Reduced Gastric Contraction in Rapid-Eye-Movement Sleep Behavior Disorder and De Novo Parkinson's Disease.

BACKGROUND: Reduced gastric motility in Parkinson's disease (PD) has been reported, but hardly any study exists in subjects with isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD), a specific prodrome of α-synucleinopathies. OBJECTIVES: We compared the gastric motility of 17 iRBD subjects with that of 18 PD subjects (15 drug naive, 3 early treated in defined off) and 15 healthy controls (HC) with real-time magnetic resonance imaging (rtMRI). METHODS: After overnight fasting, participants consumed a standardized breakfast and underwent a 3-T rtMRI of the stomach. Amplitude and velocity of the peristaltic waves were analyzed under blinded conditions. Gastric motility index (GMI) was calculated. The procedure was repeated in 12 of 17 iRBD subjects ~2.5 years later. Nine of these 12 iRBD subjects were hyposmic. RESULTS: In iRBD and PD subjects the amplitude of the peristaltic waves was significantly reduced compared with HCs (iRBD vs. HC: 8.7 ± 3.7 vs. 11.9 ± 4.1 mm, P = 0.0097; PD vs. HC: 6.8 ± 2.2 vs. 11.9 ± 4.1 mm, P = 0.0001). The amplitude in iRBD and PD subjects was decreased to the same extent. The GMI was reduced in only PD subjects (PD vs. HC: P = 0.0027; PD vs. iRBD: P = 0.0203). After ~2.5 years the amplitude in iRBD subjects did not significantly decrease further. CONCLUSION: The amplitude of the peristaltic waves was markedly reduced in iRBD, a prodrome of α-synucleinopathies. This reduction was similar to the extent observed already in manifest early PD. This finding implies that the α-synuclein pathology affects the innervation of the stomach already in the prodromal stage. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Morphometric magnetic resonance imaging (MRI) postprocessing in MRI-negative patients with first unprovoked seizure.

OBJECTIVE: The aim of the study was to evaluate the benefits of morphometric magnetic resonance imaging (MRI) postprocessing in patients presenting with a first seizure and negative MRI results and to investigate these findings in the context of the clinical and electroencephalographic data, seizure recurrence rates, and epilepsy diagnosis in these patients. METHODS: We retrospectively reviewed 97 MRI scans of patients with first unprovoked epileptic seizure and no evidence of epileptogenic lesion on clinical routine MRI. Morphometric Analysis Program (MAP; v2018), automated postprocessing software, was used to identify subtle, potentially epileptogenic lesions in the three-dimensional T1-weighted MRI data. The resulting probability maps were examined together with the conventional MRI images by a reviewer who remained blinded to the patients' clinical and electroencephalographical data. Clinical data were prospectively collected between February 2018 and May 2023. RESULTS: Among the apparently MRI-negative patients, a total of 18 of 97 (18.6%) showed cortical changes suggestive of focal cortical dysplasia. Within the population with positive MAP findings (MAP+), seizure recurrence rates were 61.1% and 66.7% at 1 and 2 years after the first unprovoked seizure, respectively. Conversely, patients with negative MAP findings (MAP-) had lower seizure recurrence rates of 27.8% and 34.2% at 1 and 2 years after the first unprovoked seizure, respectively. Patients with MAP+ findings were significantly more likely to be diagnosed with epilepsy than those patients with MAP- findings (χ2 [1, n = 97] = 14.820, p < .001, odds ratio = 21.371, 95% CI = 2.710-168.531) during a mean follow-up time of 22.51 months (SD = 16.7 months, range = 1-61 months). SIGNIFICANCE: MRI postprocessing can be a valuable tool for detecting subtle epileptogenic lesions in patients with a first seizure and negative MRI results. Patients with first seizure and MAP+ findings had high seizure recurrence rates, meeting the criteria for beginning epilepsy.

Undiagnosed obstructive sleep apnea syndrome as a treatable cause of new-onset sleepiness in some post-COVID patients.

BACKGROUND AND PURPOSE: Infection with COVID-19 can lead to persistent sequelae, such as fatigue, daytime sleepiness or disturbed sleep, that can remain for more than 12 weeks and that are summarized as post-COVID syndrome. The causes remain unclear. The present study investigated the presence of sleep disorders in patients with post-COVID syndrome using polysomnography. METHODS: Thirty-four patients with post-COVID syndrome and new-onset fatigue and sleepiness after a SARS-CoV2 infection underwent polysomnography in accordance with American Association of Sleep Medicine (AASM) standards as part of their clinical workup. Analysis was performed visually based on AASM criteria (scoring manual version 2.6, 2020). RESULTS: Polysomnography revealed a sleep efficiency of <80% in 50% of patients and a mean respiratory disturbance index (RDI) of 9.9 ± 15.4/h. Excluding central apneas, 12 patients (35%) had an RDI of ≥5/h, pointing to obstructive sleep apnea syndrome (OSAS; AASM 2014). Patients with a high RDI were significantly older (p = 0.01) and showed a trend towards a higher body mass index (p = 0.08) than patients with a normal RDI but had no other risk factors for OSAS. Six patients agreed to long-term treatment of their OSAS and all reported discontinuation of daytime symptoms. CONCLUSIONS: Post-COVID symptoms such as daytime sleepiness, fatigue and memory and concentration problems may in part be a result of reduced sleep efficiency and sleep apnea in a relevant percentage of patients. This possibly treatable cause of the symptoms should be kept in mind in patients presenting with post-COVID syndrome.

First epileptic seizure and quality of life - A prospective study.

OBJECTIVE: Impaired QoL and depression are common in patients with chronic epilepsies; however, data on the impact of a first seizure on QoL are sparse. According to the current ILAE-definition of epilepsy, patients may be diagnosed with epilepsy immediately after the first seizure, if EEG and/or imaging findings are abnormal. Patients with normal findings in imaging and EEG are not diagnosed as having epilepsy. We investigated QoL in patients after a first seizure with and without a consecutive diagnosis of epilepsy to detect differences between groups within the first year after seizure. METHODS: We examined patients (n = 152) after a first epileptic seizure and six and 12 months thereafter using demographic, clinical and QoL-related questionnaire data (Short Form-36 Health Survey (SF-36), Quality of Life in Epilepsy Inventory-31 (QOLIE-31), Beck's depression inventory II (BDI-II)). RESULTS: Patients diagnosed with epilepsy after the first seizure showed a tendency of reduced mental health-related QoL six (p =.098) and 12 months (p =.092) after the first seizure compared to patients who were not diagnosed with epilepsy, but were diagnosed as having had a single first seizure. There were no significant differences between the two groups in physical health-related QoL. Multiple regression analyses showed that especially depressive symptoms explained 22.0 - 48.7 % of the variance in mental health-related QoL six (p <.001) and 12 months (p <.001) after the first seizure. Physical health-related QoL was especially predicted by age (p <.001), group (p =.002) and recurrent seizures (p = < 0.001). In PWE, there was a statistical trend with improving QOLIE-31 overall scores from six to 12 months (p =.086). CONCLUSION: Our results suggest that QoL may be impaired in patients diagnosed with epilepsy early, immediately after the onset of disease. Early follow-up monitoring from the beginning of patient career is important for possible interventions and to improve patients' daily life in the long term.

Consultation Requests and Satisfaction with a Telehealth Network for Epilepsy: Longitudinal Analysis of the Epilepsy Network Hessen Evaluation.

Background: Telemedicine improves access to specialized medical expertise, as required for paroxysmal disorders. The Epilepsy Network Hessen Evaluation (ENHE) is a pilot cross-sectoral teleconsultation network connecting primary neurologists and pediatricians with epilepsy centers in Hessen, a federal German state. Methods: We prospectively and longitudinally evaluated telehealthcare in the ENHE. Participating physicians rated each consultation for satisfaction and impact on further management. The survey was administered at each consultation and 3 months later. Results: We analyzed 129 consultations involving 114 adult and pediatric patients. Their mean age was 34 years (standard deviation: 26, range: 0.1-91 years), 48% were female, and 34% were children and adolescents. The most common consultation requests were co-evaluation of an electroencephalogram (electroencephalogram [EEG]; 76%) and therapeutic (33%) and differential diagnosis (24%) concerns. Physicians transmitted one paraclinical examination on average (range: 1-4), predominantly EEG (85%), followed by magnetic resonance imaging (17%) and written records (9%). Response rates were 72% for the initial and 67% for the follow-up survey. Across respondents, 99% (n = 92) were satisfied with the ENHE. Overall, 80% of the consultations contributed to the diagnosis, and 90% were considered helpful for treatment, influencing it in 71% of cases. Seizure frequency had decreased more often (96%) than increased (4%) at 3 months. The initial diagnosis was confirmed in 78% of patients. Discussion: In this pilot teleconsultation network for paroxysmal disorders, diagnostic and therapeutic advice was perceived as helpful. Clinical outcomes were largely positive, suggesting tele-epileptology is viable for paroxysmal (seizure) disorders.

Diffusion magnetic resonance imaging connectome features are predictive of functional lateralization of semantic processing in the anterior temporal lobes.

Assessment of regional language lateralization is crucial in many scenarios, but not all populations are suited for its evaluation via task-functional magnetic resonance imaging (fMRI). In this study, the utility of structural connectome features for the classification of language lateralization in the anterior temporal lobes (ATLs) was investigated. Laterality indices for semantic processing in the ATL were computed from task-fMRI in 1038 subjects from the Human Connectome Project who were labeled as stronger rightward lateralized (RL) or stronger leftward to bilaterally lateralized (LL) in a data-driven approach. Data of unrelated subjects (n = 432) were used for further analyses. Structural connectomes were generated from diffusion-MRI tractography, and graph theoretical metrics (node degree, betweenness centrality) were computed. A neural network (NN) and a random forest (RF) classifier were trained on these metrics to classify subjects as RL or LL. After classification, comparisons of network measures were conducted via permutation testing. Degree-based classifiers produced significant above-chance predictions both during cross-validation (NN: AUC-ROC[CI] = 0.68[0.64-0.73], accuracy[CI] = 68.34%[63-73.2%]; RF: AUC-ROC[CI] = 0.7[0.66-0.73], accuracy[CI] = 64.81%[60.9-68.5]) and testing (NN: AUC-ROC[CI] = 0.69[0.53-0.84], accuracy[CI] = 68.09[53.2-80.9]; RF: AUC-ROC[CI] = 0.68[0.53-0.84], accuracy[CI] = 68.09[55.3-80.9]). Comparison of network metrics revealed small effects of increased node degree within the right posterior middle temporal gyrus (pMTG) in subjects with RL, while degree was decreased in the right posterior cingulate cortex (PCC). Above-chance predictions of functional language lateralization in the ATL are possible based on diffusion-MRI connectomes alone. Increased degree within the right pMTG as a right-sided homologue of a known semantic hub, and decreased hubness of the right PCC may form a structural basis for rightward-lateralized semantic processing.

Prospective, longitudinal, multicenter study on the provision of information regarding sudden unexpected death in epilepsy to adults with epilepsy.

OBJECTIVE: Despite increased awareness of the serious epilepsy complication sudden unexpected death in epilepsy (SUDEP), a substantial population of people with epilepsy (PWE) remain poorly informed. Physicians indicate concern that SUDEP information may adversely affect patients' health and quality of life. We examined SUDEP awareness and the immediate and long-term effects of providing SUDEP information to PWE. METHODS: Baseline knowledge and behaviors among PWE and behavioral adjustments following the provision of SUDEP information were evaluated in a prospective, multicenter survey using the following validated scales: Neurological Disorders Depression Inventory for Epilepsy for depression symptoms, the EuroQoL five-dimension scale for health-related quality of life (HRQoL), a visual analog scale for overall health, the revised Epilepsy Stigma Scale for perceived stigma, and the Seizure Worry Scale for seizure-related worries. The prospective study collected data through semiquantitative interviews before (baseline), immediately after, and 3 months after the provision of SUDEP information. RESULTS: In total, 236 participants (mean age = 39.3 years, range = 18-77 years, 51.7% women) were enrolled, and 205 (86.9%) completed long-term, 3-month follow-up. One patient died from SUDEP before follow-up. No worsening symptoms from baseline to 3-month follow-up were observed on any scale. At baseline, 27.5% of participants were aware of SUDEP. More than 85% of participants were satisfied with receiving SUDEP information. Three quarters of participants were not concerned by the information, and >80% of participants recommended the provision of SUDEP information to all PWE. Although most patients reported no behavioral adjustments, 24.8% reported strong behavioral adjustments at 3-month follow-up. SIGNIFICANCE: The provision of SUDEP information has no adverse effects on overall health, HRQoL, depressive symptoms, stigma, or seizure worry among PWE, who appreciate receiving information. SUDEP information provision might improve compliance among PWE and reduce but not eliminate the increased mortality risk.

Effect of the revised definition of epilepsy on treatment decisions and seizure recurrence after a first epileptic seizure.

BACKGROUND: Studies on risk factors for epilepsy and seizure recurrence after a first seizure are usually based on the old definition of epilepsy with the need for two unprovoked seizures. The current definition of epilepsy allows diagnosis and treatment of epilepsy after a first seizure if the recurrence risk is >60%. We evaluate treatment decisions, seizure recurrence and risk factors for epilepsy related to the application of the new definition of epilepsy. METHODS: Data of 629 patients with a first seizure were analyzed to investigate changes of treatment decisions and seizure recurrence after the revised definition of epilepsy. We used binary logistic regression to investigate the impact of multiple factors influencing seizure recurrence like electroencephalogram (EEG) and magnetic resonance imaging (MRI) results and administration of antiseizure medication (ASM). RESULTS: The proportion of patients receiving ASM significantly increased from 70.4% to 80.5% (p = 0.015) following the new epilepsy definition, without any significant changes in the recurrence rate (40.8% vs. 45.5% after 2 years, p > 0.05). The presence of interictal epileptiform discharges (IED) in the EEG increased (OR = 1.98) and administration of ASM decreased (OR = 0.43) recurrence rates significantly. CONCLUSIONS: The new definition of epilepsy was associated with increased application of ASM, but not with reduced recurrence rates. The study confirms the presence of IED as a strong risk factor for seizure recurrence and the protective effect of ASM. The influence of imaging findings, which have a strong impact on the new definition of epilepsy, could not be confirmed.

Supply problems of antiseizure medication are common among epilepsy patients in Germany.

OBJECTIVE: To evaluate the frequency of reported antiseizure medication (ASM) supply problems among patients with epilepsy (PWE) in Germany. METHODS: The Epi2020 study was a multicenter study focusing on different healthcare aspects of adult PWE in Germany. In addition to basic clinical and demographic characteristics, PWE were asked to answer a questionnaire regarding supply difficulties regarding their ASM, and if they had to discontinue ASM treatment due to supply problems. Generic switch of medication was recorded, and adverse effects were measured using the Liverpool Adverse Events Profile (LAEP) scale. Data were analyzed to detect predictors of supply problems. RESULTS: In total, 434 PWE with a mean age of 40 years (median 37 years, SD = 15.5, range: 18-83 years, 254 female) participated in this study. 53.7% of PWE (n = 233) reported that at least once in the past 12 months their ASM was not available at the pharmacy, and 24.9% (n = 108) reported having experienced ASM supply problems three times or more during the past 12 months. Patients with epilepsy treated with carbamazepine and zonisamide reported frequent problems with availability in 45.8% and 44.8% respectively, whereas those treated with lacosamide and valproate reported supply problems less frequently (17.0% and 16.4%, respectively). Nine patients (2.1%) were unable to take their ASM as prescribed at least once in the past 12 months due to supply problems. Forty-nine patients (11.3%) reported having to switch ASM due to supply difficulties with generic replacement occurring in 39.4% (n = 171) of patients. Those with supply problems were more likely to be treated with more ASMs and scored higher on the LAEP. CONCLUSION: Supply problems with ASM are frequent among PWE in Germany and are reported for older and newer ASMs. Supply problems contribute to ASM nonadherence and are positively correlated with the number of ASM taken and adverse events.

Unemployment and early retirement among patients with epilepsy - A study on predictors, resilience factors and occupational reintegration measures.

The primary aim of this study was to identify predictors and resilience factors for unemployment and early retirement in patients with epilepsy of working age based on data from a multicenter German cohort study performed in 2020 (n = 456) by using multivariate binary logistic regression analysis. A second aim was to assess the assumed working ability of patients as well as the use of occupational reintegration measures. The unemployment rate was 8.3%, and 18% of patients had retired early due to epilepsy. Multivariate binary logistic regression analysis identified the presence of a relevant disability and frequent seizures as significant predictors of unemployment and early retirement, while seizures in remission were the only resilience factor associated with job retention. Regarding occupational incapacity, at the time of the survey, most of the patients in early retirement or unemployment were fit for work in their original or extended occupational setting. The proportion of patients with recent epilepsy-related occupational retraining (0.4%) or job changes (0.9%) was low, and only 2.4% reported an epilepsy-related reduction in work time. These findings underline the persistent disadvantage of patients with epilepsy in the professional field and the urgent need for effective, comprehensive work reintegration measures that must be made accessible for all patients.

Use of Health-Related Apps and Telehealth in Adults with Epilepsy in Germany: A Multicenter Cohort Study.

Background: Telehealth can improve the treatment of chronic disorders, such as epilepsy. Telehealth prevalence and use increased during the coronavirus disease 2019 (COVID-19) pandemic. However, familiarity with and use of telehealth and health-related mobile applications (apps) by persons with epilepsy remain unknown. Methods: We investigated telehealth use, demographics, and clinical variables within the multicenter Epi2020 cross-sectional study. Between October and December 2020, adults with epilepsy completed a validated questionnaire, including individual questions regarding knowledge and use of apps and telehealth. Results: Of 476 included individuals (58.2% women; mean age 40.2 ± 15.4 years), 41.6% reported using health-related apps. Health apps were used more frequently (pedometer 32.1%, exercise app 17.6%) than medical apps (health insurance 15.1%, menstrual apps 12.2%) or apps designed for epilepsy (medication reminders 10.3%, seizure calendars 4.6%). Few used seizure detectors (i.e., apps as medical devices 1.9%) or mobile health devices (fitness bracelet 11.3%). A majority (60.9%) had heard the term telehealth, 78.6% of whom had a positive view. However, only 28.6% had a concrete idea of telehealth, and only 16.6% reported personal experience with telehealth. A majority (55%) would attend a teleconsultation follow-up, and 41.2% would in a medical emergency. Data privacy and availability were considered equally important by 50.8%, 21.8% considered data privacy more important, and 20.2% considered data availability more important. Current health-related app use was independently associated with younger age (p = 0.003), higher education (p < 0.001), and subjective COVID-19-related challenges (p = 0.002). Persistent seizure occurrence (vs. seizure freedom ≥12 months) did not affect willingness to use teleconsultations on multivariable logistic regression analysis. Conclusions: Despite positive telehealth views, few persons with epilepsy in Germany are familiar with specific apps or services. Socioeconomic factors influence telehealth use more than baseline epilepsy characteristics. Telehealth education and services should target socioeconomically disadvantaged individuals to reduce the digital care gap. German Clinical Trials Register (DRKS00022024; Universal Trial Number: U1111-1252-5331).

A patient-friendly 16-channel transmit/64-channel receive coil array for combined head-neck MRI at 7 Tesla.

PURPOSE: To extend the coverage of brain coil arrays to the neck and cervical-spine region to enable combined head and neck imaging at 7 Tesla (T) ultra-high field MRI. METHODS: The coil array structures of a 64-channel receive coil and a 16-channel transmit coil were merged into one anatomically shaped close-fitting housing. Transmit characteristics were evaluated in a B1+ -field mapping study and an electromagnetic model. Receive SNR and the encoding capability for accelerated imaging were evaluated and compared with a commercially available 7 T brain array coil. The performance of the head-neck array coil was demonstrated in human volunteers using high-resolution accelerated imaging. RESULTS: In the brain, the SNR matches the commercially available 32-channel brain array and showed improvements in accelerated imaging capabilities. More importantly, the constructed coil array improved the SNR in the face area, neck area, and cervical spine by a factor of 1.5, 3.4, and 5.2, respectively, in regions not covered by 32-channel brain arrays at 7 T. The interelement coupling of the 16-channel transmit coil ranged from -14 to -44 dB (mean = -19 dB, adjacent elements <-18 dB). The parallel 16-channel transmit coil greatly facilitates B1+ field shaping required for large FOV neuroimaging at 7 T. CONCLUSION: This new head-neck array coil is the first demonstration of a device of this nature used for combined full-brain, head-neck, and cervical-spine imaging at 7 T. The array coil is well suited to provide large FOV images, which potentially improves ultrahigh field neuroimaging applications for clinical settings.

Trends in resource utilization and cost of illness in patients with active epilepsy in Germany from 2003 to 2020.

OBJECTIVE: This study was undertaken to calculate epilepsy-related direct, indirect, and total costs in adult patients with active epilepsy (ongoing unprovoked seizures) in Germany and to analyze cost components and dynamics compared to previous studies from 2003, 2008, and 2013. This analysis was part of the Epi2020 study. METHODS: Direct and indirect costs related to epilepsy were calculated with a multicenter survey using an established and validated questionnaire with a bottom-up design and human capital approach over a 3-month period in late 2020. Epilepsy-specific costs in the German health care sector from 2003, 2008, and 2013 were corrected for inflation to allow for a valid comparison. RESULTS: Data on the disease-specific costs for 253 patients in 2020 were analyzed. The mean total costs were calculated at €5551 (±€5805, median = €2611, range = €274-€21 667) per 3 months, comprising mean direct costs of €1861 (±€1905, median = €1276, range = €327-€13 158) and mean indirect costs of €3690 (±€5298, median = €0, range = €0-€11 925). The main direct cost components were hospitalization (42.4%), antiseizure medication (42.2%), and outpatient care (6.2%). Productivity losses due to early retirement (53.6%), part-time work or unemployment (30.8%), and seizure-related off-days (15.6%) were the main reasons for indirect costs. However, compared to 2013, there was no significant increase of direct costs (-10.0%), and indirect costs significantly increased (p < .028, +35.1%), resulting in a significant increase in total epilepsy-related costs (p < .047, +20.2%). Compared to the 2013 study population, a significant increase of cost of illness could be observed (p = .047). SIGNIFICANCE: The present study shows that disease-related costs in adult patients with active epilepsy increased from 2013 to 2020. As direct costs have remained constant, this increase is attributable to an increase in indirect costs. These findings highlight the impact of productivity loss caused by early retirement, unemployment, working time reduction, and seizure-related days off.

EuroQOL-5D-3L does not adequately map quality-of-life deterioration in severely affected patients with epilepsy.

INTRODUCTION: The steadily increasing impact of health-related quality of life (HRQOL) on reasonable diagnostic and therapeutic decisions makes the correct mapping of HRQOL indispensable in modern epileptology. The aim of this study was to address the reliability of the often-used generic HRQOL screening questionnaire EuroQOL 5-dimension, 3-level (EQ-5D-3L) by comparing its normalized index value (calculated via the time trade-off method) and visual analog scale (VAS) to the gold standard of the extensive Quality of Life in Epilepsy Inventory (QOLIE-31). QOLIE-10 scores were compared with the extensive QOLIE-31 and EQ-5D-3L TTO. METHODS: We conducted a retrospective analysis of a monocentric study of 184 patients with epilepsy. Bivariate Spearman correlation analysis and Fisher's r-to-z transformation were used to compare the strengths of correlations of EQ-5D-3L, QOLIE-10 and QOLIE-31 with different epilepsy-specific domains (disease severity, drug interactions, emotional well-being, stigmatization, seizure-related anxiety, cognitive impairment). RESULTS: The different metrics of EQ-5D-3L, QOLIE-10 and QOLIE-31 showed moderate to very strong intra- and inter-metric correlations for overall HRQOL. Quality of Life in Epilepsy Inventory-31 VAS and EQ-5D-3L VAS did not show any significantly different strengths of correlations with respect to the domains studied. In contrast, the correlation strength of the normalized EQ-5D-3L index value differed significantly from the QOLIE-31 T-score for several domains, for example, for drug-related adverse events, neuropsychological deficits, symptoms of depression and seizure worry. In seizure-free patients, EQ-5D-3L VAS and EQ-5D-3L index values correlated significantly less with the domain of "cognitive impairment" than the QOLIE-31 T-score. In patients without relevant neuropsychological deficits, the strengths of correlations with the assessed domains did not differ significantly between EQ-5D-3L metrics and the QOLIE-31 T-score. The HRQOL mapping probability of QOLIE-10 was inferior to QOLIE-31 and comparable to EQ-5D-3L regarding the analyzed domains. CONCLUSION: In contrast to the EQ-5D-3L VAS, EQ-5D-3L index values do not adequately map health-related quality of life in severely affected patients with epilepsy and therefore should not be used as screening tools. The QOLIE-31 T-score remains the gold standard for HRQOL assessment in patients with epilepsy.

Trends in antiseizure medication prescription patterns among all adults, women, and older adults with epilepsy: A German longitudinal analysis from 2008 to 2020.

INTRODUCTION: The prescription patterns of antiseizure medication (ASM) are subject to new scientific evidence and sociodemographic and practical aspects. This study analyzed trends in ASM prescription patterns among all adults with epilepsy, with special consideration for women of childbearing potential (WOCBP) and older adult (≥65 years old) patients. METHODS: Data from four questionnaire-based cohort studies, conducted in 2008, 2013, 2016, and 2020, were analyzed for ASM prescription frequencies and common mono- and dual therapy regimens. Statistical comparisons were performed with the Chi-square test and one-way analysis of variance. RESULTS: Overall, the individual prescription patterns among 1,642 adult patients with epilepsy were analyzed. A significant increase in the prescription frequency of third-generation ASMs, from 59.3% to 84.2% (p = 0.004), was accompanied by a decrease in the frequency of first- and second-generation ASMs (5.4% to 2.1% and 34.9% to 12.6%, respectively). This trend was accompanied by a significant decrease in the use of enzyme-inducing ASMs, from 23.9% to 4.6% (p = 0.004). Among frequently prescribed ASMs, prescriptions of carbamazepine (18.6% to 3.1%, p = 0.004) and valproate (15.4% to 8.7%, p = 0.004) decreased, whereas prescriptions of levetiracetam (18.0% up to 32.4%, p = 0.004) increased significantly. The prescription frequency of lamotrigine remained largely constant at approximately 20% (p = 0.859). Among WOCBP, the prescription frequencies of carbamazepine (11.4% to 2.0%, p = 0.004) and valproate (16.1% to 6.1%, p = 0.004) decreased significantly. Levetiracetam monotherapy prescriptions increased significantly (6.6% to 30.4%, p = 0.004) for WOCBP, whereas lamotrigine prescriptions remained consistent (37.7% to 44.9%, p = 0.911). Among older adult patients, a significant decrease in carbamazepine prescriptions (30.1% to 7.8%, p = 0.025) was the only relevant change in ASM regimens between 2008 and 2020. In patients with genetic generalized epilepsies, levetiracetam was frequently used as an off-label monotherapy (25.0% to 35.3%). CONCLUSION: These results show a clear trend toward the use of newer and less interacting third-generation ASMs, with lamotrigine, levetiracetam, and lacosamide representing the current ASMs of choice, displacing valproate and carbamazepine over the last decade. In WOCBP, prescription patterns shifted to minimize teratogenic effects, whereas, among older adults, the decrease in carbamazepine use may reflect the avoidance of hyponatremia risks and attempts to reduce the interaction potential with other drugs and ASMs. Levetiracetam is frequently used off-label as a monotherapy in patients with genetic generalized epilepsy.

Temporal encephaloceles in epilepsy patients and asymptomatic cases: Size may indicate epileptogenicity.

OBJECTIVE: This study was undertaken to identify temporal encephaloceles (TEs) and examine their characteristics in patients with temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE), as well as in asymptomatic cases. METHODS: Four hundred fifty-eight magnetic resonance imaging scans were examined retrospectively to identify TE in 157 patients with TLE, 150 patients with ETLE, and 151 healthy controls (HCs). RESULTS: At least one TE was identified in 9.6% of the TLE patients (n = 15, 95% confidence interval [CI] = 5.3%-15.3%), in 3.3% of patients with ETLE (n = 5, 95% CI = 1.1%-7.6%), and in 2.0% of the HCs (n = 3, 95% CI = .4%-5.7%), indicating a significantly higher frequency in patients with TLE compared to ETLE and HC subjects (p = .027, p = .005). Examining the characteristics of TEs in both asymptomatic and epilepsy patients, we found that TEs with a diameter of less than 6.25 mm were more likely to be asymptomatic, with a sensitivity of 91.7% and a specificity of 73.3% (area under the curve = .867, 95% CI = .723-1.00, p = .001). SIGNIFICANCE: Temporal encephaloceles may occur without presenting any clinical symptoms. Patients with TLE show a higher frequency of TEs compared to the ETLE and HC groups. According to our study, TE size could be used to suggest potential epileptogenicity.

Perception of memory performance after first seizure in patients with and without an epilepsy diagnosis.

OBJECTIVES: Memory complaints in patients with epilepsy have been well-studied. Although memory complaints are commonly reported by patients with chronic epilepsy, to date, few studies exist on memory complaints at the onset of epilepsy. The present study investigated the presence of memory complaints and their relation to mood and memory performance in patients after their first seizure. Thereby, we examined differences between individuals who received a diagnosis of epilepsy immediately with the occurrence of their first seizure and those who were diagnosed as having the first epileptic seizure, without fulfilling the ILAE criteria for the diagnosis of epilepsy. METHODS: Sixty-one patients participated in the study and completed, among others, a memory task and questionnaires on memory complaints and depression after their first epileptic seizure. We investigated the level of memory complaints and their correlation and accuracy in classification with a memory measure. We compared patients who received an epilepsy diagnosis after the first seizure with those who did not. RESULTS: Memory complaints did not correlate with objective memory performance. Classification into impaired/unimpaired showed low concordance between memory complaints and neuropsychological memory measures. After their first epileptic seizure, patients reported few memory complaints overall (10%), and there were no differences in memory complaints between patients with and without an epilepsy diagnosis. CONCLUSION: At epilepsy onset, in contrast to established epilepsies, memory complaints are rare. Although influences of anticonvulsant drugs and seizures are not present at the beginning of epilepsy, this substantial absence of memory complaints at epilepsy onset emphasizes the need for comprehensive neurological and psychological treatment early with the given diagnosis. Treatment should focus on anticonvulsant drug regimens, patients' concerns and convey realistic expectations.

Patients' knowledge about epilepsy-related risks, morbidity, and mortality: A multicenter cohort study from Germany.

INTRODUCTION: Patient education is a central component of quality care. Enhancing patient knowledge can improve patients' quality of life and facilitate successful self-management. We sought to identify patients' knowledge levels and knowledge gaps regarding epilepsy-related risks, morbidity, and mortality. METHODS: Adult patients with epilepsy presenting to the university hospitals in Frankfurt, Greifswald, and Marburg between February 2018 and May 2020 were asked to participate in this questionnaire-based study. RESULTS: A total of 238 patients (52% women), with a mean age of 39.2 years (range: 18-77 years), participated in this study. Spontaneously, the majority of patients (51.3%) named driving a car, and other traffic-related accidents as possible causes of morbidity and mortality, and 23.9% of patients reported various causes of premature death, such as suffocation, drowning, and respiratory or cardiac arrest due to seizures. Falls due to epilepsy (19.7%) and injuries in general (17.6%) were named as further causes of morbidity and mortality. The vast majority were aware that alcohol (87.4%), sleep deprivation (86.6%), and risky activities in daily life (80.3%) increased the risk of seizure occurrence or increased morbidity and mortality. Regarding overall mortality, 52.1% thought that people with epilepsy were at greater risk of premature death, whereas 46.2% denied this fact to be true. Only 29.4% were aware of status epilepticus, and 27.3% were aware of sudden unexpected death in epilepsy (SUDEP). Driving ability, working ability, and seizure risk were named as major or moderate concerns among patients, but the risk of premature mortality was not a major concern. One-quarter of all patients (26.9%) indicated that they were not counseled about any risk factors or causes of morbidity or mortality by their physicians. CONCLUSIONS: A lack of knowledge concerning premature mortality, SUDEP, and status epilepticus exists among adult patients with epilepsy. A substantial number of patients indicated that these issues were not discussed adequately by their physicians.

Detection of cortical malformations using enhanced synthetic contrast images derived from quantitative T1 maps.

The detection of cortical malformations in conventional MR images can be challenging. Prominent examples are focal cortical dysplasias (FCD), the most common cause of drug-resistant focal epilepsy. The two main MRI hallmarks of cortical malformations are increased cortical thickness and blurring of the gray (GM) and white matter (WM) junction. The purpose of this study was to derive synthetic anatomies from quantitative T1 maps for the improved display of the above imaging characteristics in individual patients. On the basis of a T1 map, a mask comprising pixels with T1 values characteristic for GM is created from which the local cortical extent (CE) is determined. The local smoothness (SM) of the GM-WM junctions is derived from the T1 gradient. For display of cortical malformations, the resulting CE and SM maps serve to enhance local intensities in synthetic double inversion recovery (DIR) images calculated from the T1 map. The resulting CE- and/or SM-enhanced DIR images appear hyperintense at the site of cortical malformations, thus facilitating FCD detection in epilepsy patients. However, false positives may arise in areas with naturally elevated CE and/or SM, such as large GM structures and perivascular spaces. In summary, the proposed method facilitates the detection of cortical abnormalities such as cortical thickening and blurring of the GM-WM junction which are typical FCD markers. Still, subject motion artifacts, perivascular spaces, and large normal GM structures may also yield signal hyperintensity in the enhanced synthetic DIR images, requiring careful comparison with clinical MR images by an experienced neuroradiologist to exclude false positives.

Efficacy and safety of adjunctive lacosamide in the treatment of primary generalised tonic-clonic seizures: a double-blind, randomised, placebo-controlled trial.

OBJECTIVE: To evaluate efficacy and safety of lacosamide (up to 12 mg/kg/day or 400 mg/day) as adjunctive treatment for uncontrolled primary generalised tonic-clonic seizures (PGTCS) in patients (≥4 years) with idiopathic generalised epilepsy (IGE). METHODS: Phase 3, double-blind, randomised, placebo-controlled trial (SP0982; NCT02408523) in patients with IGE and PGTCS taking 1-3 concomitant antiepileptic drugs. Primary outcome was time to second PGTCS during 24-week treatment. RESULTS: 242 patients were randomised and received ≥1 dose of trial medication (lacosamide/placebo: n=121/n=121). Patients (mean age: 27.7 years; 58.7% female) had a history of generalised-onset seizures (tonic-clonic 99.6%; myoclonic 38.8%; absence 37.2%). Median treatment duration with lacosamide/placebo was 143/65 days. Risk of developing a second PGTCS during 24-week treatment was significantly lower with lacosamide than placebo (Kaplan-Meier survival estimates 55.27%/33.37%; HR 0.540, 95% CI 0.377 to 0.774; p<0.001; n=118/n=121). Median time to second PGTCS could not be estimated for lacosamide (>50% of patients did not experience a second PGTCS) and was 77.0 days for placebo. Kaplan-Meier estimated freedom from PGTCS at end of the 24-week treatment period (day 166) for lacosamide/placebo was 31.3%/17.2% (difference 14.1%; p=0.011). More patients on lacosamide than placebo had ≥50% (68.1%/46.3%) or ≥75% (57.1%/36.4%) reduction from baseline in PGTCS frequency/28 days, or observed freedom from PGTCS during treatment (27.5%/13.2%) (n=119/n=121). 96/121 (79.3%) patients on lacosamide had treatment-emergent adverse events (placebo 79/121 (65.3%)), most commonly dizziness (23.1%), somnolence (16.5%), headache (14.0%). No patients died during the trial. CONCLUSIONS: Lacosamide was efficacious and generally safe as adjunctive treatment for uncontrolled PGTCS in patients with IGE.