A distinctive characteristic of acute polio infection is the predilection of the poliovirus for the nerve cells that control muscles. These nerve cells, or motor neurons, consist of a cell body located in the anterior horn of the spinal cord and a long tentacle, or axon, that extends to the muscles. Near the end of each axon, tiny sprouts branch out to individual muscle cells. At the nerve-muscle interface, or synapse, the sprouts from the axon release acetylcholine, a neurotransmitter that causes the muscle fibers to contract. A motor neuron and the group of muscle cells that it activates are called a motor unit.

With uncanny precision, the poliovirus invades the motor neurons, leaving intact adjacent nerve cells that control the functions of sensation, bowel, bladder and sex. How this exquisitely targeted behavior occurs was a mystery until recently, when researchers identified poliovirus receptors at the nerve-muscle interface. These receptors apparently allow the poliovirus to enter an axon and then to migrate to the nerve cell body in the anterior horn of the spinal cord. The poliovirus typically infects more than 95 percent of the motor neurons in the spinal cord and many other cells in the brain. The infected cells either overcome the virus or die.

The extent of paralysis is unpredictable. Motor neurons that survive develop new terminal axon sprouts in response to an unknown stimulus. These new sprouts reinnervate, or reconnect, with the muscle fibers left orphaned by the death of their original motor neurons. In a sense, the growth of additional axon sprouts is the body's effort to keep as many orphaned muscle cells as possible alive and working. A single motor neuron that initially stimulated 1,000 muscle cells might eventually innervate 5,000 to 10,000 cells, creating a giant motor unit. These vastly enlarged motor units make it possible for fewer motor neurons to do the work of many.

Another adaptation that leads to increased strength is the enlargement of muscle cells when they are regularly exercised. These two compensatory adaptations--increase in muscle size and axon sprouting--are so effective that up to 50 percent of the original number of motor neurons can be lost without the muscle losing clinically normal strength. These adaptations are neither static nor permanent, however. To the contrary, after recovery from acute polio there is an ongoing process of remodeling of the motor units that consists of both denervation (losing old sprouts) and reinnervation (gaining new ones). It is this process of remodeling or constant repair that allows the motor units to achieve a steady state of muscle strength. When this steady state is disrupted, new muscle weakness occurs.

There is a growing consensus among researchers that post-polio syndrome involves a slow degeneration of the terminal axon sprouts that innervate the muscle cells. David O. Wiechers and Susan L. Hubbell, then affiliated with Ohio State University, proposed this explanation in the early 1980s after diagnostic tests indicated that the functioning of motor neurons in polio survivors progressively worsens as the number of years from their recovery increases. More recently, Daria A. Trojan and Neil R. Cashman of the Montreal Neurological Institute and Hospital, after examining the results of muscle biopsy and electromyographic (EMG) studies in their laboratory and by researchers elsewhere, postulated that there are two types of disintegration of the motor neurons: a progressive lesion and a fluctuating one.

The progressive lesion, in their view, occurs when the normal regeneration of the sprouts from the axon to the muscles is interrupted and malfunctioning sprouts are not replaced. This interruption of the repair process produces irreversible, progressive muscle weakness. The fluctuating lesion, on the other hand, is thought to be caused by defective synthesis or release of the neurotransmitter acetylcholine. Cashman, Trojan and others have demonstrated that muscle weakness and fatigue can be reversed in some patients with post-polio syndrome by the drug pyridostigmine, which enhances the effectiveness of acetylcholine in triggering muscle contractions. Other researchers are testing another class of agents known as nerve growth factors, which stimulate both nerve and muscle cell growth.