Neuropsychologische Schätzdefizite bei rechtsfrontaler und rechtstemporaler Epilepsie

Background: Previous studies revealed a right-hemispheric dominance for cognitive estimation processes. Objectives: This study explored estimation impairments in patients with focal temporal and frontal lobe epilepsies. Methods: 109 patients (right frontal, left frontal, right temporal-mesial, right temporal-neocortical, left temporal-mesial, left temporal-neocortical) and a control group with 67 subjects were included. All subjects underwent an extensive neuropsychological assessment including the Test zum kognitiven Schätzen (TKS; Brand et al., 2002). Hypothesis: It was expected that right-hemispheric lesions would be associated with impairments in cognitive estimation. Results: Patients with right-frontal and right-temporal mesial focus showed significant estimation deficits compared to the other groups. Conclusion: This study shows that the right hemisphere dominantly participates in cognitive estimation.Hintergrund: Nach dem bisherigen Forschungsstand sind neuropsychologische Beeinträchtigungen der Schätzfunktion vor allem bei rechtshemisphärischen Läsionen zu erwarten. Ziele: Es wurde die Fähigkeit des Schätzens bei Epilepsiepatient_innen und einer gesunden Kontrollgruppe untersucht. Je nach Läsionsort wurden sechs Gruppen (rechtsfrontal, linksfrontal, rechtstemporal-mesial, rechtstemporal-neokortikal, linkstemporal-mesial, linkstemporal-neokortikal) einbezogen. Methoden: Mit 176 Personen, 109 Patient_innen und 67 Kontrollpersonen, wurde der Test zum kognitiven Schätzen durchgeführt. Fragestellung: Es wurde erwartet, dass speziell Patient_innen mit rechtshemisphärischen Läsionen Defizite im Schätzen aufweisen. Ergebnisse: Patient_innen mit rechtsfrontalen und rechtstemporalen mesialen Läsionen wiesen signifikant schlechtere Schätzleistungen gegenüber Patient_innen mit linkshemisphärischen Läsionen und der Kontrollgruppe auf. Fazit: Die Ergebnisse sprechen für die vorherrschende Beteiligung der rechten Hemisphäre an der Fähigkeit des kognitiven Schätzens

Telemedizin in der Epilepsieversorgung: Arzt-zu-Arzt-Anwendungen - Teil II: Aktuelle Projekte in Deutschland

Background During the last 10 years several German epilepsy centers (Bochum, Erlangen, Greifswald, Berlin Brandenburg, Frankfurt Rhein-Main) developed telemedicine projects, which offer doc-to-doc applications in the field of epilepsy care. Objective To give an overview of the currently running telemedical projects in epilepsy care in Germany. Material and methods Project leaders present their work using a predefined schematic. Results and discussion All projects achieved technical solutions for the telemedical doc-to-doc application in the field of epileptology. The presented projects partly differ with regards to their goals and implementation, partly they share similarities. All projects aim to use their experience in the individual projects to develop a common strategy for the facilitation of epileptological telemedicine and its transfer into standard care.Hintergrund In den vergangenen 10 Jahren wurden an verschiedenen Epilepsiezentren in Deutschland (Bochum, Erlangen, Greifswald, Berlin Brandenburg, Frankfurt Rhein-Main) Projekte entwickelt, die sich mit telemedizinischen Arzt-zu-Arzt-Anwendungen im Bereich der Epilepsieversorgung beschäftigen. Ziel der Arbeit Im Folgenden wird ein Überblick über die aktuell laufenden telemedizinischen Projekte in der Epilepsieversorgung in Deutschland gegeben. Material und Methoden Die Verantwortlichen der einzelnen Projekte stellen ihr Projekt anhand einer vorgegebenen Struktur dar. Ergebnisse und Diskussion In allen Projekten konnte gezeigt werden, dass eine technische Lösung für die telemedizinische Arzt-zu-Arzt Anwendung im Bereich Epileptologie geschaffen werden kann. Die dargestellten Projekte unterscheiden sich zum Teil hinsichtlich des Zieles und der Umsetzung, zum Teil zeigen sich Übereinstimmungen. Perspektivisches Ziel ist es, aus den Erfahrungen der einzelnen Projekte eine gemeinsame Strategie zur Förderung epileptologischer Telemedizin und ihrer Überführung in die Regelversorgung zu entwickeln

Anti-seizure medication is not associated with an increased risk to develop cancer in epilepsy patients

Objective Whether anti-seizure medication (ASM) increases the risk for cancer has been debated for decades. While for some ASM, a carcinoma-promoting effect has been suspected, carcinoma-protective effects have been shown for other ASM. However, the issue remains unresolved as data from preclinical and clinical studies have been inconsistent and contradictory. Methods We collected anonymous patient data from practice neurologists throughout Germany between 2009 and 2018 using the IMS Disease Analyzer database (QuintilesIMS, Frankfurt, Germany). People with epilepsy (PWE) with an initial cancer diagnosis and antiepileptic therapy prior to the index date were 1:1 matched with a control group of PWE without cancer according to age, gender, index year, Charlson Comorbidity Index, and treating physician. For both groups, the risk to develop cancer under treatment with different ASMs was analyzed using three different models (ever use vs. never use (I), effect per one (II) and per five therapy years (III). Results A total of 3152 PWE were included (each group, n = 1,576; age = 67.3 ± 14.0 years). The risk to develop cancer was not significantly elevated for any ASM. Carbamazepine was associated with a decreased cancer risk (OR Model I: 0.699, p < .0001, OR Model II: 0.952, p = .4878, OR Model III: 0.758, p < .0004). Significance Our findings suggest that ASM use does not increase the risk of cancer in epilepsy patients

Telemedizin in der Epilepsieversorgung: Arzt-zu-Arzt-Anwendungen - Teil I: State-of-the-Art, Herausforderungen, Perspektiven

Telemedical doc-to-doc applications in epilepsy care can help to provide the special expertise of adult or pediatric epileptologists area wide, as they make it possible to provide medical services across spatial distances. Various solutions are being developed both nationally and internationally for this purpose; however, there are organizational, technical, legal and economic challenges. The long-term perspective of the various current approaches is unclear. Ultimately, business models will have to be developed in which all players (consultation providers and requesting physician, patients, health insurers, operators of telemedical platforms and, if necessary, the respective professional associations) weigh up the specific benefits and risks.Telemedizinische Arzt-zu-Arzt-Anwendungen in der Epilepsieversorgung können helfen, die spezielle Expertise von neurologischen oder pädiatrischen EpileptologInnen flächendeckend vorzuhalten, da sie es ermöglichen, medizinische Leistung über Distanzen hinweg zu erbringen. Sowohl national als auch international werden hierzu verschiedene Lösungsansätze entwickelt. Herausforderungen begegnet man auf organisatorischer, technischer, rechtlicher und ökonomischer Ebene, sodass die langfristige Perspektive der einzelnen aktuellen Lösungsansätze noch unklar ist. Letztendlich bedarf es der Entwicklung von Betriebsmodellen, bei denen alle Akteure (Konsilgeber, Konsilanforderer, Patient, Kostenträger, Betreiber der telemedizinischen Plattform und ggf. auch die jeweilige Fachgesellschaft) jeweils den spezifischen Nutzen und die Risiken abwägen

Differential influence of hippocampal subfields to memory formation: insights from patients with temporal lobe epilepsy

To clarify the anatomical organization of human memory remains a major challenge in clinical neuroscience. Experimental data suggest dentate gyrus granule cells play a major role in memory acquisition, i.e. pattern separation and rapid pattern completion, whereas hippocampal CA1 neurons are implicated in place memory and autobiographical memory retrieval. Patients with temporal lobe epilepsy present with a broad spectrum of memory impairment, which can be assessed during clinical examination. Although long seizure histories may contribute to a pathophysiological reorganization of functional connectivity, surgical resection of the epileptic hippocampus offers a unique possibility to anatomically study the differential contribution of hippocampal subfields to compromised learning and memory in humans. Herein, we tested the hypothesis of hippocampal subfield specialization in a series of 100 consecutive patients with temporal lobe epilepsy submitted to epilepsy surgery. Memory profiles were obtained from intracarotid amobarbital testing and non-invasive verbal memory assessment before surgery, and correlated with histopathologically quantified cell loss pattern in hippocampal subfields obtained from the same patients using the new international consensus classification for hippocampal sclerosis proposed by the International League against Epilepsy (HS ILAE). Interestingly, patients with CA1 predominant cell loss (HS ILAE Type 2; n = 13) did not show declarative memory impairment and were indistinguishable from patients without any hippocampal cell loss (n = 19). In contrast, 63 patients with neuronal loss affecting all hippocampal subfields including CA1, CA4 and dentate gyrus (HS ILAE Type 1), or predominant cell loss in CA4 and partially affecting also CA3 and dentate gyrus (HS ILAE Type 3, n = 5) showed significantly reduced declarative memory capacities (intracarotid amobarbital testing: P < 0.001; verbal memory: P < 0.05). Our results suggested an alternative model of how memory processing can be organized amongst hippocampal subfields, and that CA1 pyramidal cells are less critically involved in declarative human memory acquisition compared to dentate gyrus granule cells or CA4/CA3 pyramidal cells

Spectral fingerprints or spectral tilt? Evidence for distinct oscillatory signatures of memory formation

Decreases in low-frequency power (2–30 Hz) alongside high-frequency power increases (>40 Hz) have been demonstrated to predict successful memory formation. Parsimoniously, this change in the frequency spectrum can be explained by one factor, a change in the tilt of the power spectrum (from steep to flat) indicating engaged brain regions. A competing view is that the change in the power spectrum contains several distinct brain oscillatory fingerprints, each serving different computations. Here, we contrast these two theories in a parallel magnetoencephalography (MEG)–intracranial electroencephalography (iEEG) study in which healthy participants and epilepsy patients, respectively, studied either familiar verbal material or unfamiliar faces. We investigated whether modulations in specific frequency bands can be dissociated in time and space and by experimental manipulation. Both MEG and iEEG data show that decreases in alpha/beta power specifically predicted the encoding of words but not faces, whereas increases in gamma power and decreases in theta power predicted memory formation irrespective of material. Critically, these different oscillatory signatures of memory encoding were evident in different brain regions. Moreover, high-frequency gamma power increases occurred significantly earlier compared to low-frequency theta power decreases. These results show that simple “spectral tilt” cannot explain common oscillatory changes and demonstrate that brain oscillations in different frequency bands serve different functions for memory encoding

SUDEP kompakt – praxisrelevante Erkenntnisse und Empfehlungen zum plötzlichen, unerwarteten Tod bei Epilepsie

Sudden unexpected death in epilepsy (SUDEP) is the sudden and unexpected death of an epilepsy patient, which occurs under benign circumstances without evidence of typical causes of death. SUDEP concerns all epilepsy patients. The individual risk depends on the characteristics of the epilepsy and seizures as well as on living conditions. Focal to bilateral and generalized tonic-clonic seizures (TCS), nocturnal seizures and lack of nocturnal supervision increase the risk. Most SUDEP cases are due to a fatal cascade of apnea, hypoxemia and asystole in the aftermath of a TCS. Two thirds of SUDEP cases in unsupervised epilepsy patients with TCS could probably be prevented. Wearables can detect TCS and alert caregivers. SUDEP information is desired by most patients and relatives, has a favorable impact on treatment adherence and behavior and has no negative effects on mood and quality of life. Recommendations of the committee on patient safety of the German Society of Epileptology: the ultimate treatment goal is seizure freedom. If this cannot be achieved, control of TCS should be sought. All epilepsy patients and their relatives should be informed about SUDEP and risk factors. Patients and relatives should be informed about measures to counteract the elevated risk and imminent SUDEP. The counselling should be performed during a face-to-face discussion, at the time of first diagnosis or during follow-up visits. The counselling should be documented. Wearables for TCS detection can be recommended. If TCS persist, therapeutic efforts should be continued. The bereaved should be contacted after a SUDEP.„Sudden unexpected death in epilepsy“ (SUDEP) ist der plötzliche, unerwartete Tod eines Epilepsiepatienten, der unter „gutartigen“ Umständen und ohne typische Todesursachen auftritt. SUDEP betrifft alle Epilepsiepatienten. Das individuelle Risiko hängt vor allem von Merkmalen der Epilepsie und Anfälle sowie von Lebensumständen ab. Fokale zu bilateral bzw. generalisierte tonisch-klonische Anfälle (TKA), nächtliche Anfälle und fehlende nächtliche Überwachung erhöhen das Risiko. In den meisten SUDEP-Fällen kommt es nach TKA zu einer fatalen Kaskade mit Apnoe, Hypoxämie und Asystolie. Wahrscheinlich könnten zwei Drittel der SUDEP-Fälle bei nicht überwachten Epilepsiepatienten mit TKA verhindert werden. Mobile Geräte („wearables“) können nächtliche TKA erkennen und Hilfspersonen benachrichtigen. Eine SUDEP-Aufklärung wird von den meisten Patienten und Angehörigen gewünscht, beeinflusst Therapieadhärenz und Verhalten günstig und hat keine negativen Auswirkungen auf Stimmung oder Lebensqualität. Empfehlungen der Kommission „Patientensicherheit“ der Deutschen Gesellschaft für Epileptologie: Therapieziel ist Anfallsfreiheit. Wenn dies nicht möglich ist, soll versucht werden, zumindest TKA zu kontrollieren. Alle Epilepsiepatienten und ihre Angehörigen sollen über SUDEP und Risikofaktoren aufgeklärt werden. Patienten und Angehörige sollen über Maßnahmen informiert werden, die einem erhöhten Risiko bzw. einem drohenden SUDEP entgegenwirken. Die Aufklärung soll in einem persönlichen Gespräch erfolgen, bei Diagnosestellung oder später. Die Aufklärung sollte dokumentiert werden. Wearables zur Detektion von TKA können empfohlen werden. Bei persistierenden TKA sollen Therapieversuche zur Anfallskontrolle fortgeführt werden. Nach SUDEP sollten Hinterbliebene kontaktiert werden

Trends in the neurological emergency room, focusing on persons with seizures

Background and purpose Previous studies in neurological emergency rooms (nERs) have reported many non‐acute, self‐presenting patients, patients with delayed presentation of stroke, and frequent visits of persons with seizures (PWS). The aim of this study was to evaluate trends during the last decade, with special focus on PWS. Methods We retrospectively analyzed patients who presented to our specialized nER during the course of 5 months in 2017 and 2019, and included information on admission/referral, hospitalization, discharge diagnosis, and diagnostic tests/treatment in the nER. Results A total of 2791 patients (46.6% male, mean age 57 ± 21 years) were included. The most common diagnoses were cerebrovascular events (26.3%), headache (14.1%), and seizures (10.5%). Most patients presented with symptoms lasting &gt;48 h (41.3%). The PWS group included the largest proportion of patients presenting within 4.5 h of symptom onset (171/293, 58.4%), whereas only 37.1% of stroke patients presented within this time frame (273/735). Self‐presentation was the most common admission pathway (31.1%), followed by emergency service referral (30.4%, including the majority of PWS: 197/293, 67.2%). Despite known diagnosis of epilepsy in 49.2%, PWS more often underwent accessory diagnostic testing including cerebral imaging, compared to the overall cohort (accessory diagnostics 93.9% vs. 85.4%; cerebral imaging 70.1% vs. 64.1%). Electroencephalography in the nER was only performed in 20/111 patients (18.0%) with a first seizure. Nearly half of the patients (46.7%) were discharged home after nER work‐up, including most self‐presenters (632/869, 72.7%) and headache patients (377/393, 88.3%), as well as 37.2% (109/293) of PWS. Conclusion After 10 years, nER overuse remains a problem. Stroke patients still do not present early enough, whereas PWS, even those with known epilepsy, often seek acute and extensive assessment, indicating gaps in pre‐hospital management and possible over‐assessment. </sec

Localization of beta power decrease as measure for lateralization in pre-surgical language mapping with magnetoencephalography, compared with functional magnetic resonance imaging and validated by Wada test

Objective: Atypical patterns of language lateralization due to early reorganizational processes constitute a challenge in the pre-surgical evaluation of patients with pharmaco-resistant epilepsy. There is no consensus on an optimal analysis method used for the identification of language dominance in MEG. This study examines the concordance between MEG source localization of beta power desynchronization and fMRI with regard to lateralization and localization of expressive and receptive language areas using a visual verb generation task. Methods: Twenty-five patients with pharmaco-resistant epilepsy, including six patients with atypical language lateralization, and ten right-handed controls obtained MEG and fMRI language assessment. Fourteen patients additionally underwent the Wada test. We analyzed MEG beta power desynchronization in sensor (controls) and source space (patients and controls). Beta power decrease between 13 and 35 Hz was localized applying Dynamic Imaging of Coherent Sources Beamformer technique. Statistical inferences were grounded on cluster-based permutation testing for single subjects. Results: Event-related desynchronization of beta power in MEG was seen within the language-dominant frontal and temporal lobe and within the premotor cortex. Our analysis pipeline consistently yielded left language dominance with high laterality indices in controls. Language lateralization in MEG and Wada test agreed in all 14 patients for inferior frontal, temporal and parietal language areas (Cohen’s Kappa = 1, p < 0.001). fMRI agreed with Wada test in 12 out of 14 cases (85.7%) for Broca’s area (Cohen’s Kappa = 0.71, p = 0.024), while the agreement for temporal and temporo-parietal language areas were non-significant. Concordance between MEG and fMRI laterality indices was highest within the inferior frontal gyrus, with an agreement in 19/24 cases (79.2%), and non-significant for Wernicke’s area. Spatial agreement between fMRI and MEG varied considerably between subjects and brain regions with the lowest Euclidean distances within the inferior frontal region of interest. Conclusion: Localizing the desynchronization of MEG beta power using a verb generation task is a promising tool for the identification of language dominance in the pre-surgical evaluation of epilepsy patients. The overall agreement between MEG and fMRI was lower than expected and might be attributed to differences within the baseline condition. A larger sample size and an adjustment of the experimental designs are needed to draw further conclusions

Data-driven re-referencing of intracranial EEG based on independent component analysis (ICA)

Background: Intracranial recordings from patients implanted with depth electrodes are a valuable source of information in neuroscience. They allow for the unique opportunity to record brain activity with high spatial and temporal resolution. A common pre-processing choice in stereotactic EEG (S-EEG) is to re-reference the data with a bipolar montage. In this, each channel is subtracted from its neighbor, to reduce commonalities between channels and isolate activity that is spatially confined. New Method: We challenge the assumption that bipolar reference effectively performs this task. To extract local activity, the distribution of the signal source of interest, interfering distant signals, and noise need to be considered. Referencing schemes with fixed coefficients can decrease the signal to noise ratio (SNR) of the data, they can lead to mislocalization of activity and consequently to misinterpretation of results. We propose to use Independent Component Analysis (ICA), to derive filter coefficients that reflect the statistical dependencies of the data at hand. Results: We describe and demonstrate this on human S-EEG recordings. In a simulation with real data, we quantitatively show that ICA outperforms the bipolar referencing operation in sensitivity and importantly in specificity when revealing local time series from the superposition of neighboring channels. Comparison with Existing Method: We argue that ICA already performs the same task that bipolar referencing pursues, namely undoing the linear superposition of activity and will identify activity that is local. Conclusions: When investigating local sources in human S-EEG, ICA should be preferred over re-referencing the data with a bipolar montage