Clinical and experimental epileptology

Epileptology is one of the core themes at the Department of Neurology of the Charité – Universitätsmedizin Berlin and it is represented at both sites – Campus Mitte and Campus Virchow Klinikum. One focus is on outpatient and inpatient treatment, while the other is on clinical and experimental research projects. The overarching aim of these projects is to improve the understanding of the pathophysiological mechanisms of the epilepsies as well as their origin and development in order to optimise established therapeutic strategies, to generate new approaches and eventually to ameliorate treatment outcome in patients.

The research projects of the Clinical and experimental Epileptology Group are supported by the Deutsche Forschungsgemeinschaft, by the Deutsche Gesellschaft für Epileptologie by means of the Otfried-Foerster-Stipendium, and by industrial funding from collaborating companies. There are two overlapping areas of research interest.
First, the clinical and experimental focus is on status epilepticus, the most extreme expression of epilepsy, and its sequelae. We have demonstrated that status epilepticus does not respond to standard anticonvulsant drugs in about 30 % of patients; this kind of refractory status epilepticus often results in chronic epilepsy. The understanding of pathophysiological mechanisms underlying the development of epilepsy (epileptogenesis) after an acquired brain injury – such as status epilepticus – is crucial for the development of antiepileptogenic treatment strategies. The intention is to prevent the development of epilepsy instead of suppressing the symptom “epileptic seizure” pharmacologically. In our in vivo experiments, we therefore analyse dynamic and structural changes resulting from status epilepticus and investigate novel therapeutic strategies with non-pharmacological approaches such as hypothermia and deep brain stimulation.
The second focus of our research interest is on analysis of epileptic activity using optical imaging methods in vitro. In brain slice preparations, various imaging approaches are applied to scrutinize basic pathophysiological mechanisms underlying seizure generation (ictogenesis). The use of intrinsic optical signals – i.e. activity-dependent changes in optical features of brain tissue – allows us to “visualise” and analyse origin and spread of epileptic activity. We were able to demonstrate significant differences in epileptic activity during postnatal brain development, in old age, and after status epilepticus. In addition, we apply microfluometric methods using dyes or autofluoresence of the tissue to study cellular energy metabolism during epileptic activity. Currently, we analyse epileptiform discharges in brain slices from epileptic animals by means of voltage sensitive dye imaging – i.e. recording of neuronal activity using voltage-dependent dyes.

Patients are cared for predominantly in the Epilepsy Outpatient Clinics of our institution. We established a First seizure clinic for comprehensive diagnostic clarification and therapeutic counselling of patients with first epileptic seizures. More advanced diagnostic procedures, such as intensive EEG-video-telemetry, are performed on an in-patient basis. Patients with status epilepticus are treated on one of the neurological intensive care units on the respective campus. In addition to patient care, we conduct clinical research projects on epidemiology of epilepsy comorbidities such as headache and on the use of stimulants such as nicotine, alcohol and illicit drugs. In cooperation with the Department of Neurology and Stereotactic Neurosurgery of the University of  Magdeburg, we implement the novel and promising therapeutic option of deep brain stimulation in patients with intractable epilepsy who cannot undergo classical epilepsy surgery. Based on the Berlin and Heidelberg medical records of the “Janz-Archive” we analyse the long-term outcome of patients with idiopathic generalised epilepsies.

Co-operation partners:

– Prof. Dr. Douglas Coulter (Children’s Hospital of Philadelphia)

– Prof. Dr. Uwe Heinemann (Institute of Neurophysiology, Charité, Berlin)

– Dr. Julia Matzen, Dr. Friedhelm Schmitt (Department of Neurology), Dr. Lars Büntjen, Prof. Dr. Jürgen Voges (Department of Stereotactic Neurosurgery, University of Magdeburg)

– Prof. Dr. Matthew Walker (Institute of Neurology, University College London)

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Selected Publications

Meierkord H, Boon P, Engelsen B, Gocke K, Shorvon S, Tinuper P & Holtkamp M (2010)

EFNS guideline on the management of status epilepticus. Eur J Neurol 17: 348-355.

Matzen J, Buchheim K, van Landeghem F, Meierkord H & Holtkamp M (2008)

Functional and morphological changes in the dentate gyrus after experimental status epilepticus. Seizure 17: 76-83.

Prüß H & Holtkamp M (2008)

Ketamine successfully terminates malignant status epilepticus. Epilepsy Res 82: 219-222.

Holtkamp M (2007)

The anaesthetic and intensive care of status epilepticus. Curr Opin Neurol 20: 188-193.

Holtkamp M & Meierkord H (2007)

Biomedicine and diseases: anticonvulsant, antiepileptogenic and antiictogenic pharmacostrategies. Cell Mol Life Sci 64: 2023-2041.

Holtkamp M, Schmitt FC, Buchheim K & Meierkord H (2007)

Temperature regulation is compromised in experimental limbic status epilepticus. Brain Res 1127: 76-79.

Meierkord H & Holtkamp M (2007)

Non-convulsive status epilepticus: Clinical forms and treatment. Lancet Neurol 6: 329-339.

Pathak HR, Weissinger F, Terunuma M, Carlson GC, Hsu FC, Moss SJ, Coulter DA (2007)

Disrupted dentate granule cell chloride regulation enhances synaptic excitability during development of temporal lobe epilepsy. J Neurosci 27: 14012-22.

Holtkamp M, Othman J, Buchheim K & Meierkord H (2006)

Diagnosis of psychogenic non-epileptic status epilepticus in the emergency setting. Neurology 66: 1727-29.

Schmitt FC, Buchheim K, Meierkord H & Holtkamp M (2006)

Anticonvulsant properties of hypothermia in experimental status epilepticus. Neurobiol Dis 23: 689-696.

Buchheim K, Wessel O, Siegmund H, Schuchmann S, Meierkord H (2005)

Processes and components participating in the generation of intrinsic optical signal changes in vitro. Eur J Neurosci 22: 125-32.

Holtkamp M, Matzen J, van Landeghem F, Buchheim K & Meierkord H (2005)

Transient loss of inhibition precedes spontaneous seizures after experimental status epilepticus. Neurobiol Dis 19: 162-170.

Holtkamp M, Othman J, Buchheim K, Masuhr F, Schielke E & Meierkord H (2005)

A 'malignant' variant of status epilepticus. ArchNeurol 62: 1428-1431.

Holtkamp M, Othman J, Buchheim K & Meierkord H (2005)

Predictors and prognosis in refractory status epilepticus. J Neurol Neurosurg Psychiatry 76: 534-539.

Schmitt FC, Matzen J, Buchheim K, Meierkord H & Holtkamp M (2005)

Hyperthermia is not associated with limbic but with motor experimental status epilepticus. Epilepsia 46: 188-192.

Weissinger F, Buchheim K, Siegmund H, Meierkord H (2005)

Seizure spread through the life cycle: optical imaging in combined brain slices from immature, adult, and senile rats in vitro. Neurobiol Dis 19: 84-95.

Buchheim K, Obrig H, v Pannwitz W, Mueller A, Heekeren H, Villringer A, Meierkord H (2004)

Decrease in haemoglobin oxygenation during absence seizures in adult humans. Neurosci Lett 354:119-22.

Holtkamp M, Schuchmann S, Gottschalk S & Meierkord H (2004)

Recurrent seizures do not cause hippocampal damage. J Neurol  251: 458-463.

Holtkamp M, Matzen J, Buchheim K, Walker MC & Meierkord H (2003)

Furosemide terminates limbic status epilepticus in freely moving rats. Epilepsia 44: 1141-1144.

Holtkamp M, Buchheim K, Siegmund H, Meierkord H (2003)

Optical imaging reveals reduced seizure spread and propagation velocities in aged rat brain in vitro. Neurobiol Aging 24: 345-353.

Holtkamp M, Masuhr F, Harms L, Einhäupl KM, Meierkord H, Buchheim K (2003)

The management of refractory generalised convulsive and complex partial status epilepticus in three european countries. A survey among epileptologists and critical care neurologists. J Neurol Neurosurg Psychiatry 74: 1095-1099.

Holtkamp M, Tong X, Walker MC (2001)

Propofol in subanesthetic doses terminates status epilepticus in a rodent model. Ann Neurol 49: 260-263.

Weissinger F, Buchheim K, Siegmund H, Heinemann U, Meierkord H (2000)

Optical imaging reveals characteristic seizure onsets, spread patterns, and propagation velocities in hippocampal-entorhinal cortex slices of juvenile rats. Neurobiol Dis 7: 286-298.

Buchheim K, Schuchmann S, Siegmund H, Gabriel HJ, Heinemann U, Meierkord H (1999)

Intrinsic optical signal measurements reveal characteristic features during different forms of spontaneous neuronal hyperactivity associated with ECS shrinkage in vitro. Eur J Neurosci 11: 1877-1882.

Gutschmidt KU, Stenkamp K, Buchheim K, Heinemann U, Meierkord H (1999)

Anticonvulsant actions of furosemide in vitro. Neuroscience 91: 1471-1481.

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