The Phantom Called PIRA – A Silent Progression🕵️

I raised an eyebrow. “Progression Independent of Relapse Activity,” I murmured. “A suspect that makes no sound—but leaves deep tracks. Clinical worsening without any sign of relapses.”

🧠 The Case: A Disease That Changes Quietly

Multiple Sclerosis is a chameleon of diseases—sometimes loud and dramatic, with relapses and visible lesions. But PIRA is different. No fever, no contrast enhancement. And yet: the patient walks slower, thinks less clearly, lives more restricted.

A classic case of “The dog that didn’t bark,” as Holmes would put it. The riddle? How do you detect something that's trying not to be seen?

🔍 Clue 1: The MRI Scan

I started with the obvious—the imaging. But the MRI remained unimpressed. No new lesions, no contrast uptake, no outcry. Just a creeping brain atrophy. Barely measurable. Yet suspicious.

I analyzed the slow distortions near the ventricles, searched for PRLs (paramagnetic rim lesions) and slowly expanding lesions. Signs of chronic activity. But they whispered—no screaming evidence.

🔬 Clue 2: The Clinical Tests

Next, I turned to the function tests: the 25-Foot Walk, the Nine-Hole Peg Test, and the Symbol Digit Modalities Test—quiet investigative tools meant to pick up subtle changes before EDSS even stirs.

A barely noticeable delay in walking. A slight clumsiness in the peg test. A few symbols misplaced on the SDMT.

To the untrained eye: nothing. To me? A pattern. It was as if the culprit—let’s call it PIRA—knew exactly where our diagnostic blind spots were. Acting where we too often say “still stable”—and too late admit “something’s changed.”

"The devil is in the details," Holmes used to say. And it was those details that raised my suspicions.

📈 Clue 3: The Spinal Fluid Speaks

I wasn’t done. I requested CSF samples—spinal fluid, where the early whispers of neurodegeneration gather. No lie escapes this medium for long.

I asked the lab to analyze Neurofilament Light Chain (NfL)—the crime scene bloodstain of damaged neurons. And Glial Fibrillary Acidic Protein (GFAP)—a signal of astrocyte activity, those underrated guardian cells of the brain.

The results? Elevated. Not dramatically. No sirens. Just a flickering warning light.

“Not guilty,” the report said. Maybe. Or maybe just: “Not convicted yet.”
As Holmes wisely remarked: "It is a capital mistake to theorize before one has data."

🩻 Clue 4: The Eyes as a Window

I called in my colleagues from the OCT lab—Optical Coherence Tomography, a finely tuned retinal scan. A sort of MRI of the eye, if you will.

What they sent me was telling: The retinal nerve fiber layer was thinning. The ganglion cell layer had shrunk. No catastrophe. No screams. Just a whisper—soft, almost imperceptible.

If the eye is truly the mirror of the brain, then this one was not just fogged—it was cracked. To the untrained: nothing. To Sherlock MS? A clear trace. The culprit was still at large. Only now, working from the shadows.

🗃️ The Case File Grows – But the Suspicion Remains Elusive

What is PIRA, then? A mix of aging immunity, slow-burning degeneration, poorly behaved microglia? Or just the sum of many small losses, none dramatic—but devastating in daily life?

As Holmes once said: "The difference between a spark and an explosion lies not in the energy, but in the direction." PIRA does damage—silently, stealthily. And our task as neurodetectives? To catch it early.

🧾 My Verdict as Sherlock MS

• PIRA is not a shadow—it’s a quiet perpetrator that forces us to look harder.
• The key is not in one test, but in a smart combination:
  • High-resolution MRI
  • Regular, exact function testing
  • Biomarkers that capture both inflammation and neurodegeneration
  • OCT as an early warning system
• And most importantly: listen to the patient—truly listen.

As Holmes put it: “You see, but you do not observe.”

The case is far from closed. But the clues are starting to speak.

Yours truly,
Sherlock MS, Neurodetective & Specialist in Silent Progression