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Dr. Okun

Post of the Week: Combined ZI and PPN DBS for Treatment of Parkinson's Disease

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Dear forum members,


Combined ZI and PPN DBS for the treatment of Parkinson's disease is an approach that has been tried by this British team. The ZI or zona incerta is a region just above the subthalamic nucleus and is thought to be good for control of tremor, stiffness, slowness and other symptoms. The PPN is a regions in the brainstem thought to be good for gait. This study did not show superiority of either target alone on clinical scores, however there was an imaging part of the project that showed some impressive activation. We will have to wait and see if the field can refine technology and targets to improve DBS outcomes. Below is the abstract:


Neurology. 2012 Mar 7. [Epub ahead of print]

Combined pedunculopontine-subthalamic stimulation in Parkinson disease.

Khan S, Gill SS, Mooney L, White P, Whone A, Brooks DJ, Pavese N.


From the Departments of Neurosurgery (S.K., S.S.G., L.M.) and Neurology (A.W.), Institute of Neurosciences, Frenchay Hospital, Bristol; Department of Mathematics and Statistics (P.W.), University of the West of England, Bristol; and Centre for Neuroscience (D.J.B., N.P.), Department of Medicine, Imperial College London, UK.



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).


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DBS electrodes were rated with the Unified Parkinson's Disease Rating Scale motor subscale (UPDRS-III) when taking and withdrawn from medication. A block of 16 [(15)O]-H(2)O PET resting measurements of rCBF were performed in 4 different states with patients withdrawn from medication: 1) no stimulation, 2) cZi stimulation alone, 3) PPN stimulation alone, 4) combined PPN/cZi stimulation.


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.


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.Classification of evidence: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.

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