I read an article a long time ago about an Australian Karateka, John Marrable, who gained several dan rankings while in a wheelchair. The memory is a bit hazy, but IIRC he devised ways to do his kata while in the chair, and ways to fight using parts of his chair as weapons, or to block with, etc.
I've read of a high dan kenpo (I think) guy with one leg who continues to practice from a wheelchair. I think he lost his leg after he'd bee ntraining a long time, though.
I read about a US wrestler who is competitive at at least collegiate level and perhaps even higher who was born without hands or feet.
While I wouldn't wish it on anybody, I'd hope the human spirit would find away to keep on even after such an enormous setback.
As for getting into fights in a chair, I'd be looking for some sort of armoured and weaponised chair - blades that spring out from the wheel hubs per the pram in Shogun Assassin, rack mounted machine guns, rocket propelled grenades, flame throwers ...