What are the difficulties historians face in using manuscripts?

Historians faced a lot of difficulties while using manuscripts because:

1. There was no printing press in the 13th and 14th centuries. Scribes in those days made manuscripts by hand.
2. To copy was not an easy exercise. Scribes could not read the handwriting of the other writers.
3. They were forced to guess. So there were small but significant differences in the copy of the scribed.
4. These small words or sentences here and there grew over centuries of copying.
5. The manuscripts of the same text became a great extent different from the original.