...Actually, one possibility is that they've grown too big and need something like checkini ran against them.
Whenever I see this issue my first option is to run checkini, if that fails, I restore my INI from backups.
Checkini will almost immediately tell you if it can fix the issue or not. The DESKTOP handle is one of the very first things it checks, if it can not find it nor determine what it should be, it basically stops, at which point in time you know the only other fix is the INI restore.
FYI, there may be other ways of dealing with this, but the above is what my process is, similarly to Dave's I believe.