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 25/30 min and during 25/30 min 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.
authors.affiliation: Department of Neurosurgery, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: V M
authors.initials: VM
authors.lastname: Tronnier
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Maria-Goeppert-Straße 1, D-23562 Lübeck, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Domingo
authors.affiliation: Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, D-20246 Hamburg, Germany.
authors.forename: C K
authors.initials: CK
authors.lastname: Moll
authors.affiliation: Department of Neurosurgery, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Rasche
authors.affiliation: Department of Neuroradiology, University Hospital Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Mohr
authors.affiliation: XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines; Department of Neurology and Psychiatry, Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines.
authors.forename: R
authors.initials: R
authors.lastname: Rosales
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Maria-Goeppert-Straße 1, D-23562 Lübeck, Germany; Department of Neurology, University Hospital Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Capetian
authors.affiliation: XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines; Department of Neurosciences, College of Medicine-Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.
authors.forename: R D
authors.initials: RD
authors.lastname: Jamora
authors.affiliation: XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines.
authors.forename: L V
authors.initials: LV
authors.lastname: Lee
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Maria-Goeppert-Straße 1, D-23562 Lübeck, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Münchau
authors.affiliation: XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines.
authors.forename: C C
authors.initials: CC
authors.lastname: Diesta
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Maria-Goeppert-Straße 1, D-23562 Lübeck, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Tadic
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Maria-Goeppert-Straße 1, D-23562 Lübeck, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Klein
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Maria-Goeppert-Straße 1, D-23562 Lübeck, Germany; Department of Neurology, University Hospital Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Brüggemann
authors.affiliation: Department of Neurology, University Hospital Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Moser
mesh_terms: D000328:Adult; D046690:Deep Brain Stimulation / Q000379:methods*; D020821:Dystonic Disorders / Q000601:surgery / Q000628:therapy*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000601:surgery / Q000628:therapy*; D005917:Globus Pallidus / Q000737:chemistry* / Q000601:surgery; D018698:Glutamic Acid / Q000032:analysis; D006801:Humans; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D016343:Monitoring, Intraoperative / Q000379:methods*; D019635:Neurosurgical Procedures / Q000379:methods*; D005680:gamma-Aminobutyric Acid / Q000032:analysis*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
keywords: Deep brain stimulation; Dystonia; GABA; Globus pallidus; Glutamate