It was almost inevitable, given Isco's Real Madrid career. So often the right player for the wrong manager, the Spain midfielder's enforced absence after undergoing an appendectomy has come at precisely the wrong moment for the right manager.

Isco is likely to be out for a month, with a return date tentatively slated for the Camp Nou Clasico on Oct. 28. The unpredictability of it all will smart more than the scar over the next few days, as Isco ruminates on yet another setback. It has always been a case of one step forward and two steps back during his time at the Bernabeu, but until Tuesday's announcement, the pieces had finally started to fall into place for the 26-year-old.

The turnaround began toward the end of last season, when he prevented Madrid from being picked apart by Juventus in the Champions League.

A hat trick for Spain against Argentina followed, and so far in 2018-19, Isco has been a key player under Julen Lopetegui. Against Athletic Bilbao, he climbed off the bench to score with his first touch, an untracked run and glancing header breaking the deadlock against a typically obstinate Lions defence.

A week later, it was Isco's movement across the front line that prevented Espanyol from leaving the capital with a deserved point. Marco Asensio scored the only goal of the game, via a hat trick of lucky deflections, but it was Isco who conducted Madrid's attack.

Roma were hanging on in the Champions League before the Malagan magician broke the Roman wall with a delicious free kick. From there, the Italians rarely looked like getting back into it. The psychological blow had been delivered. That is the effect of having Isco on the pitch: opposition defenders never know what will come -- or when.

Unpredictability is Isco's calling card. Madrid might be impossible to stop for teams of limited resources, but their style is familiar enough that it doesn't take a tactical Sherlock Holmes to unravel the mystery afoot. For all of Gareth Bale's pace, Luka Modric's poise and Toni Kroos' precision, to a well-prepared side, Madrid's attacking play arrives long after an invitation to spoil the party.

Isco is solidifying himself as a star under Julen Lopetegui but will be out a month after appendix surgery. Gonzalo Arroyo Moreno/Getty Images

Real's next two opponents, Sevilla and Atletico Madrid, are hardly welcome guests. Madrid have been beaten on their past three visits to the Sanchez Pizjuan, and Atletico's 14 years of hurt were shown the door shortly after Diego Simeone's arrival. It's too early to talk of season-defining games, but dropped points while Barca face Leganes away and Athletic at home will ask questions of Lopetegui's craft if he cannot remedy the absence of his artful dodger.

The Real boss has exercised a level of conservatism -- at odds with his Spain career -- since his arrival at the Bernabeu, but it is no coincidence that those who served him so well during that time are enjoying greater exposure. Dani Ceballos is a natural fit to come into the midfield but scarcely a like-for-like Isco substitute. Alvaro Odriozola will start against Sevilla in another enforced change, and the inclusion of Nacho for Marcelo against Espanyol was not a high-risk strategy. Of Real's summer signings, only the former Sociedad full-back and Mariano have made it onto the pitch.

Lopetegui alluded to "rummaging about in the back of the cupboard" before the Espanyol game, but he might have to dig a little further to find someone as suited to Isco's role; perhaps he will in the January window. The midfielder attributed "all that stuff about how it was going to be Isco and 10 others" to the media after his decisive intervention in Bilbao, but subsequent games have suggested otherwise. Isco delivered in starts against Espanyol and Roma, and while Lopetegui's wealth of riches makes rotation inevitable, the Real boss' former Spain Under-21 favourite had been placing himself firmly in the best rather than the rest bracket before his appendix intervened.

Now Lopetegui, a big fan of "solutions" between the sticks, has to figure out how to cover for his most incisive player at the other end. Bale is in excellent form, scoring or assisting in every competitive game so far this season, but Karim Benzema's fast start has stuttered to a halt: the striker has not mustered a shot on goal in his past three outings.

Vinicius Junior remains the answer to a question Lopetegui refuses to ask, and in all likelihood Modric, Kroos and Casemiro will be tasked with covering for Isco with Asensio, Bale and Benzema up front. Whether that plays into the hands of Sevilla and Atletico is an inquisition the Real boss will face in the media room if results are not positive. A 4-4-2 with Mariano would add a little uncertainty, as would playing a front four or a back three in the absence of Carvajal.

Despite his qualities, Lopetegui is no risk-taker and will err on the side of caution over the next few games. Where that leaves Real before the next international break is anyone's guess, but Isco -- for so long the piece of the puzzle that seemed never to fit the whole -- will enjoy seeing if his side can cope without him.