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There is a reciprocal relationship between epilepsy and reproductive endocrine disorders. Seizures and anti-seizure medications (ASMs) can contribute to reproductive and endocrine dysfunction and reproductive dysfunction may exacerbate seizures. Epilepsy via neuroendocrine mechanisms affects the hypothalamic-pituitary-ovarian (HPO) axis, disrupting the regulation of gonadotropin secretion, and resulting in dystrophic effects on the ovaries and early menopause. Anti-seizure medications have endocrine-related side effects on sexual function and bone health. Long-term use of ASMs may result in menstrual irregularities, sexual dysfunction, anovulatory cycles, polycystic ovaries, and reduced fertility. Some ASMs also interfere with bone metabolism. Epilepsy patients treated with ASMs are at risk for bone loss and fractures. This article explores the endocrine and hormonal effects of seizures and ASMs., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Introduction: Maintaining seizure control with lamotrigine is complicated by altered pharmacokinetics and existence of subpopulations in whom clearance increases or remains constant during pregnancy., Objective: Our objective was to characterize the potential for particular dosing scenarios to lead to increased seizure risk or toxicity., Methods: Lamotrigine pharmacokinetic parameters obtained from our previous study were applied to a one-compartment model structure with subpopulations (75:25%) exhibiting different clearance changes. A single-patient simulation was conducted with typical pharmacokinetic parameter values from each subpopulation. Population-level simulations (N = 48,000) included six dosing scenarios and considered four preconception doses using the R package mrgsolve (Metrum Research Group). Thresholds for efficacy and toxicity were selected as drug concentration that are 65% lower than preconception concentrations and doubling of preconception concentrations, respectively., Results: Individual simulation results demonstrated that without dose increases, concentrations fell below 0.65 at 6-8 weeks in the high clearance change (HC) subpopulation, depending on preconception clearance. While no simulated dosing regimen allowed all women in both subpopulations to maintain preconception concentrations, some regimens provided a more balanced risk profile than others. Predicted concentrations suggested potential increased seizure risk for 7%-100% of women in the HC group depending on preconception dose and subpopulation. Additionally, in 63% of dosing scenarios for women with low clearance change (LC), there was an increased risk of toxicity (34%-100% of women)., Significance: A substantial percentage of simulated individuals had concentrations low enough to potentially increase seizure risk or high enough to create toxicity. Early clearance changes indicate possible subpopulation categorization if therapeutic drug monitoring is conducted in the first trimester. An arbitrary "one-size-fits-all" philosophy may not work well for lamotrigine dosing adjustments during pregnancy and reinforces the need for therapeutic drug monitoring until a patient is determined to be in the LC or HC group., (© 2023 The Authors. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy published by Wiley Periodicals LLC on behalf of Pharmacotherapy Publications, Inc.)

Literature review of patients with KCNQ2 developmental and epileptic encephalopathy ( KCNQ2 -DEE) reveals, based on 16 reports including 139 patients, a clinical phenotype that includes age- and disease-specific stereotyped seizures. The typical seizure type of KCNQ2 -DEE, focal tonic, starts within 0-5 days of life and is readily captured by video-electroencephalography VEEG for clinical and genetic diagnosis. After initial identification, KCNQ2 -DEE seizures are clinically apparent and can be clearly identified without the use of EEG or VEEG. Therefore, we propose that the 2019 recommendations from the International League against Epilepsy (ILAE), the Pediatric Epilepsy Research Consortium (PERC), for capturing and recording seizures for clinical trials ( Epilepsia Open , 4, 2019, 537) are suitable for use in KCNQ2 -DEE‒associated antiseizure medicine (ASM) treatment trials. The ILAE/PERC consensus guidance states that a caregiver-maintained seizure diary, completed by caregivers who are trained to recognize seizures using within-patient historical recordings, accurately captures seizures prospectively in a clinical trial. An alternative approach historically endorsed by the Food and Drug Administration (FDA) compares seizure counts captured on VEEG before and after treatment. A major advantage of the ILAE/PERC strategy is that it expands the numbers of eligible patients who meet inclusion criteria of clinical trials while maintaining accurate seizure counts ( Epilepsia Open , 4, 2019, 537). Three recent phase 3 pivotal pediatric trials investigating ASMs to treat syndromic seizures in patients as young as 2 years of age ( N Engl J Med , 17, 2017, 699; Lancet , 21, 2020, 2243; Lancet , 17, 2018, 1085); and ongoing phase 2 open-label pediatric clinical trial that includes pediatric epileptic syndromes as young as 1 month of age ( Am J Med Genet A , 176, 2018, 773), have already used caregiver-maintained seizure diaries successfully. For determining the outcome of a KCNQ2 -DEE ASM treatment trial, the use of a seizure diary to count seizures by trained observers is feasible because the seizures of KCNQ2 -DEE are clinically apparent. This strategy is supported by successful precedent in clinical trials in similar age groups and has the endorsement of the international pediatric epilepsy community., Competing Interests: Drs. Grayson, Harden, Butterfield, Pimstone, and Aycardi are employed by Xenon Pharmaceuticals Inc (“Xenon”). They receive salaries and may hold stock or stock options in Xenon. Dr Millichap reports personal fees from American Academy of Neurology, personal fees from Up‐To‐Date, personal fees from BMJ Best Practice, grants and personal fees from UCB Pharma, grants and personal fees from Mallinkrodt, personal fees from Esai, personal fees from Biomarin, personal fees from Ionis, personal fees from Greenwich, personal fees from Sunovion, personal fees from Upsher‐Smith, grants from NIH, grants from Citizens United for Research in Epilepsy, personal fees from Praxis, grants and personal fees from Trumacro, outside the submitted work; Pursuant to a Consulting Agreement between Ann and Robert H. Lurie Children's Hospital of Chicago and Xenon, it is anticipated that Dr Millichap will serve as the Global Coordinating Investigator for Xenon's planned Phase 3 study of XEN496. The Ann and Robert H. Lurie Children's Hospital of Chicago receives financial compensation from Xenon in exchange for Dr Millichap's services. In addition, Dr Millichap, in a personal capacity, is a consultant for Xenon and also serves as a member the Xenon Steering Committee for XEN496. Dr Millichap receives financial compensation from Xenon in exchange for his services. Dr French receives NYU salary support from the Epilepsy Foundation and for consulting work and/or attending Scientific Advisory Boards on behalf of the Epilepsy Study Consortium for Acadia, Adamas, Addex, Aeonian, Alexza, Anavex, Arvelle Therapeutics, Inc, Axcella Health, Axovant, Biogen, Biomotiv/Koutif, Blackfynn, Bloom Science, Bridge Valley Ventures, Cavion, Cerebral Therapeutics, Cerevel, Clinilabs, Concert Pharmaceuticals, Covance, Crossject, CuroNZ, Eisai, Empatica, Encoded, Engage Therapeutics, Encoded, Epitel, GW Pharma, Idorsia, Impax, Ionis, J&J Pharmaceuticals, Marinus, MonosolRx, Neurelis, Neurocrine, Novartis, Otsuka Pharmaceutical Development, Ovid Therapeutics Inc, Pfizer, Pfizer‐Neusentis, Praxis, Redpin, Sage, Sancillio, Shire, SK Life Sciences, Springworks, Stoke, Sunovion, Supernus, Takeda, UCB Inc, Ultragenyx, Upsher‐Smith, Vyera, West Therapeutic Development, Xenon, Xeris, Zogenix, and Zynerba. Dr French has also received research grants from Biogen, Cavion, Eisai, Engage, GW Pharma, Lundbeck, Neurelis, Ovid, SK Life Sciences, Sunovion, UCB, and Zogenix as well as grants from the Epilepsy Research Foundation, Epilepsy Study Consortium, and NINDS (#U01‐NS038455). She is on the editorial board of Lancet Neurology and Neurology Today. She is scientific officer for the Epilepsy Foundation for which NYU receives salary support. She has received travel reimbursement related to research, advisory meetings, or presentation of results at scientific meetings from the Epilepsy Study Consortium, the Epilepsy Foundation, Adamas, Arvelle Therapeutics, Inc, Axovant, Biogen, Blackfynn, Crossject, CuroNz, Eisai, Engage, Idorsia, Neurelis, Novartis, Otsuka, Ovid, Pfizer, Redpin, Sage, SK Life Science, Sunovion, Takeda, UCB, Ultragenyx, and Zynerba. Dr Dlugos receives salary support from NIH, Commonwealth of Pennsylvania Department of Health, Pediatric Epilepsy Research Foundation, and The Epilepsy Study Consortium. He is an investigator on research grants awarded to CHOP from Zogenix, Greenwich Biosciences, Brain Sentinel, Neurelis, Q‐State, Aquestive, Bio‐Pharm, SK Life Sciences, and Encoded Therapeutics. He has received travel expenses for protocol development conferences or investigator meetings from Marinus, Ovid/Takeda, Ultragenyx, Pfizer, Biogen, BioMarin, and Xenon. He received honoraria and/or travel support for CME and other educational programs from Wake Forest University School of Medicine, American Epilepsy Society, American Academy of Neurology, Epilepsy Foundation of America, Epilepsy Foundation of North Carolina, Medscape, Miller Medical Communications, Ecuador Neurology Project, Ministry of Health of the United Arab Emirates, Seoul National University, and the Chinese Pediatric Society., (© 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: To determine how early lamotrigine clearance (LTG-CL/F) increases during early pregnancy in women with epilepsy and to quantify the relationship of LTG-CL/F to estradiol concentrations and gestational week., Methods: This was a multicenter, observational study of pregnant women with epilepsy on lamotrigine and no interacting concomitant medications, employing frequent blood sampling prior to and early in pregnancy. A population mixed-effects modeling approach was used to describe the relationship between LTG-CL/F and gestational week and between LTG-CL/F and estradiol. Akaike information criterion (AIC) compared goodness of fit between final models and a generalized estimating equation to compare differences between low and high percentage LTG-CL/F change groups (p < 0.05)., Results: Twenty-five pregnancies (22 participants) were available. Increases in LTG-CL/F were present at 5 weeks gestational age. Both estradiol and gestational week were highly correlated with LTG-CL/F changes; LTG-CL/F increased at the rate of 0.115l/h for every gestational week and 0.844l/h for every 1ng/ml of estradiol, with women in the high LTG-CL/F percentage change group changing at a faster rate (p < 0.001). Models using gestational week performed better than models using estradiol., Interpretation: Gestational week was a better predictor of changes in LTG-CL/F than estradiol concentration and may reflect additional factors, although neither was robust enough to use clinically due to substantial interpatient variability. Changes in LTG-CL/F begin as early as the 5th gestational week, often before women know they are pregnant, emphasizing the importance of planning and early detection of pregnancy and consideration of early implementation of therapeutic drug monitoring. Ann Neurol 2018;84:556-563., (© 2018 American Neurological Association.)

Importance: Prior studies report lower birth rates for women with epilepsy (WWE) but have been unable to differentiate between biological and social contributions. To our knowledge, we do not have data to inform WWE seeking pregnancy if their likelihood of achieving pregnancy is biologically reduced compared with their peers., Objective: To determine if WWE without a prior diagnosis of infertility or related disorders are as likely to achieve pregnancy within 12 months as their peers without epilepsy., Design, Setting, and Participants: The Women With Epilepsy: Pregnancy Outcomes and Deliveries study is an observational cohort study comparing fertility in WWE with fertility in control women (CW) without epilepsy. Participants were enrolled at 4 academic medical centers and observed up to 21 months from November 2010 to May 2015. Women seeking pregnancy aged 18 to 40 years were enrolled within 6 months of discontinuing contraception. Exclusion criteria included tobacco use and a prior diagnosis of infertility or disorders that lower fertility. Eighteen WWE and 47 CW declined the study, and 40 WWE and 170 CW did not meet study criteria. The Women With Epilepsy: Pregnancy Outcomes and Deliveries electronic diary app was used to capture data on medications, seizures, sexual activity, and menses. Data were analyzed from November 2015 to June 2017., Main Outcomes and Measures: The primary outcome was proportion of women who achieved pregnancy within 12 months after enrollment. Secondary outcomes were time to pregnancy using a proportional hazard model, pregnancy outcomes, sexual activity, ovulatory rates, and analysis of epilepsy factors in WWE. All outcomes were planned prior to data collection except for time to pregnancy., Results: Of the 197 women included in the study, 142 (72.1%) were white, and the mean (SD) age was 31.9 (3.5) years among the 89 WWE and 31.1 (4.2) among the 108 CW. Among 89 WWE, 54 (60.7%) achieved pregnancy vs 65 (60.2%) among 108 CW. Median time to pregnancy was no different between the groups after controlling for key covariates (WWE: median, 6.0 months; 95% CI, 3.8-10.1; CW: median, 9.0 months; 95% CI, 6.5-11.2; P = .30). Sexual activity and ovulatory rates were similar in WWE and CW. Forty-four of 54 pregnancies (81.5%) in WWE and 53 of 65 pregnancies (81.5%) in CW resulted in live births. No epilepsy factors were significant., Conclusions and Relevance: Women with epilepsy seeking pregnancy without prior known infertility or related disorders have similar likelihood of achieving pregnancy, time to pregnancy, and live birth rates compared with their peers without epilepsy.

Objective: To evaluate the safety and preliminary pharmacokinetics of a pharmaceutical formulation of purified cannabidiol (CBD) in children with Dravet syndrome., Methods: Patients aged 4-10 years were randomized 4:1 to CBD (5, 10, or 20 mg/kg/d) or placebo taken twice daily. The double-blind trial comprised 4-week baseline, 3-week treatment (including titration), 10-day taper, and 4-week follow-up periods. Completers could continue in an open-label extension. Multiple pharmacokinetic blood samples were taken on the first day of dosing and at end of treatment for measurement of CBD, its metabolites 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD, and antiepileptic drugs (AEDs; clobazam and metabolite N -desmethylclobazam [N-CLB], valproate, levetiracetam, topiramate, and stiripentol). Safety assessments were clinical laboratory tests, physical examinations, vital signs, ECGs, adverse events (AEs), seizure frequency, and suicidality., Results: Thirty-four patients were randomized (10, 8, and 9 to the 5, 10, and 20 mg/kg/d CBD groups, and 7 to placebo); 32 (94%) completed treatment. Exposure to CBD and its metabolites was dose-proportional (AUC 0-t ). CBD did not affect concomitant AED levels, apart from an increase in N-CLB (except in patients taking stiripentol). The most common AEs on CBD were pyrexia, somnolence, decreased appetite, sedation, vomiting, ataxia, and abnormal behavior. Six patients taking CBD and valproate developed elevated transaminases; none met criteria for drug-induced liver injury and all recovered. No other clinically relevant safety signals were observed., Conclusions: Exposure to CBD and its metabolites increased proportionally with dose. An interaction with N-CLB was observed, likely related to CBD inhibition of cytochrome P450 subtype 2C19. CBD resulted in more AEs than placebo but was generally well-tolerated., Classification of Evidence: This study provides Class I evidence that for children with Dravet syndrome, CBD resulted in more AEs than placebo but was generally well-tolerated., (Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

OBJECTIVE The purpose of this study was to report outcomes of epilepsy surgery in 56 consecutive patients with autism spectrum disorder. METHODS Medical records of 56 consecutive patients with autism who underwent epilepsy surgery were reviewed with regard to clinical characteristics, surgical management, postoperative seizure control, and behavioral changes. RESULTS Of the 56 patients with autism, 39 were male, 45 were severely autistic, 27 had a history of clinically significant levels of aggression and other disruptive behaviors, and 30 were considered nonverbal at baseline. Etiology of the epilepsy was known in 32 cases, and included structural lesions, medical history, and developmental and genetic factors. Twenty-nine patients underwent resective treatments (in 8 cases combined with palliative procedures), 24 patients had only palliative treatments, and 3 patients had only subdural electroencephalography. Eighteen of the 56 patients had more than one operation. The mean age at surgery was 11 ± 6.5 years (range 1.5-35 years). At a mean follow-up of 47 ± 30 months (range 2-117 months), seizure outcomes included 20 Engel Class I, 12 Engel Class II, 18 Engel Class III, and 3 Engel Class IV cases. The age and follow-up times are stated as the mean ± SD. Three patients were able to discontinue all antiepileptic drugs (AEDs). Aggression and other aberrant behaviors observed in the clinical setting improved in 24 patients. According to caregivers, most patients also experienced some degree of improvement in daily social and cognitive function. Three patients had no functional or behavioral changes associated with seizure reduction, and 2 patients experienced worsening of seizures and behavioral symptoms. CONCLUSIONS Epilepsy surgery in patients with autism is feasible, with no indication that the comorbidity of autism should preclude a good outcome. Resective and palliative treatments brought seizure freedom or seizure reduction to the majority of patients, although one-third of the patients in this study required more than one procedure to achieve worthwhile improvement in the long term, and few patients were able to discontinue all AEDs. The number of palliative procedures performed, the need for multiple interventions, and continued use of AEDs highlight the complex etiology of epilepsy in patients with autism spectrum disorder. These considerations underscore the need for continued analysis, review, and reporting of surgical outcomes in patients with autism, which may aid in better identification and management of surgical candidates. The reduction in aberrant behaviors observed in this series suggests that some behaviors previously attributed to autism may be associated with intractable epilepsy, and further highlights the need for systematic evaluation of the relationship between the symptoms of autism and refractory seizures.

Competing Interests: Editor's Note: Authors have a Conflict of Interest disclosure which is posted under the Supplemental Materials link.

Objective: This study examines medication adherence among women with epilepsy via use of an electronic diary, as part of a prospective multicenter observational study designed to evaluate fertility in women with epilepsy (WWE) versus age-matched controls., Methods: WWE and healthy age-matched controls, seeking pregnancy, were given an iPod Touch using a customized mobile application (the WEPOD App) for daily data tracking. Eighty-six WWE tracked seizures and antiepileptic drugs (AEDs). Tracking of nonepilepsy medications was optional. Diary data were counted from enrollment date until date of delivery, or up to 12 months if pregnancy was not achieved. Each day that subjects reported missing one or more AED was counted as nonadherence. Because adherence can only be determined in women who track consistently, we elected to include adherence data only for women who tracked >80% of days in the study., Results: Approximately 75% of WWE tracked >80% of days and were included in medication adherence data analysis. In this group, medication adherence rate was 97.71%; 44% of women admitted to missing an AED on at least 1 day. Among the subgroup of WWE who recorded nonepilepsy medications, AED adherence rate was 98.56%, versus 93.91% for non-AEDs., Significance: The 75% compliance rate with an electronic diary suggests that it may be useful to track medication adherence in future studies and in the clinical setting. In those who tracked, the observed medication adherence rate was considerably higher than the 75% adherence rate seen in previous epilepsy studies. This might be explained in part by selection bias, but may also result from properties of the diary itself (daily reminders, real time feedback given to the provider). Women reported a higher rate of adherence to AEDs than to other prescribed medications and supplements, suggesting that perceived importance of medications likely influences medication adherence, and warrants future study., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Objective: To determine if anti-mullerian hormone (AMH), a neuroactive peptide hormone and a measure of ovarian reserve, is different between women with epilepsy (WWE) and healthy controls (HC) seeking pregnancy and to evaluate epilepsy-related factors associated with AMH concentrations., Methods: Subjects were participants in Women with Epilepsy: Pregnancy Outcomes and Deliveries (WEPOD), a multi-center prospective, observational cohort study evaluating fecundity in WWE compared to HC, ages 18-40 years. WWE were divided into a Sz+ group or a Sz- group, dependent on whether they had seizures within the 9 months prior to enrollment. Serum was collected, and AMH concentrations were measured as an exploratory analysis. Linear and logistic regression models were used to assess associations and control for covariates., Results: Serum AMH concentrations were measured in 72 out of 90 enrolled WWE and 97 out of 109 HC; the remaining subjects became pregnant before serum was obtained. Thirty WWE were in the Sz+ group and 40 in the Sz- group (retrospective seizure information was missing for two). All AMH concentrations were within the range, however, the normal inverse correlation between age and AMH was present in the HC and in the Sz- groups, but was lacking in the Sz+ group. Mean AMH concentration was higher in the Sz- group (3982pg/ml (SD+/-2452)) compared to the Sz+ group of WWE (2776pg/ml (SD+/-2308)) and HCs (3241 (SD±2647)). All values were within the expected range for age. In WWE, by linear regression, after controlling for age and BMI, seizure occurrence remained associated with AMH (p=0.025). In the prospective phase of the study, AMH concentrations were also associated with seizure occurrence during the menstrual cycle in which the serum sample was obtained (p=0.012). Antiepileptic drugs and other epilepsy factors were not associated with AMH concentrations. When analyzing the Sz- WWE group and the HC group by linear regression with AMH as the dependent variable, after controlling for age and BMI, the association with AMH was also present (p=0.017). AMH concentrations of the Sz+ group and HCs did not differ., Significance: In this exploratory analysis, seizure freedom was associated with higher AMH concentrations compared to women with ongoing seizures and to HCs. Future studies should further investigate the mechanism of the association of AMH with seizure occurrence, whether AMH could have a direct seizure-protective neuroactive hormone effect, as well as implications of AMH concentrations as a biomarker for ovarian reserve in women with epilepsy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A well-to-wheel (WTW) life cycle assessment (LCA) model is developed to evaluate the environmental profile of producing liquid transportation fuels via fast pyrolysis of perennial grasses: switchgrass and miscanthus. The framework established in this study consists of (1) an agricultural model used to determine biomass growth rates, agrochemical application rates, and other key parameters in the production of miscanthus and switchgrass biofeedstock; (2) an ASPEN model utilized to simulate thermochemical conversion via fast pyrolysis and catalytic upgrading of bio-oil to renewable transportation fuel. Monte Carlo analysis is performed to determine statistical bounds for key sustainability and performance measures including life cycle greenhouse gas (GHG) emissions and Energy Return on Investment (EROI). The results of this work reveal that the EROI and GHG emissions (gCO2e/MJ-fuel) for fast pyrolysis derived fuels range from 1.52 to 2.56 and 22.5 to 61.0 respectively, over the host of scenarios evaluated. Further analysis reveals that the energetic performance and GHG reduction potential of fast pyrolysis-derived fuels are highly sensitive to the choice of coproduct scenario and LCA allocation scheme, and in select cases can change the life cycle carbon balance from meeting to exceeding the renewable fuel standard emissions reduction threshold for cellulosic biofuels.

Objective: We sought to understand the magnitude of the risk that drivers with epilepsy (DWE) contribute to motor vehicle accidents (MVAs) compared to other drivers., Methods: We performed an evidence-based, systematic review using the American Academy of Neurology (AAN) guideline methodology., Results: Contributory evidence consisted of six Class II studies and one Class III study. Two articles reported a trend toward a decreased rate of overall MVA rates for DWE when compared with the general population with a relative risk (RR) of 0.86 (95% CI: 0.65-1.14) (Class III) and a RR of 1.00 (95% CI: 0.95-1.06) (Class II); both studies used patient report to ascertain MVA rates. Three Class II studies reported either a trend toward or an increased risk of MVA rates for DWE when compared with the general population with a RR of 1.62 (95% confidence interval (CI): 0.95-2.76), as ascertained by insurance, emergency department, and physician reporting databases, a RR of 1.73 (95% CI 1.58-1.90), as ascertained by police reports, and a RR of 7.01 (95% CI 2.18-26.13), as ascertained by casualty department visits. One Class II study showed that, compared to fatal crashes with DWE, fatal crashes were 26 times more likely to occur because of other medical conditions and 156 times more likely to occur because of alcohol abuse. Motor vehicle accident crashes due to seizures in DWE occurred in one out of every 2800 MVAs, as reported in another Class II study., Conclusions: The evidence for the difference in MVA rates in DWE compared to the general population is inconsistent, and no conclusion can be made. Important methodological differences across the studies contribute to the imprecision. Future research should be performed using objective measures rather than self-reporting of MVAs by DWE and "miles driven" as the denominator to calculate MVA rates., (Copyright © 2015. Published by Elsevier Inc.)

A patient's hormonal milieu contributes to the timing of emergence of several epilepsy syndromes that are known to begin at puberty and recede with the end of reproductive potential. One's hormonal balance at any particular moment contributes to seizure occurrence in both men and women. The best studied condition, catamenial epilepsy, refers to seizure clusters occurring in a cyclical pattern related to menses. Treatment of epilepsy using hormones complements standard antiepileptic therapy and its use will be reviewed, along with some other medications unique to catamenial epilepsy, such as diuretics.Seizures and “silent” epileptiform discharges in turn affect the hypothalamic pituitary axis and can cause release of hormones at inappropriate times leading to sexual dysfunction, menstrual irregularity, infertility and premature termination of reproductive states. Combined with psychological consequences of epilepsy, this sexual dysfunction has deleterious effects on the quality of life in patients and their partners.

Purpose of Review: This review encompasses issues regarding the management of women with epilepsy and pregnancy, including preconception planning, antiepileptic drug (AED) effects on the exposed offspring, and consequences of seizures during pregnancy, with an emphasis on counseling points and risk management., Recent Findings: In utero valproate exposure continues to show the highest risk of congenital malformations and of adverse cognitive outcomes, including autism, compared to other AEDs. In utero topiramate exposure is associated with facial clefts. In utero exposure to lamotrigine, carbamazepine, phenytoin, and levetiracetam has been evaluated in large numbers of offspring, and all of these AEDs have a low risk of major congenital malformations, near 2.5%. The risk of major congenital malformations due to in utero AED exposure is dose associated. Folic acid taken at the time of conception decreases the risk of adverse cognitive outcomes. AED polytherapy may adversely affect fertility, and in utero exposure of AED polytherapy is associated with infants who are small for their gestational age. Seizure freedom before pregnancy is a good predictor of remaining seizure free during pregnancy., Summary: Counseling points are complex for managing women with epilepsy contemplating pregnancy, including evaluation of AED choice and dose. The physician must have knowledge of the issues to enable an honest discussion and appropriate decision making in partnership with the patient.

Objective: Preapproval randomized controlled trials of antiepileptic drugs provide data in limited patient groups. We assessed the side effect and seizure reduction profile of tiagabine (TGB) in typical clinical practice., Methods: Investigators recorded adverse effect (AE), seizure, and assessment-of-benefit data prospectively in sequential patients treated open label with TGB., Results: Two hundred ninety-two patients (39 children) were enrolled to be treated long term with TGB. Seizure types were focal-onset (86%), generalized-onset (12%), both focal- and generalized-onset (0.3%), and multiple associated with Lennox-Gastaut Syndrome (2%). Two hundred thirty-one received at least one dose of TGB (median = 28 mg/day) and had follow-up seizure or AE data reported. Common AEs were fatigue, dizziness, psychomotor slowing, ataxia, gastrointestinal upset, weight change, insomnia, and "others" (mostly behavioral). Serious AEs occurred in 19 patients: behavioral effects (n = 12), status epilepticus (n = 3), others (n = 3), and sudden unexplained death (n = 1). No patients experienced suicidal ideation/behavior, rash, nephrolithiasis, or organ failure. Seizure outcomes were seizure freedom (5%), ≥75% reduction (12%), ≥50% reduction (23%), and increased number of seizures (17%), or new seizure type (1%)., Conclusions: Behavioral AEs occurred in a larger proportion of patients compared to those reported in TGB preapproval randomized controlled trials. A moderate percentage of patients had a meaningful reduction in seizure frequency. In clinical practice, TGB remains a useful antiepileptic drug., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Three suicidal ideation and suicidal behavior instruments were used to assess the prevalence of lifetime and recent suicidal ideation and suicidal behavior in patients with frequent treatment-resistant focal seizures who would be eligible for randomized clinical trials. This was done to determine which instrument was optimal for use in epilepsy., Methods: In a cross-sectional study, we compared lifetime and recent suicidal ideation and suicide attempt on the MINI International Neuropsychiatric Interview (MINI), Columbia Suicide Severity Rating Scale (C-SSRS), and Interactive Voice Response System CSSRS (E-CSSRS). A safety algorithm determined treatment referral. Coordinators and participants evaluated experiences with the C-SSRS. The proportion of participants that baseline assessment would exclude from clinical trial enrollment was determined., Key Findings: Among 208 participants, 1.6-3.9% had recent high risk suicidal ideation and 1.0-4.7% had a recent suicide attempt across all instruments. Lifetime high-risk suicidal ideation occurred in 12.1-14.1%. Lifetime suicide attempt occurred in 10.2-13.1% of participants. Of those with recent suicide attempt, 31.1% required referral to a health professional, and 3.9% needed urgent referral. Lifetime suicidal behavior (including aborted suicide attempt, interrupted suicide attempt, suicide attempt, preparatory acts or behavior, and nonsuicidal self-injurious behavior) was found in 21.1% on the E-CSSRS and 15.5% on the C-SSRS. Agreement (Kappa) was good to excellent for comparisons of all instruments. Fifty-two percent of subjects preferred either the CSSRS or E-CSSRS, whereas the rest had no preference; of those having a preference, 87.5% favored the CSSRS. Of the 18.9% of participants who might have been excluded from trials based on suicidal ideation and suicide attempt, the CSSRS identified high-risk suicidal ideation or suicide attempt in the preceding 2 years in only 4.4%., Significance: Suicidality screening is feasible in people with epilepsy. Slightly more suicidal behavior is reported with the E-CSSRS than C-SSRS, suggesting the E-CSSRS may be optimal. The proportion of patients who may be excluded from clinical trials based on worrisome suicidal ideation or suicide attempt is small, suggesting that it is possible to enroll most eligible individuals., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Complex, multidirectional interactions between hormones, seizures, and the medications used to control them can present a challenge for clinicians treating patients with epilepsy. Many hormones act as neurosteroids, modulating brain excitability via direct binding sites. Thus, changes in endogenous or exogenous hormone levels can affect the occurrence of seizures directly as well as indirectly through pharmacokinetic effects that alter the concentrations of antiepileptic drugs. The underlying structural and physiological brain abnormalities of epilepsy and the metabolic activity of antiepileptic drugs can adversely affect hypothalamic and gonadal functioning. Knowledge of these complex interactions has increased and can now be incorporated in meaningful treatment approaches for men and women with epilepsy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The outcomes of adult epilepsy patients prescribed lacosamide for additional seizure control. Responders were defined as having at least a 50% decrease in seizure frequency Sixty-seven patients were evaluated. Forty-six out of 67 patients (69%) were responders. Twelve of 14 patients not taking sodium channel-acting AEDs were responders (86%) and 34/53 patients taking sodium channel-acting AEDs were responders (64%) (difference not significant)., (Copyright © 2011 Elsevier B.V. All rights reserved.)