We had already twice the situation that the instrumentations are not active after update to the environment. Our suspicion is that it's happening on the profile add/remove from environment. However, it's only happening sometimes, so it's not something that is easily reproducible.
The state should be:
class cache exists on the agent
class cache exists on the CMR
environment update is performed (assumed, but not sure)
The problem is gone if agent cache is cleaned or CMR restarted.