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Electrical source imaging is used in presurgical epilepsy evaluation and in cognitive neurosciences to localize neuronal sources of brain potentials recorded on EEG. This study evaluates the spatial accuracy of electrical source imaging for known sources, using electrical stimulation potentials recorded on simultaneous stereo-EEG and 37-electrode scalp EEG, and identifies factors determining the localization error. In 11 patients undergoing simultaneous stereo-EEG and 37-electrode scalp EEG recordings, sequential series of 99–110 biphasic pulses (2 ms pulse width) were applied by bipolar electrical stimulation on adjacent contacts of implanted stereo-EEG electrodes. The scalp EEG correlates of stimulation potentials were recorded with a sampling rate of 30 kHz. Electrical source imaging of averaged stimulation potentials was calculated utilizing a dipole source model of peak stimulation potentials based on individual four-compartment finite element method head models with various skull conductivities (range from 0.0413 to 0.001 S/m). Fitted dipoles with a goodness of fit of ≥80% were included in the analysis. The localization error was calculated using the Euclidean distance between the estimated dipoles and the centre point of adjacent stimulating contacts. A total of 3619 stimulation locations, respectively, dipole localizations, were included in the evaluation. Mean localization errors ranged from 10.3 to 26 mm, depending on source depth and selected skull conductivity. The mean localization error increased with an increase in source depth (r(3617) = [0.19], P = 0.000) and decreased with an increase in skull conductivity (r(3617) = [−0.26], P = 0.000). High skull conductivities (0.0413–0.0118 S/m) yielded significantly lower localization errors for all source depths. For superficial sources (40 mm, high skull conductivities of 0.0413 and 0.0206 S/m yielded significantly lower localization errors. In relation to stimulation locations, the majority of estimated dipoles moved outward-forward-downward to inward-forward-downward with a decrease in source depth and an increase in skull conductivity. Multivariate analysis revealed that an increase in source depth, number of skull holes and white matter volume, while a decrease in skull conductivity independently led to higher localization error. This evaluation of electrical source imaging accuracy using artificial patterns with a high signal-to-noise ratio supports its application in presurgical epilepsy evaluation and cognitive neurosciences. In our artificial potential model, optimizing the selected skull conductivity minimized the localization error. Future studies should examine if this accounts for true neural signals.

Zusammenfassung Hintergrund Diagnose und Behandlung von Patienten mit Epilepsie oder anderen anfallsartig auftretenden Symptomen erfordert in manchen Situationen Spezialistenwissen. Um dieses auch Abteilungen ohne eigene spezialisierte Epileptologen zur Verfügung stellen zu können, wurde im Rahmen des Modellprojektes Tele-Epileptologie Ruhr (TE Ruhr) eine telemedizinische Infrastruktur zum patientenbezogenen Austausch zwischen allgemeinneurologischen Akutkliniken bzw. ausländischen Epilepsiezentren und der Ruhr-Epileptologie, Bochum, geschaffen. Methoden Die TE Ruhr ist eine multizentrische, prospektive Pilotstudie. Die telemedizinische Kommunikation inklusive Austausch von Untersuchungsdaten läuft über ein Webtool (rein webbasierte Anwendung). Es wurden Kliniken angeschlossen, mit denen bereits im Vorfeld eine Kooperation bestand. Patienten wurden nach Maßgabe der behandelnden Ärzte nach schriftlicher Einwilligung eingeschlossen. Die Zwischenevaluation wurde mit verantwortlichen Ärzten in den Kliniken per Fragebogen im Rahmen eines Telefoninterviews erstellt. Ergebnisse Zum Zeitpunkt der Befragung waren 8 regionale und 4 internationale Partnerkliniken angeschlossen. Die befragten Ärzte bewerten das Gesamtprojekt inklusive der technischen Realisierung mit einer Durchschnittsnote von 2,1 (1–4 auf einer Schulnotenskala von 1–6). Alle Befragten sehen einen Nutzen der TE Ruhr eher für Einzelfälle als für Routinevorstellungen. Wichtig für die Teilnehmer ist eine einfache und schnelle Bedienung der Konsilplattform. Diskussion Die Zwischenanalyse des Modellprojekts TE Ruhr hat gezeigt, dass die technische Etablierung einer teleepileptologischen Konsilplattform erfolgreich möglich ist. Die Ergebnisse machen über das konkrete Projekt hinaus deutlich, wo technische und organisatorische Herausforderungen telemedizinischer Anwendungen liegen und wie diesen begegnet werden kann.

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. 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.

In der Differenzialdiagnostik anfallsartig auftretender Ereignisse konnen Handyvideos ein wichtiger diagnostischer Baustein sein. Ziel dieser Ubersichtsarbeit ist es, anhand einer Literaturrecherche und Expertenmeinungen darzulegen, welchen Nutzen und welche Herausforderungen Handyvideos in der Diagnostik anfallsartig auftretender Ereignisse haben. Herausforderungen ergeben sich in der Sicherstellung einer ausreichenden Qualitat zur Erfassung und Darstellung der Anfalle und in juristischen Aspekten der Erstellung, Speicherung und Ubermittlung des Videos. Eine Verbesserung der diagnostischen Aussagekraft von Videos durch optimierte Anfallsaufzeichnung kann am ehesten durch Aufklarung und Anleitung von Angehorigen erfolgen. Fur die sichere Datenubermittlung eignen sich gesicherte Webplattformen, die sowohl das direkte Hochladen des Videos vom Handy des Patienten als auch Arzten und Kliniken den Zugriff hierauf erlauben. Eine in Schottland entwickelte DSGVO-konforme Videoplattform konnte zeigen, dass ein routinemasiger Einsatz von Handvideos in der Differenzialdiagnostik von anfallsartig auftretenden Ereignissen fur Arzte sehr hilfreich ist und durch Vermeidung weiterer diagnostischer Prozeduren Kosten reduziert.

OBJECTIVE: Focal cortical dysplasias (FCDs) are a common cause of drug-resistant focal epilepsy but frequently remain undetected by conventional magnetic resonance imaging (MRI) assessment. The visual detection can be facilitated by morphometric analysis of T1-weighted images, for example, using the Morphometric Analysis Program (v2018; MAP18), which was introduced in 2005, independently validated for its clinical benefits, and successfully integrated in standard presurgical workflows of numerous epilepsy centers worldwide. Here we aimed to develop an artificial neural network (ANN) classifier for robust automated detection of FCDs based on these morphometric maps and probe its generalization performance in a large, independent data set. METHODS: In this retrospective study, we created a feed-forward ANN for FCD detection based on the morphometric output maps of MAP18. The ANN was trained and cross-validated on 113 patients (62 female, mean age ± SD =29.5 ± 13.6 years) with manually segmented FCDs and 362 healthy controls (161 female, mean age ± SD =30.2 ± 9.6 years) acquired on 13 different scanners. In addition, we validated the performance of the trained ANN on an independent, unseen data set of 60 FCD patients (28 female, mean age ± SD =30 ± 15.26 years) and 70 healthy controls (42 females, mean age ± SD = 40.0 ± 12.54 years). RESULTS: In the cross-validation, the ANN achieved a sensitivity of 87.4% at a specificity of 85.4% on the training data set. On the independent validation data set, our method still reached a sensitivity of 81.0% at a comparably high specificity of 84.3%. SIGNIFICANCE: Our method shows a robust automated detection of FCDs and performance generalizability, largely independent of scanning site or MR-sequence parameters. Taken together with the minimal input requirements of a standard T1 image, our approach constitutes a clinically viable and useful tool in the presurgical diagnostic routine for drug-resistant focal epilepsy. ispartof: EPILEPSIA vol:62 issue:4 pages:1005-1021 ispartof: location:United States status: published

BACKGROUND Anxiety disorders remain undiagnosed in routine clinical practice in up to two thirds of affected patients with epilepsy despite their significant impact on medical and psychosocial outcomes. The study objective was to translate and validate the German 8-item "brief Epilepsy Anxiety Survey Instrument" (brEASI) to facilitate effective screening for the presence of anxiety disorders in German-speaking patients. METHODS After expert translation into German, the brEASI was completed by consecutive adult inpatients with epilepsy hospitalized for seizures at an academic reference epilepsy center. Patients also completed the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), the Generalized Anxiety Disorder scale (GAD-7) for external validity, and underwent a standardized interview (Mini-DIPS-OA) as a gold standard to determine the presence of an ICD-10 anxiety disorder (generalized anxiety disorder (GAD), panic disorder, agoraphobia, and social phobia). Receiver operating characteristics (ROC) were calculated to determine the diagnostic accuracy of the brEASI, including the associated area under the curve (AUC) statistics to determine the potential of the brEASI to identify ICD-10 anxiety disorders diagnosed by interview. For comparative purposes, these analyses were also conducted for the GAD-7. RESULTS Of 80 recruited adult inpatients with epilepsy, 18 (23 %) were found to have a current anxiety disorder through standardized interview. In this study, both brEASI and GAD-7 showed a better diagnostic performance at a cutoff of >5 than at the previously reported cutoff values of >6 and >9, respectively. The AUC of the German brEASI was outstanding (AUC = 0.90, 95 % confidence interval (CI) = 0.82-0.96) for detecting all anxiety disorders and excellent for detecting non-GAD disorders (AUC = 0.85, CI = 0.76-0.92) at a cutoff of >5. At this optimal cutoff of >5 the brEASI demonstrated better sensitivity and specificity (89 % and 84 %) for identifying anxiety disorders than the GAD-7 (83 % and 74 %). The final German version of the brEASI is free to download at https://www.v-neuro.de/veroeffentlichungen/. CONCLUSION The German version of the brEASI represents a valid and reliable epilepsy-specific anxiety screening instrument. A positive screening result should be followed by further diagnostic procedures. Appropriate therapeutic steps should be initiated if the presence of an anxiety disorder or other psychiatric disorders is confirmed.

Brain : a journal of neurology (2022). doi:10.1093/brain/awac119, Published by Oxford Univ. Press, Oxford

BACKGROUND: Dissociative seizures (DS) are a common subtype of functional neurological disorder (FND) with an incompletely understood pathophysiology. Here, gray matter variations and their relationship to clinical features were investigated.METHODS: Forty-eight patients with DS without neurological comorbidities and 43 matched clinical control patients with syncope with structural brain MRIs were identified retrospectively. FreeSurfer-based cortical thickness and FSL FIRST-based subcortical volumes were used for quantitative analyses, and all findings were age and sex adjusted, and corrected for multiple comparisons.RESULTS: Groups were not statistically different in cortical thickness or subcortical volumes. For patients with DS, illness duration was inversely correlated with cortical thickness of left-sided anterior and posterior cortical midline structures (perigenual/dorsal anterior cingulate cortex, superior parietal cortex, precuneus), and clusters at the left temporoparietal junction (supramarginal gyrus, postcentral gyrus, superior temporal gyrus), left postcentral gyrus, and right pericalcarine cortex. Dissociative seizure duration was inversely correlated with cortical thickness in the left perigenual anterior cingulate cortex, superior/middle frontal gyri, precentral gyrus and lateral occipital cortex, along with the right isthmus-cingulate and posterior-cingulate, middle temporal gyrus, and precuneus. Seizure frequency did not show any significant correlations.CONCLUSIONS: In patients with DS, illness duration inversely correlated with cortical thickness of left-sided default mode network cortical hubs, while seizure duration correlated with left frontopolar and right posteromedial areas, among others. Etiological factors contributing to neuroanatomical variations in areas related to self-referential processing in patients with DS require more research inquiry.

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. 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.

Background To prospectively analyze factors associated with detecting epileptogenic lesions on MRI within the work-sharing process of neurologists, epileptologists, radiologists and neuroradiologists. Methods We assembled four sets of six MRI scans, each set representing five typical epileptogenic lesions (hippocampal sclerosis or limbic encephalitis; focal cortical dysplasias; periventricular nodular or other heterotopias; long-term epilepsy associated tumors; gliotic scar, hemosiderin or cavernoma), and non - lesional epilepsy. At professional conferences, we invited neurologists, epileptologists, radiologists, and neuroradiologists to read two out of four MRI sets, one of which was presented with a clinical focus hypothesis. Participants were randomly assigned to MRI sets. Effects of examiners’ specialty, duration of training and professional experience on detection rate of epileptogenic lesions were investigated. Results Fourty-eight neurologists, 22 epileptologists, 20 radiologists and 21 neuroradiologists read 1323 MRI scans. Overall, 613 of 1101 (55.7%) epileptogenic lesions were detected. Long-term epilepsy associated tumors (182/221, 82.4%) were found more frequently than gliotic scar, hemosiderin or cavernoma (157/220, 71.4%), hippocampal sclerosis or limbic encephalitis (141/220, 64.1%), nodular heterotopia (68/220, 30.9%) and focal cortical dysplasias (65/220, 29.5%, p p = 0.037). Neuroradiologists and epileptologists were more likely than radiologists and neurologists to be amongst the most successful readers. In multivariable analysis, type of epileptogenic lesion, specialty of MRI reader, and provision of focus hypothesis predicted correct identification of epileptogenic lesions. Conclusions Epileptogenic lesions are often not recognized on MRI even by expert readers. Their detection can be improved by providing a focus hypothesis. These results stress the need for training in the MRI characteristics of epilepsy - specific pathology, and, most importantly, interdisciplinary communication between neurologists/epileptologists and (neuro)radiologists to improve detection of epileptogenic lesions.

Background and purpose Consensus criteria for autoimmune limbic encephalitis (ALE) allow for a diagnosis even without neuronal antibodies (Abs), but it remains unclear which clinical features should prompt neuronal Ab screening in temporal lobe epilepsy patients. The aim of the study was to investigate whether patients with temporal lobe seizures associated with additional symptoms or signs of limbic involvement may harbor neuronal Abs, and which clinical features should prompt neuronal Ab screening in these patients. Methods We identified 47 patients from a tertiary epilepsy center with mediotemporal lobe seizures and additional features suggestive of limbic involvement, including either memory deficits, psychiatric symptoms, mediotemporal magnetic resonance imaging (MRI) hyperintensities or inflammatory cerebrospinal fluid (CSF). Neuronal Ab testing was carried out at two independent reference laboratories (Bielefeld-Bethel, Germany, and Barcelona, Spain). All brain MRI scans were assessed by two reviewers independently. Results Temporal lobe seizures were accompanied by memory deficits in 35/46 (76%), psychiatric symptoms in 27/42 (64%), and both in 19/42 patients (45%). Limbic T2/fluid-attenuated inversion recovery signal hyperintensities were found in 26/46 patients (57%; unilateral: n = 22, bilateral: n = 4). Standard CSF studies were abnormal in 2/37 patients (5%). Neuronal Abs were confirmed in serum and/or CSF in 8/47 patients (17%) and were directed against neuronal cell-surface targets (leucine-rich glioma inactivated protein 1: n = 1, contactin-associated protein-2: n = 1, undetermined target: n = 3) or glutamic acid decarboxylase in its 65-kD isoform (n = 3, all with high titers). Compared to Ab-negative patients, those who harbored neuronal Abs were more likely to have uni- or bilateral mediotemporal MRI changes (8/8, 100% vs. 18/38, 47%; p = 0.01, Fisher's exact test). Conclusions In patients with temporal lobe seizures and additional limbic signs, 17% had neuronal Abs affirming ALE diagnosis. Mediotemporal MRI changes were found in all Ab-positive cases and had a positive likelihood ratio of 2.11 (95% confidence interval 1.51-2.95).

Objective. Recent advancements in electrode designs and micro-fabrication technology has allowed existence of microelectrode arrays with hundreds of channels for single-cell recordings. In such electrophysiological recordings, each implanted micro-electrode can record the activities of more than one neuron in its vicinity. Recording the activities of multiple neurons may also be referred to as multiple unit activity. However, for any further analysis, the main goal is to isolate the activity of each recorded neuron and thus called single-unit activity. This process may also be referred to as spike sorting or spike classification. Recent approaches to extract SUA are time consuming, mainly due to the requirement of human intervention at various stages of spike sorting pipeline. Lack of standardization is another drawback of the current available approaches. Therefore, in this study we proposed a standard spike sorter: SpikeDeep-Classifier, a fully automatic spike sorting algorithm. Approach. We proposed a novel spike sorting pipeline, based on a set of supervised and unsupervised learning algorithms. We used supervised, deep learning-based algorithms for extracting meaningful channels and removing background activities (noise) from the extracted channels. We also showed that the process of clustering becomes straight-forward, once the noise/artifact is completely removed from the data. Therefore, in the next stage, we applied a simple clustering algorithm (K-mean) with predefined maximum number of clusters. Lastly, we used a similarity-based criterion to keep distinct clusters and merge similar-looking clusters. Main results. We evaluated our algorithm on a dataset collected from two different species (humans and non-human primates (NHPs)) without any retraining. We also validated our algorithm on two publicly available labeled datasets., 33 Pages, 14 Figures, 10 Tables

\(\bf Objective\) To determine the utility of suggestive seizure induction for inpatient work-up of suspected psychogenic nonepileptic seizures (PNES). \(\bf Methods\) Prospective study of epilepsy center inpatient admissions with suspected PNES. Patients were randomized to undergo suggestive induction first (group A) and then, if necessary, long-term video-electroencephalography (EEG) monitoring, or vice versa (group B). Diagnostic pathways were compared. Potential clinical predictors for diagnostic success were evaluated. \(\bf Results\) Length of in-hospital stay did not significantly differ between groups. Suspicion of PNES was confirmed in 43 of 77 (56%) patients, evenly distributed between group A (22 of 39) and group B (21 of 38). In nine patients, recorded habitual seizures were epileptic and in 25 cases, no diagnostic event could be recorded. Diagnosis of PNES was ascertained primarily by recording a typical seizure through suggestive induction in 24 patients and through long-term monitoring in 19 patients. In group A (induction first), monitoring was not deemed necessary in 21% of cases. In group B (monitoring first), 13% would have remained inconclusive without suggestive induction. Patients who reported triggers to their habitual seizures were not more likely to have spontaneous or provoked PNES during monitoring or suggestive inducion, respectively. Patients with subjective seizure prodromes (auras) were significantly more likely to have a PNES during suggestive induction than those without (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.1-10.4). There was no significant difference in seizure frequency between patients with spontaneous PNES during long-term monitoring and those with nondiagnostic monitoring sessions. \(\bf Significance\) Our results support the notion that suggestive seizure induction can reduce the number of inconclusive inpatient workups, and can obviate resource-intensive long-term monitoring in one fifth of cases. Patients who are aware of prodromes might have a higher chance of having seizures induced through suggestion.

Die Magnetresonanztomographie (MRT) ist die Methode der Wahl, um bei Patienten mit fokalen Epilepsien deren Ursache und gleichzeitig kausale Therapienotwendigkeiten bzw. -optionen zu erkennen. Die Durchfuhrung der MRT im klinischen Alltag ist aber noch verbesserungswurdig, sowohl in Bezug auf die konsequente Indikationsstellung, als auch in Bezug auf die Qualitat der MRT-Protokolle und der Auswertung. Vorstellung von Indikationen fur die MRT bei Epilepsiepatienten und Erlauterung der epilepsiespezifischen MRT-Durchfuhrung, sowohl technisch, als auch organisatorisch. Literaturbasierte Empfehlung. Um das gesamte Spektrum epileptogener Lasionen mit akuter Therapienotwendigkeit oder auch im Falle von einer pharmakoresistenten Epilepsie epilepsiechirurgischer Therapieoption erkennen zu konnen, sollte ein epilepsiespezifisches MRT-Protokoll angewendet werden. Wichtig fur die Identifikation subtiler Lasionen sind das Vorhandensein einer klinischen Fokushypothese und die Expertise des Radiologen. Um redundante Untersuchungen zu vermeiden, sollte bereits die erste MRT nach Epilepsieprotokoll erfolgen – mit der Moglichkeit der qualifizierten Nachbefundung in einem Epilepsiezentrum. Um das Vorliegen kausal therapienotwendiger oder therapierbarer Ursachen fokaler Epilepsien zu erkennen, sollten interdisziplinare Anstrengungen zur grundsatzlichen Anwendung epilepsiespezifischer MRT-Protokolle bei Patienten mit epileptischen Anfallen unternommen werden.

ZusammenfassungEpilepsien zählen zu den häufigsten neurologischen Erkrankungen mit etwa 600 000 Betroffenen in Deutschland. Symptome epileptischer Anfälle, die Vielzahl möglicher Epilepsieursachen und die unterschiedlichen Krankheitsverläufe erschweren sowohl die korrekte Diagnosestellung als auch die Auswahl einer geeigneten Therapie (Antikonvulsiva, epilepsiechirurgische Eingriffe, Neurostimulationsverfahren, ketogene Ernährungstherapien, Verhaltensstrategien u. a.). Zudem haben krankheitsspezifische Risiken sowie häufig auftretende Komorbiditäten nicht selten gravierende psychosoziale Konsequenzen. Daher wird bei der Versorgung von Menschen mit Epilepsie neben der vollständigen Anfallskontrolle ohne Nebenwirkungen und der Lebensqualität auch die Kontrolle bzw. Linderung typischer Begleiterkrankungen und Risiken angestrebt. Um diese Behandlungsziele zu erreichen, sind spezifische Fachkenntnisse und Untersuchungsmöglichkeiten erforderlich, die von spezialisierten Zentren vorgehalten werden. Epilepsiezentren sind als überregionale Kompetenzzentren definiert, die über spezielle Expertise und eine besondere Ausstattung zur ambulanten und stationären Versorgung von Patienten mit Epilepsien und verwandten Erkrankungen verfügen. Zu ihren Aufgaben zählen u. a. die umfassende Diagnostik, Differenzialdiagnostik und Therapie von Epilepsiepatienten sowie die multiprofessionelle und interdisziplinäre Beratung von Angehörigen und Eltern. Dieser Artikel fasst die diagnostischen und therapeutischen Herausforderungen bei der Versorgung von Menschen mit Epilepsien zusammen, beschreibt die personellen, apparativen und institutionellen Voraussetzungen von Epilepsiezentren und gibt eine Übersicht über die Vergütung epileptologischer Spezialleistungen nach G-DRG. Darüber hinaus werden Merkmale einzelner Epilepsiezentren in Deutschland skizziert sowie Perspektiven und Möglichkeiten zur Verbesserung der Versorgung von Epilepsiepatienten diskutiert.

Psychogenic nonepileptic seizures (PNES) can remain undiagnosed for many years, leading to unnecessary medication and delayed treatment. A recent report by the International League Against Epilepsy Nonepileptic Seizures Task Force recommends a staged approach to the diagnosis of PNES (LaFrance, et al., 2013). We aimed to investigate its practical utility, and to apply the proposed classification to evaluate the role of long-term video-EEG monitoring (VEEG) and suggestive seizure induction (SSI) in PNES workup. Using electronic medical records, 122 inpatients (mean age 36.0 ± 12.9 years; 68% women) who received the diagnosis of PNES at our epilepsy center during a 4.3-year time period were included. There was an 82.8% agreement between diagnostic certainty documented at discharge and that assigned retroactively using the Task Force recommendations. In a minority of cases, having used the Task Force criteria could have encouraged the clinicians to give more certain diagnoses, exemplifying the Task Force report's utility. Both VEEG and SSI were effective at supporting high level diagnostic certainty. Interestingly, about one in four patients (26.2%) had a non-diagnostic (“negative”) VEEG but a positive SSI. On average, this subgroup did not have significantly shorter mean VEEG recording times than VEEG-positive patients. However, VEEG-negative/SSI-positive patients had a significantly lower habitual seizure frequency than their counterparts. This finding emphasizes the utility of SSI in ascertaining the diagnosis of PNES in patients who do not have a spontaneous habitual event during VEEG due to, for example, low seizure frequency.

Wie klein durfen epilepsiechirurgische Eingriffe sein, ohne das Ziel der Masnahme, die postoperative Anfallsfreiheit, zu gefahrden? Reicht es, bei Patienten mit neokortikalen Lasionen die kernspintomographisch erkennbare Pathologie zu entfernen bzw. zu zerstoren? Oder ist eine Mitresektion von Arealen mit intra- oder extraoperativem Nachweis epilepsietypischer Potenziale erforderlich? Streng lasionszentrierte Operationsverfahren wie die stereotaktische Radiofrequenz-Thermokoagulation (L-RFTC) konnen eine Antwort auf diese Frage liefern. In dieser Arbeit werden Erfahrungen geschildert, die mit L‑RFTC bei Patienten mit fokalen kortikalen Dysplasien Typ IIB (FCD IIB) gemacht wurden. Zusammengefasst deutet die Evidenzlage bei bislang nur wenigen operierten und publizierten Fallen einer einzigen Arbeitsgruppe an, dass die komplette Destruktion einer FCD IIB zumindest eine Transition von einer pharmakoresistenten hin zu einer medikamentos kontrollierbaren Epilepsie erlaubt. Ob durch die Destruktion der Lasion auch Heilung von Epilepsie (persistierende Anfallsfreiheit ohne Fortfuhrung der Antikonvulsiva) moglich ist, kann aktuell noch nicht beurteilt werden.

Antibodies against glutamic acid decarboxylase (GAD) are a hallmark of type 1 diabetes and its late-onset variant, latent autoimmune diabetes of the adult (LADA).1 While cerebrovascular disease and dementia are common causes of cognitive dysfunction and neurological deficits in diabetic patients,2,3 rare autoimmune disorders of the central nervous system such as stiff-person syndrom or limbic encephalits can also occur on the basis of shared GAD autoimmunity.4,5

Summarization: In recent years, several approaches have been introduced for estimating the spike onset zone within the irritative zone in epilepsy diagnosis for presurgical planning. One important direction utilizes source analysis from combined electroencephalography (EEG) and magnetoencephalography (MEG), EMEG, leveraging the benefits from the complementary properties of the two modalities. For EMEG source reconstruction, an average across the annotated epileptic spikes is often used to improve the signal-to-noise-ratio (SNR). In this contribution, we propose a two-phase clustering of interictal spikes with unsupervised learning methods, namely Self Organizing Maps (SOM) and K-means. In addition, we investigate the accuracy of combined EMEG source analysis on the sorted activity, using an individualized (with regard to both geometry and conductivity) six-compartment finite element head model with calibrated skull conductivity and white matter conductivity anisotropy. The results indicate that SOM eliminates the random variations of K-means and stabilizes the clustering efficiency. In terms of source reconstruction accuracy, this study demonstrates that the combined use of modalities reveals activity around two focal cortical dysplasias (FCDs), of one epilepsy patient, one in the right frontal area and one smaller in the left premotor cortex. It is worth mentioning that only EMEG could localize the left premotor FCD, which was then also found in surgery to be the responsible for triggering the epilepsy. Παρουσιάστηκε στο: 19th International Conference on Bioinformatics and Bioengineering

Objective. In electrophysiology, microelectrodes are the primary source for recording neural data (single unit activity). These microelectrodes can be implanted individually or in the form of arrays containing dozens to hundreds of channels. Recordings of some channels contain neural activity, which are often contaminated with noise. Another fraction of channels does not record any neural data, but only noise. By noise, we mean physiological activities unrelated to spiking, including technical artifacts and neural activities of neurons that are too far away from the electrode to be usefully processed. For further analysis, an automatic identification and continuous tracking of channels containing neural data is of great significance for many applications, e.g. automated selection of neural channels during online and offline spike sorting. Automated spike detection and sorting is also critical for online decoding in brain–computer interface (BCI) applications, in which only simple threshold crossing events are often considered for feature extraction. To our knowledge, there is no method that can universally and automatically identify channels containing neural data. In this study, we aim to identify and track channels containing neural data from implanted electrodes, automatically and more importantly universally. By universally, we mean across different recording technologies, different subjects and different brain areas. Approach. We propose a novel algorithm based on a new way of feature vector extraction and a deep learning method, which we call SpikeDeeptector. SpikeDeeptector considers a batch of waveforms to construct a single feature vector and enables contextual learning. The feature vectors are then fed to a deep learning method, which learns contextualized, temporal and spatial patterns, and classifies them as channels containing neural spike data or only noise. Main results. We trained the model of SpikeDeeptector on data recorded from a single tetraplegic patient with two Utah arrays implanted in different areas of the brain. The trained model was then evaluated on data collected from six epileptic patients implanted with depth electrodes, unseen data from the tetraplegic patient and data from another tetraplegic patient implanted with two Utah arrays. The cumulative evaluation accuracy was 97.20% on 1.56 million hand labeled test inputs. Significance. The results demonstrate that SpikeDeeptector generalizes not only to the new data, but also to different brain areas, subjects, and electrode types not used for training. Clinical trial registration number. The clinical trial registration number for patients implanted with the Utah array is NCT 01849822. For the epilepsy patients, approval from the local ethics committee at the Ruhr-University Bochum, Germany, was obtained prior to implantation.

Increasing evidence from neuroimaging studies points towards a hippocampal role in resolving approach-avoidance goal conflicts. Furthermore, previous neuroimaging findings suggest that the hippocampus (HC) contributes to successful conflict resolution as it is measured, for example, in a Stroop paradigm. However, it is still an open question whether the hippocampus is indeed causally relevant for resolving cognitive conflicts. Here, we investigated whether conflict resolution performance is affected by hippocampal pathology. N = 30 patients with mesial temporal lobe epilepsy (MTLE), almost exclusively showing MRI signs of hippocampal sclerosis, and an equal number of age-matched healthy controls performed an auditory Stroop paradigm. Participants listened to the words 'high' and 'low', spoken in either a high or a low pitch. Subjects' response time and accuracy to the phonetic information in the presence of incongruent (conflict trials) or congruent (non-conflict trials) semantic information were assessed. In addition, patients' regional grey matter (GM) brain volumes were analysed. We observed an increased effect of conflict on accuracy in patients with MTLE compared to healthy controls. This effect was negatively correlated with right HC volume. The results suggest that the impairment in the resolution of a response conflict is related to hippocampal structural integrity and thus add further support to the notion that the HC is not only involved but even causally relevant for successful cognitive conflict processing.

Dissociative seizures are a common and often elusive differential diagnosis in epilepsy centers. Considering their high prevalence, long diagnostic delays, and disappointing rates of treatment response, scientific research dedicated to dissociative seizures is surprisingly scarce. In order to chart the scientific landscape of dissociative seizures and to visualize thematic clusters and trends in research, a comprehensive bibliometric analysis was performed. The Web of Science database was examined to identify relevant English language documents from the last half-century. A total of 1751 documents with titles referring to dissociative seizures were identified. Automated textual analysis of all titles and abstracts revealed that research clusters around three major topics: differential diagnosis in epilepsy centers, management and treatment, and psychopathology. Time analysis of term networks revealed that the focus of clinical research has moved from diagnostic procedures to treatment approaches. Furthermore, interest within etiological research is shifting from an emphasis on early life trauma and personality traits to the role of anxiety and emotion regulation. With respect to individual contributing authors, a relatively small network of prolific scientists with a remarkable degree of collaboration emerges. By mapping relevant publications, it becomes evident that dissociative seizures still represent a subject mostly within the realm of neurology and epileptology, with a tendency to settle in the latter domain. This analysis sheds light on an important niche subject and highlights trends in research focus and output.

Small bottom-of-sulcus focal cortical dysplasias (BOS-FCD) type IIb are intrinsically epileptogenic lesions often responsible for pharmacoresistant epilepsy. They are increasingly well demarcated in vivo from surrounding cortex and white matter by 3 T magnetic resonance imaging (MRI). These facts and frequent seizure freedom after just narrow resections allow questioning the classical concept of epilepsy surgery in which the epileptogenic lesion is generally considered only one part of the epileptogenic zone and the resection volume categorically has to exceed lesion limits. This study approaches this question by analyzing procedures of strongly lesion focused stereotactic radiofrequency thermocoagulation (L-RFTC) applied to BOS-FCD IIb. Seven patients with BOS-FCD IIb were treated, three had invasive EEG recordings prior to L-RFTC, all had intraoperative stereotactic EEG-recordings. Perilesional epileptic discharges (PLD) were documented in all patients. Coagulation was planned based on MRI, the maximum extension beyond lesion limits due to PLD was 4.8 mm. Although in all patients other areas of PLD remained uncoagulated, seizure freedom was achieved in four of five patients with complete lesion coagulation. In summary, due to the minimal extensions of lesion coagulations, current experience with L-RFTC of BOS-FCD IIb is not yet sufficient to rebut the significance of PLD. It encourages, however, further research on even stronger MRI guidance and possibly even ignorance of PLD in BOS-FCD IIb. It appears possible that in some BOS-FCD IIB the complete epileptogenic zone (according to Luders) might lie inside the MRI visible lesion. This would influence the understanding of the concept of cortical zones.

Purpose Survivors of viral encephalitis can develop refractory epilepsy and hippocampal sclerosis. Both the initial infectious insult and the secondary effects of recurrent seizures have been implicated in chronic disease progression. Recently, post-infectious autoimmunity, involved in acute relapses, has also been proposed as a pathomechanism for chronic disease progression. Our case series suggests a potential role of antibodies against the N-methyl-d-aspartate receptor (NMDAR) in chronic inflammatory disease beyond acute manifestations. Methods Retrospective chart review of four patients with epilepsy, hippocampal sclerosis following viral encephalitis and NMDAR-antibodies in CSF. Results The four patients were female, developed hippocampal sclerosis (in 3/4 in a step-wise progression) after Herpes simplex or Varicella zoster virus encephalitis and harboured immunoglobulin G antibodies against the NMDAR in their CSF. Two patients were treated with short-term immunosuppression but did not benefit. Conclusion This case series presents the first tentative evidence in support of chronic autoimmune inflammation driving disease progression after viral encephalitis beyond the known acute immune-mediated relapses. The anecdotal nature of the data does not, however, permit conclusive judgement on causality. Should our findings be replicated in larger cohorts, the treatment of post-infectious epilepsy could potentially be expanded to include immunosuppressive strategies in antibody-positive cases.

Spike-based magnetoencephalography (MEG) source localization is an established method in the presurgical evaluation of epilepsy patients. Focal cortical dysplasias (FCDs) are associated with focal epileptic discharges of variable morphologies in the beta frequency band in addition to single epileptic spikes. Therefore, we investigated the potential diagnostic value of MEG-based localization of spike-independent beta band (12-30Hz) activity generated by epileptogenic lesions.Five patients with FCD IIB underwent MEG. In one patient, invasive EEG (iEEG) was recorded simultaneously with MEG. In two patients, iEEG succeeded MEG, and two patients had MEG only. MEG and iEEG were evaluated for epileptic spikes. Two minutes of iEEG data and MEG epochs with no spikes as well as MEG epochs with epileptic spikes were analyzed in the frequency domain. MEG oscillatory beta band activity was localized using Dynamic Imaging of Coherent Sources.Intralesional beta band activity was coherent between simultaneous MEG and iEEG recordings. Continuous 14Hz beta band power correlated with the rate of interictal epileptic discharges detected in iEEG. In cases where visual MEG evaluation revealed epileptic spikes, the sources of beta band activity localized within2cm of the epileptogenic lesion as shown on magnetic resonance imaging. This result held even when visually marked epileptic spikes were deselected. When epileptic spikes were detectable in iEEG but not MEG, MEG beta band activity source localization failed.Source localization of beta band activity has the potential to contribute to the identification of epileptic foci in addition to source localization of visually marked epileptic spikes. Thus, this technique may assist in the localization of epileptic foci in patients with suspected FCD.

Purpose Over the last few decades, preferred epilepsy surgical approaches have developed from standard lobectomies to individually tailored resections. Yet, it remains uncertain how small surgical interventions can be without compromising the success of the surgery. Particularly in patients with epileptogenic lesions identified by magnetic resonance imaging (MRI), it is unresolved whether resection or destruction of the lesion suffices to eliminate the epileptogenic zone. We present a minimally invasive surgical approach that may provide insight into this issue. Methods Two patients with pharmacoresistant epilepsy due to focal cortical dysplasia type IIB demonstrated by 3Tesla MRI were treated with lesion-focused stereotactic radio-frequency thermo-coagulation. In both patients, pathognomonic epileptic discharges were recorded from the lesion via a stimulation device prior to coagulation. In one patient, the suspected proximity of the lesion to the pyramidal tract was verified by eliciting motor evoked potentials from the depths of the lesion. Results Following complete and near complete lesion destruction, seizures (several per day or per week, respectively) ceased in patients A and B, with no seizures for 12 months and 5 months, respectively, at the time of this publication. Neither patient acquired persistent postoperative neurological deficits. Conclusion The fact that seizure activity stopped after destruction of small bottom-of-sulcus dysplasias implies that in these cases, the epileptogenic zone and the epileptogenic lesion may overlap. If future studies can replicate this finding, focused lesion destruction could be a further development of individually tailored epilepsy surgery. The technique described here is especially suited for high-precision surgery close to eloquent brain structures.

Purpose Magnetic resonance imaging (MRI) is a key technology in the presurgical evaluation of patients with epilepsy. Already at early outpatient stages it can contribute to the identification of patients who are, in the case of pharmacoresistance, good candidates for epilepsy surgery. Yet, "standard head" MRI examinations often fail to displaying therapeutically relevant epileptogenic lesions. The purpose of this study is to identify an epilepsy-specific MRI protocol, which is likewise sensitive for even small epileptogenic lesions and economical enough to be applied outside specialized epilepsy centers. Methods Based on a large European presurgical epilepsy program comprising 2,740 patients we identified the spectrum of common epileptogenic lesions and determine the set of MRI sequences that are required for their reliable detection. Relying on a series of small, therapeutically particularly relevant lesions we determined the required slices thickness, slice angulations, and orientations for an epilepsy-specific MRI protocol. Key findings Indispensable for early outpatient epilepsy specific MRI are fluid attenuated inversion recovery (FLAIR), T(2) -weighted, T(1) -weighted, and hemosiderin/calcification-sensitive sequences. Slice thickness for T(2) and FLAIR must not exceed 3 mm. The T(1) image should be acquired in three-dimensional technique at 1 mm isotropic voxels size. For T(2) and FLAIR, at least two slice orientations each must be demanded in hippocampal angulation. We suggest no adaption to a clinical focus hypothesis. The resulting "essential 6" sequence protocol allows the detection of virtually all common epileptogenic lesion entities. Significance The creation of a broadly accepted and abundantly applied MRI protocol for epilepsy outpatients can contribute to improved and earlier identification of potential candidates for epilepsy surgery. Our systematic analysis of MRI requirements for the detection of epileptogenic lesions can serve as basis for protocol negotiations between epileptologists, radiologists, and health care funders.

Despite general agreement on shared syntactic resources in music and language, the neuroanatomical underpinnings of this overlap remain largely unexplored. While previous studies mainly considered frontal areas as supramodal grammar processors, the domain-general syntactic role of temporal areas has been so far neglected. Here we capitalized on the excellent spatial and temporal resolution of subdural EEG recordings to co-localize low-level syntactic processes in music and language in the temporal lobe in a within-subject design. We used Brain Surface Current Density mapping to localize and compare neural generators of the early negativities evoked by violations of phrase structure grammar in both music and spoken language. The results show that the processing of syntactic violations relies in both domains on bilateral temporo-fronto-parietal neural networks. We found considerable overlap of these networks in the superior temporal lobe, but also differences in the hemispheric timing and relative weighting of their fronto-temporal constituents. While alluding to the dissimilarity in how shared neural resources may be configured depending on the musical or linguistic nature of the perceived stimulus, the combined data lend support for a co-localization of early musical and linguistic syntax processing in the temporal lobe.

Lesion guided radiofrequency thermocoagulation (L-RFTC) via stereotactically inserted coagulation probes is a further development of stereotactic thermocoagulation thalamotomy and stereo-EEG guided RFTC. In this method epileptogenic lesions detected via magnetic resonance imaging (MRI) move to the center of coagulation planning. Two surgical strategies can be applied: lesion disconnection and lesion destruction. This focused review collects all data published until January 2016 on L-RFTC for the indications hypothalamic hamartoma, periventricular nodular heterotopia and focal cortical dysplasia and describes technical issues, surgical objectives and outcomes. Special attention is given to the aspect of presurgical MRI requirements.

Summary Purpose: In patients with pharmacoresistant focal-onset seizures, invasive presurgical workup can identify epilepsy surgery options when noninvasive workup has failed. Yet, the potential benefit must be balanced with procedure-related risks. This study examines risks associated with the implantation of subdural strip and grid, and intracerebral depth electrodes. Benefit of invasive monitoring is measured by seizure outcomes. Diagnostic procedures made possible by electrode implantation are described. Methods: Retrospective evaluation of invasive workups in 242 epilepsy surgery candidates and additional 18 patients with primary brain tumors implanted for mapping only. Complications are scaled in five grades of severity. A regression analysis identifies risk factors for complications. Outcome is classified according to Engel’s classification. Key Findings: Complications of any type were documented in 23% of patients, and complications requiring surgical revision in 9%. We did not find permanent morbidity or mortality. Major risk factor for complications was the implantation of grids and the implantation of electrode assemblies comprising strip and grid electrodes. Depth electrodes were significantly correlated with a lower risk. Tumors were not correlated with higher complication rates. Chronic invasive monitoring of 3–40 days allowed seizure detection in 99.2% of patients with epilepsy and additional extensive mapping procedures. Patients with epilepsy with follow-up >24 months (n = 165) had an Engel class 1a outcome in 49.7% if epilepsy surgery was performed, but only 6.3% when surgery was rejected. Significance: The benefit of chronic invasive workup outweighs its risks, but complexity of implantations should be kept to a minimum.

Introduction Presurgical work-ups of patients with pharmacoresistant epileptic seizures can require multiple diagnostic methods if magnetic resonance imaging (MRI) combined with video-EEG monitoring fails to show an epileptogenic lesion. Yet, the added value of available methods is not clear. In particular, only a minority of epilepsy centres apply magnetoencephalography (MEG). This study explores the potential of MEG for patients whose previous sophisticated work-ups missed deep-seated, peri-insular epileptogenic lesions. Patients and methods Three patients with well documented, frequent, stereotypical hypermotor seizures without clear focus hypotheses after repeated presurgical work-ups including video-EEG-monitoring, 3Tesla (3T) magnetic resonance imaging (MRI), morphometric MRI analysis, PET and SPECT were referred to MEG source localisation. Results In two out of three patients, MEG source localisation identified very subtle morphological abnormalities formerly missed in MRI or classified as questionable pathology. In the third patient, MEG was not reliable due to insufficient detection of epileptic patterns. Here, a 1mm×1mm×1mm 3T fluid-attenuated inversion recovery (FLAIR) MRI revealed a potential epileptogenic lesion. A minimal invasive work-up via lesion-focused depth electrodes confirmed the intralesional seizure onset in all patients, and histology revealed dysplastic lesions. Seizure outcomes were Engel 1a in two patients, and Engel 1d in the third. Discussion MEG can contribute to the identification of epileptogenic lesions even when multiple previous methods failed, and when the lesions are located in deep anatomical structures such as peri-insular cortex. For epilepsy centres without MEG capability, referral of patients with cryptogenic focal epilepsies to centres with MEG systems may be indicated.

Summary Purpose: Focal cortical dysplasia type IIb (FCD IIb) lesions are highly epileptogenic and frequently cause pharmacoresistant epilepsy. Complete surgical resection leads to seizure freedom in most cases. However, the term “complete” resection is controversial with regard to the necessity of performing resections of the subcortical zone, which is frequently seen in these lesions on magnetic resonance imaging (MRI). Methods: We retrospectively analyzed 50 epilepsy patients with histologically proven FCD IIb. The extent of surgical resection was determined by SPM5-based coregistration of the preoperative and postoperative MRI scans. Postoperative outcome was analyzed with regard to (1) the completeness of the resection of the cortical abnormality and (2) the completeness of the resection of the subcortical abnormality. Key Findings: Complete resection of the cortical abnormality led to postoperative seizure freedom (Engel class Ia) in 34 of 37 patients (92%), whereas incomplete cortical resection achieved this in only one of 13 patients (8%, p

Unexplained recurrent syncope requires interdisciplinary assessment. Paroxysmal bradyand tachycardias can mimic psychiatric conditions [1, 2] and, on the other hand, epileptic seizures, panic attacks and psychogenic phenomena can be mistaken for dysrhythmias. While the former misdiagnosis can be avoided by structured cardiological workup, the latter requires neurological assessment considering the differential diagnosis psychogenic pseudosyncope [3]. A 19-year-old man with recurrent syncope of unknown origin was referred to our epilepsy center for neurological assessment. Attacks with transient loss of consciousness first occurred 2 years previously. A typical event would often be preceded by a rising sensation of pressure and pulsation in the neck and head, followed by a (usually backwards) fall. The ensuing unconsciousness usually lasted 4–5 min with reorientation afterwards lasting several minutes. No motor activity, tongue bite or enuresis during the events was reported. Within 3 months prior to neurological assessment, 1–2 events per week were noted. Previous medical history included autonomic dysfunction, arterial hypertension, nicotine addiction, obesity (135 kg) and obstructive sleep apnea; he was diagnosed in other institutions as having ‘‘Tourette’s syndrome, social phobia, Asperger syndrome’’ and ‘‘attention deficit disorder’’. Multiple cardiological investigations had led to implantation of an event recorder, which registered eventcorrelated narrow complex tachycardias of up to 187 bpm as well as bradycardias of 40 bpm. An electrophysiological study revealed no sign of habitual arrhythmia and no inducible tachycardias. ‘‘Sick sinus syndrome’’ was diagnosed and a DDD pacemaker was implanted. However, the attacks persisted with unaltered frequency. On repeated cardiological assessment, pacemaker function was intact and no signs of autonomic dysfunction or dysrhythmia were found. A neurological investigation was recommended. During 2 days of continuous electroencephalography(EEG-)video monitoring, no interictal epileptic discharges were recorded and no transient loss of consciousness occurred. Tilt-table test was impossible due to weight restrictions of the equipment; Schellong testing was normal with no sign of autonomic dysfunction. The patient was then subjected to suggestive ‘‘seizure’’ provocation through postural maneuvers (sitting down and standing up swiftly) and intravenous administration of saline (mixed with Vitamin B12 for pink coloring); he was informed that these techniques induced fits in some patients. Mattresses were placed on the floor to avoid injury. Rapid postural changes akin to Schellong testing did not elicit loss of consciousness or any significant changes in blood pressure. After three consecutive injections, however, the patient suddenly fell to the ground and was unresponsive for 92 s. Before, during and after the event Electronic supplementary material The online version of this article (doi:10.1007/s00392-014-0711-5) contains supplementary material, which is available to authorized users.