Demyelinating Diseases

MS vs GBS vs CIDP — the myelin is leaving, but the pattern tells you who's stealing it and where

Before we start — quick vignette:
A 28-year-old woman presents with blurred vision in her right eye and pain with eye movement for 3 days. She mentions that 6 months ago she had an episode of numbness and tingling in her legs that resolved on its own. MRI of the brain shows multiple periventricular white matter lesions. What is the most likely diagnosis?
Guillain-Barré syndrome
Multiple sclerosis
Neuromyelitis optica
CIDP
The Big Three: MS vs GBS vs CIDP

Three diseases that strip myelin. Three completely different patterns. The trick is knowing where (CNS vs PNS), how fast (acute vs chronic), and which direction the damage goes.

Multiple Sclerosis (MS)
Where

CNS only — brain and spinal cord. Never touches peripheral nerves.

Pattern

Relapsing-remitting (85%) — episodes come and go, separated by time. Dissemination in time AND space is the diagnostic requirement. 🔑 Multiple Sclerosis = Multiple Spots, Multiple times. If it only happened once or in one place, it's not MS.

Classic findings
  • Optic neuritis — painful vision loss, often the first attack
  • Lhermitte sign — electric shock down spine on neck flexion (hover to feel it)
  • Internuclear ophthalmoplegia (INO) — MLF lesion, can't adduct on lateral gaze
  • Uhthoff phenomenonSymptoms worsen with heat (hot bath, exercise, fever) because demyelinated axons conduct even worse when warm. The myelin normally insulates against temperature — without it, heat slows conduction further. — symptoms worsen with heat
CSF

Oligoclonal bands (IgG) present in CSF but NOT serum. Normal glucose, mildly elevated protein.

MRI

Periventricular white matter plaques — perpendicular to ventricles (Dawson fingersNamed after James Walker Dawson. The plaques form around the small veins that run perpendicular to the ventricles — so the lesions follow the veins and appear as "fingers" radiating outward. Pathognomonic for MS on MRI.). Enhancing = active. Non-enhancing = old.

Treatment

Acute flare: IV methylprednisolone. Disease-modifying: interferon-beta, natalizumab, ocrelizumab, fingolimod.

Guillain-Barré Syndrome (GBS)
Where

PNS only — peripheral nerves and nerve roots. Never the brain.

Pattern

Acute ascending paralysis — starts in the feet, climbs up over days to weeks. Symmetric weakness that ascends is the giveaway. 🔑 GBS = Goes Bottom-up, Symmetric. Starts at the feet, climbs. If it starts in the face or one side, think something else.

Classic findings
  • Ascending weakness — legs before arms before respiratory muscles
  • Areflexia — reflexes disappear because lower motor neurons are demyelinated
  • Often preceded by Campylobacter jejuniGBS is a post-infectious autoimmune attack. C. jejuni's lipooligosaccharide mimics gangliosides on peripheral nerve myelin — so the antibodies the immune system made against the bacteria also attack your own nerves. Molecular mimicry at its worst. diarrhea (1-3 weeks before) or viral URI
  • Autonomic dysfunction — cardiac arrhythmias, BP swings, urinary retention
CSF

Albuminocytologic dissociationelevated protein with NORMAL cell count. Protein is up because inflamed nerve roots leak protein into CSF. Cells stay normal because the immune attack is in the peripheral nerves, not the CSF space itself.

Danger zone

Respiratory failure. Monitor FVCForced Vital Capacity — the total volume of air you can forcefully exhale. In GBS, you monitor FVC every 4-6 hours. If it drops below 20 mL/kg (or 1 liter in an average adult), intubate. Don't wait for the patient to look like they're struggling — by then it's too late. every 4-6 hours. Intubate if FVC < 20 mL/kg.

Treatment

IVIG or plasmapheresis. NOT steroids (they don't help GBS — boards loves this trap).

CIDP (Chronic Inflammatory Demyelinating Polyneuropathy)
Where

PNS only — same as GBS, different timeline.

Pattern

Chronic and progressive — symptoms develop over >8 weeks (vs GBS which peaks in 4 weeks). Think of CIDP as "chronic GBS" — same location, slower burn.

Classic findings
  • Symmetric proximal AND distal weakness (GBS is more distal-predominant)
  • Areflexia
  • Sensory loss — more prominent than in GBS
  • Relapsing-remitting OR progressive course
CSF

Same as GBS: albuminocytologic dissociation

Key Difference from GBS

Timeline. GBS = acute (peaks <4 weeks). CIDP = chronic (>8 weeks). Same CSF, same nerve damage location, different speed.

Treatment

IVIG, plasmapheresis, AND steroids work here (unlike GBS). The chronic nature means the immune process responds to chronic immunosuppression.

MS GBS CIDP
Location CNS (brain + cord) PNS (peripheral nerves) PNS (peripheral nerves)
Timeline Relapsing-remitting (years) Acute (days to 4 weeks) Chronic (>8 weeks)
Reflexes Hyperreflexia (UMN) Areflexia (LMN) Areflexia (LMN)
CSF Oligoclonal bands High protein, normal cells High protein, normal cells
Imaging Brain MRI: white matter plaques Nerve conduction: demyelination Nerve conduction: demyelination
Steroids help? Yes (acute flares) NO Yes
Trigger Autoimmune (HLA-DR2) Post-infectious (C. jejuni, CMV) Autoimmune (often idiopathic)
Board Trap: GBS does NOT respond to steroids. Every other inflammatory demyelinating condition does. If the question asks about treatment and the patient has acute ascending paralysis — the answer is IVIG or plasmapheresis, never steroids.
MS Subtypes — Which Pattern?

Relapsing-Remitting (RRMS) — 85%

The classic. Attacks come, damage happens, symptoms partially or fully recover, then another attack months or years later. Most patients start here.

Secondary Progressive (SPMS)

Starts as RRMS, then transitions to steady decline without clear relapses. Most untreated RRMS patients convert to SPMS within 10-15 years. The relapses stop but the disability doesn't.

Primary Progressive (PPMS) — 10-15%

Progressive decline from the start. No relapses. No remissions. Just a steady downhill. More common in older males (MS overall is more common in young women). Treated with ocrelizumab.

The board pattern: Young woman + optic neuritis + periventricular plaques = RRMS. Older male + progressive myelopathy + no relapses = PPMS. Know both presentations.
NMO vs MS — The Mimic

Neuromyelitis optica (NMO / Devic disease)Previously called Devic disease. An autoimmune attack on aquaporin-4 water channels, primarily in the optic nerves and spinal cord. It was once thought to be a variant of MS — it's not. Completely different antibody, different treatment, different prognosis. looks like MS but it's a different disease with a different antibody and a different prognosis. Boards will try to trick you.

MS NMO
Antibody Oligoclonal bands (CSF) Anti-aquaporin-4 (AQP4)
Optic neuritis Usually unilateral Often bilateral, more severe
Spinal cord Short lesions (<3 segments) Longitudinally extensive (≥3 segments)
Brain MRI Periventricular plaques Often normal (or atypical lesions)
Demographics Young white women More common in non-white populations
Treatment Interferon-beta, natalizumab Rituximab, eculizumab (interferon-beta can WORSEN NMO)
Board Trap: If the spinal cord lesion extends over 3+ vertebral segments — think NMO, not MS. MS makes short, scattered lesions. NMO makes one long angry one. Also: interferon-beta worsens NMO. Getting the diagnosis wrong means giving the wrong treatment.
GBS Variants — The Board Favorites

Miller Fisher Syndrome

The GBS variant boards loves most. Classic triad:

  • Ophthalmoplegia (can't move eyes)
  • Ataxia (can't coordinate)
  • Areflexia (no reflexes)

Associated with anti-GQ1b antibodies. It's "GBS that starts at the top instead of the bottom."

AIDP vs AMAN vs AMSAN

AIDP (acute inflammatory demyelinating polyneuropathy) = the classic form. Demyelination. Slowed conduction velocity on nerve studies.

AMAN (acute motor axonal neuropathy) = axonal variant. Motor only. More common with Campylobacter. Anti-GM1 and anti-GD1a antibodies.

AMSAN = axonal variant with sensory AND motor involvement. Worst prognosis.

For boards: Ophthalmoplegia + ataxia + areflexia = Miller Fisher = anti-GQ1b. That's the testable triad.
Decision Tree: Which Demyelinating Disease?
A patient has neurological symptoms with suspected demyelination. First question: is the damage in the CNS or PNS?
CNS — brain and/or spinal cord signs (hyperreflexia, Babinski, brain MRI lesions)
PNS — peripheral weakness, areflexia, nerve conduction abnormalities
Elimination Game

Each scenario gives you clues one at a time. Eliminate the wrong diagnoses as you go.

Clinical Vignettes
Five patients walked into your neurology clinic. Figure out what's wrong with them before they fall over.