Movement disorders

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 (www.bewegungsstoerungen-charite.de). 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 recognised 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 15 years functional neurosurgery has been revived as a very effective and reversible treatment using deep brain stimulation 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 still is 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. 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 +49-30-450560038) 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.
Clinical Neuroscience (Prof. Dr. Andrea A. 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. (Ewgenia Barow, Christof Bruecke, Antje Bock, Julius Huebl, 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, Sandy Siegert)

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, Katharina Degen, in collaboration with the Department of Psychiatry, Malek Bajbouj, Angela Merkl)

Collaborations

Prof. Peter Brown, Radcliff Infirmary, Oxford, UK
Prof. Joachim K. Krauss, Dept. of Neurosurgery, Medical School Hannover
Prof. Bart Nuttin, Dept. of Neurosurgery, Katholieke Universiteit Leuven, Belgien
Dr. Tilman-Sander, National Metrology Institute, Berlin

Laboratory (Prof. Dr. Andreas Kupsch)

In close cooperation with the Institute of Pharmacology und Toxicology of the Charité (Director: Prof. Morgenstern) deep brain stimulation and neurotransplantation are further investigated in experimental animals. International cooperations (including exchange of post doc investigators) exist between groups in Bordeaux, Grenoble, Lund-Sweden Marseille and New York.

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Selected publications

Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, Daniels C, Deutschlander A, Dillmann U, Eisner W, Gruber D, Hamel W, Herzog J, Hilker R, Klebe S, Kloss M, Koy J, Krause M, Kupsch A, Lorenz D, Lorenzl S, Mehdorn HM, Moringlane JR, Oertel W, Pinsker MO, Reichmann H, Reuss A, Schneider GH, Schnitzler A, Steude U, Sturm V, Timmermann L, Tronnier V, Trottenberg T, Wojtecki L, Wolf E, Poewe W and Voges J.

A randomized trial of deep-brain stimulation for Parkinson's disease. N Engl J Med. 2006;355(9): 896-908.

Gruber D, Trottenberg T, Kivi A, Schönecker T, Kopp UA, Hoffmann KT, Schneider GH, Kühn AA and Kupsch A.

Long-term effects of pallidal deep brain stimulation in tardive dystonia. Neurology. 2009;73(1): 53-8.

Harnack D, Meissner W, Jira JA, Winter C, Morgenstern R and Kupsch A.

Placebo-controlled chronic high-frequency stimulation of the subthalamic nucleus preserves dopaminergic nigral neurons in a rat model of progressive Parkinsonism. Exp Neurol. 2008 210(1): 257-60.

Kühn AA, Kempf F, Brucke C, Gaynor Doyle L, Martinez-Torres I, Pogosyan A, Trottenberg T, Kupsch A, Schneider GH, Hariz MI, Vandenberghe W, Nuttin B and Brown P.

High-frequency stimulation of the subthalamic nucleus suppresses oscillatory beta activity in patients with Parkinson's disease in parallel with improvement in motor performance. J Neurosci. 2008;28(24): 6165-73.

Kühn AA, Tsui A, Aziz T, Ray N, Brucke C, Kupsch A, Schneider GH and Brown P.

Pathological synchronisation in the subthalamic nucleus of patients with Parkinson's disease relates to both bradykinesia and rigidity. Exp Neurol. 2009;215(2): 380-7.

Kühn AA, Williams D, Kupsch A, Limousin P, Hariz M, Schneider GH, Yarrow K and Brown P.

Event-related beta desynchronization in human subthalamic nucleus correlates with motor performance. Brain. 2004;127(Pt 4): 735-46.

Kupsch A, Benecke R, Muller J, Trottenberg T, Schneider GH, Poewe W, Eisner W, Wolters A, Muller JU, Deuschl G, Pinsker MO, Skogseid IM, Roeste GK, Vollmer-Haase J, Brentrup A, Krause M, Tronnier V, Schnitzler A, Voges J, Nikkhah G, Vesper J, Naumann M and Volkmann J.

Pallidal deep-brain stimulation in primary generalized or segmental dystonia. N Engl J Med. 2006;355(19): 1978-90.

Lipp A, Sandroni P, Ahlskog JE, Maraganore DM, Shults CW and Low PA.

Calf venous compliance in multiple system atrophy. Am J Physiol Heart Circ Physiol. 2007 293(1): H260-5.

Lipp A, Sandroni P, Ahlskog JE, Fealey RD, Kimpinski K, Iodice V, Gehrking TL, Weigand SD, Sletten DM, Gehrking JA, Nickander KK, Singer W, Maraganore DM, Gilman S, Wenning GK, Shults CW and Low PA.

Prospective differentiation of multiple system atrophy from Parkinson disease, with and without autonomic failure. Arch Neurol. 2009;66(6): 742-50.

Schönecker T, Kupsch A, Kühn AA, Schneider GH and Hoffmann KT.

Automated Optimization of Subcortical Cerebral MR Imaging-Atlas Coregistration for Improved Postoperative Electrode Localization in Deep Brain Stimulation. AJNR Am J Neuroradiol. 2009.

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