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37. Demyelinisation disorders

Introduction

Within the CNS and PNS axons are sheathed by myelin, which insulates the axon and allows the nerve signal to propagate much faster. Myelin in the CNS consists of multiple layers of plasma membranes that are assembled by oligodendrocytes. Myelin in the PNS are similar in architecture but they’re produced by Schwann cells and not oligodendrocytes, and the proteins and lipids that the sheath is made of are different. Therefore, most diseases of CNS myelin do not involve the peripheral nerves and vice versa.

Diseases of myelin are separated into two groups:

  • Demyelinating diseases – where there is secondary damage to normal myelin
    • Multiple sclerosis (MS)
    • Guillain-Barré syndrome
    • Acute haemorrhagic leukoencephalitis (AHL)
    • Acute disseminated encephalomyelitis (ADEM)
    • Central pontine myelinolysis (CPM)
    • Neuromyelitis optica (NMO)
  • Dysmyelinating diseases/leukodystrophies – where myelin isn’t formed properly

Demyelinating diseases are the diseases where something damages completely normal myelin, often caused by the immune system. The most important type is multiple sclerosis.

Dysmyelinating diseases are the diseases where myelin isn’t formed properly. These are associated with mutations of lysosomal enzymes, peroxisomal enzymes or myelin proteins. These aren’t as important and won’t be further discussed.

Multiple sclerosis

Multiple sclerosis (MS) is an autoimmune, progressive, chronic disease with multifocal demyelination in the CNS. MRI shows demyelinated sclerotic plaques in the white matter, most commonly in the periventricular areas, optic nerve and brainstem.

Risk factors: Both environmental and genetic factors are involved. The most important risk factors are:

  • Age 15 – 45
  • Female gender
  • HLA-DR2
  • Smoking
  • Vitamin D deficiency
  • Living in western countries
  • Positive family history of MS

Subtypes: We distinguish several types of MS, based on the clinical picture:

  • Relapsing-remitting / Charcot MS – 90%
    • Exacerbations occur
    • Symptoms disappear almost completely between exacerbations
  • Secondary progressive MS – develops from Charcot type
    • Exacerbations occur
    • Symptoms worsen between exacerbations
  • Primary progressive MS – 10%
    • No exacerbations
    • Symptoms worsen continuously
  • Marburg acute MS – rare
    • Acute fulminant
    • Severe disability in few years

Relapsing-remitting MS or Charcot MS is the most frequent type, as it accounts for 90% of cases at the time of diagnosis. In this case the patient experiences some days or weeks of exacerbated symptoms with long periods of remission without symptoms between the exacerbations. Charcot MS may develop into secondary progressive MS.

Marburg acute MS is an acute, fulminant type of MS where death occurs within 2 years in most cases.

Symptoms: The common symptoms of MS are:

  • Involvement of optic nerve
    • Vision abnormality
    • Sudden, temporary blindness
  • Involvement of brain stem
    • Ataxia
    • Ophthalmoplaegia
    • Nystagmus
  • Involvement of spinal cord
    • Paraesthesia
    • Paresis
    • Spasticity
    • Incontinence

Vision abnormalities are often the earliest manifestation of MS.

Pathogenesis: The pathogenesis isn’t precisely known. The current theory involves autoreactive T-cells that target a protein called myelin basic protein and proteins of the oligodendrocytes.

Pathology: The affected areas of MS show multiple well-circumscribed, glassy-appearing lesions called plaques. The plaques may be active or inactive. In active plaques there is ongoing myelin breakdown and inflammation with abundant macrophages that contain myelin debris. In inactive plaques the inflammation mostly disappears and leaves behind little to no myelin.

Other demyelination disorders

Guillain-Barré syndrome (GBS) is an acute postinfectious polyneuropathy characterised by symmetric and ascending flaccid paralysis. It mostly affects the peripheral nervous system and not the CNS. It’s associated with upper respiratory or gastrointestinal tract infection. Molecular mimicry is involved, as antibodies produced against the pathogen also targets gangliosides in the Schwann cells, causing demyelination. Around 5% die from respiratory failure.

Acute disseminated encephalomyelitis is an immune-mediated demyelinating disease that can occur after infection or very rarely, after vaccination. Symptoms resemble MS but may include coma. The disease resolves spontaneously in most cases. It is deadly in 20% of cases. Most cases involve children or young adults. The initial infection may be viral

(measles, mumps, flu), or bacterial (mycoplasma,campylobacter)

Acute haemorrhagic necrotizing leukoencephalitis is a very rare type of acute disseminated encephalomyelitis that has high mortality. Occurs after airways infection or as a paraneoplastic sign.

Central pontine myelinolysis is not associated with immune damage but rather with osmotic disturbances. It may occur after too rapid correction of hyponatraemia.