Two questions, pertaining mostly to the early stage PD patient.

First, is there a clear crisp answer (or even a consensus) whether to try to delay levodopa as long as possible, especially whether even first exposure (“challenge” or diagnostic dose) starts the clock toward dyskinesias? The literature seems contradictive/unclear, even argumentative. Some say “proven” benefits especially if start in early UPDRS stages, maybe even neuroprotective, dyskinesias due to disease progression (increasing amount of levodopa needed) not an effect of levodopa itself. Others say “proven” it produces both motor, mental complications eventually, even challenge dose starts the clock, eventually decreases dopamine receptor sensitivity, worsens disease, don’t start until you really need it.

Second, what about neurostimulation, both DBS and extradural motor cortex (EMCS). New articles appeared recently suggesting that EMCS is efficacious, safe, little if any downside. If so what if any reasons not to try it? Then on Valentine’s Day the NEJM article on the EARLYSTIM trial. If I read correctly, DBS improves motor symptoms and major secondary outcomes significantly better than medical therapy alone for earlier stage PD, no significant difference in serious adverse events, bottom line in favor for carefully chosen young patients. For patients with primarily motor symptoms the appeal of relief without starting the clock on levodopa is obvious, but I'm sure I'm ignorant of many things.

All thoughts/recommendations welcome, including additional references. Thank you!!