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Globus pallidus dopamine and Parkinson motor subtypes

Clinical and brain biochemical correlation

From the Division of Neurology, Department of Medicine (A.H.R., A.R.), and Division of Respiratory Diseases (M.E.F.), University of Saskatchewan/Saskatoon Health Region, Canada; and Center for Brain Research (H.H.S., C.P., O.H.), Medical University of Vienna, Austria.

Address correspondence and reprint requests to Dr. Ali H. Rajput, Room 1663, Royal University Hospital, Saskatoon, Saskatchewan, Canada, S7N 0W8

Background: Patients with Parkinson disease (PD) may be akinetic/rigid, be tremor dominant, or have comparable severity of these motor symptoms (classic). The pathophysiologic basis of different PD phenotypes is unknown. This study assessed pallidal and striatal dopamine level patterns in different motor subgroups of PD and normal control brains.

Methods: Globus pallidus and striatum dopamine (DA) levels were measured with high performance liquid chromatography in eight autopsy confirmed PD and five control frozen brains.

Results: DA levels in the external globus pallidus (GPe) of normal brains were nearly six times greater than in the internal pallidum (GPi). In PD, the mean loss of DA was marked (–82%) in GPe and moderate (–51%) in GPi. DA loss of variable degree was seen in different subdivisions of GPe and GPi in PD; however, DA levels were near normal in the ventral (rostral and caudal) GPi of PD cases with prominent tremor. There was marked loss of DA (–89%) in the caudate and severe loss (–98.4%) in the putamen in PD. The pattern of pallidal DA loss did not match the putaminal DA loss.

Conclusion: There is sufficient loss of dopamine (DA) in external globus pallidus and the internal globus pallidum (GPi) as may contribute to the motor manifestations of Parkinson disease (PD). The possible functional disequilibrium between GABAergic and DAergic influences in favor of DA in the caudoventral parts of the GPi may contribute to resting tremor in tremor dominant and classic PD cases.

GLOSSARY: CN = caudate nucleus; DA = dopamine; GPe = external globus pallidus; GPi = internal globus pallidum; LB = Lewy body; MDCS = Movement Disorder Clinic in Saskatoon; PD = Parkinson disease; PUT = putamen; VTA = ventral tegmental area.

ali.rajput{at}saskatoonhealthregion.ca or Linda.beatty{at}saskatoonhealthregion.ca

e-Pub ahead of print at on January 2, 2008, at www.neurology.org.

Disclosure: The authors report no conflicts of interest.

Received March 22, 2007. Accepted in final form July 23, 2007.