Guillain-Barré Syndrome: The damage mechanism

GBS: an auto-immune disease
Attack on the peripheral nerves
GBS types, based on damage caused
Destruction of nerve insulation
Chaos in the body
Hospitalisation can be a matter of life and death
Further reading

GBS: an auto-immune disease
Under normal circumstances, the body's immune system recognises the body as "itself" and ignores it, attacking only introduced particles and invading organisms. However, this mechanism can be disrupted, and the body then begins to attack itself. A disease that causes this effect/reaction is called auto-immune. In autoimmune conditions, the body's immune system mistakenly turns against itself, attacking its own tissues.
Examples of other autoimmune diseases are rheumatism, some types of diabetes, etc.

There are a number of unconfirmed theories as to why the immune system suddenly attacks GBS patients' nerves.
A popular theory suggests that the organism (e.g. virus or bacteria) responsible for the preceding infection somehow confuses the immune system, perhaps by mimicking the characteristics of the nerve cells, making it less discriminating about what cells it attacks.
Another suggests that the organism perhaps changes the characteristics of the nerve cells, causing the immune system to see them as foreign cells.

Luckily, this phase is temporary in GBS. After a while the immune system recovers, the attack stops and the patient recovers.
CIDP patients may experience relapses, and require immuntherapy in order to reduce the severity of the attacks.

Attack on the peripheral nerves
All the nerves in the human body, with the exception of the brain and spinal cord, belong to the peripheral group of nerves. i.e. the peripheral nervous system comprises most of the cranial nerves and the spinal nerves (sensory, motor, autonomic, and mixed).

The peripheral nerves transmit signals from the brain and spinal cord to, and from, the muscles, organs and skin. Depending on their function, the nerves can be classified as motor, sensory and autonomous (involuntary) peripheral nerves.

When the immune system malfunctions temporarily and GBS sets in, an attack is launched on the peripheral nerves, damaging them. This causes sensory disturbances, progressive weakening and/or acute paralysis. Metaphorically speaking, the nervous system short-circuits. Exactly how the nerves are damaged is described below.

Only the peripheral nervous system is affected, which is why GBS is also known as "peripheral neuropathy".

GBS types, based on damage caused
GBS can be divided into types on the basis of the type of destruction caused.

If the myelin sheath (described below, see figure 1) insulating an axon is damaged or destroyed, the nerve signals through the axon are disrupted or slowed down, causing symptoms such as abnormal sensations and weakness. This inflammation is the demyelinising type, and the process is called primary demyelination.

In the axonal type, the nerve axon itself is destroyed in a process called secondary demyelination. This is said to occur in patients who experience a very violent inflammation phase (see 'Syndrome Phases'). If the axon dies, the nerve signal is blocked, and cannot be transmitted further. This causes weakness and paralysis in the body area controlled by the nerve.
The axonal type occurs most frequently after preceding diarrhoea. It may be responsible for a less favourable prognosis (outcome), as axons regenerate after a long delay compared to the myelin sheath, which heals faster. There are however some kinds of axonal types that have a more favourable prognosis.

The mixed type destroys both axons and myelin. Long-term paralysis in some GBS patients is thought to be caused by permanent damage to both axons and myelin sheaths.

Peripheral nerves and spinal roots are the major sites of demyelination, but cranial nerves may also be involved.

Destruction of nerve insulation
The immune system's attack on the peripheral nerve cells starts a chain reaction:

The immune system is responsible for the production of special proteins, the antibodies or immunoglobulins (Ig), as part of the body's normal defence mechanism.
These antibodies are produced in reaction to the presence of antigens, or introduced particles in the body, such as various bacteria and vira. Antibodies match specific antigens, and when the two come in contact, they bind together and a number of destructive reactions occur. See diagram.
In GBS patients, antibodies are somehow produced against myelin. They circulate in the blood seeking myelin, which is found in nerve cells.

Nerve cells have long, thin extensions called axons, that transmit signals between nerve cells. Some axons are surrounded by a myelin sheath, a little like electrical cables are surrounded by plastic. The myelin sheath insulates and protects the nerve cells. It also increases both the speed and the distance over which nerve signals can be transmitted. For example, signals from the brain to muscles are transmitted at a speed of over 50 km/h!

Fig.1: Longitudinal section of an axon and its myelin sheath. Click to enlarge.
The axon is part of nerve cell 1, stretching toward nerve cell 2. The myelin sheath resembles tape, wrapped around the axon in several layers.
See a transverse section of the myelin sheath.

Myelin does not cover the axon in an uninterrupted tube, like an electrical cable. Instead, it resembles long beads on a string, with space between the beads (see figure above). The spaces are known as Ranvier Nodes. Axons are uncovered between these nodes of Ranvier and are therefore vulnerable to attack here.

The nerve signals transmitted are also delayed a little at the nodes, and the more nodes there are, the slower the signal becomes. This fact is important when understanding recovery - increased numbers of Ranvier nodes may be produced during nerve recovery, slowing signal transmission.

The myelin-attacking antibodies produced in the GBS patient circulate in the blood and eventually find myelin. They attack and destroy it with the help of white blood cells, producing inflammation in the nerves. The inflamed cells in turn secrete chemicals that affect the Schwann cells. These cells produce the fatty materials required to produce myelin. Affecting Schwann cells reduces myelin production, and some of them may even die, further reducing myelin production, while at the same time the existing myelin is destroyed by the antibodies.

Chaos in the body
As the attack progresses, the peripheral nerve network is gradually destroyed. Motor, sensory or autonomic nerves are attacked, signals are slowed down, blocked or disrupted and the patient's body is affected accordingly.

If the signal transmission speed of a motor nerve is reduced, the patient experiences weakness in the body area controlled by the nerve. If the signal speed is reduced further, or blocked, the patient can become paralysed. Similarly, attacks on sensory or autonomic nerves result in disturbances of the organs hooked up to the nerves.

Simultaneously, the patient's brain receives fewer signals from the body, and these may be disrupted. This results in parts of the body feeling numb, as well as strange sensations of pain, tingling, and pins and needles.

Signals to and from the arms and legs must travel furthest from the brain and spinal cord, and are therefore most susceptible to a barrage of disturbances while en route. This is why hands and feet are usually the first body areas that display GBS symptoms.
Patients suffering from Miller-Fisher syndrome may experience the first symptoms in the face.

The symptoms (weakness, tingling etc.) may gradually or very quickly increase in intensity and spread to the rest of the patient's body. Read 'Case Histories' for real-life stories of how patients experienced the onset of GBS, CIDP, etc.

Hospitalisation can be a matter of life and death
In moderately serious cases, the patient's ability to walk can be affected, and daily chores can be difficult to do.

In serious cases, the weakness may result in complete paralysis, and the patient should therefore be hospitalised immediately. The disorder is considered life-threatening in such cases, as the diaphragm and chest muscles are weakened, thus affecting both the heart and the lungs. Breathing becomes difficult, irregular heartbeat may be experienced, as well as unstable blood pressure. The patient is therefore monitored very carefully and very frequently, and hooked up to a ventilator and heart monitor as required.
Warning symptoms are described under 'Symptoms'.

- Case histories
Patients, including pregnant women and children, report on their real-life encounters with Guillain-Barré syndrome and its variants. English and foreign-language case histories are available - do consider adding yours to the collection, to inspire and support other patients and their families!