Nigral stimulation for resistant axial motor impairment in Parkinson’s disease? A randomized controlled trial

Weiß, Daniel; Walach, Margarete Teresa; Meisner, Christoph; Fritz, M.M.; Scholten, Marlieke; Breit, Sorin; Plewnia, Christian; Bender, Benjamín; Gharabaghi, Alireza; Wächter, Tobias; Krüger, Rejko

doi:10.1093/brain/awt122

Cited by 179 publications

(184 citation statements)

References 54 publications

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“…PD patients were included in the post-operative chronic follow-up period, if already pre-existing electrode contacts of the quadripolar lead (electrode model 3389, Medtronic, Minneapolis, MN, USA) reached both the STN and the caudal border zone of the STN and SNr (20). The pre-operative targeting occurred under routine clinical care (not subject to this study protocol) and primarily focused on the STN without specifically targeting the SNr.…”

Section: Materials and Methods Subjectsmentioning

confidence: 99%

“…Experimenters and patients were not blinded to the stimulation condition. Each stimulation condition was active for at least 20 min prior to the recordings in order to achieve sufficient efficacy of stimulation and in order to limit potential carry-over effects of the previous therapeutic condition in line with previous standards (20,25). As recordings took place in medication off, we did not consider longer off periods for washout, which would have led to patient discomfort.…”

Section: Experimental Setup and Paradigmmentioning

confidence: 99%

“…Pulse width and frequency of the SNr stimulation were similar to the individual STN stimulation. We did not adjust SNr to STN amplitudes, since stimulation of nigral contacts (i) generally has a lower threshold for capsular side effects and (ii) lower SNr amplitudes (as compared to STN amplitudes) were clinically effective in our previous work (20). In this sense, we designed the stimulation conditions close to current clinical reprogramming standards on subthalamic and nigral stimulation.…”

Section: Experimental Setup and Paradigmmentioning

confidence: 99%

“…There is clinical evidence that STN-DBS modulates locomotor integration and FOG (18,19). A recent trial observed that adding nigral stimulation to the conventional STN-DBS may improve gait in PD freezers (20). Efficacy of STN + SNr on FOG as primary clinical outcome measure is under investigation in a multicenter randomized controlled trial (clinicaltrials.gov NCT02588144).…”

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Effects of subthalamic and nigral stimulation on gait kinematics in Parkinson's disease

et al. 2017

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Conventional subthalamic deep brain stimulation for Parkinson's disease (PD) presumably modulates the spatial component of gait. However, temporal dysregulation of gait is one of the factors that is tightly associated with freezing of gait (FOG). Temporal locomotor integration may be modulated differentially at distinct levels of the basal ganglia. Owing to its specific descending brainstem projections, stimulation of the substantia nigra pars reticulata (SNr) area might modulate spatial and temporal parameters of gait differentially compared to standard subthalamic nucleus (STN) stimulation. Here, we aimed to characterize the differential effect of STN or SNr stimulation on kinematic gait parameters. We analyzed biomechanical parameters during unconstrained over ground walking in 12 PD patients with subthalamic deep brain stimulation and FOG. Patients performed walking in three therapeutic conditions: (i) Off stimulation, (ii) STN stimulation (alone), and (iii) SNr stimulation (alone). SNr stimulation was achieved by stimulating the most caudal contact of the electrode. We recorded gait using three sensors (each containing a tri-axial accelerometer, gyroscope, and magnetometer) attached on both left and right ankle, and to the lumbar spine. STN stimulation improved both the spatial features (stride length, stride length variability) and the temporal parameters of gait. SNr stimulation improved temporal parameters of gait (swing time asymmetry). Correlation analysis suggested that patients with more medial localization of the SNr contact associated with a stronger regularization of gait. These results suggest that SNr stimulation might support temporal regularization of gait integration.

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Section: Materials and Methods Subjectsmentioning

confidence: 99%

Section: Experimental Setup and Paradigmmentioning

confidence: 99%

Section: Experimental Setup and Paradigmmentioning

confidence: 99%

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Effects of subthalamic and nigral stimulation on gait kinematics in Parkinson's disease

et al. 2017

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“…These patients were withdrawn from dopaminergic medication overnight. Prior to the StimOFF condition, stimulation was discontinued for at least 30 minutes which is sufficient to limit clinical carry-over (Cooper et al 2013;Weiss et al 2013). …”

Section: Test Conditionsmentioning

confidence: 99%

The subthalamic nucleus modulates the early phase of probabilistic classification learning

et al. 2014

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Previous models proposed that the subthalamic nucleus (STN) is critical in the early phase of skill acquisition. We hypothesized that subthalamic deep brain stimulation modulates the learning curve in early classification learning. Thirteen idiopathic Parkinson's disease patients (iPD) with subthalamic deep brain stimulation (STN-DBS), 9 medically treated iPD, and 21 age-matched healthy controls were tested with a probabilistic classification task. STN-DBS patients were tested with stimulation OFF and ON, and medically treated patients with medication OFF and ON, respectively. Performance and reaction time were analyzed on the first 100 consecutive trials as early learning phase. Moreover, data were separated for low and high-probability patterns, and more differentiated strategy analyses were used. The major finding was a significant modulation of the learning curve in DBS patients with stimulation ON: although overall learning was similar to healthy controls, only the stimulation ON group showed a transient significant performance dip from trials '41-60' that rapidly recovered. Further analysis indicated that this might be paralleled by a modulation of the learning strategy, particularly on the high-probability patterns. The reaction time was unchanged during the dip. Our study supports that the STN serves as a relay in early classification learning and directs attention toward unacquainted content. The STN might play a role in balancing the short-term success against strategy optimization for improved long-term outcome. AbstractPrevious models proposed that the subthalamic nucleus (STN) is critical in the early phase of skill acquisition. We hypothesized that subthalamic deep brain stimulation modulates the learning curve in early classification learning. 13 idiopathic Parkinson's disease patients (iPD) with subthalamic deep brain stimulation (STN-DBS), 9 medically treated iPD, and 21 age-matched healthy controls were tested with a probabilistic classification task. STN-DBS patients were tested with stimulation OFF and ON, medically treated patients with medication OFF and ON, respectively. Performance and reaction time were analyzed on the first 100 consecutive trials as early learning phase. Moreover, data were separated for low and high probability patterns, and more differentiated strategy analyses were used.The major finding was a significant modulation of the learning curve in DBS patients with stimulation ON: although overall learning was similar to healthy controls, only the stimulation ON group showed a transient significant performance dip from trials '41-60' that rapidly recovered. Further analysis indicated that this might be paralleled by a modulation of the learning strategy, particularly on the high probability patterns. The reaction time was unchanged during the dip. Our study supports that the STN serves as a relay in early classification learning and directs attention towards unacquainted content.The STN might play a role in balancing the short-term success against strategy optimi...

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Impact of simultaneous subthalamic and nigral stimulation on dysphagia in Parkinson’s disease

Pflug

Nienstedt

Gulberti

et al. 2020

Ann Clin Transl Neurol

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Objectives: Dysphagia is a frequent and highly relevant symptom in Parkinson's disease (PD) due to high associated morbidity and mortality. To compare the effect of simultaneous stimulation of the subthalamic nucleus (STN) and substantia nigra (SNr) with conventional STN-stimulation on swallowing function in Parkinson's disease. Methods: In this controlled, randomized, doubleblind, cross-over clinical trial, 15 PD patients were assessed with DBS switched off (STIM OFF), STN-DBS, STN + SNr-DBS. Patients and 32 age-matched healthy controls were examined clinically and by flexible-endoscopic evaluation of swallowing (FEES) to evaluate the swallowing function. The primary endpoint was the assessment of residues, secondary endpoints were penetration/ aspiration, leakage, retained pharyngeal secretions, drooling, and assessments of the patient's self-perception of swallowing on a visual analog scale. Results: Compared with healthy controls PD patients showed significantly more pharyngeal residues in STIM OFF and both DBS modes. Residues or aspiration events were found in 80% of the patients under STN-stimulation. Simultaneous STN + SNr-stimulation had no additional positive effect on objective dysphagia and self-reported swallowing function compared to STN-DBS. Interpretation: Simultaneous STN + SNr-stimulation seems to have no additional beneficial effects on dysphagia when compared with conventional STN-stimulation, but did not deteriorate the swallowing function. If STN + SNr-stimulation is planned to be applied for the improvement of axial symptoms and gait disorders in PD patients, it can be considered safe in terms of dysphagia. 628

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Nigral stimulation for resistant axial motor impairment in Parkinson’s disease? A randomized controlled trial

Cited by 179 publications

References 54 publications

Effects of subthalamic and nigral stimulation on gait kinematics in Parkinson's disease

Effects of subthalamic and nigral stimulation on gait kinematics in Parkinson's disease

The subthalamic nucleus modulates the early phase of probabilistic classification learning

Impact of simultaneous subthalamic and nigral stimulation on dysphagia in Parkinson’s disease

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