title: Combined pedunculopontine-subthalamic stimulation in Parkinson disease.
abstract: OBJECTIVE
  To assess the effect of deep brain stimulation (DBS) in the pedunculopontine nucleus (PPN) and caudal zona incerta (cZi)-both separately and in combination-on motor symptoms and regional cerebral blood flow (rCBF) in patients with Parkinson disease (PD).
  
  
  METHODS
  Four patients with bilateral cZi and PPN DBS electrodes were rated with the Unified Parkinson's Disease Rating Scale motor subscale (UPDRS-III) when taking and withdrawn from medication. A block of 16 [(15)O]-H(2)O PET resting measurements of rCBF were performed in 4 different states with patients withdrawn from medication: 1) no stimulation, 2) cZi stimulation alone, 3) PPN stimulation alone, 4) combined PPN/cZi stimulation.
  
  
  RESULTS
  When patients were medicated, combined PPN/cZi stimulation produced a statistically significant improvement in UPDRS-III score compared to cZi stimulation alone. In the "off" medication state, the clinical effect of combined stimulation was not significantly different from that induced by cZi stimulation alone. Concomitant PPN/cZi stimulation had a cumulative effect on levels of rCBF, effectively combining subcortical and cortical changes induced by stimulation of either target in isolation.
  
  
  CONCLUSIONS
  These findings suggest that concomitant low frequency stimulation of PPN and cZi regions induces additive brain activation changes and provides improved control of PD symptoms when medicated.
  
  
  METHODS
  This study provides Class IV evidence that concomitant low frequency stimulation of PPN and cZI improves motor symptoms in patients with PD on dopamine replacement. It provides Class III evidence that concomitant low frequency stimulation of PPN and cZi induces additive rCBF changes in motor areas of brain.
authors.affiliation: Department of Neurosurgery, Institute of Neurosciences, Frenchay Hospital, Bristol, UK.
authors.forename: S
authors.initials: S
authors.lastname: Khan
authors.forename: S S
authors.initials: SS
authors.lastname: Gill
authors.forename: L
authors.initials: L
authors.lastname: Mooney
authors.forename: P
authors.initials: P
authors.lastname: White
authors.forename: A
authors.initials: A
authors.lastname: Whone
authors.forename: D J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: N
authors.initials: N
authors.lastname: Pavese
mesh_terms: D046690:Deep Brain Stimulation / Q000379:methods*; D004567:Electrodes, Implanted; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy*; D045042:Pedunculopontine Tegmental Nucleus / Q000000981:diagnostic imaging / Q000502:physiology*; D011877:Radionuclide Imaging; D020531:Subthalamic Nucleus / Q000000981:diagnostic imaging / Q000502:physiology*