A neuromodulation system for treating epilepsy provides therapeutic elements for modulating nerve activity to prevent or diminish (e.g., through reduced intensity or shortened duration) epileptic seizures. The therapeutic elements may be positioned in the vasculature of the patient or on the skin of the patient and are energized to modulate nerve fibers positioned outside the vascular walls. Electrode positions may include the surface of the hand and/or arm, or blood vessels within the hand and/or arm such as the vena comitans of the ulnar artery, the vena comitans of the radial arteries, the ulnar artery, or the radial artery. Alternative electrode positions are beneath the skin of the hand or arm but external to the blood vessels. Target nerves include the median nerve, radial nerve, ulnar nerve and/or branches thereof.