The working group aims to uncover mechanisms of action of deep brain stimulation therapy and to translate the pathophysiological insights into future developments. Hitherto, Parkinson’ disease, essential tremor and dystonia are incurable diseases causing severe impairment in quality of life and daily activities. Deep brain stimulation is mainly used when medication fails to achieve sufficient motor symptom control. We envisage to improve efficacy and safety of stimulation and to make deep brain stimulation available for resistant symptoms, e.g. for freezing of gait.
As current focus, we strive to improve deep brain stimulation therapy for resistant gait impairment in Parkinson’s disease. We characterize disease states by electrophysiology and sensor-based measurements. The insights translate into novel therapy concepts to approach future automated, adaptive and personalized therapy delivery.
Focus of work
As major focus, the deep brain stimulation working group (Priv. Doz. Dr. med. Daniel Weiß) aims to clarify the pathophysiological basis of gait disturbances, to translate pathophysiological insights into novel therapy concepts and to recognize motor states in Parkinson’s disease based on automated sensor-techniques.
Currently, the working group coordinates a Germany-wide clinical multi-center trial for gait freezing therapy, using a novel deep brain stimulation approach of combined stimulation of the subthalamic nucleus and the substantia nigra pars reticulata (ClinTrials.gov: NCT02588144: https://clinicaltrials.gov/ct2/show/NCT02588144).
Furthermore, in our MOVE projects we characterize electrophysiological and biomechanic correlates of freezing of gait (DFG; WE5375/1-1; WE5375/1-3).
Marlieke Scholten investigates neuromuscular network mechanisms of freezing of gait in patients with Parkinson’s disease by entirely mobile EMG/EEG measurements. Our main interest consists in characterization of pathological network mechanisms before and during freezing of gait episodes. We aim to translate these insights into pathophysiology-based therapeutic strategies.
Furthermore, the working group aims to predict effects of deep brain stimulation therapy on freezing of gait by sensor-based analysis at a stage of preoperative therapy stratification (Idil Hanci). In our StepPilot-project, we cooperate with neuro-engineers to implement sensor technologies in order to predict freezing of gait. This enables adaptive cueing in order to prevent and treat freezing episodes.
Dr. Lorenzo Pietro Roncoroni applies sensor-based detection of motor states in idiopathic Parkinson’s disease. The actual goal refers to automated detection of the patient’s motor state in time, e.g. if a patient is currently hypo- or hyperkinetic. So-called wearables are already available outside clinical applications (e.g. as step counters or fitness wristbands), and yield overwhelming potential to support neurologic therapy in future. Similarly, objective motor state classification may assist clinical routine care, e.g. when adapting individual medication or stimulation schemes to therapy along sensor-based motor profiles. Real-time classification of the motor state may even enable adaptive and personalized therapeutic strategies.
Our work group’s research issues are supported by numerous doctoral candidates. Specialized nursing support is given by Mr. Jürgen Kronmüller.
Medical doctoral theses (ongoing)
Idil Hanci: „Prediction of freezing of gait outcome from standard subthalamic nucleus stimulation “
cand. med. Johannes Klemt: „Modulation of neuromuscular locomotor integration with deep brain stimulation“
cand. med. Anna Schoellmann: „Modulation of neuromuscular synchronisation and cortical activity with transcranial direct current stimulation in patients with idiopathic Parkinson’s disease”
cand. med. Melanie Heilbronn: „Modulation of anticipatory postural adjustments with deep brain stimulation of the subthalamic nucleus and substantia nigra pars reticulata“
Margarete Walach: „Combined interleaving stimulation of the subthalamic nucleus and the substantia nigra pars reticulata for resistant gait disturbances in Parkinson’s disease“
Sonja Herrmann: „Genetic biomarkers to predict outcomes from deep brain stimulation therapy“
Medical doctoral theses (completed)
Dr. med. Rosa Klotz: „Cortical motor network modulation: Common mechanisms parallel efficient motor integration in implicit motor learning in healthy subjects and subthalamic neurostimulation in Parkinson’s disease“
SAMTIPS: Exploratory study to capture motor transitions in idiopathic Parkinson’s disease with sensor techniques.
BIOFREEZE-PARK:Evaluation of electrophysiological biomarkers for freezing of upper limb movement in Parkinson’s disease.
Early Stim, post-study follow up: Multi-center long-term observation of deep brain stimulation in patients with Parkinson’s disease and beginning motor fluctuations.
MOVE-PARK: Evaluation of cortical and cortico-muscular network activity in mobile patients with Parkinson’s disease and gait disturbances.
TDCS-PARK: Cortical stimulation for modulation of cortico-muscular network activity in Parkinson’s disease.
STN+SNr IIb: Multi-center randomized clinical study on the efficacy and safety of deep brain stimulation of STN and SNr on otherwise resistant freezing of gait in Parkinson’s disease.
Balance: Health-related quality of life in LCIG-treated and LCIG-amenable Patients with continued oral dopaminergic therapy. Non-interventional, multicentre observational trial for levodopa-carbidopa gel (LCIG) in Germany
APA-PARK: Modulation of anticipatory postural adjustments with different deep brain stimulation paradigms.
PREDICT-GAIT PD: Prediction of gait outcome from deep brain stimulation therapy.
StepPilot: Development of a sensor-based device for automated prediction and detection of freezing of gait, including adaptive cueing.
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Scholten, M., Govindan R.B., Braun, C., Bloem, B., Plewnia, C., Krüger, R., Gharabaghi, A., Weiss, D. Cortical correlates of susceptibility to upper limb freezing in Parkinson’s disease. Clin Neurophysiol 2016; 127(6):2386-93
Scholten, M., Klotz, R., Plewnia, C., Wächter, T., Mielke, C., Bloem, B., Braun, C., Ziemann, U., Govindan, R.B., Gharabaghi, A., Krüger, R., Weiss, D. Neuromuscular correlates of subthalamic stimulation and upper limb freezing in Parkinson’s disease. Clin Neurophysiol 2016: 127(1):610-20
Weiss, D., Mielke, C., Wächter, T., Liscic, R.M., Scholten, M., Plewnia, C., Gharabaghi, A., Krüger, R. Long-term outcome of deep brain stimulation in three patients with Fragile X-associated tremor/ataxia syndrome. Park Rel Disord 2015; 21(3): 310-3
Weiss, D., Klotz, R., Govindan, R.B., Scholten, M., Naros, G., Murguialday, A.R., Bunjes, F., Meisner, C., Plewnia, C., Krüger, R., Gharabaghi, A. Subthalamic stimulation modulates cortical network activity and synchronization in Parkinson’s disease. Brain 2015; 138:679-93
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Weiss, D., Wächter, T., Breit, S., Jacob, S.N., Pomper, J.K., Asmus, F., Valls-Solé, J., Plewnia, C., Gasser, T., Gharabaghi, A., Krüger, R., Involuntary eyelid closure after STN-DBS: evidence for different pathophysiological entities. J Neurol Neurosurg Psychiatry 2010; 81(9):1002-7
Deutsche Forschungsgemeinschaft (WE5375/1-1; WE5375/1-3)