Movement Disorders Unit

Movement disorders comprise different disease entities such as Parkinson's disease, tremor, dystonias, tics, Huntington’s chorea and other hereditary movement disorders and cerebellar disorders.

Team Bewegungsstörungen CVK

The common denominator of these disorders constitutes the affection of so called subcortical brain nuclei (basal ganglia) on the one hand, but also the public character of the disorders on the other hand. Patients can be readily recognized by their apparent affection, they, indeed, are stigmatized. The treatment of movement disorders reflects the change of neurology from a predominantly diagnostic to a therapeutic discipline. Thus, highly effective therapeutic strategies have been developed during the last 50 years such as the introduction of levo-dopa for Parkinson's disease more than 40 years ago. In addition, in the last 20 years functional neurosurgery has been revived as a very effective and reversible treatment using deep brain stimulation (DBS) for movement disorders like Parkinson's disease and dystonia. Despite these remarkable improvements the distinct need for further research is underlined by the fact that there is still no cure for most, if not all movement disorders.

Clinic

More than 1000 patients with movement disorders are treated annually in the outpatient clinic both at the Charité Campus Virchow Klinikum (CVK) and Charité Campus Benjamin Franklin (CBF). Routine treatments comprise injections with botulinum toxin for dystonia and various drug therapies for Parkinson’s diesease. Diverse (partially multicenter) studies, both at the national and international level, aim at improving the therapeutic potentials in the treatment of movement disorders and allow a careful management of individual patients. At the Campus Virchow Klinikum deep brain stimulation has emerged as powerful tool for the treatment of Parkinson's disease, essential tremor, and various types of dystonias (appointments for the deep brain stimulation outpatient clinic can be scheduled via Frau Zielinski, Secretariat of Professor Kühn, T: +49 30 450 560 123). Furthermore, there is research in progress dealing with new therapeutic strategies for atypical Parkinsonian syndromes. Special consultation for patients with tic disorders on an out-patient basis and for patients with spasticity following ischemic brain injury for treatment with botulinum toxin (call +49 30 450 560 038) have been installed.

Research projects

The members of the department of movement disorders at the Charité are both clinically and scientifically involved in further refining and improving therapy and diagnostics for movement disorders.  In 2010 a clinical research unit focusing on deep brain stimulation (funded by the German Research Foundation) was established under the direction of Prof. Andrea Kühn at the department of neurology at the Charité (Opens external link in current windowwww.kfo247.de/en).

Clinical neuroscience and neurophysiology (Professor Kühn)

Research in the "Motor Neuroscience Group" focuses on basic and clinical research related to the physiology of cortico-basal ganglia-thalamic loops. Several research methodologies are used in the lab to record neuronal activity from the basal ganglia and the cortex. The principal methodology covers invasive recordings of deep brain activity from different basal ganglia nuclei in humans, which are the targets for deep brain stimulation (DBS) electrodes in various pathologies like Parkinson's disease, dystonia, tremor, Tourette's syndrome, obsessive-compulsive disorder or severe depression. This approach permits intraoperative recordings of single-unit activity via microelectrodes and postoperative recordings of local field potential (LFP) activity via the implanted DBS-macroelectrodes. In addition, cortical activity is investigated by means of electroencephalography (EEG) and magnetoencephalography (MEG). Finally, the modulation of cortical excitability is studied with transcranial magnetic stimulation (TMS).
Our current research programme extends from the work on understanding the mechanisms of action of DBS to the investigation of different motor, cognitive and emotional aspects of the cortico-basal ganglia physiology:

Motor Function
One of our main interests is the investigation of cortical and basal ganglia motor functions in patients suffering from different movement disorders. Interactions within the cortico-basal ganglia network during motor tasks as well as its modulation leading to abnormal movements can be explored using simultaneous deep brain (LFP) and cortical (EEG/MEG) recordings. Moreover, analysing single and multi-unit activity in combination with LFP activity from the basal ganglia offers the opportunity to investigate basic neuronal encoding mechanisms for movement parameters. Finally, we further explore the mechanism of action of deep brain stimulation. (Christof Brücke, Julian Neumann, Daniel Kroneberg)


Executive Functions
Further projects investigate the role of the basal ganglia in conflict processing and error detection during action-monitoring. A special focus is the study of error detection and motor prediction via forward models. To this end, we investigate direct recordings from the STN and GPi in patients undergoing DBS during performance of reaction-time conflict tasks and overlearned motor programmes. (María Herrojo Ruiz, Julian Neumann)


Emotion
Studying DBS-related changes in emotional processing are of special clinical relevance in PD patients with chronic DBS. Here, we record LFP activity from basal ganglia structures during emotional paradigms and correlate our findings with neuropsychiatric parameters. Furthermore, neurophysiological parameters of affective processing are also studied in patients suffering from severe depression undergoing DBS of the subgenulate cingulum. (Julius Huebl, Wolf-Julian Neumann, in collaboration with the Department of Psychiatry, Malek Bajbouj, Angela Merkl)

Collaborations
Opens external link in current windowProf. Peter Brown, Department of Clinical Neurology, Radcliff Infirmary, University of Oxford, UK
Opens external link in current windowProf. Joachim K. Krauss, Dept. of Neurosurgery, Medical School Hannover
Opens external link in current windowDr. Vladimir Litvak, The Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, UK
Opens external link in current windowProf. Bart Nuttin, Dept. of Neurosurgery, Katholieke Universiteit Leuven, Belgien
Opens external link in current windowDr. Tilman Sander-Thömmes, National Metrology Institute, Berlin

Animal laboratory (Daniel Harnack and Christoph van Riesen)

The main focus of our group is to elucidate the functional principle of deep brain stimulation using animal models of PD (6-OHDA and MPTP). Using a fully implantable DBS-system for rodents, developed by our group, we investigate how chronic DBS influences the brain's structure (light & electron microscopy), neurochemistry (HPLC, western blot, ELISA) and information processing (in vivo electrophysiology of freely moving subjects). Focussing especially on the spatiotemporal dynamics of PD, we hope to contribute to the development of improved DBS paradigms to reduce the disease burden of patients.

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Selected Publications

Herrojo Ruiz M, Rusconi M, Brücke C, Haynes JD, Schönecker T, Kühn AA
Encoding of sequence boundaries in the subthalamic nucleus of patients with Parkinson's disease.
Brain 2014; Oct; 137(Pt. 10):2715-30.
Barow E, Neumann WJ, Brücke C, Huebl J, Horn A, Brown P, Krauss JK, Schneider GH, Kühn AA
Deep brain stimulation suppresses pallidal low frequency activity in patients with phasic dystonic movements.
Brain 2014; Sep 10
Huebl J, Spitzer B, Brücke C, Schönecker T, Kupsch A, Alesch F, Schneider GH, Kühn AA
Oscillatory subthalamic nucleus activity is modulated by dopamine during emotional processing in Parkinson's disease.
Cortex 2014; Mar 6:[Epub ahead of print].
Neumann WJ, Huebl J, Brücke C, Gabriëls L, Bajbouj M, Merkl A, Schneider GH, Nuttin B, Brown P and Kühn AA.
Different patterns of local field potentials from limbic DBS targets in patients with major depressive and obsessive compulsive disorder.
Mol Psychiatry 2014; Feb 11 (Epub ahead of print)
Siegert S, Herrojo Ruiz M, Brücke C, Huebl J, Schneider GH, Ullsperger M, Kühn AA
Error signals in the subthalamic nucleus are related to post-error slowing in patients with Parkinson's disease.
Cortex 2014; Jan 10 (Epub ahead of print)
Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L, Hälbig TD, Hesekamp H, Navarro SM, Meier N, Falk D, Mehdorn M, Paschen S, Maarouf M, Barbe MT, Fink GR, Kupsch A, Gruber D, Schneider GH, Seigneuret E, Kistner A, Chaynes P, Ory-Magne F, Brefel Courbon C, Vesper J, Schnitzler A, Wojtecki L, Houeto JL, Bataille B, Maltête D, Damier P, Raoul S, Sixel-Doering F, Hellwig D, Gharabaghi A, Krüger R, Pinsker MO, Amtage F, Régis JM, Witjas T, Thobois S, Mertens P, Kloss M, Hartmann A, Oertel WH, Post B, Speelman H, Agid Y, Schade-Brittinger C, Deuschl G; EARLYSTIM Study Group
Neurostimulation for Parkinson's disease with early motor complications.
N Engl J Med 2013; Feb 14;368(7):610-22.
Volkmann J, Wolters A, Kupsch A, Müller J, Kühn AA, Schneider GH, Poewe W, Hering S, Eisner W, Müller JU, Deuschl G, Pinsker MO, Skogseid IM, Roeste GK, Krause M, Tronnier V, Schnitzler A, Voges J, Nikkhah G, Vesper J, Classen J, Naumann M, Benecke R; DBS study group for dystonia
Pallidal deep brain stimulation in patients with primary generalised or segmental dystonia: 5-year follow-up of a randomised trial.
Lancet Neurol 2012; 2012 Dec(12):1029-38.
Brücke C, Huebl J, Schonecker T, Neumann WJ, Yarrow K, Kupsch A, Blahak C, Lutjens G, Brown P, Krauss JK, Schneider GH and Kühn AA.
Scaling of movement is related to pallidal gamma oscillations in patients with dystonia.
J Neurosci 2012; 32(3):1008-19.
Huebl J, Schoenecker T, Siegert S, Brücke C, Schneider GH, Kupsch A, Yarrow K and Kühn AA.
Modulation of subthalamic alpha activity to emotional stimuli correlates with depressive symptoms in Parkinson's disease.
Mov Disord 2011; 26(3):477-83.
Neumann WJ, Huebl J, Brücke C, Ruiz MH, Kupsch A, Schneider GH and Kühn AA.
Enhanced low-frequency oscillatory activity of the subthalamic nucleus in a patient with dystonia.
Mov Disord 2012; 27(8):1063-6.

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Leaders

Professor Andrea Kühn, MD
(Head of movement disorders unit CVK and of the clinical research unit "Opens external link in current windowdeep brain stimulation")
t: +49 30 450 560 123 (Secretary)
f: +49 30 450 560 901

Axel Lipp, MD
(Head of movement disorders unit CVK and of the autonomic function laboratory)
t: +49 30 450 560 172 (Secretary)
f: +49 30 450 560 938

Doctoral candidates

  • Laura Arntz
  • Tobias Ellermeyer
  • Katharina Degen
  • Katharina Lauritsch
  • Sandra Köppe
  • Ana Luísa Marcelino
  • Tobias Scholz
  • Adrian Seidel
  • Franziska Staub
  • Nicole Trabs