Diseases of myelin

1. Myelin Basics

• Myelin: 75 % lipids + 25 % proteins; electrical insulator forming the myelin sheath around axons → rapid (saltatory) propagation of impulses.
• CNS myelin: oligodendrocytes — one cell wraps multiple internodes; gaps = nodes of Ranvier.
• PNS myelin: Schwann cells — one cell = one internode.

Categories

• Demyelinating diseases: acquired; damage to originally normal myelin.
• Dysmyelinating diseases: inherited; abnormal myelin formation → leukodystrophies.

2. Multiple Sclerosis (MS)

Definition

• Autoimmune demyelinating disease.
• Distinct relapsing + remitting episodes of neurological deficits → white matter lesions.
• Women > men (3:1).
• Age: 15–45 years.
• HLA-DRB1⁺ associations; northern latitudes; low vitamin D; EBV.

Pathogenesis

• Combination of genetic + environmental factors → loss of tolerance to self-proteins (myelin antigens).
• CD4⁺ T cells (Th1, Th17) attack myelin.

Morphology

• Gross: grayish plaques in white matter — typically periventricular, optic nerve, brainstem, spinal cord.
• Histology — lesions depend on age:
  • Active plaque: foamy macrophages, ongoing myelin degradation.
  • Chronic active plaque: central axon loss, gliosis, demyelination at edge.
  • Inactive (silent) plaque: no inflammation; myelin loss + gliosis only.

Clinical Features

• Relapses (new symptoms) followed by remissions → accumulating neurological deficits over time.
• Common symptoms:
  • Unilateral visual impairment (optic neuritis).
  • Brain stem symptoms: internuclear ophthalmoplegia (MLF lesion), ataxia.
  • Spinal cord symptoms: spasticity, bladder dysfunction.
  • Cognitive function changes.
• 4 clinical courses: relapsing-remitting (#1), secondary progressive, primary progressive, progressive-relapsing.

Diagnostics

• MRI: periventricular white matter plaques (Dawson fingers).
• CSF: oligoclonal bands (Igs accumulating in CSF), ↑ IgG index.

3. Central Pontine Myelinolysis

• Non-immune process; loss of myelin in center of pons.
• Most often after rapid correction of hyponatremia.
• Clinical: “locked-in” syndrome (quadriplegia with preserved consciousness).

4. Leukodystrophies

Definition

• Inherited dysmyelinating diseases due to abnormal myelin synthesis/turnover.
• Most autosomal recessive (enzyme deficiencies).
• Examples: metachromatic leukodystrophy (arylsulfatase A def), Krabbe disease (galactocerebrosidase), adrenoleukodystrophy (X-linked).

Morphology

• White matter shrinks, becomes grayish + transparent.
• Eventually → diffuse cerebral atrophy.

Clinical Features

• Begins at younger ages than MS (often infancy/childhood).
• Slow, insidious progression.
• Motor disturbances, spasticity, hypotonia, ataxia.

5. Acquired Metabolic Disorders of the Brain

A) Thiamine (Vitamin B1) Deficiency — Wernicke-Korsakoff Syndrome

• Wernicke encephalopathy: classic triad — confusion + ocular motor defects (ophthalmoplegia, nystagmus) + ataxia.
• Korsakoff syndrome: irreversible memory impairment + confabulation.
• Sites: mammillary bodies, periaqueductal gray, dorsomedial thalamus.
• Alcoholics, malnourished.

B) Vitamin B12 Deficiency (Subacute Combined Degeneration)

• Involves ascending + descending fibers of spinal cord (dorsal columns + lateral corticospinal tracts).
• Symptoms: numbness of lower extremities → spastic weakness → complete paraplegia.

C) Systemic Metabolic Disturbances

• Hypoglycemia: resembles hypoxia (global hypoxic damage).
• Hyperglycemia: confusion, stupor, coma (osmotic effect).
• Hepatic encephalopathy:
  • ↓ Hepatic function → ↑ ammonia → altered synaptic transmission + astrocyte changes (Alzheimer type II astrocytes).
  • Symptoms: confusion, asterixis (flapping tremor), coma.

6. Acquired Toxic Disorders of the Brain

• Ethanol (chronic): cerebellar dysfunction (nystagmus, unsteady gait, ataxia); anterior vermis atrophy.
• Ionizing radiation: coagulative necrosis in white matter with edema.
• Chemotherapeutic agents: neurotoxic side effects.
• Heavy metals (lead, arsenic, mercury): diffuse encephalopathy.
• CO poisoning: hypoxia; selective toxicity in globus pallidus.
• Industrial compounds: organophosphates (pesticides), methanol (→ blindness/retinal damage).

7. Summary Table

Disease	Key features
Multiple sclerosis	Autoimmune, women 15–45, periventricular Dawson fingers, oligoclonal bands in CSF, optic neuritis, INO (MLF), foamy macrophages
Central pontine myelinolysis	Rapid correction of hyponatremia; locked-in syndrome
Leukodystrophies	Inherited; AR; childhood onset; metachromatic, Krabbe, adrenoleukodystrophy
Wernicke-Korsakoff	B1 deficiency; confusion + ophthalmoplegia + ataxia → irreversible memory loss; mammillary bodies
B12 deficiency	Subacute combined degeneration: dorsal columns + lat. corticospinal tracts
Hepatic encephalopathy	↑ NH₃; asterixis; Alzheimer type II astrocytes
CO poisoning	Globus pallidus necrosis

💡 High-yield: CNS myelin = oligodendrocytes, PNS myelin = Schwann cells. MS = autoimmune demyelination, women 15–45, periventricular plaques (Dawson fingers), CSF oligoclonal bands, optic neuritis + INO (MLF); foamy macrophages in active plaques. Central pontine myelinolysis = rapid correction of hyponatremia; locked-in. Leukodystrophies = inherited AR (metachromatic, Krabbe, adrenoleukodystrophy). Wernicke-Korsakoff = B1 def in alcoholics: confusion + ophthalmoplegia + ataxia → irreversible memory loss + confabulation (mammillary bodies). B12 def = subacute combined degeneration (dorsal columns + lateral corticospinal). Hepatic encephalopathy = ↑ NH₃, asterixis. CO poisoning = globus pallidus necrosis. Methanol = retinal/optic damage → blindness.