptic cortical perfusion (r = 0.564, df = 58, t = 5.20, p < 0.05). The results showed that progressive hypoperfusion of the epileptic focus correlated with a decreased seizure interval (increased epileptogenicity). Increased perfusion of the epileptic focus correlated with an increased seizure interval (decreased epileptogenicity). The fact that CBF alterations precede ECoG seizure activity suggests that vasomotor changes may produce electrical and clinical seizure onset.
• Weinand, M., El-Saadany, W., Labiner, D., Carter, L., Oommen, K., Talwar, D., & Ahern, G. (1996). Abnormal vasomotor response of human epileptogenic cortex to reversal of hyperventilation a long-term surface cerebral blood flow monitoring study. Pathophysiology, 3(1). doi:10.1016/0928-4680(95)00050-X
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  Human epileptogenic and nonepileptogenic surface cerebral blood flow (CBF) was studied during hyperventilation (HV) recovery. Bilateral subdural temporal lobe CBF probes were placed for long-term monitoring. Epileptic cortex became ischemic as an inverse linear function of HV duration (r = 0.923, df = 9, P < 0.05). During 5 min recovery from 13 hyperventilation periods in 8 patients, mean CBF remained significantly reduced below baseline in epileptic versus non-epileptic temporal lobe (7.5 ± 2.4 vs 1.8 ± 0.9 ml/100gm-min below baseline, respectively, P < 0.05). Epileptic CBF response to HV reversal was an inverse and direct linear function of HV duration and focus ischemia during HV, respectively (r = 0.890, df = 9, P < 0.05 and r = 0.784, df = 5, P < 0.05, respectively). During HV recovery, nonepileptic CBF increased linearly with increasing HV duration (r = 0.782, df = 9, P < 0.05). The data suggest that epileptic cortex has abnormal vasomotor response to recovery from hyperventilation. We propose that abnormal cortical vasomotor control represents a fundamental pertubation in the pathogenesis of human epilepsy. Cortical vasomotor analysis may provide a new physiologic basis for localization of the epileptic focus.
• Ahern, G. L., Herring, A. M., Labiner, D. M., Talwar, D., & Weinand, M. E. (1995). Quantitative analysis of the electroencephalogram in the intracarotid amobarbital procedure: II. Coherence analysis.. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society, 12(3), 285-90. doi:10.1097/00004691-199505010-00006
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  Thirty-seven subjects underwent bilateral internal carotid artery injections of amobarbital before surgery for intractable epilepsy. The electroencephalograms (EEG) of these patients were continuously monitored during these 74 procedures and were later subjected to quantitative analysis. Analysis of interhemispheric coherence in the delta, theta, alpha, and beta 1 bands was performed. Prominent changes occurred in interhemispheric coherence, which showed a precipitous drop in the first 2 min after amobarbital injection, followed by a gradual return to near baseline levels. These results suggest that interhemispheric relationships are significantly disrupted by intracarotid amobarbital injection.
• Ahern, G., El-saadany, W. F., Labiner, D. M., Talwar, D., & Weinand, M. E. (1995). Subdural strip electrode monitoring and surgical decision making in refractory epilepsy: validity and prognostic value of noninvasive localizing data☆. Journal of Epilepsy, 8(2), 131-138. doi:10.1016/0896-6974(95)00020-e
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  Abstract We analyzed the rationale for invasive monitoring in refractory epilepsy. In 54 selected patients, video/scalp-EEG was insufficient for seizure focus localization. Therefore, bilateral subdural electrodes were implanted for ictal recording. In 40 (74.1%) of 54 patients, ictal electrocorticography (ECoG) localized a seizure focus amenable to resection. Fourteen (25.9%) of 54 patients, had multiple foci or primary generalized seizures. Among 36 patients who had focal resection with at least 1-year follow-up, 32 (88.9%) are either seizure-free or significantly improved. Magnetic resonance imaging (MRI) and interictal single photon emission computed tomography (SPECT) had the highest sensitivity and specificity (80.0 and 81.8%, respectively) and the greatest diagnostic value (64.0 and 77.8%, respectively) for seizure focus localization. Independent of electrophysiologic data, MRI determination of focal abnormality was prognostic for seizure-free outcome. Concordance of one or more noninvasive techniques with ictal ECoG seizure focus localization was statistically significant in predicting seizure-free outcome. Although interest in noninvasive selection of candidates for focal resection is increasing, there remains a role for invasive monitoring of epileptogenic foci that are difficult to localize. Our study should improve selection of patients with refractory epilepsy for focal resection when ictal ECoG is used in conjunction with noninvasive data for surgical decision making.
• Weinand, M. E., Philip Carter, L., Oommen, K. J., Hutzler, R., Labiner, D. M., Talwar, D., El-Saadany, W., & Ahern, G. L. (1995). Response of human epileptic temporal lobe cortical blood flow to hyperventilation. Epilepsy Research, 21(Issue 3). doi:10.1016/0920-1211(95)00021-2
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  Bilateral long-term surface cortical cerebral blood flow (CBF) and electrocorticographic (ECoG) monitoring were performed in eight patients with complex partial seizures. In each patient, the epileptic temporal lobe was localized using ictal ECoG. Mean seizure interval (frequency-1) off anticonvulsant medication, a clinical measure of epileptogenicity, was 1.0 ± 0.3 h (range: 0.4 to 2.5 h). During 13 interictal hyperventilation periods, 3.6 ± 0.6 min in duration, the mean decrease in epileptic and nonepileptic temporal cortical CBF was 13.7 ± 2.3 versus 6.4 ± 1.9 ml/(100g min) (t = 2.230, d.f. = 16, P < 0.05), representing 20.9% and 10.8% reduction from baseline CBF during hyperventilation, respectively. Seizure interval decreased (i.e. frequency increased) with increasing magnitude of seizure focus CBF reduction during hyperventilation. Seizure interval was significantly correlated with epileptic temporal lobe CBF decrease during hyperventilation (R = 0.763, d.f. = 5, P < 0.05). The data suggest that, compared to nonepileptic brain, epileptic temporal lobe is particularly prone to hypoperfusion during hyperventilation. Epileptogenicity is a function of this seizure focus susceptibility to ischemia. The finding of abnormal seizure focus autoregulation during hyperventilation has implication for epileptic focus localization with cerebral blood flow analysis. © 1995.
• Weinand, M., El-Saadany, W., Labiner, D., Talwar, D., & Ahern, G. (1995). Subdural strip electrode monitoring and surgical decision making in refractory epilepsy: validity and prognostic value of noninvasive localizing data. Journal of Epilepsy, 8(2). doi:10.1016/0896-6974(95)00020-E
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  We analyzed the rationale for invasive monitoring in refractory epilepsy. In 54 selected patients, video/scalp-EEG was insufficient for seizure focus localization. Therefore, bilateral subdural electrodes were implanted for ictal recording. In 40 (74.1%) of 54 patients, ictal electrocorticography (ECoG) localized a seizure focus amenable to resection. Fourteen (25.9%) of 54 patients, had multiple foci or primary generalized seizures. Among 36 patients who had focal resection with at least 1-year follow-up, 32 (88.9%) are either seizure-free or significantly improved. Magnetic resonance imaging (MRI) and interictal single photon emission computed tomography (SPECT) had the highest sensitivity and specificity (80.0 and 81.8%, respectively) and the greatest diagnostic value (64.0 and 77.8%, respectively) for seizure focus localization. Independent of electrophysiologic data, MRI determination of focal abnormality was prognostic for seizure-free outcome. Concordance of one or more noninvasive techniques with ictal ECoG seizure focus localization was statistically significant in predicting seizure-free outcome. Although interest in noninvasive selection of candidates for focal resection is increasing, there remains a role for invasive monitoring of epileptogenic foci that are difficult to localize. Our study should improve selection of patients with refractory epilepsy for focal resection when ictal ECoG is used in conjunction with noninvasive data for surgical decision making. © 1995.
• Ahern, G. L., Herring, A. M., Hutzler, R., Labiner, D. M., Oommen, K. J., Osburn, C., Tackenberg, J. N., Talwar, D., & Weinand, M. E. (1994). Quantitative analysis of the EEG in the intracarotid amobarbital procedure. I. Amplitude analysis.. Electroencephalography and clinical neurophysiology, 91(1), 21-32. doi:10.1016/0013-4694(94)90015-9
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  Thirty-seven subjects underwent bilateral internal carotid artery injections of amobarbital prior to surgery for intractable epilepsy. The electroencephalogram (EEG) of these patients was continuously monitored during these 74 procedures and was later subjected to quantitative analysis. Topographic mapping of these data suggested that the areas of inactivation were largely restricted to the anterior 2/3 of the hemisphere injected, corresponding to the vascular distributions of the anterior and middle cerebral arteries. Graphical representation of the data demonstrated that delta and theta band activity peaked in the first 2 min post injection and decreased gradually thereafter, becoming stable at around 12 min post injection. Examination of the alpha, beta 1, and beta 2 bands suggested that activity increased and decreased more gradually than that for delta and theta, with perhaps a longer latency. Although EEG changes were most prominent in the anterior 2/3 of the inactivated hemisphere, similar (though smaller) changes were also observed in both ipsilateral and contralateral zones thought to be outside of the vascular distribution of the internal carotid artery.
• Ahern, G. L., Herring, A. M., Tackenberg, J. N., Schwartz, G. E., Labiner, D. M., Oommen, K. J., Seegei, J. F., & Weinand, M. E. (1994). Affective Self-Report During the Intracarotid Sodium Amobarbital Test. Journal of Clinical and Experimental Neuropsychology, 16(Issue 3). doi:10.1080/01688639408402647
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  Changes in internal affective state were investigated in patients undergoing the intracarotid sodium amobarbital test. It was found that when the left hemisphere was inactivated, patients rated their mood as significantly more negative than during baseline conditions. No significant change in affective state was observed during the inactivation of the right hemisphere. The findings are interpreted in terms of a differential lateralization model of emotion, in which the right hemisphere is more involved in the more powerful and salient negative affects. © 1994, Taylor & Francis Group, LLC. All rights reserved.
• Huxtable, R. J., Labiner, D. M., Lleu, P. L., & Weinand, M. E. (1994). Neuroactive amino acids in synaptosomes from focal and nonfocal temporal lobe tissue of patients with intractable complex partial seizures.. Advances in experimental medicine and biology, 359, 435-43. doi:10.1007/978-1-4899-1471-2_47
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  The putative involvement of disturbances in amino acid patterns in the pathogenesis of epilepsy has been vigorously debated (13,34,36,47,50). Amino acid levels in whole tissue removed from epileptic foci at surgery or autopsy have been compared with levels in surrounding nonfocal tissue or with tissue removed at autopsy or surgery from nonepileptic subjects. The advantages and disadvantages of each procedure have been argued at length (13,34,36,47,50). No clear pattern of changes has emerged, however (2,5,7,10,12,13,15,1–8,19,21,23,26,30,32,35,36,38,40,48,50). The literature on changes in amino acids in epilepsy has been reviewed (9,16).
• Weinand, M. E., Hermann, B., Wyler, A. R., Carter, L. P., Oommen, K. J., Labiner, D., Ahern, G., & Herring, A. (1994). Long‐Term Subdural Strip Electrocorticographic Monitoring of Ictal Déjà Vu. Epilepsia, 35(Issue 5). doi:10.1111/j.1528-1157.1994.tb02554.x
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  Summary: We report a series of 8 patients with ictal déjà vu. Subdural strip electrocorticographic (ECoG) monitoring localized the ictal epileptogenic focus as follows: right (n = 6) and left (n = 2) mesiotemporal lobe. In all 8 patients, the left hemisphere was dominant for language function based on intracarotid amytal testing. In 6 right‐handed patients, ictal déjà vu was associated with a right temporal lobe focus. However, in the 2 left‐handed patients, the ictal focus was left temporal lobe. Although ictal déjà vu localizes the epileptic focus to temporal lobe, this experiential phenomenon appears to lateralize to the hemisphere nondominant for handedness. Copyright © 1994, Wiley Blackwell. All rights reserved
• Weinand, M., Carter, L., Patton, D., Oommen, K., Labiner, D., & Talwar, D. (1994). Long-term surface cortical cerebral blood flow monitoring in temporal lobe epilepsy. Neurosurgery, 35(4). doi:10.1227/00006123-199410000-00011
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  LONG-TERM SUBDURAL SURFACE cortical cerebral blood flow (CBF) and electrocorticographic monitoring was performed in 12 patients with complex partial seizures. A total of 40 seizures were analyzed. Baseline CBF values from nonepileptic and epileptic temporal lobe (mean ± standard error) were 60.0 ± 1.0 and 50.2 ± 1.8 ml/100 g per minute, respectively (P < 0.05). In general, clinical seizure onset was preceded by a 20-minute preictal CBF increase from baseline in the epileptic temporal lobe. Peak early postictal CBF values of nonepileptic and epileptic temporal lobes were 57.7 ± 13.3 and 89.0 ± 21.7 ml/100 g per minute (P > 0.05) at 5.2 ± 2.2 and 2.4 ± 1.0 minutes (P > 0.05) after clinical seizure onset, respectively. Statistically significant differences between nonepileptic and epileptic temporal lobe CBF were detected at 50 minutes (74.0 ± 14.2 and 37.5 ± 9.2 ml/100 g per minute, respectively; P < 0.05) and 60 minutes (75.6 ± 13.6 and 36.1 ± 8.5 ml/100 g per minute, respectively; P < 0.05) postictal. The data suggest that the optimal times for CBF analysis to differentiate epileptic from nonepileptic temporal lobe are 1) during the interictal period and 2) late (50 to 60 minutes) postictal. The results of this study should improve the understanding of the dynamic cerebral perfusion patterns in the epileptic human brain. Copyright © by the Congress of Neurological Surgeons.
• Ahern, G. L., Herring, A. M., Labiner, D. M., Oommen, K. J., Seeger, J. F., Tackenberg, J. N., & Weinand, M. E. (1993). The association of multiple personality and temporolimbic epilepsy. Intracarotid amobarbital test observations.. Archives of neurology, 50(10), 1020-5. doi:10.1001/archneur.1993.00540100017009
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  What is the relationship of "multiple personality disorder" in patients with temporolimbic epilepsy to certain types of hemispheric interaction?.Case series..Tertiary care referral center..Two patients with temporolimbic epilepsy considered to be surgical candidates referred for the intracarotid amobarbital sodium procedure (IAP). Each individual had presented with different "personalities" in a characteristic temporal relationship to their seizures..Intracarotid amobarbital sodium procedure, Wada test, and electroencephalogram..Behavioral observations made during the performance of the IAP..During the IAP, each patient's peri-ictal "personality" changes were precisely replicated. No seizure activity was noted during the IAPs..These observations suggest that the association of multiple personality and temporolimbic epilepsy is not dependent on seizure discharges per se, but rather may be related to certain types of hemispheric interaction.
• Labiner, D., Butler, L., Cao, Z., Hosford, D., Shin, C., & McNamara, J. (1993). Induction of c-fos mRNA by kindled seizures: Complex relationship with neuronal burst firing. Journal of Neuroscience, 13(2).
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  Expression of the immediate-early gene c-fos has been advanced as a marker of neuronal activity in the adult nervous system. We sought to test the validity of c-fos mRNA expression as a marker of neuronal activity during seizures and to elucidate specific neurotransmitter receptors whose activation was necessary for seizure-evoked c-fos mRNA expression. We correlated c-fos mRNA expression, measured with in situ hybridization, with kindled seizure-induced firing of hippocampal dentate granule cells or substantia nigra pars compacta and pars reticulata neurons. We found that the occurrence of seizure-evoked synchronous action potentials during the seizure exhibited a perfect qualitative correlation with the presence of c-fos mRNA expression in the granule cells 30 min following the seizure (Fisher's exact test, p = 0.002). However, there was no quantitative correlation between the number of seizure-induced population action potentials and the magnitude of c-fos mRNA expression in the granule cells. In the substantia nigra, where neuronal populations have previously been demonstrated to exhibit synchronous firing during kindled seizures, no induction of c-fos mRNA was detected in either pars compacta or pars reticulata. Pretreatment with antagonists of the NMDA subtype of glutamate receptor selectively and markedly decreased seizure-induced c-fos mRNA expression in the dentate granule cells, despite increasing the number of granule cell population action potentials. These findings illustrate the complexity of the relationship between c-fos induction and neuronal burst firing during kindled seizures. We caution that c-fos mRNA expression is not a simple marker of neuronal activity. We suggest that seizure-induction of c-fos mRNA expression may correlate better with sustained neuronal depolarization and subsequent rise of intracellular calcium evoked by multiple factors, one of which is NMDA receptor activation.
• Sorock, G. S., & Labiner, D. M. (1992). Peripheral neuromuscular dysfunction and falls in an elderly cohort. American Journal of Epidemiology, 136(Issue 5). doi:10.1093/oxfordjournals.aje.a116536
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  In a prospective study of 169 tenants of senior citizen housing in New Jersey in 1986-1987, the relations between tests of peripheral sensory and motor functions in the lower extremities and the rate of first falls were evaluated. The mean age of the cohort was 79.8 years. Fifty-seven persons fell at least once during the follow-up period (mean. 5.6 months). After adjustment for history of stroke, heart failure, emphysema, and use of a walker or cane, rate ratios for first falls were elevated in subjects with reduced toe joint position sense (rate ratio (RR) = 2.2) and sharp-dull discrimination (RR = 2.0), but to a lesser extent for reduced ankle strength (RR = 1.5). Presence of one or more of these three deficits was defined as a peripheral neuromuscular dysfunction and was associated with first falls after adjustment for multiple covariates (RR = 2.4, 95% confidence interval 1.3-4.5). Having two or all three sensory or motor deficits increased the rate of falling 3.9 times (95% confidence interval 2.1-7.0) compared with persons without these deficits. These data suggest that impaired sensory and motor function of the lower extremities plays an important role in falls in the elderly. Am J Epidemiol 1992; 136: 584-91 © 1992 by The Johns Hopkins University School of Hygiene and Public Health.
• Simonato, M., Hosford, D., Labiner, D., Shin, C., Mansbach, H., & McNamara, J. (1991). Differential expression of immediate early genes in the hippocampus in the kindling model of epilepsy. Molecular Brain Research, 11(2). doi:10.1016/0169-328X(91)90113-C
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  Kindling is a phenomenon in which brief afterdischarges (ADs) evoked by periodic electrical stimulation of the brain eventually result in generalized clonic motor seizures. Once present, the enhanced sensitivity to electrical stimulation is lifelong. The mechanism by which brief ADs produce this long-lasting effect may involve a change in gene expression. To begin to investigate changes in gene expression that occur during kindling, we used in situ hybridization histochemistry to examine the time course of expression of mRNAs of the immediate early genes (IEGs) c-fos, c-jun, NGFI-A, and c-myc within the dorsal hippocampus of rats following a kindling AD. Three principal findings resulted from this study. First, the expression of all mRNAs except c-myc was significantly increased (P < 0.05) within discrete neuronal populations. Second, the time course of expression of the IEGs differed markedly within the same neuronal population. Third, for a given IEG, the time course and anatomic pattern of expression were strikingly different neong different neuronal populations of the hippocampus. The prolonged and distinctly different patterns of IEG expression suggest that target genes are differentially regulated in these neuronal populations for prolonged periods following a kindling AD. © 1991.
• Smith, D. B., Sidman, R. D., Flanigin, H., Henke, J., & Labiner, D. (1985). A reliable method for localizing deep intracranial sources of the EEG. Neurology, 35(Issue 12). doi:10.1212/wnl.35.12.1702
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  We have demonstrated the reliability of a noninvasive method for successfully localizing the intracranial origin of the EEG. The dipole localization method (DLM) is a computer-assisted, mathematical method based on electrical field theory and is similar to localization methods currently used by electrocardiologists. In 12 patients with intractable epilepsy who were being evaluated for surgery, a known current source was introduced between two adjacent depth electrodes. Using scalp-recorded EEG only, DLM accurately and reliably localized the source to within 2 cm of the known origin in all instances where a discrete source was present. We conclude that DLM is a valid and reliable noninvasive method for localizing the intracranial source of some scalp-recorded EEG potentials, and that in some patients, use of this method may obviate the need for depth electrode implantation. © 1985 American Academy of Neurology.

Proceedings Publications

• Shegog, R., Sepulveda, R., Czerniak, K., Guerrero, R., Garcia-Quintana, A., Addy, R., Martin, K., Jackson, L., & Labiner, D. (2022). MINDSETPLUS: THE ‘MANAGEMENT AND INFORMATION DECISION SUPPORT EPILEPSY TOOL’ TO PROMOTE ASSESSMENT, GOAL-BASED SKILLS TRAINING, AND SERVICE LINKAGE FOR PEOPLE WITH EPILEPSY. In 15th International Conference on ICT, Society and Human Beings, ICT 2022, 19th International Conference on Web Based Communities and Social Media, WBC 2022 and 14th International Conference on e-Health, EH 2022 - Held at the 16th Multi Conference on Computer Science and Information Systems, MCCSIS 2022.
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  Introduction: People with epilepsy can adhere to epilepsy self-management behaviors to improve seizure control, medication adherence, and lifestyle factors that contribute to seizures. Responsive online interventions can assist patients and providers to assess self-management, set treatment goals, and decide on education and social service programs. The Management Information & Decision Support Epilepsy Tool (MINDSET) is a bilingual online program designed to improve patient-provider communication to enhance epilepsy self-management. MINDSET may have utility for community health workers when assisting patients to improve their self-management. Purpose: To enhance MINDSET to include recommendations for education and social service programs (‘MINDSETPlus’) and to establish an implementation framework to facilitate use of MINDSETPlus by community health workers in community-based neurology clinics. Methods: An expert advisory group, comprising stakeholders from the Epilepsy Foundations in Texas and the Universities of Texas and Arizona provided formative review and consensus on MINDSET enhancements. Implementation theory and expert consensus informed a phased implementation framework. Results: MINDSETPlus enables patients to assess their self-management, select behavioral goals (for seizure, medication and lifestyle management), receive recommendations for further training tailored on current self-management and/or co-morbidities (depression and memory), and cue their community health worker to priority social determinants. A phased framework was derived for onboarding, training and implementing the MINDSETPlus-mediated intervention in neurology clinics. Conclusion: MINDSETPlus provides decision support for community health workers that may improve fidelity and metrics for quality improvement and assist to navigate, assess, reinforce, educate, and link epilepsy patients to community programs and services. Feasibility and efficacy testing of the intervention is in progress.
• Labiner, D. M., & Ahern, G. L. (2002). Neurologic consultation for seizures: When, why, and how to pursue. In n/a, 111.

Presentations

• Labiner, D. M., Addy, R., Martin, K., Garcia Quintana, A., Czerniak4, K., Shegog, R., Sepulveda, R., & Sepulveda, R. (2023). Advancing epilepsy care and self-management for Latino Spanish speaking patients through the use of a mobile web-based application (MINDSET 2.0). . American Public Health AssociationAmerican Public Health Association.
• Labiner, D. M., Martin, K., Addy, R., Shegog, R., & Sepulveda, R. (2023). Translation of MINDSETPlus Into Clinical Practice: Results of Clinical Feasibility Testing of Web-Based Epilepsy Self-Management Decision Support Tool. American Epilepsy SocietyAmerican Epilepsy Society.
• Labiner, D. M. (2016, January). Pain & Your Brain. University of Arizona: Living Healthy with Arthritis Conference. Tucson, Arizona.
• Labiner, D. M. (2015, December). Partnering epilepsy centers in the Americas: the Costa Rica experience. Global Health Special Interest Group at the Annual Meeting of the American Epilepsy Society. Philadelphia, PA.
• Labiner, D. M., & Skoch, J. (2015, September). Cortical gene expression associated with seizure outcome following temporal lobectomy with amygdalohippocampectomy. Western Neurosurgical Society meeting. Kauai, HI.

Poster Presentations

• Sepulveda, R., Halavacs, N., Begley, C., Chong, J. W., Shegog, R., Martin, K., & Labiner, D. M. (2016, December). Spanish-MINDSET: Usability and feasibility of epilepsy self-management decision support for Spanish speaking patients. 2016 Annual Meeting of the American Epilepsy Society. Houston, TX: American Epilepsy Society.
• Labiner, D. M., Addy, R., Shegog, R., & Sepulveda, R. (2023). Considerations of Using the MINDSET Self-Management Mobile Health Application Among Latino Patients with Epilepsy: Results of a Qualitative Study. American Epilepsy SocietyAmerican Epilepsy Society.
• Labiner, D. M., Addy, R., Thomas, S., Moreau, R., Guerrero, R., Ardis, D., Garcia-Quintana,, A., Czerniak, K., Shegog, R., & Sepulveda, R. (2023). A New MINDSET: Assessing CHW Readiness for Implementing Epilepsy Self-Management Educational Support Using Adapted Knowledge, Self-Efficacy, and Attitude Scales. American Epilepsy SocietyAmerican Epilepsy Society.
• Labiner, D. M. (2015, December). Development of an epilepsy self-management decision-support tool: Spanish-MINDSET 4.1. Annual Meeting of the American Epilepsy Society. Philadelphia, PA.
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  poster 1.376
• Rueda, S., Sepulveda, R., Chong, J. W., Begley, C., Shegog, R., & Labiner, D. M. (2015, December 4-8). Development of an epilepsy self-management decision-support tool: Spanish-MINDSET 4.1. 69th Annual Meeting of the American Epilepsy Society.
• Rueda, S., Sepulveda, R., Chong, J. W., Begley, C., Shegog, R., Labiner, D. M., Rueda, S., Sepulveda, R., Chong, J. W., Begley, C., Shegog, R., & Labiner, D. M. (2015, December 4 – 8, 2015). Poster 1.376 Development of an epilepsy self-management decision-support tool: Spanish-MINDSET 4.1. 69th Annual Meeting of the American Epilepsy Society. Philadelphia, PA.: Rueda S, Sepulveda R, Chong J, Begley C, Shegog R, Labiner D (2015).