The brain’s early whisper

Before anyone says “MS?”, the nervous system is already whispering:

• Myelin signals first: signs of myelin damage appear on average ~7 years before symptom onset. 
• Axons follow: hints of axonal damage show up about ~6 years beforehand. 
• Astrocytes get loud: only at clinical onset do they report, “Now it’s really burning!” 
  

First, the insulation crumbles, then the cables suffer, and only when it crackles do the neighbors notice.

📡 The immune system’s quiet prelude

In the pre-symptomatic stage, the lines are already busy:

• Alarm pathways (e.g., IL-3/NF-κB-like signals) start humming early. 
• B cells & NK cells behave as if they’ve already taken the night shift. 
  In short: it simmers in a coordinated way long before the siren goes off.
  

🧪 The bloodhound in the blood

The file tells of many proteins measured from large serum collections samples before and after symptom onset. From this emerged a compact panel (~21 proteins) that detects many pre-symptomatic cases.
👉 Not an “MS stamp” for tomorrow, but an early-warning bloodhound for at-risk groups (e.g., family history, RIS): it could trigger targeted imaging/CSF work-up before the cables tear. 

🗺️ The city

Picture the brain as a city:

• Myelin = the insulation of power cables 🧵🔌
• Axons = the cables themselves 🧰⚡️
• Astrocytes = city police & fire brigade 🚒👮‍♂️

First the insulation crumbles (barely visible), then the cables suffer (performance drops), and only when the streetlights flicker does the fire brigade roll out. That’s why some people feel “not quite right” for years while standard MRIs politely nod.

🎯 Why this matters

• Earlier detection: if myelin chirps ~7 years in advance, we can guide at-risk people more closely—smarter, earlier, sharper.
• Timing therapy: those who grasp the sequence (Myelin → Axon → Astrocyte) can place treatments at the right moment.
• Honest counseling: Symptoms ≠ MRI; the biomarker cascade explains the apparent paradox. 

📔 Sherlock’s case cover (with a tea ring)

• 🕰️ Timeline: Myelin (~−7 yrs) → Axon (~−6 yrs) → Astrocyte (≈ onset)
• 📡 Early alarms: immune signals & cells are already at work
• 🐾 Tool: small protein panel as an early bloodhound (solid first concept; more validation to come)
• 🧭 Practice idea: refine risk profiles, stage monitoring, and bring interventions to where things go wrong first

I close the file, sip the cold tea, and jot on the envelope:
“The case begins in a whisper; those who hear it prevent the bang.”
More detective work? Gladly. But first: fresh tea.