In 1500, Henry VII travelled to Calais to meet with Philip of Burgundy (also, interestingly, known as Philip the Handsome). This visit was to reassure Philip that any trouble between the warring Lancastrians and Yorkists had been put to rest and thus trade could resume as normal. Also, he wished to pursue potential marriage alliances for Prince Henry and Princess Mary.
During this visit, Ferdinand of Aragon, who is yet to send his daughter Katherine to England to wed Prince Arthur, became suspicious that Henry was infact looking for a new bride for his eldest son - which led to concern that the marriage treaty would not be upheld.
Philip and Juana were quite the power couple. Philip was the son of Maximillian, the Holy Roman Emperor, meaning he was due to inherit quite a hefty title, and Juana, elder sister of Katherine of Aragon, became the heir of Castile in 1500 after her older brother (Juan) and sister (Maria) passed away.
In 1500, Juana gave birth to a boy named Charles, who would go on to be the King of Spain. She had another son who became a lieutenant and four daughters who became queens of various places.
However, Juana had what has been described as melancholia; meaning that she probably suffered from severe bouts of depression. This surfaced at various points in her life but intensified in 1506 when Philip died, and it has been said that she refused to leave his embalmed body.
Her father, Ferdinand, then pushed her to one side, ruling in her place. When he died, her son Charles did the same after having her declared unfit to rule.
Mistreated and misunderstood are two words which could easily replace the 'mad' so often attached to her name. Though personally I may choose to reinterpret that 'mad' as angry, as I certainly feel angry on her behalf.