The role of cortisol in trust behavior: Results from an experimental study on healthy controls and patients with juvenile myoclonic epilepsy.

Trust is one of the foundations of human society and pervades all aspects of human live. Research on humans focused primarily on identifying the biological basis of trust behavior in healthy subjects, and this evidence hints to certain brain areas, hormones, and genetic factors to be fundamentally involved. The contribution of cortisol in trust has not yet elicited much attention in research, especially when specifically examined at basal cortisol levels. Trust has been previously studied in some neurological diseases but not in patients with epilepsy, and the influence of hormones on trust in these diseases remains yet unknown. Against this background, we designed an experimental study with a group of patients with juvenile myoclonic epilepsy and a group of healthy controls to compare trust behavior and plasma cortisol levels between the two groups. This economic game is frequently used in research to operationalize trust behavior. All participants further underwent neuropsychological assessment. Our results showed that there was no significant difference in trust behavior during the trust game, but a trend toward lower trust in patients. Furthermore, there was a significant difference in cortisol levels between groups with lower levels in patients. Interestingly, cortisol levels correlated with trust only in the patient group, but not in the control group. Future studies should specifically differentiate the effect of induced cortisol increases (e.g., acute stress) versus the effect of basal cortisol levels reflecting homeostasis or chronic stress on trust behavior and leverage the potential of comparison between patients and healthy controls.

Sexual dysfunction in people with epilepsy.

Sexual dysfunction is a common comorbidity in people with epilepsy (PWE) that adversely affects their quality of life. Nearly one-half of men and women with epilepsy have sexual dysfunction, but in the majority, this often goes unnoticed. The wide variation in the reported prevalence of sexual dysfunction in PWE is due to the significant heterogeneity among the studies with regard to patient population, type and severity of epilepsy, number and type of antiseizure drugs (ASDs) used, and the tools used for assessing sexual dysfunction. Generally, patients with uncontrolled epilepsy, longer duration of epilepsy, focal epilepsy, higher seizure frequency, and those receiving enzyme-inducing and multiple ASDs are more likely to have sexual dysfunction. Women generally have dysfunction in the domains of desire, while males usually have arousal disorders such as erectile dysfunction and premature ejaculation. There is limited evidence to indicate that sexual function improves in patients rendered seizure-free following epilepsy surgery. Multiple mechanisms including direct effects of epilepsy, effects of ASDs, and psychosocial factors contribute to sexual dysfunction in epilepsy. Circumstantial evidence indicates that seizures and interictal epileptiform discharges can directly affect the hypothalamic-pituitary axis as well as production of gonadal steroids. Enzyme-inducing ASDs cause sexual dysfunction by affecting the metabolism of gonadal steroids. Limited data suggest that newer ASDs including oxcarbazepine, lamotrigine, and levetiracetam cause no or minimal sexual dysfunction. Depression and anxiety significantly contribute to sexual dysfunction in PWE. A multipronged and multidisciplinary approach is essential for optimizing the sexual functions. Every effort should be made to identify and treat reversible causes including changing to nonenzyme-inducing ASDs and to provide symptomatic relief. Large, prospective studies are required to improve our understanding on prevalence and mechanisms of sexual dysfunction in PWE.

Generalized nonmotor (absence) seizures-What do absence, generalized, and nonmotor mean?

OBJECTIVE: Clinical absences are now classified as "generalized nonmotor (absence) seizures" by the International League Against Epilepsy (ILAE). The aim of this paper is to critically review the concept of absences and to put the accompanying focal and motor symptoms into the context of the emerging pathophysiological knowledge. METHODS: For this narrative review we performed an extensive literature search on the term "absence," and analyzed the plethora of symptoms observed in clinical absences. RESULTS: Arising from the localization and the involved cortical networks, motor symptoms may include bilateral mild eyelid fluttering and mild myoclonic jerks of extremities. These motor symptoms may also occur unilaterally, analogous to a focal motor seizure with Jacksonian march. Furthermore, electroencephalography (EEG) abnormalities may exhibit initial frontal focal spikes and consistent asymmetries. Electroclinical characteristics support the cortical focus theory of absence seizures. Simultaneous EEG/functional magnetic resonance imaging (fMRI) measurements document cortical deactivation and thalamic activation. Cortical deactivation is related to slow waves and disturbances of consciousness of varying degrees. Motor symptoms correspond to the spike component of the 3/s spike-and-wave-discharges. Thalamic activation can be interpreted as a response to overcome cortical deactivation. Furthermore, arousal reaction during drowsiness or sleep triggers spikes in an abnormally excitable cortex. An initial disturbance in arousal mechanisms ("dyshormia") might be responsible for the start of this abnormal sequence. SIGNIFICANCE: The classification as "generalized nonfocal and nonmotor (absence) seizure" does not covey the complex semiology of a patient's clinical events.

Computer-based monitoring and evaluation of epilepsy-related health variables and their impact on treatment decision.

OBJECTIVE: This study aimed to determine the effectiveness of electronic patient-reported outcomes (ePROs) with focus on epilepsy-specific quality of life, psychiatric and psychosocial burden, drug side effects, and patient satisfaction via the Computer-based Health Evaluation System (CHES) and to evaluate their impact on treatment regimen. METHODS: Forty consecutive patients with drug-resistant focal epilepsy undergoing prolonged video-electroencephalography (EEG) monitoring at the Department of Neurology, Innsbruck Medical University were included and randomized to an intervention group (questionnaire results accessible to the physicians) and a control group (questionnaire results inaccessible to the physicians). Patients had to complete questionnaires on the day of admission (T0) and the day of discharge (T1). RESULTS: Overall, twenty-five patients (25/40, 62.5%) showed abnormal assessment results, twelve of them exclusively due to pathological scores on the Liverpool Adverse Events Profile (LAEP). Mean LAEP score was within the pathological range of 48.8 points (48.8 ±â€¯7.2). The psychosocial burden with respect to the Performance, Socio-Demographic Aspects, Subjective Evaluation (PESOS) scale "fear" (48.7 ±â€¯21.4) was also moderately affected. Moreover, mean anxiety (9.1 ±â€¯4.4) and depression (7.6 ±â€¯4.5) scores were both slightly abnormal. Quality of life (as measured using the Quality of Life Inventory in Epilepsy (QOLIE-31)) was moderately impaired (seizure worry: 46.5 ±â€¯21.3, overall quality of life: 52.6 ±â€¯18.6, well-being: 54.1 ±â€¯16.3, energy-fatigue: 39.4 ±â€¯14.7, cognitive functioning: 41.4 ±â€¯19.5, medication effects: 46.2 ±â€¯23.4, social functioning: 51.1 ±â€¯20.8, and total score: 47.2 ±â€¯12.3). Careful medical history-taking and patient-physician consultations alone failed to detect needs for psychological/psychiatric help in three out of 7 patients in the control group (42.8%). Changes over time in Hospital Anxiety and Depression Scale (HADS) and QOLIE-31 scores were not significant. CONCLUSION: The use of ePROs was feasible and well accepted in the clinical setting. Treatment-associated adverse effects were the most frequently reported health-related restrictions. In particular, psychometric evaluation by applying ePROs can detect health-related problems in patients with epilepsy.

Potential years lost and life expectancy in adults with newly diagnosed epilepsy.

OBJECTIVE: Studies using relative measures, such as standardized mortality ratios, have shown that patients with epilepsy have an increased mortality. Reports on more direct and absolute measure such as life expectancy are sparse. We report potential years lost and how life expectancy has changed over 40 years in a cohort of patients with newly diagnosed epilepsy. METHODS: We analyzed life expectancy in a cohort of adult patients diagnosed with definite epilepsy between 1970 and 2010. Those with brain tumor as cause of epilepsy were excluded. By retrospective probabilistic record linkage, living or death status was derived from the national death registry. We estimated life expectancy by a Weibull regression model using gender, age at diagnosis, epilepsy etiology, and year of diagnosis as covariates at time of epilepsy diagnosis, and 5, 10, 15, and 20 years after diagnosis. Results were compared to the general population, and 95% confidence intervals are given. RESULTS: There were 249 deaths (105 women, age at death 19.0-104.0 years) in 1,112 patients (11,978.4 person-years, 474 women, 638 men). A substantial decrease in life expectancy was observed for only a few subgroups, strongly depending on epilepsy etiology and time of diagnosis: time of life lost was highest in patients with symptomatic epilepsy diagnosed between 1970 and 1980; the impact declined with increasing time from diagnosis. Over half of the analyzed subgroups did not differ significantly from the general population. This effect was reversed in the later decades, and life expectancy was prolonged in some subgroups, reaching a maximum in those with newly diagnosed idiopathic and cryptogenic epilepsy between 2001 and 2010. SIGNIFICANCE: Life expectancy is reduced in symptomatic epilepsies. However, in other subgroups, a prolonged life expectancy was found, which has not been reported previously. Reasons may be manifold and call for further study.

Calcium-binding proteins in focal cortical dysplasia.

OBJECTIVE: Alterations in γ-aminobutyric acid (GABA)-ergic cortical neurons have been reported in focal cortical dysplasia (FCD)Ia/IIIa, a malformation of cortical development associated with drug-resistant epilepsy. We compared numbers of neurons containing calcium-binding proteins parvalbumin (PV), calbindin (CB), and calretinin (CR) and densities of respective fibers in lateral temporal lobe surgical specimens of 17 patients with FCD with 19 patients who underwent anterior temporal lobe resection due to nonlesional temporal lobe epilepsy (non-FCD) as well as with 7 postmortem controls. METHODS: PV-, CB-, and CR-immunoreactive (IR) neurons were quantitatively investigated with use of two-dimensional cell counting and densitometry (reflecting mainly IR fibers) in cortical layers II, IV, and V. RESULTS: Numbers of PV-IR neurons, ratios of PV-containing to Nissl-stained neurons (correcting for eventual cell loss), and densities of PV-IR were higher in layer II of the cortex of FCD compared to non-FCD patients. Similarly, densities of CB-IR and CR-IR were also higher in layers II and V, respectively, of FCD than of non-FCD patients. Comparison with postmortem controls revealed significant higher cell numbers and fiber labeling for all three calcium-binding proteins in FCD cortex, whereas numbers of Nissl-stained neurons did not vary between FCD, non-FCD, and postmortem controls. In non-FCD versus postmortem controls, ratios of calcium-binding protein-IR cells to Nissl-stained neurons were unchanged in most instances except for increased CB/Nissl ratios and CB-IR densities in all cortical layers. SIGNIFICANCE: Increased numbers of PV neurons and fiber labeling in FCD compared to nondysplastic epileptic temporal neocortex and postmortem controls may be related to cortical malformation, whereas an increased number of CB-IR neurons and fiber labeling both in FCD and non-FCD specimens compared with postmortem controls may be associated with ongoing seizure activity. The observed changes may represent increased expression of calcium-binding proteins and thus compensatory mechanisms for seizures and neuronal loss in drug-resistant epilepsy.

Reproductive endocrine health in pubertal females with epilepsy on antiepileptic drugs: time to screen?

OBJECTIVES: Although previous studies suggest that valproate (VPA) may induce reproductive endocrine disorders, the effects of newer antiepileptic drugs (AEDs) on reproductive endocrine health have not been widely investigated and compared with those of older AEDs. Therefore, this multicenter cross-sectional study aimed to evaluate the prevalence of reproductive endocrine dysfunctions in pubertal females with epilepsy receiving VPA, lamotrigine (LTG), or levetiracetam (LEV) monotherapy. PATIENTS AND METHODS: Pubertal girls on VPA (n = 11), LTG (n = 8), or LEV (n = 13) monotherapy for at least 6 months were recruited. Healthy sex-matched and age-matched subjects were enrolled as controls (n = 32). Each participant underwent a comprehensive physical examination concerning signs of hyperandrogenism. The Ferriman-Gallwey score of hirsutism was assessed. In addition, all patients completed a standardized questionnaire regarding epilepsy, menstrual cycle, and hirsutism features. Adiposity indices were measured and weight gain was documented for each subject. RESULTS: Hirsutism score, occurrence of hyperandrogenism features, and adiposity indices were significantly higher in the VPA group when compared with LEV and control groups. VPA therapy was more frequently associated with weight gain when compared with LTG and controls, whereas no significant differences with regard to signs of hyperandrogenism were found between VPA and LTG groups. Furthermore, no differences in menstrual disorders were observed between groups. CONCLUSIONS: Pubertal girls with epilepsy receiving VPA monotherapy were more likely to develop signs of hyperandrogenism, that is, hirsutism and acanthosis, than those on LEV or controls. However, no differences in occurrence of menstrual disorders and other reproductive dysfunctions were found between VPA, LTG, LEV, and control groups. These findings do not allow us to clearly determine whether or not VPA, LEV, and LTG monotherapies considerably affect reproductive endocrine health in pubertal girls with epilepsy. Therefore, further prospective studies of larger sample sizes are needed to establish if screening tests should be recommended.

Primary headache types in adult epilepsy patients.

BACKGROUND: Headache is among the most common comorbidities in epilepsy. This study examined the distribution of different primary headache disorders in a large cohort of patients with diagnosed epilepsy. Headache types were analysed with regard to gender, type of epilepsy and antiepileptic drugs (AEDs). METHODS: In this prospective single-centre study, 500 patients with epilepsy (250 female, mean age: 45.52 ± 17.26 years) were evaluated with regards to primary headache types using a validated German headache questionnaire categorizing for migraine (MIG), tension-type headache (TTH) or trigeminal autonomic cephalalgias (TAC), their combinations and unclassifiable headache. Data regarding type of epilepsy, seizure-associated headache, AED treatment and seizure freedom were collected. RESULTS: Of 500 patients with epilepsy, 163 (32.6%) patients (108 female and 55 male) reported suffering from headaches at least 1 day per month. MIG (without aura, with aura) and TTH were the most frequent headache type (MIG 33.1%, TTH 33.1%). Female epilepsy patients reported headaches significantly more often than male patients (x2 = 8.20, p = 0.0042). In contrast, the type of epilepsy did not significantly affect headache distribution. Of 163 patients with headache, 66 (40.5%) patients reported seizure-associated headache and AEDs were used by 157 patients. Of importance, patients with AED monotherapy suffered from MIG less often when compared to patients on polytherapy (x2 = 4.79, p = 0.028). CONCLUSION: MIG and TTH are the most common headache types in epilepsy patients and headache is more frequent among female epilepsy patients. Monotherapy in AEDs might have a beneficial effect on the frequency of headache compared to polytherapy.

Simultaneous online SPE-LC-MS/MS quantification of six widely used synthetic progestins in human plasma.

Co-administration of synthetic progestin containing hormonal contraceptives (HCs) and antiepileptic drugs (AEDs) is a common clinical situation which needs specific considerations due to drug interactions. Several studies have demonstrated that lamotrigine plasma levels are significantly decreased during co-medication with HCs, and that this interaction is associated with increased seizure frequency in most of the cases. Additionally, an increase in contraceptive failure and unintended pregnancy could be observed during co-medication. Hence, monitoring of progestin plasma levels in patients with AED co-medication is of interest. A rapid and reliable online solid-phase extraction-high performance liquid chromatography-tandem mass spectrometry (online SPE-LC-MS/MS) method using gradient elution in the LC domain was established and validated for the simultaneous quantitative determination of gestodene, dienogest, drospirenone, etonogestrel, cyproterone acetate, and levonorgestrel in human plasma. The online SPE-LC-MS/MS method covered a quantification concentration range of 5-100 ng/ml for dienogest, 1-100 ng/ml for etonogestrel and 2-100 ng/ml for all other analytes. Stable isotope-labeled internal standards were used for analyte quantification based on selected reaction monitoring experiments. Inter- and intra-assay precision and accuracy were determined from quality control (QC) samples at the lower limits of quantification and at low, medium, and high concentration levels within the calibration range. Inter-assay reproducibility at the QC levels was better than 10% (relative standard deviation, RSD), accuracy at these levels ranged from -3.7% to 11.3%. Total extraction efficiency, tested at three concentrations, ranged from 92.5% to 106.4%. Matrix interferences were excluded by post-column infusion experiments. To prove the applicability of the assay in clinical cohorts, a sample set (n = 298) stemming from study patients under AED/oral HC co-medication was screened for progestin plasma levels. This method has to be considered a research-use-only assay and must not be used for diagnostic or therapeutic purposes, since it did not undergo formal performance evaluation in the sense of the IVD directive (98/79/EG) of the European Community.

Video-EEG monitoring: safety and adverse events in 507 consecutive patients.

PURPOSE: Video-electroencephalography (EEG) monitoring plays a central role in the presurgical evaluation of medically refractory epilepsies and the diagnosis of nonepileptic attack disorders (NEADs). The aim of this study was to analyze safety and adverse events (AEs) during video-EEG monitoring. METHODS: We retrospectively evaluated 596 video-EEG sessions in 507 patients (233 men, mean age 36 years, standard deviation = 14, range 9-80 years) within a 6-year period. AEs were examined in detail and their risk factors were assessed using multiple logistic regression analysis. KEY FINDINGS: Forty-four patients (9%) experienced 53 AEs: 20 had psychiatric events (17 postictal psychosis, 2 panic attacks, 1 interictal psychosis), 15 had injuries (14 falls with minor injuries, 2 falls with fractures, 2 fractures without fall, 1 fall with epidural hematoma), 10 patients had 13 episodes of status epilepticus (SE), and one AE was treatment-related (valproic acid--induced encephalopathy). Patients with AEs were older (p = 0.036) and had a longer duration of epilepsy (p = 0.019). All AEs resulted in a prolonged hospital stay (p < 0.001). Ninety-one percent of the AEs occurred within the first 4 days of monitoring. Independent risk factors were duration of epilepsy >17 years [odds ratio (OR) 3.096; 95% confidence interval (CI) 1.548-6.189], a previous history of psychiatric illness (OR 16.882; 95% CI 5.469-52.110), a history of seizure-related injuries (OR 3.542; 95% CI 1.069-11.739), or a history of SE (OR 3.334; 95% CI 1.297-8.565). SIGNIFICANCE: The most common AEs were postictal psychosis, falls, and SE. Patients with an older age, long disease duration, psychiatric comorbidity, history of injuries, and SE have a higher risk.

Old and new antiepileptic drugs during pregnancy and lactation--report of a case.

We describe a case of a woman with epilepsy treated with primidone/phenobarbital (so-called "old" antiepileptic drug) and levetiracetam (so-called "new" antiepileptic drug) who was discouraged from breastfeeding, resulting in clinically significant withdrawal seizures in her newborn. As a consequence, even when two or more antiepileptic drugs are needed for the treatment of women with epilepsy, breastfeeding should be recommended, mothers should be informed about the possibility of drug effects on the neonate, and infants of mothers treated with primidone/phenobarbital should be closely monitored for possible signs of sedation.

Emotional Recognition in Patients With Mesial Temporal Epilepsy Associated With Enlarged Amygdala.

BACKGROUND: Amygdalae play a central role in emotional processing by interconnecting frontal cortex and other brain structures. Unilateral amygdala enlargement (AE) is associated with mesial temporal lobe epilepsy (mTLE). In a relatively large sample of patients with mTLE and AE, we aimed to evaluate functional integration of AE in emotion processing and to determine possible associations between fMRI activation patterns in amygdala and deficits in emotion recognition as assessed by neuropsychological testing. METHODS: Twenty-two patients with drug resistant unilateral mTLE due to ipsilateral AE were prospectively recruited in a large epilepsy unit and compared with 17 healthy control subjects in terms of amygdala volume, fMRI activation patterns and performance in emotion recognition as assessed by comprehensive affect testing system (CATS) and Ekman faces. All patients underwent structural and functional 1.5 Tesla MRI, electro-clinical assessment and neuropsychological testing. RESULTS: We observed BOLD signal ipsilateral to AE (n = 7; group PAT1); contralateral to AE (n = 6; group PAT2) and no activation (n = 9; group PAT3). In the region of interest (ROI) analysis, beta estimates for fearful face > landscape contrast in the left amygdala region did not differ significantly in patients with left TLE vs. patients with right TLE [T (16) = -1.481; p = 0.158]. However, beta estimates for fearful face > landscape contrast in the right amygdala region were significantly reduced in patients with right TLE vs. patients with left TLE [T (16) = -2,922; p = 0.010]. Patients showed significantly lower total scores in CATS and Ekman faces compared to healthy controls. CONCLUSION: In our cohort, patients with unilateral mesial TLE and ipsilateral AE, an amygdala could display either functional integration in emotion recognition or dysfunction as demonstrated by fMRI. Perception and recognition of emotions were impaired more in right-sided mTLE as compared to left-sided mTLE. Neuropsychological tests showed deficits in emotion recognition in patients as compared to healthy controls.

Hormonal alterations following seizures.

Postictal increases in prolactin (PRL), luteinizing hormone, and follicle-stimulating hormone have been recorded in patients with both generalized tonic-clonic and partial seizures. Elevations of PRL and luteinizing hormone were seen immediately and at 20 minutes after generalized tonic-clonic seizures in male and female patients. Usually, PRL blood levels return to normal values within 1 hour. Previous studies have evaluated the utility of the transient increases in PRL, neuron-specific enolase, and S-100 protein as markers of epileptic seizures in children and adults. The conclusion was that measurement of serum PRL is a reliable confirmatory test in the presence of a seizure, but only modestly effective as a screening test for suspected seizures. Temporal lobe epilepsy is associated with abnormalities of reproductive physiology, but the mechanisms of hormonal dysregulation are not clear. A direct influence of epilepsy on the reproductive endocrine system is suggested by acute changes in PRL and gonadotropin levels following generalized and partial seizures, pointing to a possible relationship between temporolimbic epileptiform discharges and particular reproductive endocrine disorders. Chronic effects of the epileptic state and the acute impact of seizures could alter hypothalamic function, as indicated by downstream pulsatile secretion of luteinizing hormone. The brain controls reproductive function primarily through hypothalamic regulation of pituitary secretion regions of the hypothalamus. These are areas that are involved in the regulation, production, and secretion of gonadotropin-releasing hormone and receive extensive direct connections from the cerebral hemispheres, especially from temporolimbic structures, most notably from the amygdala, that are commonly involved in temporal lobe epilepsy. Significant relationships have been uncovered through which ictal and postictal effects of seizures and epilepsy may influence the function of this complex neuroendocrine system.

Chronic antiepileptic monotherapy, bone metabolism, and body composition in non-institutionalized children.

AIM: The aim of this study was to determine the influence of chronic monotherapy with antiepileptic drugs (AEDs) on vitamin D levels, bone metabolism, and body composition. METHOD: Eighty-five children (38 males, 47 females; mean age 12 y 5 mo, SD 3 y 4 mo) were treated with valproate and 40 children (28 males, 12 females; mean age 11 y 10 mo, SD 3 y) were treated with other AEDs (lamotrigine, sulthiame, or oxcarbazepine), comprising the non-valproate group. Forty-one healthy children (29 males 12 females; mean age 12 y 1 mo, SD 3 y 5 mo) served as a comparison group. Height, weight, body impedance analysis, 25-hydroxyvitamin D, calcium, phosphate, two bone resorption markers (receptor activator of nuclear factor kappaB ligand [RANKL] and tartrate-resistant acid phosphatase 5b [TRAP5b]), osteoprotegerin, and leptin were measured. RESULTS: No child was vitamin D deficient as defined by a 25-hydroxyvitamin D (25OHD) level of less than 25 nmol/l (<10 ng/ml). Leptin, body fat, weight standard deviation score (SDS), and body mass index (BMI) SDS were all significantly higher (each p<0.001) in valproate-treated children than in the non-valproate group, as were calcium (p=0.027) and RANKL (p=0.007) concentrations. Similarly, leptin was significantly higher in the valproate group than in control participants (p<0.001), as were body fat (p=0.023), weight SDS (p=0.046), BMI SDS (p=0.047), calcium (p<0.001), and RANKL (p<0.001), whereas TRAP5b concentrations were significantly lower in the valproate-treated group (p=0.002). Furthermore, calcium and RANKL levels were significantly higher in the non-valproate group than in comparison participants (p<0.001 and p=0.016 respectively). INTERPRETATION: Non-enzyme-inducing or minimal enzyme-inducing AED monotherapy does not cause vitamin D deficiency in otherwise healthy children with epilepsy. Valproate therapy is associated with increases in weight, body fat, and leptin concentration, as well as with a bone metabolic profile that resembles slightly increased parathyroid hormone action.

Repetitive miniature spikes - An underreported EEG pattern.

OBJECTIVES: Low-voltage repetitive spikes are mainly described with invasive recordings and considered highly suggestive for focal cortical dysplasia (FCD). This EEG pattern has received less attention in routine scalp EEG. METHODS: Prospective collection of EEGs with low-voltage (<50 µV) repetitive spikes (repetitive miniature spikes - RMS) between July 1982 and July 2017 at the EEG laboratory of the Medical University of Innsbruck. We analyzed patterns of RMS on routine scalp EEG recordings and examined the relationship to clinical and brain imaging data. RESULTS: Overall, RMS were seen in 38 patients representing zero to four observations out of 5000 records per year. RMS occurred rhythmically in 14, periodically in 17 and irregularly in seven patients. The EEG pattern appeared with a frontal and central predominance. All but five patients had epilepsies; eleven patients had non-convulsive status epilepticus. Cerebral magnetic resonance imaging (cMRI) detected malformations of cortical development in eleven patients, including six patients with focal cortical dysplasias. CONCLUSIONS: RMS are rare EEG patterns indicating focal epilepsy. Their observation on routine scalp EEGs should prompt further clinic-radiologic investigation. SIGNIFICANCE: RMS resemble a clearly recognizable pattern in routine EEG, which is highly associated with focal epilepsy. The term is descriptive and can be added to the red flags, which can be found on routine EEG indicating underlying structural brain pathology, often in form of focal cortical dysplasia.

Bidirectional interaction between oral contraception and lamotrigine in women with epilepsy - Role of progestins.

PURPOSE: To investigate the effects of various progestins in combined oral contraceptives (COCs) on lamotrigine (LTG) serum concentrations and, vice versa, the potential impact of LTG on progestin serum levels during the menstrual cycle. METHODS: Twenty women with epilepsy (WWE) undergoing LTG monotherapy and COC (LTG group; mean ± SD [median; range] age 24.2 ± 4.6 [23.0; 18-37] years) as well as fourteen controls on COC (24.9 ± 5.6 [22.5; 20-39] years) were assessed for eligibility and all agreed to participate in the study and remained for data analyses. RESULTS: LTG levels differed significantly between phases of inactive pill and active pill use (p= 0.004), particularly with drospirenon (p= 0.018) and levonorgestrel (p= 0.068) as progestogen component but not with gestoden (p= 0.593). Furthermore, the LTG group showed significantly lower progestin levels during inactive pill when compared to active pill use with respect to levonorgestrel (p= 0.042) and drospirenon (p= 0.018) but not to gestoden (p= 0.109). Progestin concentrations did not differ between patients and controls (p> 0.05). CONCLUSIONS: The findings suggest that drospirenon and levonorgestrel but not gestoden seem to reduce LTG serum concentrations when being co-administered in WWE which might be of importance concerning seizure risk. Vice versa, no effect of LTG on several progestins could be demonstrated, arguing against a potential loss of contraception safety with LTG.

Female issues in epilepsy: a critical review.

The focus on gender-related issues for women with epilepsy has heightened in recent years. The emphasis, however, has been on the childbearing years. Epilepsy and antiepileptic drug treatment affect sexual development, the menstrual cycle, and aspects of contraception, fertility, and reproduction. Female patients with epilepsy at a reproductive age face a unique set of reproductive issues, ranging from descriptions of disorders of reproduction in epilepsy and its causes, to contraception, pregnancy, sexuality, menopause, and osteoporosis. Conditions and diseases that specifically affect women are discussed. The role of hormones across the life cycle--endogenous and exogenous hormones and their effects on drug interactions, drug metabolism, and therapeutic outcomes--is described. Contraception and pregnancy issues for women with epilepsy have received the appropriate attention.

Epilepsy and hormones: a critical review.

Especially during growth, puberty, and menopause, profound changes including maturation of the growth hormone, sex steroid, and thyroid axes, as well as alterations in lipid homeostasis, cardiac integrity, and other enzyme systems, occur physiologically. With epilepsy, however, things are often changing, and there may be a complicated interplay between hormones, epilepsy, and antiepileptic drugs (AEDs). On the one hand, epilepsy itself possibly elicits diverse effects on different enzyme systems including sex steroids, the neuro-cardio-endocrine axis, and bone health. On the other hand, different AEDs are known to induce neuroendocrine changes (e.g., lipid metabolism) that may have deleterious consequences on health and well-being later in life. It is important for physicians and epileptologists to have in mind and to consider the endocrine effects induced by epilepsy itself or by a certain AED when starting antiepileptic therapy, especially when it is expected that long-term treatment will be necessary.

Differential effects of levetiracetam, carbamazepine, and lamotrigine on reproductive endocrine function in adults.

Animal studies have shown endocrine changes after levetiracetam treatment. The present study investigated reproductive and sexual function in patients with epilepsy (aged 18-45) treated with levetiracetam (LEV: 30 men/26 women), carbamazepine (CBZ: 63 men/30 women), or lamotrigine (LTG: 37 men/40 women) monotherapy and in healthy controls (36 men/44 women). In women, no endocrine changes were observed during LEV treatment, whereas steroid hormone-binding globulin levels were greater and progesterone levels lower in women using CBZ. Dehydroepiandrosterone sulfate levels were higher and androstenedione levels lower in LTG-treated women. Arizona Sexual Experience Scale scores, which were significantly lower in females using LTG or LEV, suggesting they have better sexual function than CBZ users and controls. In men, no drug-specific hormonal pattern was observed after LEV treatment. Male patients in all treatment groups had lower androstenedione and free testosterone. Those using CBZ had lower free androgen indices and dehydroepiandrosterone sulfate levels, and higher steroid hormone-binding globulin, follicle-stimulating hormone, and luteinizing hormone levels. Arizona Sexual Experience Scale scores for men were similar in all groups. In conclusion, LEV treatment apparently has no drug-specific sexual or endocrine side effects in men or women in this age group.