Optimal deep brain stimulation sites and networks for cervical vs. generalized dystonia

Horn, Andreas; Reich, Martin M.; Ewert, Siobhan; Li, Ningfei; Al‐Fatly, Bassam; Lange, Florian; Roothans, Jonas; Oxenford, Simón; Horn, Isabel; Paschen, Steffen; Runge, Joachim; Wodarg, Fritz; Witt, Karsten; Nickl, Robert; Wittstock, Matthias; Schneider, Gerd‐Helge; Mahlknecht, Philipp; Poewe, Werner; Eisner, Wilhelm; Helmers, Ann‐Kristin; Matthies, Cordula; Krauss, Joachim K.; Deuschl, Günther; Volkmann, Jens; Kühn, Andrea A.

doi:10.1073/pnas.2114985119

Cited by 46 publications

(72 citation statements)

References 90 publications

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“…(9)(10)(11) Posteroventral GPi intersection supports the brainstems involvement in mediating therapeutic networks, given that this area of the pallidum is widely regarded as the DBS hotspot for cervical dystonia, and occupies somatotopic cervical territory. (15,73,74) The observed cortical motor fibre intersection corroborates the somatotopic head and neck areas, as the terminus of white matter tracts associated with optimal clinical motor symptom reduction, in cervical dystonia. (15) Structural changes to primary and pre-motor regions, (22,(75)(76)(77) and decreased resting-state functional MRI activity between cerebellar and primary motor cortex, (78) have been identified in patients with cervical dystonia relative to healthy controls, supporting a role of motor circuit changes in the disorder's pathophysiology.…”

Section: Discussionsupporting

confidence: 70%

“…(15,73,74) The observed cortical motor fibre intersection corroborates the somatotopic head and neck areas, as the terminus of white matter tracts associated with optimal clinical motor symptom reduction, in cervical dystonia. (15) Structural changes to primary and pre-motor regions,(22,75–77) and decreased resting-state functional MRI activity between cerebellar and primary motor cortex,(78) have been identified in patients with cervical dystonia relative to healthy controls, supporting a role of motor circuit changes in the disorder’s pathophysiology.…”

Section: Discussionsupporting

confidence: 58%

“…When normative structural connectivity was mapped from the surface area showing inwards deflation, probabilistic streamlines connected with cerebellar, subcortical and cortical motor regions, which corroborate a literature-defined network in cervical dystonia. (10,15) Analysis of electric field overlap with cerebellar tracts revealed that the non-decussating DRTT was significantly correlated with clinical outcome. Importantly, differences in clinical outcomes between patient groups appeared to not be driven by the accuracy of electrode placement, further enforcing the need to identify biomarkers beyond surgical accuracy.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…(10) Furthermore, recent work using functional and tractography-derived connectivity identified the same network pattern, encapsulating the cerebellum and somatosensory cortex, as "optimal" pathways for therapeutic DBS outcomes in patients with cervical dystonia. (15) Assessing the structure of the cerebellum and brainstem through imaging offers an alternative approach to explore these insights in relation to DBS outcomes. Cortico-ponto-cerebellar and cerebello-thalamo-cortical tracts form the structural connections that interlink the cerebellum, brainstem, regions of the basal ganglia and sensorimotor cortices.…”

Section: Introductionmentioning

confidence: 99%

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WITHDRAWN: Infratentorial Morphometry and Deep Brain Stimulation Outcome in Cervical Dystonia

Andrews

Keller

Osman-Farah

et al. 2023

Preprint

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Background: Cervical dystonia is a movement disorder, characterised by involuntary head and neck muscle contractions. Although deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective treatment option, motor outcomes can vary even when sufficient targeting accuracy is achieved. Increasing evidence supports a role of brainstem and cerebellum dysfunction in cervical dystonia pathogenesis. Objective: To determine whether morphometry of brainstem and dentate nuclei, and DBS stimulatory overlap with cerebello-thalamic tracts modelled from normative connectivity, were related to DBS clinical motor outcomes. Methods: 27 patients with idiopathic cervical dystonia underwent bilateral targeting of the GPi. and were separated into suboptimal and optimal motor outcome groups. Dentate nuclei and brainstem volumes were quantified in association with clinical outcomes. A brainstem shape analysis was conducted and used as a seed to assess connectivity from a normative structural connectome. Patient-specific electrodes were modelled to quantify stimulatory overlap with the GPi and proximity to cerebellothalamic tracts. Results: GPi implantation accuracy did not significantly differ between groups. Significantly reduced dentate nuclei and brainstem volumes were observed in patients with poorer clinical outcomes. Regional surface shape change of the brainstem was also observed in patients with poorer responses. Fibre tracking from this area intersected cerebellar, pallidal and cortical motor regions. Electrode field intersection with the non-decussating dentatorubrothalamic tract in the right, and in both hemispheres were also positively associated with clinical outcome. Conclusions: Variability in cerebellar and brainstem morphometry, and stimulation of non-decussating cerebello-thalamic pathways may contribute to the mediation of DBS motor outcomes.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

WITHDRAWN: Infratentorial Morphometry and Deep Brain Stimulation Outcome in Cervical Dystonia

Andrews

Keller

Osman-Farah

et al. 2023

Preprint

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Improvement of obsessive–compulsive disorder after pallidothalamic tractotomy for cervical dystonia

Horisawa

Kamba

Sato

et al. 2023

Ann Clin Transl Neurol

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A 30-year-old woman with tardive dystonia in the cervical region from longterm antipsychotic meds was treated with radiofrequency ablation of the right pallidothalamic tract in the fields of Forel. The patient showed improvement in both cervical dystonia and obsessive-compulsive disorder after the procedure, with 77.4% improvement in cervical dystonia and 86.7% improvement in obsessive-compulsive disorder. Although the treatment site in this case was intended to treat cervical dystonia, the lesion was located in the optimal stimulation network for both obsessive-compulsive disorder and cervical dystonia, suggesting that neuromodulation of this region could potentially treat both simultaneously.

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Connectivity Profile for Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson Disease

Hacker

Rajamani

Neudorfer

et al. 2023

Annals of Neurology

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Objective This study was undertaken to describe relationships between electrode localization and motor outcomes from the subthalamic nucleus (STN) deep brain stimulation (DBS) in early stage Parkinson disease (PD) pilot clinical trial. Methods To determine anatomical and network correlates associated with motor outcomes for subjects randomized to early DBS (n = 14), voxelwise sweet spot mapping and structural connectivity analyses were carried out using outcomes of motor progression (Unified Parkinson Disease Rating Scale Part III [UPDRS‐III] 7‐day OFF scores [∆baseline➔24 months, MedOFF/StimOFF]) and symptomatic motor improvement (UPDRS‐III ON scores [%∆baseline➔24 months, MedON/StimON]). Results Sweet spot mapping revealed a location associated with slower motor progression in the dorsolateral STN (anterior/posterior commissure coordinates: 11.07 ± 0.82mm lateral, 1.83 ± 0.61mm posterior, 3.53 ± 0.38mm inferior to the midcommissural point; Montreal Neurological Institute coordinates: +11.25, −13.56, −7.44mm). Modulating fiber tracts from supplementary motor area (SMA) and primary motor cortex (M1) to the STN correlated with slower motor progression across STN DBS subjects, whereas fiber tracts originating from pre‐SMA and cerebellum were negatively associated with motor progression. Robustness of the fiber tract model was demonstrated in leave‐one‐patient‐out (R = 0.56, p = 0.02), 5‐fold (R = 0.50, p = 0.03), and 10‐fold (R = 0.53, p = 0.03) cross‐validation paradigms. The sweet spot and fiber tracts associated with motor progression revealed strong similarities to symptomatic motor improvement sweet spot and connectivity in this early stage PD cohort. Interpretation These results suggest that stimulating the dorsolateral region of the STN receiving input from M1 and SMA (but not pre‐SMA) is associated with slower motor progression across subjects receiving STN DBS in early stage PD. This finding is hypothesis‐generating and must be prospectively tested in a larger study. ANN NEUROL 2023;94:271–284

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Optimal deep brain stimulation sites and networks for cervical vs. generalized dystonia

Cited by 46 publications

References 90 publications

WITHDRAWN: Infratentorial Morphometry and Deep Brain Stimulation Outcome in Cervical Dystonia

WITHDRAWN: Infratentorial Morphometry and Deep Brain Stimulation Outcome in Cervical Dystonia

Improvement of obsessive–compulsive disorder after pallidothalamic tractotomy for cervical dystonia

Connectivity Profile for Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson Disease

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