It's posited that Howard Hughes' increasingly strange behavior and eventual withdrawal into reclusion was precipitated by a series of TBIs he suffered in test pilot crashes.
There is also a theory that he began taking pain medication for back pain related to injuries suffered in crashes, and the dosage/addiction added up over time, all the while none of this staff or medical experts tried to wean him off it. Very much like the situation with Michael Jackson and painkillers.