Mouse Losing Game Focus?

Randomly in the middle of my matches, my mouse loses focus of the game and I can't left click, right click, or even mouse over anything in the game. My cursor turns back into the windows cursor. Keyboard still retains full functionality, I can type and use abilities even while my cursor won't click.

I can fix it by alt tabbing out and then back in and my mouse works again. No clue what's causing this? Anyone experienced this before? I've tried changing from windowed/fullscreen/borderless and changing graphics settings, and closing other background software but it keeps happening... halp.