Never had this problem before, but after returning from a long break, (and a windows 10 update), Most of the time when I start up the game, the in-game mouse will disappear, and be replaced with my desktop mouse, and I won't be able to interact with anything. (Including the "are you sure" popup when you attempt to ALT+F4).

The whole thing's very frustrating, and I can't seem to find a solution for this anywhere.