The most obvious sign is when they can't grasp food in their paws or when one or more front paws are "clubbed" (fingers curled in). But usually the rat has been a little off for at least a week before that happens. Often they get less active and less curious, sometimes confused looking. Sometimes they lose interest in food or can't seem to coordinate their mouth to eat. Sometimes they have motor difficulties. There should be some good info on the Rat Health site (can't recall the site URL).
When one of my rats over 18 months looks not quite right, I watch carefully for PT. With younger ones the problem is much more likely to be something else.
Wish they could talk!