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March 13, 2012; 78 (11) Articles

The tremor network targeted by successful VIM deep brain stimulation in humans

J.C. Klein, M.T. Barbe, C. Seifried, S. Baudrexel, M. Runge, M. Maarouf, T. Gasser, E. Hattingen, T. Liebig, R. Deichmann, L. Timmermann, L. Weise, R. Hilker
First published February 29, 2012, DOI: https://doi.org/10.1212/WNL.0b013e318249f702
J.C. Klein
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M.T. Barbe
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C. Seifried
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S. Baudrexel
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M. Runge
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M. Maarouf
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T. Gasser
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E. Hattingen
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T. Liebig
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Citation
The tremor network targeted by successful VIM deep brain stimulation in humans
J.C. Klein, M.T. Barbe, C. Seifried, S. Baudrexel, M. Runge, M. Maarouf, T. Gasser, E. Hattingen, T. Liebig, R. Deichmann, L. Timmermann, L. Weise, R. Hilker
Neurology Mar 2012, 78 (11) 787-795; DOI: 10.1212/WNL.0b013e318249f702

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Abstract

Objective: Deep brain stimulation (DBS) of the ventral intermediate nucleus of thalamus (VIM) is a treatment option in medically intractable tremor, such as essential tremor or tremor-dominant Parkinson disease (PD). Although functional studies demonstrated modulation of remote regions, the structural network supporting this is as yet unknown. In this observational study, we analyzed the network mediating clinical tremor modulation.

Methods: We studied 12 patients undergoing VIM stimulation for debilitating tremor. We initiated noninvasive diffusion tractography from tremor-suppressive VIM electrode contacts. Moreover, we tested for the contribution of primary motor projections in this structural correlate of a functional tremor network, comparing the connectivity of effective DBS contacts with those of adjacent, but clinically ineffective, stimulation sites.

Results: VIM stimulation resulted in decrease of tremor and improvement in quality of life. Tractography initiated from the effective stimulation site reconstructed a highly reproducible network of structural connectivity comprising motor cortical, subcortical, and cerebellar sites and the brainstem, forming the anatomic basis for remote effects of VIM stimulation. This network is congruent with functional imaging studies in humans and with thalamic projections found in the animal literature. Connectivity to the primary motor cortex seemed to play a key role in successful stimulation.

Conclusions: Patients undergoing DBS provide a unique opportunity to assess an electrophysiologically defined seed region in human thalamus, a technique that is usually restricted to animal research. In the future, preoperative tractography could aid with stereotactic planning of individual subcortical target points for stimulation in tremor and in other disease entities.

GLOSSARY

DBS=
deep brain stimulation;
DT=
diffusion tractography;
EPI=
echo-planar imaging;
ET=
essential tremor;
FTM=
Fahn-Tolosa-Marin;
PC=
posterior commissure;
PD=
Parkinson disease;
rCBF=
regional cerebral blood flow;
ROI=
region of interest;
tPD=
tremor-dominant Parkinson disease;
UPDRS-III =
Unified Parkinson's Disease Rating Scale part III;
VIM=
ventral intermediate nucleus of thalamus;
VLa =
ventral lateral anterior nucleus;
VLp =
ventral lateral posterior nucleus

Footnotes

  • Study funding: Supported by the German Research Foundation via the Clinical Research group 219 “Basal Ganglia-Cortex-Loops: Mechanisms of Pathological Interaction and Their Therapeutic Modulation” (Dr. Barbe and Prof. Timmermann).

  • Supplemental data at www.neurology.org

  • Received July 28, 2011.
  • Accepted November 4, 2011.
  • Copyright © 2012 by AAN Enterprises, Inc.
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Disputes & Debates: Rapid online correspondence

  • Reply to Zhang and colleagues
    • Johannes C. Klein, Goethe-University Frankfurtklein@med.uni-frankfurt.de
    • Johannes C. Klein, R?diger Hilker; Frankfurt, Germany
    Submitted April 18, 2012
  • Differential reproducible network between STN and VIM stimulation: reconstruct different structural connectivity?
    • Jian-guo Zhang, Director, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical Universityneurosurgeon@126.com
    • Fan-gang Meng, MD, PhD, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; Chris C. Kao, MD, PhD, Department of Neurological Surgery, Vanderbilt University Medical Center,T-4224 MCN, Nashville, TN; Jian-guo Zhang, MD, PhD, Depart
    Submitted April 10, 2012
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