What are demyelinating diseases?

Demyelinating Diseases

Demyelinating diseases are a group of conditions characterized by damage to the myelin sheath that surrounds and protects nerve fibers in the central and peripheral nervous systems, leading to impaired nerve signal transmission and various neurological deficits. 1

Types of Demyelinating Diseases

Central Nervous System Demyelinating Disorders

• Multiple Sclerosis (MS)

  • Most common demyelinating disease
  • Characterized by lesions affecting the spinal cord and brain
  • Clinical defects disseminated in space and time
  • Spinal cord involvement in 80-90% of patients, most commonly in cervical cord 1
  • Typically shows periventricular, pericallosal, cerebellum, brain stem, and spinal cord hyperintensive lesions on MRI T2 and FLAIR sequences 2
  • Oligoclonal bands in CSF are characteristic 2

• Neuromyelitis Optica (NMO)

  • Characterized by optic neuritis and transverse myelitis
  • Associated with postrema and diencephalic area syndrome
  • MRI lesions distributed in areas rich with aquaporin-4 channels: hypothalamus, third and fourth ventricle, optic nerves, and spinal cord 2
  • Anti-AQP4 antibodies are useful for diagnosis but not essential 2

• Acute Disseminated Encephalomyelitis (ADEM)

  • Typically monophasic condition
  • Characterized by acute encephalopathy
  • MRI shows large, bilateral, irregular asymmetric hyperintense lesions on T2 and FLAIR sequences 2
  • Spinal cord involvement in approximately 25% of cases 1

Other Demyelinating Conditions

• Transverse Myelitis

  • Can be associated with various underlying conditions including demyelinating diseases and systemic autoimmune diseases 3
  • Longitudinally extensive transverse myelitis (lesions extending over ≥3 vertebral segments) is often associated with NMO 3

• Metachromatic Leukodystrophy (MLD)

  • Caused by deficiency of arylsulfatase A enzyme
  • Results in progressive demyelination of central and peripheral nervous systems 1
  • Classified into late infantile, juvenile, and adult subtypes based on age of onset 1

Causes of Demyelination

Primary Demyelination

• Autoimmune etiology directed against myelin of the central nervous system 2
• Often preceded by nonspecific viral infections 2

Secondary Demyelination

• Represents a spectrum of white matter disease characterized by damage to neurons or axons with resultant breakdown of myelin 4
• Associated with various conditions:
  • Infections/vaccinations
  • Nutritional/vitamin deficiencies (e.g., vitamin B12 deficiency)
  • Chemical agents
  • Genetic abnormalities
  • Vascular insults 4

Clinical Manifestations

Symptoms vary depending on the specific disease and location of demyelination:

• Multiple Sclerosis: Polyfocal neurological deficits, commonly optic neuritis, transverse myelitis, and encephalic trunk involvement 2

• Vitamin B12 Deficiency: Associated with subacute combined degeneration of the spinal cord and polyneuropathies

  • Extensive demyelination in CNS, most prominently in the spinal cord
  • Focal demyelination in white matter of the brain
  • Demyelination in peripheral nervous system with axonal degeneration 1
  • Clinical symptoms include paraesthesia, numbness, muscle weakness, abnormal reflexes, tendon jerks, spasticity, gait ataxia, myelopathies and myelo-neuropathies 1

• Progressive Multifocal Leukoencephalopathy (PML): A serious complication associated with some MS treatments

  • Symptoms include progressive weakness on one side of the body, clumsiness of limbs, visual disturbances, and changes in thinking, memory, and orientation 5

Diagnosis

• MRI: Gold standard for imaging evaluation

  • Superior soft-tissue resolution and multiplanar capability
  • Can identify spinal cord lesions suggestive of demyelinating disease 1
  • Contrast-enhanced imaging recommended for initial diagnostic evaluation 1

• Cerebrospinal Fluid Analysis:

  • May show pleocytosis and hyperproteinorrachia
  • Presence of oligoclonal bands characteristic of MS 2

• Laboratory Tests:

  • Antibody tests for NMO and MOG antibody-associated disorders 3

Treatment

Acute Treatment

• High-dose intravenous corticosteroids (1g/day IV methylprednisolone for 3-5 days)

  • Should be initiated as soon as possible, ideally within hours of diagnosis 3, 2

• Plasmapheresis for non-responsive cases 2

• Intravenous immunoglobulin (IVIG) at a dose of 2g/kg divided over 5 days as second-line treatment 3

Long-term Treatment

• Both MS and NMO require long-term treatment to prevent relapse and recurrent disease 2

• Disease-modifying therapies for MS:

  • Medications like fingolimod and natalizumab may be used but carry risks:
    • Fingolimod: Risk of progressive multifocal leukoencephalopathy (PML), macular edema 6
    • Natalizumab: Risk of PML, herpes infections, hepatotoxicity 5

Prognosis

• Transverse Myelitis: Follows a rule of thirds:

  • One-third recover with few or no sequelae
  • One-third develop moderate permanent disability
  • One-third suffer severe disability 3

• Poor prognostic factors include:

  • Extensive lesions on MRI
  • Reduced muscle strength or sphincter dysfunction at onset
  • Delayed treatment initiation (>2 weeks) 3

Important Considerations

• Demyelinating diseases can present as emergencies due to severe inflammatory destruction of CNS tissues 7
• Early diagnosis and treatment lead to better outcomes 7
• When switching between immune-modulating medications, consider the duration of their effects and mode of action to avoid unintended additive immunosuppressive effects 6
• Monitor for development of PML in patients on certain MS treatments, as early detection and discontinuation of treatment may improve outcomes 6