Kerstin Alexandra Klotz / Julia Jacobs
Kerstin Alexandra Klotz, MD, local lead
T: +49 761 270 43000
Julia Jacobs, MD, adjunct professor
Medical Center – University of Freiburg
Center for Pediatrics
Department of Neuropediatrics and Muscle Disorders
Our research focuses on clinical and translational research in pediatric epilepsies. The main themes include research of high frequency oscillations in EEG and epileptogenic networks using functional MRI as well as clinical picture and treatment of rare, pharmacoresistant epilepsies. The group is also participating in several pharmaceutical clinical trials.
Dr. Kerstin A. Klotz, group leader and physician mainly working on Cannabidiol, hypothalamic hamartoma and High-Frequency Oscillations as predictors of epilepsy, also investigator in several ongoing clinical trials.
Prof. Dr. Julia Jacobs, senior associate group leader mainly working on High-Frequency Oscillations, epileptogenic networks using functional MRI and EEGfMRI and hypothalamic hamartoma.
Dr. Victoria San Antonio, working on clinical variety and systematic evaluation of pediatric epilepsy syndromes and outcome in patients with focal cortical dysplasias, investigator in several ongoing clinical trials.
Dr. Jan Schönberger, physician mainly working on High-Frequency Oscillations, single-neuron recordings, and epileptic encephalopathy, also investigator in several ongoing clinical trials.
Dr. Jonas Bruder, physician and postdoc, mainly working on High-Frequency Oscillations, also investigator in several ongoing clinical trials.
Daniel Lachner, biomedical engineer
Inka Lotz, study nurse
Sabine Wider, study nurse
Medical Students: Anja Knopf, Anna Wagner-Siegel, Anne-Kathrin König, Charlotte Elsa Huber, Christoph Schmelzeisen, Daniel Grob, Friederike Scheerer, Jasmin Özcan, Jennifer Weinreich, Lea Wrede, Lisa Rieder, Michaela Anna Lehmann, Miriam Jaiser, Paula Hauck, Sarah Metzger, Stephan Steinhoff, Tianjia Liu, Tim Guth, Yusuf Sag
The Pediatric Epilepsy research group focusses on improving diagnostics and treatment in pediatric epilepsies. Most studies are tailored to improve the life of children with refractory epilepsies, but we are also interested in early diagnostics and interventions in patients at risk of developing seizures.
Two main methods for diagnostics are EEG, including intracranial EEG, and MRI studies.
Our group is specialized and has substantial expertise in the analysis of High-Frequency Oscillations (HFO) in EEG. These oscillations are biomarkers for epileptic activity. We work on technical improvements that enable HFO to be used as a precise biomarker for the definition of the seizure onset zone; this helps optimize outcome in epilepsy surgery.
We also evaluate the predictive value of HFO in children with early brain injury or in children with a first unprovoked seizure to assess their risk of developing epilepsy. Another important theme is the evaluation of HFO in the context of physiological processes as memory consolidation and sleep. Together with the Epilepsy Center for adults, we try to understand mechanisms of HFO generation by looking at single cell recordings.
In collaboration with the Department of Medical Physics we have used simultaneous EEG-fMRI to improve the understanding of epileptic networks in children with epilepsy. The main aim is to use fMRI to localize metabolic changes in patients with epilepsy. Our work groups focus on technical improvement, such as new methods of EEG and fMRI analysis.
In pediatric epilepsies we often face rare and difficult to treat epilepsies. Our group focusses on providing personalized and optimized treatment for some of these conditions. This includes improving understanding of clinical presentation with a special focus on comorbidities, as well as optimizing therapy options and outcome.
One focus in this context is the research of Hypothalamic hamartomas, a rare brain malformation that causes severe epilepsy and several comorbidities. We also participate with other pediatric epilepsy centers to gather data on conditions like Tuberous Sclerosis, Dravet syndrome and other rare genetic encephalopathies.
In recent years new anti-seizure treatment has become available for refractory epilepsies and our center focusses on making these treatments available for children. We have a dedicated research unit that allows participation in international pharmaceutical trials. Additionally, we have a special focus on using Cannabidiol (CBD) for refractory epilepsies. Interest in using CBD to epilepsies has grown over the last few years; our focus is on the open label use of CBD in childhood epilepsies as well as impact on cognition and quality of life.
Current HFO Projects
- Analysis of ripple and fast ripple oscillations during electrical stimulation in areas with functional response
- Automatic analysis of High-Frequency Oscillations and interictal epileptic spikes helps to identify the primary focus in patients with dual pathology in temporal lobe epilepsy
- Analysis of sleep spindle ripple co-occurrence helps to predict memory performance and postsurgical seizure outcome in patients with mesial-temporal epilepsy.
- Single-cell activity of spike-associated High-Frequency Oscillations in the mesial temporal lobe of patients with focal epilepsy.
- High-Frequency Oscillations as a biomarker for prediction of further seizures or epilepsy after a first, unprovoked seizure in childhood
Current network projects
- Spontaneous and electrically-induced cortical excitability changes of epileptic networks after radio-frequency thermo-coagulation
- Network analysis in patients with rolandic epilepsy
- Analysis of High-Frequency Oscillations in intracranial EEG-fMRI
- Networks of IED and ictal activity in patients with hypothalamic hamartomas
- High-Frequency Oscillations in infants with and without epilepsy
- Metabolic correlates of HFO in patients with refractory epilepsy
Other current projects
- Ictal tachycardia in children with epilepsy
- The use of synthetic cannabidiol in children and adults with intractable epilepsy
- Influence of a structured follow-up management („First Seizure Clinic“) on anxiety in children and parents after first unprovoked seizure – randomized controlled pilot study
- Outcome in HH in children with thermocoagulation
- Effect of seizures and inter-ictal epileptic discharges on sleep quality in patients with Hypothalamic Hamartomas Effect of seizures and inter-ictal epileptic discharges during slow wave sleep on memory function in patients with Hypothalamic Hamartomas
- Lateralizing signs in patients with Hypothalamic Hamartomas
- Remaining corpus callosum connections influence seizure outcome after functional hemispherectomy
- Investigation local sleep phenomena in pediatric epileptic encephalopathy
- Outcome in patients with focal cortical dysplasia
SELECTED RECENT PUBLICATIONS
Complete list of publications for Kerstin A. Klotz, Julia Jacobs, Jan Schönberger and Victoria San-Antonio Arce.
- Expectations and knowledge of cannabidiol therapy for childhood epilepsy – A German caregiver survey. Klotz KA, Schönberger J, Nakamura L, San Antonio-Arce V, Bast T, Wiemer-Kruel A, Schubert-Bast S, Borggraefe I, Syrbe S, Jacobs J. Epilepsy Behav, 2020 Jul 6;111:107268. doi: 10.1016/j.yebeh.2020.107268.
- Efficacy and tolerance of synthetic cannabidiol for treatment of drug resistant epilepsy. Klotz KA, Grob D, Hirsch M, Metternich B, Schulze-Bonhage A, Jacobs J. Front Neurol, 2019 Dec 10;10:1313. doi: 10.3389/fneur.2019.01313.
- High-frequency oscillations mirror severity of human temporal lobe seizures. Schönberger J, Birk N, Lachner-Piza D, Dümpelmann M, Schulze-Bonhage A, Jacobs J. Ann Clin Transl Neurol, 2019 Dec;6(12):2479-2488. doi: 10.1002/acn3.50941.
- Removing high-frequency oscillations: A prospective multicenter study on seizure outcome. Jacobs J, Wu JY, Perucca P, Zelmann R, Mader M, Dubeau F, Mathern GW, Schulze-Bonhage A, Gotman J. Neurology, 2018 Sep 11;91(11):e1040-e1052. doi: 10.1212/WNL.0000000000006158.
- Cognitive and behavioral comorbidities in Rolandic epilepsy and their relation with default mode network’s functional connectivity and organization. Ofer I, Jacobs J, Jaiser N, Akin B, Hennig J, Schulze-Bonhage A, LeVan P. Epilepsy Behav, 2018 Jan;78:179-186. doi: 10.1016/j.yebeh.2017.10.013.
COLLABORATIONS, CO-OPERATIONS AND NETWORKS
- Prof. Dr. Jürgen Beck
- Prof. Dr. Andreas Schulze-Bonhage
- Prof. Dr. Juergen Hennig, MP
- Dr. Mukesch Shah
- Dr. Barbara Puhahn-Schmeiser
- Dr. Ing. Matthias Dümpelmann
- Dr. Lukas Kunz
- PD Dr. Thomas Bast, Epilepsieklinik für Kinder und Jugendliche der Diakonie Kork
- Dr. Susanne Schubert-Bast und Prof Dr. Adam Strzelczyk, Epilepsiezentrum Rhein-Main Frankfurt
- PD Dr. Steffen Syrbe, University Hospital Heidelberg
- Univ. Prof. Mag. Dr. Eugen Trinka und Aljoscha Thomshewski, University Hospital Salzburg/Austria
- Dipl.-Ing. Mag. Yvonne Hoeller, Iceland
- Olivier David und Prof. Dr. Philippe Kahane, Grenoble/France
- Prof. Dr. Courtney Wusthoff, Stanford University/USA
- Prof. Dr. Jean Gotman, McGill University Montreal/Canada
Kerstin A. Klotz and Jan Schönberger are Fellows in the Berta-Ottenstein Programme for Clinician Scientists (Freiburg University Medical Center)
DFG 1725/4-1: Spontaneous and electrically-induced cortical excitability changes of epileptic networks after radio-frequency thermo-coagulation
CSC Grant: Investigation local sleep phenomena in pediatric epileptic encephalopathy