Demyelinating Diseases

Demyelination Basics - Myelin Under Siege

• Myelin: Vital lipid-protein sheath insulating nerve axons.
  • CNS: Formed by oligodendrocytes (one cell supports multiple axons).
  • PNS: Formed by Schwann cells (one cell per axon segment).
  • Function: Facilitates saltatory conduction for rapid (↑) nerve impulse velocity.
• Demyelination: Pathological loss or damage to myelin; axons initially preserved.
  • Impact: Slows, blocks, or desynchronizes nerve signals, causing neurological deficits.
  • Prolonged demyelination can lead to secondary axonal degeneration and permanent loss.

⭐ The CNS has limited capacity for remyelination compared to the PNS, contributing to chronic disability in diseases like MS.

Multiple Sclerosis - Plaque Attack Central

• Autoimmune CNS demyelination; HLA-DR2, EBV, ↓Vit D.
• Patho: T-cell attack on myelin/oligodendrocytes → axonal damage.
• Key Features:
  • Optic neuritis (painful ↓vision, RAPD).
  • Internuclear Ophthalmoplegia (INO).
  • Lhermitte’s sign (spinal shock on neck flexion).
  • Uhthoff's phenomenon (symptoms worsen with heat).
  • Charcot's Neurologic Triad (📌 NISS): Nystagmus, Intention Tremor, Scanning Speech.
  • Sensory loss, weakness, fatigue, bladder/bowel issues.
• Diagnosis: McDonald Criteria (DIS & DIT).
  • MRI: Periventricular plaques (Dawson's fingers), corpus callosum, brainstem, spinal cord. Active lesions: Gd-enhancement.
  • CSF: ↑IgG index, Oligoclonal Bands (OCBs).
• Plaques: Demyelination foci. Acute (inflammation) → Chronic (gliosis, axonal loss). Shadow plaques (remyelination).
• Types: RRMS (~85%), SPMS, PPMS.

> ⭐ Periventricular white matter plaques (Dawson's fingers) are highly characteristic on MRI.

• Acute Relapse: IV Methylprednisolone. Refractory: Plasma exchange.
• DMTs: IFN-β, Glatiramer acetate, Fingolimod, Natalizumab, Ocrelizumab.

MS Variants & NMOSD - Mimicry Mayhem

• MS Variants (Atypical):
  • Marburg: Acute, fulminant; large, destructive lesions. Often fatal.
  • Balo's Concentric Sclerosis: Rare; concentric rings of demyelination.
  • Schilder's Disease: Extensive, bilateral demyelination; typically children.
• NMOSD (Devic's Disease):
  • Key: AQP4-IgG positive (most cases).
  • Classic triad: Optic neuritis (often bilateral, severe) + Transverse myelitis (longitudinally extensive, ≥3 segments) + Area postrema syndrome.
  • Brain lesions: Periependymal, hypothalamus, brainstem; not typical MS pattern.

⭐ NMOSD is an astrocytopathy (targeting AQP4 on astrocytes), whereas MS is primarily a disease of oligodendrocytes/myelin.

Other CNS Demyelinators - Swift Sheath Strippers

• Progressive Multifocal Leukoencephalopathy (PML)
  • Etiology: JC virus reactivation.
  • Risk: Immunocompromised (AIDS, immunosuppressants).
  • Patho: Lysis of oligodendrocytes → multifocal demyelination.
  • Clinical: Rapid, progressive neurological deficits; often fatal.
  • Dx: JC virus DNA in CSF.
• Osmotic Demyelination Syndrome (ODS)
  • A.k.a. Central Pontine Myelinolysis (CPM).
  • Etiology: Rapid correction of severe hyponatremia.

    ⭐ Prevention is key: correct hyponatremia slowly, typically ≤ 8-10 mEq/L in 24 hours.

  • Site: Pons (classic), extrapontine areas.
  • Clinical: Quadriparesis, dysarthria, dysphagia, "locked-in" syndrome.
• Marchiafava-Bignami Disease (MBD)
  • Rare; associated with chronic alcoholism & nutritional deficiency.
  • Patho: Demyelination & necrosis of corpus callosum.
• Subacute Sclerosing Panencephalitis (SSPE)
  • Etiology: Persistent, aberrant measles virus infection.
  • Onset: Years after initial measles.
  • Clinical: Progressive cognitive decline, myoclonic jerks, seizures.
  • Dx: ↑ measles antibodies in CSF/serum; EEG: periodic complexes. Fatal.

High‑Yield Points - ⚡ Biggest Takeaways

• MS: Most common, autoimmune; relapsing-remitting course; periventricular plaques (Dawson's fingers), oligoclonal bands in CSF.
• ADEM: Monophasic, post-infectious/vaccinial, common in children; widespread perivenular demyelination.
• PML: JC virus in immunocompromised (HIV); non-inflammatory demyelination of oligodendrocytes.
• Osmotic Demyelination Syndrome (CPM): Rapid correction of hyponatremia; affects pons, may cause locked-in syndrome.
• GBS (AIDP): Ascending paralysis, areflexia, post-Campylobacter; albumino-cytological dissociation in CSF.