SherlockMS and the Case of the Stolen Insulation

My brother, Sherlock Holmes, solves cases with footprints in mud and cigar ash on carpets. Admirable. Truly.
I, on the other hand, solve cases where the clues live in milliseconds, micrometers, and molecules. And yes: that is the pinnacle of creation. It is me. It is the brain. And the combination most of all.

That evening a letter lay on my desk, as if the city itself had placed it there:

“Progression despite no disease activity in MS. No new relapses. No new enhancing lesions. But she’s becoming more progressive. We need you.” I smiled. “Ah. The classic case: the culprit works quietly.”

The Crime Scene: “Stable” and Yet Someone Is Losing Something

At the hospital, the patient was waiting for me; let’s call her Mrs. L. No drama, no theatrics. Just that slow, sticky decline: stairs growing longer, legs heavier, concentration shorter.

“But the imaging looks good,” the resident said in the tone of a man who believes an MRI is a moral judgment. “No activity, no contrast enhancement, no new lesions.”

I looked at him the way I would look at someone claiming they understood London because they once walked past Big Ben.
“My dear friend,” I said, “even when no new fire is burning, the wiring can still melt.”

Because this was not about the usual burglar called inflammation.
This was about something more elegant: repair that fails to happen.

The Victim: Myelin: the Coat Nobody Misses Until It’s Gone

I explained it to Mrs. L. in a way she could feel: “Imagine your nerve pathways as electrical cables. Myelin is the insulation. Without it, things flicker, spark, and eventually the cable burns through.”

She nodded. People love cable metaphors. They make the body feel logical. Adorable. Then came the question that always amuses me personally:

“Can the body repair that?” “Yes,” I said. “It can. And that is precisely our crime.”

Because repair in the nervous system means remyelination. And for that, you need cells that arrive like skilled workers at a construction site: precursor cells that mature into myelin-making specialists. The problem is: in some cases, the workers are standing at the door, but nobody picks up the toolbox.

First Trace: Traffic at the Construction Site—and the Curse of Ageing

I asked to see everything: timeline, age, disease duration, lesion patterns, clinical course.

And then I said the sentence nobody enjoys hearing because it sounds too banal to be true: “The culprit is called age.” The resident protested immediately: “But there are older patients who recover well!”

“Of course,” I replied. “There are also people who stroll through London rain and claim the weather is ‘quite pleasant.’ Exceptions are not arguments; they’re decoration.”

The point is subtle: with increasing age, remyelination often becomes less efficient, not necessarily impossible. There is no magical switch at “42” or “50” that clicks and stops everything. It’s more like an old watch: it still runs, but it runs worse.

Second Trace: The Real Mechanism: A Differentiation Blockade

I walked the team through the biology the way I walk my brother through motives:

“Precursor cells can often still arrive—migration, proliferation, recruitment. That part may work reasonably well. But the decisive step is the final one: maturing. The precursor must become a professional myelin-maker.”

And right there, in many ageing systems, the crime takes place: the cells get stuck in the waiting room like guests stranded at reception because no one lets them into the ballroom. “And who stops them?” someone asked.

I smiled. “Ah. Now we’re at the network of culprits. No good crime story has only one.”

Accomplices: Environment, Timing of Inflammation and Location of the Crime 

I explained it in my preferred order: first the truth, then the humiliation, then the punchline.

Accomplice 1: The lesion environment
The construction site itself changes. Signals, metabolism, inflammatory architecture; everything influences whether workers build or merely loiter.

Accomplice 2: Timing
Acute, “fresh” lesions are often more repairable than old, chronic ones. Not because time is evil, but because it leaves fingerprints: axonal damage, scarring milieu, brakes everywhere.

Accomplice 3: Location
And now it gets truly interesting: not every brain region plays by the same rules. Some regions seem capable of remyelination for a surprisingly long time especially in areas we long underestimated. Others are far stingier.

“So,” I concluded, “we have age as the main culprit, but the crime is committed differently depending on the neighborhood.”

London, as always.

The Investigators’ Mistake: When Measurement Becomes a False Witness

Now came my favorite part: forensic criticism.

“You say the imaging is ‘good.’ But what do you mean by that? That no new lesions appear? Or that myelin truly returns?”

Silence. I nodded. “Exactly.”

Because measuring remyelination in humans is… let’s say: complicated.

In tissue you sometimes see pale-repaired areas; people call them shadow plaques, as if naming them were already a confession. But even shadows can deceive: sometimes they’re repair, sometimes they’re something else entirely. 🌫️

For true precision, you would ideally think in terms of a g-ratio: how thick is the insulation relative to the cable? Elegant in pathology, rather… impractical in clinical routine. One typically avoids drilling holes into brains merely to satisfy my detective instincts. (Though I would understand.)

My Forensic Strategy: Milliseconds Don’t Lie

So I chose classic neuro-detective tools:

Visual evoked potentials (VEP)
“If insulation is poor, conduction slows. Remyelination speeds it up again.” I love VEPs: telegraph wires from the 19th century, only inside the skull. 📡
But I warned them at once: “Mind the age effect. VEP latencies slow with normal ageing anyway. If you don’t adjust for that, you interrogate the innocent.”

OCT (as the alibi checker)
“Before you celebrate remyelination, check whether the cable is still there. No axon, no real repair.”

Myelin-sensitive imaging
MTR, myelin water, diffusion models, useful, yes, but riddled with traps. Inflammation, iron, density changes: many things can impersonate myelin loss or return. The brain is a master of disguise.

The Turning Point: Mrs. L. Isn’t “Too Old”…She’s in the Wrong Chapter

In the end I stood at the ward window, watching London rain, and said:

“Mrs. L. is not ‘too old’ for repair. But we may be too late in the right part of the story.”

Because the key insight here is: there is no hard cut-off, no door that slams shut at a certain age. Remyelination can, in principle, occur across the lifespan sometimes surprisingly well in certain regions and in certain people. But on average it becomes more unreliable, slower, more heterogeneous.

And then the second punchline, which I particularly enjoy:

“Perhaps some people are simply good remyelinators and others are poor, and age is only part of the script.”

Doctors take that personally. They want to believe everything is controllable through therapy. But biology has its own humor.

The Second Culprit: “Biological Ageing” the Modifiable Villain

Now the case became truly criminalistic.

Chronological age is stubborn. It can’t be bribed.
But biological ageing, the functional “wear and tear” inside cells and tissues, is a different character. Less like a rock, more like a con artist: sometimes slowed, sometimes even partially reversed.

In this case that means: if specific ageing processes (for example cellular senescence) brake precursor cells, then in theory you could intervene right there, release the brakes, shift the milieu, make the workers work again.

I told the team: “Imagine fighting not only MS, but the biology of ageing as an amplifier. That would finally be a case with style.”

Closing: I Solve the Case and the Brain Still Outgrows My Arroganc

Back on Baker Street I sat in my room again. Naturally. The circle always closes with me. I wrote in my notebook:

• The crime: remyelination fails although inflammation seems quiet
• The main culprit: age (no strict cut-off; a slow efficiency dip)
• The accomplices: lesion age, location, milieu, axonal integrity, measurement pitfalls
• The refined side villain: biological ageing, potentially modifiable
• The key investigative tool: timing, region, and the humility to accept that “no new enhancement” does not mean “all is well”

Then I leaned back and smiled. “Most detectives chase criminals in the dark,” I said to myself. “I chase criminals in the light of imaging, electrophysiology, and cell biology. And still the brain is always the better storyteller.”

Outside, London hissed with rain. Inside, I was already thinking of the next case.

Because somewhere, in some neuron, something is being stolen again; and only a neuro-detective notices the difference between stillness and failed repair.

Your SherlockMS