The Case of the Vanishing MS Drawers

Me? I had something far more interesting: a Nature Medicine paper with a mega-dataset: thousands of MS cases, tens of thousands of visits, and an algorithm that calculates with more sense than most textbooks.

The question: Are our beloved drawers “RRMS, SPMS, PPMS” actually just a polite misunderstanding?

🗄️ Old labels, new map

So far, we’ve been dutifully sorting MS into three boxes:

• relapsing
• secondary progressive
• primary progressive

Convenient for forms and for our bureaucratic colleagues, scientifically… a bit coarse.

The algorithm in the Nature Medicine paper ignored those labels and looked only at the naked facts:

• physical disability (EDSS, walking and hand function tests)
• total brain damage (lesion burden + atrophy)
• clinical relapses
• silent MRI activity (gadolinium-enhancing lesions without symptoms)

The result wasn’t a new alphabet soup. It was a more detailed MS subway map.

🚇 Four “lines” instead of three drawers

To keep it memorable, I translated and rebranded the new states. Forget EME-MS & friends, we’re speaking, from now on, in:

• F-MS = Early MS
  • Low damage, low disability, the “blue zone.”
• S-MS = Silent Active MS
  • MRI is on fire, patient looks clinically calm, the “yellow zone.”
• R-MS = Relapsing MS
  • The classic symptomatic relapse, the “orange zone.”
• A-MS = Advanced MS
  • Marked disability, high brain damage, little acute inflammation, the “red zone.”

The algorithm estimates how likely someone is to move from one zone to the next like switching lines in the Underground.

And here’s where it gets interesting:

• You almost always start in F-MS.
• From there, activity pushes you into S-MS (silent MRI activity) or straight into R-MS (a relapse).
• Only through these active states do you eventually drift into A-MS.
• And from A-MS, practically nobody goes back. End of the line.

In other words: Every episode in S-MS or R-MS is a transfer toward the red line.

My brother would say: “The culprit always returns to the crime scene.”
I’ll add: “And each time, he takes a little brain with him.”

📉 PIRA: silent worsening as the hidden accomplice

The model can also estimate risk for PIRA: progression independent of relapse. The kind of deterioration where the letter says, “No new relapse,” while the patient wonders why a walking stick suddenly feels… realistic.

The pattern:

• In F-MS, PIRA is rare.
• After time spent in S-MS and R-MS, risk rises noticeably.
• In A-MS, PIRA becomes the default mode: few relapses, but steadily increasing disability.

The unromantic message: Every inflammatory activity visible or silent pays into the account called “later silent progression.”

💊 DMTs as the anti-gang special unit

Of course I wanted to know what our therapies do on this map. Comparing untreated patients with those on modern DMTs, the picture is clear:

• transitions from F-MS → S-MS/R-MS become much less frequent
• people stay longer in the blue zone and enter yellow/orange later or not at all
• the path toward A-MS is delayed in a way that matters statistically and clinically

  
  

It’s like adding extra patrol units exactly where most street fights usually break out.

🎩 So what does this change about how we think?

Here comes the mildly arrogant bit you’re here for: anyone still acting as if RRMS, SPMS and PPMS are three completely different species is holding an outdated map.

The data suggest:

• MS is a continuum, not a three-drawer cabinet.
• The relevant questions are no longer: “Is this SPMS yet?”
• But rather:
  • Which zone is the person in right now: F-MS, S-MS, R-MS, or A-MS?
  • How often do they visit S-MS and R-MS?
  • How much brain has already been lost along the way?

    
    

For practice, that translates into:

• Protect F-MS: treat early, don’t hesitate.
• Take S-MS seriously: there is no such thing as “only MRI activity” anymore, yellow is on the way to red.
• Limit R-MS: relapses aren’t just annoying; they’re real track switches.
• Avoid A-MS as long as possible: once you’re there, you typically stay there.

🧠 Closing words from Baker Street

Downstairs, my brother keeps chasing Moriarty: diamonds, blackmail, dramatic confessions. Me? I’m chasing a quieter, more stubborn enemy: the habit of squeezing MS into crude drawers and underestimating silent activity.

This new data map shows MS behaves more like an Underground network than three terminal stations. And if we understand the lines F-MS, S-MS, R-MS, A-MS, we can target therapies better, explain risk more honestly, and maybe keep more people on the blue line for as long as possible. The case “New MS classification” isn’t fully solved. But at last, we’ve got a map that deserves the name.

Yours, naturally, just a little superior,

Sherlock MS