Abstract

Gait disturbances and akinesia are disabling symptoms in advanced Parkinson's disease (PD). The pedunculopontine nucleus (PPN) is involved in locomotion, control of posture, and behavioral states [i.e. wakefulness, rapid eye movement (REM) sleep]. Some reports have suggested that modulation of the activity of the PPN with deep brain stimulation (DBS) may be beneficial in the treatment of gait dysfunction and akinesia. To gain some insights on effects of PPN-DBS in the human brain, we used [(15)O] H(2)O positron emission tomography (PET) to measure changes in regional cerebral blood flow (rCBF) at rest during Off and On stimulation in an advanced PD patient with unilateral PPN-DBS. PPN-DBS increased rCBF in different subcortical areas most notably the thalamus, bilaterally. Double-blinded clinical evaluation revealed an improvement in motor function by approximately 20%. The PET changes provide for the first time evidence in the human brain that PPN-DBS may be able to influence and modify rCBF of closely connected subcortical structures. Given the importance of the PPN in locomotion, control of posture, and behavioral states, DBS may have significant implication for more complicated forms of movement disorders where deterioration of gait, postural instability, and REM sleep behavior disorders are very disabling.

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