key: cord-0076636-4nuo4khq authors: nan title: 60. Jahrestagung der Deutschen Gesellschaft für Epileptologie date: 2022-04-05 journal: Z DOI: 10.1007/s10309-022-00476-x sha: f5b2b6db085499219978c4480e374cf89aa42abf doc_id: 76636 cord_uid: 4nuo4khq nan Pathogenic missense variants in GRIN2A and GRIN2B may result in gain or loss of function ( GoF/ LoF) of the N-methyl-D-aspartate receptor ( NMDAR). This observation gave rise to the hypothesis of successfully treating GRINrelated disorders due to LoF variants with co-agonists of the NMDAR. In this respect, we describe a retrospectively collected series of nine individuals with GRIN2A-or GRIN2B-related disorders who were treated with L-serine, each within an independent n-of-1 trial. Our cohort comprises one individual with a LoF missense variant with clinical improvements confirming the above hypothesis and replicating a previous n-of-1 trial. A second individual with a GoF missense variant was erroneously treated with L-serine and experienced temporary behavioral deterioration further supporting the supposed functional pathomechanism. Seven additional individuals with null variants (that had been interpreted as loss-of-function variants despite not being missense) again showed clinical improvements. Among all eight individuals with LoF missense or null variants, Lserine treatment was associated with improvements in behavior in seven (88 %), in development in three (38 %) and/or in EEG or seizure frequency in four (50 %). None of these eight individuals experienced side effects or adverse findings in the context of L-serine treatment. In summary, we describe first evidence that L-serine treatment may not only be associated with clinical improvements in GRIN-related disorders due to LoF missense but particularly also null variants. Epilepsy affects approximately 1 % of individuals worldwide. Making an epilepsy diagnosis is often difficult with estimates that up to 25 % of epilepsy could initially be misdiagnosed. The SNP heritability of genetic generalized epilepsy is high (32 %) and it has recently been shown that individuals with epilepsy also have elevated epilepsy polygenic risk scores ( PRS). However, systematic investigation of PRS for distinct epilepsy diagnoses has so far been lacking. Here, we studied epilepsy PRS in detailed longitudinal electronic health records of > 269k Finns including ICD codes and drug purchases of over 50 years. Our dataset included 9660 individuals with epilepsy related diagnoses. We could confirm an elevated PRS for generalized epilepsy (PRSgen) in individuals with generalized epilepsy. This was particularly high for juvenile myoclonic epilepsy, which could be because it represented the largest diagnosis group of the GWAS that was used to construct the PRS. We also made multiple surprising discoveries e. g. one ICD diagnosis G40.1 de-fined as a focal epilepsy had an elevated PRSgen but no increased PRS for focal epilepsy (PRSfocal). We further found that over half of individuals with specific diagnoses of generalized or focal epilepsy were initially diagnosed with unclear convulsions (R56.8) or unclear epilepsy (G40.9). Their PRSgen and PRSfocal was significantly higher than of those individuals who had only one unclear seizure event and did not later receive an epilepsy diagnosis. These results indicate a future potential for epilepsy PRS to help in predicting progression to epilepsy in clinical practice. FV 03 Das Sigma1-Protein als Zielstruktur: Wirksamkeit des positiven Sigma1-Modulators E1R im Kindling-Modell Zeitschrift für Epileptologie course of the disease, thus affecting their quality of life and that of their peers. However, the general administration of antiepileptic medication is not recommended, mostly due to the inability of stratifying patients into low-and high-risk groups for the onset of seizures. Such therapy for all GBM patients is therefore not recommended in the updated SNO and EANO guideline. However, the identification of patients at high risk for seizure development is still highly desired. Methoden: 112 patients, who underwent surgery for a GBM, were included. Genome-wide DNA methylation profiling was performed, before methylation subclasses and copy number changes inferred from methylation data were correlated with clinical characteristics. Independently, global gene expression was analyzed in GBM methylation subclasses from TCGA datasets (n = 68). Ergebnisse: Receptor tyrosine Kinase ( RTK) II GBM showed a significantly higher incidence of seizures than RTK I and mesenchymal ( MES) GBM (p < 0.01). Accordingly, RNA expression datasets revealed an upregulation of genes involved in neurotransmitter synapses and vesicle transport in RTK II glioblastomas. In a multivariate analysis, temporal location (p = 0.01, OR 6.35) and RTK II (p = 0.03, OR 5.56) were most predictive for preoperative seizures. During postoperative follow-up, only RTK II remained significantly associated with the development of seizures (p < 0.01, OR 8.23). Consequently, the need for antiepileptic medication and its increase due to treatment failure was highly associated with the RTK II methylation subclass (p < 0.01). Our study provides strong evidence that the RTKII methylation subclass is mainly associated with glioma associated seizures. Furthermore, it appears that the RTK II is the most important factor for the occurrence of a seizure during the clinical course of the disease and that 70 % RTK II glioblastoma patients will experience a failure of their AED treatment. In conclusion, our study provides the basis for methylationbased stratification of glioblastoma patients into high and low risk groups for seizures. Patients with a RTKII glioblastoma are of high risk for the development of a seizure and might therefore benefit from AED treatment after diagnosis, which should be addressed in future clinical trials. Einleitung: Epileptische Anfälle, die in der Insel generiert werden, können ein breites Spektrum von Symptomen zeigen, die z. T. auch in Anfällen des Temporallappens auftreten können. Die Fehldiagnose insulärer Epilepsie als Temporallappenepilepsie wurde als Ursache für einen Teil des Versagens von Temporallobektomien diskutiert. Die Identifikation der Insel als epileptogener Zone ist besonders komplex, da die Inselrinde in der Tiefe Multivariate analysis revealed that the RTK II subclass was the only independent factor for the development of seizures during the course of the disease des Gehirns liegt und wenig zugänglich für den Oberflächen-EEG ist. Daher war das Ziel dieser Arbeit, die iktalen Symptome zu identifizieren, die insuläre Epilepsien von mesiotemporalen Epilepsien unterscheiden können. Material/Methode: In der vorgelegten Studie wurden Patienten mit der Diagnose einer insulären Epilepsie retrospektiv analysiert. Die Diagnose wurde auf der Grundlage von potenziellen epileptogenen Läsionen im MRT oder dem elektrophysiologischen Nachweis eines insulären Anfallsursprungs gestellt. Die Anfallssemiologie von Patienten mit insulärer Epilepsie wurde hierfür mit gematchten Patienten mit einer mesiotemporalen Epilepsie verglichen. Ergebnisse: 46 Patienten mit einer insulärer Epilepsie und 46 gematchte Patienten mit einer mesiotemporalen Epilepsie wurden eingeschlossen. Als häufigstes iktale Phänomen traten bei Patienten mit insulärer Epilepsie motorische Symptome auf (80,4 % bei insulären vs. 52,2 % bei mesiotemporalen Patienten). Bei mesiotemporaler Anfallsgenerierung waren Tonisierungen, Kloni, versive Anfälle und sensible Symptome häufiger kontralateral zum Anfallsursprung, während sie bei insulären Epilepsien sowohl ipsilateral als auch kontralateral auftraten. Bei mesiotemporalen Fällen wurden häufiger ipsilaterale manuelle Automatismen nachgewiesen (p = 0,010). Eine multivariante Analyse klassifizierte mittels 5 iktaler Merkmale (epigastrische Sensationen, Aphasie, iktale Sprache, Automatismen und hyperkinetische Phänomene) 78,3 % der insulären Epilepsiepatienten und 84,8 % der mesiotemporalen Epilepsiepatienten richtig (Chisquare = 53,79, p < 0,0001). Eine Subanalyse auf Grundlage der initialen iktalen Symptome zeigte, dass sensible Symptome signifikant häufiger in insulären Epilepsien auftreten (p = 0,010), während in mesiotemporalen Epilepsien Automatismen signifikant häufiger sind (p = 0,06). Zwei insuläre Symptomcluster wurden identifiziert: eines mit Angst, olfaktorischen, gustatorischen und auditorischen, sensorischen und sensiblen Symptomen, Déjà-vu-Erlebnissen, cephalen oder epigastrischen Sensationen, iktaler Sprache und hyperkinetischen Bewegungen, das andere Cluster mit Areagibilität, Automatismen, Aphasie, autonomen und fokalen motorischen Symptomen. Diskussion: Die nachgewiesenen Unterscheidungsmerkmale sind relevant für eine korrekte diagnostische Einordnung sowie zur Lokalisation von Anfallsgeneratoren im Rahmen präoperativer Diagnostik und epilepsiechirurgischer Eingriffe. Introduction: Nearly one-third of all infants with epilepsy develop drugresistant epilepsy. Although epilepsy surgery is a well-established therapy across all age groups, there is a reluctance to operate infants in the first six months of life due to the unique surgical and anesthesiologic difficulties in this age group. Methods: We performed a meta-analysis and systematic review to assess the outcome and complication rate of epilepsy surgery in infants operated in the first six month of life. Statistical analysis was performed using the "metafor" and "meta" package with RStudio using a random effect model incorporating any heterogeneity between studies. Results: 158 infants reported in 16 studies underwent epilepsy surgery in the first six months of life. Overall seizure freedom after surgery was 65.61 % [0.5785; 0.7261]. Hemispherotomy was the most frequent surgery type performed (62.03 %, 98/158), and this was associated with a higher seizure-freedom rate (71 %) compared with those who underwent focal surgery (58 %). Complications occurred in 30.21 % of patients, most prominently a hydrocephalus developed in 23 out of 136 cases (16.91 %). In 21.51 % [0.1431; 0.3100] of 93 reported patients all anti-seizure medication ( ASM) could be discontinued. Furthermore, 85.88 % [0.5150; 0.9721] of all patients took less ASM than preoperatively. In four studies reporting on cognitive development preoperatively 84.61 % (22/26) infants showed cognitive impairment (development quotient ( DQ) <85). After surgery, there was a trend toward cognitive improvement with an average increase of 5.77 ±29.89 DQ points. Cognitive improvement was seen almost exclusively in seizure-free patients (+13.82 ±25.59 DQ points), while non-seizure free patients on average lost DQ points postoperatively (-9.44 ±32.92 DQ points) (p = 0.058). Discussion: We demonstrated that excellent seizure control can be achieved with epilepsy surgery in the first six months of life. In addition, ASM could be reduced or discontinued in a large proportion of patients postoperatively. The limited available data regarding cognitive outcome are promising, but also show that the primary goal should be to achieve seizure freedom. For this reason, as well as the more difficult surgical conditions, epilepsy surgery in the first six months of life should only be performed by specialized centers. Background: Transsylvian selective amygdalo-hippocampectomy (tsSA-HE) is a valid surgical treatment option for drug-resistant mesial temporal lobe epilepsy (mTLE) with seizure freedom rates of about 70 %. In a recently published study, we showed that resection of at least 27 % of piriform cortex strongly correlated with seizure freedom one year following tsSA-HE. However, the impact of piriform cortex resection on long-term seizure outcome is currently unknown. The aim of this study was to evaluate how the resection of piriform cortex impacts the long-term seizure outcome after tsSAHE in patients with mTLE. Methods: Long-term follow-up ( FU) was defined as at least two years postoperative. Between 2012 and 2017, 64 patients with mTLE who underwent tsSAHE at our center with a completed dataset for long-term FU were included in the analysis. The seizure outcome at the last available follow-up was assessed according to the International League against Epilepsy ( ILAE). Patients were stratified according to favorable ( ILAE class 1) and unfavorable ( ILAE class 2-6) seizure outcome and resected proportions of hippocampus, amygdala and piriform cortex were volumetrically assessed. Results: In the whole cohort, the mean follow-up duration was 3.75 years (y) with the range of 2-9y. Patients with favorable long-term seizure outcome available on the last FU revealed a significantly larger proportion of resected piriform cortex compared to patients with unfavorable seizure outcome (mean resected proportion was 42 % versus (vs.) 22 %, p = 0.0011). Resected proportions of hippocampus and amygdala did not significantly differ for these groups. Among those patients with at least 27 % resected proportion of piriform cortex, there were significantly more patients with seizure freedom at the last FU compared to the patients with less than 27 % resected proportion of pirirform cortex (83 % vs. 39 %, p = 0.0007) Conclusions: Our results show a strong impact of resected proportion of piriform cortex on long-term seizure outcome following tsSAHE in mTLE. Therefore, we suggest constituting the piriform cortex as a key target volume to achieve long-term seizure freedom following tsSAHE. Fragestellung: Die genetisch generalisierte Epilepsie ( GGE) ist durch eine abweichende neuronale Dynamik und subtilen strukturellen Verände-rungen gekennzeichnet. Wir haben untersucht, ob eine Kombination aus magnetischen und elektrischen neuronalen Signalen und der kortikalen Dicke ergänzende Informationen über die Netzwerkpathologie bei GGE liefern würde. Wir untersuchten auch, ob diese bildgebenden Phänotypen bei gesunden Geschwistern der Patienten vorhanden waren, um einen genetischen Einfluss zu prüfen. Methoden: In dieser prospektiven Querschnittsstudie analysierten wir Ruhezustandsdaten von 23 Patienten mit GGE, 18 gesunden Geschwister der Patienten, und 35 Kontrollen, die mittels Elektroenzephalographie ( EEG) und Magnetoenzephalographie ( MEG) erhoben wurden. Wir berechneten die Amplitudenstärke (power) und phasen-basierte Konnektivität (imaginary part of coherency) in sechs klassischen Frequenzbändern (1-40 Hz) auf kortikaler Oberfläche (5 min Datenlänge). Kortikale Dicke der Individuen wurde mittels T1-gewichteten MR-Kontrasten (3 T) ermittelt. Statistische Unterschiede zwischen den Gruppen wurden mit Hilfe von Permutationsanalysen linearer Modelle für jede Modalität separat und gemeinsam für alle Modalitäten unter Verwendung einer nichtparametrischen Kombinationsfunktion bewertet. Ergebnisse: Patienten mit einer GGE wiesen in allen Frequenzbändern eine höhere Ruhezustandsaktivität auf als Kontrollpersonen, wobei der Fokus im MEG eher in posterioren Regionen lag im Vergleich zum EEG. Die Konnektivität war ebenfalls erhöht, insbesondere in fronto-temporalen und zentralen Regionen in Theta-(am stärksten in EEG) und niedrigen Beta-Frequenzen (am stärksten im MEG), was in der kombinierten Analyse besonders hervortrat. Konnektivitätsunterschiede in höheren Frequenzen waren im EEG schwächer, was möglicherweise auf Medikamenteneffekte zurückzuführen ist. Die Einbeziehung der kortikalen Dicke in der kombinierten Analyse verstärkte die Gruppenunterschiede in der Aktivität und Konnektivität. Die funktionellen und strukturellen Befunde gesunder Geschwister waren intermediär, das heisst, sie lagen statistisch gesehen zwischen dem Niveau der Patienten und der Kontrollgruppe. Schlussfolgerungen: EEG wies bei GGE eine erhöhte Konnektivität und Power nach, ähnlich wie das MEG, allerdings mit unterschiedlicher spektraler Empfindlichkeit, was die Bedeutung der Theta-und Beta-Oszillationen bei GGE hervorhob. Die Verringerung der kortikalen Dicke bei GGE entsprach den Mustern der funktionellen Bildgebung. Unser multimodaler Ansatz erweitert das Verständnis des Ruhezustands bei GGE und weist auf genetische Grundlagen der untersuchten Bildgebungsmarker hin, was neue Einblicke in die Ursachen und Folgen der Epilepsie ermöglicht. Universitätsklinik Tübingen, Department für Neurochirurgie und Neurotechnologie, Tübingen, Germany; 2 Universitätsklinik Tübingen, Abteilung für Neurologie mit Schwerpunkt Epileptologie, Tübingen, Germany; 3 Universitätsklinik Tübingen, Abteilung für pädiatrische Neurologie, Tübingen, Germany Background: As the connectivity matrix of the human insula is complex, insular epilepsy presents a very heterogenous semiology. While stereoelectro-encephalography ( SEEG) helps to delineate the insular seizure onset zone ( SOZ), the relationship between the seizure propagation pattern and the corresponding semiology remains obscure. Based on the recent advances in connectome-based evaluation of functional motor networks in movement disorders (i. e., Parkinson's), we aimed to disentangle the cortical epilepsy network from the insular SOZ and to correlate the propagation pattern to the clinical presentation. Methods: This retrospective study enrolled a total of 57 insular SEEG electrodes in 19 patients. After spatial normalization of the patients' postoperative MRI scans and delineation of the SEEG electrodes, connectomebased analyses of functional and structural networks originating from contacts depicting epilepsy-related SEEG activity was performed using the Lead-DBS software. The resulting epilepsy networks were correlated to the corresponding semiology. Results: Epilepsy-related activity was depicted in 28/57 (49 %) of insular SEEG leads. 10/28 (36 %) electrodes were located in the anterior insula, while 12/28 (43 %) and 6/28 (21 %) were implanted in the middle or posterior insula, respectively. Structural and functional connectomic analyses indicated distinct connectivity matrices for different epileptic semiologies (i. e., sensory, somatosensible/motoric). In seizures with somatosensible/ motoric signs, SOZ projected to the somatosensory cortex. In contrast, sensory symptoms were linked to temporal areas. Conclusion: The semiology of insular epilepsy is mirrored in the functional and structural connectivity of the insular SOZ. Combining SEEG and connectomic analyses could provide additional information about seizure propagation within the epilepsy network and might enable new treatment options in future. Einleitung: MR-Bildgebungsstudien und neuropathologische Befunde bei Personen mit 22q11.2-Deletionssyndrom (22q11.2DS), dem häufigsten Mikrodeletionssyndrom, lassen auf eine anomale frühe Gehirnentwicklung schließen 1,2 . Rezazadeh et al. haben in einer kleinen Kohorte (n = 29) von Individuen mit 22q11.2DS ein gehäuftes Auftreten von periventrikulären nodulären Heterotopien ( PNH) beschrieben und die Hypothese aufgestellt, dass es sich hierbei um bei ihrer Wanderung gestoppte Arc-Zellen handeln könnte 2 . In dieser Studie wurden morphologische Veränderungen des Gehirns bei Personen mit 22q11.2DS mit einem besonderen Fokus auf die Detektion von Heterotopien untersucht 3 . Methoden: Ein Datensatz mit MRT-Aufnahmen (3D T1, T2*) von 75 Individuen mit genetisch gesichertem 22q11.2DS (27 w; 15,5 ± 7,4 Jahre) und 53 gesunden Kontrollen (24 w; 12,6 ± 4,7 Jahre) wurde von drei Neuroradiolog* innen auf das Vorliegen von PNH und anderen morphologischen Auffälligkeiten untersucht. Ergebnisse: Bei 10 der Individuen mit 22q11.2DS konnten PNH gefunden werden (. Abb. 1). Zudem konnten bei 29 Individuen Heterotopien in der weißen Substanz mit einer Betonung frontal beobachtet werden. Weitere Auffälligkeiten waren ein Cavum septi pellucidi und/oder Vergae bei 20 Individuen, periventrikuläre Zysten bei 10 und eine rechtsseitige Polymikrogyrie im Bereich der Sylvischen Fissur bei 3 Individuen. Die gesunden Kontrollen wiesen keine dieser Veränderungen auf. Diskussion: Bei 33 der Individuen mit 22q11.2DS konnten wir Heterotopien periventrikulär oder in der weißen Substanz finden, deren Auftreten und Lokalisation die Hypothese der unterbrochenen Arc-Zellwanderung 2 bekräftigen. Sowohl das Vorliegen von PNH im Allgemeinen, als auch das 22q11. DS werden mit epileptischen Anfällen in Verbindung gebracht. In der Studie von Rezazadeh et al. 2 hatten 6/7 Personen mit 22q11.2DS mit PNH eine Anfallsanamnese, was darauf hindeutet, dass Anfälle die Folge der PNH sein könnten. Leider waren die Informationen zur Epilepsiediagnose in unserer Kohorte unzureichend. Zusammengenommen geben unsere Befunde Hinweise auf die durch das 22q11.2-Deletionssyndrom verursachte Hirnentwicklungsstörung. The correct identification of an epileptogenic lesion ( EL) by MRI is challenging but is highly relevant as it improves the likelihood to be referred for presurgical diagnosis. The etiology of the epileptogenic lesion is directly related to indication and outcome of surgical intervention. Therefore, it is of great importance to identify EL and their etiology correctly presurgically. The final histopathological diagnoses of all patients with DRFE undergoing epilepsy surgery at our center between 2015 and 2021 were compared with MRI diagnoses given before consulting our epilepsy center and after presurgical diagnosis at our epilepsy center including MRI evaluation by epilepsy expert neuroradiologists. Additionally we analyzed the outcome of different subgroups. Results: A total of 137 patients were included. The disconcordance rate between histopathology and MRI diagnoses was reduced from 63 % in non-expert MRI evaluation ( NEMRI) to 25 % in epilepsy center MRI evaluation ( ECMRI). The MRI-negative rate was reduced from 32.4 % in NEMRI to 2.5 % in ECMRI. The differentiation of Dysembryoplastic Neuroepithelial Tumors ( DNET) and Gangliogliomas ( GG) as well as the identification of Focal Cortical Dysplasia ( FCD) was most challenging for both subgroups. While 67.7 % of patients with negative NEMRI were rendered seizure free (Engel IA) postoperatively, none of the patients with negative ECMRI achieved an Engel IA outcome. Mean duration of epilepsy until surgical intervention was 13.6 years in patients with initial negative NEMRI and 9.4 years in patients with a recognized lesion in NEMRI. This study provides evidence, that in patients with DRFE-especially with initial MRI-negative findings-an early consultation of an epilepsy center including MRI evaluation by epilepsy expert neuroradiologists is important to identify candidates for epilepsy surgery. Patients with DRFE that remain MRI-negative after initial NEMRI should be referred to an epilepsy center for presurgical diagnosis. Nonreferral based on NEMRI negativity may be harmful for such patients and delays surgical intervention. On the other hand, ECMRI-negative patients do have a reduced chance to become seizure free after epilepsy surgery. Further improvements of MRI-technique and evaluation are needed and should be directed towards a better discrimination of different LEAT types and improvement in FCD sensitivity. The P/Q-type voltage-gated calcium channels CaV2.1 in humans are encoded by the CACNA1A gene. The remarkable variability of neurological phenotypes induced by mutations in this gene is further enhanced by the fact that some, but not all phenotypes are associated with epileptic seizures. While some of these may be secondary to brain edema, the pathophysiology of others may lie in neuronal hyperexcitability. We hypothesize that under these circumstances part of the mutation-derived variance of CaV2.1 channel activation could originate from the nanotopology of presynaptic active zones, which strongly influence the discharge of neurotransmitter laden synaptic vesicles. To examine whether this idea can be tested experimentally, we here asked whether functional dichotomy of Drosophila melanogaster neuromuscular nerve terminals corresponds to nanostructural differences of calcium channels. We used direct stochastic optical reconstruction microscopy (dSTORM) in combination with hierarchical density-based spatial clustering of applications with noise ( HDBSCAN) to investigate differences in the arrangement of Cacophony, the Drosophila homologue of voltage-gated P/Q-type calcium channels, between presynaptic active zones of phasic and tonic terminals. Our preliminary findings show that presynaptic active zones from phasic terminals exhibited more and smaller channel clusters with a higher molecular density compared to tonic nerve endings. These findings suggest that investigating differential nanostructural details of neuronal synapses is a feasible approach, promising to reveal potentially important information on the functional heterogeneity of CACNA1A gene mutations. If successful, elucidating the nanostructural consequences of different CACNA1A mutations could improve our understanding of the molecular pathophysiology of associated epilepsy, and inspire new therapeutic approaches that target molecular interactions at presynaptic active zones. [2] . We epidemiologically investigated the impact of the COVID-19 pandemic on the admission and management of patients with status epilepticus ( SE) in the Cologne urban area. Material/Methods: We performed a retrospective analysis based on medical records of all SE patients admitted to the neurological clinics in Cologne in the first pandemic year compared with the last prepandemic year. Patients admitted between 03/2020 and 03/2021 were grouped as the pandemic group ( COV), while patients admitted between 03/2019 and 02/2020 served as the pre-pandemic control group (preCOV). All patients met the ILAE criteria for SE. In the case of generalized tonicclonic SE ( GCSE), the diagnosis was based on the typical clinical manifestation. In the case of non-GCSE, the "Salzburg-EEG-criteria" were used [3] . Patients were screened for demographics, SE etiology, onset, semiology, treatment, and outcome. Results: 328 SE patients were analyzed: 157 patients in preCOV and 171 patients in COV. When comparing the two subgroups, we found no differences in median age at onset (preCOV: 66 years, range 18-92 vs. COV: 66 years, range 18-93) or gender distribution (women preCOV 45 % vs. COV 47 %, p = 0.7). Furthermore, GCSE was equally common in preCOV (37 %) and in COV (42 %, p = 0.3). The most common SE causes were remote cerebrovascular disease (preCOV 52 % vs. COV 29 %, p < 0.001) and brain tumor (preCOV 9 % vs. COV 13 %, p = 0.2). Hospitalization occurred in less than 30 min in 25 % of preCOV but only 15 % of COV (p = 0.03), while 26 % of preCOV and 42 % of COV were hos-pitalized within 30-60 min (p = 0.003). SE ceased in (97 %) of preCOV and in (94 %) of COV (p = 0.2). In-hospital mortality was twice as high for COV (9 %) than for preCOV (4 %, p = 0.1). MRS before SE onset and at discharge did not differ between groups. SARS-CoV-2 infection was found in only three patients. Discussion: We provide epidemiologic data of SE management in the COVID-19 pandemic from the fourth largest German city. The pre-pandemic and pandemic subgroups did not differ in their epidemiological characteristics. However, during the COVID-19 pandemic, we found a shift toward fewer cerebrovascular SE etiologies and delayed hospitalization with likely higher mortality rates. Introduction: Patients with CASPR2 and LGI-1 encephalitis typically present with epileptic seizures, cognitive deficits, and/or psychiatric symptoms. Seizures typically occur several times per day at disease onset. Patients usually respond very well to immunosuppressive therapy, but not to anti-seizure medication ( ASM) in the acute phase of the disease. In sev- eral case series, the long-term seizure outcome seems to be favorable, prompting the concept of acute symptomatic seizures secondary to autoimmune encephalitis. However, the results of the studies are mostly based on self-reported seizure freedom, favoring under-reporting of seizures. Methods: Clinical records from our tertiary epilepsy center were screened for patients with LGI-1 and CASPR2 encephalitis. We included all patients who reported seizure freedom for at least 3 months during follow-up and underwent video-EEG monitoring for at least 24 h in the seizure free interval. We then screened for patients who had seizures during video-EEG despite previously indicating they were seizure free. Results: Out of 32 patients with LGI-1 (n = 24) and CASPR2 (n = 8) encephalitis, 23 underwent video-EEG for at least 24 h during follow-up. Of these, 20 (15 LGI1, 5 CASPR2) reported seizure freedom lasting at least 3 months. We recorded seizures in four patients (20 %) during video-EEG even though they reported seizure freedom. Reported seizure-free intervals before the recorded seizure ranged from 3 to 27 months. All patients were taking ASM at the time of video-EEG. Conclusion: Our study challenges the concept of acute symptomatic seizures and calls for a consistent prolonged video EEG telemetry in people with CASPR2 and LGI-1 encephalitis who report seizure freedom. Purpose: MR-negative refractory epilepsy is a challenge for the diagnosis and treatment of the affected patients. 7T MRI has been shown to allow localization of morphological alterations in a number of these cases. We propose the addition of a new generation of metabolic imaging based on fast and high-resolution magnetic resonance spectroscopic imaging ( MRSI). This overcomes many previous limitations in order to define metabolic changes in suspected lesions like decreased N-acetylaspartate ( NAA) and increased total choline (tCho) and total creatine (tCr). To investigate its utility, we conducted a patient study, now presenting the first results. Materials and Methods: Fourteen patients were included with refractory focal epilepsy. The 3D-MRSI protocol at a Siemens Magnetom 7T had the following main parameters: Scan time 15:30 min, 64×64×39 matrix, 220×220×133 mm 3 FOV, 3.4 mm nominal resolution. The reconstructed voxel spectra were fitted using linear combination using LCmodel (basis set with 14 distinct molecules and a macromolecular baseline). Quantities (in institutional units) were collated into metabolic maps which were compared to a clinical neurological assessment based on MRI and EEG and, if available, post-resection histology. We achieved acceptable image quality in 13 of 14 patients and found hot spots with at least partial correspondence to available clinical preoperative assessment in 11/13 cases. While tCho and tCr were increased in all of these hotspots, in accordance with literature expectations, we found variable changes for glutamate (Glu), myo-inositol (Ins), glutamine, taurine, and most importantly, NAA. We generally found that the NAA increases were eclipsed by stronger changes such as in tCho. In three FCD cases, the defined hot spots aligned well to a later resection, as demonstrated in . Fig. 1 Objective: MRI-negative drug-resistant epilepsy presents a challenge when it comes to surgical planning, and surgical outcome is worse than in cases with an identifiable lesion. Whereas in temporal lobe epilepsy a standardized resection approach is applicable in many cases, the surgical management of extratemporal lesions is always individual. Here, we present a strategy for surgical planning in patients with extratemporal MRInegative epilepsy focus and report our histological findings and patient outcomes. Methods: Patients undergoing epilepsy surgery in the Department of Neurosurgery of the University Hospital Erlangen between 2012 and 2020 were included in the study. Inclusion criteria were: (1) failure to identify a structural lesion on preoperative high-resolution 3 T MRI with a standardized epilepsy protocol and (2) preoperative EEG diagnostics revealing an extratemporal epilepsy focus. Results: We identified 8 patients corresponding to the inclusion criteria. Second look MRI analysis by an experienced neuroradiologist including the most recent analysis algorithm utilised in our clinic revealed a possible lesion in two patients. One of the patients with a clear focal cortical dysplasia ( FCD) finding on a second look was excluded from further analysis. Of the other 7 patients, in one patient invasive EEG was performed with subdural electrodes, whereas the other 6 were subjected to depth electrode EEG. Magnetoencephalography ( MEG) was performed preoperatively in all but one patient. An MEG focus was implemented in the resection planning in 3 patients. FDG PET was performed in all, but only implemented in the surgical planning in one patient. Preoperative fMRI was integrated in the surgical planning in order to identify eloquent brain regions. Intraoperative MRI was utilized for resection control and lead to continued resection in two patients. Histopathological evaluation revealed one nonlesional case, four cases with FCD (3 × FCD IIa and 1 × FCDIIb) as well as two cases with mild developmental malformation. All patients with depth electrodes EEG analysis had Engel 1A outcome on follow-up whereas one case with subdural electrode monitoring had Engel 1B outcome. Background: Invasive video-encephalography (iVEEG) is the gold standard for pre-surgical evaluation of refractory epilepsy. Traditionally, the presumed epileptic focus was covered with subdural electrodes ( SDE), a very invasive procedure prone to complications. The introduction of stereoencephalography ( SEEG) promised a reduction of invasiveness and surgical risk. However, SEEG surgery with conventional frame-based stereotaxy turned out to be very time-consuming and impeded by the geometry of the frame. The introduction of robot-assisted SEEG simplified trajectories to the temporal lobe. The aim of the present study was to described the evolution of invasive video-encephalography of the temporal lobe focusing on the impact of the robotic technology. Methods: This retrospective study enrolled 57 consecutive patients with medically intractable epilepsy who underwent iVEEG of a potential temporal seizure onset zone ( SOZ) by SDE (n = 40) or SEEG (n = 17). Surgical time efficiency was analyzed by the skin-to-skin time ( STS) and the total procedure time ( TPT The collected data will be used for establishing standardized reference values ("benchmarks") for this type of surgical procedure. The primary endpoints include seizure outcomes according to the International League Against Epilepsy ( ILAE) classification and defined postoperative complications. Schlussfolgerung: The EASINESS will define robust and standardized outcome references after amygdalohippocampectomy for temporal lobe epilepsy. After the successful definition of benchmarks from an international cohort of renowned centers, these data will serve as reference values for the evaluation of novel surgical techniques and comparisons among centers for future clinical trials. Practical aspects of High-density Electric Source Imaging of interictal epileptic discharges in the pre-surgical workflow: amount of spikes and semi-automated spike detection E. C. Heide, D. van de Velden, N. K. Focke Universitätsmedizin Göttingen, Klinik für Neurologie, Göttingen, Deutschland Introduction: One third of patients with epilepsy is pharmacoresistant and undergoes pre-surgical evaluation. High-density Electric Source Imaging (hdESI) of interictal epileptic discharges ( IED) plays an important role in the pre-surgical work-up. However, hdESI is only used in a limited number of epilepsy centers worldwide due to the complex and timeconsuming workflow including limited measurement time. Therefore, we analyzed the minimum number of spikes needed and compared the efficiency of a visual with a semi-automated spike-detection using Persyst. Methods: We retrospectively evaluated hdESI (256 channels) and individual MRI headmodels of 20 patients with pharmacoresistant focal epilepsy. The distance between the resected zone and the source reconstructed IED served as primary outcome parameter to test the effect of spike numbers on the accuracy of hdESI. As secondary outcome parameters, we analyzed the operator time needed and accuracy of visual compared to semi-automated Persyst spike marking. The data was analyzed in MATLAB (version R2018b), using the Fieldtrip Toolbox (revision: 20191127; http:// www.ru.nl/neuroimaging/fieldtrip/). The source reconstruction was performed on a 5 × 5 × 5 mm volumetric grid and later interpolated to an anatomical space of 1 × 1 × 1 mm. For each patient's IED source reconstruction the regularization parameter lambda was estimated individually and the weighted minimum-norm estimation (wMNE) was used. The distance between the resected zone and the source reconstructed IED did not change more than 1 mm above a mean number of 31 spikes. We found spikes in all of the 20 patients with a mean number of 74 spikes per patient (visual markings) and 113 spikes per patient (semiautomated Persyst markings) in a mean hdEEG length of 13 h and 14 min ±5 h and 39 min. The time to mark spikes in the full-length hdEEG was significantly shorter with a semi-automated Persyst marking compared to a purely visual marking by 275 ± 17 min (p < 0.0001, unpaired t-Test Introduction: The aim of this study is to determine the prevalence of anti-Drebrin autoantibodies in a cohort of 620 patients with suspected limbic encephalitis ( LE). Methods: Subsequently, the clinical features, outcome and neuropathological changes after epilepsy surgery of this novel autoantibody-related syndrome in a series of patients positive for the intracellular dendritic spine scaffolding protein antigen Drebrin with adult-onset epilepsy will be retrospectively analyzed. Anti-Drebrin autoantibody-positivity was detected by western blotting and confirmed by analysis of various control samples. Cryopreserved hippocampal human tissue of two patients underwent single nuclei isolation for RNA sequencing. Results: Anti-Drebrin autoABs was detected in nine patients by western blotting (m:f = 4:5) with a median age at neurological symptom onset of 44.9 ± 22.0 SD years (16-74 years). Cerebral magnetic resonance imaging of all patients presented increased amygdalohippocampal T2-signaling, change in volumetry of hippocampus or amygdala and hippocampal sclerosis affecting the temporal lobe unilaterally or bilaterally. A significantly increased cell number of activated CD3+/ HLA-DR+ T cells was detected by FACS analysis. All nine patients received classical anti-convulsive drugs ( ACD), but six patients were pharmacoresistant. Four patients were additionally treated with immunosuppressive therapy ( IS) and three patients underwent neurosurgical brain resection of the epileptic focus for seizure relief. Neuropathological examinations of hippocampal biopsies (n = 2) revealed hippocampal sclerosis. Cortical biopsy (n = 1) showed fibrillar and cellular astrogliosis, microglial infiltration, and CD3+ and CD8+ T cells in intraparenchymal and perivascular arrangements. Single nuclei RNA sequencing of hippocampal tissue (n = 2) was assessed to define specific immune signaling pathways, characterize individual B and T cell profiles and to identify neuronal subtypes and gene expression underlying epileptogenesis in anti-Drebrin-associated LE. Discussion: Anti-Drebrin-autoantibody-positive LE represents a novel autoimmune syndrome associated with epilepsy that is characterized by a hallmark clinical presentation. Cell type-specific isolation and transcriptomic profiling provide insight into immune pathology in anti-Drebrin-associated LE. Objective: To report the case of two patients-aged nine and 13-with GLUT1 deficiency GLUT1 deficiency syndrome is a treatable autosomal dominant disorder leading to a reduced glucose transport into the brain. While the classical type presents with therapy-resistant epileptic seizures and mild developmental delay, the atypical forms are characterized by ataxia, hypotonia or spasticity in the absence of epilepsy. Methods: We made the diagnosis genetically and via lumbar puncture. The cGH array was used as a genetic method: the SLC2A1 gene was amplified via PCR and then examined by using the MLPA method. The nine-year-old boy presented with a severe ataxia, and his 13-year-old brother suffered from absence epilepsy, receiving valproate therapy. He also demonstrated a less severe form of ataxia induced by physical strain. Their mother, a carrier of the gene, had absence seizures as a child herself and currently has a psychiatric disorder and movement disorder, while their father is healthy. A lower glucose account in the cerebrospinal fluid was shown in both patients. It was found that the two brothers have a heterozygote de novo mutation on the SLC2A1 gene. Ketogenic diet was initiated in both cases. After two months of therapy the ataxia had improved in both patients and disappeared altogether after four months of treatment. Consequently, valproate therapy was discontinued in the older patient, who has since stayed free of absences and seizures. A psychological test was conducted with both patients, revealing a minor improvement in their short-term memory and an increase in their range of vocabulary. Moreover, their motor skills and cognitive development have significantly improved. In conclusion, ketogenic diet has proven highly effective in patients with GLUT1 deficiency. However, compliance concerning ketogenic diet remains problematic as a successful treatment option. Objective: Endogenous glucocorticoids are released in a circadian manner with additional peaks during stressful events. Glucocorticoids exert their action by inducing numerous intracellular cascades affecting cell signaling. Thus, effects on memory and synaptic plasticity have been described both for glucocorticoids and acute and chronic stress. We assessed whether glucocorticoids affect human synaptic plasticity in the cortex of patients with drug-resistant temporal lobe epilepsy. Methods: Human cortical acute slices were prepared from temporal cortex specimens obtained during surgery for drug-resistant epilepsy and transferred to an interface recording chamber. Extracellular field potential recordings were obtained during repetitive stimulation by well-established protocols for induction of short-and long-term synaptic potentiation. Bath perfusion was performed with the glucocorticoid receptor ( GR) -agonist dexamethasone, the GR-and progesterone receptor antagonist mifepristone as well as with the neurosteroid progesterone. Perioperative cortisol levels were assessed to exclude effects of stress-induced cortisol release. Results: Synaptic plasticity was affected in opposite directions by the corticosteroid dexamethasone, which showed an inhibitory effect on synaptic plasticity, and its antagonist mifepristone, whereas progesterone showed no effect on long-term potentiation. Perioperative cortisol levels were low-normal and comparable to those of patients undergoing surgery for non-epileptic pathologies. Conclusion: The study demonstrates a detrimental effect of GR-blockage by dexamethasone on synaptic potentiation in the human temporal cortex. This effect is in agreement with corticosteroid effects observed during chronic stress. Chronic recurrent cortisol release during ictal stress events may supress synaptic plasticity to prevent strengthening of pathologic ictogenic rewiring. Bi-allelic variants in BDP1 are associated with a novel neurodevelopmental disorder with epilepsy Introduction: RNA polymerase III (Pol III) synthesizes short non-coding RNAs such as all tRNAs, 5S-rRNA, and U6 snRNA that are pivotal for basic cellular functions. The transcription factor TFIIIB recruits the polymerase initiation complex which is required for Pol III-catalyzed transcription [1] . Several subunits of Pol III and TFIIIB are known to cause neurodevelopmental disorders (NDDs) [2, 3] . In contrast, heterozygous variants of the TFIIIB component Bdp1 have only been associated with hereditary hearing loss [4] . Homozygous and compound heterozygous BDP1 variants were identified in an international cohort of four subjects with unsolved NDDs using whole exome sequencing. Clinical data and genetic variants were assessed and classified. For in-vitro analysis of Pol III-dependent downstream products, ribosome profiling was performed in patient-derived skin fibroblasts of the index patient harboring the bi-allelic, truncating variant p.(Glu2283*). Results: Affected subjects showed a variable spectrum of a NDD with global developmental delay. All but one subject were alive at last follow-up. Three of four subjects had epilepsy with mainly generalized febrile, myoclonic, or absence seizures. Neuroradiological features included progressive cerebellar atrophy, white matter changes suggestive for hypomyelination, hypoplastic frontal lobes, as well as infantile thalamic and ventricular hemorrhage. Sporadic organ manifestations further comprised retinal dystrophy, cataract, dilated cardiomyopathy, and facial dysmorphisms. Ribosomal profiling with differential gene expression analysis of fibroblasts derived from the index patient suggest downregulation of genes involved in autophagy and cellular response to hypoxia in comparison to control fibroblasts. Discussion: We present a novel progressive neurodevelopmental disorder associated with bi-allelic loss-of-function variants in BDP1. Affected subjects present a phenotypic spectrum partially overlapping with hypomyelinating leukodystrophies and pontocerebellar hypoplasia that have previously been associated with variants in components of the Pol III machinery [2, 3] . Ribosomal profiling suggests a possible pathophysiologic involvement of cellular autophagy and hypoxia pathways. Introduction: Limbic Encephalitis ( LE) is increasingly recognized as a cause of temporal lobe epilepsy ( TLE) with the damage pattern of hippocampal sclerosis ( HS) including segmental neuronal loss accompanied by extensive micro-and cellular astrogliosis. A particular clinical challenge is given by LE with autoantibodies to intracellular antigens. In this context, cytotoxic T cells represent key pathogenetic drivers in the early LE phase inducing irreversible neuronal damage and a chronic hyperexcitable hippocampal condition that is manifested by chronic recurrent epileptic seizures and memory deficits. A solely CD8 + T cell-mediated inflammation is sufficient to induce the disease pattern of LE in mice but the exact underlying inflammatory mechanisms leading to hyperexcitable hippocampal network activity in autoimmune encephalitis are not well understood. Methods: To study the pathophysiological process of inflammation and its correlation with epileptogenesis, we used a mouse model for cytotoxic T cell-driven LE ( OVA-CD8 + LE model) characterized by HS as well as a chronic recurrent seizure phenotype. Here, expression of the model-autoantigen ovalbumin ( OVA) was initiated by injection of a recombinant adeno-associated virus ( AAV) in the hippocampal CA1 area of transgenic mice genetically harboring T cells with a TCR specific for the OVA peptide. 3" mRNA Next Generation Sequencing approaches of whole hippocampi are used to analyze the time course of activation of cell-type-specific host defense signatures and hyperexcitability-related genes. The abundance of NK cells shows a progressive increase during the different stages of the model. In contrast, monocytes are transiently increased during the acute stage of the model. Additionally, specific epilepsy-related mechanisms also seem to play a major role in this CD8 + T cell-driven LE model. Accordingly, vascular cell adhesion molecules were increased on the mRNA level. These molecules promote leukocyte recruitment to the luminal surface of vessels at sites of inflammation suggesting that leukocytes may also promote seizures and epileptogenesis from the luminal side of the vasculature without entering the brain. Also, specific cytokines showed an augmented time-dependent expression profile indicating a neuroinflammatory response after an initial precipitating injury. Discussion: Our data provide detailed insights into the functional impact of CD8 + T cell-driven LE on the expression patterns of transcripts relevant to altered excitability of neuronal circuits and indicate what may be the underlying inflammatory mechanisms representing intriguing information to derive new pathogenetic concepts. This work was supported by the Deutsche Forschungsgemeinschaft (SFB1089, FOR2715), Else Kröner-Fresenius-Foundation and the BONFOR program of the University Hospital Bonn. Introduction: ATP-sensitive potassium channels ( KATP channels) essentially mediate cell metabolism and electrical activity by coupling intracellular ATP levels to K+ membrane conductance. Gain-of-function mutations of KATP channels result in developmental delay and epilepsy with neonatal diabetes, i. e., DEND syndrome. While the role of KATP channels in beta cells and the cause of neonatal diabetes in this syndrome is well understood, the pathophysiology of the neurological symptoms remains to be elucidated. We hypothesized that KATP channels are key players in parvalbumin+ interneurons ( PV-INs), which play a pivotal role in generating both hippocampal sharp-wave ripples (SWRs) and gamma frequency oscillations (30-100 Hz) and whose dysfunction is associated with epilepsy and cognitive comorbidities. Therefore, we asked whether constitutively open KATP channels in PV-INs may be responsible for the neurological symptoms of the DEND syndrome. Methods: We investigated this question by using in vitro and in vivo local field potential ( LFP) recordings as well as patch-clamp recordings of PV-INs in the hippocampal area CA1 of adult mice. Results: We found that opening KATP channels pharmacologically in all neurons reduces both the frequency and magnitude of in vitro hippocampal SWRs and gamma oscillations. To specifically investigate the role of KATP channels in PV-INs, we expressed the most common human Kir6.2 gain-of-function mutation V59M heterozygously in PV-INs ( PV-V59M) and found that SWRs and gamma oscillations were severely impaired in PV-V59M mice similar to our pharmacological findings. Additionally, we found a reduction in power of hippocampal gamma oscillations during wakefulness as well as seizures in in vivo LFP recordings of PV-V59M mice. To study underlying cellular properties, we performed patch-clamp recordings of PV-INs in hippocampal slices showing no major alterations in passive membrane and active firing properties in PV-V59M mice. However, the power of intrinsic membrane potential oscillations in the gamma range was significantly decreased and fewer cells revealed gamma as their peak frequency. Moreover, the proportion of neurons revealing gamma resonance behaviour was significantly reduced in PV-V59M mice. Discussion: Thus, our findings provide evidence that the KATP channel mutation V59M expressed only in PV-INs can account for altered network oscillations and seizures potentially underlying the neurological symptoms developmental delay and epilepsy of the DEND syndrome and highlight the crucial role of PV-INs in oscillatory activity and network inhibition. Hintergrund: BEPK sind häufige EEG-Muster bei Patienten mit idiopathischen fokalen Epilepsien, insbesondere bei Kindern mit Rolando-Epilepsie. Aber sie treten auch bei strukturellen Formen der Epilepsie und bei neurologischen nicht-epileptischen Erkrankungen im Zusammenhang mit der "Pathologie der Gehirnreifung" auf. Bei idiopathischen Epilepsieformen finden sich BEPK-EEG-Muster ausschließlich im Kindesalter, in der Regel zwischen 3 und 15 Jahren. Eine Remission tritt vor der Adoleszenz auf. Wenn das Nervensystem reift, können auch die BEPK-Muster allmählich verschwinden. BEPKs können auf unterschiedliche Weise blockiert werden: Augenöffnen, jede manuelle Tätigkeit kontralateral zum Fokus (Schreiben, Faustschluss, Zusammenbau des Puzzles usw.). Fragestellung: die Rolle und Blockierung der BEPK im EEG für die Diagnosestellung bei idiopathischen und strukturellen Epilepsieformen, und bei neurologischen Erkrankungen ohne Epilepsie. Material/Methode: Es wurden 40 Video-EEG-Untersuchungen mit EEG-Amplitudenmapping, EEG-Frequenzmapping analysiert: 8 Kinder-Rolando-Epilepsie, 2-Panayiotopoulos-Syndrom (idiopathische fokale Epilepsien); 5 Kinder-Zerebralparese mit Epilepsie, 1-Tumor, 1-Atrofie der linken Hirnhemisphäre, 1-kortikaler zystischer Defekt, 2-Schädel-Hirn-Trauma (strukturelle Epilepsieformen); 10 Kinder-Sprachentwicklungsverzögerung, 10-Aufmerksamkeitsdefizit-Hyperaktivitätsstörung ( ADHS) (neurologische nicht-epileptische Erkrankungen). Ergebnisse: Unterschiede zwischen Erkrankungen finden sich bei der Blockierung der BEPK-EEG-Muster. Augenöffnen führte zu einer Blockierung oder Verringerung der BEPK-EEG-Muster im EEG bei idiopathischen fokalen Epilepsien und bei Kindern mit neurologischen nicht-epileptischen Er-krankungen. Im Gegensatz dazu wurden BEPK bei strukturellen Epilepsieformen nicht blockiert. Diskussion: Das Auftreten von BEPK im EEG basiert auf einer genetischen Prädisposition und organischen Störung des ZNS, insbesondere antenatal und perinatal. Die Blockierung der BEPK-EEG-Muster zeigt sich bei idiopathischen fokalen Epilepsien im Vergleich zu strukturellen Epilepsieformen. Im EEG bei strukturellen Epilepsieformen werden BEPK oft in streng definierten anatomischen Bereichen über viele Jahre lokalisiert. Es zeigt sich auch eine Kombination von BEPK-EEG-Mustern mit der regionalen Verlangsamung der EEG-Aktivität oder mit einer schweren Allgemeinveränderung. Aber alle Methoden der neurophysiologischen Blockierung von BEPK im EEG müssen zusammen mit klinischen, neurologischen, psychologischen und anderen diagnostischen Untersuchungen interpretiert werden. Background: Establishing the diagnosis of epilepsy can be challenging if interictal epileptic discharges (IEDs) or seizures are undetectable. Many individuals with epilepsy experience sleep disturbances, and a reduced percentage of REM sleep ( REM%) has been observed following seizures. We aimed to assess whether REM% differed in individuals with epilepsy compared with individuals with differential diagnoses. Methods: We performed a retrospective, monocentric, two-armed casecontrol study with 128 age-matched individuals who underwent ≥72 h of continuous video-EEG monitoring at the epilepsy monitoring unit ( EMU) for evaluation of potential epileptic events. We assessed REM% on the first and the last night of EMU admission. Binary logistic regressions models were used to evaluate the predictive value of REM%. Results: Upon discharge, 64 individuals were diagnosed with epilepsy, 64 with a differential diagnosis. Mean REM% in the epilepsy group was significantly lower [12. [3] ). Ziel unserer Untersuchung war es deshalb, die Dynamik neuronaler Komplexität in Epilepsiepatienten bei sich ändernder HE -ausgelöst durch die Abdosierung der antiepileptischen Medikation ( AED) -zu untersuchen. Material/Methode: Wir analysierten die Änderung der neuronalen Komplexität -quantifiziert als sample entropy [4] in temporalen Elektroden des Oberflächen-EEGs -in konsekutiven EEG-Ruhemessungen von 29 Patienten mit unilateraler Temporallappenepilepsie, deren antiepileptische Medikation ( AED) im Rahmen eines Video-EEG Monitoring reduziert wurde. Pro Tag des stationären Aufenthalts erfolgte eine Ruhe-Messung. Als Vergleichsmaß diente die spektrale Power im Delta-Band. Quantifiziert wurde die Änderung der neuronalen Komplexität sowie der Delta-Power mittels linearer Regression (linear fits) als Funktion der konsekutiven Rußmessungen. Patienten mit psychogenen nicht-epileptischen Anfällen dienten als Kontrollgruppe. Ergebnisse: Begleitend zur Reduktion der AED zeigte sich die neuronale Komplexität in Epilepsiepatienten über die konsekutiven Ruhe-Messungen abnehmend. Hierzu passend fand sich die Steigung der linear fits der neuronalen Komplexität signifikant negativ (p = 5,6 × 10 -4 , n = 29). Die durchschnittliche Steigung der linear fits basierend auf der Delta-Power war dagegen positiv (p = 0,049, n = 29). Bei Patienten mit ausschließlichen psychogenen nicht-epileptischen Anfällen zeigte die neuronale Komplexität unter Medikamentenreduktion keine signifikante Änderung (p = 0,95, n = 8). Diskussion: Die Reduktion von antiepileptischer Medikation führt in Epilepsiepatienten zu einem Verlust an neuronaler Komplexität im Oberflächen-EEG. Die fehlende signifikante Veränderung bei PNES-Patienten spricht hierbei gegen einen Medikamenteneffekt und für eine Korrelation mit der epileptischen Hyperexzitabilität. Background: Family burden in pediatric patients who suffer from drug resistant epilepsy ( DRE) is a significantly higher than in those with non-DRE. Epilepsy surgery is an established approach to treat DRE. This study examines the impact of pediatric epilepsy surgery on family burden. Methods: We retrospectively analyzed the data of all families and pediatric patients treated for DRE in our epilepsy surgery program from April 2018 to November 2021. We examined the relationship between cognitive, behavioral and epilepsy specific data and the family burden measured with the German version of the Impact on Family Scale (FaBel) before and after epilepsy surgery. Results: Cognitive impairment is correlated with family burden in children with DRE. Surprisingly, a high seizure frequency has a lower impact on mastery in families with children suffering from DRE than a low seizure frequency. Following epilepsy surgery test results reveal a decreased family burden. A higher duration of epilepsy and lower pre-surgical behavioral problems are associated with a higher perceived reduction of post-surgical family stress. Conclusion: Epilepsy surgery reduces the family burden in children with DRE. In our study family burden is significantly affected by epilepsy specific factors and cognitive impairment. Furthermore, family burden might be associated with structural health-care problems due to a long process for the family to find their way to epilepsy surgery evaluation. Purpose: Aromatic l-Amino Acid Decarboxylase ( AADC) deficiency is a rare autosomal recessive disorder resulting in marked dopamine loss, impeding normal motor development. A common symptom of AADC deficiency is oculogyric crises ( OGC), which is frequently linked to decreased dopamine levels and characteristic involuntary eye movement. OGCs can also be accompanied by limb stiffness, torso rigidity, and autonomic signs. Eladocagene exuparvovec, a recombinant adeno-associated viral vector containing the human cDNA encoding the AADC enzyme, was studied in 3 AADC clinical trials. The effectiveness of CBD as the standard therapy for seizures associated with tuberous sclerosis ( TSC) has been demonstrated with an acceptable safety profile in a randomized, placebo-controlled phase III study (GWPCARE6; NCT02544763). In this post-hoc analysis, the decrease in seizure frequency was evaluated and the proportion of TSC patients taking CBD or placebo who continuously reached all threshold values for the responder rate and the longest seizure-free intervals was determined. Material/method: The patients received a highly purified plant-based CBD drug (Epidyolex ®, 100 mg/ml oral solution) at a dose of 25 mg/kg/ day (CBD25) or 50 mg/kg/day or an equivalent for 16 weeks Placebo. The effectiveness of CBD25 (n = 75) compared to placebo (n = 76) was assessed using the percentage decrease in TSC-related seizure frequency from baseline and the longest seizure-free intervals. As part of the statistical analysis, the treatment ratios and the associated 95 % confidence intervals and p-values were calculated. Infection fatality rate of SARSCoV2 in a superspreading event in Germany Analysis of Nationwide Stroke Patient Care in Times of COVID19 Pandemic in Germany Unified EEG terminology and criteria for nonconvulsive status epilepticus Structural basis of RNA polymerase III transcription initiation Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy BRF1 mutations alter RNA polymerase IIIdependent transcription and cause neurodevelopmental anomalies Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss Language dominance in mesial temporal lobe epilepsy: a functional transcranial Doppler sonography study of brain plasticity Probabilistic machine learning for the evaluation of presurgical language dominance Is it possible to detect cerebral dominance via EEG signals by using deep learning? The classical pathways of occipital lobe epileptic propagation revised in the light of white matter dissection Okzipital und Parietallappenepilepsien -Klinische Anfallssemiologie und Elektrophysiologie Brauchitsch 1 , A. Strzelczyk 1,2 , F. Rosenow 1,2 , E. Neuhaus 1,3 Deutschland; 3 Institut für Neuroradiologie Epilepsy meets cancer: when, why, and what to do about it? Epilepsy in the end of life phase of brain tumor patients: a systematic review VSB) = 3,775, p = 0,052; χ²( ISAS) = 2,4128, p = 0,12), während bei 15 % der Patient: innen ohne MR-Befund, die eine VSB erhielten, und bei 36 % der Patient:innen ohne MR-Befund, die eine ISAS erhielten, keine kFH generiert werden kann. 44 (22 %) Patient:innen wurden operiert. Zwischen postoperativer Anfallsfreiheit (Engel-Klasse 1) und lokalisierender (Kategorie A, B) VSB und ISAS konnte kein signifikanter Zusammenhang nachgewiesen werden Die Ergebnisse zeigen die Notwendigkeit der Entwicklung von SPECT-Nachbearbeitungs-Methoden und die Schwierigkeit auf, eine AUZ mittels SPECT bei extratemporalen Epilepsien zu erkennen. Unklar bleibt, welchen Einfluss VSB und ISAS tatsächlich auf eine Behandlungsentscheidung haben Frühere Fallberichte und retrospektive Studien weisen auf eine erhöhte Konzentration der mTORC1-Inhibitoren (Mammalian Target of Rapamycin Complex 1) im Blut bei gleichzeitiger Verabreichung mit CBD hin. In dieser offenen Phase-I-Studie mit fester Abfolge wurde die Wirkung von CBD-Mehrfachdosen auf die pharmakokinetischen Parameter ( PK-Parameter) einer Everolimus-Einzeldosis bei gesunden Freiwilligen untersucht. Material/Methode: Tag 1: Die Teilnehmer erhielten 5 mg Everolimus (orale Tablette). Tag 2-8: Auswaschzeitraum. Tag 9-17: Die Teilnehmer erhielten 12,5 mg/kg BID eines hochgereinigten CBD-Arzneimittels (Epidyolex®, 100 mg/ml Lösung zum Einnehmen) auf pflanzlicher Basis. Tag 13: Die Teilnehmer erhielten 5 mg Everolimus gleichzeitig mit ihrer CBD-Morgendosis Fläche unter der Kurve von der Verabreichung bis zur letzten Beobachtung Ergebnisse: 15 männliche Teilnehmer mit einem mittleren Alter (Altersbereich) von 28 (20-45) Jahren haben die Studie abgeschlossen. Die Konzentration von Everolimus war bei gleichzeitiger Verabreichung mit CBD im Vergleich zu Everolimus allein erhöht. Das Verhältnis des geometrischen Mittels unter Prüfbedingungen im Vergleich zu Bezugsbedingungen für 2) Stunden im Vergleich zu 40,0 (± 5,1) Stunden. Unerwünschte Ereignisse wurden bei 10 Teilnehmern (63 %) berichtet. Alle UE waren nur leicht ausgeprägt und bildeten sich spontan zurück. Diskussion: Die Ergebnisse deuten darauf hin, dass CBD die Resorption von Everolimus, bei Verabreichung als orale Tablettenformulierung erhöht, ohne erkennbaren Einfluss auf die systemische Clearance. Bei gleichzeitiger oraler Gabe von CBD sind daher Anpassungen der Everolimus-Dosis zu erwägen = 21) von Patienten mit DS (n = 14) bzw. LGS (n = 7) rekrutiert, die ≥ 6 Monate mit einem hochgereinigten CBD-Arzneimittel (Epidyolex®; 100 mg/ml Lösung zum Einnehmen) auf pflanzlicher Basis behandelt wurden. Den Teilnehmern wurde ein Fragebogen zu Hintergrundinformationen gesendet. In Telefongesprächen wurden die Symptome und die Auswirkungen des DS und des LGS sowie die nicht-anfallsbezogenen Wirkungen von CBD besprochen First onset of the most common AEs emerged throughout the double-blind and OLE, mostly during titration. In C021 the peak occurred when dosing reached ≥50 mg/day. Median duration in days (doubleblind, all occurrences) was: somnolence 32 cenobamate versus 22 placebo, dizziness 11 cenobamate versus 8 placebo, and fatigue 34 cenobamate versus 20.5 placebo. AEs in the double-blind were primarily mild or moderate, with few severe AEs. In C021, more patients reported mild AEs and fewer reported moderate and severe AEs. Conclusion: Onset of the most common AEs occurred primarily during titration; AEs were generally self-limited in duration and mainly mild or moderate Fragestellung: Bisherige Studien haben gezeigt, dass Menschen mit Epilepsie häufig Gedächtnisprobleme angeben. Diese subjektive Einschätzung hängt nicht konsistent und höchstens gering mit den Leistungen zusammen, die in neuropsychologischen Untersuchungen zum Gedächtnis erhoben werden. Jedoch scheinen sie von der Stimmung der Patienten beeinflusst zu sein, die bei Epilepsiepatienten häufig durch eine komorbide Depression geprägt wird (Hall et al., 2009 ). Menschen, die neu mit Epilepsie diagnostiziert waren und keine bedeutsame depressive Symptomatik aufzeigten, gaben in einer Befragung überwiegend keine subjektiven Gedächtniseinschränkungen an (Gorny et al., 2021). Hier soll untersucht werden, ob Epilepsiepatienten im Verlauf des ersten Jahres nach der Diagnose subjektive Gedächtnisprobleme entwickeln und wie diese mit depressiver Symptomatik zusammenhängen. Methode: Bisher wurden 72 Patienten, die mit einem ersten epileptischen Anfall hospitalisiert waren, und an der laufenden Studie teilnahmen in die Untersuchung eingeschlossen. Davon erhielten 46 die Diagnose Epilepsie (Epi) und 26 nicht (NoEpi). Dabei wurden sie gebeten über Fragebögen ihre kognitive Leistungsfähigkeit (FLei) und ihre depressive Symptomatik ( BDI-II) einzuschätzen (Zeitpunkt t1). Nach einem Jahr wurden die subjektiven Maße erneut erhoben (Zeitpunkt t2; n = 41). Ergebnisse: Der BDI-II-Wert war zu t1 in der Epi-Gruppe größer (Mdn = 8), als in der NoEpi-Gruppe (Mdn = 3) (U = 753,50, z = 2,975; p = 0,003; r = 0,36). Dies galt auch für Zeitpunkt t2 (W = 279,50; z = 2,01 p = 0,044; r = 0,31). In der Epi-Gruppe gab es zu beiden Zeitpunkten einen signifikanten Zusammenhang von BDI-II-Wert und subjektiv wahrgenommenen Gedächtnisproblemen (rt1 = 0,430; p = 0,004; rt2 = 0,672; p = 0,001), dies war bei der NoEpi-Gruppe nur zum Zeitpunkt t1 der Fall (rt1 = 0,521; p = 0,008; rt2 = 0,034; p = 0,898). Nach Herauspartialisierung des Einflusses der depressiven Symptomatik gab es in der Epi-Gruppe in einer Varianzanalyse keine signifikanten Veränderungen in der subjektiven Gedächtnisleistung über die Zeit (n = 17; F = 0,566; p = 0,461; η 2 = 0,029). Diskussion: Die Ergebnisse zeigen, dass eine depressive Symptomatik schon zu Beginn der Diagnose und auch nach einem Jahr ein wichtiger Einflussfaktor auf subjektive kognitive Leistungsfähigkeit ist. In der untersuchten Stichprobe wurden im ersten Jahr nach der Diagnose über den Einfluss depressiver Symptomatik hinaus keine subjektiven Gedächtnisprobleme entwickelt. Purpose: Cenobamate is a new antiseizure medication ( ASM) approved in the US for uncontrolled focal seizures in adults and in the EU as adjunctive treatment of uncontrolled focal seizure in adults after failure of at least 2 ASMs. Two international, double-blind, placebo-controlled trials (C013/ C017) demonstrated cenobamate efficacy and safety. Here we report time to onset of efficacy during titration of cenobamate in these studies. Method: Adults with uncontrolled focal seizures and taking 1-3 concomitant ASMs were enrolled in Studies C013/C017. Concomitant ASM changes were not allowed during the double-blind period. Time to onset of cenobamate efficacy was evaluated during the 6-week cenobamate titration (C013: 50 mg/day initial dose, increased 50 mg/week every 2 weeks to the 200 mg/day target dose. Amended C017: 50 mg/day initial dose, increased 50 mg/week until target dose of 100 or 200 mg/day; patients randomly assigned to 400 mg/day were up-titrated by 100 mg/day per week after the 200 mg/day dose). Post-hoc analysis of efficacy examined the percent reduction in seizure frequency from baseline to each week during titration using a Wilcoxon rank-sum test (C013) or an ANCOVA model fit to ranked values of baseline seizure rate and treatment group (C017). Results: Patients receiving cenobamate had significant reductions in median percent seizure frequency versus placebo starting from the first 1-2 weeks of cenobamate titration at the initial dose of 50 mg/day (C013: -26.7 % cenobamate vs -15.1 % placebo, P < 0.05; C017: -36.4 % cenobamate vs -20.0 % placebo, P < 0.05). Sustained significant decreases in seizure frequency versus placebo were seen throughout the 6-week titration in both studies, reaching -39.5 % versus -12.8 % at week 6 in C013. Median reduction in seizure frequency was progressively higher with cenobamate doses of 100 (-39.0 %), 200 (-52.2 %), and 400 mg/day (-55.5 %) versus -12.5 % at week 6 in C017. Conclusion: Onset of cenobamate efficacy in significantly reducing seizure frequency occurs early and at lower doses than the target dose for maintenance therapy; efficacy improves at higher doses. Studies sponsored by SK Life Science; analyses supported by Arvelle Therapeutics.