Unravelling delayed therapy escape after thalamic deep brain stimulation for essential tremor? – Additional clinical and neuroimaging evidence

NeuroImage Clinical, vol. 36, pp. 103150

Abstract

Delayed therapy escape after thalamic deep brain stimulation (DBS) for essential tremor is a serious yet frequent condition. It is often difficult to detect this process at onset due to its gradual evolution. Here we aim to identify clinical and neuroimaging hallmarks of delayed therapy escape. We retrospectively studied operationalized and quantitative analyses of tremor and gait, as well as [18F]fluorodeoxyglucose (FDG) PET of 12 patients affected by therapy escape. All examinations were carried out with activated DBS (ON) and 72 hours after deactivation (OFF72h); gait and tremor were also analyzed directly after deactivation (OFF0h). Changes of normalized glucose metabolism between stimulation conditions were assessed using within-subject analysis of variance and statistical parametric mapping. Additionally, a comparison to the [18F]FDG PET of an age-matched control group was performed. Exploratory correlation analyses were conducted with operationalized and parametric clinical data. Of the immediately accessible parametric tremor data (i.e. ON or OFF0h) only the rebound (i.e. OFF0h) frequency of postural tremor showed possible correlations with signs of ataxia at ON. Regional glucose metabolism was significantly increased bilaterally in the thalamus and dentate nucleus in ON compared to OFF72h. No differences in regional glucose metabolism were found in patients in ON and OFF72h compared with the healthy controls. Rebound frequency of postural tremor seems to be a good diagnostic marker for delayed therapy escape. Regional glucose metabolism suggests that this phenomenon may be associated with increased metabolic activity in the thalamus and dentate nucleus possibly due to antidromic stimulation effects. We see reasons to interpret the delayed therapy escape phenomenon as being related to long term and chronic DBS.

Authors 13

1. Bastian Sajonz

   University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   Department of Stereotactic and Functional Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany. Electronic address: bastian.sajonz@unikllinik-freiburg.de

   Department of Stereotactic and Functional Neurosurgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

2. Marvin L. Frommer

   University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   Department of Stereotactic and Functional Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

   Department of Stereotactic and Functional Neurosurgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

3. Isabelle Walz

   University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   Department of Neurology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany; Department of Sport and Sport Science, University of Freiburg, Freiburg im Breisgau, Germany

   Department of Neurology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

4. Marco Reisert

   University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   Department of Stereotactic and Functional Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

   Department of Stereotactic and Functional Neurosurgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

5. Michel Rijntjes

   University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   Department of Neurology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

   Department of Neurology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

6. Tobias Piroth

   University of Freiburg · University Medical Center Freiburg · Kantonsspital Aarau

   Affiliation as printed

   Department of Neurology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany; Department of Neurology, Kantonsspital Aarau, Aarau, Switzerland

   Department of Neurology, Kantonsspital Aarau, Aarau, Switzerland

   Department of Neurology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

7. Nils Schröter

   University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   Department of Neurology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

   Department of Neurology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

8. Carolin Jenkner

   University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   Clinical Trials Unit, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

9. Peter Christoph Reinacher Aachen Fraunhofer Institute for Laser Technology (ILT)

   Fraunhofer Institute for Laser Technology · University of Freiburg · University Medical Center Freiburg

   Affiliation as printed

   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

   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

10. Joachim Brumberg

    University of Freiburg · University Medical Center Freiburg

    Affiliation as printed

    Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

    Department of Nuclear Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

11. Philipp Tobias Meyer

    University of Freiburg · University Medical Center Freiburg

    Affiliation as printed

    Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

    Department of Nuclear Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

12. Ganna Blazhenets

    University of Freiburg · University Medical Center Freiburg

    Affiliation as printed

    Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

    Department of Nuclear Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

13. Volker Arnd Coenen

    University of Freiburg · University Medical Center Freiburg

    Affiliation as printed

    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; Center for Basics in Neuromodulation (Neuromod Basics), Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

    Center for Basics in Neuromodulation (Neuromod Basics), Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

    Center for Deep Brain Stimulation, University of Freiburg

    Department of Stereotactic and Functional Neurosurgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany