Disbalanced recruitment of crossed and uncrossed cerebello-thalamic pathways during deep brain stimulation is predictive of delayed therapy escape in essential tremor

Bastian E.A. Sajonz; Marvin L. Frommer; Marco Reisert; Ganna Blazhenets; Nils Schröter; Alexander Rau; Thomas Prokop; Peter C. Reinacher; Michel Rijntjes; Horst Urbach; Philipp T. Meyer; Volker A. Coenen

NeuroImage: Clinical (Jan 2024)

Disbalanced recruitment of crossed and uncrossed cerebello-thalamic pathways during deep brain stimulation is predictive of delayed therapy escape in essential tremor

Bastian E.A. Sajonz,
Marvin L. Frommer,
Marco Reisert,
Ganna Blazhenets,
Nils Schröter,
Alexander Rau,
Thomas Prokop,
Peter C. Reinacher,
Michel Rijntjes,
Horst Urbach,
Philipp T. Meyer,
Volker A. Coenen

Affiliations

Bastian E.A. Sajonz: Department of Stereotactic and Functional Neurosurgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany; Corresponding author.
Marvin L. Frommer: Department of Stereotactic and Functional Neurosurgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
Marco Reisert: Department of Stereotactic and Functional Neurosurgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany; Division of Medical Physics, Department of Diagnostic and Interventional Radiology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Germany
Ganna Blazhenets: Department of Nuclear Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
Nils Schröter: Department of Neurology and Neurophysiology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
Alexander Rau: Department of Neuroradiology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
Thomas Prokop: Department of Stereotactic and Functional Neurosurgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
Peter C. Reinacher: Department of Stereotactic and Functional Neurosurgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany; Fraunhofer Institute for Laser Technology (ILT), Aachen, Germany
Michel Rijntjes: Department of Neurology and Neurophysiology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
Horst Urbach: Department of Neuroradiology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
Philipp T. Meyer: Department of Nuclear Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
Volker A. Coenen: Department of Stereotactic and Functional Neurosurgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany; Center for Deep Brain Stimulation, University of Freiburg, Germany

Journal volume & issue: Vol. 41
p. 103576

Abstract

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Background: Thalamic deep brain stimulation (DBS) is an efficacious treatment for drug-resistant essential tremor (ET) and the dentato-rubro-thalamic tract (DRT) constitutes an important target structure. However, up to 40% of patients habituate and lose treatment efficacy over time, frequently accompanied by a stimulation-induced cerebellar syndrome. The phenomenon termed delayed therapy escape (DTE) is insufficiently understood. Our previous work showed that DTE clinically is pronounced on the non-dominant side and suggested that differential involvement of crossed versus uncrossed DRT (DRTx/DRTu) might play a role in DTE development. Methods: We retrospectively enrolled right-handed patients under bilateral thalamic DBS >12 months for ET from a cross-sectional study. They were characterized with the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS) and Scale for the Assessment and Rating of Ataxia (SARA) scores at different timepoints. Normative fiber tractographic evaluations of crossed and uncrossed cerebellothalamic pathways and volume of activated tissue (VAT) studies together with [18F]Fluorodeoxyglucose positron emission tomography were applied. Results: A total of 29 patients met the inclusion criteria. Favoring DRTu over DRTx in the non-dominant VAT was associated with DTE (R2 = 0.4463, p < 0.01) and ataxia (R2 = 0.2319, p < 0.01). Moreover, increasing VAT size on the right (non-dominant) side was associated at trend level with more asymmetric glucose metabolism shifting towards the right (dominant) dentate nucleus. Conclusion: Our results suggest that a disbalanced recruitment of DRTu in the non-dominant VAT induces detrimental stimulation effects on the dominant cerebellar outflow (together with contralateral stimulation) leading to DTE and thus hampering the overall treatment efficacy.

Published in NeuroImage: Clinical

ISSN: 2213-1582 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General): Computer applications to medicine. Medical informatics; Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: http://www.journals.elsevier.com/neuroimage-clinical/

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