Can the brain’s glial cells be a point of attack for novel ASM treatments?
This is a major project in which, among other approaches, a mouse model is being used to investigate how epilepsy arises and evolves over time. The main question is how glia cells behave during the development and worsening of epilepsy, and whether these changes can be affected by various drugs such as ASMs, anti-inflammatory drugs, drugs that affect intracellular cell signalling etc. Within this project the group has hosted a Special Issue in Frontiers of Neurology in 2020 with Kjell Heuser as editor. See also Berger et al, PLoS One 23019, Frontiers in Neurol, 2020; 2022.
In extension to this study, we are now also investigating possible epigenetic changes taking place during epileptogenesis. This is done in collaboration with Dr. Kaja K. Selmer and her group in Research Group for Neurogenetics, Division of Clinical Neuroscience, OUS. Studying possible mechanisms involved in epileptogenesis may open new treatment strategies to prevent epilepsy, i.e. after stroke and brain injuries.
One PhD degree was completed within this research area with dissertation in February 2022 (Toni Berger: A translational view on epileptogenesis).
Is epilepsy a progressive disease?
This long-term study focuses on changes in the clinical, radiological and neuropsychological picture in patients with temporal lobe epilepsy (Pro-TLE). Comprehensive investigations are conducted on patients with newly diagnosed temporal lobe epilepsy at various time points over a 10-year period. Two papers were recently published: Bjørke AB et al, Epilepsy & Behav 2021 and Bjørke AB et al, Front Neurol 2022.
Long-term effects of ASMs
Patients starting treatment with the ASMs levetiracetam and lamotrigine will be followed prospectively for 2-years in terms of immunological, hormonal, and haematological adverse reactions, and possible changes in bone health. The data will be collected through interviews, questionnaires, blood tests, and bone density measurements. This project is supported with a 50 % PhD student from Østfold Hospital Trust.
As part of this project, studies on the effect of ASMs on gene expression related to immune genes in zebra-fish have also recently been finished in collaboration with NMBU (Norwegian University of Life Sciences)(Mochol M et al Epilepsy Res 2021), and a study on the effect of ASMs on markers for inflammation in humans with epilepsy is performed together with collaborators in OUH(See Mochol M et al, Acta Neurol Scand 2023 (in press).
Epilepsy and cardiology
It has become increasingly clear that several epilepsies are channelopathies, as are many cardiac arrhythmias, and are associated with many of the same channels and ions. The relationship between epilepsy and cardiac arrhythmias like the long QT syndrome (LQTS) is studied. This is also of central importance for understanding sudden unexpected death in epilepsy (SUDEP). We have also studied the impact of several years of active epilepsy on cardiac function. Studies will be finished in 2023. (see i.e. González A, et al, Epilepsy Res 2020; González et al, Case Rep Neurol 2022).
National registration of refractory status epilepticus
We are collating national experiences on how patients with this condition are treated in Norway and how this can be improved. As there are only a few such patients at each centre, joint exchange of experiences is essential. Collection of data commenced in 2015. A national reference group for SE has been established.
Recently, an international collaboration with prof. Christoph Patrick Beier and his group in Odense, Denmark has been started focusing on prognosis of status epilepticus.
(see also: Ulvin LB et al, 2018/2019, Habhab SF et al, Epilepsy Behav 2020; Roberg L et al, JAMA Neurology 2022, Heuser K et al, Exon Publ 2022).
Deep brain stimulation (DBS) in epilepsy
In this study, patients with hard-to-treat epilepsy are treated with DBS using a blinded study design. The clinical work is now completed and most results published. A phd thesis will be submitted for evaluation within 2023.
Traumatic brain injury and posttraumatic epilepsy
A project to study the possible predictive value of different parameters, especially related to inflammation, measured immediately after traumatic brain injuries on the frequency of posttraumatic epilepsy was started in 2021. This is an international collaborative work with groups from US and Europe and with financial support from the US Department of Defence.
The Prehospital Seizure Control trial – (PreCtrl)
ERGO is one of several collaborators in this study that will start in 2023. The intention is to describe the prehospital and initial inhospital pathways and treatment of patients with seizures, to standardize national EMS guidelines and improve time to control in seizure management for better prognosis for the patients. We also plan to implement a new model for standardizing competence, communication and treatment for prehospital seizure assessment – the PreCTRL model.
The other collaborators are: The Norwegian Air Ambulance Foundation, Faculty of Health Science, Oslo Metropolitan University, and Department of Prehospital services, OUH.