Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism

V. M. Tronnier; A. Domingo; C. K. Moll; D. Rasche; C. Mohr; R. Rosales; P. Capetian; R. D. Jamora; L. V. Lee; A. Münchau; C. C. Diesta; V. Tadic; C. Klein; N. Brüggemann; A. Moser

doi:10.1016/j.parkreldis.2015.06.010

Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism

V. M. Tronnier, A. Domingo, C. K. Moll, D. Rasche, C. Mohr, R. Rosales, P. Capetian, R. D. Jamora, L. V. Lee, A. Münchau, C. C. Diesta, V. Tadic, C. Klein, N. Brüggemann^*, A. Moser

^*Corresponding author for this work

11 Citations (Scopus)

Abstract

Objective: Invasive techniques such as in-vivo microdialysis provide the opportunity to directly assess neurotransmitter levels in subcortical brain areas. Methods: Five male Filipino patients (mean age 42.4, range 34-52 years) with severe X-linked dystonia-parkinsonism underwent bilateral implantation of deep brain leads into the internal part of the globus pallidus (GPi). Intraoperative microdialysis and measurement of gamma aminobutyric acid and glutamate was performed in the GPi in three patients and globus pallidus externus (GPe) in two patients at baseline for 25/30min and during 25/30min of high-frequency GPi stimulation. Results: While the gamma-aminobutyric acid concentration increased in the GPi during high frequency stimulation (231±102% in comparison to baseline values), a decrease was observed in the GPe (22±10%). Extracellular glutamate levels largely remained unchanged. Conclusions: Pallidal microdialysis is a promising intraoperative monitoring tool to better understand pathophysiological implications in movement disorders and therapeutic mechanisms of high frequency stimulation. The increased inhibitory tone of GPi neurons and the subsequent thalamic inhibition could be one of the key mechanisms of GPi deep brain stimulation in dystonia. Such a mechanism may explain how competing (dystonic) movements can be suppressed in GPi/thalamic circuits in favour of desired motor programs.

Original language	English
Journal	Parkinsonism and Related Disorders
Volume	21
Issue number	8
Pages (from-to)	954-959
Number of pages	6
ISSN	1353-8020
DOIs	https://doi.org/10.1016/j.parkreldis.2015.06.010
Publication status	Published - 01.01.2015

Funding

Dr. Tronnier received honoraria from St. Jude, Medtronic, EISAI and Codman for scientific presentation. He is member of the advisory boards of EISAI and Medtronic. Dr. Domingo reports no disclosures. Dr. Moll reports no disclosures. Dr. Rasche reports no disclosures. Dr. Mohr reports no disclosures. Dr. Rosales reports no financial disclosures. Dr. Capetian receives his salary from the University medical center Schleswig–Holstein (UKSH), research funds from the Scientific Society Freiburg and the University of Lübeck. He maintains no financial or personal relationship with any private companies. Dr. Jamora reports no disclosures. Dr. Lee reports no disclosures. Dr. Münchau received grants from Pharm Allergan, Ipsen, Merz Pharmaceuticals and Actelion. He received honoraria for lectures from Pharm Allergan, Ipsen, Merz Pharmaceuticals, Actelion, GlaxoSmithKline and Desitin. He was supported from non-profit foundations or societies (Possehl-Stiftung, Lübeck, Dystonia Coalition (USA), Tourette Syndrome Association (Germany), European Huntington Disease Network, N.E.MO. Charity supporting the research of paediatric movement disorders). He received academic research support from Deutsche Forschungsgemeinschaft (MU 1692/3-1; SFB 936) and the University of Lübeck. Dr. Diesta reports no financial disclosures related to this study. Dr. Tadic reports no disclosures. Dr. Klein is a member of the editorial board of “Neurology” and has served as editor of the “Continuum Issue Neurogenetics 2008” and as faculty at the Annual Meetings of the American Academy of Neurology since 2004. She serves as a medical advisor to Centogene. She is the recipient of a career development award from the Hermann and Lilly Schilling Foundation. She is funded by the Deutsche Forschungsgemeinschaft, the Possehl Foundation and received institutional support from the University of Luebeck for genetics research. Dr. Brüggemann was funded by the German Research Foundation (BR 4328/1-1) and received speaker's honoraria from the Schleswig–Holstein Chamber of pharmacists and the German Neurological Society. He received travel grants from Ipsen, Merz and St. Jude Medical. Dr. Moser reports no disclosures. We gratefully thank all participants for their invaluable participation. We also thank St. Jude Medical and Medtronic for providing the neurostimulation devices. In addition, this work was supported by a research grant covering the hospital costs from the University Hospital Schleswig–Holstein, Campus Lübeck and by the Deutsche Forschungsgemeinschaft (DFG; SFB 936/project C5), Collaborative Center for X-linked Dystonia Parkinsonism.

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SDG 10 Reduced Inequalities

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10.1016/j.parkreldis.2015.06.010

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Tronnier, V. M., Domingo, A., Moll, C. K., Rasche, D., Mohr, C., Rosales, R., Capetian, P., Jamora, R. D., Lee, L. V., Münchau, A., Diesta, C. C., Tadic, V., Klein, C., Brüggemann, N., & Moser, A. (2015). Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism. Parkinsonism and Related Disorders, 21(8), 954-959. https://doi.org/10.1016/j.parkreldis.2015.06.010

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title = "Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism",

abstract = "Objective: Invasive techniques such as in-vivo microdialysis provide the opportunity to directly assess neurotransmitter levels in subcortical brain areas. Methods: Five male Filipino patients (mean age 42.4, range 34-52 years) with severe X-linked dystonia-parkinsonism underwent bilateral implantation of deep brain leads into the internal part of the globus pallidus (GPi). Intraoperative microdialysis and measurement of gamma aminobutyric acid and glutamate was performed in the GPi in three patients and globus pallidus externus (GPe) in two patients at baseline for 25/30min and during 25/30min of high-frequency GPi stimulation. Results: While the gamma-aminobutyric acid concentration increased in the GPi during high frequency stimulation (231±102\% in comparison to baseline values), a decrease was observed in the GPe (22±10\%). Extracellular glutamate levels largely remained unchanged. Conclusions: Pallidal microdialysis is a promising intraoperative monitoring tool to better understand pathophysiological implications in movement disorders and therapeutic mechanisms of high frequency stimulation. The increased inhibitory tone of GPi neurons and the subsequent thalamic inhibition could be one of the key mechanisms of GPi deep brain stimulation in dystonia. Such a mechanism may explain how competing (dystonic) movements can be suppressed in GPi/thalamic circuits in favour of desired motor programs.",

author = "Tronnier, \{V. M.\} and A. Domingo and Moll, \{C. K.\} and D. Rasche and C. Mohr and R. Rosales and P. Capetian and Jamora, \{R. D.\} and Lee, \{L. V.\} and A. M{\"u}nchau and Diesta, \{C. C.\} and V. Tadic and C. Klein and N. Br{\"u}ggemann and A. Moser",

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doi = "10.1016/j.parkreldis.2015.06.010",

language = "English",

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Tronnier, VM, Domingo, A, Moll, CK, Rasche, D, Mohr, C, Rosales, R, Capetian, P, Jamora, RD, Lee, LV, Münchau, A, Diesta, CC, Tadic, V , Klein, C , Brüggemann, N & Moser, A 2015, 'Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism', Parkinsonism and Related Disorders, vol. 21, no. 8, pp. 954-959. https://doi.org/10.1016/j.parkreldis.2015.06.010

TY - JOUR

T1 - Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism

AU - Tronnier, V. M.

AU - Domingo, A.

AU - Moll, C. K.

AU - Rasche, D.

AU - Mohr, C.

AU - Rosales, R.

AU - Capetian, P.

AU - Jamora, R. D.

AU - Lee, L. V.

AU - Münchau, A.

AU - Diesta, C. C.

AU - Tadic, V.

AU - Klein, C.

AU - Brüggemann, N.

AU - Moser, A.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Objective: Invasive techniques such as in-vivo microdialysis provide the opportunity to directly assess neurotransmitter levels in subcortical brain areas. Methods: Five male Filipino patients (mean age 42.4, range 34-52 years) with severe X-linked dystonia-parkinsonism underwent bilateral implantation of deep brain leads into the internal part of the globus pallidus (GPi). Intraoperative microdialysis and measurement of gamma aminobutyric acid and glutamate was performed in the GPi in three patients and globus pallidus externus (GPe) in two patients at baseline for 25/30min and during 25/30min of high-frequency GPi stimulation. Results: While the gamma-aminobutyric acid concentration increased in the GPi during high frequency stimulation (231±102% in comparison to baseline values), a decrease was observed in the GPe (22±10%). Extracellular glutamate levels largely remained unchanged. Conclusions: Pallidal microdialysis is a promising intraoperative monitoring tool to better understand pathophysiological implications in movement disorders and therapeutic mechanisms of high frequency stimulation. The increased inhibitory tone of GPi neurons and the subsequent thalamic inhibition could be one of the key mechanisms of GPi deep brain stimulation in dystonia. Such a mechanism may explain how competing (dystonic) movements can be suppressed in GPi/thalamic circuits in favour of desired motor programs.

AB - Objective: Invasive techniques such as in-vivo microdialysis provide the opportunity to directly assess neurotransmitter levels in subcortical brain areas. Methods: Five male Filipino patients (mean age 42.4, range 34-52 years) with severe X-linked dystonia-parkinsonism underwent bilateral implantation of deep brain leads into the internal part of the globus pallidus (GPi). Intraoperative microdialysis and measurement of gamma aminobutyric acid and glutamate was performed in the GPi in three patients and globus pallidus externus (GPe) in two patients at baseline for 25/30min and during 25/30min of high-frequency GPi stimulation. Results: While the gamma-aminobutyric acid concentration increased in the GPi during high frequency stimulation (231±102% in comparison to baseline values), a decrease was observed in the GPe (22±10%). Extracellular glutamate levels largely remained unchanged. Conclusions: Pallidal microdialysis is a promising intraoperative monitoring tool to better understand pathophysiological implications in movement disorders and therapeutic mechanisms of high frequency stimulation. The increased inhibitory tone of GPi neurons and the subsequent thalamic inhibition could be one of the key mechanisms of GPi deep brain stimulation in dystonia. Such a mechanism may explain how competing (dystonic) movements can be suppressed in GPi/thalamic circuits in favour of desired motor programs.

UR - https://www.scopus.com/pages/publications/84937525411

U2 - 10.1016/j.parkreldis.2015.06.010

DO - 10.1016/j.parkreldis.2015.06.010

M3 - Journal articles

C2 - 26093890

AN - SCOPUS:84937525411

SN - 1353-8020

VL - 21

SP - 954

EP - 959

JO - Parkinsonism and Related Disorders

JF - Parkinsonism and Related Disorders

IS - 8

ER -

Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism

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Funding

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