Acute levodopa may worsen motor plasticity in late-stage PD

By Lauretta Ihonor

Administering acute doses of levodopa appears to worsen motor cortex plasticity as Parkinson's disease (PD) advances, researchers report.

They say that "repeated non-physiological surges in synaptic dopamine during acute [levodopa] dosing could potentially lead to persistent dysfunction of key enzymes of the intracellular signalling cascade that are involved in the induction and maintenance of both forms of plasticity."

Motor complications are known to develop in response to levodopa therapy as PD progresses. Asha Kishore (Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India) and co-investigators show that motor complications are associated with a loss in both the long- and short-duration response of motor cortex plasticity to levodopa.

"Whether the impairment in plastic response of motor cortex is a cause or a consequence of the motor complications remains an open question," they write in Brain. "Some of the results presented here may favour the former hypothesis."

Kishore and colleagues observed the responses of 55 PD patients to levodopa therapy. They found that 17 showed a stable motor response, 18 had fluctuating nondyskinesis, and 20 had fluctuating dyskinesis.

All patients underwent artificial motor cortex stimulation in an off-levodopa condition (after overnight withdrawal of drugs) and in an on-levodopa condition (after a morning dose of drugs).

The investigators found that when off levodopa, stable responders could express both types of motor plasticity: depression-like and potentiation-like plasticity.

But the long-duration response was lost in the other two groups; fluctuating nondyskinetics exhibited potentiation-like plasticity, but no depression-like plasticity in an off state, and fluctuating dyskinetics exhibited neither type of plasticity.

When the plasticity of all patients was assessed in on state after administration of acute doses of levodopa, potentiation-like plasticity worsened in the patients with fluctuating nondyskinesis and depression-like plasticity worsened in stable responders and patients with fluctuating nondyskinesis.

In the patients with fluctuating dyskinesis, acute levodopa resulted in "paradoxical" potentiation-like plasticity occurring when depression-like plasticity was induced.

The researchers conclude: "A greater understanding of the pathophysiological role of changes in motor cortex plasticity may open the field of more specific therapeutic approaches aimed at modulating the plasticity of the motor cortex."

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