What can we learn from the effect of trihexyphenidyl on motor fluctuations during continuous levodopa-carbidopa intestinal gel infusion (LCIG)? - First documented case

Motor fluctuations can be seen even during treatment with continuous levodopa-carbidopa intestinal gel infusion (LCIG). We report on a middle-aged man with advanced Parkinson's disease (PD) on LCIG in which motor fluctuations have been improved with an anticholinergic. To the best of our knowledge, there have been no previous LCIG cases reported with motor fluctuations responding to non-dopaminergic agent, which might reveal some clues to its pathophysiology. Long-term oral levodopa treatment is associated with development of potentially disabling motor complications including motor fluctuations and dyskinesias in the majority of patients with PD. It has been suggested that motor complications are related to the nonphysiological restoration of brain dopamine with intermittent administration of standard oral levodopa. LCIG significantly reduces "off" time and increases "on" time without dyskinesia in comparison to standard oral levodopa through consistent plasma concentration of levodopa to restore brain dopamine in a more physiological manner. However, it has been reported that PD patients on LCIG often worsen during the afternoon hours, even with stable plasma concentration of levodopa. This raises the possibility that additional factors to dopamine deficiency could play a role in occurrence of motor fluctuations. Here we offer a hypothesis that altered cholinergic signaling could also be involved in the pathophysiology of motor fluctuations, based on our clinical evidence that anticholinergic drug has eliminated motor fluctuations during LCIG in a patient with PD. Further studies for non-dopaminergic along with dopaminergic signaling may be needed to better understand the pathophysiological basis of motor complications in PD.