Demyelinating Diseases

Demyelinating Diseases: Overview - Myelin Under Siege

• Definition: Pathological process causing loss or damage to myelin, the protective sheath around nerve fibers.
• Impact: Disrupts nerve impulse conduction → neurological deficits.
• Sites & Cells:
  • Central Nervous System (CNS): Oligodendrocytes targeted.
  • Peripheral Nervous System (PNS): Schwann cells affected.
• Types:
  • Primary: Myelin or myelin-forming cells are direct targets (e.g., MS).
  • Secondary: Axonal damage leads to myelin loss.
• Mechanisms: Often immune-mediated; also viral, ischemic, metabolic, toxic.

⭐ Multiple Sclerosis (MS) is the most common demyelinating disease of the CNS, primarily affecting young adults, especially women (F:M ≈ 2-3:1).

Multiple Sclerosis (MS) - The Great Masquerader

• Autoimmune CNS demyelination & axonal damage. Peak 20-40 yrs, F>M.
• Presentation: Symptoms disseminated in time & space.
  • Optic neuritis (painful vision loss, Uhthoff's phenomenon), Internuclear ophthalmoplegia (INO).
  • Lhermitte's sign (electric shock on neck flexion), sensory loss, motor weakness, spasticity.
  • Cerebellar ataxia, fatigue, bladder/bowel issues.
• Diagnosis: McDonald Criteria (clinical + MRI).
  • MRI: Periventricular (Dawson's fingers), juxtacortical, infratentorial, spinal lesions. Gadolinium+ = active.
  • CSF: Oligoclonal bands (OCBs), ↑IgG index.
• Management:
  • Acute relapse: IV Methylprednisolone.
  • Disease-Modifying Therapies (DMTs): Interferons, Glatiramer acetate, Fingolimod, Natalizumab, Ocrelizumab.
  • Symptomatic: Spasticity (Baclofen), Fatigue (Amantadine).
• 📌 McDonald Criteria: Dissemination In Time and Space (DITS).

⭐ Oligoclonal bands in CSF are present in >95% of MS patients but are not specific.

NMOSD & ADEM - MS Mimics & More

Key MS mimics; distinct antibodies, features, and management.

• 📌 NMO: Not MS, Optic nerve & cord focus.

Guillain-Barré Syndrome (GBS) - Nerve Strippers

• Acute immune-mediated polyradiculoneuropathy, often post-Campylobacter jejuni infection.
• Pathophys: Molecular mimicry; antibodies (anti-GM1, anti-GD1a) target peripheral nerve myelin/axons.
• Key Features: Rapidly progressive, symmetrical ascending weakness/paralysis; areflexia/hyporeflexia.
  • Sensory symptoms (paresthesia, pain).
  • Autonomic dysfunction (tachycardia, BP changes).
  • Cranial nerve involvement (e.g., facial palsy); respiratory failure risk (monitor FVC).
• Variants:
  • Miller Fisher Syndrome (MFS): Ophthalmoplegia, ataxia, areflexia (anti-GQ1b Ab).
• Diagnosis:
  • CSF: Albuminocytologic dissociation (↑ protein, normal cells) - typically after 1 week.
  • NCS/EMG: Demyelinating features (↓ conduction velocity).

⭐ Albuminocytologic dissociation in CSF (↑ protein, normal cells) is a classic diagnostic hallmark, usually appearing 1-2 weeks post-symptom onset.

• Treatment: IVIG or Plasma Exchange (PLEX). Supportive care crucial. Steroids NOT effective. 📌 Gradual Bilateral Symmetrical weakness.

High-Yield Points - ⚡ Biggest Takeaways

• Multiple Sclerosis (MS): Oligoclonal bands (CSF), periventricular plaques (MRI). Key signs: Uhthoff's, Lhermitte's.
• Optic Neuritis: Common MS onset; painful monocular vision loss, Marcus Gunn pupil.
• Neuromyelitis Optica (NMO): AQP4-IgG+; severe optic neuritis & longitudinal transverse myelitis (LETM).
• Acute Disseminated Encephalomyelitis (ADEM): Monophasic, post-infectious/vaccinial (children); diffuse white matter lesions.
• Guillain-Barré Syndrome (GBS): Ascending paralysis, areflexia; CSF: albuminocytologic dissociation (↑protein, normal cells).
• Progressive Multifocal Leukoencephalopathy (PML): JC virus in immunocompromised; non-enhancing white matter lesions on MRI.