#1 thing that helped me was running d2r in compatibility mode. Windows 7.
Tried a bunch of other crap but nothing really helped: setting the d2r processes in task manager to realtime, limiting FPS to your refresh rate etc.
if running on laptop i would make sure that you are on maximum performance settings for your power options, and video card settings.
Dont know how to do it, as i use d2rloader script.
Im suspecting is a problem with the gpu, it has like a "negative" spike before the actual spike. Im mostly getting these spikes when there are a lot of things happening on the screen, such as bolts from scarabs, or when using town portal with the other accounts. But it also happens when im still standing in town sometimes, so don't know where the real problem is, yet.
Thanks to everyone for the responses