The world reacts, and people within the world react.
With the world reacting, you're looking at first order effects that have two purposes:
- to signal the presence of an artifact of great power disturbing the natural order to the players
- to signal that presence to other people
Thus, you'll have the artifact animating a bunch of zombies in the night, especially if the party has the misfortune to enter a battlefield. (take a look at some of the answers here) to see how to signal the battlefield beforehand.
This signals that there is necromantic stuff going on. By having it become a pattern of "random" encounters that increase in scope, not only does it become a major campaign arc, but the players are likely to talk about it in game. Streetwise checks can be incredibly dangerous in situations like this.
If the players make any effort to find out what's going on from other sentients, the fact that they're asking questions signals to people who care that they not only have it, but they don't know what they have.
This may lead to typical Mr. Johnson quests (shadowrun term, references the people who hire the party) that end up in "unexpected and overwhelming force" for the evil, other adventuring parties ambushing them when they're on that quest, and good NPCs arriving, saving them, and generally complicating matters. Here, it's critical that no-one know where the MacGuffin is, only that the players are tainted by it. Each of the major powers will be using their own distinctive brand of force and persuasion to get their hands on it.
Make sure that at least one NPC offers to hire them to recover the artifact.
This way, there's no need to impose "madness" on the PC carrying the artifact, just on the world around him. If you're subtle, the rest of the party won't suspect. If the PC's subtle, he'll plant it somewhere or send the party on a quest to "recover" it without anyone being the wiser.