The cause of post-polio syndrome is not fully known. Several theories have been proposed, and it may be that post-polio syndrome is a result of a combination of these effects, exacerbated by the aging process.

Neural Fatigue

The most widely accepted theory is that of neural fatigue. This theory proposes that as motor neurons are damaged in the initial polio infection, neighbouring neurons compensate by sprouting new nerve fibres. This leads to a case where there are too few motor neurons working too many muscles. Consequently, the overworked neurons gradually become ‘fatigued’ and lose the ability to regenerate, leading to loss of muscle function.

Mitochondrial Disruption

This theory attributes the loss of muscle strength to disruption to the functioning of mitochondria in the muscle cells such that they do not produce enough energy for the cells. The mitochondrial disruption is believed to be due to hormonal imbalances in the body brought about by damage to the hypothalamus part of the brain in the initial polio infection.

Reticular Activating System Damage

Damage to the reticular activating system in the brain, caused by the initial polio infection, may also lead to hormonal changes, reducing the ability to manage stress and leading to muscle weakness.

Mechanical Overwork

This simple theory suggests that the muscle tiredness comes from prolonged overworking of muscles damaged in the initial infection or of other muscles that must compensate for the damaged muscles.

Reactivated Polio

It has been suggested that post-polio syndrome is merely a reactivation of the polio virus. This theory is generally considered to be unlikely as active polio viruses have not been found in polio survivors.