KETAMINE shows promise in managing levodopa-induced dyskinesia by disrupting abnormal brain activity and promoting lasting neuroplasticity, new research has shown.
Levodopa-induced dyskinesia is a common complication in Parkinson’s disease patients undergoing long-term dopamine-replacement therapy. Parkinson’s disease is characterised by the progressive loss of dopamine, a chemical critical for smooth motor control. While levodopa restores dopamine levels, prolonged use often leads to uncontrollable, involuntary movements. A study led by the University of Arizona has revealed that these movements result from a “disconnect” in the motor cortex rather than direct causation, offering a fresh perspective on dyskinesia’s underlying mechanism.
Researchers examined the activity of over 3,000 motor cortex neurons in animal models of Parkinson’s disease, revealing reduced coordination between neuronal activity and movement during dyskinesia. This motor cortex “disconnect” highlights how downstream neural circuits spontaneously generate abnormal movements when coordination from the motor cortex is lost. The study also explored ketamine, a well-known anesthetic, as a potential treatment. By disrupting pathological gamma-band oscillations in the brain, ketamine restored some control to the motor cortex and promoted neuroplasticity—enabling neurons to form or strengthen connections. Early clinical trials using low-dose ketamine infusions have shown encouraging results, with some patients reporting relief lasting weeks after a single treatment.
These findings mark a potential paradigm shift in treating Parkinson’s complications. Ketamine not only addresses the motor symptoms but also triggers long-lasting changes in neural connectivity, making it a promising option for sustained symptom relief. The ongoing clinical trials aim to refine dosing strategies, minimising side effects while maximising therapeutic benefits.
If these results are replicated in larger human studies, ketamine could revolutionise the management of levodopa-induced dyskinesia, providing a lifeline to patients struggling with current therapies. Understanding the motor cortex’s role also opens doors to innovative treatments targeting the root cause of dyskinesia rather than just its symptoms, offering hope for improved quality of life in Parkinson’s patients.
Katrina Thornber, EMJ
Reference
Vishwanath A et al. Decoupling of motor cortex to movement in Parkinson’s dyskinesia rescued by sub-anaesthetic ketamine. Brain. 2024;awae386.
