Some good thoughts here already.
The 22wmr was designed as a rifle cartridge. Thus it is a slow powder burn to take advantage of the long rifle barrel. Out of a short barrel (pistol) it spews unburned powder - it looks spectacular - big flash - but doesn't help the bullet with extra energy very much.
So a 22 lr is nearly as good out of a pistol - but without the huge powder burn flash. (Yes, I have these guns and yes, they do behave this way.)
A Walther ppk 22 has had many reports of cycling troubles - ftf, fte, stovepipe, ... I've shot them and can back up those reports.
A revolver will be a little thicker than the Walther - but they may not bother your wife - depends on how she carries.
A 22 for self defense is a heck of a lot better than nothing. I would not have a problem with that, myself.
The going to a 380 thing... (I've had two 380's and use a 380 for most of my carry) ... The small ones - most are small - they are after all for conceal carry - have a pretty substantial recoil to them - because they are so light.