A 51-year-old man with a 12-year history of Parkinson disease presents to clinic complaining of unpredictable episodes where his medications "wear off" within 2-3 hours of taking them, alternating with periods of involuntary writhing movements of his limbs during peak drug effect. He reports these fluctuations have worsened over the past 2 years despite increasing his carbidopa-levodopa dose to five times daily. Examination during an "on" period reveals prominent dyskinesias. Brain MRI shows no structural abnormalities. Which of the following best explains the development of both motor fluctuations and dyskinesias in this patient?
- A)Depletion of striatal dopamine storage capacity due to progressive loss of substantia nigra neurons
- B)Pulsatile rather than continuous dopaminergic stimulation of supersensitive striatal receptorsGABARITO
- C)Accumulation of levodopa metabolites that competitively inhibit dopamine receptor binding
- D)Development of antibodies against dopamine transporter proteins reducing medication efficacy
- E)Downregulation of dopamine receptors from chronic high-dose levodopa exposure
Explicação
In early Parkinson disease, surviving nigral neurons maintain buffering capacity to store levodopa-derived dopamine and release it tonically. As neuronal loss progresses, this storage capacity diminishes, making the striatum increasingly dependent on exogenous... Ver explicação completa e trilha adaptativa →