Levodopainduced

Levodopainduced dyskinesias (LID) are involuntary movements that arise in some people with Parkinson's disease during chronic levodopa therapy. They typically present as choreiform or dystonic movements of the face, tongue, limbs, and trunk, and most often occur at the peak effect of the levodopa dose. Less commonly, dyskinesias are biphasic, appearing near dose initiation or near the end of a dosing interval. Onset usually follows several years of treatment and is more common in younger patients and in those with higher lifetime levodopa exposure.

Pathophysiology is not fully understood but involves pulsatile dopaminergic stimulation from intermittent dosing, leading to sensitization of striatal dopamine receptors and alterations in downstream signaling and plasticity. Non-dopaminergic systems, including serotonergic neurons that convert levodopa to dopamine, may contribute. These changes result in abnormal motor output when levodopa levels rise.

Clinical impact varies; for some, LID is mild and does not limit function, while for others it can impair speech, gait, sleep, and overall quality of life. Diagnosis is clinical, based on timing relative to levodopa dosing and exclusion of other movement disorders or medication effects.

Management aims to maintain motor control while reducing dyskinesias. Approaches include adjusting the levodopa regimen (smaller, more frequent doses or continuous dopaminergic delivery), and the use of amantadine, which has demonstrated anti-dyskinetic effects. In refractory cases, deep brain stimulation of the GPi or STN, or advanced levodopa-delivery systems, may reduce dyskinesias. Combinations with non-levodopa therapies are tailored to individual response. Prognosis depends on disease progression and treatment response; LID can persist but is often mitigated with optimized therapy.