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For me, it was the unlikely combination of Guillotine, Monstro's Lung, Cupid's Arrow, Placenta and Small Rock. All together, clutched Isaac so hard, then Lost Contact in The Chest was sealing the deal against MS. Though, the damned horsemen nearly killed me due to the ♥♥♥♥♥♥♥♥ patterns of Death & War summoning in explosives out of nowhere..
Best item I've gotten on the challenge to date was juda's shadow. Every other item's been crap.
Then the stupid curse of maze teleports me as I go back into the battery room and curse of the lost means I never found the battery again. Basically lost all my hp to my own tears then lil horn room and I can't fire or I die. Death by horn balls waiting for rotton baby to take out the lil horns.
It probably only protects you from curse of can't see your hp since its the only random curse in the challenge.
Yup, I held R looking for mom's knife or tech x. Found tech x and still only managed to beat it with a single red heart.
It is much easier, because:
No "challenge", which can be beaten by simply restarting the run till Mom's Knife, Tech-X or some good defensive item (Scapular, Holy Mantle, etc.) can be considered even close to being difficult.
I still dislike the challenge. It's just tedious if you do it "no cheese". No challenge whatsoever (you know, how one would expect from a challenge). Sh*t just takes an eternity to kill. Now add the dreaded portals into the mix and you may fight in the same room for like 5 minutes.
With a lack of health drops, you really rely on high DPS more than anything else there, so i blame no one for "Hold R to win".
And i liked the BRAINS!! challenge, btw. Speed was (and still is) the only really, really bad one.