RESUMEN
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.
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Anticonvulsivantes/sangre , Epilepsia/sangre , Estradiol/sangre , Edad Gestacional , Lamotrigina/sangre , Complicaciones del Embarazo/sangre , Adulto , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Femenino , Humanos , Lamotrigina/uso terapéutico , Tasa de Depuración Metabólica/efectos de los fármacos , Tasa de Depuración Metabólica/fisiología , Embarazo , Complicaciones del Embarazo/tratamiento farmacológicoRESUMEN
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.
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Epilepsia/psicología , Cumplimiento de la Medicación , Embarazo/psicología , Adulto , Anticonvulsivantes/uso terapéutico , Estudios de Casos y Controles , Epilepsia/tratamiento farmacológico , Femenino , Humanos , Complicaciones del EmbarazoRESUMEN
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.
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Accidentes de Tránsito/estadística & datos numéricos , Conducción de Automóvil , Epilepsia/complicaciones , Convulsiones/complicaciones , Servicio de Urgencia en Hospital , Femenino , Humanos , Seguro , Persona de Mediana Edad , Vehículos a Motor , RiesgoRESUMEN
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.
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Anticonvulsivantes/uso terapéutico , Epilepsia , Neurobiología , Reproducción/fisiología , Caracteres Sexuales , Epilepsia/tratamiento farmacológico , Epilepsia/metabolismo , Epilepsia/fisiopatología , Femenino , Humanos , MasculinoRESUMEN
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.
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Anticonvulsivantes/uso terapéutico , Epilepsias Parciales/complicaciones , Epilepsias Parciales/psicología , Escalas de Valoración Psiquiátrica , Conducta Autodestructiva/etiología , Ideación Suicida , Adolescente , Adulto , Anciano , Algoritmos , Estudios Transversales , Electroencefalografía , Epilepsias Parciales/tratamiento farmacológico , Epilepsias Parciales/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Intento de Suicidio/psicología , Adulto JovenRESUMEN
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.
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Anticonvulsivantes/uso terapéutico , Síntomas Conductuales/tratamiento farmacológico , Síntomas Conductuales/etiología , Epilepsia , Ácidos Nipecóticos/uso terapéutico , Adolescente , Adulto , Anciano , Niño , Preescolar , Epilepsia/complicaciones , Epilepsia/tratamiento farmacológico , Epilepsia/psicología , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Tiagabina , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
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.
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Epilepsia , Complicaciones del Embarazo , Embarazo , Femenino , Humanos , Lamotrigina/uso terapéutico , Epilepsia/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Anticonvulsivantes/uso terapéutico , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológicoAsunto(s)
Derechos Civiles/legislación & jurisprudencia , Comercio/legislación & jurisprudencia , Anticonceptivos Femeninos , Cobertura del Seguro/legislación & jurisprudencia , Programas Obligatorios/legislación & jurisprudencia , Patient Protection and Affordable Care Act , Religión y Medicina , Femenino , HumanosRESUMEN
In 2011, there are greater than 20 antiepileptic medications available. These medications work by modulating neuronal excitability. Reproductive hormones have been found to have a role in the pathogenesis and treatment of seizures by also altering neuronal excitability, especially in women with catamenial epilepsy. The female reproductive hormones have in general opposing effects on neuronal excitability; estrogens generally impart a proconvulsant neurophysiologic tone, whereas the progestogens have anticonvulsant effects. It follows then that fluctuations in the levels of serum progesterone and estrogen throughout a normal reproductive cycle bring about an increased or decreased risk of seizure occurrence based upon the serum estradiol/progesterone ratio. Therefore, using progesterone, its metabolite allopregnanolone, or other hormonal therapies have been explored in the treatment of patients with epilepsy.
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Epilepsia/tratamiento farmacológico , Estrógenos/uso terapéutico , Pregnanolona/uso terapéutico , Progesterona/uso terapéutico , Anticonvulsivantes/uso terapéutico , Humanos , Ciclo Menstrual/fisiología , Neuronas/fisiología , Pregnanolona/metabolismo , Progesterona/metabolismo , Testosterona/uso terapéuticoRESUMEN
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-DEEâassociated 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.
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Encefalopatías/genética , Síndromes Epilépticos/genética , Canal de Potasio KCNQ2/genética , Convulsiones , Grabación en Video , Ensayos Clínicos como Asunto , Diarios como Asunto , Electroencefalografía , Humanos , Lactante , Recién Nacido , Pediatría , Estudios Prospectivos , Convulsiones/clasificación , Convulsiones/diagnóstico , Convulsiones/genética , Estados UnidosRESUMEN
We sought to determine whether the testosterone increase found with levetiracetam exposure in animal studies also occurs in patients. Adult male patients were evaluated for reproductive hormone levels before and 1 month after levetiracetam therapy. Eight subjects met inclusion/exclusion criteria (mean age 46 years, range 29-75 years). Total testosterone prior to starting levetiracetam ranged from 206-787 ng/dl [mean 445, standard deviation (SD) 227]. The mean total testosterone after levetiracetam therapy increased to 592 ng/dl (range 216-981, SD 297), an increase of 16% (p = 0.036). The free testosterone increased from a mean of 64 pg/ml (range 36-115, SD 30) to a mean of 76 pg/ml (range 35-155, SD 44), an increase of 19% (p = 0.080). The magnitude of change in testosterone levels correlated with the initial testosterone level (p = 0.038, r = 0.734). These results suggest that levetiracetam increases testosterone levels and that an initial testosterone level may predict the magnitude of increase.
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Anticonvulsivantes/efectos adversos , Epilepsia/tratamiento farmacológico , Piracetam/análogos & derivados , Testosterona/sangre , Adolescente , Adulto , Anciano , Anticonvulsivantes/uso terapéutico , Epilepsia/sangre , Hormona Folículo Estimulante/sangre , Humanos , Levetiracetam , Hormona Luteinizante/sangre , Persona de Mediana Edad , Piracetam/efectos adversos , Piracetam/uso terapéutico , Valores de Referencia , Globulina de Unión a Hormona Sexual/metabolismo , Adulto JovenRESUMEN
A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy. The committee evaluated the available evidence according to a structured literature review and classification of relevant articles. For WWE who are taking antiepileptic drugs (AEDs), there is probably no substantially increased risk (>2 times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (>1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. WWE should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84-92%) of remaining seizure-free during pregnancy. WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery.
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Epilepsia/epidemiología , Complicaciones del Embarazo/epidemiología , Aborto Espontáneo/epidemiología , Anticonvulsivantes/uso terapéutico , Cesárea , Epilepsia/tratamiento farmacológico , Femenino , Humanos , Hipertensión/epidemiología , Trabajo de Parto Prematuro/epidemiología , Oportunidad Relativa , Preeclampsia/epidemiología , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Recurrencia , Riesgo , Fumar/epidemiología , Estado Epiléptico/tratamiento farmacológico , Estado Epiléptico/epidemiología , Hemorragia Uterina/epidemiologíaRESUMEN
A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including antiepileptic drug (AED) teratogenicity and adverse perinatal outcomes. It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine (CBZ), and possibly compared to phenytoin (PHT) or lamotrigine (LTG). It is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. AED polytherapy probably contributes to the development of MCMs and reduced cognitive outcomes compared to monotherapy. Intrauterine exposure to VPA monotherapy probably reduces cognitive outcomes and monotherapy exposure to PHT or phenobarbital (PB) possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of <7. If possible, avoidance of VPA and AED polytherapy during the first trimester of pregnancy should be considered to decrease the risk of MCMs. If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered and avoidance of PHT and PB throughout pregnancy may be considered to prevent reduced cognitive outcomes.
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Anomalías Inducidas por Medicamentos/etiología , Anticonvulsivantes/efectos adversos , Trastornos del Conocimiento/inducido químicamente , Epilepsia/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Anticonvulsivantes/uso terapéutico , Peso al Nacer/efectos de los fármacos , Contraindicaciones , Quimioterapia Combinada , Femenino , Humanos , Recién Nacido , Embarazo , Efectos Tardíos de la Exposición Prenatal , Riesgo , Ácido Valproico/efectos adversos , Ácido Valproico/uso terapéuticoRESUMEN
A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid and prenatal vitamin K use and the clinical implications of placental and breast-milk transfer of antiepileptic drugs (AEDs). The committee evaluated the available evidence based on a structured literature review and classification of relevant articles. Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in clinically important amounts. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentrations of lamotrigine, phenytoin, and, to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative (MHD). Supplementing WWE with at least 0.4 mg of folic acid before pregnancy may be considered. Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered, and monitoring of levetiracetam and oxcarbazepine (as MHD) levels may be considered. A paucity of evidence limited the strength of many recommendations.
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Anticonvulsivantes/uso terapéutico , Lactancia Materna , Anomalías Congénitas/prevención & control , Epilepsia/tratamiento farmacológico , Ácido Fólico/administración & dosificación , Complicaciones del Embarazo/tratamiento farmacológico , Vitamina K/administración & dosificación , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/farmacocinética , Anomalías Congénitas/epidemiología , Epilepsia/epidemiología , Epilepsia/fisiopatología , Femenino , Humanos , Recién Nacido , Leche Humana/metabolismo , Placenta/metabolismo , Embarazo , Riesgo , Sangrado por Deficiencia de Vitamina K/epidemiología , Sangrado por Deficiencia de Vitamina K/etiología , Sangrado por Deficiencia de Vitamina K/prevención & controlRESUMEN
We sought to determine the type of personality disorder cluster associated with patients with nonepileptic psychogenic seizures (NES) compared with that of patients with epileptic seizures (ES). Consecutive adult patients admitted for video/EEG monitoring found to have NES were compared with a simultaneously admitted patient with confirmed epilepsy. Personality was assessed using the Structured Clinical Interview for DSM-IV-TR Axis II Personality Disorders. Personality disorders were then divided into personality clusters described in the DSM-IV-TR: A = paranoid, schizotypal, schizoid; B = borderline, histrionic, antisocial, narcissistic; or C = avoidant, dependent, obsessive-compulsive. Thirteen of 16 patients with NES and 12 of 16 patients with ES met criteria for personality disorders. Patients with NES were more likely to meet criteria for a personality disorder in Cluster A or B, compared with patients with ES, who were more likely to have Cluster C personality disorders (chi(2) test, P=0.007). We propose that the personality traits of patients with NES contribute to the development of nonepileptic psychogenic seizures. However, the large proportion of patients with ES with Cluster C personality disorders was unexpected, and further, for the patients with epilepsy, the direction of the association of their personality traits with the development of epilepsy is unknown.
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Epilepsia/psicología , Trastornos de la Personalidad/psicología , Convulsiones/psicología , Adulto , Anciano , Análisis por Conglomerados , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Personalidad , Escalas de Valoración PsiquiátricaRESUMEN
Affective disorders in people with epilepsy (PWE) have become increasingly recognized as a primary factor in the morbidity and mortality of epilepsy. To improve the recognition and treatment of affective disorders in PWE, an expert panel comprising members from the Epilepsy Foundation's Mood Disorders Initiative have composed a Consensus Statement. This document focuses on depressive disorders in particular and reviews the appearance and treatment of the disorder in children, adolescents, and adults. Idiosyncratic aspects of the appearance of depression in this population, along with physiological and cognitive issues and barriers to treatment, are reviewed. Finally, a suggested approach to the diagnosis of affective disorders in PWE is presented in detail. This includes the use of psychometric tools for diagnosis and a stepwise algorithmic approach to treatment. Recommendations are based on the general depression literature as well as epilepsy-specific studies. It is hoped that this document will improve the overall detection and subsequent treatment of affective illnesses in PWE.
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Consenso , Epilepsia/complicaciones , Trastornos del Humor/complicaciones , Epilepsia/diagnóstico , Epilepsia/terapia , Estudios de Evaluación como Asunto , Humanos , Trastornos del Humor/diagnóstico , Trastornos del Humor/terapiaRESUMEN
PURPOSE OF REVIEW: Much new information has now become available regarding outcomes of women with epilepsy (WWE) and pregnancy. RECENT FINDINGS: Valproate is associated with a risk of major congenital malformations within a range of 6.2-10.7%, though antiepileptic drugs (AEDs) other than valproate when used as monotherapy are associated with major congenital malformation rates ranging from 2.9 to 3.6%; the rate of major congenital malformations in WWE not treated with AEDs was similar to this at 3.1%. Seizure freedom in 9-12 months before pregnancy is associated with seizure freedom during pregnancy. A decline in AED levels can be expected during pregnancy, most dramatically for lamotrigine (but with marked variability between patients) and least with carbamazepine. Neonates born to WWE taking AEDs who receive vitamin K 1 mg intramuscularly at birth are not at additional risk of hemorrhagic disease of the newborn. SUMMARY: The use of valproate and polytherapy with any AED combinations should be avoided, if clinically appropriate, during pregnancy. Seizure freedom in 9-12 months before pregnancy should be a goal. AED levels should be maintained at or near the therapeutic level known for that individual patient, with frequent monitoring during pregnancy as appropriate for the patient and the AED.
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Epilepsia/complicaciones , Epilepsia/diagnóstico , Complicaciones del Embarazo/diagnóstico , Anomalías Inducidas por Medicamentos/etiología , Anomalías Inducidas por Medicamentos/prevención & control , Anticonvulsivantes/uso terapéutico , Carbamazepina/uso terapéutico , Epilepsia/terapia , Femenino , Ácido Fólico/metabolismo , Hemorragia/prevención & control , Humanos , Lamotrigina , Obstetricia/métodos , Embarazo , Complicaciones del Embarazo/terapia , Riesgo , Convulsiones/complicaciones , Triazinas/uso terapéutico , Ácido Valproico/farmacologíaRESUMEN
Interest in the years of reproductive changes for women with epilepsy (WWE), specifically perimenopause, menopause and postmenopause has been emerging in the epilepsy community. This article discusses evidence for changes in seizure frequency during perimenopause and postmenopause. Further, a catamenial epilepsy pattern during the reproductive years may be a hallmark for the observed seizure frequency change during these years; that is, an increase at perimenopause but a decrease at menopause. This finding implies that a subset of WWE are particularly susceptible to endogenous reproductive hormonal changes. An adverse effect on seizure frequency with the use of hormone replacement therapy (HRT) during postmenopause for WWE was reported in questionnaires, and was later borne out in a clinical trial. The laboratory counterpart of this human trial, HRT in ovariectomized rodent seizure models, shows that estrogen and progesterone are neuroprotective and do not uniformly increase seizure frequency. Possible reasons for the discrepancy between "the lab and the clinic" are presented. Strategies for managing HRT in symptomatic postmenopausal WWE using estrogenic and progestogenic compounds that may be less likely to promote seizures are discussed.
Asunto(s)
Anticonvulsivantes/metabolismo , Anticonvulsivantes/uso terapéutico , Terapia de Reemplazo de Hormonas/métodos , Convulsiones/tratamiento farmacológico , Animales , Interacciones Farmacológicas , Femenino , Humanos , Masculino , Menopausia/efectos de los fármacosRESUMEN
Sexual dysfunction in women with epilepsy (WWE) is an important comorbidity. A significant minority of WWE have markedly decreased sexual interest and it appears that orgasmic dysfunction occurs more frequently in WWE than in control women. Enzyme-inducing antiepileptic drugs can adversely affect sexual functioning by decreasing bioactive testosterone levels. Temporal lobe epilepsy of right-sided versus left-sided origin may also be a risk factor for sexual dysfunction. In addition to these factors, emerging evidence suggests that the serotonin transporter protein is related to temporal lobe epilepsy and it is postulated that this transporter may play a role in altered sexual functioning in epilepsy, perhaps through the serotonergic effects of antiepileptic drugs (AEDs). Strategies for modifying the contributors to sexual dysfunction in WWE will be discussed as well as the role of the neurologist in initiating management of this challenging comorbidity.
Asunto(s)
Epilepsia/complicaciones , Disfunciones Sexuales Fisiológicas/etiología , Disfunciones Sexuales Psicológicas/etiología , Sexualidad , Epilepsia/epidemiología , Femenino , Humanos , Disfunciones Sexuales Fisiológicas/epidemiología , Disfunciones Sexuales Psicológicas/epidemiologíaRESUMEN
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.