This usually happens when mIRC isn't closed properly, e.g. after a crash or power outage. It might also happen when shutting down Windows without closing mIRC first.

The reason is that mIRC keeps certain things in memory, but doesn't write them to disk regularly (only when you exit the program or open/close the options dialog or the scripts editor, afaik). That way, changes may get lost if the program terminates unexpectedly.

So if you're not in the habit of closing programs before shutting down your computer, that's generally a good idea to avoid data loss of any kind.

Another thing you could do is type /saveini after making changes from the command line, e.g. via /ignore. This will make mIRC update its settings files right then.