Late CNS Reactions

The central nervous system primarily consists of the cerebrum, the brainstem, the cerebellum and the spinal cord. The cerebellum and cerebrum are usually considered together from radiobiological issues. Radiation typically affects the white matter, or both the white matter and gray matter - isolated lesions in the gray matter are usually of a different aetiology.

Brain

The brain is a difficult organ to classify as its functional subunits are in both serial and parallel. For instance, the cerebral cortex is made up of several levels of neuronal cell bodies and axons, which communicate with other areas through long axonal fibers in the white matter. Each area of cerebral cortex functions in this way (parallel arrangement). However, due to the specialisation of different areas of the brain (eg. motor cortex, sensory cortex, Broca's area etc) the brain also has a serial arrangement of function.
For the purposes of radiobiology, the brain contains:

  • Neurons, which are considered terminally differentiated and highly resistant to radiation
  • Glial cells, which surround and nourish the neuronal cell bodies and axon. In the CNS these cells are oligodendrocytes.
    • Glial cells provide myelination to nerve fibres, enhancing the speed of electrical conduction
  • Blood vessels, including larger arteries and veins as well as capillaries

Damage to glial cells, endothelial cells or both can lead to various late effects in the brain.

Demyelination

Demyelination occurs when there is death of oligodendrocytes, leading to loss of the myelin sheaths which enable neuronal function. Demyelination may cause local effects and occurs between 1 - 3 months in most cases. Demyelination is usually more symptomatic in the spinal cord.

Radiation necrosis of the brain

Vascular changes are thought to be an important cause of brain necrosis, but demyelination and loss of glial cells may also contribute. The usual observed effects include increased permeability and oedema around capillaries, which may be followed by haemorrhage or thrombosis. These changes may induce demyelination due to poor supply of nutrients to the glial cells. Brain necrosis, which typically involves the white matter, may lead to severe neurological defects which are dependant on the site involved. Other problems include seizures.
In the most recent toxicity paper, brain tolerance has been given as:

  • < 3% risk of necrosis if Dmax is less than 60 Gy
  • 5% risk of necrosis if Dmax is 72 Gy
  • 10% risk of necrosis if Dmax is 90 Gy

Radiation necrosis is usually progressive and can be fatal.

Glial atrophy

Loss of white matter can occur due to depletion of glial stem cells.

Gray matter lesions

Unlike typical brain necrosis which involves the white matter, gray matter lesions may also develop. In general, there is more evidence of vascular changes than glial involvement when compared with white matter lesions.

Brainstem

The brainstem consists of the midbrain, pons and medulla and is the common point of communication between the cerebrum, the cerebellum and the spinal cord. Lesions in the brainstem cause catastrophic problems in most cases and it is considered a serial organ. The brainstem suffers from similar pathological processes as the brain.

Dose Guidelines

The brainstem, being a serial organ, uses point doses to determine tolerance. The endpoint in the brainstem is symptomatic neuropathy and/or necrosis (as opposed to the brain, which is just symptomatic necrosis).

  • If the maximum dose at a point is under 54 Gy, the risk of brainstem necrosis is under 5%
  • If the maximum dose is below 59 Gy, and the region of maximum dose is less than 10 cm3, then the risk of brainstem necrosis is under 5%
  • If the maximum dose is below 64 Gy, and the volume of this dose is under 1 cm3, then the risk of brainstem necrosis is under 5%

This suggests that the brainstem is able to tolerate doses of up to 64 Gy, provided these doses are only over a tiny volume.

Spinal Cord

The spinal cord contains the same populations of neurons, glial cells and vascular cells and can undergo similar processes which have different names. Myelopathy is the general name for conditions causing damage to levels within the spinal cord; radiation myelopathy is when this is due to radiation necrosis of white matter tracts. The spinal cord is another example of serial arrangement of functional sub units, and again point doses seem to be important.

Transient Demyelination

In the spinal cord, transient demyelination gives rise to Lhermitte's sign which is characterised by an electric shock-like feeling that travels down the back and into the limbs. This is thought to be due to loss of oligodendrocytes on the nerve tracts of the spinal cord. It does not predict for later development of myelopathy. Lhermitte's sign usually occurs 2 - 4 months after exposure to ionising radiation and is more common than myelopathy.

Radiation Myelopathy

Radiation myelopathy is a progressive loss of spinal cord function due to the white matter necrosis described in the brain section above. Symptoms are dependant on the region of spinal cord affected, although extensive lesions may give rise to complete loss of motor and sensory function at and below the involved level.

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