Abstract: Objective Circadian and multidien cycles of seizure occurrence are increasingly discussed as to their biological underpinnings and in the context of seizure forecasting. This study analyzes if patient reported seizures provide valid data on such cyclical occurrence. Methods We retrospectively studied if circadian cycles derived from patient-based reporting reflect the objective seizure documentation in 2003 patients undergoing in-patient video-EEG monitoring. Results Only 24.1% of more than 29000 seizures documented were accompanied by patient notifications. There was cyclical underreporting of seizures with a maximum during nighttime, leading to significant deviations in the circadian distribution of seizures. Significant cyclical deviations were found for focal epilepsies originating from both, frontal and temporal lobes, and for different seizure types (in particular, focal unaware and focal to bilateral tonic-clonic seizures). Interpretation Patient seizure diaries may reflect a cyclical reporting bias rather than the true circadian seizure distributions. Cyclical underreporting of seizures derived from patient-based reports alone may lead to suboptimal treatment schemes, to an underestimation of seizure-associated risks, and may pose problems for valid seizure forecasting. This finding strongly supports the use of objective measures to monitor cyclical distributions of seizures and for studies and treatment decisions based thereon

Abstract: Although epilepsy surgery is the only curative therapeutic approach for lesional drug-resistant epilepsy (DRE), there is reluctance to operate on infants due to a fear of complications. A recent meta-analysis showed that epilepsy surgery in the first 6 months of life can achieve seizure control in about two thirds of children. However, robust data on surgical complications and postoperative cognitive development are lacking. We performed a retrospective multicenter study of infants who underwent epilepsy surgery in the first 6 months of life. 15 infants underwent epilepsy surgery at a median age of 134 days (IQR: 58) at four centers. The most common cause was malformation of cortical development, and 13 patients underwent a hemispherotomy. Two thirds required intraoperative red blood transfusions. Severe intraoperative complications occurred in two patients including death in one infant due to cardiovascular insufficiency. At a median follow-up of 1.5 years (IQR: 1.8), 57% of patients were seizure-free. Three patients where reoperated at a later age, resulting in 79% seizure freedom. Anti-seizure medication could be reduced in two thirds, and all patients improved in their development. Our findings suggest that early epilepsy surgery can result in good seizure control and developmental improvement. However, given the perioperative risks, it should be performed only in specialized centers

Abstract: Objective Clinical care of rare and complex epilepsies is challenging, because evidence-based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies. Methods Members of the European Reference Network for rare and complex epilepsies (EpiCARE) were invited to participate in a web-based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht-like diseases. A consensus-based questionnaire was generated for each disease. Results Twenty-six of 30 invited epilepsy centers participated. Cohorts were present in most responding centers for TSC (87%), Dravet syndrome (85%), and autoimmune encephalitis (71%). Patients with TSC and Dravet syndrome represented the largest cohorts in these centers. The antiseizure drug treatments were rather consistent across the centers especially with regard to Dravet syndrome, infantile spasms in TSC, and Unverricht Lundborg / Unverricht-like disease. Available, widely used targeted therapies included everolimus in TSC and immunosuppressive therapies in autoimmune encephalitis. Screening for comorbidities was routinely done, but specific treatment protocols were lacking in most centers. Significance The survey summarizes the current clinical practice for selected rare epilepsies in tertiary European epilepsy centers and demonstrates consistency as well as heterogeneity in the treatment, underscoring the need for controlled trials and recommendations. The survey also provides estimates for potential participants of clinical trials recruited via EpiCARE, emphasizing the great potential of Reference Networks for future studies to evaluate new targeted therapies and to identify novel biomarkers

Abstract: Objective. We propose a novel automated method called the S-Transform Gaussian Mixture detection algorithm (SGM) to detect high-frequency oscillations (HFO) combining the strengths of different families of previously published detectors. Approach. This algorithm does not depend on parameter tuning on a subject (or database) basis, uses time-frequency characteristics, and relies on non-supervised classification to determine if the events standing out from the baseline activity are HFO or not. SGM consists of three steps: the first stage computes the signal baseline using the entropy of the autocorrelation; the second uses the S-Transform to obtain several time-frequency features (area, entropy, and time and frequency widths); and in the third stage Gaussian mixture models cluster time-frequency features to decide if events correspond to HFO-like activity. To validate the SGM algorithm we tested its performance in simulated and real environments. Main results. We assessed the algorithm on a publicly available simulated stereoelectroencephalographic (SEEG) database with varying signal-to-noise ratios (SNR), obtaining very good results for medium and high SNR signals. We further tested the SGM algorithm on real signals from patients with focal epilepsy, in which HFO detection was performed visually by experts, yielding a high agreement between experts and SGM. Significance. The SGM algorithm displayed proper performance in simulated and real environments and therefore can be used for non-supervised detection of HFO. This non-supervised algorithm does not require previous labelling by experts or parameter adjustment depending on the subject or database considered. SGM is not a computationally intensive algorithm, making it suitable to detect and characterize HFO in long-term SEEG recordings

Abstract: Purpose To evaluate the diagnostic accuracy of epilepsy-dedicated 3 Tesla MRI including post-processing by correlating MRI, histopathology, and postsurgical seizure outcomes. Methods 3 Tesla-MRI including a magnetization-prepared two rapid acquisition gradient echo (MP2RAGE) sequence for post-processing using the morphometric analysis program MAP was acquired in 116 consecutive patients with drug-resistant focal epilepsy undergoing resection surgery. The MRI, histopathology reports and postsurgical seizure outcomes were recorded from the patient's charts. Results The MRI and histopathology were concordant in 101 and discordant in 15 patients, 3 no hippocampal sclerosis/gliosis only lesions were missed on MRI and 1 of 28 focal cortical dysplasia (FCD) type II associated with a glial scar was considered a glial scar only on MRI. In another five patients, MRI was suggestive of FCD, the histopathology was uneventful but patients were seizure-free following surgery. The MRI and histopathology were concordant in 20 of 21 glioneuronal tumors, 6 cavernomas, and 7 glial scars. Histopathology was negative in 10 patients with temporal lobe epilepsy, 4 of them had anteroinferior meningoencephaloceles. Engel class IA outcome was reached in 71% of patients. Conclusion The proposed MRI protocol is highly accurate. No hippocampal sclerosis/gliosis only lesions are typically MRI negative. Small MRI positive FCD can be histopathologically missed, most likely due to sampling errors resulting from insufficient harvesting of tissue

Abstract: Die Kallosotomie ist eine palliative Operation, die seit fast 80 Jahren bei Patienten mit therapierefraktären, bilateralen Anfällen eingesetzt wird, wenn ein resektives Verfahren nicht möglich ist. Neuere, minimal-invasive Techniken wie die MRT-gesteuerte laserinduzierte Thermokoagulation sind vermutlich vergleichbar bezüglich Outcome und Komplikationsraten, die Datenlage ist aber insgesamt noch spärlich. In vielen Fallserien war die Kallosotomie v. a. in der Reduktion von Sturzanfällen effektiv, in geringerem Ausmaß auch für epileptische Spasmen. Eine vollständige Anfallsfreiheit wird nur sehr selten erreicht. Chirurgische Komplikationen wie Blutungen oder Infektionen treten in etwa 5 % auf. Die wichtigste, jedoch sehr seltene Nebenwirkung der Kallosotomie ist ein Diskonnektionssyndrom mit Apraxie, taktiler und visueller Anomie, Neglect oder SMA(supplementär-motorisches Areal)-Syndrom. Besonders bei Kindern ist das Diskonnektionssyndrom in aller Regel transient. Ob eine anteriore oder eine komplette Kallosotomie durchgeführt wird, variiert von Zentrum zu Zentrum. Komplette Kallosotomien sind hinsichtlich der Anfallsreduktion effizienter, gehen aber mit einem höheren Risiko für Komplikationen und Nebenwirkungen einher. Eine Option ist eine zweistufige Kallosotomie, bei der zunächst eine anteriore Diskonnektion durchgeführt wird und in den Fällen ohne hinreichenden postoperativen Nutzen in einem zweiten Schritt vervollständigt wird

Las discapacidades intelectuales y del desarrollo tienen una prevalencia de entre 1 y 3% y suponen un impacto significativo en el funcionamiento del individuo que se prolonga a lo largo de toda su vida, así como elevados costes para los sistemas de salud y para la sociedad en su conjunto. En más del 50% de los casos la causa de la discapacidad intelectual y del desarrollo es desconocida, lo que impide indicar un tratamiento específico en caso de que lo hubiese, emitir un pronóstico, evitar exploraciones inútiles y llevar a cabo un consejo genético familiar y reproductivo. El desarrollo y la aplicación a la práctica clínica de técnicas moleculares de cribado genómico, en concreto del array de hibridación genómica comparada (array-CGH), que permite detectar pequeñas pérdidas y ganancias de material genético con una resolución de hasta miles de veces la correspondiente a un cariotipo convencional, han duplicado la tasa de diagnósticos de reordenamientos cromosómicos submicroscópicos como causa de discapacidad intelectual o del desarrollo, al detectarlos en alrededor del 15% de los casos. Justificación del trabajo Aunque hoy día se considera el array-CGH una prueba de primer nivel en el diagnóstico etiológico de las discapacidades intelectuales y las discapacidades del desarrollo sin causa aparente y sin una sospecha sindrómica clara, y a pesar de que su precio ha ido progresivamente disminuyendo, sigue siendo una técnica cara y de realización e interpretación costosa en términos de tiempo y personal. Por ese motivo, es importante establecer en nuestra población pediátrica el rendimiento de esta técnica en el estudio de las discapacidades intelectuales y del desarrollo. Demostrar en nuestra cohorte de pacientes un rendimiento al menos similar al reportado en otras poblaciones puede servir de argumento para salvar las limitaciones de acceso a este estudio que en la actualidad existen en nuestro país...