Demyelinating diseases of the central nervous system
CNS axons are ensheathed by myelin which helps to increase the speed of neural impulses, it is most dominant in the white matter of the brain. There are two broad groups of myelin diseases:
- Demyelinating diseases - where normal myelin is attacked and damaged (e.g. MS)
- Dysmyelination diseases - where myelin is not properly formed to begin with
MS
- An autoimmune demyelinating disorder characterised by episodes of neurologic defects, separated in time, with lesions separated by space
- It is defined as having two ‘sclerotic’ lesions within the CNS system
- PG/ genetic + immune. Possibly triggered by an infectious agent, with risk 15x greater if a family member has, immune mediated myelin destruction has a central role.
- Predominantly a white matter disease, we see well-circumscribed, depressed, glassy-appearing, gray lesions known as plaques .These can be active or inactive.
- Active plaques have lymphocytes and macrophages which are breaking down myelin, they have four classes (types I-IV) based on margins and content
- Inactive plaques do not have active inflammatory cells, there is no myelin left, and only astrocytic proliferation and gliosis
- Clinical features are that of neurologic attack, in relapse and remission pattern
Multiple sclerosis: grey, glassy, well-demarcated plaque in the periventricular white matter, next to the lateral ventricle (cavity at left).
Image: “MS, lesion adjacent lateral ventricle” by Narraburra, CC0, via Wikimedia Commons.
Remember: MS plaques favour the white matter next to the lateral ventricles, the optic nerves and chiasm, the brainstem and the spinal cord. In a plaque the myelin is lost but the axons are relatively preserved (myelin stains such as Luxol fast blue show the pale plaque).
Other demyelinating diseases
- Immune mediated demyelination can occur after a number of infectious illnesses, and are thought to be due to immune cell responding to pathogen
- In general there are two patterns
- Acute disseminated encephalomyelitis
- 20% fatal, others make recovery
- Acute necrotizing hemorrhagic encephalomyelitis
- More devastating form of the above
- Neuromyelitis optica
- Inflammatory demyelinating disease of the optic nerve and spinal cord (previously thought to be a form of MS)
- Central pontine myelinolysis
Example: a malnourished alcoholic patient with severe hyponatraemia has the sodium corrected too quickly and days later develops rapidly evolving quadriplegia - central pontine myelinolysis, a symmetric loss of myelin in the basis pontis.
Leukodystrophies
- Inherited dysmyelinating diseases where there is abnormal myelin synthesis or turn over.