According to The Athletic's Jon Krawczynski, Butler couldn't put any weight on his leg and had to be carried to the locker room by Karl-Anthony Towns and Cole Aldrich.
Shams Charania of Yahoo Sports reported X-rays on the knee came back negative and an MRI is scheduled for Saturday, adding that the team has some hope that the injury isn't severe.
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Butler has been instrumental in leading the Timberwolves to the fourth-best record in the Western Conference. He leads the team with 22.4 points and 1.9 steals and ranks second with five assists per game.
The loss of Butler leaves a significant void in the Timberwolves' backcourt. Jamal Crawford will likely receive a majority of the playing time for head coach Tom Thibodeau.
Towns, Andrew Wiggins and Jeff Teague will have to carry the load for the Timberwolves until Butler is able to return.