Add-on treatment with cenobamate is already effective at low doses in refractory focal epilepsy: A prospective observational study.

OBJECTIVE: Cenobamate, a novel antiseizure medication with a dual mechanism of action, has been shown in pivotal trials to significantly improve seizure control in treatment-resistant focal epilepsy. We aimed to evaluate whether these promising results could be confirmed in a real-world setting with a follow-up period of up to 12 months. METHODS: Patients from a tertiary epilepsy center who received cenobamate add-on between June 2021 and October 2023 were followed up prospectively at 3, 6, and 12 months after treatment initiation for assessment of seizure outcomes and treatment-related adverse events. RESULTS: The clinical cohort included 112 adult patients with 30% nonlesional cases and a wide spectrum of epileptogenic lesions underlying refractory focal epilepsy. We observed a significant reduction in monthly seizure frequency of all seizure types already after 3 months of treatment at a median cenobamate dose of 100 mg/day. Forty-six percent of patients were responders with a ≥50% seizure reduction, 26% had a ≥75% seizure reduction, and 9% became seizure-free. Among the 74 patients with available follow-up of 12 months, the responder rates reached 55%, 35%, and 19% for ≥50%, ≥75%, and 100% seizure reduction, respectively. After 3 months of treatment, 38% of patients reported adverse effects, mainly (84%) mild to moderate in intensity. Adjustment of comedication allowed successful management of adverse effects in 32% of patients. At a group level, there was no correlation between the cenobamate daily dose and the incidence of adverse events. SIGNIFICANCE: We found a clinically relevant response to cenobamate already at a low daily dose of 100 mg also in a patient cohort with a higher degree of drug resistance than in pivotal trials. Our prospectively collected data provide real-world evidence for high efficacy and good tolerability of the drug, although no standardized treatment protocol or comparison with a control group was applied.

Cognitive and behavioral effects of cannabidiol in patients with treatment-resistant epilepsy.

PURPOSE: Therapeutic use of cannabidiol (CBD) in intractable epilepsies has increased considerably over the last ten years. As more evidence for the potentially beneficial effects of CBD on different epilepsy types is emerging, it is important to monitor potential cognitive and behavioral side effects. So far, studies including standardized neuropsychological data in the context of treatment with CBD in epilepsy patients are sparse. The present open-label study examines cognitive and behavioral effects of CBD in children and adults with treatment resistant epilepsy. METHOD: Thirty-nine patients with treatment-resistant epilepsy completed the study protocol, i.e. they were tested at baseline (T0) and after three months of CBD treatment (T1). Patients completed standardized neuropsychological tests on memory, executive functions and attention if they were capable. For cognitively impaired patients who could not complete cognitive tests, caregiver interviews were conducted and caregiver questionnaires completed. RESULTS: Significant cognitive decline from T0 to T1 was observed on none of the included measures. There was a significant improvement on a measure of selective attention and on a caregiver-rated behavioral measure. More than 89% of all individual test results remained stable or showed reliable improvement from T0 to T1. Cognitive and behavioral changes from T0 to T1 were not significantly correlated with CBD dose. Improvements in short-term/working memory were significantly related to better therapy response. CONCLUSION: No adverse group-level effects of CBD treatment were detected. On an individual level, most test results remained stable or were improved. Cognitive change was not related to CBD dose. The present results show that, from a cognitive and behavioral point of view, CBD seems to have an encouraging side-effect profile. The results need to be replicated with larger samples.

Functional cognitive disorder in subjective cognitive decline-A 10-year follow-up.

OBJECTIVES: In memory clinics, patients with significant memory complaints without objective neuropsychological findings are common. They are classified as subjective cognitive decline (SCD) and, as a group, face a heightened risk for future dementia. However, the SCD group is heterogeneous and comprises patients suffering from a somatoform condition, namely functional cognitive disorder (FCD). These patients make up at least 11% of memory clinics' attendees. The aim of this long-term follow-up study was to investigate if patients diagnosed with FCD also face a higher risk of developing dementia. METHODS: Forty-two Patients were recruited at a university hospital memory clinic. FCD was diagnosed according to the Schmidtke criteria (see Table 1). Ten years later, all were invited again. Participants were interviewed, screened for depression and given neuropsychological tests of verbal memory and information processing speed. Cognitive impairment was defined as performance below 1.5 standard deviations (SD) of the age-related mean. RESULTS: Twenty-eight of 42 patients (67%) took part in this follow-up. The group's mean results in both cognitive measures were stable over time. All individual performances were within 1.5 SD. With 10 patients (24%), brief contact was successful and manifest dementia could be excluded. Four patients (10%) could not be contacted. CONCLUSIONS: In retrospect, the Schmidtke criteria for FCD safely identified memory clinic attendees with SCD who did not proceed to Mild Cognitive Impairment or dementia. None of the patients who could be contacted for this follow-up after a decade (90% of baseline participants) showed signs of dementia.

Effects of hippocampus-sparing resections in the temporal lobe: Hippocampal atrophy is associated with a decline in memory performance.

OBJECTIVE: In patients with temporal lobe epilepsy (TLE) with a nonlesional and nonepileptogenic hippocampus (HC), in order to preserve functionally intact brain tissue, the HC is not resected. However, some patients experience postoperative memory decline, possibly due to disruption of the extrahippocampal memory network and secondary hippocampal volume (HV) loss. The purpose of this study was to determine the extent of hippocampal atrophy ipsilateral and contralateral to the side of the surgery and its relation to memory outcomes. METHODS: Hippocampal volume and verbal as well as visual memory performance were retrospectively examined in 55 patients (mean age ± standard deviation [SD] 30 ± 15 years, 25 female, 31 left) before and 5 months after surgery within the temporal lobe that spared the entire HC. HV was extracted based on prespecified templates, and resection volumes were also determined. RESULTS: HV loss was found both ipsilateral and contralateral to the side of surgery (P < .001). Postoperative left HV loss was a significant predictor of postoperative verbal memory deterioration after left-sided surgery (P < .01). Together with the preoperative verbal memory performance, postoperative left HV explained almost 60% of the variance (P < .0001). However, right HV was not a clear predictor of visual memory performance. Larger resection volumes were associated with smaller postoperative HV, irrespective of side of surgery (left: P < .05, right: P < .01). SIGNIFICANCE: A disruption of the memory network by any resection within the TL, especially within the language-dominant hemisphere, may lead to HC atrophy and memory decline. These findings may further improve the counseling of patients concerning their postoperative memory outcome before TL resections sparing the entire HC.

Association between seizure freedom and default mode network reorganization in patients with unilateral temporal lobe epilepsy.

RATIONALE: The spontaneous synchronized activity and intrinsic organization of the Default Mode Network (DMN) has been found to be altered because of epileptic activity of temporal lobe origin. Thus, the aim of the present study was to compare DMN's topological properties in patients with seizure-free (SF) and not seizure-free (NSF) temporal lobe epilepsy (TLE). METHODS: Functional connectivity within the DMN was determined from an 8-minute resting state functional magnetic resonance imaging (fMRI) in 27 patients with TLE (12 SF, 15 NSF) and 15 healthy controls (HC). The DMN regions of interest were extracted according to the automated anatomical labeling (AAL) atlas. Network properties were assessed using standard graph-theoretical measures. RESULTS: Analyses revealed, irrespectively of focus lateralization, borderline significance for longer paths (p = 0.049) and in trend reduced local efficiency within the DMN of SF when compared with that of NSF (p = 0.075). The SF and NSF patients did not differ in global network topology from HC (p > 0.05). At the nodal network level, the degree of central hubs was significantly reduced in SF when compared with that in NSF (0.002 ≤ p ≤ 0.080) and HC (0.001 ≤ p ≤ 0.066) while simultaneously, right anterior superior temporal gyrus revealed significantly higher degree in SF than in NSF (p = 0.005) and HC (p = 0.016). CONCLUSION: Seizure freedom seems to be associated with hub redistributions that may underlie longer paths and (in trend) reduced local efficiency of the network. An associated slower system response might reduce the probability of a rapid spread of epileptic discharges over the whole network and may help to prevent hypersynchronous neuronal activity in brain networks that may result in epileptic seizures.

Reduced glucose metabolism in neocortical network nodes remote from hypothalamic hamartomas reflects cognitive impairment.

The clinical appearance of patients with hypothalamic hamartomas is very heterogeneous, and interindividual variability of intellectual abilities is not completely understood. We retrospectively investigated cerebral dysfunction as indicated by reduced regional glucose metabolism in 29 patients (age range 7-49 years) with epilepsy due to hypothalamic hamartomas. Brain metabolism assessed by [18 F]FDG-PET was compared between patients with and without cognitive impairment controlled for unevenly distributed hamartoma lateralization seen on magnetic resonance imaging (MRI). Due to the broad age range, the variable "age" was included in the imaging analyses as a covariate. Additional voxel-wise analysis with hamartoma volume, disease duration, seizure severity, seizure frequency, and antiepileptic drug (AED) load as well as dosage and gender as further covariates was accomplished. Furthermore, global visual ratings on laterality of hypometabolism patterns were assessed according to clinical standards and related to hamartoma lateralization on MRI as well as lateralization of electroencephalography (EEG) abnormalities. Cognitively impaired patients showed significantly reduced glucose metabolism in bilateral frontal as well as right parietal and posterior midline cortices (p < 0.005), irrespective of hamartoma lateralization seen on MRI. Additional voxel-wise analysis with the above-mentioned further covariates revealed comparable results. FDG uptake values within the main right frontal cluster obtained from group comparison were not associated with hamartoma volume, disease duration, or AED load. Irrespective of cognitive functioning, lateralization of reduced FDG uptake in global visual ratings was associated with lateralization of hypothalamic hamartomas seen on MRI (p < 0.01), but not with EEG abnormalities. We found regions of reduced glucose metabolism in cognitively impaired patients remote from the hypothalamic hamartomas in frontal and parietal regions, which have been identified as important network nodes in the human brain and are linked to higher cognitive functions.

Third International Congress on Epilepsy, Brain and Mind: Part 1.

Epilepsy is both a disease of the brain and the mind. Here, we present the first of two papers with extended summaries of selected presentations of the Third International Congress on Epilepsy, Brain and Mind (April 3-5, 2014; Brno, Czech Republic). Epilepsy in history and the arts and its relationships with religion were discussed, as were overviews of epilepsy and relevant aspects of social cognition, handedness, accelerated forgetting and autobiographical amnesia, and large-scale brain networks.

Transient global amnesia after the right temporal epilepsy surgery: A case report.

Transient global amnesia (TGA) is characterized by sudden and temporary memory impairment, while transient epileptic amnesia (TEA) represents amnestic attacks as the main manifestation of focal epilepsy with presumed temporal origin. We present a 48-year-old patient who experienced transient amnesia 10 weeks after right selective amygdalo-hippocampectomy for right temporal lobe epilepsy. Despite TEA being a plausible explanation for amnesia in patients with temporal lobe epilepsy, no epileptiform discharges were found during the amnestic episode and key features indicative of TGA, including long duration, isolated occurrence, and dense anterograde amnesia of the episode, argued against a diagnosis of TEA in this case. Notably, the patient has remained seizure-free (now 4,5 years) and stopped taking antiseizure medication 32 months after surgery. Although TGA clinical criteria formally exclude patients with recent active epilepsy, neurologists should be aware that TGA can occur after epilepsy surgery in the temporal lobe. Therefore, we consider it of high clinical relevance to establish a careful differential diagnosis between TGA and epileptic amnestic attacks after epilepsy surgery to avoid unnecessary reintroduction or continuation of antiseizure medication. Additionally, this case presents the first comparison of detailed neuropsychological test results before and after a presumed TGA episode, revealing a complete recovery of anterograde memory functions within 1 day. PLAIN LANGUAGE SUMMARY: A 48-year-old patient experienced an episode of transient amnesia 10 weeks after epilepsy surgery. Given the patient's history, an epileptic origin of the episode initially seemed likely. However, tests revealed no seizure activity during the episode and the characteristics matched a condition called transient global amnesia. This case highlights the importance of correctly diagnosing memory impairments after epilepsy surgery to prevent unnecessary treatment.

Dynamic facial emotion recognition and affective prosody recognition are associated in patients with temporal lobe epilepsy.

Deficits in facial emotion recognition have frequently been established in temporal lobe epilepsy (TLE). However, static, rather than dynamic emotion recognition paradigms have been applied. Affective prosody has been insufficiently studied in TLE, and there is a lack of studies investigating associations between auditory and visual emotion recognition. We wished to investigate potential deficits in a dynamic morph task of facial emotion recognition and in an affective prosody recognition task, as well as associations between both tasks. 25 patients with TLE and 24 healthy controls (CG) performed a morph task with faces continuously changing in their emotional intensity. They had to press a button, as soon as they were able to recognize the emotion expressed, and label it accordingly. In the auditory task, subjects listened to neutral sentences spoken in varying emotional tones, and labeled the emotions. Correlation analyses were conducted across both tasks. TLE patients showed significantly reduced prosody recognition compared to CG, and in the morph task, there was a statistical trend towards significantly reduced performance for TLE. Recognition rates in both tasks were significantly associated. TLE patients show deficits in affective prosody recognition, and they may also be impaired in a morph task with dynamically changing facial expressions. Impairments in basic social-cognitive tasks in TLE seem to be modality-independent.

Memory outcome after hippocampus sparing resections in the temporal lobe.

BACKGROUND AND OBJECTIVE: Epilepsy surgery within the temporal lobe of the language dominant hemisphere bears the risk of postoperative verbal memory decline. As surgical procedures have become more tailored, the question has arisen, which type of resection within the temporal lobe is more favourable for memory outcome. Since the hippocampus (HC) is known to play an essential role for long-term memory, we examined whether HC sparing resections help to preserve verbal memory functions. METHODS: We retrospectively analysed neuropsychological data (prior to and 1 year after surgery) of patients undergoing either HC sparing resections (HC-S, N=65) or resections including the hippocampus (HC-R, N=62). RESULTS: Prior to surgery, the HC-R group showed worse memory performance as compared to HC-S patients. Both patient groups revealed further deterioration over time, but in verbal learning HC-R patients demonstrated a stronger decline. Predictors for verbal learning decline were left-sided surgery, better preoperative performance, higher age at surgery, hippocampus resection, and lower preoperative IQ. In patients with spared HC, resection of the left-sided parahippocampal gyrus was rather accompanied by a decline in verbal learning performance. For visual memory, better preoperative performance best predicted deterioration after surgery. Seizure outcome was comparable between the two groups (HC-S: 66%, HC-R: 65% Engel 1a). CONCLUSIONS: Temporal lobe resections within the language dominant hemisphere can be accompanied by a decline in verbal memory performance, even if the HC is spared. Yet, HC sparing surgery is associated with a benefit in verbal learning performance. These results can help when counselling patients prior to epilepsy surgery.

Who needs a Wada test? Present clinical indications for amobarbital procedures.

INTRODUCTION: The Wada test has been the gold standard for testing cerebral language localisation during presurgical investigation in the past decades. However, during the last few years a shift has occurred in epilepsy surgery programmes towards the use of non-invasive methods, predominantly functional MRI (fMRI). However, Wada tests are still performed, albeit in a considerably smaller number of patients at many epilepsy centres. METHODS: A retrospective monocentric analysis of remaining clinical indications for performing a Wada procedure was undertaken. The clinical data of patients who participated in Wada tests (42 hemispheric and 8 superselective procedures) during recent years were retrospectively evaluated. RESULTS: Reasons for conducting a Wada test were (1) a patient's inability to perform the fMRI task due to agitation, mental disablement, or perceptual impairment, (2) validation of atypical, inconclusive or not clearly lateralised language activation shown with fMRI, (3) evaluation of propagation of ongoing interictal bilateral epileptiform EEG activity, (4) region selective testing of language and other cognitive functions, or (5) assessment of motor localisation. Patients who were not able to perform the fMRI task or in whom fMRI did not provide interpretable results were significantly younger (p<0.05). CONCLUSION: It is argued that fMRI is eligible to replace Wada tests in the majority of patients who are compliant with clearly lateralised language localisation, but in patients who are agitated or mentally impaired as well as in the case of the above-mentioned specific clinical indications and bilateral fMRI activations, Wada tests still provide additional information. Additionally, non-invasive methods less sensitive to movement artefacts are discussed as possible alternatives for these patients.

Validation of a German version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E).

INTRODUCTION: Goal of the present study was the validation of a German version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). METHODS: 197 adult epilepsy patients completed the NDDI-E (185 completed both the NDDI-E and BDI). 95 patients received psychiatric consults. RESULTS: 33 patients received a diagnosis of major depression according to ICD-10 criteria. Internal consistency of the NDDI-E was .83. Receiver operating characteristics (ROC) showed an area under the curve of 0.92. Applying a cutoff score of ≥14 resulted in both sensitivity and specificity of 0.85. In the subsample with psychiatric consult, at the same optimal cutoff, sensitivity was 0.92, and specificity was 0.86. Further analyses showed a high concurrent validity with the BDI. DISCUSSION: The German version of the NDDI-E constitutes a brief and reliable depression screening instrument for epilepsy patients.

Assessment of Anxiety in Patients With Epilepsy: A Literature Review.

Objective: Approximately 20% of people with epilepsy (PWE) suffer from anxiety. These fears are quite diverse and may manifest periictally or interictally, be part of the seizure's semiology, or an expression of reactive psychological distress from seizures themselves. Our review addresses the question of what screening tools are used in clinical care and epileptological research to capture the complexity of epilepsy-specific anxieties. Method: On 2021/11/11, we entered a search string in PubMed that covered our research interest as completely as possible. We also screened the bibliographies of our findings and followed PubMed's recommendations. From the assessments we found in the included studies, we extracted domains that represent the range of manifestations of anxiety, in order to compare the tools and to discuss to what extent they are suitable for assessing epilepsy-specific anxieties. Results: We screened 1,621 abstracts. In total, we identified 24 different anxiety assessments. In addition to the psychiatric assessments in use, we found 7 tools that were designed to assess epilepsy-specific anxieties. The latter focus on different aspects of epilepsy-specific anxieties. In some cases, the conceptual frameworks are not sufficiently transparent or divergent. Conclusion: Because a diagnosis of epilepsy can result in, or seizures may appear as, anxiety, it is important to better understand this psychological burden and address it therapeutically, if necessary. There is a need for screening tools that integrate specific points of a variety of assessments, so as to cover the broad range of epilepsy-specific fears. None of the assessments we found meets this integrative perspective. At the same time, the appropriate design of such a required tool presupposes a conceptual framework of what should be considered as epilepsy-specific anxiety.

Affective Empathy, Theory of Mind and Social Functioning in Patients With Focal Epilepsy.

Objective: Social cognition comprises basic and more complex functions, such as theory of mind (ToM) and affective empathy. Although everyday social interactions may be impaired if such higher-order social cognitive functions are compromised, associations between social functioning and social cognition in people with focal epilepsy (PWFE) are still poorly understood. We used a novel, naturalistic approach to investigate ToM in PWFE by applying the Movie for the Assessment of Social Cognition (MASC). Furthermore, we studied affective empathy, the relationship between social cognitive parameters and measures of social functioning, as well as between epilepsy focus and ToM. Methods: Thirty patients with either temporal (TLE) or frontal lobe epilepsy (FLE) were compared to 29 healthy control subjects (HC). In addition to the MASC, we applied questionnaire measures assessing empathy and everyday social functioning. Results: PWFE, especially with FLE, performed significantly worse than HC on the MASC. Perceived social integration and social activities, but not affective empathy, were reduced in PWFE. Regression analyses revealed associations between perceived social integration, clinical group status, affective empathy and ToM. Conclusion: PWFE displayed ToM deficits during a naturalistic task, whereas affective empathy was unimpaired. FLE may be associated with especially compromised ToM performance. Social cognition and social functioning appear to be interrelated in PWFE, whose self-perceived levels of social integration and social activities are lower than those of HC. More research into the association between social cognition and social functioning in PWFE is needed, in order to develop tailored intervention programs for these patients.

Eye-movement patterns during emotion recognition in focal epilepsy: An exploratory investigation.

BACKGROUND: Eye-movement patterns during facial emotion recognition are under-researched in patients with focal epilepsy (PWFE). Previous studies including other neurological patients indicate that bilateral mesiotemporal damage could be associated with impaired emotion recognition and abnormal eye-movement patterns. AIMS: The current study addresses the question whether PWFE, in whom fronto-(mesio-)temporal networks are often disturbed, also show abnormal eye-movement patterns during facial emotion recognition. METHOD: 24 PWFE and a group of 29 healthy controls (HC) performed a facial emotion recognition task and a gender recognition task while eye movements were recorded with an eye-tracker. For this purpose, Areas of Interest (AOI) were defined in the presented faces: the eye region and the mouth region. In addition to the proportion of correctly recognized emotions, the following eye-tracking parameters were recorded: Relative fixation duration (FD)/fixation count (FC) in the mouth region/eye region (relative to the FD/FC on the entire screen). RESULTS: PFWE showed an emotion recognition deficit compared to HC, whereas gender recognition performance did not differ between groups. In addition, PWFE showed significantly fewer and shorter fixations in the mouth region than HC, in both the emotion recognition task and the gender recognition task. CONCLUSIONS: When looking at faces, PFWE show eye-movement patterns different from those of healthy controls. Behaviorally, PWFE are only impaired in emotion recognition. Hence, PWFE possibly scan facial regions that are relevant to successful emotion recognition more diffusely and less efficiently than healthy control subjects. Future studies should investigate the etiology of such abnormal eye-movement patterns in PWFE.

Effects of cenobamate on cognitive performance of epilepsy patients.

PURPOSE: Cenobamate (CNB) is a new antiseizure medication (ASM) for the treatment of focal epilepsy in adults. While efficacy of CNB was confirmed in controlled clinical trials, its effects on cognition are unclear. Cognitive adverse effects of ASM affect quality of life and retention rate. Therefore, we investigated whether the adjunctive treatment with CNB is associated with changes in cognitive performance. METHOD: Efficacy and tolerability of CNB were investigated in an observational study. Fifty patients with pharmacoresistant focal epilepsy aged 18 to 71 years (Mdn = 37.5 years) were tested before (T0) and after reaching the first target dose of CNB, usually after three months (T1). Cognitive performance was assessed using the EpiTrack©, a change-sensitive screening tool for attention and executive functions. RESULTS: The median CNB dose at T1 was 125 mg/day (range: 50 - 250 mg/day). Most patients received 2-3 concomitant ASMs. Individual test scores remained stable in 72%, significantly improved in 16%, and significantly deteriorated in 12% of the patients from T0 to T1. The total group showed a significant improvement in EpiTrack scores (p < .01). Changes in EpiTrack performance from T0 to T1 occurred independently of CNB dose, changes in the total drug load or reduction in seizure frequency. CONCLUSION: Most of the patients showed stable or improved cognitive performance. Thus, there is preliminary evidence that adjunctive CNB is not associated with an increased risk of cognitive side effects for the majority of patients. These findings need to be confirmed in controlled trials encompassing higher doses.

Effect of Cannabidiol on Interictal Epileptiform Activity and Sleep Architecture in Children with Intractable Epilepsy: A Prospective Open-Label Study.

BACKGROUND: Cannabidiol has been shown to be effective in seizure reduction in patients with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis. However, very little is known about its potential to reduce interictal epileptiform activity and improve sleep architecture. OBJECTIVE: The objective of this prospective study was to evaluate the influence of cannabidiol therapy on the frequency of interictal epileptiform discharges (IEDs) and sleep microstructure in a cohort of children with drug-resistant epilepsy. METHODS: Children with drug-resistant epilepsy were prospectively followed from November 2019 to January 2021 during an open-label trial of cannabidiol at a dose of 20 mg/kg/day (to a maximum of 50 mg/kg/day) and stable concomitant medication. Electroencephalograms were recorded at baseline (T0) and after 3 months (T1). Two independent raters, blinded to clinical outcome, evaluated 5-min segments of sleep stage 2 or low-noise awake state. IEDs were visually identified and rates per minute calculated. Sleep microstructure was considered improved if sleep structures were seen at T1 that were not present at T0. IED rates at T0 and T1 were compared and correlated with seizure outcome, cannabidiol dose, initial IED rate, and disease duration. RESULTS: In total, 35 children (mean ± standard deviation age 10.1 ± 0.86) were included. The IED rate at T1 was significantly lower than at T0 (19.6 ± 19.5 vs. 36.8 ± 27.2, respectively; p < 0.0001). We found a moderate correlation between IED reduction and percentage of seizure reduction compared with baseline (Pearson's r = 0.39; p = 0.02), a moderate negative correlation between IED reduction and IED rate at T0 (r = - 0.34; p = 0.04), and a trend towards a moderate negative correlation between IED reduction and disease duration (r = - 0.32; p = 0.06). Sleep was recorded in 23 patients. Sleep microstructure was initially abnormal in 56.5% of sleep recordings and improved in 84.6% of those cases. CONCLUSION: Our results strongly suggest the utility of cannabidiol in reducing IEDs and improving sleep microstructure in children with drug-resistant epilepsy. Larger controlled studies are needed to evaluate the clinical relevance of this effect in different epilepsy types. TRIAL REGISTRATION: DRKS00013177; 25 June 2019.

[Development and evaluation of a group therapy for functional memory and attention disorder]. / Konzeption und Erprobung eines gruppentherapeutischen Behandlungskonzepts für die funktionelle Gedächtnis- und Konzentrationsstörung.

OBJECTIVES: Functional Memory and Attention Disorder (FMD) is regularly seen in patients presenting in psychosomatic or memory clinics. The aim of this study was the evaluation of a novel group therapy for FMD in a randomized controlled trial. METHODS: 40 FMD patients were randomly assigned to either the experimental (EG) or the wait-list control group (CG). Out of these 35/31 were analysed (intent to treat vs. observed cases respectively). The intervention consisted of psychoeducation, cognitive restructuring, stress management, relaxation and mindfulness techniques. Data were collected at baseline, three months (post-intervention) and six months (follow-up). Primary outcome was the memory self-efficacy measure of the Metamemory in Adulthood Questionnaire (MSE). Secondary outcomes were the sum scores of the Perceived Stress Questionnaire (PSQ) and the SCL-90-R. RESULTS: The EG showed a significantly higher improvement on MSE at follow-up than the CG. No significant group differences emerged on PSQ or SCL-90-R. The CG showed stable MSE scores during the waiting period without intervention. However, after the CG received their therapy the same pattern on MSE scores as seen in the EG emerged. CONCLUSIONS: This study provides preliminary evidence for an improvement of memory self efficacy in FMD through a newly devised group therapy program consisting of different modules. This result ought to be replicated in larger studies.

Preoperative depressive symptoms predict postoperative seizure outcome in temporal and frontal lobe epilepsy.

OBJECTIVE: Recent research has pointed to the possibility of a bidirectional relationship between seizure frequency in epilepsy and depressive symptoms. The study described here investigated the relationship between preoperative depressive symptomatology and postoperative seizure outcome in a sample of patients with temporal (TLE) and frontal (FLE) lobe epilepsy. METHODS: A retrospective analysis was conducted on the data from 115 eligible patients with TLE (N=97) and FLE (N=18) and resections limited to one cortical lobe who were evaluated preoperatively and 1year after epilepsy surgery with respect to depressive symptoms (Beck Depression Inventory, BDI) and seizure outcome. The latter was assessed in terms of actual total seizure frequency as well as a dichotomous variable (seizure free vs. not seizure free) for the 1-year outcome. Repeated-measures analyses of variance and regression analyses were applied. RESULTS: Seizure-free patients had significantly lower BDI scores preoperatively as well as postoperatively than patients who were not seizure free. In the regression analyses, the preoperative BDI score was a significant predictor of postoperative seizure frequency as well as seizure freedom. When only patients with TLE were analyzed, the results for the association between preoperative BDI and postoperative seizure frequency and seizure freedom remained consistent. CONCLUSION: The present results provide evidence for a statistical bidirectionality of the relationship between depressive symptoms and postoperative seizure status in a mixed sample of patients with TLE and FLE. Possible reasons for this bidirectional association include an underlying common pathology in both depression and epilepsy, for example, structural changes or functional alterations in neurotransmitter systems.

Efficacy and Tolerance of Synthetic Cannabidiol for Treatment of Drug Resistant Epilepsy.

Objective: Controlled and open label trials have demonstrated efficacy of cannabidiol for certain epileptic encephalopathies. However, plant derived cannabidiol products have been used almost exclusively. Efficacy of synthetically derived cannabidiol has not been studied before. The objective of this study was to evaluate tolerability and efficacy of synthetic cannabidiol in patients with pharmacoresistant epilepsy. Methods: In this prospective, open-label study (DRKS00013177), patients with pharmacoresistant epilepsy received synthetic cannabidiol in addition to their previously stable anticonvulsive treatment. Starting dose was 5 mg/kg/day, up-titrated to a maximum of 50 mg/kg/day. Primary efficacy endpoint was monthly frequency of motor seizures at 3 months. Results: Between April 2017 and May 2019, 35 patients were enrolled in the study. Mean age was 19.7 years (SD 14.6). Median motor seizure frequency decreased from 21.8 (IQR 7.5-52.5) seizures per month at baseline to 8.5 (IQR 3.7-28.3, p < 0.001) at 3 months, effect not influenced by AED changes and drop-outs. Adjusted percentage reduction was 40.0% (IQR 18.2-58.5). Adverse events (AE) were reported in 25 patients (71.4%), most frequently somnolence (40%), diarrhea (34.3), and loss of appetite (20%). Two patients (5.7%) discontinued treatment due to AE. Median (range) of treatment duration was 321 days (range 36-824). With ongoing treatment up to date in 21 patients (60%). Conclusion: Efficacy and tolerance in our study of synthetic CBD treatment in pharmacoresistant epilepsy is similar to open label studies using plant derived CBD. Regarding economic and ecological aspects, synthetic cannabidiol might be a reasonable alternative to plant derived cannabidiol.