J Neurol Neurosurg Psychiatry 74:844-851 doi:10.1136/jnnp.74.7.844
  • Paper

Long term treatment and disease severity change brain responses to levodopa in Parkinson’s disease

  1. T Hershey1,3,
  2. K J Black1,2,3,
  3. J L Carl3,
  4. L McGee-Minnich3,
  5. A Z Snyder2,3,
  6. J S Perlmutter2,3,4
  1. 1Department of Psychiatry, Washington University School of Medicine, USA
  2. 2Department of Radiology, Washington University School of Medicine
  3. 3Department of Neurology, Washington University School of Medicine
  4. 4Department of Anatomy and Neurobiology, Washington University School of Medicine
  1. Correspondence to:
 Dr J S Perlmutter, Campus Box 8225,4525 Scott Avenue, St Louis, MO 63110, USA; 
  • Received 25 July 2002
  • Accepted 4 February 2003


Objectives: Degeneration of nigrostriatal neurons and subsequent striatal dopamine deficiency produce many of the symptoms of Parkinson disease (PD). Initially restoration of striatal dopamine with oral levodopa provides substantial benefit, but with long term treatment and disease progression, levodopa can elicit additional clinical symptoms, reflecting altered effects of levodopa in the brain. The authors examined whether long term treatment affects the brain’s response to levodopa in the absence of these altered clinical responses to levodopa.

Methods: Positron emission tomography (PET) measurements were used of brain-blood flow before and after an acute dose of levodopa in three groups: PD patients treated long term with levodopa without levodopa induced dyskinesias, levodopa naive PD patients, and controls.

Results: It was found that the PD group treated long term responded to acute levodopa differently from controls in left sensorimotor and left ventrolateral prefrontal cortex. In both regions, the treated PD group had decreased blood flow whereas the control group had increased blood flow in response to levodopa. Levodopa naive PD patients had little or no response to levodopa in these regions. Within the treated PD group, severity of parkinsonism correlated with the degree of abnormality of the sensorimotor cortex response, but not with the prefrontal response.

Conclusions: It is concluded that long term levodopa treatment and disease severity affect the physiology of dopaminergic pathways, producing altered responses to levodopa in brain regions associated with motor function.


  • Funding: this work was supported by NIH grants NS41248, NS32318, NS10787, NS01898, NS41509, NS39913 the Greater St Louis Chapter of the American Parkinson’s Disease Association (APDA), the APDA Advanced Center at Washington University in St Louis, Alzheimer’s Disease and Related Disorders Program, National Alliance for Research in Schizophrenia and Depression, a donation from Ruth Kopolow and the McDonnell Center for the Study of Higher Brain Function.

  • Competing interests: none declared.

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