RESCUE_ESESResearchers: Jansen, van den Munckhof
Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) is a rare pediatric epilepsy syndrome with abundant significant aggravation of interictal epileptiform discharges in sleep and acquired impairment of cognition or behavior. Treatment with conventional anti-epileptic drugs yields limited effects. Observational data has suggested that clobazam and steroid treatment may be beneficial. Evidence from randomized controlled trials (RCT) to prove efficacy of both treatment options, or superiority of one over the other, is mandatory and still lacking.
RESCUE ESES is a European randomized controlled clinical trial in 140 patients aged 2 – 12 years with recent onset epileptic encephalopathy with ESES. This clinical trial will compare the effects of steroids versus clobazam on cognitive functioning. Clobazam treatment will be increased to 0.5-1.2 mg/kg/day if tolerated. Steroids will be given either intravenously (pulsed methylprednisolone 20 mg/kg/day for 3 days, once monthly) or orally (prednisolone 2 mg/kg/day for at one month, followed by tapering in 20 weeks). Primary outcome is cognitive functioning after six months. Secondary outcomes include cognitive functioning at 18 months, spike wave index in sleep, seizure frequency, safety and tolerability. The collaboration with multiple centers (12) within the European network is unique and enables randomization of a large series of patients.
HFO STUDYResearchers: Zijlmans, Van ‘t Klooster, Zweiphenning
Start-end date: 2014-2021
Here we will compare the use of a new EEG biomarker, high frequency oscillations (HFOs), to the use of interictal spikes in acute corticography during epilepsy surgery. The aim is to see whether HFOs can guide the neurosurgeon better than spikes. Primary objective is to investigate whether delineation of the epileptogenic tissue during aECoG-guided surgery, using HFOs instead of epileptiform spikes, will lead to an equal or improved outcome with respect to postoperative seizure freedom. Secondary objectives are the volume of tissue resected, cognitive functioning, neurologic deficits, surgical complications and duration and health related quality of life (pre- vs. postoperative change).
This will be a single blinded randomized controlled trial. The study population will consist of patients of all ages with refractory epilepsy undergoing epilepsy surgery with aECoG to guide the extent of the cortical resection. At study completion 78 patients should be included in the study.
Algorithm for Neonatal Seizure Recognition (ANSeR) is a multicentre, randomised, two arm, parallel controlled, clinical investigation of the ANSeR Software System for Neonatal Seizure Recognition. The performance of the ANSeR Software System is assessed by quantifying and comparing the diagnostic accuracy (sensitivity, specificity) of investigation personnel using the ANSeR Software System with the diagnostic accuracy of investigation personnel not using the ANSeR Software System, for the diagnosis of neonatal seizures. An Expert Committee will be used as the diagnostic reference standard.
- Primary endpoint: diagnostic accuracy of investigation personnel in detecting neonatal seizures with and without the use of ANSeR Software System using an expert EEG review panel as the reference standard.
- Secondary endpoint: total duration of estimated seizure burden measured in minutes in the ANSeR Software System and non ANSeR Software System groups.
CONSORTIA AND INTERNATIONAL COHORT STUDIES
EPISTOPResearchers: Jansen, Hulshof
Start-end date: 2013-2019
This is the first prospective study of epileptogenesis in humans, beginning before seizures and continuing through age 2+ years, permitting detailed analysis of the onset, drug resistance, and comorbidities of epilepsy. To maximize information derived from the study, we have chosen a homogenous group of patients with prenatal or early infantile diagnosis of tuberous sclerosis complex (TSC). A clinical randomized study of pre-seizure treatment in TSC infants is part of the project. The aim of EPISTOP is to examine the risk factors and biomarkers of epilepsy and to identify possible new therapeutic targets to block or otherwise modify epileptogenesis in humans.
Biomarker analysis will be performed by a multidisciplinary, systematic approach in three clinical settings:
- Prospective study of epilepsy development in infants with TSC, including analysis of clinical, neuroimaging, and molecular, blood-derived biomarkers at predefined time points: before the onset of seizures, at the onset of epileptiform discharges on EEG, at seizure onset and at the age of 24 months.
- Prospective study of blood-based biomarkers in infants with TSC treated with antiepileptic drugs prior to seizure onset in comparison to children treated only after clinical seizures appearance.
- Analysis of biomarkers of epileptogenesis and drug resistant epilepsy in brain specimens obtained from TSC patients who have had epilepsy surgery and TSC autopsy cases.
EUROPEAN EPILEPSY SURGERY STUDIESResearchers: Kees Braun, Pieter van Eijsden, Wim Otte, Monique van Schooneveld, Kim Boshuisen, several PhD students
Start-end date: since 2010, ongoing
The UMCU has a coordinating role in several multicenter research projects, based on the collection of retrospective data from large epilepsy surgery cohorts in Europe, in order to reach sufficient statistical power to answer clinical questions about presurgical diagnostics, epilepsy surgery outcome, and antiepileptic drug policies:
- TimeToStop studies: the correlation between (timing of) AED withdrawal and seizure and cognitive outcomes in a cohort of 766 children who underwent epilepsy surgery in 15 European centers
- European Epilepsy Brain Bank (EEBB) studies: to correlate histopathological diagnosis with seizure and drug outcomes in a cohort of 9147 patients who underwent epilepsy surgery between 2000 and 2012 in 37 centers
- HemiHOPE studies: seizure, cognitive and functional outcomes of 456 children who underwent hemispherectomy in Utrecht, London, Freiburg and Paris
- Invasive EEG studies: to compare patient characteristics, results and surgical outcomes of subdural grids versus stereo-EEG monitoring in a cohort of 857 patients who underwent presurgical invasive EEG monitoring in Utrecht, Milano and London
CONSORTIUM EpiCoreConsortium between UMCU, SEIN, productzaken and Inomed for the development of an intra-operative device to guide the neurosurgeon during epilepsy surgery.
- EpiSign: retrospective study with signal analysis on electrocorticography data; database ‘Respect’
- Core of Epilepsy: prospective study, funded with ERC starting grant, to prospectively gather electrocorticography data with advanced recording and signal analysis methods
- Heart of Epilepsy: prospective proof of principle study for the development of an intraoperative device to guide the neurosurgeon during epilepsy surgery.
CIRCRTRAINResearchers: Jeroen Pasterkamp
Start-end date: 1-1-2017 – 1-1-2021
Circular RNAs are a novel class of non-coding RNAs with roles in gene expression. CircRNAs are particularly enriched in brain tissue and regulated by activity. Our preliminary studies show that circRNA expression is dramatically altered in different experimental and human epilepsies. Our role in circRTrain is to identify the dysregulated circRNAs, analyse their expression and manipulate their function in cellular and other models of epilepsy. This work aims to identify circRNAs as biomarkers and therapeutic targets in epilepsy