Long term treatment and disease severity change brain responses to levodopa in Parkinson's disease.
OBJECTIVE
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.
Hershey
T
T
Department of Psychiatry, Washington University School of Medicine, USA.
Black
K J
KJ
Carl
J L
JL
McGee-Minnich
L
L
Snyder
A Z
AZ
Perlmutter
J S
JS
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D019957:Motor Skills Disorders / Q000503:physiopathology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology*; D011954:Receptors, Dopamine / Q000502:physiology; D012039:Regional Blood Flow; D012720:Severity of Illness Index; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D011954:Receptors, Dopamine; D007980:Levodopa