Optimizing Deep Brain Stimulation for Movement Disorders –
from preoperative target planning to postoperative programming and everyday patient care
Als Satellit des Deutschen Kongresses für Parkinson und Bewegungsstörungen 2024 veranstaltet die Arbeitsgemeinschaft Tiefe Hirnstimulation e.V. am 24.04.2024 ein Symposium, zu dem Sie herzlich eingeladen sind.
Ort
Universitätsmedizin Rostock
Klinik und Poliklinik für Neurologie
Hörsaal im Zentrum für Nervenheilkunde
Gehlsheimer Str. 20, D-18147 Rostock
Zeit
Mittwoch, 24. April 2024, 14:00– 19:00 Uhr
Get together / Abendessen 20 Uhr
Braugasthaus "Zum Alten Fritz"
Organisationskommitee
René Reese, Rostock
Thomas Köglsperger, München
Carsten Buhmann, Hamburg
Die Tiefe Hirnstimulation ist eine hocheffektive Therapie, für deren Gelingen eine spezialisierte multidisziplinäre und multiprofessionelle Zusammenarbeit von der präoperativen Auswahl geeigneter Patient:innen bis zur (ambulanten) Langzeitversorgung notwendig ist. Für die postoperative Programmierung der Tiefen Hirnstimulation stehen derzeit verschiedene technische Methoden und Systeme zur Verfügung, die die klinische Arbeit erleichtern sollen und für unsere Patient:innen eine individualisierte Therapie versprechen. Welches System ist für wen geeignet? Erleichtern diese Techniken den klinischen Alltag? Was ist möglicherweise alternativ oder zusätzlich notwendig? Diesen und weiteren Fragen zur postoperativen Programmierung wollen wir in einer offenen PRO / CON – Diskussion nachgehen.
Die derzeitigen Strukturen der Akut- und Langzeitversorgung von Patient:innen mit einer Tiefen Hirnstimulation werden wir in einer Podiumsdiskussion multidisziplinär und multiprofessionell erörtern. Wie ist der Stand der klinischen Versorgung in den einzelnen Strukturbereichen? Was brauchen wir zur Verbesserung der Versorgungslandschaft? Worin bestehen derzeit (noch) Herausforderungen und wie können wir diesen begegnen?
Kurze Beiträge in Form von eingereichten Postern und Freien Vorträgen sollen zudem Einblicke zu aktueller Forschungsaktivität auf dem Gebiet der Tiefen Hirnstimulation geben.
Wir hoffen, mit dem Programm ihr Interesse zu wecken und freuen uns schon jetzt, sie in Rostock zu begrüßen!
Für den Vorstand der Arbeitsgemeinschaft Tiefe Hirnstimulation
René Reese Thomas Köglsperger Carsten Buhmann
Programm und Zeitplan (vorläufig)
14:00 - 14:05 | Begrüßung | |
14:05 - 15:35 | Key Note Lecture
| |
15:35 - 16:20 | Pause und Posterbegehung | |
16:20 - 17:20 | Lightning Talks / Freie Vorträge
| |
17:20 - 17:50 | Pause und Posterbegehung | |
17:50 - 19:20 | Podiumsdiskussion
| |
19:20 | Verabschiedung und Taxitransfer zum Restaurant | |
ab 20:00 | Get together / Abendessen im Braugasthaus "Zum Alten Fritz", Warnowufer Rostock |
Abstracttexte
Autor:innen: Charlotte Büttner und Prof. Dr. med. Karsten Witt, Abteilung für Neurologie, Carl-von-Ossietzky Universität Oldenburg
Während sich die Tiefe Hirnstimulation (THS) bereits im klinischen Alltag etablieren konnte, gibt es in Deutschland bisher keinen einheitlichen Standard für die neuropsychologische präoperative Diagnostik. In den THS-Zentren haben sich verschiedene Vorgehen etabliert. Wir haben im vergangenen Jahr die unterschiedlichen neuropsychologischen Routinen freiwillig teilnehmender Mitgliedszentren der AG-THS gesammelt und nebeneinandergestellt. Gerne möchten wir diese Ergebnisse präsentieren und diskutieren. Das Ziel ist es, einen Standard zu erarbeiten und diesen z.B. zu einem Konsensus zusammenzufassen und eine Empfehlung für die klinische Praxis zu entwickeln. Diese soll sowohl aus den bereits vorliegenden mehrheitsbasierten Standards der THS-Zentren, als auch aus evidenzbasierten Überlegungen entstehen und eine Batterie aus Tests bieten, die je nach Fragestellung und Kapazitäten angepasst werden kann.
Autor:innen: Christina van der Linden (1), Thea Berger (1), Till A. Dembek (1), Gregor A. Brandt (1), Joshua N. Strelow (1, 2), Juan Carlos Baldermann (1,3), Hannah Jergas, Veerle Visser-Vandewalle (1), Michael T. Barbe (2) und Jan Niklas Petry-Schmelzer (1), 1: Klinik und Poliklinik für Neurologie, Uniklinik Köln und Medizinische Fakultät der Universität zu Köln, 2: Klinik für Stereotaxie und Funktionelle Neurochirurgie, Uniklinik Köln und Medizinische Fakultät der Universität zu Köln, 3: Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum Freiburg
Hintergrund: Bildgebungsgestützte Strategien zur zielgerichteten THS-Programmierung gewinnen zunehmend an Bedeutung. Für das Zielsymptom Tremor bei Essentiellem Tremor (ET) und Parkinson-Krankheit (PK) fehlen hierzu klar definierte Paradigmen. Retrospektive Studien deuten darauf hin, dass die Überlappung von dentato-rubro-thalamischem Trakt (DRTT) und Stromfeld (volume of tissue activated, VTA) den Stimulationseffekt prädizieren könnte.
Methode: Der tremorsuppressive Stimulationseffekt wurde bei 16 Patient*innen mit ET (n = 28 Hemisphären mit kontralateralem Tremor) und 24 Patient*innen mit PK (n = 29 Hemisphären mit kontralateralem Tremor) nach Implantation direktionaler THS-Elektroden in VIM/PSA (ET) bzw. STN (PK) mittels monopolarer Testung evaluiert und durch Akzelerometrie objektiviert. Der Effekt des klinisch effektivsten Kontaktes wurde mit dem Effekt des Kontaktes mit der größten Überlappung von VTA und DRTT, ermittelt durch individuelle Traktographie, verglichen.
Ergebnisse: Die Tremorkontrolle durch den bildgebungsbasiert ausgewählten Kontakt war sowohl für ET (mediane Differenz klinische Auswahl vs. bildgebungsbasierte Auswahl -8 %, 95 % KI [-11.5, -3.5]) als auch für PK (mediane Differenz -10%; 95 % KI [-20, -4]) der Tremorkontrolle des klinisch ausgewählten Kontaktes nicht signifikant unterlegen (Nicht-Unterlegenheitsgrenze 20%).
Schlussfolgerung: Diese Studie liefert Klasse-1-Evidenz, dass die Überlappung des Stromfeldes mit dem individuellen DRTT ein geeigneter Marker für bildgebungsgestützte THS-Programmierung bei Parkinson- und Essentiellem Tremor ist. Die Ergebnisse müssen im Langzeitverlauf überprüft werden.
Autor:innen: Florian Lange (a), Jens Volkmann (a), und Martin M Reich (a) for this abstract, Philipp Mahlknecht (b), Joachim K Krauss (c), Andrea A Kühn (d) und Günther Deuschl (e) for the multicenter cohort, a: Department of Neurology, University of Würzburg, Germany, b: Department of Neurology, Innsbruck Medical University, Austria, c: Department of Neurosurgery, MHH Hannover, Germany, d: Movement Disorders and Neuromodulation Unit, Department of Neurology, Charite-Universitätsmedizin Berlin, Germany, e: Department of Neurology, University Kiel, Germany
Introduction: Despite the efficacy of pallidal deep brain stimulation (DBS) in treating dystonia, many patients experience stimulation-induced bradykinesia or other PD-like motor signs as side effects. The pathophysiology and risk factors of developing PD-like motor features with effective, antidystonic pallidal neurostimulation remain enigmatic.
Methods: The study employed both retrospective and prospective approaches to examine stimulation-induced bradykinesia in dystonia patients treated with pallidal neurostimulation (GPi target). The retrospective cohort consisted of 86 adults, whereas the prospective cohort had 11 patients. Bradykinesia was assessed clinically by respective UPDRS-III items and hand movements recorded during pre- and postoperative video assessments were kinematically analyzed using Mediapipe machine-learning toolbox. Statistical analyses, including Spearman correlations and Generalized Linear Models, were employed to identify predictors and correlations related to stimulation-induced bradykinesia. Spatial analysis was conducted to explore the role of active contact positioning in inducing the side effect.
Results: We found that gender, age of symptom onset, disease duration, and stimulation pulse width are key determinants of stimulation-induced bradykinesia. Using two distinct cohorts, our findings revealed consistent trends. A significantly higher prevalence of bradykinesia was observed in females (77.8%) compared to males (42.9%, χ² = 6.984, p < 0.008). There was a significant positive correlation between age of symptom onset and bradykinesia severity (rho = 0.326, p = 0.017), whereas a negative correlation was noted between disease duration and severity of the condition (rho = -0.366, p = 0.007). Notably, stimulation pulse width was strongly associated with the severity of bradykinesia (B = 0.005, SE = 0.001, β = 0.556, p < 0.001). No significant associations were found with other variables like stimulation amplitude, frequency, and motor symptom control response. Prospective kinematic assessments in 11 patients showed that there is a detrimental effect of GPi-DBS regarding the velocity and precision of movements in 9/11 patients, indicating a stimulation-induced PD-like symptoms. Active contact location location (e.g. the proximity to the internal capsule or location within subregions of GPi or GPe) did not explain the occurrence of stimulation induced bradykinesia.
Conclusion: In conclusion, our study highlights female sex, older age at onset of dystonia, shorter disease duration, and a larger DBS pulse width as risk factors for stimulation-induced bradykinesia in dystonia patients. Reducing stimulation acutely improved movement speed and amplitude in our prospective analysis. Interestingly, despite high prevalence, stimulation-induced bradykinesia didn't correlate with reduced quality of life.
Autor:innen: Ghadir Abbas, Hao Ding, Tanmoy Sil, Shawn Hiew, Pavel Navratíl, Muthuraman Muthuraman, Jens Volkmann und Martin Reich, Department of Neurology, University Hospital and Julius Maximilian University Würzburg
Introduction: Deep Brain Stimulation (DBS) is a recognized Parkinson's Disease treatment, but it may cause cognitive decline. Our prior research linked enhanced connectivity from stimulation sites to cognitive decline and identified connections to the anterior cingulate, caudate nucleus, hippocampus, and cerebellum. This study investigates the relationship between cognitive decline following STN-DBS and other possible contributing factors like metabolic activity, neurotransmitter interplay, and brain oscillations.
Methods: We analyzed two STN-DBS stimulation settings in 10 Parkinson’s patients. Volume of Tissue Activated (VTA) models assessed cognitive decline inducing settings and non-cognitive sideeffect settings, both with equal motor benefits. We derived whole-brain connectivity profiles from these VTAs using normative resting-state fMRI data (n=1000) and estimated first-neuron connectivity with the LEAD-DBS toolbox and MGH-32 connectome. We used the Neuromaps Toolbox for similarity analysis with metabolic activity, neurotransmitter distribution, and brain oscillation maps.
Results: The Neuromaps analysis showed a significant correlation between cognitive declineinducing VTAs' first-neuron connections and the MEG-theta oscillation map (r = 0.267, p = 0.04). Additionally, negative correlations were observed with the AChM1 receptor (r = - 0.245, p = 0.04), and GABAa receptor (r = -0.254, p = 0.04), specifically for VTAs inducing cognitive decline.
Conclusion: This study demonstrates significant correlations between cognitive decline-inducing stimulation areas, theta oscillations, and ACh M1/GABAa receptor distributions, highlighting the influence of neurotransmitter systems and neural oscillations in cognitive decline post STN-DBS.
Autor:innen: Gregor A. Brandt, Vasilija Stopic, Christina van der Linden, Joshua N. Strelow, Jan N. Petry-Schmelzer, Juan Carlos Baldermann, Veerle Visser-Vandewalle, Gereon R. Fink, Michael T. Barbe und Till A. Dembek
Hintergrund: Das herkömmliche Vorgehen bei der Programmierung der tiefen Hirnstimulation (THS) im Nucleus subthalamicus (STN) mit zeitaufwändiger Akutaustestung und iterativen Anpassungen über Wochen bedarf grundlegender Verbesserung um optimale Therapieergebnisse zu erreichen.
Methoden: Mittels individueller Bildgebung wurden retrospektiv für 28 Parkinson-Patient:innen mit direktionaler STN-THS mittels zweier visueller und zweier algorithmischer Strategien jeweils eine Kontaktauswahl getroffen und mit der klinischen Kontaktauswahl anhand eines standardisierter Einzelkontaktaustestung verglichen. Die visuelle Kontaktauswahl mithilfe einer kommerziellen Software wurde anhand zwei verschiedener Strategien (posterodorsaler STN bzw. posterodorsaler STN + 10-25% dorsale weiße Substanz) definiert. Die algorithmische Kontaktauswahl nutzte entweder den atlas-definierten motor-STN bzw. einen probabilistischen Sweet-Spot als Zielstruktur (Dembek, T. A. et al. Probabilistic sweet spots predict motor outcome for deep brain stimulation in Parkinson disease. Annals of Neurology 86, 527–538 (2019)). Quantitative Ähnlichkeitsindizies (Dice-Koeffizienten) zwischen den chronischen Stimulationseinstellungen und den verschiedenen Kontaktauswahlen wurden mit der Verbesserung der motorischen Symptomatik nach 12 Monaten (MED OFF/ STIM ON) korreliert.
Ergebnisse: Für eine der beiden visuellen Strategien (posterodorsaler STN) korrelierte die chronische Symptomkontrolle hoch signifikant mit den entsprechenden Dice-Koeffizienten (Rho = 0.36, p = 0.007). Ähnliche Korrelationen zeigten sich nicht für die klinische Kontaktauswahl oder die anderen untersuchten Strategien.
Schlussfolgerung: Unsere Ergebnisse deuten darauf hin, dass eine anatomisch informierte Kontaktauswahl mit guter langfristiger Symptomkontrolle in Zusammenhang gebracht werden kann. Dieser Zusammenhang hängt von der gewählten Herangehensweise ab.
Autor:innen: Jing Dong (1), Sophia Peschke (1), Angelina Kirchner (1), Elisabeth Kauffmann (1) und Thomas Köglsperger (1+2), 1: Department of Neurology, Ludwig Maximilian University, Munich, Germany, 2: Department of Translational Brain Research, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
Objective: To determine if patient’s subjective rating can be a feedback signal for DBS programming.
Background: STN DBS is an effective treatment for the motor symptoms of Parkinson’s disease (PD), and has shown great effectiveness in relieving tremor, rigidity, and bradykinesia [1]. Correct placement of electrodes and individualized, precise postoperative programming directly affect the surgical outcome of DBS [2,3]. Once the electrodes are implanted, adjusting the stimulation parameters is the only way to optimize the efficacy of DBS. Numerous studies have demonstrated that fine-tuning DBS parameters enhances patient outcomes and reduces the need for unnecessary lead revisions [4]. As the DBS programming process can require a significant investment of time and human resources, it is important to it is particularly important to develop an innovative method to adjust stimulus parameters and lead configurations quickly, accurately, and efficiently.
Methods: 262 settings from 11 STN-DBS patients were retrospectively included in this study. We tested the utility of patients' subjective visual analogue scale (VAS) scores for real-time adjustment of DBS parameters and mapped into standard space, sweet spots mapping and connectivity analyses for best clinical outcomes (highest VAS) were carried out by voxelwise and nonparametric permutation statistics. Another independent cohort (7 patients, 227 settings) was used to cross validation if the sweet spot and connectivity profile could predict acute motor outcome.
Results: The highest VAS values segregated to the dorsolateral STN and overlapped almost entirely with published sweet spots derived from clinical data. Fibers tracts originating from supplementary motor area (SMA) and primary motor cortex (M1) to the STN associated with higher VAS values across STN DBS subjects, the connectivity profiles derived from one patient cohort can predict clinical outcome in an independent cohort and the effectiveness was validated in leave-one-cohort out (R = 0.28, p＜0.001) cross-validation paradigms.
Conclusions: Although further research would be required to access the effectiveness of VAS-based DBS programming through multi-centre and long-term studies, our results supported the investigation of patient’s subjective rating as a valid feedback signal for individualized DBS setting.
Reference:
[1] Krauss, J. K., Lipsman, N., Aziz, T., Boutet, A., Brown, P., Chang, J. W., Davidson, B., Grill, W. M., Hariz, M. I., Horn, A., Schulder, M., Mammis, A., Tass, P. A., Volkmann, J., & Lozano, A. M. (2021). Technology of deep brain stimulation: current status and future directions. Nature reviews. Neurology, 17(2), 75–87. https://doi.org/10.1038/s41582-020-00426-z
[2] Hell F, Palleis C, Mehrkens JH, Koeglsperger T, Bötzel K. Deep Brain Stimulation Programming 2.0: Future Perspectives for Target Identification and Adaptive Closed Loop Stimulation. Front Neurol 2019;10:314. https://doi.org/10.3389/fneur.2019.00314.
[3] Koeglsperger T, Palleis C, Hell F, Mehrkens JH, Bötzel K. Deep Brain Stimulation Programming for Movement Disorders: Current Concepts and Evidence-Based Strategies. Front Neurol 2019;10:410. https://doi.org/10.3389/fneur.2019.00410.
[4] Okun MS, Tagliati M, Pourfar M, Fernandez HH, Rodriguez RL, Alterman RL, et al. Management of referred deep brain stimulation failures: a retrospective analysis from 2 movement disorders centers. Archives of Neurology 2005;62:1250–5. https://doi.org/10.1001/archneur.62.8.noc40425.
Autor:innen: Hagena K, Gülke E, Paschen S, Domschikowski M, Buhmann C, Juárez Paz LM und Pötter-Nerger M
Introduction: Advances in deep-brain stimulation (DBS), like directional leads and multiple input current control, necessitate new programming strategies to reduce clinicians' programming burden and fully leverage technical capabilities. This study evaluates a semi-automatic closed-loop programming algorithm based on composite clinical scores.
Methods: In this two-center, randomized, double-blind, crossover study we compared Algorithm-guided programming (AgP) to standard of care programming (SoC) Parkinson’s disease subjects with bilateral directional-lead STN-DBS. AgP optimized stimulation settings using a weighted combination of sensor- and clinician-assessed symptoms.
Results: Compared to therapy absence, AgP and SoC DBS settings improved significantly the total Unified Parkinson’s Disease Rating Scale III scores. Despite their similar clinical results, AgP and SoC DBS settings differed substantially. Individual motor symptoms responded differently to specific AgP DBS settings. During the continuous development of the AgP versions, programming steps and time burden could be reduced with excellent clinical benefit.
Discussion: Algorithm-guided programming offers a viable alternative to standard monopolar review, achieving similar clinical results with a potentially reduced programming burden, while covering the entire stimulation space.
Autor:innen: Kai Grimm (1*), Alessandro Gulberti (1*), Wolfgang Hamel (2), Monika Pötter-Nerger (1), Carsten Buhmann (1), Christian K.E. Moll (3) und Simone Zittel (1), 1: Department of Neurology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany, 2: Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany, 3: Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
* Those authors contributed equally to the work.
Background: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) represents a treatment option for Meige syndrome. Potential side effects include bradykinesia, speech impairment, and visual disturbances. Mood changes following GPi-DBS are uncommon and, if present, often beneficial.
Methods: We present a patient with Meige syndrome with severe GPi-DBS-induced mood lability despite a 50% improvement in motor symptoms compared to pre-surgery. Systematic testing of electrode contacts was conducted, along with comparative double-blind assessments during one-week periods of verum and sham DBS. Clinical examination included standardized evaluation of motor symptoms (Burke-Fahn-Marsden Dystonia Rating Scale, BFMDRS), mood (Hospital Anxiety and Depression Scale, HADS; Visual Analog Mood Scales, VAMS), and quality of life (Craniocervical Dystonia Questionnaire, CDQ-24).
Results: Activating the second-most ventral contact of the right electrode consistently evoked sudden depressive mood swings and crying, deteriorating all negative affective scores on the VAMS. Verum GPi-DBS worsened anxiety and quality of life compared to sham, with stable scores on the HADS depression subscale and BFMDRS. 3-D electrode reconstruction, utilizing recent CT images, confirmed correct placement within the GPi.
Conclusion: Mood lability can occasionally result from GPi-DBS in Meige syndrome. This highlights the need for careful monitoring of psychological effects in these patients.
Autor:innen: Florian Lange, Jens Volkmann, Martin M Reich, Philipp Mahlknecht, Joachim K Krauss, Andrea A Kühn, Günther Deuschl
Introduction: Despite the efficacy of pallidal deep brain stimulation (DBS) in treating dystonia, many patients experience stimulation-induced bradykinesia or other PD-like motor signs as side effects. The pathophysiology and risk factors of developing PD-like motor features with effective, antidystonic pallidal neurostimulation remain enigmatic.
Methods: The study employed both retrospective and prospective approaches to examine stimulation-induced bradykinesia in dystonia patients treated with pallidal neurostimulation (GPi target). The retrospective cohort consisted of 86 adults, whereas the prospective cohort had 11 patients. Bradykinesia was assessed clinically by respective UPDRS-III items and hand movements recorded during pre- and postoperative video assessments were kinematically analyzed using Mediapipe machine-learning toolbox. Statistical analyses, including Spearman correlations and Generalized Linear Models, were employed to identify predictors and correlations related to stimulation-induced bradykinesia. Spatial analysis was conducted to explore the role of active contact positioning in inducing the side effect.
Results: We found that gender, age of symptom onset, disease duration, and stimulation pulse width are key determinants of stimulation-induced bradykinesia. Using two distinct cohorts, our findings revealed consistent trends. A significantly higher prevalence of bradykinesia was observed in females (77.8%) compared to males (42.9%, χ² = 6.984, p < 0.008). There was a significant positive correlation between age of symptom onset and bradykinesia severity (rho = 0.326, p = 0.017), whereas a negative correlation was noted between disease duration and severity of the condition (rho = -0.366, p = 0.007). Notably, stimulation pulse width was strongly associated with the severity of bradykinesia (B = 0.005, SE = 0.001, β = 0.556, p < 0.001). No significant associations were found with other variables like stimulation amplitude, frequency, and motor symptom control response.
Prospective kinematic assessments in 11 patients showed that there is a detrimental effect of GPi-DBS regarding the velocity and precision of movements in 9/11 patients, indicating a stimulation-induced PD-like symptoms. Active contact location location (e.g. the proximity to the internal capsule or location within subregions of GPi or GPe) did not explain the occurrence of stimulation induced bradykinesia.
Conclusion: In conclusion, our study highlights female sex, older age at onset of dystonia, shorter disease duration, and a larger DBS pulse width as risk factors for stimulation-induced bradykinesia in dystonia patients. Reducing stimulation acutely improved movement speed and amplitude in our prospective analysis. Interestingly, despite high prevalence, stimulation-induced bradykinesia didn't correlate with reduced quality of life.
Autor:innen: Nicoló G. Pozzi, Muthuraman Muthuraman, Thomas Musacchio, Philipp Capetian und Jens Volkmann, Neurologische Klinik des Uniklinukmus Würzburg
Background: Alterations in subthalamic neural activity are associated with motors symptoms of Parkinson’s disease (PD) and can be corrected with deep brain stimulation (STN-DBS). Mutations in GBA gene have been recently associated with a severe form of PD and poor clinical outcome after STN-DBS, thus questioning DBS application in these patients. To understand the basis of these differences, we investigated the STN neural activity of idiopathic and GBA-mutated PD.
Materials and methods: We analysed bilateral STN intraoperative microelectrode recordings of 16 PD patients with pathological GBA mutations (GBA-PD) and compared them with 27 genetic-negative PD patients (iPD). We assessed both STN oscillatory- and spike-activity, which was described as burst- or irregular-firing and investigated in term of firing rate, inter-spike interval and its coefficient of variation (CV-ISI).
Results: STN neural activity of GBA-PD differed form iPD. Spike-analysis of burst-firing neurons showed a higher firing rate and CV-ISI in GBA-PD as compared to iPD. Furthermore, STN neurons of GBA-PD showed a higher oscillatory-activity in the high-beta frequency range (21-35Hz) as compared to iPD.
Conclusion: Our findings showed that STN neural activity differs in idiopathic and GBA-mutated PD, providing first neurophysiological evidence to understand their clinical differences.
Autor:innen: Pavel Navratil (1), Hazem FE Eldebakey (1), Abdullah Elmas (1), Florian L Lange (1), Ghadir Abbas (1), Vincent J Odekerken (4), Rob MA de Bie (4), ChenCheng Zhang (2), Katsuo Kimura (3), Jonas Rothans (1), Jens Volkmann (1) und Martin M Reich (1), 1: University Hospital Wuerzburg, Department of Neurology, 2: Ruijin Hospital, Shanghai Jiao Tong University, 3: Yokohama City University, Department of Neurology, 4: Academic Medical Center, Amsterdam
Background: GPi DBS is an effective and safe therapeutic approach in patients with Parkinson´s disease (Odekerken et al. 2016). However, Sobesky et al, 2022 found a significant worsening of bradykinesia in several PD patients treated with GPi DBS, although most patients improved. The induction of bradykinesia through GPi DBS is well known in dystonia patients. (Tisch et al., 2007; Berman et al., 2009; Zauber et al., 2009; Blahak et al., 2011; Schrader et al., 2011)
Objective: Our aims were to analyse the modulation of bradykinesia in PD patients treated with GPi DBS, to identify beneficial and detrimental regions in GPi related to bradykinesia modulation and to improve electrode placement and DBS programming.
Methods: We analysed a cohort of 47 patients diagnosed with idiopathic Parkinson’s disease treated with GP DBS from tree different DBS centres. Patients with available imaging data and pre- and postoperative UPDRS III or MDS UPDRS III scores in medication off were included. We quantified bradykinesia as a sum of pre – and postoperative MDS UPDRS III items 3.4- 3.8 and the modulation of bradykinesia by GPi DBS as a difference of these sums. We used the well-established Lead DBS pipeline (Horn et al., 2019) to process the imaging data and the Lead Group toolbox (Treu et al., 2020) to perform the voxelwise statistical analysis. We created a map of most beneficial and most detrimental voxels in relation to bradykinesia modulation and verified its clinical applicability by leave one out cross validation. (Reich et al, 2019)
Results: In our cohort, we found a significant reduction of bradykinesia after GPi DBS with p = 0.025. The mean difference of the summed bradykinesia items was -1,8 ± 4,2. There was 28 patients who significantly improved and 12 patients who significantly worsened, with clinically significant change of MDS UPDRS III scores defined according to Sánches-Ferro et al, 2018. We identified a small cluster of beneficial voxels in the central posterolateral GPi and a large area of detrimental voxels extending to the posterolateral GPe and Putamen. In the LOOCV, simulating a prediction of an unseen subject, our predictive model provided estimations of the individual clinical response which was correlated with the empirical data with R = 0.34, p = 0.009.
Conclusion: Although GPi DBS effectively reduces bradykinesia on the group level, there is a significant number of patients who showed a worsening induced by GPi-DBS. Lateral stimulation fields, extending to GPe and Putamen, are related to this worsening of bradykinesia. Our voxelwise model could be used to digitally predict the clinical response and to assist DBS programming in future.
References:
Odekerken VJ, Boel JA, Schmand BA, de Haan RJ, Figee M, van den Munckhof P, Schuurman PR, de Bie RM; NSTAPS study group. GPi vs STN deep brain stimulation for Parkinson disease: Three-year follow-up. Neurology. 2016 Feb 23;86(8):755-61. doi: 10.1212/WNL.0000000000002401. Epub 2016 Jan 27. PMID: 26819458.
Tisch, S., Rothwell, J. C., Bhatia, K. P., Quinn, N., Zrinzo, L., Jahanshahi, M., ... & Limousin, P. (2007). Pallidal stimulation modifies after-effects of paired associative stimulation on motor cortex excitability in primary generalized dystonia. Experimental Neurology, 206(1), 80-85.
Berman, B. D., Starr, P. A., Marks, W. J., & Ostrem, J. L. (2009). Induction of bradykinesia with pallidal deep brain stimulation in patients with cranial-cervical dystonia. Stereotactic and Functional Neurosurgery, 87(1), 37- 44.
Zauber, S. E., Watson, N., Comella, C. L., Bakay, R. A., & Metman, L. V. (2009). Stimulation-induced parkinsonism after posteroventral deep brain stimulation of the globus pallidus internus for craniocervical dystonia. Journal of Neurosurgery, 110(2), 229-233.
Blahak, C., Capelle, H. H., Baezner, H., Kinfe, T. M., Hennerici, M. G., & Krauss, J. K. (2011). Micrographia induced by pallidal DBS for segmental dystonia: A subtle sign of hypokinesia? Journal of Neural Transmission, 118(4), 549-553.
Schrader, C., Capelle, H. H., Kinfe, T. M., Blahak, C., Bäzner, H., Lütjens, G., ... & Krauss, J. K. (2011). GPiDBS may induce a hypokinetic gait disorder with freezing of gait in patients with dystonia. Neurology, 77(5), 483-488.
Horn, A., Li, N., Dembek, T. A., Kappel, A., Boulay, C., Ewert, S., Tietze, A., Husch, A., Perera, T., Neumann, W. J., Reisert, M., Si, H., Oostenveld, R., Rorden, C., Yeh, F.C.
Autor:innen: Dr. P. Pawlakowitsch¹, Prof. J. Volkmann¹, Prof. C. Matthies² und Dr. P. Capetian¹, ¹University Hospital Würzburg, Department of Neurology, ²University Hospital Würzburg, Department of Neurosurgery
Background: New deep brain stimulation (DBS) devices facilitate the recording of oscillations of local field potentials (LFP) in the Nucleus ventralis intermedius (VIM) in patients with essential tremor. However, the role of VIM-LFP-oscillations in essential tremor and the impact for guiding DBS programming remains unclear.
Objective: To investigate the interplay between VIM-LFP-beta-oscillations, DBS and essential tremor.
Materials and methods: VIM-LFP-beta oscillations were recorded bilaterally in two patients with essential tremor 18 months after implantation of a Medtronic Percept device. The VIM-LFP-beta-oscillations at rest during a stimulation-off state were qualitatively compared with the VIM-LFP-beta oscillations at rest during a gradual increase in stimulation and then correlated with tremor severity.
Results: Under the stimulation-off condition at rest, one patient showed a peak in the low beta frequency band in one VIM, while the other patient showed a peak in beta band in both VIMs. When stimulation was initiated, a gradual increase in stimulation intensity led to a decrease in beta power and a clinical reduction in tremor severity. After switching off the DBS, the VIM-LFP-beta-oscillations returned to baseline as did the tremor.
Conclusion: Further studies are needed to verify these results and to investigate whether VIM-LFP-Beta-oscillations could be a reliable biomarker in essential tremor.
Autor:innen: Patrick Fricke MD, Cordula Matthies MD, Vera Nickl MD, Martin M Reich MD, Robert C Nickl MD
Objective: Deep Brain Stimulation (DBS) is an established treatment modality for various movement disorders and psychiatric conditions. The effectiveness of DBS largely hinges on the precise placement of electrode leads. In Parkinson's Disease (PD), for example, optimal stimulation sites are identified within the dorsolateral subthalamic nucleus. However, inaccuracies in electrode positioning can lead to reduced treatment efficacy and adverse side effects. This study aims to compare the accuracy of electrode placement in bilateral DBS versus a four-lead DBS session, correlating the outcomes with clinical effectiveness.
Methods: 52 patients with 128 leads, (40 patients in the bilateral group with 80 leads & 12 four-lead group with 48 leads) who received DBS at the University Hospital of Wuerzburg between 2013 and 2019 were reviewed. Preoperative planning and postoperative imaging (MRI and CT scans) were reviewed to assess lead placement accuracy for centrally implanted trajectories. Clinical outcomes, surgical sequelae, and stimulation parameters were evaluated through patient records.
Results: The bilateral group exhibited a mean radial deviation of 1.40 mm from the planned trajectory, with a significant difference in accuracy between the first and second implanted leads. In the four-lead group, while there was an increasing trend in deviation between the first and the fourth electrode, it was not statistically significant. Brain shift, particularly due to cerebro-spinal fluid (CSF) leakage, was identified as a primary factor affecting lead placement accuracy. No significant correlations were found between lead displacement and clinical outcomes, including motor function and stimulation parameters.
Conclusions: This study contributes novel insights into the complexities of implanting multiple leads in a single DBS session. It highlights the importance of minimizing brain shifts during surgery to improve lead placement accuracy. The findings recommend prioritizing the implantation of the most clinically significant lead first, given the observed decrease in placement accuracy for subsequent leads.
Autor:innen: Slavnov, A. (1), Kaufmann, J. (2), Voges, J. (1) und Buentjen, L. (1), 1: Klinik für Stereotaktische Neurochirurgie, OVGU Magdeburg, 2: Klinik für Neurologie, OVGU Magdeburg
Objective: Deep brain stimulation for various forms of tremor is a well established trement option. Traditionally neurosurgeons have been using indirect targetting of the ventrointermediate nucleus of the thalmus(VIM) to place electrode contacs for therapeutic purposes. Recently debate arose that bypassing fibers or the dentatorubrothalamic tract might represent the effect mediating structures in DBS for tremor [1, 2]. While usually well tolerated VIM/ DRTT DBS can also be associated with side effects like atactic gait or dysarthria, which might be caused by over stimulation of fibers needed to learn [5] and coordinate these specific activities [3]. Segmentation of electrodes tries to deliver current with higher spatial precision and surgeons develop techniques to align these segments to anatomy [4]. Superselective activation of tremor mediating fibers might be a strategy to prevent such unwanted effects. To achive this goal knowlege of the somatotopic arrangement of DRT fibers is a first prerequisit. Therefore we investigated the course of specific DRT fibers using functional localisation of specific motor cortex (M1) regions as seeds to demonstrate the somatotopic architecture of the DRT at niveau of the thalamus.
Methods: We functionally defined seed regions in M1 in one patient by perfoming specific motor tasks for foot , hand and voice activation. Extensive effort was undertaken to develop a „neck“ paradigm. We then manually transferred activated cortical regions to an MNI-template. Via nonlinear transformation these zones were matched onto the individual T1 MRIs of 23 healthy subjects. Further filter regions were the ipsilateral red nucleus and the ipsi-and contralateral dentate nucleus, which we determined seperatly for each individual. We performed probabilistic fiber tracking for all individuals. The resulting tracts were analysed for their stereotactic coordinates at level of the thalamus.
Results: At level of the thalamus the DRTT somatotopy shows an anterior- posterior orientation, demonstrating a turn of about 90 degrees compared to the lateraly-medially oriented somatotopy of M1.
Discussion: Our findings challange older somatotopic visualisations of the thalamus which are showing a medial-lateral orientation(Kelley1990). However, we have mapped fiber tracts not the VIM itself. Furthermore, differentiation of specific fiber tracts within the dentato-rubro-thalamic tract is possible. Knowledge of individual fiber anatomy it is one prerequisite to conceptually aim for superselective activation of therapeutically effective fiber tracts.
References:
[1] Abdulbaki, A., Kaufmann, J., Galazky, I., Buentjen, L., and Voges, J. 2021. Neuromodulation of the subthalamic nucleus in Parkinson's disease: the effect of fiber tract stimulation on tremor control. Acta neurochirurgica 163, 1, 185–195.
[2] Coenen, V. A., Sajonz, B., Prokop, T., Reisert, M., Piroth, T., Urbach, H., Jenkner, C., and Reinacher, P. C. 2020. The dentato-rubro-thalamic tract as the potential common deep brain stimulation target for tremor of various origin: an observational case series. Acta neurochirurgica 162, 5, 1053–1066.
[3] Groppa, S., Herzog, J., Falk, D., Riedel, C., Deuschl, G., and Volkmann, J. 2014. Physiological and anatomical decomposition of subthalamic neurostimulation effects in essential tremor. Brain : a journal of neurology 137, Pt 1, 109–121.
[4] Schmidt, J. M., Buentjen, L., Kaufmann, J., Gruber, D., Treuer, H., Haghikia, A., and Voges, J. 2022. Deviation of the orientation angle of directional deep brain stimulation leads quantified by intraoperative stereotactic X-ray imaging. Neurosurgical review 45, 4, 2975–2982.
[5] Terzic, L., Voegtle, A., Farahat, A., Hartong, N., Galazky, I., Nasuto, S. J., Andrade, A. d. O., Knight, R. T., Ivry, R. B., Voges, J., Buentjen, L., and Sweeney-Reed, C. M. 2022. Deep brain stimulation of the ventrointermediate nucleus of the thalamus to treat essential tremor improves motor sequence learning. Human brain mapping 43, 15, 4791–4799.
[6] Kelly PJ: Principles of stereotactic surgery, in Youmans JR (ed): Neurological Surgery, ed 3. Philadelphia: WB Saunders, 1990, Vol 6, pp 4183–4226.
Autor:innen: Sophia Peschke (1), Jing Dong (1), Angelina Kirchner (1) und Thomas Köglsperger (1,2), 1: Department of Neurology, Ludwig Maximilian University, Munich, Germany, 2: Department of Translational Brain Research, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
Deep Brain Stimulation (DBS) is a standard treatment for medically intractable essential tremor (ET). In addition to the correct surgical device implantation, effective programming is regarded to be the most important factor for clinical outcome. While neuronal biosignals like local field potentials (LFPs) are currently explored in Parkinson's disease (PD), DBS programming remains time- and resource-intensive, emphasizing the need for novel programming strategies for accurate parameter and electrode configuration adaptation in ET.
We previously proposed using patient subjective ratings via a visual analog scale (VAS) as a potential feedback signal in PD [1]. Here, we tested the utility of a VAS for real-time DBS parameter adjustment in ET. Stimulation parameters (contact and amplitude) for VIM-DBS in ET patients (n = 13) were optimized using the patient's VAS rating. Minkowski distance (Md) compared individual parameter combinations with those from classical programming based on clinical signs.
Results showed no statistically significant difference in clinical outcomes (Fahn-Tolosa-Marín tremor rating scale) between VAS-based and classical programming. Minkowski distances indicated comparable amplitude and contact selection, with VAS-based programs having significantly lower stimulation amplitudes and total electrical energy delivered (TEED). In conclusion, our data suggest that VAS-based and classical programming yield similar short-term results in ET at the expense of reduced energy consumption.
While further research is needed to validate VAS-based DBS programming, our findings support using the patient's subjective rating as an additional and valid feedback signal for personalized DBS adjustment in ET.
1. Palleis C, Gehmeyr M, Mehrkens JH, Bötzel K, Koeglsperger T (2020) Establishment of a Visual Analog Scale for DBS Programming (VISUAL-STIM Trial). Front Neurol 11:561323. doi: 10.3389/fneur.2020.561323.
Autor:innen: Dr. med. Steffen Paschen, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Neurologie
Hintergrund: Die Parkinson-Erkrankung (PD) wird mit Parkinson-spezifischen Medikamenten behandelt, die die Verfügbarkeit von Dopamin im Gehirn erhöhen und dadurch die motorischen Symptome verbessern. Als Nebenwirkung können die behandelten Patientinnen und Patienten Störungen der Impulskontrolle und assoziierte Verhaltensstöruungen (ICBDs) entwickeln, wie z. B. Spielsucht, Hypersexualität, ausuferndes Einkaufen, Essattacken und der übermäßige Gebrauch von Parkinson-Medikamenten. Obwohl ICBDs bei bis zu 14% der Patienten vorkommen, gibt es kaum wissenschaftliche Erkenntnisse darüber, wie sie am besten zu behandeln sind. Die verfügbaren Studien deuten darauf hin, dass sich ICBDs in den meisten Fällen durch eine STN-DBS verbessern.
Ziel: Im freien Vortrag sollen die Empfehlungen zur bestmöglichen medikamentösen Therapie (BMT) aus dem kürzlich publizierten Consensuspaper (Debove I., Paschen S., et al. Mov Disord. 2024) sowie die geplante Studie zum Effekt der Tiefen Hirnstimulation (DBS) des Nucleus subthalamicus (STN) und BMT gegenüber alleiniger BMT zur Therapie von ICBDs (STIMPulseControl) vorgestellt werden.
Autor:innen: Tanmoy Sil, Ibrahem Hanafi, Hazem Eldebakey, Chiara Palmisano, Jens Volkmann, Muthuraman Muthuraman, Robert Peach und Martin M. Reich († Senior Author), Department of Neurology, Uniklinikum Würzburg
Studies have shown that beta band activity is not tonically elevated but comprises exaggerated phasic bursts of varying durations and magnitudes, for Parkinson’s disease (PD) patients. Current methods for detecting beta bursts target a single frequency peak in beta band, potentially ignoring bursts in the wider beta band. In this study, we propose a new robust framework for beta burst identification across wide frequency ranges. Chronic local field potential at-rest recordings were obtained from seven PD patients implanted with Medtronic SenSight™ deep brain stimulation (DBS) electrodes. The proposed method uses wavelet decomposition to compute the time–frequency spectrum and identifies bursts spanning multiple frequency bins by thresholding, offering an additional burst measure, ∆f, that captures the width of a burst in the frequency domain. Analysis included calculating burst duration, magnitude, and ∆f and evaluating the distribution and likelihood of bursts between the low beta (13–20 Hz) and high beta (21–35 Hz). Finally, the results of the analysis were correlated to motor impairment (MDS-UPDRS III) med off scores. We found that low beta bursts with longer durations and larger width in the frequency domain (∆f) were positively correlated, while high beta bursts with longer durations and larger ∆f were negatively correlated with motor impairment. The proposed method, finding clear differences between bursting behavior in high and low beta bands, has clearly demonstrated the importance of considering wide frequency bands for beta burst behavior with implications for closed-loop DBS paradigms.
To this effect, we have developed an algorithm integrated into a MATLAB™-based application. The said app accepts input from both ring and segmented electrode recordings from a Medtronic SenSight™ IPG, enabling it to identify the optimal electrode based on either power or burst duration. This approach offers clinicians a streamlined alternative to the traditional monopolar review process when selecting electrodes. While the effectiveness of this algorithm requires further testing, its potential success could significantly enhance the efficiency of electrode selection for stimulation purposes.
Autor:innen: Yaroslav Winter, Dumitru Ciolac, Gabriel Gonzales-Escamilla und Sergiu Groppa, Zentrum für Epilepsie und Schlafmedizin, Klinik für Neurologie, Universitätsmedizin Mainz
Therapierefraktäre Epilepsien werden zunehmend als Störungen von neuronalen Netzwerken konzeptualisiert, während die Merkmale und Architekturen der Schaltkreise und ihre Bedeutung für die Behandlung weitgehend unklar bleiben. Die Tiefenhirnstimulation und die neu entwickelte direkte kortikale Gleichstromstimulation (EASEE-System) sind neue Therapien, die ein vielversprechendes Profil für die Anfallskontrolle aufweisen. Gezielte Neuromodulationsmethoden könnten auf dieselben Netzwerke oder miteinander verbundene Bereiche abzielen und zu einer Verschiebung der pathologischen Konnektivität des Gehirns hin zu einem physiologischen Bereich führen. Dieser Vortrag wird die Netzwerkkonzepte zusammenfassen, die für therapeutische Maßnahmen zur Anfallskontrolle relevant sind. Es werden aktuelle eigene Arbeiten zu innovativen Topographiekonzepten der epileptogenen Netzwerke vorgesellt, die Relevanz der an der motorischen Kontrolle und dem Bewusstsein beteiligten Hirnregionen diskutiert und deren Bedeutung für die Entstehung und Aufrechterhaltung refraktärer Anfälle hervorhoben. Unsere jüngsten Arbeiten und die entwickelten Konzepte tragen dazu bei, die therapeutischen Strategien für die Anfallskontrolle bei refraktären Epilepsien zu verbessern. Diese werden vorgestellt und kritisch diskutiert und ebnen neue Wege für die allgemeine Anwendung der tiefen Hirnstimulation und der direkten kortikalen Stimulation bei Epilepsien, die auf der Grundlage von Hirnnetzwerkkonzepten entwickelt wurden und in künftigen klinischen Studien untersucht werden können.
Relevante Publikationen:
1. Groppa S, Gonzalez-Escamilla G, Tinkhauser G, Baqapuri HI, Sajonz B, Wiest C, Pereira J, Herz DM, Dold MR, Bange M, Ciolac D, Almeida V, Neuber J, Mirzac D, Martín-Rodríguez JF, Dresel C, Muthuraman M, Adarmes Gomez AD, Navas M, Temiz G, Gunduz A, Rotaru L, Winter Y, Schuurman R, Contarino MF, Glaser M, Tangermann M, Leentjens AFG, Mir P, Torres Diaz CV, Karachi C, Linden DEJ, Tan H, Coenen VA; EuroDBS. Perspectives of Implementation of Closed-Loop Deep Brain Stimulation: From Neurological to Psychiatric Disorders. Stereotact Funct Neurosurg. 2024;102(1):40-54.
2. Winter Y, Sandner K, Glaser M, Ciolac D, Sauer V, Ziebart A, Karakoyun A, Chiosa V, Saryyeva A, Krauss J, Ringel F, Groppa S. Synergistic effects of vagus nerve stimulation and antiseizure medication. J Neurol. 2023 Oct;270(10):4978-4984.
3. Schulze-Bonhage A, Hirsch M, Knake S, Kaufmann E, Kegele J, Rademacher M, Vonck K, Coenen VA, Glaser M, Jenkner C, Winter Y, Groppa S; EASEE Study Group. Focal Cortex Stimulation With a Novel Implantable Device and Antiseizure Outcomes in 2 Prospective Multicenter Single-Arm Trials. JAMA Neurol. 2023 Jun 1;80(6):588-596.
4. Vataman A, Ciolac D, Chiosa V, Aftene D, Leahu P, Winter Y, Groppa SA, Gonzalez-Escamilla G, Muthuraman M, Groppa S. Dynamic flexibility and controllability of network communities in juvenile myoclonic epilepsy. Neurobiol Dis. 2023 Apr;179:106055.
5. Chiosa V, Groppa SA, Ciolac D, Koirala N, Mişina L, Winter Y, Moldovanu M, Muthuraman M, Groppa S. Breakdown of Thalamo-Cortical Connectivity Precedes Spike Generation in Focal Epilepsies. Brain Connect. 2017 Jun;7(5):309-32.