Anti-NMDA receptor encephalitis and MOG-associated demyelination - a case report with long-term follow-up and a systematic review.

BACKGROUND: Overlap syndromes of anti-NMDA receptor encephalitis and MOG-mediated demyelination have been reported. In this case we provide a long-term longitudinal follow-up of clinical and imaging characteristics as well as of antibody dynamics. CASE PRESENTATION: We report a 32-year-old male patient who presented with psychosis, decreased consciousness and movement disorders and was tested positive for anti-NMDA receptor antibodies. Forty-four months after symptom onset and diagnosis of autoimmune encephalitis, he suffered from relapse. At this time, the patient developed anti-MOG and anti-Caspr2 antibodies. Treatment with plasmapheresis, steroids and rituximab eventually led to substantial clinical and radiological improvement. Anti-Caspr2 antibodies persisted, anti-NMDA receptor antibodies decreased, while anti-MOG antibodies turned negative again. CONCLUSION: We provide long-term longitudinal follow-up of a patient with anti-NMDA receptor encephalitis who developed triple antibody positivity at the time of relapse. Antibody dynamics were associated with clinical disease course.

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.

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.

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.

A prospective controlled study about sleep disorders in drug resistant epilepsy.

OBJECTIVE: To evaluate sleep disorders and chronotype in patients with drug resistant focal and generalised epilepsy compared to healthy controls. METHODS: Sixty four patients with focal and six with generalised, drug resistant epilepsy were included and compared to 70 age- and gender-matched healthy controls. Patients with any relevant comorbidity were excluded. Sleep disorders and chronotype were investigated by validated questionnaires. The impact of epilepsy on quality of life was also documented in patients. RESULTS: The median Pittsburgh Sleep Quality Index (PSQI) was 4 in patients and 3 in controls (median [range], IQR; patients: 4 [1-17], 3-6; controls: 3 [0-11], 2-4; p = 0.024). Self-reported confusional arousals and probable REM sleep behaviour disorder (RBD) were more frequent in patients (30.4% vs. 8.6%, p = 0.036 and 10.6% vs. 1.4%, p = 0.030, respectively). A higher risk for possible sleep apnea was identified in patients (22.9% vs. 5.7%, p = 0.042), whereas Epworth Sleepiness Score was normal in both groups (p = 1). Chronotype, assessed by the midsleep on free days, did not differ between groups (p = 0.540). Quality of life was worse in patients with PSQI scores >5 (p = 0.016). CONCLUSION: Self-reported confusional arousals, probable RBD and a high risk for sleep apnea occurred significantly more often in patients with drug resistant epilepsy. Sleep quality differed significantly between both groups. Whether these results are due to motor activity during nocturnal epileptic seizures, parasomnia episodes, or sleep-related breathing disorder, needs further evaluation via video-polysomnography. We could confirm, at least in some cases, the previously reported mutual relationship between sleep disorders and epilepsy.

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.

Risky Decision Making in Juvenile Myoclonic Epilepsy.

It is not known whether patients with juvenile myoclonic epilepsy (JME) differ from healthy people in decision making under risk, i.e., when the decision-making context offers explicit information about options, probabilities, and consequences already from the beginning. In this study, we adopted the Game of Dice Task-Double to investigate decision making under risk in a group of 36 patients with JME (mean age 25.25/SD 5.29 years) and a group of 38 healthy controls (mean age 26.03/SD 4.84 years). Participants also underwent a comprehensive neuropsychological assessment focused on frontal executive functions. Significant group differences were found in tests of psychomotor speed and divided attention, with the patients scoring lower than the controls. Importantly, patients made risky decisions more frequently than controls. In the patient group, poor decision making was associated with poor executive control, poor response inhibition, and a short interval since the last seizure episode. Executive control and response inhibition could predict 42% of variance in the frequency of risky decisions. This study indicates that patients with JME with poorer executive functions are more likely to make risky decisions than healthy controls. Decision making under risk is of major importance in every-day life, especially with regard to treatment decisions and adherence to long-term medical therapy. Since even a single disadvantageous decision may have long-lasting consequences, this finding is of high relevance.

Sleep disorders and circadian rhythm in epilepsy revisited: a prospective controlled study.

OBJECTIVE: Sleep disturbance is reported to be frequent in epilepsy. The role of comorbidity, which is frequently accompanied by sleep disturbance, has not been investigated. The present study assessed sleep disorders and circadian rhythm in patients with epilepsy, in whom relevant comorbidity was carefully excluded. METHODS: Two hundred patients with epilepsy (100 generalized, 100 partial), without relevant psychiatric, neurological or internal comorbidity, were compared with 100 matched controls. The questionnaire contained specifically tailored questions to address the association between epilepsy and sleep disturbance, and validated questionnaires aimed at sleep quality, excessive daytime sleepiness (EDS), circadian rhythm, sleep disorders, and quality of life. RESULTS: Forty-one percent of the participants reported on the acute effects of present or past seizures on sleep-wake rhythm, whereas chronic effects were not evident. Participants and controls did not differ in the rates of chronic sleep disturbance, EDS, and presence of sleep disorders (all p-values non-significant or n.s.). Apart from earlier sleep times on workdays (p = 0.001) in those with epilepsy, circadian variables were similarly distributed. Epilepsy was well controlled, with 75.9% being seizure free for ≥ 1 year. Longer durations of epilepsy showed a negative correlation with sleep quality (rho = -0.256, p < 0.001). Participants with generalized and partial epilepsies did not differ in rates of sleep disturbance, EDS, sleep disorders, and variables of circadian rhythm (all p-values n.s.). CONCLUSION: The present study demonstrated that chronic sleep disturbance is not increased in patients with well-controlled epilepsy without relevant comorbidity. This supports comorbidity and insufficient seizure control as major contributors of sleep disturbance in epilepsy.

Generalized tonic-clonic seizures and antiepileptic drugs during pregnancy--a matter of importance for the baby?

This study investigates the impact of generalized tonic-clonic seizures (GTCS) and antiepileptic drugs (AED) during pregnancy on gestational age (GA) and anthropometric data of newborns. One hundred twenty-nine singleton pregnancies resulting in live births from September 1999 to October 2010 in 106 women with epilepsy on AED therapy, recorded within the framework of the EURAP (International Registry of Antiepileptic Drugs and Pregnancy) program at the Department of Neurology, Medical University Innsbruck, Austria, were studied. Occurrence of ≥ 1 GTCS during pregnancy was associated with a shorter GA [median (range) 37.5 [35.1-41.6] vs. 39.7 [29.1-46.3] weeks; p ≤ 0.001], an overall five times higher preterm risk (p = 0.042) and a reduced birth weight in boys (2,900 [2,050-3,870] vs. 3,205 [1,575-4,355] g; p = 0.040). In primipara, when compared to multipara, GTCS ≥ 1 significantly reduced the GA (37.9 [35.1-41.6] vs. 39.7 [29.4-44.9] weeks; p = 0.020) and raised the incidence of low birth weight (LBW) (p = 0.022) in neonates. Antiepileptic drug polytherapy significantly increased the risk for small-for-gestational-age regarding weight (SGA(W); p = 0.035) and regarding weight and/or length (SGA(W/L); p = 0.046) when compared to monotherapy. GTCS during pregnancy was associated with diverse negative effects comprising shorter GA, an increased incidence of prematurity and LBW in primiparous women. Furthermore, AED polytherapy was correlated with an enhanced risk for SGA delivery. Re-evaluating the need for drug therapy (in particular polytherapy), maintaining seizure control for a given period before pregnancy and counseling about the importance of preventing GTCS might improve pregnancy outcome in women with epilepsy.