I recently tried to do the GRS route, picking it up at Cape Girardeau, after doing the Katy Trail in MO.
I abandoned the trip because I found the maps so hard to follow.
My original plan had been to camp the first night at the Lion's Club Park (to the east of Karnak, according to the commentary), only to find it was west of town, so I backtracked, and is currently used to store aggregate for the highway department. Since what little ground that wasn't covered with aggregate seemed to be covered with trash, I decided to push on to the next stop in Golconda, but I never made it, since I couldn't correlate the map with the ground.
Directions such as "6.5(11)Mermet. Turn right onto US 45. Turn left onto CR 1375N..." sent me to scanning the area on my GPS, since CR 1375 isn't visible when you first get on US45 -- it's another half a mile, and I assumed I must have missed a turn (which in this area always got me on a road with heavy trucks that refuse to move over, a 50MPH+ speed limit and no shoulders).
A GPS is of no help when the directions say "At T, turn right" without specifying the road. Since I wasn't carrying detailed backup maps for the whole distance, I got irretrievably lost on the Mermet Road section (which came up on my GPS with a different name). Apparently, when the directions say bear left, they mean "take a left at the T onto Staton Ridge Road", and when they say "At T, turn right", they really mean "bear right on New Columbia".
If there had been several of me, so I could have checked out all the confusing areas by checking all directions, maybe it would have been different. Of course, not being surprised by the camp ground being a big pile of rocks would have left me fresher, and not trying to figure all this out after doing 80 miles with full gear on a hot day.
In the end, I spent some time driving the area, and have come to the conclusion that its road system really isn't particularly suitable for biking anyway -- narrow lanes, combined with no shoulders is not a happy combination.
In putting in the turn-by-turn directions, please always name the road -- even if ther's no signage when the route is first mapped, signs can get put up, and locals can't point you towards "unnamed road". When you have to backtrack, it takes some time to resynch your mileage with the maps, and then it's easy to get confused at turns, if the directions are only as precise as "At T, turn right".